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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 61 - Treatment of Urinary Tract Infections in Non-Pregnant Women

“If the world is saved, it will not be saved by old minds with new programs but by new minds with no programs at all." - Daniel Quinn


2018 Cabernet Sauvignon from La Freynelle

PB#91 - Published October 2009 (Reaffirmed 2016)


Five Pearls

1. E. coli are the most common bug in UTI.

2. Presence at at least 1,000 CFU/mL on culture or presence of leukocyte esterase or nitrite on UA, particularly if bacteria 2+ or greater in a symptomatic patient is pretty much a slam dank for UTI diagnosis

3. 3-day antibiotic course is sufficient for uncomplicated acute cystitis (trimethoprim-sulfamethaxazole is the preferred agent)

4. Treatment of pyelonephritis can be done as outpatient unless patient is very sick, in which hospitalization w/ parenteral antibiotics may be warranted

5. If symptoms persist beyond 7 days of antimicrobial therapy or if clinical condition worsens, further evaluation through repeat cultures and contrast imaging may be warranted.


First some definitions

- asymptomatic bacteriuria: bacteria in urine but no symptoms

- cystitis: infection confined to lower urinary tract

- acute pyelonephritis: infection of the renal parenchyma and/or renal pelvis

- relapse: recurrent urinary tract infection (UTI) with the same organism after adequate initial therapy

- reinfection: recurrent UTI caused by previously isolated bacteria after adequate treatment and a negative intervening urine culture


UTI is common in women

- >50% will have a UTI in their lifetime

- more common by a longshot in women compared to men

- 3-5% will have multiple recurrences

- asymptomatic bacteriuria also more common in women; 5-6% of young, sexually active women (this jumps to 20% for 65 years or older)


How does this happen?

- the female urethra is quite short (far shorter than in men...think about it)

- most UTIs are caused when bugs creep up the urethra to the bladder and beyond (though lymphatic and hematogenous spread is also possible, but much less common; e.g. staph endocarditis spreading to the kidney)

- E. coli is present 80% of the time (makes sense given E. coli is found in the gut, and the anus is quite close to the urethra)

- specific virulence factors that enable E. coli to colonize the genitourinary (GU) system also provide resistance to treatment and the immune system

- for example: type 1 fimbriae, P-fimbriae, and S-fimbriae enhance binding to vaginal epithelium and urothelial cells

- P-fimbriated E. coli are especially adapted for climbing the ureters to infect the kidneys (pyelonephritis)

- other bugs: staph saprophyticus (3% of UTIs), proteus, pseudomonas, klebsiella, Enterobacter, enterococcus

- group B streptococcus and fungal strains also found, esp in patients w/ indwelling foley


Risk factors

- girls: congenital anomalies and new onset of sexual activity

- adult women:


Clinical presentation

- an infected bladder can present with dysuria (painful urination), urinary frequency, urinary urgency, and suprapubic pain; fever is rare in uncomplicated acute cystitis

- also with back/flank pain, fever, or chills? consider pyelonephritis

- what if the flank pain radiates to the groin? consider kidney stones ("renal calculi")

- acute urethritis can be caused by Neisseria gonorrhoeae, Chlamydia trachomatis, or herpes, so certainly don't miss that! (clinical signs and symptoms can be similar)

- pelvic inflammatory disease, cholecystitis, cholelithiasis, gastric ulcers, and appendicitis may also be on your differential depending on her presentation


The basics of urine studies

- your job as a clinician is to be discriminate in diagnosing real infection, as poor stewardship of antibiotics leads to the further development of antibiotic-resistance microbes

- on dipstick: leukocyte esterase or nitrites on urinalysis have 75% sensitivity, 82% specificity for acute cystitis

- if patient is symptomatic and dipstick is negative, urinalysis and culture are the next step

- on urinalysis (UA): if bacteriuria (bacteria 5+) and pyuria (10 leukocytes/mL) together, high likelihood of UTI

- on culture: If 100,000 CFU/mL, very specific, but only 50% sensitivity. If >1,000 CFU/mL in a symptomatic patient, higher sensitivity and similar specificity


Note: Pyuria without bacteriuria on UA when the patient presents with dysuria might be suggestive of mycoplasm or ureaplasma urethritis



Complicated versus uncomplicated UTI


Treatment


Uncomplicated acute cystitis: 3 days of antibiotics is sufficient; 90% eradication rate; Table 1 lists preferred antimicrobial agents (trimethoprim-sulfamethoxazole is the preferred agent except in areas with high resistance); some times 7 days may be warranted (e.g. symptoms haven't resolved after 3 days of therapy)

- nitrofurantoin is best in 7-day regimen (it's bacteriostatic versus bactericidal), and it's a great 2nd-line agent to trimethoprim-sulfamethoxazole because it concentrates in the urine and resistance rates are low (but it's ineffective against proteus)


Fun fact: nitrofurantoin macrocrystal formulation requires four times daily dosing and often causes GI distress; nitrofurantoin monohydrate macrocrystals can be dosed twice daily and has less side effects. It, along with trimethoprim-sulfamethoxazole, have less detrimental impact on the microbiome than amoxicillin and beta-lactam antibiotics.



