Urinary Tract Infections

Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess that can result in sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock and death. Urinary tract infections are most commonly caused by Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli, but may also be caused by other 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: Overview and fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology: Overview. Depending on the location of the infection, patients can present with dysuria, urinary urgency, increased urinary frequency, suprapubic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Urinalysis and urine culture along with the clinical presentation help in the diagnosis of UTIs. Management options include oral or IV antibiotics such as 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, nitrofurantoin, and ceftriaxone. In certain instances, further workup may be needed to determine the underlying conditions that predispose an individual to UTIs.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Urinary tract infection (UTI) is a pathogenic process that develops when a microorganism (usually 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: Overview) enters the body through the urethra and travels to the bladder and/or kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys.

Epidemiology

Prevalence:

  • Asymptomatic bacteriuria ( 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: Overview in the urine):
    • 1%–5% of non-pregnant, premenopausal women
    • 1.5%–9.8% of pregnant women
    • 2.8%–8.6% of postmenopausal women
  • Uncomplicated cystitis:
    • Up to 60% of women may have ≥ 1 UTI at some time.
    • Up to 10% of women have ≥ 1 UTI each year.
    • Approximately 2%–5% of women have recurrent UTI.
    • Most common in sexually active, 18–24-year-old women
  • Men:
    • < 0.1% overall
    • ↑ Risk if uncircumcised or in case of anal-insertive intercourse

Risk factors

  • Women > men: 
    • Short urethra predisposes all women:
      • Less distance for 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: Overview to ascend to the bladder
      • Less time for micturition to wash away ascending 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: Overview in the urethra
    • Additional risk factors are usually needed for UTIs to occur in men.
  • Comorbidities:
    • Immunocompromised state
    • Diabetes (glucosuria provides a food source for 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: Overview)
    • History of UTIs
  • Behavioral:
    • Poor hygiene and fecal incontinence (↑ genital/periurethral colonization)
    • Sexual intercourse:
      • Facilitates bacterial infections in women
      • Anal-insertive intercourse may result in bacterial infections in men.
  • Anatomical (causes of urinary stasis/obstruction):
    • Posterior urethral valves → ureteral reflux → 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
    • Benign prostatic hyperplasia Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a condition indicating an increase in the number of stromal and epithelial cells within the prostate gland (transition zone). Benign prostatic hyperplasia is common in men > 50 years of age and may greatly affect their quality of life. Benign Prostatic Hyperplasia (BPH)
    • Urethral stricture
    • Cystocele
    • Neurogenic bladder
    • 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
  • Foreign body (nidus for infection and/or allows entry into body):
    • Foley catheter
    • Suprapubic catheter
    • Ureteral stent
    • Urologic instrumentation (i.e., cystoscopy)
  • Medications:
    • Anticholinergics (i.e., diphenhydramine):
      • Can cause incomplete emptying of the bladder
      • Elderly primarily affected
    • Antibiotics (frequent use = ↑ resistance)

Etiology and Pathophysiology

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

  • 75%–95% of all UTIs due to uropathogenic E. coli
  • Virulence factors aid in colonization, ascension, and invasion of the urinary tract:
    • Type 1 fimbriae (in mannose-sensitive E. coli) of bacterium:
      • Attach to the uroepithelial cells (on the mannose residues of surface glycoproteins)
      • Prevent E. coli from being flushed out by the urine stream
    • P fimbriae: 
      • Hair-like projections that interact with renal epithelial cells
      • Important role in 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
  • Uromodulin (human defense factor), which has mannose residues, prevents E. coli from binding to the uroepithelial cells.

Other 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: Overview

Non-E. coli 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: Overview are associated with risk factors for drug resistance or in specific clinical scenarios.

  • Urease-producing 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: Overview:
    • Associated with ↑ risk of staghorn kidney stones
    • Alkaline urine → ↓ solubility of phosphate → precipitation of magnesium ammonium phosphate (struvite) → staghorn kidney stones
    •   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. Enterobacteriaceae: Proteus mirabilis and Ureaplasma urealyticum
    • 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 pneumoniae: associated with hospital-acquired infections
    • 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 saprophyticus: associated with UTIs in women following sexual intercourse
  • Enterococci (i.e., 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): 
    • Can cause true infections or can be a contaminant (i.e., from feces)
    • Associated with hospital-acquired infections

Fungi and viruses

  • Fungi:
    • Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis: most common cause of fungal UTIs
    • Seen in hospitalized patients (↑ risk with indwelling catheters)
    • Treatment (fluconazole or amphotericin) is not required if asymptomatic (i.e., colonization only).
  • Viruses:
    • Rare cause ( adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus, JC/BK polyomavirus)
    • In the setting of extreme immunosuppression (i.e., patients who have undergone a transplant)
    • Presentation (i.e., hemorrhagic cystitis) is not that of a classic UTI.

