{"id":8174,"date":"2026-11-12T21:02:08","date_gmt":"2026-11-13T04:02:08","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=8174"},"modified":"2026-11-13T06:54:59","modified_gmt":"2026-11-13T13:54:59","slug":"misguided-populist-advice","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2026\/11\/12\/8174\/misguided-populist-advice\/","title":{"rendered":"Misguided Populist Advice"},"content":{"rendered":"\n<figure class=\"wp-block-image alignwide size-full\"><a href=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/11\/TEST-FORMS.bannerpsd-1-e1794541734858.jpg?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" width=\"530\" height=\"149\" src=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/11\/TEST-FORMS.bannerpsd-1-e1794541734858.jpg?resize=530%2C149&#038;ssl=1\" alt=\"\" class=\"wp-image-8185\"\/><\/a><\/figure>\n\n\n\n<ul class=\"wp-block-list\">\n<li class=\"has-text-color has-link-color wp-elements-1\" style=\"color:#113b6f\"><em>Is it true that the FDA \u2018focuses on bugs instead of patients\u2019 when they approve new antibiotics?<\/em><\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-2\" style=\"color:#113b6f\"><em>Is it true that the call for \u2018new MRSA drugs\u2019 is misguided because the real problem lies with the failure of existing drugs that do not work although they should based on susceptibility testing?<\/em><\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-3\" style=\"color:#113b6f\"><em>Is it true that the FDA is focused on getting \u2018more antibiotics to market\u2019 using \u2018smaller and shorter\u2019 studies with \u2018less evidence\u2019?<\/em><\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-4\" style=\"color:#113b6f\"><em>Is the FDA neglecting non-antibiotic microbiome therapy for infectious diseases?<\/em><\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-5\" style=\"color:#113b6f\"><em>Should the FDA demand that new antibiotics show on evidence that they \u2018save lives\u2019?<\/em><\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">It\u2019s not clear whether or not Zuckerman and Powers just want to be provocative or actually believe what they write.<a href=\"#_ftn1\" id=\"_ftnref1\">[1]<\/a>&nbsp;&nbsp; Let\u2019s start by stating the obvious:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>There is no other field in medicine that has a better, more solid, scientifically defined biomarker of outcome.&nbsp; It is the infecting organism that drives the pathology.&nbsp;<\/li>\n\n\n\n<li>No regulatory \u2018breaks\u2019 have been given for the few antibiotics approved in the last 15-25 years.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Truth be told, we are lucky to have a good number of antibiotics that still work well for most patients, esp. in outpatient care. &nbsp;It is rare to run into an infection caused by more resistant organisms that is not treatable with the existing armamentarium, and that\u2019s a good thing.&nbsp; Thanks to research in academia and industry, we have antibiotics that can even handle many MDR pathogens.&nbsp; This situation may not last forever.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Big Pharma has lost interest in developing antibacterials.&nbsp; The change in attitude was also prompted by some misguided policies at the FDA in the early 2000s, when guidances were drawn up that ran counter to medical practice, resulting in regulatory uncertainty for almost a decade, creating FDA standards not harmonized with other agencies, and pushing the concept of placebo-controlled superiority studies.&nbsp; Overall result: Pharma drifted away from antimicrobials to oncology and other fields.&nbsp; This happened at a time when FDA regulatory zealots were in charge, driving a highly controversial agenda of \u2018Guidance reform\u2019.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Once the FDA finally approves an antibiotic, it has undergone rigorous testing for safety and efficacy.&nbsp; Phase 3 studies are large and indication-specific.&nbsp; The outcome of the new drug is invariably compared to another already approved antibiotic best suited for the indication; the days of \u2018biocreep\u2019 are over and done with.&nbsp; The design of studies is codified in numerous guidances, which are updated every 10 years or so.&nbsp; For almost all indications, antibiotic efficacy is evaluated clinically rather than microbiologically.&nbsp; The FDA still adheres to the \u2018feel, function, survive\u2019 logic for efficacy evaluation, although we have much better predictors of response, namely microbiologic eradication of the causative organism.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Contrarians feel a need to publish simplistic answers to complex problems.&nbsp; They see themselves as heroes cutting the Gordian knot with a single stroke.&nbsp; Zuckerman is entitled to her opinion, but the accusations don\u2019t resonate for those of us who have followed the field.