{"id":4964,"date":"2025-08-15T14:20:30","date_gmt":"2025-08-15T20:20:30","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=4964"},"modified":"2025-09-12T14:19:58","modified_gmt":"2025-09-12T20:19:58","slug":"new-idsa-cuti-guideline","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2025\/08\/15\/4964\/new-idsa-cuti-guideline\/","title":{"rendered":"NEW IDSA cUTI GUIDELINE"},"content":{"rendered":"

\"\"<\/a>A new Guideline for the treatment of cUTI just arrived.[1]<\/a><\/p>\n

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 recognition and treatment is paramount.\u00a0 The days are gone when almost all infections were caused by pan-susceptible E. coli.\u00a0 Therefore, antibiotic selection is no longer straightforward.<\/p>\n

The new Guideline is a 59 page monster.\u00a0 Even without references, it runs 49 pages long, virtually guaranteeing that no one will read the full document.\u00a0 Thankfully, it comes with an abridged Executive Summary which covers the essentials (still running 13 pages long without references).\u00a0 Here are some key points and our take on them.<\/p>\n

First, gone is the tripartite classification: we are back to the older 2-tiered classification which recognizes uUTI and cUTI, with pyelonephritis now back under the cUTI heading.\u00a0 This makes perfect sense to us and we sincerely hope that the next cUTI Guideline keeps things this way too.<\/p>\n

Second, we like the new tiered approach for antibiotic selection based on severity.\u00a0 Assessment should follow a step-wise approach:<\/p>\n

(1) severity of illness, OF COURSE, MAKES SENSE
<\/span>(2) risk factors for resistance, \u00a0YEP, WE AGREE
<\/span>(3) patient-specific considerations, SURE THING!
<\/span>(4) if septic, consider the antibiogram (if local, recent, relevant). \u00a0Hmm, NOT SO SURE…<\/span><\/p>\n

Using a recent antibiogram to help with initial empirical\u00a0 antibiotic selection is a recommendation without supporting evidence.\u00a0 The authors acknowledge this by qualifying it as a \u201cconditional recommendation, very low certainty of evidence\u201d.\u00a0 \u00a0We find this problematic.<\/p>\n

\n

Guidelines should be based on hard evidence.\u00a0 This is a higher standard than opinion pieces or ex-cathedra declarations of faith.\u00a0 We feel that (4) has no place in decision making.\u00a0\u00a0<\/p>\n<\/blockquote>\n

Third, we like the lists of antibiotics that are considered appropriate (see below). These were selected based on recent Phase 3 submission trials.\u00a0 While it seems the best source of efficacy data, it creates a dilemma as far as MDR pathogens are concerned.\u00a0\u00a0<\/p>\n

Registration trials are designed to enroll cUTI cases caused by uropathogens susceptible<\/u> to BOTH the study drug AND<\/u> the comparator.\u00a0 This is an FDA stipulation which can be found in all recent protocols.\u00a0 It eliminates from efficacy evaluation those organisms that are not susceptible to both antibiotics, esp. MDR pathogens that are susceptible to the newer test antibiotic but not to the older comparator.\u00a0\u00a0<\/p>\n

The primary efficacy analysis in FDA pivotal trials analyses is based on the microbiological intent-to-treat (micro-ITT) population (i.e., all patients with a documented bacterial infection).\u00a0 By definition, in this population randomized patients have a baseline bacterial pathogen on culture of urine or blood that causes cUTI against which the investigational drug and control drug have antibacterial activity<\/span>.[2]<\/a><\/p>\n<\/div>\n

Fourth, we are not happy that antibiotic stewardship considerations feature so prominently in the Guideline.\u00a0 Complicated UTI, regardless of severity, is not uUTI for which stewardship considerations have a major role.\u00a0 The entire \u2018stewardship\u2019 concept rings hollow and self-serving when one considers the amount of antibiotic abuse in veterinary medicine.\u00a0 Let’s not forget that cUTIs are not trivial infections, even if mortality is low under the somewhat artificial conditions of clinical trials.\u00a0 Urosepsis and pyonephrosis are very serious conditions that are complications of cUTI one wants to prevent.\u00a0 Actress and Bond girl Tanya Roberts died from fulminant urosepsis and multiorgan failure.<\/p>\n

