{"id":432,"date":"2014-06-28T22:38:11","date_gmt":"2014-06-28T22:38:11","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=432"},"modified":"2015-11-23T02:52:00","modified_gmt":"2015-11-23T07:52:00","slug":"qt-prolongation-with-azithromycin-and-levofloxacin","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2014\/06\/28\/432\/qt-prolongation-with-azithromycin-and-levofloxacin\/","title":{"rendered":"QT Prolongation with Azithromycin and Levofloxacin"},"content":{"rendered":"
\"Levofloxacin_ball-and-stick<\/a>
Levoquin<\/figcaption><\/figure>\n

Several antibiotic classes are associated with QTc prolongation: macrolides, quinolones, the antimalarials that share the quinine structure, and many azole antifungals.\u00a0 FDA warned about the proarrhythmic effects of azithromycin in 2013 [i] but it is a recent publication by Rao which brings the message home again with some very disquieting quantitative figures [ii].<\/p>\n

Analyzing a very large sample size (approx. 1.6 mio courses of antibiotics in a VA population) the authors found that \u2013 compared to amoxicillin \u2013 mortality was increased by 47% and 149% with azithromycin (Zithromax\u00ae) and levofloxacin (Levoquin\u00ae), respectively, during the first 5 days of drug administration.<\/p>\n

Didn\u2019t they teach us in medical school that erythromycin was one of the safest antibiotics?\u00a0 Well, it can prolong the QT interval by >40 msec.\u00a0 I very much doubt that it would be approved today.<\/p>\n

Much of our understanding about QTc prolongation and its impact is based on the moxifloxacin (Avelox\u00ae) program.\u00a0 Moxifloxacin has a linear dose-related QT effect.\u00a0 Fortunately, 400 mg is an effective dose resulting in minimal (5-7 msec) QT prolongation.\u00a0 It certainly helped that Bayer studied the issue upfront and in great detail. An unintended byproduct of this effort: Moxifloxacin became the de-facto positive control for all future Thorough QT studies.<\/p>\n

Several antibiotics failed because of QT prolongation.\u00a0 Remember sparfloxacin (Zagam\u00ae) and grepafloxacin (Raxar\u00ae)?\u00a0 Both were eventually taken off the market.<\/p>\n

However, levofloxacin and azithromycin have been on the market for a long time now, and both have accumulated an impressive safety record.\u00a0 In contrast to most other fluoroquinolones, levofloxacin has a very small effect on QT prolongation, and azithromycin is clearly safer than erythromycin.<\/p>\n

Are the reported results by an aberration, a population-specific finding only, restricted to a predominantly male, elderly VA population with significant comorbidities and subject to all kinds of drug interactions?\u00a0 I don\u2019t think so.\u00a0 There are other studies that confirm these findings [iii].\u00a0 The Rao study suggests that even a small effect is not benign.\u00a0 Nonetheless, we need to put this into perspective.<\/p>\n

First, we value antibiotics for their benefits over, well, not having antibiotics.\u00a0 There is no need to study millions when comparing mortality ratios of antibiotic vs placebo treatment: it does not take more than a small cohort to demonstrate their value.<\/p>\n

Secondly, there are considerable differences among the classes of antibiotics which make them individually useful.\u00a0 For example, in upper respiratory tract infections, macrolides provide coverage for atypical bacteria, legionella, and even pseudomonas.\u00a0 The entire class also has an anti-inflammatory component.\u00a0 Quinolones improve on this profile by excellent tissue penetration, bactericidal MoA and even broader coverage.\u00a0 Ampicillin is good for S. pneumoniae\u00a0and H. influenzae only, not much else.<\/p>\n

As mentioned before, both azithromycin and levofloxacin are safe drugs.\u00a0 Their QT-related risks are small compared to the overall benefit they provide. \u00a0And yes, they carry a small cardiovascular risk.<\/p>\n

Rao\u2019s study reminds us to\u00a0use these drugs less liberally.\u00a0 Recent data show that physicians are heeding the call to avoid antibiotics for trivial infections like the common cold, sinusitis or otitis that are most likely viral in nature. \u00a0Nonetheless, over half of all practitioners still prescribe antibiotics in order to cover the mere possibility of a bacterial infection, even if unlikely.<\/p>\n

I guess what we really need are better diagnostics to distinguish viral from bacterial infections.\u00a0 Talking about \u201cappropriate\u201d vs \u201cinappropriate\u201d use is a judgement call that does not solve much.<\/p>\n

Last, we need to relearn the chapter on erythromycin, that great old antibiotic, recognizing that it isn\u2019t quite so\u00a0safe after all.<\/p>\n

\n

 <\/p>\n

References<\/strong><\/p>\n

[i] http:\/\/www.fda.gov\/drugs\/drugsafety\/ucm341822.htm
\n[ii] Rao. Ann Fam Med. 2014 Mar-Apr;12(2):121-7
\n[iii] Owens. Clin Infect Dis. 43: 1603, 2006<\/p>\n","protected":false},"excerpt":{"rendered":"