Infectious process

  • Initial invasion to urethritis:
    • Contamination of the periurethral area → colonization of the urethra + migration to the bladder
    • Development of urethritis
  • Once in the bladder:
    • Colonization → invasion + inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the bladder → accumulation of fibrinogen
    • At this stage, the patient presents with cystitis.
  • Neutrophil infiltration and immune response:
    • Bacteria start multiplying → neutrophils infiltrate the urinary bladder → systemic immune reaction
    • Accompanied by leukocytosis and systemic symptoms and signs
  • A biofilm is formed and the uroepithelial surface of the ureters is extensively damaged by bacterial toxins and proteases.
  • Bacterial organisms ascend to the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys 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

Clinical Presentation

Characteristic features

  • Dysuria + bacteriuria
  • UTIs can be:
    • Uncomplicated:
      • UTIs of the lower urinary tract
      • No associated systemic symptoms
    • Complicated:
      • UTIs extending beyond the bladder (kidney/upper urinary tract)
      • Accompanied by systemic symptoms (i.e., 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, sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock, altered mental status)
  • Other considerations:
    • Historically, the following situations were considered complicated UTIs automatically:
      • UTIs in men
      • Immunocompromised (including diabetics) individuals
      • Urologic abnormalities (i.e., kidney stones and ureteral stents)
    • Antibiotic stewardship (i.e., concern for antibiotic resistance due to overuse) has shifted the trend:
      • If the patient is stable or without systemic symptoms, treat as an outpatient. 
      • Monitor these patients (listed above) with awareness of their increased risk for serious infections.

Uncomplicated UTIs

  • Also known as “simple UTI,” “simple cystitis,” or “uncomplicated cystitis”
  • Almost exclusively in women (possible, but rare in men)
  • UTI of the lower urinary tract (cystitis):
    • Painful urination (dysuria)
    • Sensation of needing to urinate immediately (urgency)
    • Increased frequency of urination (frequency)
    • Suprapubic abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  •  The patient has:
    • No systemic symptoms
    • No signs of 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 (flank pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, costovertebral angle tenderness)
    • No suspicious symptoms of:
      • STIs (urethritis, pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease (PID), urethral/vaginal discharge, dyspareunia)
      • 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 (perineal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, prostatic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, urethral discharge)
  • Symptoms may be more vague in the elderly.

Complicated UTIs

  • Pyelonephritis:
    • UTI of the upper urinary tract (i.e., kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys)
    • Most are 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 (some use the terms interchangeably).
    • Characteristic symptoms:
      • Fever, chills, rigors
      • Flank pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
      • Costovertebral angle tenderness
    • Symptoms of cystitis may or may not be present.
  • Complicated cystitis:
    • Patients are often febrile or show sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock
    • No signs of 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
    • Without any other identified sources of infection

Diagnosis

Diagnostic approach

  • History: risk factors and characteristic symptoms
  • Test: Check for the presence 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: Overview in urine (identified based on urinalysis and culture).
  • Categorization: determines additional workup and treatment

Urinalysis

  • Normal urine:
    • Sterile (i.e., no normal flora)
    • Without WBCs
  • Proper urine-collection technique:
    • Urogenital area frequently colonized → ↑ risk for contamination
    • Minimize risk of contamination via:
      • Cleansing of genitals and urethra prior to collection
      • Midstream urine collection (i.e., discard initial volume of urine)
    • Option in infants and toddlers in diapers: straight catheterization of the urethra
  • Pyuria is a marker for bacteriuria:
    • Microscopy: ≥ 10 leukocytes/µL → clinically significant pyuria
    • Detectable before results of Gram stain and culture:
      • Very sensitive for UTIs
      • Consider alternative diagnoses if pyuria is absent.
      • Pyuria + characteristic symptoms → may proceed with empiric treatment
  • Leukocyte esterase and nitrite:
    • Leukocyte esterase: 
      • Enzyme released from WBCs
      • Sensitive and specific for UTIs
    • Nitrite: 
      • Reflects + Enterobacteriaceae (i.e., E. coli), which has the bacterial enzyme that converts dietary nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates to nitrites
      • Index of bacteriuria (can be negative if incubation time in the bladder is insufficient to convert nitrate to nitrite)
  • Other markers of UTIs:
    • Microscopic hematuria:
      • RBCs enter the urine due to local tissue inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.
      • Repeat urinalysis after treatment (to ensure there are no other serious causes of hematuria).
      • Non-UTI causes: bladder tumors, glomerulonephritis, and kidney stones
    • Alkaline urine:
      • Urine pH > 7: consistent with urease-producing 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: Overview
      • Not sufficient alone to make diagnosis
  • Other considerations:
    • Point of care (i.e., dipstick) urinalysis:
      • Performed in an outpatient setting
      • May be used alone in classic uncomplicated cystitis in women
      • Provides information on Leukocyte esterase and nitrite
      • No quantitative information on urine WBC count
      • Performed when there is no opportunity for urine culture
    • Lab-based urinalysis:
      • In outpatient or inpatient settings
      • Provides quantitative information on urine WBC count
      • Urine culture is often “reflexed” if pyuria is present.

