Urinary Tract Infection

Epidemiology

  • Outpatient UTI: accounts for 7 million office visits per year in US

Sex and Age-Related Factors Associated with UTI

  • Female UTI
    • Incidence of UTI increases markedly after onset of sexual actvity in adolescence
    • Incidence of Symptomatic UTI in Sexually Active Females (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” UTI

  • Demographic Features
    • Advanced Age
    • Male Sex
    • Pregnancy
  • Comorbid Conditions
    • Diabetes Mellitus
    • History of a Childhood UTI
    • Immunosuppression
    • Renal Failure
    • Renal Transplantation
  • Infection-Related Characteristics
    • Hospital-Acquired UTI
    • 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
    • Prostatic Hypertrophy
    • Urethral Stricture
    • Urinary Tract Instrumentation
      • Foley Catheter
      • Nephrostomy
      • Urinary Diversion
      • Urinary Tract Stent
    • Urinary Tract Obstruction

Etiology

  • Candida Albicans (see Candida, [[Candida]])
    • Clinical Manifestations
      • Emphysematous Cystitis
  • Chlamydia Trachomatis (see Chlamydia Trachomatis, [[Chlamydia Trachomatis]]): may present with combination of acute urinary symptoms, pyuria, and a negative urine culture in young sexually active female
  • Citrobacter (see Citrobacter, [[Citrobacter]])
  • Clostridium Perfringens (see Clostridium Perfringens, [[Clostridium Perfringens]])
    • Clinical Manifestations
      • Emphysematous Cystitis
  • Enterobacter (see Enterobacter, [[Enterobacter]])
    • Clinical Manifestations
      • Emphysematous Cystitis: may occur with Enterobacter Aerogenes (see Enterobacter Aerogenes, [[Enterobacter Aerogenes]])
  • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
    • Epidemiology
      • Most common etiology of UTI: accounts for 75-95% of both male and female UTI cases
    • Clinical Manifestations
      • Emphysematous Cystitis: most common microbial etiology of emphysematous cystitis
      • Emphysematous Pyelonephritis
  • Herpes Simplex Virus (HSV1 or HSV2) (see Herpes Simplex Virus, [[Herpes Simplex Virus]]): may present with combination of acute urinary symptoms, pyuria, and a negative urine culture in young sexually active female
  • Klebsiella (see Klebsiella, [[Klebsiella]]): common etiology
    • Epidemiology: common etiology
    • Clinical Manifestations
      • Emphysematous Cystitis: may occur with Klebsiella Pneumoniae (see Klebsiella Pneumoniae, [[Klebsiella Pneumoniae]])
      • Emphysematous Pyelonephritis: may occur with Klebsiella Pneumoniae (see Klebsiella Pneumoniae, [[Klebsiella Pneumoniae]])
  • Neisseria Gonorrhoeae (Gonococci) (see Neisseria Gonorrhoeae, [[Neisseria Gonorrhoeae]]): may present with combination of acute urinary symptoms, pyuria, and a negative urine culture in young sexually active female
  • Mycoplasma Genitalium (see Mycoplasma Genitalium, [[Mycoplasma Genitalium]]): may present with urethritis or cystitis
  • Mycoplasma Hominis (see Mycoplasma Hominis, [[Mycoplasma Hominis]]): may present with pyelonephritis
  • Proteus Mirabilis (see Proteus Mirabilis, [[Proteus Mirabilis]])
    • Clinical Manifestations
      • Emphysematous Cystitis: may occur
  • Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa, [[Pseudomonas Aeruginosa]])
  • Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
    • Mechanisms of Infection
      • Ascending Infection Due to Foley Catheter
      • Hematogenous Seeding (via Bacteremia)
    • Clinical Manifestations
      • Emphysematous Cystitis: may occur
  • Staphylococcus Epidermidis (see Staphylococcus Epidermidis, [[Staphylococcus Epidermidis]])
  • Staphylococcus Saprophyticus (see Staphylococcus Saprophyticus, [[Staphylococcus Saprophyticus]])
  • Streptococcus (see Streptococcus, [[Streptococcus]])
    • Clinical Manifestations
      • Emphysematous Cystitis: may occur
  • Ureaplasma Urealyticum (see Ureaplasma Urealyticum, [[Ureaplasma Urealyticum]])
    • Clinical Manifestations
      • Acute Cystitis
      • Acute Pyelonephritis
      • Epididymitis (see Epididymitis, [[Epididymitis]])
      • Urethritis (see Urethritis, [[Urethritis]])

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

  • General Comments
    • Dipstick positivity for leukocyte esterase or nitrite has 75% sensitivity/82% specificity for detection of UTI -> conclusion: 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:
  • 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

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

Urine Culture

  • 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: 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

Imaging Studies

  • Abdominal/Pelvic CT
    • Diagnostic of nephrolithiasis and hydronephrosis
    • May demonstrate emphysematous pyelonephritis or emphysematous cystitis
  • KUB: may occasionally detect nephrolithiasis
  • Renal Ultrasound: may be required to rule out hydronephrosis (due to obstruction), anatomic abnormailities, nephrolithiasis, etc

Clinical Presentations

Asymptomatic Bacteriuria

  • Definition: positive urine culture in the absence of symptoms
    • Male: defined as single clean-catch voided urine with single bacterial species isolated in count >100k CFU/mL in absence of symptoms
    • Female: xxxx
  • 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

