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Renal/urol- UTI

Primary Care Corner with Geoffrey Modest MD: Urinary tract infections review article

26 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

JAMA published a good up-to-date review article on the diagnosis and treatment of uncomplicated urinary tract infections, defined as acute onset of dysuria, frequency or urgency in a healthy, nonpregnant woman without known functional or anatomical abnormalities of the urinary tract (see doi:10.1001/jama.2014.12842), incorporating all articles published until July 2014 (and not including treatment articles before 2000 since the bacterial resistance patterns have changed so much). They assessed 27 RCTs and clinical trials with 6463 patients, 6 systematic reviews and 11 observational studies with >250K patients. Their conclusions:

–Diagnosis: women with at least 2 symptoms of UTI (dysuria, urgency or frequency) and the absence of vaginal discharge have >90% probability of acute cystitis. adding a urine dipstick for leukocyte esterase does not really change the probability, and studies show no benefit of urine culture. so, unless this is relapse/recurrent infection (>2 UTIs within 6 months), complicated infections, or women with a history of multi-drug resistant organisms, telephone-based therapy is as good as coming in to see a clinician (documented by studies). also patient-initiated therapy is good (small studies, but women were correct in diagnosis >90% of the time) — i.e., giving the woman antibiotics to have at home and take as soon as they get symptoms (not-so-shockingly, the sooner they start therapy, the sooner they feel better).
–Treatment: best are trimethoprim/sulfamethoxazole (TMP/SMX) DS bid x3 days, with clinical cure rates 85-100%; nitrofurantoin 100mg bid for 5-7 days (one study showing 5 days was as good as 7). No difference in clinical cure rates compared to TMP/SMX​; fosfomycin 3-g as a single dose. May be a little less effective (I have prescribed it only once in my life, under slight duress from an insistent patient). Of note, the relative cost for a course of therapy for self-paying patient at our pharmacy: TMP/SMX $20.45, Nitrofurantoin $44.10, Fosfomycin (can only get as 3-pak) $198.20
–NOT use: fluoroquinolones (unlike the above, this gets good serum levels and should be reserved for complicated UTIs. Does get good cure rates, but there is increasing bacterial resistance in the community); b-lactams (amoxicillin-clavulanate and cefpodoxime-proxetil) are less effective. non-antibiotics, including ibuprofen, placebo, and cranberry products seem mostly to delay antibiotics.
–In terms of resistance: good to know what the sensitivities are in your area to the different antibiotics and contour therapy to that. It should be noted, however, that many UTIs respond to resistant antibiotics: e.g., for TMP/SMX in one study 84% or susceptible organisms responded vs. 41% of resistant ones, presumably because there is such concentration of antibiotics in the urine that they still work in many cases, which seems better than other studies with placebos. one rule-of-thumb is to use another antibiotic when the resistance rate is above approx. 20%.
–Other groups — not much data. The sense of the authors (under the guise of “expert opinion”) is that men do well with a 14-day course (1 RCT, 1 observational study) in those with febrile UTI involving the prostate, but the experts suggested a 7-day course was likely as good; for diabetic women (1 observational trial), the experts side with treating them as above for nondiabetics.

So, this article basically reinforces immediate treatment of women with uncomplicated UTI symptoms with mostly TMP/SMX or nitrofurantoin, keeping in mind the local resistance patterns. My personal approach for women with relatively frequent infections is to give them a big bottle of TMP/SMX and have them dose themselves. Seems to work well, assuming one chooses appropriate patients (which is really a pretty large % in my practice).

Primary Care Corner with Geoffrey Modest MD: Prophylactic Antibiotics in Kids with UTI and Vesicoureteral Reflux

18 Jun, 14 | by EBM

Vesicoureteral reflux is common in kids, is present in the third of children with febrile UTIs, and is associated with increased risk of renal scarring.  Studies have found mixed results on the efficacy of prophylactic antibiotics.  New England Journal with an article — a two-year randomized control trial in 607 children with vesicoureteral reflux diagnosed after a first or second febrile or symptomatic UTI, randomized to trimethoprim-sulfamethoxazole prophylaxis (3 mg trimethoprim, 15 mg sulfamethoxazole per kg of body weight) or placebo.  Primary outcome was preventing recurrent infections.  Secondary outcome was assessment of renal scarring, treatment failure (a composite of recurrences and scarring) and antimicrobial resistance (see DOI: 10.1056/NEJMoa1401811).  All urines were collected by catheterization or suprapubic aspiration.  Renal scanning was done at baseline and after 1 and 2 years.  Results:

–Average age 12 mo, 92% girls, 80% white, 40% with grade 2 and 40% with grade 3 reflux, 96% without any renal scarring at baseline
–Recurrent UTI in 39 of 302 children on prophylaxis versus 72 with 305 children on placebo (HR 0.50; CI 0.34-0.74).  8 children would need to be treated for 2 years to prevent one case of febrile or symptomatic UTI.
–In children whose index infection was febrile, prophylaxis even more effective (HR 0.41; CI 0.26-0.64)
–children with grade 3 or 4 reflux at baseline were at higher risk, with 22.9% versus 14.3% having a febrile or symptomatic recurrence
–Renal scarring did not differ between groups (11.9% with medication versus 10.2% with placebo)
–Voiding cystourethrography was performed at 2 years, was resolved in 51%, improved in 23%, unchanged in 18.5%, and worse in 7.2%.
–In 87 children with a first recurrence caused by Escherichia coli, proportion of isolates resistant to trimethoprim-sulfamethoxazole was 63% of prophylaxis group, and 19% in the placebo group

so, what does this all mean?   On the one hand, there clearly was benefit of prophylaxis to prevent symptomatic recurrence, and recurrent UTI could result in kids getting very sick quickly and needing to be hospitalized.  On the other hand, the fact that there was no significant increase in renal scarring without antibiotics is reassuring and the increase in antimicrobial resistance is concerning.  Some concerns with the study include the fact that only one antibiotic was used, and the fact that renal scarring was only assessed after 2 years, though the potential for renal scarring may extend beyond that time.  One option (from my secondary analysis of the data) might be to risk stratify patients: use prophylaxis if their first event was a febrile UTI and they have grade 3 or 4 reflux, or patients with multiple recurrent UTIs, or those with bladder or bowel dysfunction (who had a higher rate of recurrence in above study).  Another option, also not explored, is to give parents a prescription for full course antibiotics at home, with instructions to call the on-call primary care physician as soon as a child gets sick (allowing the option for very early treatment of an incipient infection).

geoff

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