Multidrug-resistant Organisms and Nosocomial Infections

Overview

Multidrug-resistant organisms (MDROs)

• Multidrug resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing is considered when an isolate is resistant to at least 1 drug in 3 or more classes of medications.
• Organisms:
  • Vancomycin-resistant enterococci (VRE)
  • Methicillin-resistant Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus ( MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus)
  • Extended spectrum beta-lactamase Beta-Lactamase Penicillins ( ESBL ESBL Klebsiella)-producing organisms
  • Multidrug resistant Multidrug resistant Resistant to at least 1 agent in > 3 antibiotic categories Pseudomonas gram-negative bacilli Bacilli Shigella (MDRGNB) (especially carbapenem-resistant bacilli Bacilli Shigella and difficult-to-treat resistant Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa)

Hospital-acquired infection (HAI)

• Nosocomial infection
• An infection transmitted within a hospital or healthcare facility
• Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Central line-associated bloodstream infection (CLABSI)
  • Catheter-associated urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection (CAUTI)
  • Ventilator-associated pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia (VAP) and hospital-acquired pneumonia Hospital-Acquired Pneumonia Pneumonia in Children (HAP)
  • Clostridioides difficile infection (CDI)
  • Surgical site infection Surgical site infection Infection occurring at the site of a surgical incision. Surgical Complications ( SSI SSI Surgical site infection (SSI) is a type of surgical infection that occurs at or near a surgical incision within 30 days of the procedure or within 90 days if prosthetic material is implanted. Surgical site infections are classified according to the depth of involvement as superficial, deep, or organ/space. Surgical Site Infections)

Epidemiology

• United States:
  • Annually: ≥ 2.8 million people acquire antibiotic-resistant infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease with ≥ 35,000 associated deaths.
  • In the year 2015: 687,000 HAIs HAIs Carbapenems and Aztreonam in acute care hospitals and 72,000 associated deaths
• MDRO trends:
  • MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus:
    • Between 1995 and 2001, hospital-acquired MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus bloodstream infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease in the United States increased from 22% to 57%.
    • With infection prevention measures, infection rates have declined yearly by 17% between 2005 and 2012.
  • VRE:
    • The early 1990s: accounted for approximately 15% of enterococcal isolates
    • The early 2000s: accounted for approximately 29% of enterococcal isolates
  • Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology resistant to fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones, ESBLs, carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam, and aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides have increased significantly over the last 2 decades.
• HAIs HAIs Carbapenems and Aztreonam: 
  • Increased likelihood to be caused by antibiotic-resistant organisms
  • Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (UTIs) are the most common type of HAI.
  • 75% are associated with catheter use.
  • Up to 25% of hospitalized individuals receive urinary catheters.

Methicillin Resistant Staphylococcus Aureus (MRSA)

MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus

• MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus is a group of Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus resistant to beta-lactam Beta-Lactam Penicillins antibiotics including cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins:
  • Oxacillin minimum inhibitory concentration ≥ 4 μg/mL
  • Community-associated MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus infection (CA-MRSA): MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus infection without healthcare exposure Exposure ABCDE Assessment 
  • Healthcare-associated MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus infection (HA-MRSA): 
    • MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus infection > 48 hours following hospitalization Hospitalization The confinement of a patient in a hospital. Delirium; OR
    • MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus infection outside the hospital within 12 months of healthcare exposure Exposure ABCDE Assessment (e.g., surgery, hospitalization Hospitalization The confinement of a patient in a hospital. Delirium, dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis)
• Mechanism of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
  • MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing is due to the presence of a mec gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (required in methicillin Methicillin One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection. Penicillins resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing). 
  • The gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics has a mecA component, which generates penicillin Penicillin Rheumatic Fever binding protein 2a (PBP2a):
    • PBP2a ( peptidase Peptidase Tubular System enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes in the bacterial membrane) lowers the affinity for the organism to bind BIND Hyperbilirubinemia of the Newborn to beta-lactam Beta-Lactam Penicillins antibiotics.
    • Detection of the mec gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics and PBP2a is the most accurate way to determine methicillin Methicillin One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection. Penicillins resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing.
• Risk factors:
  • Healthcare-associated risk factors:
    • Recent hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
    • Residence in a long-term care facility
    • Recent surgery
    • Hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome
  • Additional risk factors:
    • HIV HIV Anti-HIV Drugs infection
    • Injection drug use
    • Prior antibiotic use
  • Factors associated with MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza:
    • Incarceration Incarceration Inguinal Canal: Anatomy and Hernias
    • Military service
    • Sharing sports equipment
    • Sharing needles, razors, or other sharp objects

Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and antibiotics

• Common infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and soft tissue Soft Tissue Soft Tissue Abscess infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis
    • Necrotizing fasciitis Necrotizing fasciitis Necrotizing fasciitis is a life-threatening infection that causes rapid destruction and necrosis of the fascia and subcutaneous tissues. Patients may present with significant pain out of proportion to the presenting symptoms and rapidly progressive erythema of the affected area. Necrotizing Fasciitis
    • Diabetic foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy ulcers
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and joint infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis of the spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy
    • Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis of long bones Long bones Length greater than width. Bones: Structure and Types of the upper and lower extremities
    • Septic arthritis Septic arthritis Septic arthritis is an infection of the joint due to direct inoculation, contiguous extension, or hematogenous spread of infectious organisms into the joint space. This process causes an acute, inflammatory, monoarticular arthritis. Septic Arthritis of native and prosthetic joints Prosthetic joints Prostheses used to partially or totally replace a human or animal joint. Soft Tissue Abscess
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
• Antibiotic options:
  • Oral:
    • Trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim, sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim
    • Tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines: doxycycline, minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines
    • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides
    • Oxazolidinones Oxazolidinones The oxazolidinones (linezolid and tedizolid) are bacterial protein synthesis inhibitors. Their unique binding site on the 23S ribosomal RNA of the 50S ribosome gives them zero cross-resistance with other antibiotics. Oxazolidinones: linezolid Linezolid An oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract. Oxazolidinones, tedizolid Tedizolid Oxazolidinones
    • Delafloxacin Delafloxacin Fluoroquinolones
  • Parenteral:
    • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
    • Daptomycin Daptomycin A cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Lipopeptides and Lipoglycopeptides
    • Dalbavancin Dalbavancin Lipopeptides and Lipoglycopeptides
    • Oritavancin Oritavancin Lipopeptides and Lipoglycopeptides
    • Telavancin Telavancin Lipopeptides and Lipoglycopeptides
    • Ceftaroline Ceftaroline Cephalosporins
    • Oxazolidinones Oxazolidinones The oxazolidinones (linezolid and tedizolid) are bacterial protein synthesis inhibitors. Their unique binding site on the 23S ribosomal RNA of the 50S ribosome gives them zero cross-resistance with other antibiotics. Oxazolidinones: linezolid Linezolid An oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract. Oxazolidinones, tedizolid Tedizolid Oxazolidinones
    • Delafloxacin Delafloxacin Fluoroquinolones

Prevention

• Hand hygiene Hand hygiene Practices involved in preventing the transmission of diseases by hand. Surgical Infections and contact precautions (e.g., gowns, gloves)
• Some healthcare institutions utilize active surveillance Surveillance Developmental Milestones and Normal Growth of individuals at high risk: 
  • Screening Screening Preoperative Care cultures Cultures Klebsiella of the nares Nares Staphylococcal Scalded Skin Syndrome (SSSS), oropharynx Oropharynx The middle portion of the pharynx that lies posterior to the mouth, inferior to the soft palate, and superior to the base of the tongue and epiglottis. It has a digestive function as food passes from the mouth into the oropharynx before entering esophagus. Pharynx: Anatomy, or perineum Perineum The body region lying between the genital area and the anus on the surface of the trunk, and to the shallow compartment lying deep to this area that is inferior to the pelvic diaphragm. The surface area is between the vulva and the anus in the female, and between the scrotum and the anus in the male. Vagina, Vulva, and Pelvic Floor: Anatomy to identify individuals colonized with antibiotic-resistant bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
  • Interventions may include decolonization, contact isolation, or comprehensive cleaning.
• Decolonization regimen can vary depending on circumstances (e.g., postdischarge, presurgery), but can include:
  • Chlorhexidine bath
  • Mupirocin nasal treatment
• Environmental cleaning
• Antibiotic stewardship (i.e., avoid excessive antibiotic use)

Vancomycin-Resistant Enterococci (VRE)

VRE

• Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus are resistant to vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides (most isolates are Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus faecium)
• Minimum inhibitory concentration ( vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides resistant): ≥ 32 μg/mL
• Mechanism of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
  • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides binds to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of bacterial cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic precursors → disruption in bacterial cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic synthesis Synthesis Polymerase Chain Reaction (PCR)
  • Resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing is due to modification of the D-Ala-D-Ala binding site of the peptidoglycan Peptidoglycan Penicillins building block:
    • The terminal D-Ala is replaced by D-lactate → loss of hydrogen bond facilitating high-affinity binding of vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides to the target 
    • Encoded by several vancomycin-resistance gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics clusters (i.e., vanA, vanB, vanC, vanD, and vanE)
• Risk factors:
  • Previous antimicrobial therapy (especially cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins and vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides)
  • Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium > 72 hours (especially ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus stay)
  • End-stage renal disease (ESRD) requiring dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis
  • Transplant recipients
  • Proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitor use
  • Invasive devices
  • Contaminated surfaces or equipment (e.g., thermometers, bedrails)
  • Residence in long-term care facilities

Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and antibiotics

• Common infection types:
  • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
  • UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs)
• Antibiotic options:
  • Linezolid Linezolid An oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract. Oxazolidinones
  • Daptomycin Daptomycin A cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Lipopeptides and Lipoglycopeptides
  • Tigecycline Tigecycline A tetracycline derivative that acts as a protein synthesis inhibitor. It is used as an antibacterial agent for the systemic treatment of complicated skin and intra-abdominal infections. It is also used for the treatment of community-acquired pneumonia. Tetracyclines
  • Oritavancin Oritavancin Lipopeptides and Lipoglycopeptides
  • Teicoplanin Teicoplanin Lipoglycopeptide antibiotic from actinoplanes teichomyceticus active against gram-positive bacteria. It consists of five major components each with a different fatty acid moiety. Glycopeptides
  • Telavancin Telavancin Lipopeptides and Lipoglycopeptides

Prevention

• Hand hygiene Hand hygiene Practices involved in preventing the transmission of diseases by hand. Surgical Infections and contact precautions
• Chlorhexidine bath (benefit most noted in ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus admissions)
• Surveillance Surveillance Developmental Milestones and Normal Growth cultures Cultures Klebsiella for VRE in high-risk individuals:
  • Samples obtained from rectal swabs, perirectal swabs, stool sample, areas of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions breakdown, and draining wounds
  • Healthcare workers may spread infection to other individuals: Appropriate isolation and contact measures are instituted with positive cultures Cultures Klebsiella.
• Environmental cleaning

Extended Spectrum Beta-Lactamase (ESBL)

ESBL ESBL Klebsiella

• Beta-lactamases or enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes expressed in organisms resistant to penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins, cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins, and aztreonam Aztreonam The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam (a monobactam)
• Beta-lactamases open the beta-lactam ring Beta-Lactam Ring Penicillins, leading to antibiotic activation.
• Generally found in gram-negative organisms, predominantly in:
  • Klebsiella pneumoniae Klebsiella Pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Aminoglycosides
  • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella oxytoca
  • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
  • Proteus Proteus Proteus spp. are gram-negative, facultatively anaerobic bacilli. Different types of infection result from Proteus, but the urinary tract is the most common site. The majority of cases are caused by Proteus mirabilis (P. mirabilis). The bacteria are part of the normal intestinal flora and are also found in the environment. Proteus mirabilis
• Mechanism of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
  • Production of beta-lactamase Beta-Lactamase Penicillins enzyme leads to resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to most beta-lactam Beta-Lactam Penicillins antibiotics.
  • ESBLs have different varieties:
    • TEM beta-lactamases: Amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids substitutions produce enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, which hydrolyze penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins and narrow-spectrum cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins.
    • SHV beta-lactamases: amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids substitutions
    • CTX-M beta-lactamases: arise from plasmid acquisition of beta-lactamase Beta-Lactamase Penicillins genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure
• Risk factors:
  • Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Residence in a long-term care facility
  • Hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome use
  • Presence of an intravascular catheter
  • Recent antibiotic therapy
  • Use of corticosteroids Corticosteroids Chorioretinitis
  • Presence of a percutaneous feeding tube

Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and antibiotics

• Common infection types:
  • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
  • UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs)
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
• Antibiotic options:
  • Carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam:
    • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam
    • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam
    • Doripenem Doripenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of infections such as hospital-acquired pneumonia, and complicated intra-abdominal or urinary-tract infections, including pyelonephritis. Carbapenems and Aztreonam
    • Ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam
  • Combination cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins– beta-lactamase Beta-Lactamase Penicillins inhibitor agents:
    • Ceftolozane-tazobactam
    • Ceftazidime-avibactam
  • Piperacillin-tazobactam (for isolated UTIs)
  • Fosfomycin and nitrofurantoin (for simple cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary tract infections (UTIs))

Prevention

• Contact precautions
• Antibiotic restrictions ( beta-lactam Beta-Lactam Penicillins drugs)
• Environmental cleaning

Multidrug Resistant Gram-Negative Bacilli (MDRGNB)