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

If you made it to Page 30 of the Guideline, you find an interesting section on the Prognostic Impact of Inappropriate Empiric Antibiotic Therapy (IEAT) in cUTI.\u00a0<\/p>\n

We quote:<\/p>\n

\n

\u201can increase in mortality was observed in patients at high risk of mortality with cUTI receiving IEAT, with a pooled adjusted OR of 1.56 (0.99 to 2.46), as compared to patients receiving appropriate empiric antibiotic therapy.\u201d<\/p>\n<\/div>\n<\/blockquote>\n

This suggests a 56% improvement in survival with ‘appropriate’ antibiotic therapy.\u00a0 While this sounds convincing – after all, it confirms our bias that ID docs can make a difference by selecting \u2018appropriate\u2019 antibiotics – there are some major caveats: this analysis was based on a meta-analysis of low quality observational studies with all of their inherent shortcomings. No need to say more.<\/p>\n

The authors state that using the broadest of coverage in high-risk patients would be defensible to lower mortality; however, they also mention the downside to this approach as it affects antibiotic stewardship and safety \/ tolerability issues with antibiotic cocktails in order to achieve the most complete coverage (Page 33).\u00a0 We agree, in general, but would also point out that one can exclude gram-positive pathogen coverage like for enterococci right from the get-go.\u00a0 To clarify, there is no need to include vancomycin in any empiric antibiotic combo, if GPCs are absent.<\/p>\n

As someone who has stained urine samples during residency, I respectfully disagree with the notion that we need trained microbiologists for this simple task.\u00a0 Good riddance to guidelines that make no use of older diagnostics like Gram stains!\u00a0\u00a0 This quick and informative bedside test still should have a role, esp. in the context of antibiotic stewardship and UTIs.<\/p>\n

\n

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

\"\"<\/a>ABBREVIATIONS
<\/strong>IEAT\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 inappropriate Empiric Antibiotic Therapy
GPC\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 Gram-positive cocci
MDR\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 multidrug-resistant
micro-ITT\u00a0 \u00a0 \u00a0microbiological intent-to-treat<\/p>\n

REFERENCES
<\/strong>[1]<\/a> Trautner.\u00a0 Clinical Practice Guideline by Infectious Diseases Society of America (IDSA): 2025 Guideline on Management and Treatment of Complicated Urinary Tract Infections.
[2]<\/a> Complicated Urinary Tract Infections: Developing Drugs for Treatment.\u00a0 Guidance for Industry.\u00a0 FDA CDER 2018<\/p>\n\n\n