http://amrls.cvm.msu.edu/pharmacology/antimicrobials/effect-on-bacteria




Acute pyelonephritis: hospitalization and parenteral antibiotics no longer required; if patient is reliable, collect a culture and let this guide your outpatient therapy;

- a great plan is to start with a single dose of IV antibiotic then continue with oral therapy for full 14 days; cure rate is nearly 100%

- clinical improvement should be seen within 48-72 hrs

- repeat urine culture after completion of 2-week course as test of cure

- on your first culture, getting a gram stain can be helpful in identifying gram positivity in the very least so that you can responsibly choose an antibiotic to start with

- for both uncomplicated acute cystitis and acute pyelonephritis, many organisms have developed resistance to ampicillin and a relatively high risk of recurrence has been found with β-lactams; therefore neither are considered first line (except if a gram stain shows Gram+ cocci in clusters --> Staph)

- amoxicillin or amoxicillin+clavulanic acid (Augmentin) may be reasonable if a Gram+ bug is isolated on culture

- first line outpatient therapy is a fluoroquinolone

- if patient has urosepsis or otherwise requires hospitalization, parenteral regimens include: aminoglycosides + ampicillin, piperacillin, first-gen cephalosporins, third-gen cephalosporins, aztreonam, or fluoroquinolones




Recurrent UTI

- isolate risk factors: frequent intercourse, long-term spermicide use, diaphragm use, new sexual partner, young at age of first UTI, and maternal history of UTI --> counseling and change of behavior whenever reasonable

- same initial 3-day treatment as in otherwise uncomplicated acute cystitis; get urine culture for test of cure 1-2 weeks after completing course

- if recurrence is frequent, consider daily suppression with a low dose antibiotic (Table 1) for 6-12 months followed by reassessment (decreases risk of recurrence by 95%)

- if recurrences are associated with sexual activity, you can suggest one dose after intercourse


UTI in post-menopausal women

- E. coli still most common, but gram negative bugs are more commonly isolated than in premenopausal women

- options listed in Table 1 remain the best option, and 3-day course is still the recommended duration of therapy


Should I ever prescribe antibiotics to women to initiate themselves?

- the idea here is that if a patient has a propensity for UTI, perhaps a standing order for antibiotics is sufficient rather than going through all of the repeat urine studies every time they develop symptoms

- reasonable to offer a 3-day regimen to be self-initiated, but if symptoms don't improve in 24-48 hrs, they should be evaluated


Why do I need to do urine studies at all if symptoms seem to line up...

- for many women, especially postmenopausal women, intermittent dysuria/frequency/urgency are not related to UTI

- recall that in a hypoestrogenic state, the tissues begin to atrophy, and this in and of itself and present with UTI-like symptoms

- therefore we must be good stewards of antibiotics and think critically when older women report UTI symptoms

- in the very least, using a dipstick or UA to detect pyuria and/or bacteria should be performed

- on the other hand, if your postmenopausal patient has been evaluated before, and cultures have grown out bugs, then it's reasonable to treat empirically


When is urine culture necessary?

- initially, it's not necessary

- start empiric antibiotics and perform urine culture if no improvement of symptoms in 24-48 hrs


When should further evaluation be recommended?

- if patient declines clinically despite adequate therapy that corresponds w/ sensitivities on culture, renal ultrasound may reveal peri-renal abscess

- confirm with IV pyelography or contrast MRI/CT


Is single dose therapy an option?

- data is insufficient but promising

- reserved only for young, healthy women who have had symptoms for no longer than 1 week


Can anything apart from antibiotics be done to prevent/treat recurrent UTI?

- aggressive hydration hasn't been shown to be helpful (and may even dilute the antimicrobial agents in the urine)

- nor has post-coital voiding

- nor has douching or vaginal wiping techniques

- insufficient data on vaginal lactobacilli administration

- cranberry juice and tablets WORK for symptomatic UTI: it works by inhibiting pathogen attachment to urothelium (400 mg TID or four times daily for acute infection; 400 mg 1-2 times daily for prophylaxis)

- remove common dietary irritants that could cause bladder irritation: alcohol, chocolate, citrus fruits, coffee, black tea, tomatoes, vinegar, and sugar

- other alternative and herbal treatments for treatment and/or prevention: methenamine salts, burdock seed, chickweed, nettle leaves and stalks, seaweed, consuming fermented foods, lactobacilli oral supplements, vitamin C, D-Mannose, uva-ursi, pipsissewa, goldenseal, acupuncture

- vaginal estrogen is worth a shot in postmenopausal women (several small RCTs have supported vaginal estrogen as helpful for preventing UTI, though Cochrane concluded no benefit)


When should asymptomatic bacteriuria be treated?

- pregnant women, women undergoing urologic procedures in which mucosal injury is anticipated, or in whom catheter-acquired bacteriuria persists after 48 hrs of therapy

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