MDRGNB

• Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology resistant to a number of antibiotics include: 
  • Acinetobacter baumannii: 67% resistant to carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam
  • Enterobacter spp: 37% resistant to 3rd or 4th generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
  • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli:
    • 42% resistant to fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
    • 19% resistant to 3rd or 4th generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
    • 2% resistant to carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam
  • Klebsiella pneumoniae Klebsiella Pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Aminoglycosides:
    • 29% resistant to 3rd or 4th generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
    • 13% resistant to carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam 
  • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa:
    • 31% resistant to fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
    • 26% resistant to 3rd or 4th generation cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
    • 26% resistant to carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam
• Mechanisms of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing: 
  • Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology have innate resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (exhibit no response to vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides due to the inability of the drug to penetrate the outer membrane).
  • Some produce beta-lactamases.
  • Biofilm Biofilm Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an extracellular polymeric substance matrix that is secreted by the microbes. They occur on body surfaces such as teeth (dental deposits); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with dentifrices; disinfectants; anti-infective agents; and anti-fouling agents. Staphylococcus formation (reduces diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis of antimicrobial agent)
  • Resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure (can be transferred between bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology via vectors (e.g., plasmids Plasmids Extrachromosomal, usually circular DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in genetic engineering as cloning vectors. DNA Types and Structure, transposons)):
    • Produce antibiotic-inactivating enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes such as carbapenemases, which leads to carbapenem Carbapenem The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
    • Others downregulate the outer membrane protein OprD (a carbapenem-specific porin), decreasing diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis of the antibiotic.
    • Drug efflux pumps Efflux Pumps Lincosamides are created, which expel antimicrobial agents.
    • Transfer of a 16S rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure methylase gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics from Actinomycetes to Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa confer aminoglycoside resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
• Risk factors include:
  • ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus stay
  • Chronic hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome
  • Transplant recipients
  • Frequent use of certain antibiotics (e.g., broad-spectrum Broad-Spectrum Fluoroquinolones cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins, aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides, carbapenems Carbapenems A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. Carbapenems and Aztreonam, fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones)
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy failure
  • Pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis
  • Albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests < 3 g/dL
  • HIV HIV Anti-HIV Drugs

Carbapenem-Resistant Enterobacterales (CRE)

• Organisms in the order:
  • Are resistant to ≥ 1 carbapenem Carbapenem The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam antibiotic
  • Produce a carbapenemase enzyme ( Klebsiella pneumoniae Klebsiella Pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Aminoglycosides carbapenemases are the most common carbapenemase in the United States)
• Common infection types:
  • VAP
  • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
  • Intra-abdominal abscesses Intra-abdominal abscesses An abscess located in the abdominal cavity, i.e., the cavity between the diaphragm above and the pelvis below. Proteus
  • UTIs (e.g., cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary tract infections (UTIs), pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess)
• Antibiotic options:
  • Treatment is limited, especially for serious infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g., bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides).
  • Resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure for other antibiotics are often present.
  • For infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease resistant to ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam, but susceptible to meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam:
    • Extended infusion meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam can be used.
    • If carbapenemase testing is positive, do not use meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam (even if susceptibility is positive).
  • For uncomplicated cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary tract infections (UTIs):
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones, levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones
    • Trimethoprim-sulfamethoxazole
    • Nitrofurantoin
    • Single-dose aminoglycoside
  • Complicated UTIs and infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease outside the urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy:
    • Ceftazidime-avibactam
    • Meropenem-vaborbactam
    • Imipenem-cilastatin-relebactam
    • Cefiderocol

Difficult-to-treat resistant Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa

• Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa not susceptible to the following: 
  • Piperacillin-tazobactam
  • Ceftazidime Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for pseudomonas and other gram-negative infections in debilitated patients. Cephalosporins, cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins
  • Aztreonam Aztreonam The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam
  • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam, imipenem-cilastatin
  • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones, levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones
• Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • VAP
  • UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs)
  • Device-related infection (e.g., catheter)
  • Wounds or burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns
• Antibiotic options:
  • Ceftolozane-tazobactam
  • Ceftazidime-avibactam
  • Imipenem-cilastatin-relebactam
  • Cefiderocol

Prevention

• Hand hygiene Hand hygiene Practices involved in preventing the transmission of diseases by hand. Surgical Infections
• Isolation precautions
• Antibiotic stewardship
• Environmental cleaning

Central Line-Associated Bloodstream Infection (CLABSI)

CLABSI

• Infection related to the placement or prolonged use of a central venous catheter Central Venous Catheter Central venous catheters are IV lines placed into the large central veins for monitoring of central venous pressure (CVP), prolonged drug administration, or administration of parenteral nutrition. The most common sites of insertion are the internal jugular and subclavian veins. Central Venous Catheter
• Risk factors:
  • Host factors:
    • Chronic illness
    • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow transplantation
    • Immune deficiency (especially neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia)
    • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
    • Total parenteral nutrition Parenteral nutrition The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). Central Venous Catheter administration
    • Previous bloodstream infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Extremes of age
    • Loss of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions integrity (e.g., burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns)
  • Catheter factors:
    • Location of catheter (e.g., subclavian catheter carries less risk)
    • Duration of catheterization
    • Type of catheter (e.g., non-tunneled catheters carry higher risk of infection)
    • Conditions of insertion
    • Catheter site care
    • Skill of operator performing insertion
• Sources of infection:
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions colonization Colonization Bacteriology
  • Intraluminal contamination
  • Hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases seeding Seeding The local implantation of tumor cells by contamination of instruments and surgical equipment during and after surgical resection, resulting in local growth of the cells and tumor formation. Grading, Staging, and Metastasis
  • Infusate contamination
• Common organisms:
  • Coagulase-negative staphylococci Coagulase-negative staphylococci Staphylococcus ( CoNS CoNS Staphylococcus)
  • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
  • Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus
  • Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis spp
  • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella spp
  • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
  • Enterobacter spp
  • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas spp

