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Carbapenems and Aztreonam

The carbapenems and aztreonam are both members of the bactericidal Bactericidal Penicillins beta-lactam Beta-Lactam Penicillins family of antibiotics (similar 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). They work by preventing 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 from producing their 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, ultimately leading to bacterial cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death. There are 4 available carbapenems, all ending in “-penem,” and 1 available monobactam, which is aztreonam. The carbapenems are all broad-spectrum Broad-Spectrum Fluoroquinolones antibiotics used for a variety of serious, often MDR and/or hospital-acquired 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 (HAIs) that can occur throughout the body. Aztreonam has a narrower spectrum and is typically used for aerobic gram-negative bacilli Bacilli Shigella 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 patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have a serious beta-lactam Beta-Lactam Penicillins allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction but require beta-lactam Beta-Lactam Penicillins therapy, as there is no significant cross-allergenicity between aztreonam and the other beta-lactams.

Last updated: Mar 22, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Chemistry and Classification

Beta-lactam Beta-Lactam Penicillins classification

Carbapenems and monobactams are both members of the beta-lactam Beta-Lactam Penicillins family of antibiotics. They are all cell-wall synthesis Synthesis Polymerase Chain Reaction (PCR) inhibitors. Members of the beta-lactam Beta-Lactam Penicillins family include:

  • 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
  • Carbapenems:
    • Imipenem
    • Doripenem
    • Meropenem
    • Ertapenem
  • Monobactams: 
    • Aztreonam

Carbapenem structure

Carbapenems consist of:

  • A beta-lactam Beta-Lactam Penicillins ring: a 4-member ring containing 2 carbons (the α and β carbons), a nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle, and a carbonyl group (carbon double-bonded to oxygen)
    • The antibacterial Antibacterial Penicillins portion of the structure
    • Can be hydrolyzed (i.e., broken) by beta-lactamases, which are produced by certain 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
    • If this ring is broken, the medication loses its antibacterial Antibacterial Penicillins properties.
    • All beta-lactams contain a beta-lactam Beta-Lactam Penicillins ring.
  • A side chain known as the R group: 
  • A 5-member amide ring with a second R group
Structure of beta-lactams

Structure of beta-lactams:
All beta-lactam Beta-Lactam Penicillins antibiotics contain the same core 4-member “ beta-lactam Beta-Lactam Penicillins” ring (highlighted in red). This ring is responsible for the antibacterial Antibacterial Penicillins properties of these medications because it is the region that binds to and inhibits the penicillin-binding proteins Penicillin-Binding Proteins Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins ( PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins). The PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins catalyze formation of the 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 by forming cross-links between peptide chains in peptidoglycan Peptidoglycan Penicillins molecules; the PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins form these cross-links between acyl-D-Ala-D-Ala peptides, which have a similar structure to the beta-lactam Beta-Lactam Penicillins ring.

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Monobactam structure

Monobactams are also beta-lactam Beta-Lactam Penicillins antibiotics. Their structure is different enough from penicillin Penicillin Rheumatic Fever that there is no cross-allergy with 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. Azetreonam is the only marketed monobactam. Monobactam structures include:

Structure of aztreonam carbapenems and aztreonam

Structure of aztreonam, the only marketed monobactam in the United States

Image: “Chemical structure of aztreonam” by Mysid. License: Public Domain

Mechanisms of Action and Resistance

All beta-lactams, including carbapenems and monobactams, work by inhibiting 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).

Background: Understanding Understanding Decision-making Capacity and Legal Competence cell walls

  • Bacterial cell walls contain peptidoglycan Peptidoglycan Penicillins chains (large, thick layers in gram-positive Gram-Positive Penicillins organisms, and relatively smaller/thinner layers in gram-negative organisms)
  • The peptidoglycan Peptidoglycan Penicillins chains are made up of:
    • A sugar backbone with 2 alternating sugars: 
    • Short peptide side chains off the NAM sugars
  • These short peptides form cross-linked bridges between adjacent peptidoglycan Peptidoglycan Penicillins chains, creating a fishnet-like structure.
    • These bridges are necessary for the peptidoglycan Peptidoglycan Penicillins (and thus 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) structure.
    • PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins are the 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 that create these cross-linked bridges.
Structure of bacterial cell walls cephalosporins

Structure of bacterial cell walls

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Mechanism of action

All beta-lactams work by irreversibly binding to and inhibiting the PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins beta-lactam Beta-Lactam Penicillins antibiotics inhibit 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)

Bactericidal Bactericidal Penicillins activity

Beta-lactams, including the carbapenems and monobactams, are bactericidal Bactericidal Penicillins (rather than bacteriostatic Bacteriostatic Sulfonamides and Trimethoprim). 

