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Proteus

Proteus

Proteus spp. are gram-negative, facultatively anaerobic bacilli Bacilli Shigella. Different types of infection result from Proteus, but 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 is the most common site. The majority of cases are caused by Proteus mirabilis (P. mirabilis). 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 part of the normal intestinal flora and are also found in the environment. Proteus spp. exhibit a characteristic swarming motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility and strong urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis activity, which enable initiation of infection. Hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides of urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle by urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis leads to alkaline 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 with an ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance-like odor. With the elevated pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance 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, struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis renal stones form, which eventually can cause obstruction and 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. Treatment is with antibiotics (e.g., 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) for the infection and surgical removal of the stones, if present.

Last updated: 10 Mar, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Classification

Gram negative bacteria classification flowchart

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:
Most 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 can be classified according to a lab procedure called Gram staining Gram staining Bacteriology.
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 with cell walls that have a thin layer of peptidoglycan Peptidoglycan Penicillins do not retain the crystal violet stain utilized in Gram staining Gram staining Bacteriology. These 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 do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative Gram negative Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Yersinia spp./Yersiniosis. These 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 can be further classified according to morphology (diplococci, curved rods, bacilli Bacilli Shigella, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). 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 can be more narrowly identified by growing them on specific media ( triple sugar iron Triple sugar iron Shigella ( TSI TSI Shigella) agar) where their 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 can be identified ( urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis, oxidase Oxidase Neisseria) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain Gram stain Klebsiella
** Pleomorphic Pleomorphic Bacteroides rod/coccobacillus
*** Require special transport media

Image by Lecturio.

General Characteristics

Proteus spp.

  • Structure: bacilli Bacilli Shigella
  • Gram stain Gram stain Klebsiella: gram negative Gram negative Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Yersinia spp./Yersiniosis
  • Oxygen requirement: facultative anaerobic
  • Lactose fermentation: Non-lactose fermenting
  • 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 or biochemical test(s):
    • Oxidase Oxidase Neisseria negative
    • Strong urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis activity
    • Indole: positive in Proteus vulgaris (P. vulgaris); negative in P. mirabilis
  • Swarming motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility (organism’s motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility has a spreading effect over the blood agar Blood agar Nocardia/Nocardiosis plate) 
  • Produce H2S ( hydrogen sulfide Hydrogen sulfide A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. Salmonella) on triple sugar iron Triple sugar iron Shigella ( TSI TSI Shigella) agar
  • Associated diseases:
    • 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 ( 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))
    • Soft tissue Soft Tissue Soft Tissue Abscess infection
    • Intra-abdominal infection

Clinically relevant species

  • P. mirabilis 
  • P. vulgaris

Epidemiology

  • P. mirabilis: etiology for 90% of Proteus 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, most commonly 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)
  • Proteus 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):
    • 5% of hospital-acquired UTIs 
    • 10%–15% of complicated 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 (especially catheter-associated 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)) 
  • P. mirabilis 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 acquired in the community, while the rest are mostly from hospitals and long-term care facilities.

Related videos

3:59
Proteus Mirabilis

Pathogenesis

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 and transmission

  • 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:
    • Normal flora of the human intestinal tract
    • Environment (soil and water)
  • Transmission: spread to 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 via fecal contamination

Virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus

  • Fimbriae Fimbriae Thin, hairlike appendages, 1 to 20 microns in length and often occurring in large numbers, present on the cells of gram-negative bacteria, particularly enterobacteriaceae and Neisseria. Unlike flagella, they do not possess motility, but being protein (pilin) in nature, they possess antigenic and hemagglutinating properties. They are of medical importance because some fimbriae mediate the attachment of bacteria to cells via adhesins. Bacterial fimbriae refer to common pili, to be distinguished from the preferred use of ‘pili’. Escherichia coli or pili Pili Filamentous or elongated proteinaceous structures which extend from the cell surface in gram-negative bacteria that contain certain types of conjugative plasmid. These pili are the organs associated with genetic transfer and have essential roles in conjugation. Normally, only one or a few pili occur on a given donor cell. This preferred use of ‘pili’ refers to the sexual appendage, to be distinguished from bacterial fimbriae, also known as common pili, which are usually concerned with adhesion. Salmonella:
    • Surface projections that enable attachment Attachment The binding of virus particles to virus receptors on the host cell surface, facilitating virus entry into the cell. Virology to host tissue
    • Initiates release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of interleukins Interleukins Interleukins are a type of cytokines (signaling proteins) that communicate messages between different parts of the immune system. The majority of interleukins are synthesized by helper CD4 T lymphocytes along with other cells such as monocytes, macrophages, and endothelial cells. Interleukins
  • Motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility of Proteus (“swarm cell differentiation”):
    • Long flagella Flagella A whiplike motility appendage present on the surface cells. Prokaryote flagella are composed of a protein called flagellin. Bacteria can have a single flagellum, a tuft at one pole, or multiple flagella covering the entire surface. In eukaryotes, flagella are threadlike protoplasmic extensions used to propel flagellates and sperm. Flagella have the same basic structure as cilia but are longer in proportion to the cell bearing them and present in much smaller numbers. Helicobacter forms
    • Facilitates invasion of 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
  • Urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis: 
    • Results in hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides of urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle, releasing ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance
    • 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 becomes alkaline, which leads to the formation of:
      • Struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis ( magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes ammonium phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes) and carbonate–apatite crystals
      • Biofilms on catheters
      • Calculi/stones
  • Endotoxin:
    • Component 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
    • On invasion of the bloodstream, triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) an inflammatory response in 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