Antibiotics and management

• Empiric therapy Empiric Therapy Meningitis in Children:
  • Gram-positive Gram-Positive Penicillins organisms: vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
  • Gram-negative bacilli Bacilli Shigella if no hemodynamic instability, neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia, or burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns present: ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins
  • Gram-negative bacilli Bacilli Shigella if hemodynamic instability, neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia, or severe burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns present (use antipseudomonal agents): 
    • Ceftazidime Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for pseudomonas and other gram-negative infections in debilitated patients. Cephalosporins, cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins
    • Piperacillin-tazobactam
    • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam, meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam
• Directed therapy for Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus:
  • Methicillin Methicillin One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection. Penicillins susceptible:
    • Nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS)
    • Oxacillin
    • Cefazolin Cefazolin A semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine. Cephalosporins
    • Flucloxacillin
  • Methicillin Methicillin One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection. Penicillins resistant:
    • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
    • Daptomycin Daptomycin A cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Lipopeptides and Lipoglycopeptides
• Directed therapy for Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus:
  • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins susceptible: ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins
  • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins resistant, vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides susceptible: vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
  • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins resistant, vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides resistant: daptomycin Daptomycin A cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Lipopeptides and Lipoglycopeptides, linezolid Linezolid An oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract. Oxazolidinones
• Enterobacteriaceae Enterobacteriaceae A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock. Cephalosporins (e.g., Escherichia coli, Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella spp, Enterobacter spp):
  • ESBL ESBL Klebsiella negative:
    • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
  • ESBL ESBL Klebsiella positive:
    • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam
    • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam
    • Ertapenem Ertapenem A carbapenem derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of gram-positive and gram-negative bacterial infections including intra-abdominal infections, acute gynecological infections, complicated urinary tract infections, skin infections, and respiratory tract infections. It is also used to prevent infection in colorectal surgery. Carbapenems and Aztreonam
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
• Pseudomonas spp:
  • Preferred:
    • Ceftazidime Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for pseudomonas and other gram-negative infections in debilitated patients. Cephalosporins
    • Cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins
    • Piperacillin-tazobactam
  • Alternative:
    • Imipenem Imipenem Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. Carbapenems and Aztreonam
    • Meropenem Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. Carbapenems and Aztreonam
    • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones
• Catheter management:
  • Remove in the following cases:
    • Hemodynamic instability
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Blood clot or suppurative thrombophlebitis
    • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
    • Subcutaneously tunneled central venous catheter Tunneled Central Venous Catheter Central Venous Catheter tract infection or subcutaneous port reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli infection
    • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides persists even after 72 hours of appropriate antibiotics.
    • Organisms identified: Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus, Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa, MDRGNB, or Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis spp
  • Salvage in the following cases:
    • Uncomplicated infection from CoNS CoNS Staphylococcus
    • Does not generally involve orthopedic hardware or endovascular implant
    • Antibiotic lock therapy (antibiotic instillation in the lumen) with systemic antibiotics given

Prevention

• Handwashing
• Full barrier precautions with insertion of central venous catheter Central Venous Catheter Central venous catheters are IV lines placed into the large central veins for monitoring of central venous pressure (CVP), prolonged drug administration, or administration of parenteral nutrition. The most common sites of insertion are the internal jugular and subclavian veins. Central Venous Catheter
• Chlorhexidine for skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disinfection
• Avoidance of the femoral insertion site 
• Removal of catheters when no longer indicated

Catheter-Associated Urinary Tract Infection (CAUTI)