  • The 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 is necessary for its survival → without it, cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death is initiated
  • When 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 attempt to replicate, they shed their cell walls.
  • In the presence of beta-lactams, however, they are unable to form new cell walls.
  • The 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 are unable to effectively divide, and the remaining cell autocatalyzes and dies.
Bacteria attempting to divide in the presence of penicillin

Bacterium attempting to divide in the presence of penicillin Penicillin Rheumatic Fever:
The bacterium ends up shedding its wall and becoming a spheroplast. The spheroplast is unable to survive and autocatalyzes (dies).

Image by Lecturio. License: CC BY-NC-SA 4.0

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

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 employ 3 primary mechanisms to resist beta-lactams:

  • Beta-lactamase resistance Beta-Lactamase Resistance Penicillins
    • Beta-lactamase Beta-Lactamase Penicillins is an enzyme that cleaves the beta-lactam Beta-Lactam Penicillins ring and inactivates the antibiotic.
    • Most common type 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
    • Although most carbapenems and monobactams are resistant to beta-lactamases, there is increasing 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, especially among gram-negative organisms.
    • Carbapenemases are beta-lactamases that can hydrolyze carbapenems and other beta-lactam Beta-Lactam Penicillins antibiotics (e.g., penicillin Penicillin Rheumatic Fever, 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).
  • PBP-mediated resistance Pbp-Mediated Resistance Penicillins (↓ binding to PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins)
    • Mutations in the PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins → result in ↓ affinity of the beta-lactams to the PBP 
    • Despite the mutations, these PBPs PBPs Bacterial proteins that share the property of binding irreversibly to penicillins and other antibacterial agents derived from lactams. The penicillin-binding proteins are primarily enzymes involved in cell wall biosynthesis including muramoylpentapeptide carboxypeptidase; peptide synthases; transpeptidases; and hexosyltransferases. Penicillins are still able to produce a 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.
  • ↓ Membrane permeability 
    • Carbapenems enter cells through specialized channels Channels The Cell: Cell Membrane
      • Evidence suggests carbapenems do not use the porin channels Channels The Cell: Cell Membrane used by other beta-lactams; they use a different channel.
      • Although less common, this channel can be altered to ↓ carbapenem permeability
    • ↓ Permeability → ↓ antibiotic within the cell → antibiotic 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
    • A common 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 against carbapenems in Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas

Mechanism of imipenem degradation

  • Renal dehydropeptidase: a different type of enzyme produced by the kidney, which is capable of inactivating imipenem
  • Cilastatin is a dehydropeptidase inhibitor and is always given in combination with imipenem.

Beta-lactamase inhibitors Beta-Lactamase Inhibitors Endogenous substances and drugs that inhibit or block the activity of beta-lactamases. Cephalosporins

Due to the increasing problem 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 from beta-lactamases, beta-lactamase inhibitors Beta-Lactamase Inhibitors Endogenous substances and drugs that inhibit or block the activity of beta-lactamases. Cephalosporins have been developed and are often combined with different beta-lactam Beta-Lactam Penicillins antibiotics. Available carbapenem and monobactam/ beta-lactamase Beta-Lactamase Penicillins inhibitor combinations include:

Carbapenems

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

  • Distribution: penetrates well into all bodily fluids and tissues, including the peritoneal fluid, pulmonary fluid, 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, bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy, and 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
  • Protein binding: 
    • < 20%: meropenem, imipenem, doripenem
    • > 85%: ertapenem
  • Metabolism:
    • Imipenem:
      • Metabolized in the proximal renal tubule by renal dehydropeptidase
      • To prolong drug activity, imipenem is combined with cilastatin, a dehydropeptidase inhibitor.
    • Others: 
      • Stable against renal dehydropeptidase I, so can be administered without cilastatin
      • Hepatic hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides of the beta-lactam Beta-Lactam Penicillins ring to inactive metabolites
  • Half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics:
    • Ertapenem: approximately 4 hours → once daily dosing
    • Others: 1–2 hours; require more frequent dosing
  • Excretion: 
    • Primarily in the 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 as unchanged drug
    • Some have very small levels of fecal excretion.

