GENITOURINARY INFECTIONS









Bacterial vaginosis (BV)

Overview

  • Bacterial Vaginosis (BV) is a condition where the normal vaginal flora (Lactobacillus sp) is replaced with a high concentrations of anaerobic bacteria, G. vaginalis, Ureaplasma, Mycoplasma, and numerous fastidious or uncultivated anaerobes.
  • BV is prevalent in about 20 - 25% of young women and 15% of pregnant women.
  • The cause of BV is not well-understood. It has been linked to douching, sexual intercourse, and lack of vaginal lactobacilli.
  • Symptoms of BV include vaginal discharge and a fishy malodor. Most women with BV are asymptomatic.

Diagnosis

  • Diagnosis can be made in a lab with a gram stain or with PCR tests that detect the presence of G. vaginalis, A. vaginae, and mobiluncus species
  • A wet mount of the vaginal discharge can be performed bedside to look for the diagnostic clue cells which are epithelial squamous cells covered with coccobacilli in the absence of rods
  • Home vaginal pH tests are widely available, and they can help provide clues to the type of infection. BV typically occurs at a pH ≥ 4.7 while yeast infections occur at the normal vaginal pH of < 4.7.

Treatment overview

  • Treatment is only recommended for women with symptoms
  • Treatment of male sex partners has not been shown to prevent recurrence
  • Women who do not respond to treatment may actually have desquamative inflammatory vaginitis [1,10]

Treatment regimens (2015 CDC)

First line (one of the following)
Alternative regimens

Epididymitis

Overview

  • Epididymitis typically presents with pain that localizes to the posterior testicle. The pain may radiate to the lower abdomen. Symptoms such as fever, urinary frequency, hematuria, and dysuria may also be present.
  • In men aged 14 - 35 years, it is most commonly caused by gonorrhea and chlamydia
  • In men > 35 years, it is most commonly caused by urinary tract pathogens such as E. coli. Patients with bladder outlet obstruction (ex. BPH), recent prostate biopsy, urinary tract instrumentation or surgery may be at greater risk.
  • Chronic epididymitis (≥ 6 weeks) is typically caused by Mycobacterium tuberculosis (TB)
  • In men who give insertive anal intercourse, enteric pathogens like E. coli are possible pathogens
  • Urine tests including urinalysis, culture, and nucleic acid amplification tests (NAATs) for gonorrhea and chlamydia can help to make the diagnosis
  • Empiric treatment is recommended [1,2]

Treatment regimens (2015 CDC)

Epididymitis likely caused by gonorrhea or chlamydia
Epididymitis likely caused by enteric or urinary tract pathogen (one of the following)
Epididymitis that may be caused by gonorrhea, chlamydia, and/or enteric organisms (insertive anal intercourse)

Prostatitis

Symptoms

  • Symptoms of prostatitis include both inflammatory urinary symptoms (urinary frequency, urgency, dysuria) and obstructive urinary symptoms (hesitancy, poor stream, incomplete emptying)
  • Symptoms are often accompanied by genitourinary, pelvic, or rectal pain. Sexual dysfunction (ejaculatory discomfort and hematospermia) may also be present. In acute bacterial prostatitis, systemic signs of infection (fever, nausea, tachycardia) are often present.
  • Acute prostatitis is marked by sudden onset of fever, pain, and urinary symptoms. Sicker patients may require intravenous antibiotics.
  • Chronic prostatitis is marked by recurrent pain and urinary symptoms that last greater than 3 months

Diagnosis

  • There is a lack of professional consensus on what defines a diagnosis of prostatitis
  • Laboratory testing in prostatitis has limited diagnostic value. All patients should have a urinalysis with culture. Prostatic massage tests are cumbersome, have not been adequately validated, and are rarely performed.
  • Patients with risk factors for STDs should be tested for chlamydia and gonorrhea
  • Diagnosis of prostatitis is typically based on symptoms. In practice, < 10% of men diagnosed with prostatitis have a proven bacterial infection while about 50% of these patients receive antibiotics.
  • Risk factors for prostatitis include recent urinary tract instrumentation, urethral stricture, and urinary tract infection
  • Bacterial prostatitis is typically caused by E. Coli [3,4]

Treatment regimens

Acute prostatitis
Chronic prostatitis

Pyelonephritis (kidney infection)