CAUTI

• A urinary infection related to the use of a urinary catheter (foley catheter)
• Differentiation according to the Infectious Infectious Febrile Infant Diseases Society of America:
  • Symptomatic bacteriuria Bacteriuria The presence of bacteria in the urine which is normally bacteria-free. These bacteria are from the urinary tract and are not contaminants of the surrounding tissues. Bacteriuria can be symptomatic or asymptomatic. Significant bacteriuria is an indicator of urinary tract infection. Urinary Tract Infections (UTIs) in Children ( UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs)): 
    • Culture growth of ≥ 10³ colony forming units (CFU)/mL of uropathogenic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
    • UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs) signs and symptoms without another identifiable source
    • Symptoms can include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, suprapubic or costovertebral angle tenderness, altered mental status Altered Mental Status Sepsis in Children, and hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension.
    • Indwelling urethral, indwelling suprapubic, or intermittent catheterization currently or within 48 hours
  • Asymptomatic bacteriuria Bacteriuria The presence of bacteria in the urine which is normally bacteria-free. These bacteria are from the urinary tract and are not contaminants of the surrounding tissues. Bacteriuria can be symptomatic or asymptomatic. Significant bacteriuria is an indicator of urinary tract infection. Urinary Tract Infections (UTIs) in Children:
    • Culture growth of ≥ 10⁵ CFU/mL of uropathogenic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
    • No UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs) symptoms noted in an individual with indwelling urethral, indwelling suprapubic, or intermittent catheterization
• Risk factors:
  • Longer duration of catheterization
  • Female
  • Older age
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus
  • Drainage bag is colonized by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology.
  • Catheter maintenance problems (i.e., errors in sterile technique Sterile Technique Surgical Infections, not maintaining a closed drainage system)
• Pathogenesis:
  • Extraluminal (more common): Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology enter the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess along the biofilm Biofilm Encrustations formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedded in an extracellular polymeric substance matrix that is secreted by the microbes. They occur on body surfaces such as teeth (dental deposits); inanimate objects, and bodies of water. Biofilms are prevented from forming by treating surfaces with dentifrices; disinfectants; anti-infective agents; and anti-fouling agents. Staphylococcus (forms around the catheter).
  • Intraluminal: drainage failure (promotes urinary stasis or ascending infection Ascending Infection Urinary Tract Infections (UTIs) in Children from a contaminated urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat collection bag)
• Common organisms:
  • Escherichia coli
  • Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis spp
  • Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus spp
  • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa
  • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella spp

Management

• Antimicrobial options:
  • Depend on culture and susceptibility results
  • Require consideration of the following factors:
    • Past urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat cultures Cultures Klebsiella
    • Prior antimicrobial therapy
    • Healthcare exposures
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of antimicrobial resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
    • Antibiotic allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency
• Minimize use of indwelling catheters Indwelling catheters Catheters designed to be left within an organ or passage for an extended period of time. Pseudomonas:
  • Intermittent catheterization carries a lower risk of UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary tract infections (UTIs).
  • If an indwelling catheter Indwelling catheter Catheters designed to be left within an organ or passage for an extended period of time. Urinary tract infections (UTIs) is necessary, replacement is recommended along with the initiation of antibiotics.
• Prevention:
  • Avoid unnecessary catheterization.
  • Use sterile Sterile Basic Procedures techniques while placing the catheter.
  • Remove the catheter as soon as no longer needed.

Nosocomial and Ventilator-Associated Pneumonias (VAPs)

Pneumonias in the hospital

• Definitions:
  • HAP or nosocomial pneumonia Nosocomial pneumonia Pneumonia in Children: lung infection Lung infection Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia occurring ≥ 48 hours after admission and not incubating at the time of admission
  • VAP: pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia developing ≥ 48 hours after endotracheal intubation Intubation Peritonsillar Abscess
• Risk factors:
  • Mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing: Most HAPs occur in individuals not on mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing (mechanically ventilated individuals carry the highest risk of HAP).
  • Older age
  • Chronic lung disease
  • Depressed consciousness
  • Aspiration
  • Chest or upper abdominal surgery
  • Agents that increase gastric pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance
  • Previous antibiotic exposure Exposure ABCDE Assessment (especially broad-spectrum Broad-Spectrum Fluoroquinolones antibiotics)
  • Reintubation or prolonged intubation Intubation Peritonsillar Abscess
  • Increased opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation use
  • Trauma
  • Paralysis
  • Numerous central venous catheter Central Venous Catheter Central venous catheters are IV lines placed into the large central veins for monitoring of central venous pressure (CVP), prolonged drug administration, or administration of parenteral nutrition. The most common sites of insertion are the internal jugular and subclavian veins. Central Venous Catheter placements and surgeries
  • Use of muscle relaxants or glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
  • Presence of an intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension monitor
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
  • Chronic renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
  • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • Previous hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
• Common organisms:
  • Gram-negative bacilli Bacilli Shigella:
    • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
    • Klebsiella pneumoniae Klebsiella Pneumoniae Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans. Aminoglycosides
    • Enterobacter spp
    • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa
    • Acinetobacter spp
• Gram-positive Gram-Positive Penicillins bacilli Bacilli Shigella:
  • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus (including MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus)
  • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus spp