Indications

  • Considered to be very broad-spectrum Broad-Spectrum Fluoroquinolones antibiotics with activity against:
    • Gram-positive Gram-Positive Penicillins organisms:
      • 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.
      • 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 (not active 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)
      • 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 faecalis
      • Listeria Listeria Listeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes/Listeriosis spp.
    • Most 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
      • 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 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 
      • 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
      • Serratia Serratia A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the natural environment (soil, water, and plant surfaces) or as an opportunistic human pathogen. Acute Cholangitis 
      • Enterobacter Enterobacter Multidrug-resistant Organisms and Nosocomial Infections
      • Citrobacter Citrobacter Multidrug-resistant Organisms and Nosocomial Infections 
    • Beta-lactamase-producing H. influenzae H. influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. Haemophilus and N. gonorrhoeae N. gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria
    • Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas
    • Anaerobes Anaerobes Lincosamides:
      • Bacteroides Bacteroides Bacteroides is a genus of opportunistic, anaerobic, gram-negative bacilli. Bacteroides fragilis is the most common species involved in human disease and is part of the normal flora of the large intestine. Bacteroides
      • Fusobacterium Fusobacterium A genus of gram-negative, anaerobic, rod-shaped bacteria found in cavities of humans and other animals. No endospores are formed. Some species are pathogenic and occur in various purulent or gangrenous infections. Dog and Cat Bites
      • Clostridium 
      • Peptostreptococcus Peptostreptococcus A genus of gram-positive, anaerobic, coccoid bacteria that is part of the normal flora of humans. Its organisms are opportunistic pathogens causing bacteremias and soft tissue infections. Perianal and Perirectal Abscess
  • Typically reserved for:
    • Serious and/or life-threatening 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 
    • MDR 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
    • Hospital-acquired 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 (HAIs)
  • Common clinical uses include:
    • Severe intra-abdominal and pelvic 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., ruptured appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. Appendicitis, septic abortions)
    • Complicated 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 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
    • Bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis
    • Intracranial and spinal abscesses
    • 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
    • Complicated and/or healthcare-associated pneumonia Healthcare-associated pneumonia Infection of the lung often accompanied by inflammation that is acquired through an interaction within a healthcare institution often through a therapeutic experience (e.g., use of catheters or ventilators). Pneumonia (HCAP)
    • Complicated urinary tract infections Urinary tract infections 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) (UTIs)
    • 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
    • Neutropenic 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
  • The carbapenems cross the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity but generally are considered safe in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care if they are otherwise thought to be required.

Adverse effects

  • CNS toxicity Toxicity Dosage Calculation (especially in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with underlying CNS disease or impaired renal function):
    • Mental status changes
    • Myoclonus Myoclonus Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous system diseases; (e.g., epilepsy-myoclonic). Nocturnal myoclonus is the principal feature of the nocturnal myoclonus syndrome. Neurological Examination
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures (especially imipenem)
  • Hematologic effects:
    • 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
    • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • GI upset
  • ↑ Serum transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis
  • Rash Rash Rocky Mountain Spotted Fever
  • Superinfection:
    • Fungal 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
    • Clostridioides difficile/pseudomembranous 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

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

  • Beta-lactam Beta-Lactam Penicillins 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
  • Use in caution with patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have:
    • Underlying CNS disease
    • Impaired renal function
  • Imipenem is contraindicated in pediatric CNS 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 due to seizure potential.

Monobactams: Aztreonam

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

  • Distributed widely in body tissues, CSF, bronchial secretions, peritoneal fluid, bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy, and 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
  • Protein binding: approximately 50%
  • Metabolism: 
    • Minor hepatic metabolism
    • Not degraded by certain types of beta-lactamases
  • Half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics: 1–2 hours with normal renal function
  • Excretion:
    • 60%–70% in the 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 as unchanged drug
    • Approximately 10% in feces

Indications

  • Narrower spectrum than carbapenems
  • Typically used for aerobic gram-negative rod 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 patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with serious beta-lactam Beta-Lactam Penicillins 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 who require beta-lactam Beta-Lactam Penicillins therapy:
    • Lower respiratory tract 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 (LRTIs)
    • UTIs
    • 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 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
    • Intra-abdominal and pelvic 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
    • Bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis
  • Have activity against:
    • 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 that do not produce beta-lactamase Beta-Lactamase Penicillins
    • Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas
  • Not active against:
  • Synergistic with 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

Adverse effects

  • ↑ Serum transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis
  • 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 in children
  • Rash Rash Rocky Mountain Spotted Fever
  • GI upset
  • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo, headaches
  • Superinfection

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

  • Allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction to aztreonam
  • Cross-allergenicity with other beta-lactams is extremely rare, though possible.