Disease process

  • 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) and renal stones:
    • Risk factors for infection: 
      • Colonization Colonization Bacteriology of the vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy
      • Urinary catheters
      • 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 abnormalities (strictures, valves, and stones)
    • Persistent infection → ↑ ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance production → stone formation
    • Staghorn calculi develop in the renal pelvis Renal pelvis Kidneys: Anatomy → obstruction → 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
    • Calculi also serve as the nidus for recurrent infections Recurrent infections Common Variable Immunodeficiency (CVID).
  • Other 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:
    • 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 developing commonly from a 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)
    • Surgical site/ soft tissue Soft Tissue Soft Tissue Abscess infection (decubitus and diabetic ulcers) and 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 (from a contiguous site)
    • 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 long-term care and hospital settings)
    • Intra-abdominal abscesses
    • Neonatal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis (often coming from the umbilicus)
Pathogenesis of proteus infection

Pathogenesis of Proteus infection
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 increase 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 pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance by enhancing urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis activity. Urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis metabolizes urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle into ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance and carbon dioxide. These byproducts increase the pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance of 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, predisposing the patient to struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis stone formation. The stone and bacterial infection lead to uroepithelial damage.

Image by Lecturio.

Clinical Presentation

  • 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:
    • 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 may have an ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance-like odor.
    • Dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs), pyuria Pyuria The presence of white blood cells (leukocytes) in the urine. It is often associated with bacterial infections of the urinary tract. Pyuria without bacteriuria can be caused by tuberculosis, stones, or cancer. Urinary tract infections (UTIs), suprapubic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and urinary frequency
    • If with 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, symptoms may 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, flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Renal calculi Renal calculi Stones in the kidney, usually formed in the urine-collecting area of the kidney (kidney pelvis). Their sizes vary and most contains calcium oxalate. Imaging of the Urinary System: 
    • Small stones may be asymptomatic.
    • 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, flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma, hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma in stones complicated with 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:
    • 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, chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, abdominal/ flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma with 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
    • 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, 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 in severe cases
  • 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: open wound(s) or ulcers, signs of 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

Diagnosis and Management

Diagnosis

  • Specimen dictated by localization of disease:
  • Gram-stained smear and culture:
    • “Swarming” (spreading) effect over the blood agar Blood agar Nocardia/Nocardiosis plate 
    • Non–lactose-fermenting colonies on eosin–methylene blue (EMB) or MacConkey’s agar 
    • Production of H2S on TSI TSI Shigella agar
  • Other laboratory studies:
    • 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: 
      • Alkaline 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
      • Positive leukocyte esterase Leukocyte esterase Kidney Function Tests, nitrite Nitrite Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrates of the type mno2 (where m=metal) are all insoluble, except the alkali nitrites. The organic nitrites may be isomeric, but not identical with the corresponding nitro compounds. Kidney Function Tests 
      • Microscopic 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
      • Pyuria Pyuria The presence of white blood cells (leukocytes) in the urine. It is often associated with bacterial infections of the urinary tract. Pyuria without bacteriuria can be caused by tuberculosis, stones, or cancer. Urinary tract infections (UTIs)
    • Complete blood count: may show leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus
    • Creatinine: abnormal in chronic obstruction, causing 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
  • Imaging studies:
    • Abdominal X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests: shows renal stones
    • Ultrasound and computed tomography (CT) scan: 
      • Detects stones and renal changes (e.g., abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease, hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis)
      • Obtained if the infection does not respond to initial treatment
  • Proteus mirabili swarm

    Proteus mirabilis: culture illustrating the swarming phenomenon

    Image: “ProteusMirabilis Schwärmen” by the CDC. License: Public domain.
  • Staghorn calculi from proteus infection

    Staghorn calculi from a Proteus infection
    A: abdominal X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests showing bilateral complete staghorn calculi
    B: part of the staghorn calculi extracted via open surgery

    Image: “A middle-aged woman with bilateral staghorn complete calculi” by El Anzaoui J, Touiti D. License: CC BY 2.0.