Management

• Antibiotic options:
  • Include coverage for:
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
    • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa
    • Other gram-negative bacilli Bacilli Shigella
  • Consider local pathogens and risks for MDROs.
• Regimen:
  • Individuals with no risk for MDRO and low risk for MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus: 1 agent against Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa, other GNB, and methicillin-sensitive Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus:
    • Piperacillin-tazobactam
    • Cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins
    • Levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones 
  • Individuals at risk for MDRO (including MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus): 2 agents against Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa and other GNB, and 1 agent with activity against MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus:
    • Piperacillin-tazobactam/ cefepime Cefepime A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia. Cephalosporins/ ceftazidime Ceftazidime Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for pseudomonas and other gram-negative infections in debilitated patients. Cephalosporins/ carbapenem Carbapenem The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam/ aztreonam Aztreonam The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam; AND, 
    • An aminoglycoside (e.g., amikacin, gentamicin Gentamicin Aminoglycosides); AND,
    • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides/ linezolid Linezolid An oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract. Oxazolidinones/ telavancin Telavancin Lipopeptides and Lipoglycopeptides
• Prevention:
  • Use of non-invasive positive pressure ventilation Positive pressure ventilation Application of positive pressure to the inspiratory phase when the patient has an artificial airway in place and is connected to a ventilator. Flail Chest when possible (avoiding intubation Intubation Peritonsillar Abscess)
  • Weaning Weaning Techniques for effecting the transition of the respiratory-failure patient from mechanical ventilation to spontaneous ventilation, while meeting the criteria that tidal volume be above a given threshold (greater than 5 ml/kg), respiratory frequency be below a given count (less than 30 breaths/min), and oxygen partial pressure be above a given threshold (pao2 greater than 50mm hg). Weaning studies focus on finding methods to monitor and predict the outcome of mechanical ventilator weaning as well as finding ventilatory support techniques which will facilitate successful weaning. Present methods include intermittent mandatory ventilation, intermittent positive pressure ventilation, and mandatory minute volume ventilation. Invasive Mechanical Ventilation protocols
  • Minimize sedation
  • Facilitate physical conditioning and early mobility Mobility Examination of the Breast
  • Prevent aspiration:
    • Bed elevation
    • Drainage of subglottic secretions
  • Approaches to help lower VAP:
    • Probiotics
    • Oral care (chlorhexidine)
    • Stress ulcer prophylaxis Prophylaxis Cephalosporins
    • Silver-coated endotracheal tubes

Clostridioides difficile Infection (CDI)

CDI

• Infection caused by the spore-forming bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology Clostridioides difficile
• One of the most common hospital-acquired infections Hospital-Acquired Infections Carbapenems and Aztreonam
• Risk factors:
  • Antibiotic use
  • Advanced age
  • Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Severe comorbid illness
• Microbiology and disease:
  • Clostridioides difficile:
    • Anaerobic gram-positive Gram-Positive Penicillins, spore-forming, toxin-producing bacillus Bacillus Bacillus are aerobic, spore-forming, gram-positive bacilli. Two pathogenic species are Bacillus anthracis (B. anthracis) and B. cereus. Bacillus
    • Releases 2 potent exotoxins Exotoxins Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment. Bacteriology that mediate colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea: enterotoxin A Enterotoxin A Clostridia ( diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea) and toxin B ( pseudomembranous colitis Pseudomembranous colitis Pseudomembranous colitis is a bacterial disease of the colon caused by Clostridium difficile. Pseudomembranous colitis is characterized by mucosal inflammation and is acquired due to antimicrobial use and the consequent disruption of the normal colonic microbiota. C. difficile infections account for the most commonly diagnosed hospital-acquired diarrheal illnesses. Pseudomembranous Colitis)
  • Pseudomembranous colitis Pseudomembranous colitis Pseudomembranous colitis is a bacterial disease of the colon caused by Clostridium difficile. Pseudomembranous colitis is characterized by mucosal inflammation and is acquired due to antimicrobial use and the consequent disruption of the normal colonic microbiota. C. difficile infections account for the most commonly diagnosed hospital-acquired diarrheal illnesses. Pseudomembranous Colitis (severe inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the bowel lining):
    • Abdominal pain Abdominal Pain Acute Abdomen
    • Profuse watery diarrhea Watery diarrhea Rotavirus (may occasionally be bloody)
    • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus
    • Associated with recent antibiotic use (e.g., clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides, fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones, cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins, penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins)

