Urinary Tract Infection


Epidemiology

Demographics

  • Outpatient UTI Accounts for 7 Million Office Visits Per Year in US

Sex and Age-Related Factors Associated with Urinary Tract Infection

  • Female UTI
    • Incidence of UTI Increases Markedly After Onset of Sexual Actvity in Adolescence
    • Incidence of Symptomatic UTI in Sexually Active Females (In a University Population): 0.5-0.7 cases per person-year
      • Risk Factors
        • Sexual Intercourse
        • Recent Spermicide Use
        • History of UTI
    • Incidence of Cystitis in Post-Menopausal Female: 0.07 cases per person-year
    • Incidence of Pyelonephritis: 12-13 cases per 10k females per year (lower incidence than that for cystitis)
  • Male UTI
    • Incidence: 5-8 UTI per 10k young adult males per year
    • Most Male UTI’s Occur in Infants and Elderly (Usually Associated with Urologic Abnormalities or Instrumentation)
      • However, UTI May Occur in Males age 15-50 y/o (with Risk Factors Being Anal Insertive Intercourse and Lack of Circumcision)
  • Factors Related to Lower Incidence of Symptomatic Bacteruria/Symptomatic UTI in Males than Females
    • Longer Urethral Length
    • Drier Peri-Urethral Environment: with less frequent peri-urethral colonization
    • Antibacterial Substances Contained in Prostatic Fluid

Factors Suggesting “Complicated” Urinary Tract Infection

  • Demographic Features
    • Advanced Age
    • Male Sex
    • Pregnancy (see Pregnancy)
  • Comorbid Conditions
  • Infection-Related Characteristics
    • Hospital-Acquired Urinary Tract Infection
    • Recent Antibiotic Use
    • Recent Urinary Tract Instrumentation
    • Resistant Urinary Pathogen
    • Symptoms For At Least 7 Days Before Seeking Medical Attention
  • Urinary Tract Functional/Anatomic Abnormalities


Etiology


Physiology

Route/Mechanism of Urinary Tract Infection

  • Ascending Infection: in female, colonization of vaginal introitus with pathogens from fecal flora -> ascension via urethra into bladder (and ultimately to kidneys, via ureters)
  • Bacteremic Seeding of Kidney: causes some cases of pyelonephritis
  • Seeding of Kidneys from Bacteria Within Lymphatics: may play a role in some cases of pyelonephritis


Diagnosis

Urinalysis (see Urinalysis)

  • General Comments
    • Dipstick positivity for leukocyte esterase or nitrite has 75% sensitivity/82% specificity for detection of UTI: test is not helpful to rule out UTI if symptoms are consistent with UTI and dipstick is negative for both (due to low sensitivity)
  • Nitrite
    • Assay: dietary nitrate (normally present in the urine) is converted to nitrite by the nitrate reductase enzyme in certain Gram-negative bacteria -> results in pink color change on dipstick
      • Specific Gram-negative bacteria (E Coli, Citrobacter, Klebsiella, Proteus, Serratia) possess nitrate reductase and are capable of this conversion
        • Pseudomonas and Gram-positive bacteria (Enterococcus, etc) do not possess the nitrate reductase enzyme
      • False-Positive: use of phenazopyridine, beet ingestion
    • Interpretation: positive nitrite indicates presence of the specific Gram-negative bacteria noted above
  • Leukocyte Esterase
    • Assay: granulocyte leukocyte esterase catalyzes the hydrolysis of an amino acid ester to liberate 3-hydroxy-5-phenyl pyrrole! which reacts with a diazonium salt -> results in purple color change on dipstick
      • Sensitivity: 75-96%/Specificity: 94-98% for >10 WBC per hpf
    • Interpretation: positive nitrite indicates presence of pyuria
  • Protein: xxx
  • Ketone: may be mildly positive in cases with associated dehydration and starvation ketoacidosis or with concomitant diabetic ketoacidosis
  • RBC (on Microscopy): elevated RBC (microscopic or gross hematuria) may be seen
    • Hematuria is Common in UTI, But Not in Urethritis or Vaginitis
  • WBC (on Microscopy): >10 WBC/uL (pyuria) indicates UTI (cystitis or pyelonephritis)
    • Pyuria May Be Absent in Some Cases of Pyelonephritis with Urinary Tract Obstruction
  • Casts
    • WBC Casts: indicate pyelonephritis