Overview

  • Symptoms of pyelonephritis include urinary urgency, frequency, and dysuria accompanied by fever, flank pain, and nausea and vomiting
  • Urinalysis and urine culture should be performed
  • In otherwise healthy patients, most cases of pyelonephritis can be managed on an outpatient basis
  • E. coli causes up to 95% of cases of pyelonephritis. Other pathogens include Klebsiella pneumoniae and Staphylococcus saprophyticus [5,6]

Treatment regimens (2011 IDSA)

First line
Alternative regimens
  • Sulfamethoxazole-trimethoprim 800/160 mg twice a day for 14 days ($)
    • If this regimen is used empirically, then also give Ceftriaxone 1000 mg IM one time dose
  • Oral cephalosporins are not as effective as the other choices. If one is used, then also give Ceftriaxone 1000 mg IM one time dose

Urinary tract infection, ADULTS | UTI | Cystitis

Overview

  • UTI symptoms include burning with urination, urinary frequency, blood in urine, urgency, and suprapubic pain and pressure
  • After first UTI, 25% of women have recurrence within 6 months
  • A positive urinalysis for leukocyte esterase or nitrites has a sensitivity of 75% and a specificity of 82%
  • Asymptomatic bacteriuria should not be treated in most patients (exceptions - pregnant women, patients undergoing urological procedures)
  • E. coli causes up to 95% of cases of UTI. Other pathogens include Klebsiella pneumoniae and Staphylococcus saprophyticus

Recurrent UTIs

  • For women with ≥ 3 UTIs in 12 months, preventative therapy may be tried
  • Imaging studies (e.g. ultrasounds, CT scans) and urological referrals have low yield in women and are not recommended
  • For continuous antibiotic therapy, a six month trial is recommended. After 6 months, stop and observe. About 50% of women will have a return to recurrent UTIs. Antibiotics may be restarted if needed.
    • Measures that may help prevent recurrent UTIs include:
      • Reduction in intercourse
      • Avoid spermicides
      • Urinate after intercourse
      • Drink more fluids - one study found that drinking an additional 1.5 liters/day reduced recurrent UTIs [PMID 30285042]
      • Avoid douching
      • Wipe front to back
      • Avoid tight-fitting underwear
      • Cranberry juice, capsules, or tablets - no clear benefit in studies [PMID 23076891, 21148516, 22305026, 27787564]
      • Topical estrogen in postmenopausal women
      • D-mannose - in one unblinded study, 2 grams once daily was found to be effective [PMID 23633128]
    • NOTE: None of these interventions have been conclusively proven to reduce infections [5,6]

Treatment (2011 IDSA)

First line
Second line
Other (typically less effective)
  • Augmentin 875/125 twice a day for 3 - 7 days ($)
  • Cefdinir 300 mg twice a day for 3 - 7 days ($)
  • Cefadroxil 1 - 2 grams/day given once daily or divided into 2 doses for 3 - 7 days ($)
  • Cefpodoxime 100 mg twice a day for 3 days ($$)
  • Cefuroxime 250 mg twice a day for 7 days ($)
  • Cephalexin 500 mg twice a day for 7 days ($)

Prophylactic therapy for recurrent UTIs

Postcoital (single dose)
Continuous (try for 6 months, then reevaluate)

Studies

Nitrofurantoin vs Fosfomycin for UTI, JAMA (2018) [PubMed abstract]
  • Design: Randomized, controlled trial (N=513 | length = 28 days) in women with uncomplicated UTI
  • Treatment: Nitrofurantoin 100 mg three times a day for 5 days vs Fosfomycin 3000 mg one time
  • Primary outcome: clinical response in the 28 days following therapy completion, defined as clinical resolution (complete resolution of symptoms and signs of UTI without prior failure), failure (need for additional or change in antibiotic treatment due to UTI or discontinuation due to lack of efficacy), or indeterminate (persistence of symptoms without objective evidence of infection)
  • Results:
    • Primary outcome: Nitrofurantoin - 70%, Fosfomycin - 58% (p=0.004)
  • Findings: Among women with uncomplicated UTI, 5-day nitrofurantoin, compared with single-dose fosfomycin, resulted in a significantly greater likelihood of clinical and microbiologic resolution at 28 days after therapy completion

Norfloxacin vs Diclofenac for UTI, BMJ (2017) [PubMed abstract]
  • Design: Randomized, controlled trial (N=253 | length = 3 days) in women with uncomplicated UTI
  • Treatment: Norfloxacin 400 mg once daily for 3 days vs Diclofenac 75 mg once daily for 3 days
  • Primary outcome: resolution of symptoms at day 3 (72 hours after randomization and 12 hours after intake of the last study drug)
  • Results:
    • Primary outcome: Norfloxacin - 80%, Diclofenac - 54% (p<0.001)
  • Findings: Diclofenac is inferior to norfloxacin for symptom relief of UTI and is likely to be associated with an increased risk of pyelonephritis, even though it reduces antibiotic use in women with uncomplicated lower UTI.

