- ACRONYMS AND DEFINITIONS
- BV - Bacterial vaginosis
- CDC - Centers for Disease Control and Prevention
- IDSA - Infectious Diseases Society of America
- RCT - Randomized controlled trial
- UTI - Urinary tract infection
- VUR - Vesicoureteral reflux
Bacterial vaginosis (BV)
- Bacterial Vaginosis (BV) is a condition where the normal vaginal flora (Lactobacillus sp) is replaced with a high concentration of 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. After treatment, recurrence is common, with up to 75% of women experiencing reinfection in some studies.
- 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; however, most women with BV are asymptomatic
- 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 vaginal discharge can be performed to look for the diagnostic clue cells, which are squamous epithelial 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 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]
2021 CDC recommendations
- Metronidazole 500 mg twice a day for 7 days ($)
- Metronidazole gel 0.75% - one full applicator (5 grams) intravaginally once daily for 5 days ($)
- Clindamycin cream 2% - one full applicator (5 grams) intravaginally at bedtime for 7 days ($-$$)
- Alternative regimens
- Design: Randomized placebo-controlled trial (N=228 | length = 12 weeks) in women diagnosed with BV who were treated with vaginal metronidazole gel
- Treatment: Lactobacillus crispatus (Lactin-V) powder (2×109 CFU) intravaginally once daily for 4 days then twice weekly vs Placebo powder
- Primary outcome: Recurrent bacterial vaginosis on testing done at 4, 8, and 12 weeks
- Primary outcome: Lactobacillus crispatus - 30%, Placebo - 45% (p=0.01)
- Findings: The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks.
- Epidemiology - there are approximately 600,000 cases of epididymitis in the U.S. each year, with peak incidences occurring between the ages of 16 - 30 and 51 - 70.
- Pathology - epididymitis may be caused by infectious agents and noninfectious processes. Bacterial agents typically reach the epididymis through retrograde ascent; one exception is tuberculosis, which seeds the epididymis through hematogenous spread. Urinary pathogens such as E. coli are most common in boys < 14 years and men > 35, while gonorrhea and chlamydia predominate in sexually-active young adults. Chronic epididymitis, defined as ≥ 6 weeks, may be caused by M. tuberculosis and other granuloma-inducing processes (e.g. sarcoidosis). Nonbacterial causes of epididymitis include trauma, postprostatic biopsy and postvasectomy epididymal inflammation, sarcoidosis, Behcet disease, enterovirus and adenovirus (in children), and vasculitis.
- Risk factors - risk factors for epididymitis include sexual activity, insertive anal intercourse, bladder outlet obstruction (ex. BPH), recent prostate biopsy, and urinary tract instrumentation or surgery
- Symptoms - epididymitis typically presents with localized pain in the posterior testicle that can radiate to the lower abdomen. Symptoms such as fever, urinary frequency, hematuria, penile discharge, and dysuria may be present. Testicular torsion is a urologic emergency that can present with similar symptoms. Torsion is most commonly seen in boys 12 to 18 years old and is rare after age 35.
- Diagnosis - diagnostic testing includes urinalysis, culture, and nucleic acid amplification tests (NAATs) for gonorrhea and chlamydia. Empiric treatment is recommended [1,2,14,17]
Treatment regimens (2021 CDC)
Epididymitis likely caused by gonorrhea or chlamydia
Epididymitis likely caused by enteric or urinary tract pathogen
- Levofloxacin 500 mg once daily for 10 days ($)
- Epidemiology - there is no reference standard for diagnosing prostatitis, so epidemiologic data is based on patients with typical symptoms. In studies, the prevalence of prostatitis ranges from 2.2 - 9.7%, with acute bacterial prostatitis being more common in younger patients (< 35 years) and chronic prostatitis predominating in older men.
- Etiology - acute prostatitis is typically caused by gram-negative bacteria, including Escherichia coli, Enterobacter, Serratia, Pseudomonas, Proteus, and Klebsiella. Gonorrhea and chlamydia are also seen, particularly in sexually-active young men. In chronic prostatitis (symptoms > 3 months), gram-negative bacteria still predominate, but other etiologies should be considered, including gram-positive bacteria (e.g. Enterococci), atypical pathogens (e.g. M. tuberculosis, Candida spp), and noninfectious causes.