Urine Gram Stain (see Urine Culture)

  • Assay: performed on spun urine
  • Interpretation: should be positive if there are >100k colonies in culture (which is performed on unspun urine)

Urine Culture (see Urine Culture)

Performance of Urinary Culture in Patient with Foley Catheter (Centers for Disease Control and Prevention, CDC) [LINK]

  • Appropriate Uses of Urine Culture
    • Presence of Symptoms/Signs of Urinary Tract Infection (UTI)
      • Acute Hematuria (see Hematuria)
      • Flank Pain/Costovertebral Angle Tenderness (see Flank Pain)
      • New Pelvic Discomfort/Pain
    • New Onset/Worsening Sepsis Without Historical/Physical Examination/Laboratory Evidence of Another Source (see Sepsis)
      • Including Any SIRS and/or SOFA/qSOFA Criteria (Altered Mental Status, Fever, Hypotension, etc)
    • Presence of Unique Physiologic Features in A Patient with Spinal Cord Injury (SCI) (see Spinal Cord Injury)
  • Inappropriate Uses of Urine Culture
    • Odorous, Cloudy, or Discolored Urine in the Absence of Other Localizing Symptoms/Sighs (as Noted Above)
    • Reflex Urine Cultures Based on Urinalysis Results (Such as Pyuria) in the Absence of Other Indications
      • Note: the Absence of Pyuria Suggests a Diagnosis Other than Catheter-Associated Urinary Tract Infection (CAUTI)
    • Urine Culture to Routinely Document Response to Therapy (Unless Symptoms Fail to Resolve)

Assay

  • Clean-Catch (in female: after cleansing of external urethra prior to collection) or via Foley Catheter

Interpretation

  • *Historically considered positive if there are >100k CFU/mL in culture (this originated from literature in pregnant females with first void morning urine samples)
  • However, urinary tract infection may occur with colony counts <100k CFU/mL
    • Male: colony count >10k CFU/mL is considered positive
  • Lower colony counts of coliforms (E Coli, etc) are likely to represent significant bacteriuria
  • In some female cases with infection due to Chlamydia Trachomatis/Neisseria Gonorrhoeae/HSV, culture may be negative

Isolation of Other Organisms from Urine Culture

  • Lactobacillus, Enterococcus, Staphylococcus Epidermidis and group B Streptococcus isolated from a voided urine culture in female may suggest contamination
    • However, presence of organism in midstream voided urine at high colony count and with pure growth may suggest that organism is etiologic

    Abdominal/Pelvic Computed Tomography (CT) (see Abdominal-Pelvic Computed Tomography)

    • Diagnostic of nephrolithiasis and hydronephrosis
    • May demonstrate emphysematous pyelonephritis or emphysematous cystitis

    KUB (see Kidneys-Ureters-Bladder X-Ray)

    • May occasionally detect nephrolithiasis

    Renal Ultrasound (see Renal Ultrasound)

    • May be required to rule out hydronephrosis (due to obstruction), anatomic abnormailities, nephrolithiasis, etc


    Clinical Presentations

    Asymptomatic Bacteriuria

    Definition

    • Asymptomatic Bacteriuria is Defined as Positive Urine Culture in the Absence of Clinical Symptoms
      • Male: defined as single clean-catch voided urine with single bacterial species isolated in count >100k CFU/mL in absence of symptoms
      • Female: XXXXXX

    Differentiation of Catheter-Associated Asymptomatic Bacteriuria (CA-ASB) vs Catheter-Associated Urinary Tract Infection (CAUTI) (Centers for Disease Control and Prevention, CDC) [LINK]

    Epidemiology

    • Prevalence of Male Asymptomatic Bacteriuria
      • Young Male: rare
      • Elderly Male: prevalence of 6%
    • Prevalence of Female Asymptomatic Bacteriuria
      • Young Female: xxx
      • Elderly Female: prevalence of 18%

    Indications to Preoperatively Screen for Asymptomatic Bacteriuria

    • Other than urologic procedures, the risk of surgical site infection for other surgical procedures (including procedures with high risk of infection, like joint arthroplasty) with pre-operative asymptomatic bacteriuria probably does not warrant screening
      • Pre-Trans-Urethral Resection of Prostate (TURP): due to risk of bacteremia/sepsis
      • Pre-Urologic Procedures Where Mucosal Bleeding is Anticipated: due to risk of bacteremia/sepsis