Fosfomycin vs Ibuprofen for UTI, BMJ (2015) [PubMed abstract]
  • Design: Randomized, controlled trial (N=484 | length = 28 days) in women with UTI
  • Treatment: Fosfomycin 3000 mg one time vs Ibuprofen 400 mg three times a day for 3 days
  • Primary outcome: number of all courses of antibiotic treatment on days 0 - 28 (for UTI or other conditions) and burden of symptoms on days 0 - 7
  • Results:
    • Primary outcome (antibiotic courses during follow-up): Fosfomycin - 40 courses, Ibuprofen - 94 courses (p<0.001)
    • Women who received antibiotics during follow-up for UTI: Fosfomycin - 12%, Ibuprofen - 31% (p<0.001)
  • Findings: Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms.

Urinary tract infection, PEDIATRIC | UTI | Cystitis

Overview

  • Approximately 7 - 8% of girls and 2% of boys have a UTI during the first 8 years of life.
  • Children 2 months to 2 years with first febrile UTI should have a renal and bladder ultrasound. Voiding Cystourethrography (VCUG) is not routinely recommended in these children. A recent study evaluated the utility of VCUG in infants (0 - 3 months) with first febrile UTI. See pediatric UTI studies for more.
  • For children 2 months to 2 years, urine specimen should be obtained through catheterization or suprapubic aspiration. Infection is confirmed by presence of pyuria and/or bacteriuria, and the presence of at least 50,000 colony-forming units (CFUs) per mL of a uropathogen cultured from a urine specimen. [7,8]

Vesicoureteral reflux (VUR)

  • Treatment of children with Vesicoureteral Reflux (VUR) is controversial
  • VUR ranges from Grade I (mild) to Grade V (severe)
  • Treatment options include surveillance, antibiotic prophylaxis, surgical repair, and endoscopic injection of bulking agent
  • Studies comparing surgery to antibiotic prophylaxis have found no significant difference between the two [PMID 1433585, 11343739, 2888509]
  • The RIVUR trial [PMID 24795142] compared prophylaxis with sulfamethoxazole-trimethoprim to placebo in children 2 to 71 months with grade I - IV reflux. The trial found that antibiotic prophylaxis halved the risk of recurrent UTI over 2 years, but had no effect on renal scarring.
  • The optimal duration of prophylaxis has not been determined. In trials, it has typically been for 1 - 2 years [7,8,9]

Treatment

Typical regimens
  • Sulfamethoxazole-trimethoprim 6 - 12 mg/kg/day (trimethoprim component) given in 2 divided doses for 7 - 14 days ($)
  • Augmentin 20 - 40 mg/kg/day given in 3 divided doses for 7 - 14 days ($)
  • Cefixime 8 mg/kg/day (max 400 mg/day) given once daily for 7 - 14 days ($)
  • Cefpodoxime 10 mg/kg/day (max 400 mg/day) given in 2 divided doses for 7 - 14 days ($$)
  • Cefuroxime 20 - 30 mg/kg/day (max 1000 mg/day) given in 2 divided doses for 7 - 14 days ($)
  • Cephalexin 50 - 100 mg/kg/day (max 2000 mg/day) given in 4 divided doses for 7 - 14 days ($)
Other

Prophylactic therapy for vesicoureteral reflux


Studies

Avoidance of voiding cystourethrography in infants younger than 3 months with Escherichia coli urinary tract infection and normal renal ultrasound - Archives of Disease in Childhood (2017) [PMID 28408468]
  • Design: Cohort study (N=122)
  • Inclusion criteria: Infants aged 0 - 3 months with a first febrile UTI undergoing renal ultrasound (US) and VCUG
  • Primary outcome: Risk factors for high-grade vesicoureteral reflux (VUR) defined as grade ≥ III
  • Results: The probability of high-grade VUR was 3% in the presence of urinary E. coli infection. Adding a normal renal US finding decreased this probability to 1%. However, in the presence of non-E. coli bacteria, the probability of high-grade VUR was 26%, and adding an abnormal US finding increased further this probability to 55%.
  • Findings: In infants aged 0 - 3 months with a first febrile UTI, the presence of E. coli and normal renal US findings allow to safely avoid VCUG. Performing VCUG only in infants with UTI secondary to non-E. coli bacteria and/or abnormal US would save many unnecessary invasive procedures, limit radiation exposure, with a very low risk (<1%) of missing a high-grade VUR.

