{"id":2246,"date":"2016-01-21T09:01:19","date_gmt":"2016-01-21T14:01:19","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2246"},"modified":"2016-03-23T04:39:08","modified_gmt":"2016-03-23T08:39:08","slug":"ibuprofen-for-uuti-part-2-antibiotic-or-nsaid-or-both-or-neither","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2016\/01\/21\/2246\/ibuprofen-for-uuti-part-2-antibiotic-or-nsaid-or-both-or-neither\/","title":{"rendered":"Ibuprofen for uUTI (Part 2): Antibiotic or NSAID? Or Both? Or Neither?"},"content":{"rendered":"

\"ibuprofen<\/a><\/p>\n

While the news is\u00a0abuzz with reports of Zika virus coming to a place near you, an interesting article on a much more mundane topic \u2013 the treatment of uncomplicated UTIs \u2013 should be\u00a0competing for your attention. It is a\u00a0publication we have been\u00a0waiting for, as mentioned in an earlier blog<\/a>. Results from a small\u00a0pilot study comparing\u00a0antibiotic therapy to analgesic therapy (ibuprofen) in acute cystitis patients were intriguing: similar relief of symptoms was seen in both arms, with the antibiotic-sparing regimen demonstrating no harm from withholding microbe-directed therapy [1]<\/a>. A more definitive study was in the works, and the publication is out now.

In\u00a0a remarkable\u00a0first, Gagyor et al. compare causative with symptomatic therapy for uUTI<\/span>\u00a0<\/p>\n<\/div><\/p>\n

Now the BMJ gives us detailed results\u00a0from this more definitive trial\u00a0[2]<\/a>. In this much larger well-controlled study of 494 women presenting with acute cystitis in an outpatient setting, antibiotics were\u00a0not needed by\u00a067% of women. However, without antibiotics it took longer to get over an episode of uUTI. Patients assigned to ibuprofen also were\u00a0more symptomatic with\u00a0dysuria and frequency\/urgency than those started on antibiotic right away. In other words, the \u2018burden of symptoms\u2019 as the authors call it was increased.<\/p>\n

The study was well-designed, multi-center, placebo-controlled, double-blind, and adequately\u00a0powered. Patients with clinical symptoms of acute cystitis were eligible for inclusion; treatment consisted of either ibuprofen at a dose of 400 mg tid x 3 days or a single dose of fosfomycin (3 gram). Patients presenting with signs\/symptoms of pyelonephrits were\u00a0excluded. Follow-up was for 28 days and symptoms were recorded\u00a0by patients using a reasonable (but not yet validated)\u00a0scoring system.\u00a0

This trial\u00a0has all the trappings of a landmark study<\/span><\/p>\n<\/div>. A DSMB was in place for adjudication.<\/p>\n

As so often, depending on point of view, proponents of standard antibiotic therapy will find their preference confirmed, and proponents of \u2018watchful waiting\u2019 will now have data justifying their\u00a0approach to uUTI treatment.<\/p>\n

The designers of the study took a practical approach and enrolled patients based on symptoms without waiting for culture results. Thus, the\u00a0primary analysis is based on the ITT population. These are reasonable design\u00a0features; after all, this was not a registration study which had to\u00a0follow guidelines (which no longer exist for this indication). The authors chose to use standard\u00a080-125%\u00a0bioequivalence margins\u00a0as a\u00a0test of non-inferiority. This seems\u00a0a reasonable choice as well.<\/p>\n

However, there are a few questions about the inclusion\u00a0criteria and how they influenced\u00a0outcomes. Only approx. 76% of women had positive urine\u00a0cultures\u00a0at entry.\u00a0By ITT analysis, only 33% of women in the ibuprofen arm were in need of antibiotic therapy but this percentage went up for the subset of patients with positive urine cultures (defined as >102<\/sup> CFU\/mL) who needed \u00a0antibiotic therapy in 49%. We would have liked to have seen further breakdown of the data based on the older cut-off of \u2265105<\/sup> CFU\/mL, predicting that this would be identify a population with an even higher percentage of antibiotic need. Similarly, patients with a higher symptom score at presentation may have done better with antibiotics than with ibuprofen. Hence, stratification by initial symptom score may be way to discern which patients should be started on antibiotics right away.<\/p>\n