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

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 Continue reading NEW IDSA cUTI GUIDELINE<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":4975,"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":[3,18],"tags":[1271,403,2362,334,2364,879,355,967,2363,1583,27,1485,1104,226,2365,48],"class_list":["post-4964","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-the_news","category-the_viewpoint","tag-allphase-pharma-consulting","tag-antibiotic-blog","tag-antibiotic-selection-criteria","tag-antibiotic-stewardship","tag-appropriate-use","tag-complicated-uti","tag-cuti","tag-enterococci","tag-fda-guidance-for-cuti","tag-harald-reinhart","tag-idsa","tag-idsa-guideline","tag-mdr-uropathogens","tag-mortality","tag-unsupported-recommendations","tag-vancomycin"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/cUTI-slider.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-1i4","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":1301,"url":"https:\/\/allphasepharma.com\/dir\/2015\/03\/15\/1301\/the-new-cuti-guideline-a-look-at-the-evolving-thinking-at-fda\/","url_meta":{"origin":4964,"position":0},"title":"The New cUTI Guideline: A Look at the \u2018Evolving Thinking\u2019 at FDA","author":"Harald","date":"March 15, 2015","format":false,"excerpt":"Just to refresh everyone\u2019s memory: First, we had the Points-To-Consider document of 1993, then the 1998 Guidance, followed by the 2012 Guidance and now the 2015 Guidance for the conduct of registration studies in cUTI.\u00a0 They all have served us well and I cannot recall a situation when a drug\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3577,"url":"https:\/\/allphasepharma.com\/dir\/2025\/06\/02\/3577\/__trashed-2__trashed\/","url_meta":{"origin":4964,"position":1},"title":"The 10 x \u201920 Initiative – A Retrospective","author":"Harald","date":"June 2, 2025","format":false,"excerpt":"It started all so well with fanfare and great expectations.\u00a0Fifteen years ago, the 10 x \u201920 initiative got underway. Its goals were spelled out clearly: To \u2018Pursue a Global Commitment to Develop 10 New Antibacterial Drugs by 2020 \u2019[3].\u00a0 It was driven by ID clinicians and by antibiotic developers concerned\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"BBND","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2020\/06\/BBND.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2020\/06\/BBND.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2020\/06\/BBND.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":1887,"url":"https:\/\/allphasepharma.com\/dir\/2015\/08\/26\/1887\/avicaz-approval-and-labeling-restrictions\/","url_meta":{"origin":4964,"position":2},"title":"Avycaz Approval and Labeling Restrictions","author":"Harald","date":"August 26, 2015","format":false,"excerpt":"On Feb 25, 2015 the combination of ceftazidime\/avibactam (Avycaz) was approved by FDA for cUTI and cIAI infections in\u00a0patients \u2018who have limited or no alternative treatment options\u2019.\u00a0 As a QIDP drug, Avycaz\u00a0received priority review.\u00a0 Its label states that it is indicated for infections caused by pathogens proven or \u2018suspected to\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"Avycaz - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/Avycaz-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/Avycaz-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/Avycaz-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2563,"url":"https:\/\/allphasepharma.com\/dir\/2016\/06\/22\/2563\/progress-report-new-antibacterials-in-the-fight-against-mdr-bacteria\/","url_meta":{"origin":4964,"position":3},"title":"Progress Report: New Antibacterials In the Fight against MDR Bacteria","author":"Harald","date":"June 22, 2016","format":false,"excerpt":"Since the beginning of this millennium we have seen antibiotic R&D dwindle year after year. There are many reasons for this; while economics are often cited for this decline, the FDA and the \u2018Guideline Wars\u2019, i.e., those never ending discussions about regulatory requirements, have contributed to this trend in a\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"Pipeline - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/06\/Pipeline-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/06\/Pipeline-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/06\/Pipeline-slider.jpg?resize=525%2C300 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":4964,"position":4},"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":[]},{"id":3144,"url":"https:\/\/allphasepharma.com\/dir\/2017\/02\/09\/3144\/smiles-press-conference-plazomicin-delivers\/","url_meta":{"origin":4964,"position":5},"title":"All Smiles at the Press Conference: Plazo+Levo Delivers","author":"Harald","date":"February 9, 2017","format":false,"excerpt":"This December, Achaogen released much data on 2 plazomicin trials[1]: the pivotal EPIC study comparing plazomicin \/ levofloxacin with meropenem\u00a0\/ levofloxacin in cUTI is the one we want to look at today because it is interpretable, while the other trial called CARE is not. CARE is one of those observational\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\/2017\/02\/Plazomicin-sldier.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/02\/Plazomicin-sldier.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/02\/Plazomicin-sldier.jpg?resize=525%2C300 1.5x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/4964","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=4964"}],"version-history":[{"count":16,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/4964\/revisions"}],"predecessor-version":[{"id":4987,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/4964\/revisions\/4987"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/4975"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=4964"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=4964"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=4964"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}