UTI in men: 7 day Rx okay

 A recent randomized controlled trial found that for men with urinary tract infections, 7 days of antibiotics was as good as 14 days (see UTI men 7 day rx JAMA2023 in dropbox or doi:10.1001/jama.2021.9899), finding noninferiority of the 2 treatment durations 

 

Details: 

-- 272 men from two VA medical centers were enrolled in the study to determine whether 7 days of UTI treatment was as good as 14 days, using either ciprofloxacin or trimethoprim/sulfamethoxazole (TMP/SMX). The study was from 2014-2020. All men were afebrile 

-- mean age 69, 79% white/19% Black, Charlson comorbidity index 1 (i.e. not very sick), 

-- prior UTI in 60%, BPH in 38%, urinary incontinence in 35%, intermittent catheter use in 18%, prostate cancer 16%, urethral stricture 13%, prior prostatitis 12% 

-- diabetes 34%, stroke 7%, spinal cord injury 4%, CKD 8%

-- symptoms: dysuria 67%, frequency 55%, urgency 33% 

-- urinalysis was done in 253 men (93%), and 239 men (88%) had pretreatment urine culture done (neither of these were tests were required for the study, with the goal to simulate actual clinical practice)

-- urine culture results:

    -- 145 (61%) had >100K CFU/ml

        -- organism involved: E. coli 41%, Klebsiella 16%, enterococcus 9%, coagulase-negative staph 10%; 9 other species were all less than 5%

    -- 39 (16%) had colony counts <100K CFU/ml

    -- 55 (23%) had no growth

-- exclusion criteria:  prior UTI in past 14 days, fever >100.4F, growth of organism not susceptible to the agent initially prescribed (when cultures were done)

-- antibiotics prescribed: 57% had cipro, 43% TMP/SMX

-- all were prescribed 7 or 14 days of antibiotics initially. all men came to the center by day 8 and were randomized to matching antibiotics or placebo for the last 7 days

-- Main outcome: resolution of UTI symptoms by 14 days after completion of antibiotic treatment (those in the 7-day group only had 7 days of active antibiotics), assessing noninferiority of the 7-day regimen

    -- noninferiority of treatment regimens was defined as <10% difference

-- primary analysis: the as-treated group, those who took at least 26 of their 28 doses of medication and missed no more than two consecutive doses 

-- secondary analysis: assessment of all patients as randomized, as well as recurrence of UTI symptoms and/or adverse events within 28 days of stopping their study medications 

 

Results: 

-- UTI resolution: 233/254 (92%) of patients in the as-treated group and 248/272 (91%) in the as-randomized group n(ie, no difference)

 

-- symptom resolution, comparing the 7-day versus 14-day treatment groups: 

    -- primary, as-treated analysis: 

        -- 122/131 (93.1%) taking meds 7 days versus 111/123 (90.2%) taking meds 14 days  

            -- difference: 2.9%, meeting non-inferiority criterion

    -- secondary, as-randomized analysis: 

        -- 125/136 (91.9%)participants versus 123/136 (90.4%) 

            -- difference 1.5%, meeting non-inferiority criterion

-- recurrence of UTI symptoms within 28 days of finishing the 14-day intervention, comparing the 7-day versus 14-day treatmentgroups: 

    -- 13/131 (9.9%) in the 7-day group versus 15/123 (12.9%) in the 14-day group 

            -- difference -3.0%, meeting non-inferiority criterion

 

--post-hoc analyses:

    -- by antibiotic:  symptom improvement with cipro in 147/156 men (94%) vs with TMP/SMX 101/116 (87%), p=0.054 (almost significant statistically)

    -- no difference by duration of treatment by drug used

    -- by urine culture results in the 239 patients with pretreatment urine culture:

        -- >100K CFU/mL: 69/75 (92%) had symptom resolution

        -- <100K CFU/mL: 83/91 (91%) had symptom resolution

        -- no bacteriuria: 28/30 (93%) had symptom resolution

            -- ie, no difference

 

-- adverse events, comparing the 7-day versus 14-day groups: 

    -- 28/136 (20.6%) versus 33/136 (24.3%) 

        -- most common adverse effect was diarrhea, in 8.8% of participants

    -- both groups were quite similar in adverse events, though abnormal blood glucose was more common in the 7-day group, and muscle/joint aches and allergy were more common in the 14-day group 

 

Commentary: 

-- though it is likely that most of us are prescribing 7-day courses of antibiotics in men, the importance of the study is that it was a randomized controlled trial supporting this approach. The issue is that urinary tract infections are really uncommon in men, and that the treatment in men is largely based on the relatively large amounts of data on women 

-- they chose these antibiotics because they were the prevalent ones used during this study time period (as per above, since UTIs in men are pretty infrequent, they analyzed data back to 2014 when we were less tuned into the long-term adverse effects of antibiotics). TMP/SMX is a pretty routine antibiotic (though can have very serious adverse effects, uncommonly) ,and cipro is a much more aggressive one. But cipro has a quite profound effects on our gut microbiome (including being in the worst antibiotic group for causing C difficile infections), as well as other severe musculoskeletal and neurologic adverse effects (see http://gmodestmedblogs.blogspot.com/2016/12/fluoroquinolone-warning.html ).  i personally would also be hesitant to use amoxacillin/clavulanate unless needed, given its profound microbiome effects and potential C difficile infections....