This was not a placebo-controlled study. A small but not negligible percentage of patients on ibuprofen required hospital admission for serious AEs unrelated to infection, including a patient with significant GI bleeding. There were also a few patients that progressed to pyelonephritis in the ibuprofen\u00a0but not in the fosfomycin group.<\/p>\n

Comparing symptom improvement scores is a tricky business. Should symptom relief with an analgesic or spasmolytics not be offered equally to patients in both treatment arms? Was concomitant analgesic use captured in the fosfomycin arm? We could not find answers to these questions in the publication nor in the published protocol [3]<\/a>. Hopefully, the authors will be able to address these and other questions in a subsequent publication.<\/p>\n

This study had a long gestation period; it was planned and executed with great attention to detail. The authors offer data sharing upon request, a very generous offer which should become the rule. Funding was provided by a government research fund.\u00a0 Well done \u2013 Congratulations!<\/p>\n

\n

PLEASE TAKE A MOMENT FOR THIS TOTALLY NON-SCIENTIFIC POLL<\/span><\/strong><\/p>\n

[poll id=”6″]<\/p>\n

References:
\n<\/strong>[1]<\/a> Bleidorn J. Symptomatic treatment (ibuprofen) or antibiotics \u00a0(ciprofloxacin) for uncomplicated urinary tract\u00a0infection? – Results of a randomized controlled pilot trial BMC Medicine 2010, 8:30
\n[2]<\/a> Gagyor I.\u00a0 Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial.\u00a0 BMJ 2015;351:h6544
\n[3]<\/a> Gagyor I. Immediate versus conditional treatment of uncomplicated urinary tract infection – a randomized-controlled comparative effectiveness study in general practices.\u00a0 BMC Infectious Diseases 2012, 12:146<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