<a><\/a><a href=\"#_ftn1\" id=\"_ftnref1\">[1]<\/a>&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">We believe it is too simplistic for them to state the following:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li class=\"has-text-color has-link-color wp-elements-6\" style=\"color:#113b6f\">There is no need for new antibiotics addressing MDR pathogens, as most patients die from infections treatable with existing antibiotics<\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-7\" style=\"color:#113b6f\">Microbial \u2018test tube results\u2019 are not relevant for clinical outcome assessment<\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-8\" style=\"color:#113b6f\">\u2018Microbiome therapy\u2019 is or can be better than antibiotics<\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-9\" style=\"color:#113b6f\">Steroid use in ICU pneumonia is life-saving<\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-10\" style=\"color:#113b6f\">Immune weakness calls for concomitant steroid therapy in \u2018other infections\u2019 as well<\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-11\" style=\"color:#113b6f\">Deaths and SAEs caused by antibiotics outweigh their benefits<\/li>\n\n\n\n<li class=\"has-text-color has-link-color wp-elements-12\" style=\"color:#113b6f\">Clinical testing of antibiotics should center on improved survival<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">We\u2019ve been there, heard it before. How can one ignore the role of microbiology or be ignorant of numerous failed studies on concomitant steroid use in bacterial pneumonia? <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">We also would have expected a better grasp of the regulatory history concerning clinical trial conduct and approval which the authors certainly knew but chose to ignore.&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In the 90s, FDA vehemently defended the concept of new HIV therapeutics that had to show either (1) improved survival, or (2) a reduction in opportunistic infections.&nbsp; This may have seemed reasonable at first glance, but for clinical studies such endpoints were entirely misconceived:&nbsp; it would have taken 8-10 years of therapy to get a read-out.&nbsp; In the meantime, patients were left to die.&nbsp; Then VL reduction became a gold standard marker of efficacy replacing survival and AIDS-related infections.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">We are glad that companies like Shionogi are still interested in the development of antibiotics like cefiderocol \/ Fetroja, a novel cephalosporin with dual MoA.&nbsp; The FDA knows about the mortality differences in VAP studies, an imbalance which was thoroughly investigated but remained unexplained.&nbsp; It is mentioned prominently in the label though.&nbsp; Similar things have happened before (tigecycline!).&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Clinical outcomes, including deaths, are multifactorial and not solely a result of antibiotic efficacy.&nbsp; Clinical outcomes are influenced by comorbidities, supportive care and immune status of the individual, plus several other factors.&nbsp; To evaluate antibiotic efficacy we should primarily care about micro results, tissue penetration, and PK\/PD.&nbsp; In our opinion, antibiotics primarily affect pathogens and secondarily the disease caused by pathogens.&nbsp; The \u2018Feel-function-survival\u2019 mantra are downstream events of antibiotic action and quite insensitive for outcome evaluations.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Antibiotics cure diseases by killing bugs.&nbsp; That\u2019s all they do: kill bugs.&nbsp; Antibiotics don\u2019t determine clinical outcomes alone. &nbsp;&nbsp;We don\u2019t need to judge antibiotics on their effect on pain relief, reduction of inflammation, QoL, days of hospitalization or normalization of labs.&nbsp; In antiinfectives, we have the best of biomarkers for the occasion: microbial eradication and VL reduction.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Zuckerman and Powers seem to enjoy the limelight feeling good in the role of provocateurs.&nbsp; They have never developed a single antibiotic but see themselves as enlightened judges and gatekeepers. &nbsp;Let\u2019s find them a soap box, a megaphone and a corner at Hyde Park!<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><a href=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/11\/HP2-cropped.jpg?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" width=\"240\" height=\"300\" src=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/11\/HP2-cropped.jpg?resize=240%2C300&#038;ssl=1\" alt=\"\" class=\"wp-image-8180\" style=\"aspect-ratio:0.8000312532555475;width:170px;height:auto\"\/><\/a><\/figure>\n<\/div>\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>ABBREVIATIONS<\/strong><br \/>VAP      ventilator-associated pneumonia<br \/>MDR     multi-drug resistant<br \/>QoL      quality-of-life<br \/>VL         viral load<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>REFERENCE<\/strong><br \/><a href=\"#_ftnref1\" id=\"_ftn1\">[1]<\/a> Zuckerman D.&nbsp; The FDA\u2019s misguided thinking on antibiotics.&nbsp; STAT \u2013 First Opinion.&nbsp; Feb 10, 2025<\/p>\n","protected":false},"excerpt":{"rendered":"<p>It\u2019s not clear whether or not Zuckerman and Powers just want to be provocative or actually believe what they write.[1]&nbsp;&nbsp; Let\u2019s start by stating the obvious: Truth be told, we are lucky to have a good number of antibiotics that still work well for most patients, esp. in outpatient care. <a class=\"more-link\" href=\"https:\/\/allphasepharma.com\/dir\/2026\/11\/12\/8174\/misguided-populist-advice\/\">Continue reading <span class=\"screen-reader-text\">  Misguided Populist Advice<\/span><span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":8185,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"advanced_seo_description":"","jetpack_seo_html_title":"","jetpack_seo_noindex":false,"jetpack_seo_schema_type":"","_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_hide_featured_image":false,"_jetpack_featured_image_duplicate_dismissed":0,"_jetpack_feature_clip_id":0,"_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},"jetpack_post_was_ever_published":false},"categories":[227,3,18],"tags":[2810,1271,403,2192,1955,2808,5,1714,2114,1583,2809,2807,83,200,669],"class_list":["post-8174","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","category-the_viewpoint","tag-aids-outcomes-as-endpoints","tag-allphase-pharma-consulting","tag-antibiotic-blog","tag-biocreep","tag-cefiderocol","tag-clinical-study-endpoints","tag-fda","tag-fda-guidances","tag-fetroja","tag-harald-reinhart","tag-microbiologic-study-endpoints","tag-microbiome","tag-mrsa","tag-shionogi","tag-viral-load"],"jetpack_publicize_connections":[],"jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-27Q","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":249,"url":"https:\/\/allphasepharma.com\/dir\/2014\/06\/05\/249\/here-they-are-dalbavancin-oritavancin-the-new-long-acting-lipoglycopeptides\/","url_meta":{"origin":8174,"position":0},"title":"Here They Are:  Dalbavancin and Oritavancin \u2013 The New Long-Acting Lipoglycopeptides","author":"Harald","date":"June 5, 2014","format":false,"excerpt":"The development history of glycopeptide drugs is anything but normal.