      Asymptomatic Candiduria (see Candida)

      • xxx

      Acute Cystitis

      • Definition: infection of urinary bladder (lower urinary tract)
        • May occur alone or in conjunction with pyelonephritis or prostatitis
      • General Comments
        • Males with Recurrent Cystitis: should undergo evaluation for prostatitis
      • Cloudy Urine
      • Dysuria (see Dysuria)
      • Gross Hematuria (see Hematuria)
      • Suprapubic or Low Abdominal Pain (see Abdominal Pain)
      • Urinary Frequency
      • Urinary Urgency

      Emphysematous Cystitis

      • Epidemiology: rare
      • Risk Factors
        • Diabetes Mellitus (see Diabetes Mellitus)
        • Female Sex
        • Immunocompromised State
        • Neurogenic Bladder
        • Prior Urinary Tract Infection
        • Renal Transplant (see Renal Transplant)
        • Urinary Stasis
      • Specific Microbial Etiologies
      • Mechanism: gas may appear in the wall of the bladder by either transluminal dissection of gas or true infection of the bladder wall with pathogens
      • Diagnosis: abdominal/pelvic CT scan
      • Clinical Manifestations
        • Abdominal Pain (see Abdominal Pain)
        • Gas In Bladder Wall (Seen on CT Scan): due to bacterial or fungal fermentation
        • Pneumaturia (see Pneumaturia): highly suggestive (although not usually noted by the patient)
      • Prognosis: delayed diagnosis and treatment may result in overwhelming infection, extension to ureters and renal parenchyma, bladder rupture, and death

      Acute Pyelonephritis

      • Definition: infection of kidney (upper urinary tract)
        • May occur alone or in conjunction with cystitis
      • General Comments
        • Symptoms may co-exist with those of acute cystitis
      • Abdominal Pain (see Abdominal Pain)
      • Costovertebral Angle Tenderness
      • Fever/Chills (see Fever)
      • Flank Pain (see Flank Pain): present in cases with pyelonephritis
      • Diarrhea (see Diarrhea)
      • Nausea and Vomiting (see Nausea and Vomiting)

      Emphysematous Pyelonephritis

      • Risk Factors
        • Diabetes Mellitus with Escherichia Coli Urinary Tract Infection (see Escherichia Coli)
        • Diabetes Mellitus with Klebsiella Pneumoniae Urinary Tract Infection (see Klebsiella Pneumoniae)
      • Staging (Huang and Tseng, 2000)
        • Class 1: gas confined to the collecting system
        • Class 2: gas confined to the renal parenchyma alone
        • Class 3A: perinephric extension of gas or abscess
        • Class 3B: extension of gas beyond the Gerota fascia
        • Class 4: bilateral emphysematous pyelonephritis or pyelonephritis in a solitary kidney
      • Diagnosis : abdominal/pelvic CT scan
      • Clinical Manifestations
      • Prognosis: may be fatal, if not rapidly treated

      Complications


      Prevention

      Measures Which Do Not Have Demonstrated Clinical Efficacy

      • Chlorhexidine Gluconate Skin Decontamination (see Chlorhexidine Gluconate)
        • Clinical Efficacy
          • Randomized Trial of Daily Chlorhexidine Bathing to Prevent Healthcare-Associated Infections ( JAMA, 2015) [MEDLINE]
            • Daily Chlorhexidine Gluconate Bathing Did Not Decrease the Incidence of Healthcare-Associated Infections (Central Line-Associated Bloodstream Infections, Catheter-Related Urinary Tract Infection, Ventilator-Associated Pneumonia, or Clostridium Difficile)