Urine culture

  • Multiple organisms growing simultaneously is suggestive of contamination.
  • Common contaminants: 
    • Lactobacilli
    • Enterococci
    • Group-B streptococci
    • Coagulase-negative staphylococci (other than S. saprophyticus)
  • Gram staining:
    • Available prior to culture results and can guide therapy
    • Identifies possible contaminants (i.e., not true UTIs)
  • Quantitative bacterial count:
    • ≥ 105 colony forming units (CFUs)/mL reflect bladder bacteriuria:
      • A high threshold helps differentiate from contamination.
      • The urine culture may be repeated to ensure that bacterial counts are consistent.
    • ≥ 102 CFUs/mL: adequate, if characteristic symptoms of UTI are present
  • Not necessary in uncomplicated cystitis in non-pregnant women

Categorization

  • Categories considered before diagnosing uncomplicated cystitis and determining further workup:
    • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care:
      • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care test for all women of child-bearing age
      • Requires avoidance of teratogenic antibiotics
    • Indwelling catheters (Foley, suprapubic catheter): consider removal
    • Men:
      • Overall, UTIs are rare.
      • Often need a further workup (i.e., imaging, urology consult) to determine the possible anatomic cause of the UTI
    • Kidney transplant:
      • Different microorganisms may be present (including JC/ BK virus BK Virus BK virus (BKV) is a small, nonenveloped, single-stranded DNA virus belonging to the Polyomaviridae family, which are ubiquitous in the human population. While the primary infection is usually asymptomatic, the infection leads to lifelong latency in the kidneys and lymphoid organs. JC Virus and BK Virus).
      • Consider nephrology and/or infectious disease consults.
    • Recurrent UTI:
      • Requires a thorough review of past culture results
      • Consider an infectious disease consult.
    • Genitourinary features (i.e., vaginal discharge):
      • Rule out STIs (i.e., gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea, chlamydia).
      • Pelvic exam
  • Complicated UTIs:
    • May require admission and IV antibiotics
    • May require diagnostic imaging (ultrasound or CT scan):
      • Urinary tract obstruction Urinary tract obstruction Urinary tract obstruction (UTO) refers to the blockage of the urinary tract, which can occur anywhere in the urinary tract. Urinary tract obstruction can be acute or chronic, partial or complete, and unilateral or bilateral. Urinary tract obstruction can cause acute or chronic kidney disease. Urinary Tract Obstruction (i.e., tumors, BPH)
      • Kidney stones (nidus for infection)
      • Retained ureteral stent (nidus for infection)
      • Perinephric abscess
  • Assessment of possible multi-drug resistant (MDR) 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: Overview:
    • Risk factors: 
      • Recent antibiotic use
      • Recent high-risk travel
      • Previous MDR 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: Overview on urine culture
      • Recent hospitalization or nursing-home stay
    • May require different antibiotics and closer monitoring even if with uncomplicated cystitis
Ct scan showing the left renal stone

A CT scan showing left renal stone

Image: “Surgical Clips Migration up to Renal Collecting System from Ileal Conduit Postcystectomy” by Journal of Endourology Case Reports. License: CC BY 4.0
Ultrasound showing renal abscess

Ultrasound showing a renal abscess that appears as a hypoechoic area measuring 1.19 × 0.96 cm within the cortex of the left kidney

Image: “Transient Monoclonal Gammopathy Induced by Disseminated Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus Infection” by Stoimenis D, Spyridonidou C, Papaioannou N. License: CC BY 3.0