Treatment

  • Antibiotics for the infection:
    • Proteus spp.: naturally resistant to nitrofurantoin
    • Options:
      • 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, quinolone, cephalosporin Cephalosporin Multidrug-resistant Organisms and Nosocomial Infections
      • Broad coverage and longer course of treatment in complicated 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)
    • Adjust regimen based on susceptibility testing.
  • Surgical management for renal stones:
    • Struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis renal stones from a Proteus infection must be removed. 
    • Prevents severe clinical outcomes (e.g., 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) 
    • Eliminates sources of recurrent infection

Comparison with UTI-associated bacteria

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 (E. coli) and Proteus spp. are common etiologies of 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.

Table: Different factors of Proteus spp. versus E. coli
Proteus spp. E. coli
Characteristics Gram-negative bacilli Bacilli Shigella Gram-negative bacilli Bacilli Shigella
Habitat Intestinal tract Intestinal tract
Lactose fermentation Non-lactose fermenting Lactose fermenting
Indole P. mirabilis: negative P. vulgaris: positive Positive
TSI TSI Shigella agar Produce H2S Does not produce H2S
Infection 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) Most common cause 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)

Clinical Relevance

  • Acute pyelonephritis Acute pyelonephritis Inflammation of the kidney involving the renal parenchyma (the nephrons); kidney pelvis; and kidney calices. It is characterized by abdominal pain; fever; nausea; vomiting; and occasionally diarrhea. Imaging of the Urinary System: infection of the renal pelvis Renal pelvis Kidneys: Anatomy with the involvement of the renal parenchyma. Ascending infection Ascending Infection Urinary Tract Infections (UTIs) in Children with E. coli is by far the most common cause, but Proteus spp. 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) can also lead to 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. Typical symptoms are flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma, 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, and chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever with dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs). Management is with antibiotics.
  • Xanthogranulomatous Xanthogranulomatous A chronic inflammatory condition of the kidney resulting in diffuse renal destruction, a grossly enlarged and nonfunctioning kidney associated with nephrolithiasis and kidney stones. Pyelonephritis and Perinephric Abscess 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: chronic 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 that develops commonly from renal obstruction due to infected stones. Xanthogranulomatous Xanthogranulomatous A chronic inflammatory condition of the kidney resulting in diffuse renal destruction, a grossly enlarged and nonfunctioning kidney associated with nephrolithiasis and kidney stones. Pyelonephritis and Perinephric Abscess 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 is associated with granulomatous tissue with lipid-laden macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, which destroy the affected kidney, and can occur in Proteus infection as well as in infection with other 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)-causing 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.
  • Acute prostatitis Prostatitis Prostatitis is inflammation or an irritative condition of the prostate that presents as different syndromes: acute bacterial, chronic bacterial, chronic prostatitis/chronic pelvic pain, and asymptomatic. Bacterial prostatitis is easier to identify clinically and the management (antibiotics) is better established. Prostatitis: infection of the prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate, Seminal, and Bulbourethral Glands: Anatomy gland. 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 and Proteus spp. are among the causative agents. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have 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, chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs), perineal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and, in severe cases, urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium. Digital rectal examination Digital Rectal Examination A physical examination in which the qualified health care worker inserts a lubricated, gloved finger of one hand into the rectum and may use the other hand to press on the lower abdomen or pelvic area to palpate for abnormalities in the lower rectum, and nearby organs or tissues. The method is commonly used to check the lower rectum, the prostate gland in men, and the uterus and ovaries in women. Prostate Cancer Screening shows a swollen, tender prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate, Seminal, and Bulbourethral Glands: Anatomy and 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 indicates infection. Treatment is with antibiotics.
  • Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis: Proteus infection is associated with struvite Struvite The mineral magnesium ammonium phosphate with the formula NH4mgpo4. It is associated with urea-splitting organisms in a high magnesium, high phosphate, alkaline environment. Accumulation of crystallized struvite is found in the urinary tract as struvite calculi and as scale on sewage system equipment and wastewater pipes. Nephrolithiasis stones, which form in alkaline 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. Other stone compositions include uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis crystals, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes or oxalate crystals, and cystine Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Nephrolithiasis crystals. Most stones contain calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes. Stone analysis helps differentiate the composition, because this helps determine related diseases contributing to lithiasis.

References

  1. Levinson, W., Chin-Hong, P., Joyce, E.A., Nussbaum, J., & Schwartz, B. (Eds.) (2020). Review of Medical Microbiology & Immunology: A Guide to Clinical Infectious Diseases, 16th ed. McGraw-Hill. 
  2. Mazudamer, S. (2020). Proteus infections. Medscape. https://emedicine.medscape.com/article/226434-overview
  3. Riedel, S., et al. (Ed.) (2019). Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed. McGraw-Hill.
  4. Russo, T.A., & Johnson, J.R. (2018). Diseases caused by gram-negative enteric bacilli. Jameson J, et al. (Ed.), Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill.
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