\u00a0 Daptomycin (Cubicin\u00ae) was abandoned by Lilly but resurrected by Francis Tally at Cubist by adjusting the dosing schedule to once daily and careful uptitration.\u00a0 The drug did superbly in a landmark endocarditis trial and everything looked rosy.\u00a0 Then we learned\u2026","rel":"","context":"In &quot;The News&quot;","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"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":8174,"position":1},"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 &quot;Recent Literature&quot;","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":4723,"url":"https:\/\/allphasepharma.com\/dir\/2025\/07\/13\/4723\/microbiological-response-as-primary-efficacy-endpoint-for-antibacterials\/","url_meta":{"origin":8174,"position":2},"title":"Microbiological Response as Primary Efficacy Endpoint for Antibacterials","author":"Harald","date":"July 13, 2025","format":false,"excerpt":"We have often mentioned the central importance of microbiological response as an endpoint in trials of antibacterials. This is contrary to other therapeutic areas, in which the etiology is less understood and where surrogate markers are needed. In bacterial infectious diseases we have the luxury of knowing exactly what causes\u2026","rel":"","context":"In &quot;Did you know...?&quot;","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/HR_SLIDER-MICROBIOLOGY-STUPID.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/HR_SLIDER-MICROBIOLOGY-STUPID.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/HR_SLIDER-MICROBIOLOGY-STUPID.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":1408,"url":"https:\/\/allphasepharma.com\/dir\/2015\/05\/07\/1408\/no-such-thing-as-a-free-ride\/","url_meta":{"origin":8174,"position":3},"title":"No Such Thing as a Free Ride\u2026","author":"Harald","date":"May 7, 2015","format":false,"excerpt":"..when it comes to FDA review of antibiotic NDAs.\u00a0 Some seem to have forgotten the dismal record of antibiotic approvals in the last 15 years, and the long list of failed submissions.\u00a0 Many failed not because of lack of efficacy or a bad safety profile but because of changes in\u2026","rel":"","context":"In &quot;QIDP Antibiotics&quot;","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"theBMJ","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/05\/theBMJ.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":1869,"url":"https:\/\/allphasepharma.com\/dir\/2015\/08\/19\/1869\/most-anti-infective-guidelines-get-no-respect-let-alone-use\/","url_meta":{"origin":8174,"position":4},"title":"Most Anti-Infective Guidelines Don&#8217;t Get No Respect (Let Alone Use!)","author":"Harald","date":"August 19, 2015","format":false,"excerpt":"It is no secret that most existing antibiotic guidelines are not getting much use these days.\u00a0 The only indications pursued with any regularity are the feasible ones: ABSSSI, cUTI, and cIAI, much less CABP.\u00a0 Yes, the occasional HABP\/VABP trial is being undertaken by the intrepid but no company has taken\u2026","rel":"","context":"In &quot;Did you know...?&quot;","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"indications - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/indications-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/indications-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/08\/indications-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1543,"url":"https:\/\/allphasepharma.com\/dir\/2015\/06\/12\/1543\/vancomycin-vs-tmpsmx-for-mrsa-not-the-final-word\/","url_meta":{"origin":8174,"position":5},"title":"Vancomycin vs TMP\/SMX for MRSA \u2013 Not the Final Word","author":"Harald","date":"June 12, 2015","format":false,"excerpt":"Vancomycin got a bad reputation since the early 90ies when it became clear that it\u00a0was slow to provide clinical improvement and microbiologic cure in MRSA patients. \u00a0It was associated with prolonged bacteremia even when combined with rifampin\u00a0[1]. \u00a0And for MSSA, anti-staph penicillins like nafcillin were always the better choice. Then,\u2026","rel":"","context":"In &quot;Recent Literature&quot;","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"vanquish","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/vanquish.jpg?resize=350%2C200","width":350,"height":200},"classes":[]}],"jetpack_likes_enabled":true,"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/11\/TEST-FORMS.bannerpsd-1-e1794541734858.jpg?fit=640%2C180&ssl=1","_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/8174","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=8174"}],"version-history":[{"count":24,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/8174\/revisions"}],"predecessor-version":[{"id":8205,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/8174\/revisions\/8205"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/8185"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=8174"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=8174"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=8174"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}