Management

Treatment approach

  • Antibiotics:
    • Choose antibiotics depending on culture sensitivities (if possible).
    • Minimize fluoroquinolone use:
      • Spectrum is too broad for uncomplicated UTIs.
      • Emergent antibiotic resistance
      • Many side effects (i.e., tendon rupture)
  • Relieve obstruction, if present:
    • Foley catheter for bladder outlet obstruction (i.e., BPH)
    • Urologic intervention for nephrolithiasis, ureteral obstruction, or perinephric abscess
    • Gynecological intervention for pelvic tumors
  • Reassessment needed:
    • If an uncomplicated UTI does not improve after 48 hours of commencement of antibiotics:
      • The patient may actually have a complicated UTI.
      • Additional imaging may be needed to determine obstruction/abscess.
    • If hematuria (nonspecific for UTIs) was found on initial urinalysis:
      • Repeat urinalysis after completion of treatment.
      • Do not want to miss coincidental occult bladder cancer
Table: Antibiotics
Type of UTI Antibiotics
Uncomplicated UTI (simple cystitis)
  • Nitrofurantoin
  • Trimethoprim-sulfamethoxazole
  • Fosfomycin
  • Pivmecillinam (not available in the United States)
Complicated UTI (including 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)
  • Outpatient: oral ciprofloxacin or levofloxacin
  • Inpatient options:
    • No risk factors for multi-drug resistance:
      • IV ceftriaxone
      • IV piperacillin-tazobactam
      • IV ciprofloxacin/levofloxacin
    • With risk factors for multi-drug resistance:
      • IV piperacillin-tazobactam
      • IV carbepenem (meropenem/imipenem/doripenem)
    • Critically ill: IV carbepenem plus IV vancomycin
UTI: urinary tract infection

Special Cases

The following patient populations may require a different standard of care, as they do not fall into the usual categories of UTIs:

Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care

  • ↑ Risk of UTIs due to physiological changes:
    • Urinary stasis (progesterone inhibits contraction of smooth muscles)
    • Ureteral smooth muscle relaxation and dilation 
    • ↑ Pressure on the bladder from the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Posterior Abdominal Wall
    • Immunosuppression
  • Obstetric outcomes associated with UTIs:
    • Preterm birth Preterm birth Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth
    • Low birth weight
    • ↑ Perinatal mortality
  • Asymptomatic bacteriuria:
    • Approximately ⅓ of cases progress to UTIs. 
    • Screening: at approximately 12–16 weeks of gestation
    • Treat if found, and obtain a follow-up urine culture.
  • Antibiotics:
    • Amoxicillin-clavulanic acid, cephalexin, fosfomycin
    • Do not use in the 1st trimester or at term:
      • Trimethoprim-sulfamethoxazole
      • Nitrofurantoin
    • Avoid 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.
  • Treat complicated UTIs (i.e., 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) aggressively:
    • Due to association with worse obstetric outcomes
    • Usually requires hospitalization and IV antibiotics
  • Post-treatment urine culture is always ordered to ensure eradication.

Asymptomatic bacteriuria

  • Bacteriuria (≥ 105 CFUs/mL) without characteristic symptoms of UTIs
  • Often found incidentally and treated unnecessarily
  • Usually do not require treatment, unless:
    • Pregnant
    • Recent kidney transplant
    • With planned urologic procedure (risk for seeding the bloodstream)

Catheter-associated UTI (CAUTI)

  • Characterized by:
    • Bacteriuria (from urine sample obtained midstream or newly replaced catheter)
    • Indwelling urinary catheter (or removed within 48 hours)
    • Symptoms attributable to infection 
  • Presentation and considerations:
    • Patients will often not exhibit classic dysuria/urgency/frequency:
      • Characteristic symptoms blunted by urinary catheter
      • Systemic symptoms ( 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, costovertebral angle tenderness, sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock) are helpful in diagnosis.
    • All catheters will eventually become colonized with 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: Overview.
    • Treating asymptomatic bacteriuria in catheterized patients does not improve outcomes.
  • Management:
    • Removal and replacement of the catheter
    • May require switching to intermittent straight catheterization

Kidney transplant

  • Consider additional pathogens due to the suppressed immune system.
  • Presentation:
    • Classic symptoms of UTI with common organisms (i.e., E. coli)
    • Hemorrhagic cystitis (due to BK/ JC virus JC Virus JC virus (JCV) is a small, nonenveloped, single-stranded DNA virus belonging to the Polyomaviridae family, which are ubiquitous in the human population. While the primary infection is usually asymptomatic, the infection leads to lifelong latency in the kidneys and lymphoid organs. JC Virus and BK Virus)
  • Ensure that antibiotics do not interfere with transplant medications.