Several antibiotic classes are associated with QTc prolongation: macrolides, quinolones, the antimalarials that share the quinine structure, and many azole antifungals.\u00a0 FDA warned about the proarrhythmic effects of azithromycin in 2013 [i] but it is a recent publication by Rao which brings the message home again with some very disquieting Continue reading QT Prolongation with Azithromycin and Levofloxacin<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":859,"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":[227,18],"tags":[403,215,211,225,220,221,224,216,516,213,223,226,47,222,217,218,219,212],"class_list":["post-432","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_viewpoint","tag-antibiotic-blog","tag-avelox","tag-azithromycin","tag-azole","tag-bayer","tag-erythromycin","tag-fluoroquinolone","tag-grepafloxacin","tag-levaquin","tag-levofloxacin","tag-macrolide","tag-mortality","tag-moxifloxacin","tag-qt-prolongation","tag-raxar","tag-sparfloxacin","tag-zagam","tag-zithromax"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/QTnl-abnl.jpe","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-6Y","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":839,"url":"https:\/\/allphasepharma.com\/dir\/2014\/09\/03\/839\/the-futile-quest-of-proofing-a-negative-in-the-presence-of-overwhelming-absence-of-harm\/","url_meta":{"origin":432,"position":0},"title":"The Futile Quest of Proofing a Negative in the Presence of Overwhelming Absence of Harm","author":"Harald","date":"September 3, 2014","format":false,"excerpt":"The cartilage damage caused by fluoroquinolones in juvenile beagle dogs is not subtle:\u00a0 blister formation and erosions occur in a dose-dependent fashion resulting in reversible cartilage damage.\u00a0 These lesions can be seen not just histologically but even macroscopically.\u00a0 The animals are unable to walk as weight-bearing joints are predominantly affected.\u00a0\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"beagle dog","src":"http:\/\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/09\/beagle-dog.jpe","width":350,"height":200},"classes":[]},{"id":2942,"url":"https:\/\/allphasepharma.com\/dir\/2016\/12\/15\/2942\/antibiotic-inhalers-galore-part-1-more-combinations-permutations-rubiks-cube\/","url_meta":{"origin":432,"position":1},"title":"Antibiotic Inhalers Galore (Part 1): \u00a0More Combinations and Permutations than a Rubik\u2019s Cube","author":"Harald","date":"December 15, 2016","format":false,"excerpt":"There is much interest in inhaled antibiotics these days.\u00a0 Prima facie, the logic for this approach is compelling: Getting the antibiotic (and a lot of it) directly to the site of infection, while avoiding systemic toxicity, sounds like optimized efficacy plus optimized safety combined.\u00a0 However, some high-profile failures were published\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\/2016\/12\/Inhalational-Abx-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/12\/Inhalational-Abx-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/12\/Inhalational-Abx-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1488,"url":"https:\/\/allphasepharma.com\/dir\/2015\/05\/26\/1488\/treating-gc-in-the-face-of-dwindling-antibiotic-options-1\/","url_meta":{"origin":432,"position":2},"title":"Treating GC in the Face of Dwindling Antibiotic Options \u2013 (1)","author":"Harald","date":"May 26, 2015","format":false,"excerpt":"Looking across the Northern border it is clear that CDC Guidelines are not universally followed even in North America. Public Health Canada still recommends cefixime for uncomplicated gonorrhea (GC), albeit at the high single oral dose of 800 mg\u00a0[1]. In the US, CDC has opted for combination treatment with ceftriaxone\u2026","rel":"","context":"In "Did you know...?"","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\/2015\/05\/GC-slider1.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/05\/GC-slider1.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/05\/GC-slider1.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1608,"url":"https:\/\/allphasepharma.com\/dir\/2015\/06\/25\/1608\/why-moxifloxacins-approval-for-plague-is-so-disturbing\/","url_meta":{"origin":432,"position":3},"title":"Why Moxifloxacin\u2019s Approval for Plague Is So Disturbing","author":"Harald","date":"June 25, 2015","format":false,"excerpt":"PLEASE SHARE YOUR OPINION AND VOTE\u00a0BELOW On May 8th, 2015 moxifloxacin\/Avelox was approved for treatment of inhalational plague.[1]\u00a0\u00a0 We learn that the approval followed the \u2018animal rule\u2019 process, and that treatment with moxifloxacin was 100% effective in the African Green Monkey (AGM) model of lung infection.\u00a0 By contrast, 0% of\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"AGM - slider copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/AGM-slider-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/AGM-slider-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/AGM-slider-copy.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2676,"url":"https:\/\/allphasepharma.com\/dir\/2016\/09\/13\/2676\/timely-new-information-on-next-generation-tetracyclines-part-1-omadacycline-and-cardiac-aes\/","url_meta":{"origin":432,"position":4},"title":"Timely New Information on Next-Generation Tetracyclines \u2013 Part 1: Omadacycline and Cardiac AEs","author":"Harald","date":"September 13, 2016","format":false,"excerpt":"Several\u00a0interesting articles appeared recently which shed light on the efficacy of eravacycline and the safety of\u00a0omadacycline, both in Phase 3 and both in a head-to-head race to the market.\u00a0 Well, the term \u2018race\u2019 is bit of a stretch as both drugs have seen very significant delays in development. 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