- Symptoms - prostatitis is marked by inflammatory symptoms (e.g. urinary frequency, urgency, dysuria), obstructive symptoms (e.g. hesitancy, poor stream, incomplete emptying), and pain in the pelvis and/or rectum that is poorly localized. Sexual dysfunction (e.g. ejaculatory discomfort, hematospermia) is also common. In acute bacterial prostatitis, systemic symptoms may be present, including fever, nausea, and tachycardia.
- Diagnosis - there is a lack of professional consensus on what defines a diagnosis of prostatitis. Prostatic fluid is difficult to obtain, and an etiologic agent is identified in less than 10% of cases. Urinalysis and mid-stream urine culture are recommended in all patients. Sexually-active men should be tested for gonorrhea and chlamydia. The prostate may be tender and swollen on exam; however, digital rectal exams are uncomfortable for most patients, making these findings difficult to discern. Prostatic massage with a 4-glass test (Meares-Stamey test) is cumbersome and rarely performed. PSA levels are elevated in 60% of men with acute bacterial prostatitis, but they are not recommended for diagnostic purposes. [3,4,15,16]
- First line
- Ciprofloxacin 500 mg twice a day for 4 - 6 weeks ($)
- Levofloxacin 500 mg once daily for 4 - 6 weeks ($)
- Sulfamethoxazole-trimethoprim 800/160 mg twice a day for 4 - 6 weeks ($)
Pyelonephritis (kidney infection)
- Symptoms of pyelonephritis include urinary urgency and frequency, dysuria, fever, flank pain, nausea, and vomiting
- Most healthy patients with manageable nausea can be treated as outpatients
- E. coli is found in up to 95% of cases. Other less common pathogens include Klebsiella pneumoniae and Staphylococcus saprophyticus. [5,6]
Treatment regimens (2011 IDSA)
- Ciprofloxacin 500 mg twice a day for 7 days ($)
- Ciprofloxacin extended-release 1000 mg once daily for 7 days ($$)
- Levofloxacin 750 mg once daily for 5 days ($)
- If community resistance to fluoroquinolones is > 10%, then give Ceftriaxone 1000 mg IM one time dose in addition to one of the above regimens
Urinary tract infection, ADULTS | UTI | Cystitis
- UTI symptoms include dysuria, urinary frequency, hematuria, urgency, and suprapubic pain and pressure
- Women account for about 80% of UTI cases, and recurrence is common; after a first UTI, 25% of women will have another UTI within 6 months
- UTIs are less common in males, but as men age and benign prostatic hyperplasia (BPH) becomes more prevalent, the risk increases. BPH obstructs normal urine flow, and this facilitates the ascension of uropathogens into the bladder and prostate. Prostatitis and UTI have overlapping symptoms, so men with UTI symptoms are often treated for acute prostatitis.
- E. coli accounts for up to 95% of cases. Other pathogens include Klebsiella pneumoniae, Enterococcus species, and Staphylococcus saprophyticus.
- A positive urinalysis for leukocyte esterase or nitrites has a sensitivity of 75% and a specificity of 82%
- Asymptomatic bacteriuria should not be treated with the exception of pregnant women and patients undergoing urological procedures [5,6,11]
Treatment (2011 IDSA)
Other (typically less effective)
- Augmentin 875/125 twice a day for 3 - 7 days ($)
- 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 ($)
- For women with ≥ 3 UTIs in 12 months, preventative therapy may be tried
- Imaging studies (e.g. ultrasounds, CT scans) and urologic 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 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]
- Methenamine hippurate 1 gram twice daily was found to be noninferior to antibiotic prophylaxis in an open-label trial that allowed crossovers [PMID 35264408]
- NOTE: None of these interventions have been conclusively proven to reduce infections [5,6]
Prophylactic therapy for recurrent UTIs
Postcoital (single dose)
Continuous (try for 3 - 6 months, then reevaluate)
- Design: Randomized, placebo-controlled trial (N=272 | length = 28 days) in men prescribed 7 - 14 days of ciprofloxacin or trimethoprim/sulfamethoxazole for afebrile UTI
- Treatment: After receiving their prescribed antibiotic for 7 days, patients were randomized to continue their antibiotic or switch to placebo for days 8 - 14. Ciprofloxacin was prescribed in 57% of patients and trimethoprim/sulfamethoxazole in 43%.