      Treatment

      Acute Cystitis

      Oral (PO) Antibiotics

      • Amoxicillin (see Amoxicillin)
        • Resistance rates are typically >20% in most regions -> avoid empiric use
      • Amoxicillin-Clavulanic Acid (Augmentin) (ee Amoxicillin-Clavulanic Acid)/First and Second-Generation Cephalosporins (Cefpodoxime, Cefaclor, Cefdinir) (see Cephalosporins)
        • Resistance rates are <10% in most regions -> acceptable for empiric use for female cystitis (7 day regimen)
      • Fluoroquinolone (see Fluoroquinolones)
        • General Comments
          • Clinical Efficacy: effective for female cystitis (3 day regimen)
          • However, should probably be reserved for more serious conditions than acute cystitis (due to concerns about increasing resistance to these agents)
        • Agents
      • Fosfomycin
        • Female Cystitis: 91% clinical efficacy (single dose)
        • Male Cystitis: data for use in male UTI is limited
        • Avoid use if early pyelonephritis is suspected (due to inadequate renal tissue levels)
      • Nitrofurantoin (Macrodantin) (see Nitrofurantoin)
        • Female Cystitis: 90-95% clinical efficacy (5-7 day course), but may be inferior to other first-line agents
        • Male Cystitis: contraindicated, as agent is less effective for occult prostatitis
        • Contraindication: creatinine clearance <60 mL/min
        • Avoid use if early pyelonephritis is suspected (due to inadequate renal tissue levels)
      • Trimethoprim-Sulfamethoxazole (Bactrim) (see Sulfamethoxazole-Trimethoprim)
        • Female Cystitis: 86-100% clinical efficacy (3-7 day course)
        • Avoid empiric use of this agent if community urinary tract pathogen resistance is >20% (>20% threshold is based on mathematical models)
        • Risk Factors for Trimethoprim-Sulfamethoxazole Resistance
          • Use of Trimethoprim-Sulfamethoxazole in Prior 3-6 mo
          • Foreign Travel (Especially International Travel)

      Intravenous (IV) Antibiotics (usually not required for acute cystitis, unless concomitant acute pyelonephritis is present)

      Clinical Guidelines for Short-Course Antibiotics in Common Infections (Annals of Internal Medicine, 2021) [MEDLINE]

      • In women with uncomplicated bac- terial cystitis, clinicians should prescribe short-course antibi- otics with either nitrofurantoin for 5 days, trimethoprim– sulfamethoxazole (TMP–SMZ) for 3 days, or fosfomycin as a single dose
      • In men and women with uncomplicated pyelo- nephritis, clinicians should prescribe short-course therapy either with fluoroquinolones (5 to 7 days) or TMP–SMZ (14 days) based on antibiotic susceptibility

      Emphysematous Cystitis

      • Intravenous Antibiotics
      • Bladder Drainage

      Acute Pyelonephritis

      Oral (PO) Antibiotics

      • Amoxicillin-Clavulanic Acid (Augmentin) (ee Amoxicillin-Clavulanic Acid)/Second or Third-Generation Cephalosporins (Cefpodoxime, Cefaclor, Cefdinir) (see Cephalosporins)
        • Less effective for treatment of pyelonephritis
        • However, if pathogen is known to be susceptible, need to use at least a 14 day regimen
      • Fluoroquinolone (see Fluoroquinolones): fluoroquinolones are the only recommended outpatient PO treatment for pyelonephritis

      Intravenous (IV) Antibiotics

      Emphysematous Pylelonephritis

      • Intravenous Antibiotics
      • Nephrectomy (see Nephrectomy): may be required

      Treatment Duration

      • Male Treatment Duration
        • Cystitis: 7 days is generally adequate
          • Persistent or recurrent symptoms despite treatment indicate need for evaluation for possible prostatitis
        • Pyelonephritis: presence of bacteremia with pyelonephritis does not mandate longer antibiotic course (assuming no other complicating factors)
      • Female Treatment Duration
        • Cystitis: some agents can be used in 3-day course, although most courses are 7 days
        • Pyelonephritis: presence of bacteremia with pyelonephritis does not mandate longer antibiotic course (assuming no other complicating factors)

      Urinary Tract Analgesic

      Treatment of Pre-Operative Asymptomatic Bacteriuria

      • Treatment of pre-operative asymptomatic bacteriuria does not decrease the risk of subsequent UTI or risk of surgical wound infection

      Treatment of Pre-Operative Symptomatic Urinary Tract Infection

      • Indicated

      Management of Staphylococcus Aureus Bacteriuria

      • In Presence of Foley Catheter (see Foley Catheter): in absence of systemic signs of infection, work-up for bacteremia is not necessary
      • In Absence of Foley Catheter: may be indicative of bacteremia, therefore, work-up for bacteremia is required

      Management of Candiduria


      Prognosis


      References