    -- It would be very useful to have analyses of even less toxic antibiotics, such as nitrofurantoin and fosfomycin. 

        -- one of the issues in choosing antibiotics is that there could be underlying chronic prostatitis, which is associated with recurrent urinary tract infections (eg, see https://pubmed.ncbi.nlm.nih.gov/10190383/ ). But in a healthy man with a UTI of recent onset and afebrile, it is reasonable to consider nitrofurantoin or fosfomycin as first-line therapy. Perhaps that will be documented in a subsequent study???

        -- and longer courses of perhaps more potent antibiotics may be needed for men with UTIs who have altered physiology, such as with spinal cord injury or atonic bladders

-- it was also interesting that in the post-hoc analysis, symptom resolution occurred independent of whether there was a clear UTI or not, and this was independent of the length of treatment, or likely the choice of antibiotics (no granular info on this latter claim, but quite likely given the 93% symptom resolution)

    -- of note, acupuncture seems to work well in men with Chronic Prostatitis /Chronic Pelvic Pain Syndrome (CP/CPPS): see http://gmodestmedblogs.blogspot.com/2021/11/a-chinese-randomized-trial-found-that.html 

-- one positive outcome to this study is that it adds to other recent studies finding that shorter courses of antibiotics seem to work just fine, eg for pneumonia (eg see http://gmodestmedblogs.blogspot.com/2019/07/pneumonia-overprescribed-antibiotics.html ), UTIs in women, osteomyelitis, cellulitis, and intra-abdominal infections. And, lower doses are really helpful in decreasing antibiotic overuse and the attendant  increased likelihood of developing drug-resistant bugs

    -- another article suggested that taking the "full course of antibiotics" may be counterproductive: see http://gmodestmedblogs.blogspot.com/2017/07/take-full-course-of-antibiotics.html 

 

Limitations:

-- as with any VA study, there are concerns about the generalization of the results to the non-VA participants (though the VA is certainly a fertile ground for assessment of male treatments/outcomes... ) And, they have a great national database to assess very large numbers of men, making it very, very useful for less prevalent conditions. And their studies are not so often drug company intiated/supported

-- there were some differences in medication adherence in the 7-day group (5 men did not take meds as directed) vs the 14-day group (13 men), though the level of cures found above suggest this was not much of a factor; and the study did have an analysis excluding these less-adherent men, and there was no real difference in outcomes

-- this study did have the very long 2014-2020 time period. And there may have been clinical and therapeutic changes that occurred from beginning to end that might have affected the results. And, perhaps the choice of antibiotics prescribed also changed during this interval. All of this could have affected the results.

-- we do not know the reasons why the initial clinicians chose one antibiotic over another:  there could well be an important bias in antibiotic choice, which could affect generalizability of their results

    -- there was no breakdown of antibiotic effectiveness by prior history of a UTI (in 60% of these men).  were those with prior UTIs more likely to be on cipro? Were the 12% who did not have a urine culture put on TMP/SMX because they were not so sick.  These issues might affect the generalizability of results to those stratified by specific symptoms, comorbidities, and also history of UTIs.

 

so, good to have confirmation that a 7-day course of antibiotics worked so well in a pretty well-designed study (since the patients were not initially randomized to the different antibiotics, leading to the "pretty well-designed" modifier). the study did provide good support for using a 7-day course TMP/SMX. would be great to have more rigorous data on even shorter courses of antibiotics and including less aggressive antibiotics. Would make our microbiomes (and therefore us) happier….

 

geoff

-----------------------------------

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@bidmc.harvard.edu

  

to get access to all of the blogs (2 options):

 

1. go to http://gmodestmedblogs.blogspot.com/ to see the blogs in reverse chronological order

  -- click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

  -- or you can just click on the magnifying glass on top right, then type in a name in the search box and get all the blogs with that name in them

2. go to https://bucommunitymed.wpengine.com/, a website from the Community Medicine section at Boston Medical Center.  This site does have a very searchable and accessible list of my blogs and is the easiest to view blogs and displays more at a time.

 

please feel free to circulate this to others. also, if you send me their emails (gmodest@bidmc.harvard.edu), i can add them to the list