- Primary outcome: Resolution of the initial UTI symptoms by day 14 after completion of active antibiotic treatment
- Primary outcome: Seven days - 93%, Fourteen days - 90% (seven days noninferior)
- Findings: Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI.
- 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)
- 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
- 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)
- 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.
- 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
- 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
- Epidemiology - UTIs are the most common bacterial infection in children. Approximately 8% of girls and 2% of boys have a UTI during the first 8 years of life. The incidence for males is around 5.3% during the first 6 months and drops to 2% after the age of one. In females, the opposite is true, as their risk goes from 2% during the first 6 months to 11% after one year.
- Pathology - most UTIs occur when bacteria ascend the urethra and reach the bladder. Infections confined to the bladder typically lack systemic symptoms (e.g. fever) and are easily eradicated with antibiotics. Infections that ascend the ureters and reach the kidneys usually cause fever, and in children, can be a sign of underlying urinary tract abnormalities, including vesicoureteral reflux, which is a risk factor for recurrent infections. Recurrent febrile UTIs can lead to renal scarring and loss of kidney function. The most common cause of UTIs in children is E. coli (up to 90%). Other less common pathogens include Proteus Mirabilis, Klebsiella species, Pseudomonas Aeruginosa, and Enterococcus.
- Symptoms - infections confined to the bladder cause dysuria, frequency, enuresis, hematuria, suprapubic pain/pressure, and urgency. Infections that reach the kidneys are marked by fever, chills, flank pain, nausea, vomiting, and in severe cases, sepsis and shock.
- Diagnosis - collecting good urine samples in young children can be challenging. A two-step approach that can minimize invasive procedures involves first obtaining a urine sample from a clean-catch or plastic bag attached to the patient and performing a urinalysis on it; the risk of contamination with these methods is high (50 - 60% for a bag, 26% for clean-catch), but they can be used to rule out a UTI. If the urinalysis is negative, a bladder infection is unlikely, and a culture does not need to be performed. If the urinalysis is positive, a new urine specimen should be obtained through catheterization or suprapubic bladder aspiration; these methods have a much lower risk of contamination so that a UTI can be definitively diagnosed. In toilet-trained children, midstream samples after careful cleaning of the genitalia are acceptable. The presence of at least 50,000 colony-forming units (CFUs) per mL of a uropathogen is consistent with a UTI.
- Genitourinary tract evaluation - febrile UTIs in children can be a sign of anatomical abnormalities; therefore, imaging of the GU tract is recommended in some cases. Children 2 months to 2 years with first febrile UTI should have a renal and bladder ultrasound, which will find irregularities in about 15% of cases. Voiding cystourethrography (VCUG) is the gold standard for diagnosing vesicoureteral reflux, but it is invasive and exposes the patient to radiation. Recommendations for performing VCUG vary, but the following high-risk features are typically listed as indications: (1) abnormal findings on ultrasound consistent with VCUG (e.g. hydronephrosis, scarring) (2) UTI not caused by E. coli, (3) recurrent febrile UTI, (4) UTI with complicated clinical course (e.g. sepsis). A recent study evaluated the utility of VCUG in infants (0 - 3 months) with first febrile UTI. See pediatric UTI studies for more. [7,8,12]
Vesicoureteral reflux (VUR)
- Vesicoureteral reflux (VUR) is a condition where urine is able to flow up the ureter from the bladder. Under normal conditions, a valve at the junction of the ureter and bladder prevents the retrograde flow of urine. VUR is associated with recurrent febrile UTIs that lead to renal scarring and loss of kidney function. VUR is graded on a scale of I (mild) to V (severe).