Management

• Antibiotic options:
  • Oral fidaxomicin
  • Oral vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides
  • Metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess
• Recurrent CDI: Add bezlotoxumab (monoclonal antibody).
• Discontinue the inciting antibiotic.
• Supportive care: Manage fluid and electrolyte losses.
• Other:
  • Fecal microbiota transplant (FMT):
    • Processed stool from a healthy donor is instilled into the intestinal tract.
    • Administered via oral capsules, colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening, retention enema, or a nasojejunal/nasoduodenal tube
  • Consider surgery in the case of fulminant disease (i.e., hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock, ileus Ileus A condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced. Small Bowel Obstruction, or megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon).
• Prevention:
  • Infection control:
    • Hand hygiene Hand hygiene Practices involved in preventing the transmission of diseases by hand. Surgical Infections
    • Use soap and water rather than alcohol-based hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy sanitizer (Clostridioides difficile spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax are resistant to alcohol).
  • Minimize antibiotic use.
  • Oral vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides prophylaxis Prophylaxis Cephalosporins for individuals at high risk for CDI

Surgical Site Infections (SSIs)

SSIs

• An infection in the area of a recent surgery 
• 38% of nosocomial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Risk factors:
  • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Older age
  • Vascular disease
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Immunosuppressive therapy
  • Presence of recent or remote infection at the surgical site
  • Recent surgery
  • Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Transfusion
  • Local wound factors:
    • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Proximity to other open or contaminated wound sites
    • Presence of remote infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease 
• Microbiology and disease:
  • Common organisms:
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and mucosal surfaces: gram-positive Gram-Positive Penicillins bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology (e.g., Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus, CoNS CoNS Staphylococcus).
    • Groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination and inguinal areas can be contaminated by gram-negative bacilli Bacilli Shigella and anaerobic organisms. 
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease can be:
    • Superficial (e.g., swelling Swelling Inflammation, warmth, discharge): determined by observation
    • Deeper (e.g., fascia Fascia Layers of connective tissue of variable thickness. The superficial fascia is found immediately below the skin; the deep fascia invests muscles, nerves, and other organs. Cellulitis, muscle, or organ involvement): Imaging and exploration are needed.

Management

• Drainage of infected fluid
• Exploration and debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome if necessary (especially in necrotic tissue)
• Antibiotic therapy:
  • Consider the extent of infection, comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus, and systemic manifestations.
  • Use for deep infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (not always necessary for superficial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease).
  • Generally guided by culture and sensitivities: Empiric selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions is based on initial Gram stain Gram stain Klebsiella, wound site, and type.
  • The most common organisms to cover:
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus
    • CoNS CoNS Staphylococcus
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus spp
    • Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus spp 
• Prevention:
  • Patient:
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
    • Bowel preparation before colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy surgery
  • Infection control:
    • Hand hygiene Hand hygiene Practices involved in preventing the transmission of diseases by hand. Surgical Infections
    • Surgical attire and barrier devices
    • Antimicrobial prophylaxis Prophylaxis Cephalosporins
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus decolonization
    • Application of antiseptics to the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
    • Hair removal: Avoid shaving with razors at the planned operative site.
  • Other perioperative measures:
    • Maintain normothermia.
    • Limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation people and entry into the operating room.
    • Use of laminar airflow
    • Supplemental oxygen Supplemental Oxygen Respiratory Failure
    • Minimize red cell transfusion.
    • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance control
    • Topical and local antibiotic delivery
    • Intraoperative wound protectors
  • Prophylactic negative pressure wound therapy

Clinical Relevance

• Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease: a wide spectrum of diseases from simple cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary tract infections (UTIs) (self-limited) to severe pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess. Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are most commonly caused by Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli. Features include dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs), urinary urgency Urinary Urgency Normal Pressure Hydrocephalus, frequency, suprapubic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children and culture are used to establish the diagnosis. Management is with antibiotics (e.g., trimethoprim-sulfamethoxazole, nitrofurantoin, ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins). Further workup may be needed if no resolution.
• Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia: infection of the lung parenchyma most commonly caused by a bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology or virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology. Community-acquired pneumonia Community-Acquired Pneumonia Pneumonia in Children (CAP) accounts for 80% of cases. If the infection is acquired while admitted to a healthcare facility, the infection is termed a healthcare-associated pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia (HCAP). The diagnosis is based on a clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, productive cough, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, rales Rales Respiratory Syncytial Virus, and consolidation Consolidation Pulmonary Function Tests on chest X-ray Chest X-ray X-ray visualization of the chest and organs of the thoracic cavity. It is not restricted to visualization of the lungs. Pulmonary Function Tests. Atypical pneumonia Atypical pneumonia Mycoplasma may present with milder symptoms and less remarkable imaging. Empiric antibiotic treatment is generally appropriate for CAP, while pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia in the ventilated patient often requires culture-based therapy. 
• Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock: organ dysfunction resulting from a dysregulated systemic host response to infection. Etiology is mainly bacterial with pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia as the most common source. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship commonly present with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, and/or altered mentation. Septic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock is diagnosed during treatment when vasopressors Vasopressors Sepsis in Children are necessary to control hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension. Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock and septic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock are medical emergencies and antibiotics are given within 1 hour of diagnosis.