Recurrent UTIs

  • Characterized by:
    • ≥ 2 UTIs in 6 months or ≥ 3 UTIs in 1 year
    • Usually uncomplicated UTIs (i.e., simple cystitis)
    • Usually reinfection (more common) and not relapse, even if the same organism is found repeatedly
  • Risk factors: 
    • Anatomical urologic abnormalities
    • Sexual intercourse
    • Spermicide use
  • Evaluate for reinfection versus relapse: 
    • Reinfection (new infection after adequate treatment): 
      • True even if same organism is found again after 2 weeks of treatment
      • Relatively common for uncomplicated cystitis in women
    • Relapse (inadequate initial treatment):
      • The same organism colonizes within 2 weeks of treatment.
      • Imaging to screen for anatomical problems (especially if accompanied by hematuria, 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. Enterobacteriaceae: Proteus infection due to ↑ risk of struvite stones)
  • Treatment: same as that use for isolated cases of UTI
  • Prevention:
    • Increase oral fluid intake.
    • Post-coital voiding
    • Avoid spermicides.
    • Minimize fecal contamination by wiping front to back.
    • Topical estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries in post-menopausal women (promotes healthy vaginal flora)
    • Consider prophylactic antibiotics (daily versus post-coital).

Differential Diagnosis

  • Vaginitis: a vaginal infection (bacterial vaginosis, trichomoniasis, candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis) that may present with dysuria. Signs that are not found in UTIs may be present, including odor, vaginal discharge, and pruritus. Urinalysis may show pyuria; however, hematuria will not be present. Treatment depends on etiology (often metronidazole or fluconazole).
  • PID: an infection of the uterus Uterus The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Posterior Abdominal Wall, fallopian tubes Fallopian tubes The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. Posterior Abdominal Wall, and/or ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries that can present with suprapubic abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain similar to that experienced in a UTI. Sexual intercourse is a major risk factor, as the etiology is an STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections (i.e., gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea, chlamydia). Inadequately treated PID can cause infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility; thus, the diagnosis of PID must always be considered in a sexually active woman with UTI. Treatment is with broad-spectrum IV antibiotics.
  • 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: an acute or chronic 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 and other Male Reproductive Glands infection that presents with dysuria, perineal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and voiding difficulties. Since 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 and other Male Reproductive Glands gland drains into the urine, pyuria and a positive urine culture can be expected. Similar 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: Overview plus gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea and chlamydia cause prostatitis. Examination reveals a very 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 and other Male Reproductive Glands (gentle exam only, to avoid the risk of inducing bacteremia). Patients with acute prostatitis are usually very ill and present with signs similar to those seen in complicated UTI/ 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 prostatitis is often mistaken as recurrent UTI. Treatment is using antibiotics, with coverage for gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea and chlamydia, if suspected.
  • Urethritis: an STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections of the urethra (usually gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea and/or chlamydia) that presents with dysuria and purulent urethral discharge. Diagnosis is made by Gram stain of the urethral discharge and testing for gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea and chlamydia. Urinalysis will show pyuria, but the urine culture will be negative (“sterile pyuria”). Treatment options include ceftriaxone (for gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea) and azithromycin or doxycycline (for chlamydia). As coinfection with chlamydia is common, both conditions are treated simultaneously even if only gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea is isolated on testing.
  • Interstitial cystitis (“bladder pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain syndrome”): noninfectious, chronic (> 6 weeks) bladder pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain with an unknown etiology. Interstitial cystitis may present similarly to a UTI; however, the urine culture will be negative. Management includes supportive care for pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain control and certain urologic procedures. Overall, interstitial cystitis is difficult to treat.

References

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  3. Cox, G.M., Kauffman, C.A. (2020). Candida infections of the bladder and kidneys. UpToDate. Retrieved March 23, 2021, from https://www.uptodate.com/contents/candida-infections-of-the-bladder-and-kidneys
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  6. Hirsch, H.H. (2019). Overview of JC polyomavirus, BK polyomavirus, and other polyomavirus infections. UpToDate. Retrieved March 23, 2021, from https://www.uptodate.com/contents/overview-of-jc-polyomavirus-bk-polyomavirus-and-other-polyomavirus-infections
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