- The treatment of VUR is controversial, and in many cases, the condition resolves spontaneously as the child grows. Treatment options for more severe disease include surveillance, antibiotic prophylaxis, surgical repair, and endoscopic injection of bulking agents. Studies that have compared surgery to antibiotic prophylaxis have found no significant difference between the two. [PMID 1433585, 11343739, 2888509] A trial comparing prophylaxis with sulfamethoxazole-trimethoprim to placebo in children 2 to 71 months with grade I - IV reflux found that antibiotic prophylaxis halved the risk of recurrent UTI over 2 years but had no effect on renal scarring. [PMID 24795142]. [7,8,9]
- 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 ($)
- Cephalexin 50 - 100 mg/kg/day (max 2000 mg/day) given in 4 divided doses for 7 - 14 days ($)
Prophylactic therapy for vesicoureteral reflux
- Sulfamethoxazole-trimethoprim 3 mg/kg/day (trimethoprim component) given once daily [Based on PMID 24795142]
- Trimethoprim 1 - 2 mg/kg/day given once daily [Based on PMID 11343739]
- Nitrofurantoin 1 - 2 mg/kg/day given once daily [Based on PMID 11343739]
- The optimal duration of prophylaxis has not been determined; in trials, it has typically been given for 1 - 2 years
- 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.
- 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)
- 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
- 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, and it can be treated with prolonged episodic therapy or maintenance therapy for 6 months (see below). In 2022, the azole antifungal oteseconazole (Vivjoa®) was FDA-approved to treat recurrent yeast infections.
- 30 - 50% of women will have recurrent disease after maintenance therapy is discontinued
- 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)
- Clotrimazole (Lotrimin®) - cream; use as directed ($)
- Miconazole (Monistat®) - cream, vaginal suppository; use as directed ($)
- Tioconazole - cream; use as directed ($)
- Butoconazole 2% cream (Gynazole®) - one applicatorful of cream (approximately 5 grams of the cream) intravaginally for one dose ($$)
- Terconazole (Terazol®)
- 0.4% cream 5 grams intravaginally for 7 days ($)
- 0.8% cream 5 grams intravaginally for 3 days ($)
- 80 mg vaginal suppository, one suppository daily for 3 days ($)
- Fluconazole 150 mg one time dose ($)
Treatment for recurrent infections
- Prolonged topical therapy - 7 to 14 days of therapy
- Fluconazole 100 - 200 mg every third day for a total of 3 doses ($)
- Fluconazole 100 - 200 mg once weekly for 6 months ($)
- Oteseconazole (Vivjoa®)
- Vivjoa-only regimen
- On Day 1: 600 mg as a single dose
- On Day 2: 450 mg as a single dose
- Beginning on Day 14: 150 mg once weekly for 11 weeks
- Take with food. Do not chew, crush, dissolve, or open the capsules.
- Fluconazole/Vivjoa regimen
- On Day 1, Day 4, and Day 7: fluconazole 150 mg
- On Days 14 through 20: Vivjoa 150 mg once daily for 7 days
- Beginning on Day 28: Vivjoa 150 mg once weekly for 11 weeks
- Take with food. Do not chew, crush, dissolve, or open the capsules.
- PRICE ($) INFO
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- 1 - PMID 26042815 - CDC 2015 STD recs
- 2 - PMID 19378875 - AFP epididymitis review
- 3 - PMID 20459324 - IDSA prostatitis review
- 4 - PMID 20704171 - AFP prostatitis review
- 5 - PMID 21888302 - AFP review of pyelo
- 6 - PMID 21292654 - IDSA Pyelo GL
- 7 - PMID 21774712 - NEJM review of ped uti
- 8 - PMID 21873693 - AAP UTI GL
- 9 - PMID 24795142 - RIVUR trial
- 10 - PMID 30575452 - Bacterial Vaginosis and Desquamative Inflammatory Vaginitis, NEJM (2018)
- 11 - PMID 31615788 - GPs’ attitudes towards the diagnosis and treatment of male urinary tract infections: a qualitative interview study in Ireland, BJGP Open (2019)
- 12 - PMID 33589366 - Update of the EAU/ESPU guidelines on urinary tract infections in children, Journal of Pediatric Urology (2021)
- 13 - PMID 34292926 - Sexually Transmitted Infections Treatment Guidelines, MMWR Recomm Rep (2021)
- 14 - PMID 26602616 - Epididymitis, Clin Infect Dis (2015)
- 15 - PMID 18164907 - Epidemiology of prostatitis, Int J Antimicrob Agents (2008)
- 16 - Prostatitis, Medscape