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, [[Dysuria]])
  • Gross Hematuria (see Hematuria, [[Hematuria]])
  • Suprapubic or Low Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
  • Urinary Frequency
  • Urinary Urgency

Emphysematous Cystitis

  • Epidemiology: rare
  • Risk Factors
    • Diabetes Mellitus (see Diabetes Mellitus, [[Diabetes Mellitus]])
    • Female Sex
    • Immunocompromised State
    • Neurogenic Bladder
    • Prior Urinary Tract Infection
    • Renal Transplant (see Renal Transplant, [[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, [[Abdominal Pain]])
    • Gas In Bladder Wall (Seen on CT Scan): due to bacterial or fungal fermentation
    • Pneumaturia (see Pneumaturia, [[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, [[Abdominal Pain]]):
  • Costovertebral Angle Tenderness
  • Fever/Chills (see Fever, [[Fever]])
  • Flank Pain (see Flank Pain, [[Flank Pain]]): present in cases with pyelonephritis
  • Diarrhea (see Diarrhea, [[Diarrhea]])
  • Nausea and Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])

Emphysematous Pyelonephritis

  • Risk Factors
    • Diabetes Mellitus with Escherichia Coli Urinary Tract Infection (see Escherichia Coli, [[Escherichia Coli]])
    • Diabetes Mellitus with Klebsiella Pneumoniae Urinary Tract Infection (see Klebsiella Pneumoniae, [[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
    • Pyelonephritis with Gas Accumulation in Kidney
    • Pneumomediastinum (see Pneumomediastinum, [[Pneumomediastinum]]): case reports
    • Subcutaneous Emphysema (see Subcutaneous Emphysema, [[Subcutaneous Emphysema]]): case reports
  • Prognosis: may be fatal, if not rapidly treated

Complications


Treatment

Acute Cystitis

Oral (PO) Antibiotics

  • Amoxacillin (see Amoxacillin, [[Amoxacillin]])
    • Resistance rates are typically >20% in most regions -> avoid empiric use
  • Amoxacillin-Clavulanic Acid (Augmentin) (ee Amoxacillin-Clavulanic Acid, [[Amoxacillin-Clavulanic Acid]])/First and Second-Generation Cephalosporins (Cefpodoxime, Cefaclor, Cefdinir) (see Cephalosporins, [[Cephalosporins]])
    • Resistance rates are <10% in most regions -> acceptable for empiric use for female cystitis (7 day regimen)
  • Fluoroquinolone (see Fluoroquinolones, [[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, [[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, [[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)

  • Ampicillin (see Ampicillin, [[Ampicillin]])
    • Resistance rates are typically >20% in most regions -> avoid empiric use
  • Fluoroquinolone (see Fluoroquinolones, [[Fluoroquinolones]])
    • Agents

Emphysematous Cystitis

  • Intravenous Antibiotics
  • Bladder Drainage

Acute Pyelonephritis

Oral (PO) Antibiotics

  • Amoxacillin-Clavulanic Acid (Augmentin) (ee Amoxacillin-Clavulanic Acid, [[Amoxacillin-Clavulanic Acid]])/Secondor Third-Generation Cephalosporins (Cefpodoxime, Cefaclor, Cefdinir) (see Cephalosporins, [[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]]): fluoroquinolones are the only recommended outpatient PO treatment for pyelonephritis
    • Agents

Intravenous (IV) Antibiotics

  • Aminoglycoside (see Aminoglycosides, [[Aminoglycosides]])
  • Aztreonam (see Aztreonam, [[Aztreonam]])
  • Carbapenem (see Carbapenems, [[Carbapenems]]): may be used for pyelonephritis (especially cases due to extended-spectrum beta-lactamase (ESBL)-producing strains)
  • Extended-Spectrum/Anti-Pseudomonal Cephalosporin (see Cephalosporins, [[Cephalosporins]])
    • Cefepime (Maxipime) (see Cefepime, [[Cefepime]])
    • Cefoperazone (Cefobid) (see Cefoperazone, [[Cefoperazone]])
    • Ceftazidime (Ceftaz) (see Ceftazidime, [[Ceftazidime]])
  • Extended-Spectrum/Anti-Pseudomonal Penicillin
  • Fluoroquinolone (see Fluoroquinolones, [[Fluoroquinolones]]): commonly used
    • Agents
  • Third-Generation Cephalosporin (see Cephalosporins, [[Cephalosporins]])
    • Ceftriaxone (Rocephin) (see Ceftriaxone, [[Ceftriaxone]])

Emphysematous Pylelonephritis

  • Intravenous Antibiotics
  • 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 UTI

  • Indicated

Management of Staphylococcus Aureus Bacteriuria

  • In Presence of 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

Prognosis

  • Presence of bacteremia with pyelonephritis does not predict a worse prognosis

References

  • Emphysematous pyelonephritis: clinicoradiological classification, management, prognosis, and pathogenesis. Arch Intern Med. Mar 27 2000;160(6):797-805 [MEDLINE]
  • Emphysematous cystitis: An unusual disease of the Genito-Urinary system suspected on imaging. Ann Clin Microbiol Antimicrob. 2004; 3: 20 [MEDLINE]