Comparison of Antibiotic Coverage

Comparison based on mechanisms of action

Antibiotics can be classified in several ways. One way is to classify them by mechanism of action:

Table: Antibiotics classified by primary mechanism of action
Mechanism Classes of antibiotics
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) inhibitors
  • 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
  • Penems
  • Miscellaneous
Bacterial protein synthesis Synthesis Polymerase Chain Reaction (PCR) inhibitors
  • 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
  • Macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides
  • Ketolide
  • Lincosamides Lincosamides The lincosamides, lincomycin and clindamycin, are inhibitors of bacterial protein synthesis. Drugs in this class share the same binding site as that of macrolides and amphenicols; however, they differ in chemical structure. Lincosamides target the 50S ribosomal subunit and interfere with transpeptidation. Lincosamides
  • Streptogramins
  • 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
Agents acting against DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure and/or folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12
  • Sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim
  • 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
  • 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
Antimycobacterial agents Antimycobacterial Agents Antimycobacterial agents represent a diverse group of compounds that have activity against mycobacterial infections, including tuberculosis, leprosy and Mycobacterium avium complex (MAC) disease. The 1st-line agents for tuberculosis are rifampin, isoniazid, pyrazinamide, and ethambutol. Antimycobacterial Drugs
  • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis agents
  • Leprosy Leprosy Leprosy, also known as Hansen’s disease, is a chronic bacterial infection caused by Mycobacterium leprae complex bacteria. Symptoms primarily affect the skin and peripheral nerves, resulting in cutaneous manifestations (e.g., hypopigmented macules) and neurologic manifestations (e.g., loss of sensation). Leprosy agents
  • Atypical mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium agents

Comparison based on coverage

Different antibiotics have varying degrees of activity against different 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. The table below outlines which antibiotics have activity against 3 important classes of 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, including gram-positive Gram-Positive Penicillins cocci Cocci Bacteriology, gram-negative bacilli Bacilli Shigella, and anaerobes Anaerobes Lincosamides.

Antibiotic sensitivity chart

Antibiotic sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques:
Chart comparing the microbial coverage of different antibiotics for gram-positive Gram-Positive Penicillins cocci Cocci Bacteriology, gram-negative bacilli Bacilli Shigella, and anaerobes Anaerobes Lincosamides.

Image by Lecturio. License: CC BY-NC-SA 4.0

References

  1. McCormack, J, Lalji, F. (2019). The “best” antibiotic sensitivity chart. Retrieved July 12, 2021, from https://therapeuticseducation.org/sites/therapeuticseducation.org/files/Antibiotic_Sensitivity_FINAL_Nov_2019.pdf 
  2. Letourneau, AR. (2019). Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects. In Bloom, A. (Ed.), Uptodate. Retrieved May 20, 2021, from https://www.uptodate.com/contents/beta-lactam-antibiotics-mechanisms-of-action-and-resistance-and-adverse-effects
  3. Letourneau, AR. (2019).  Combination beta-lactamase inhibitors, carbapenems, and monobactams. In Bloom, A. (Ed.), Uptodate. Retrieved July 12, 2021, from https://www.uptodate.com/contents/combination-beta-lactamase-inhibitors-carbapenems-and-monobactams 
  4. Pandey, N. (2021). Beta Lactam Antibiotics. StatPearls. Retrieved July 12, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/18243/ 
  5. Werth, BJ. (2020). Carbapenems. Merck Manual. Retrieved July 12, 2021, from https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/carbapenems 
  6. Werth, BJ. (2020). Monobactams. Merck Manual. Retrieved July 12, 2021, from https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/monobactams?query=aztreonam 
  7. Lexicomp, Inc. (2021). Drug Information Sheets, UpToDate, Retrieved July 12, 2021, from:

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