Association Between Uropathogen and Pyuria - Pediatrics (2016) [PMID 27328921]
  • Design: Retrospective Cohort study (N=1181)
  • Inclusion criteria: Children evaluated in the ER with symptoms of UTI who had paired urinalysis and urine cultures
  • Primary outcome: Association between pyuria and uropathogens
  • Results: Children with Enterococcus species, Klebsiella species, and Pseudomonas aeruginosa were significantly less likely to exhibit pyuria than children with Escherichia coli (odds ratio of 0.14, 0.34, and 0.19, respectively). Children with these organisms were also less likely to have a positive leukocyte esterase on dipstick urinalysis.
  • Findings: We found that certain uropathogens are less likely to be associated with pyuria in symptomatic children. Identification of biomarkers more accurate than pyuria or leukocyte esterase may help reduce over- and undertreatment of UTIs.

Yeast infection (vulvovaginal candidiasis)

Overview

  • An estimated 75% of women have at least one yeast infection during their lifetime, and 40 - 45% will have ≥ 2 episodes
  • Symptoms of a yeast infection include vaginal itching, soreness, pain with intercourse, painful urination, redness, and thick, white, curdy discharge
  • Yeast infections are typically caused by Candida albicans

Diagnosis

  • Definitive diagnosis is made by observing hyphae or pseudohyphae on a wet preparation. 10% KOH solution improves the visualization of yeast and mycelia by disrupting cellular material that might obscure the yeast or pseudohyphae.
  • A large number of home vaginal pH tests are available. Yeast infections typically occur at the normal vaginal pH which is < 4.7 while bacterial vaginosis occurs at a vaginal pH ≥ 4.7.

Recurrent yeast infections

  • Recurrent vulvovaginal candidiasis is defined as ≥ 4 episodes in 1 year
  • Recurrent vulvovaginal candidiasis can be treated with prolonged episodic therapy or maintenance therapy for 6 months (see below. 30 - 50% of women will have recurrent disease after maintenance therapy is discontinued.

Treatment overview

  • Creams and suppositories are oil-based and might weaken latex condoms
  • Yeast infections are not acquired through sexual intercourse and sex partners should not be treated

Treatment regimens (2015 CDC)

Over-the-counter
  • Clotrimazole (Lotrimin®) - cream; use as directed ($)
  • Miconazole (Monistat®) - cream, vaginal suppository; use as directed ($)
  • Tioconazole - cream; use as directed ($)
Prescription
  • Butoconazole 2% cream (Gynazole®) - one applicatorful of cream (approximately 5 grams of the cream) intravaginally for one dose ($$)
  • Terconazole (Terazol®)
    • 0.4% cream 5 grams intravaginally for 7 days ($)
    • 0.8% cream 5 grams intravaginally for 3 days ($)
    • 80 mg vaginal suppository, one suppository daily for 3 days ($)
  • Fluconazole 150 mg one time dose ($)

Treatment for recurrent infections

Prolonged therapy
  • Prolonged topical therapy - 7 - 14 days of therapy
  • Fluconazole 100 - 200 mg every third day for a total of 3 doses ($)
Maintenance therapy
  • Fluconazole 100 - 200 mg once weekly for 6 months ($)

Studies

Oral fluconazole during pregnancy and risk of spontaneous abortion and stillbirth, JAMA (2016) [PubMed abstract]
  • Design: Register-based cohort study among pregnant women with propensity score matching (N=1,405,663)
  • Exposure: Oral fluconazole vs None
  • Primary outcome: Hazard ratios for spontaneous abortion and stillbirth, estimated using proportional hazards regression
  • Results: There was a significantly increased risk of spontaneous abortion associated with fluconazole exposure (HR 1.48; 95% CI, 1.23-1.77). There was no significant association between fluconazole exposure and stillbirth (HR 1.32 [95% CI, 0.82-2.14])
  • Findings: In this nationwide cohort study in Denmark, use of oral fluconazole in pregnancy was associated with a statistically significant increased risk of spontaneous abortion compared with risk among unexposed women and women with topical azole exposure in pregnancy. Until more data on the association are available, cautious prescribing of fluconazole in pregnancy may be advisable. Although the risk of stillbirth was not significantly increased, this outcome should be investigated further.



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