While the news is\u00a0abuzz with reports of Zika virus coming to a place near you, an interesting article on a much more mundane topic \u2013 the treatment of uncomplicated UTIs \u2013 should be\u00a0competing for your attention. It is a\u00a0publication we have been\u00a0waiting for, as mentioned in an earlier blog. Results Continue reading Ibuprofen for uUTI (Part 2): Antibiotic or NSAID? Or Both? Or Neither?<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2255,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,3],"tags":[1502,1271,298,898,1583,1501,1375,1110],"class_list":["post-2246","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","tag-acute-cystitis","tag-allphase-pharma-consulting","tag-e-coli","tag-fosfomycin","tag-harald-reinhart","tag-ibuprofen","tag-uti","tag-uuti"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/01\/ibuprofen-fosfomycin-slider-copy.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-Ae","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":2129,"url":"https:\/\/allphasepharma.com\/dir\/2015\/11\/14\/2129\/ibuprofen-for-uuti-interesting-pilot-trial-but-more-to-come-soon\/","url_meta":{"origin":2246,"position":0},"title":"Ibuprofen For uUTI: Interesting Pilot Trial But More to Come Soon","author":"Harald","date":"November 14, 2015","format":false,"excerpt":"At the recent AMDAC, the frequent mention of an unusual uUTI study caught my attention.\u00a0 In their review of placebo-controlled trials, FDA mentioned a study comparing ciprofloxacin with Ibuprofen (Motrin), an NSAID drug without any antibacterial activity[1].\u00a0 By the outcome of total symptom relief, there was no difference. 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Dose-finding in its most basic form involves ascending amounts of drug for efficacy and safety; for antibiotics, however, an effective dose can be predicted nowadays\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/03\/Tipping-Point-2.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/03\/Tipping-Point-2.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/03\/Tipping-Point-2.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2095,"url":"https:\/\/allphasepharma.com\/dir\/2015\/11\/03\/2095\/amdac-november-5-2015-on-fluoroquinolones-in-as-aecb-uuti-part-1\/","url_meta":{"origin":2246,"position":2},"title":"AMDAC November 5, 2015 on Fluoroquinolones in ABS, ABECB, uUTI\u00a0 – Part 1","author":"Harald","date":"November 3, 2015","format":false,"excerpt":"Only now, a few days before the actual AMDAC meeting, the\u00a0FDA\u2019s Briefing Document becomes available to the public.\u00a0 The topic of the December 5th meeting:\u00a0 Reappraisal of the risk\/benefit of fluoroquinolones (FQ) in approved but \u201cmild, self-limiting\u201d disease indications in light of new post-approval safety issues. The document is 617\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"AMDAC - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":4964,"url":"https:\/\/allphasepharma.com\/dir\/2025\/08\/15\/4964\/new-idsa-cuti-guideline\/","url_meta":{"origin":2246,"position":3},"title":"NEW IDSA cUTI GUIDELINE","author":"Harald","date":"August 15, 2025","format":false,"excerpt":"A new Guideline for the treatment of cUTI just arrived.[1] First, we are glad that this somewhat mundane topic receives the attention it deserves.\u00a0 UTIs are often downplayed as minor infections, but the cUTI variety should not be taken lightly.\u00a0 Many patients still are admitted with life-threatening infections, so prompt\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/cUTI-classification.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/cUTI-classification.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/cUTI-classification.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/cUTI-classification.jpg?resize=700%2C400&ssl=1 2x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/cUTI-classification.jpg?resize=1050%2C600&ssl=1 3x"},"classes":[]},{"id":4126,"url":"https:\/\/allphasepharma.com\/dir\/2025\/04\/03\/4126\/blujepa-gepotidacin-fda-approval-uuti-efficacious-e-coli-nitrofurantoin\/","url_meta":{"origin":2246,"position":4},"title":"BLUJEPA \/ Gepotidacin APPROVED FOR UNCOMPLICATED UTI – 1","author":"Harald","date":"April 3, 2025","format":false,"excerpt":"GSK\u2019s pipeline in anti-infectives is impressive. It comprises drugs for bacterial, mycobacterial, fungal, viral infections, and for malaria; in addition, they have a number of vaccines in development.\u00a0 Several antibiotics are listed on their website targeting UTI pathogens, and one of them was just approved, namely gepotidacin \/ Blujepa, a\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/04\/HR_Gepotidacin-in-uUTI-SLIDER.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/04\/HR_Gepotidacin-in-uUTI-SLIDER.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/04\/HR_Gepotidacin-in-uUTI-SLIDER.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":1958,"url":"https:\/\/allphasepharma.com\/dir\/2015\/09\/24\/1958\/after-icaac-some-more-thoughts-on-eravacycline-in-cuti-and-ignite-2\/","url_meta":{"origin":2246,"position":5},"title":"After ICAAC: Some More Thoughts on Eravacycline in cUTI and IGNITE-2","author":"Harald","date":"September 24, 2015","format":false,"excerpt":"When a well-designed pivotal Phase 3 trial fails to show NI, it demands an explanation.\u00a0 While awaiting the company\u2019s analysis of the data, many possible explanations are bandied about.\u00a0 So it was not surprising that the eravacycline cUTI study (IGNITE-2) was mentioned quite often during ICAAC 2015, in sessions and\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"Erava2blog copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=525%2C300 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=700%2C400 2x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/Erava2blog-copy.jpg?resize=1050%2C600 3x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2246","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/comments?post=2246"}],"version-history":[{"count":21,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2246\/revisions"}],"predecessor-version":[{"id":2269,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2246\/revisions\/2269"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/2255"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=2246"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=2246"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=2246"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}