Daptomycin<\/figcaption><\/figure>\nThe median penetration into synovial fluid was calculated as 54%, and into bone as 9%.<\/p>\n
The study showed that daptomycin reliably achieves bone levels above the MIC breakpoint for Staphylococci (1 \u00b5g\/mL) with a high dose regimen.<\/p>\n
There was 1 serious adverse event (bullous pemphigoid) which occurred 28 days after surgery.\u00a0 It was considered possibly related to study drug.<\/p>\n
Implications<\/h2>\n
Prosthetic joint infections (PJI) caused by S. aureus and post-operative osteomyelitis, esp. vertebral, are notoriously difficult to treat.\u00a0 With higher doses of daptomycin found to be reasonably safe, this study shows that a 8-10 mg\/kg intravenous dose can provide adequate bone penetration.\u00a0 With animal data showing efficacy in acute osteomyelitis models, this study builds the case for use in recent bone infections, post-surgical osteomyelitis, and PJI.<\/p>\n
It stands to reason that other long-acting (lipo)glycopeptide, i.e., dalbavancin (Dalvance\u00ae) and oritavancin (Orbactiv\u00ae), will try to replicate these results in their quest to expand the market beyond skin\/skin structure infections.\u00a0 We should soon see a flurry of osteomyelitis studies.<\/p>\n
This is a challenging arena as good clinical bone infection studies have not been done for a very long time and FDA Guidance is lacking.\u00a0 Entering uncharted territory should not frighten Cubist which has tackled similar challenges successfully in the past: Just think of their brilliant endocarditis program orchestrated by Francis Tally.\u00a0 Let\u2019s hope his spirit is still alive and well.<\/p>\n
\nReferences:\u00a0<\/strong><\/p>\n[1] Montange.\u00a0 Antimicrob Agents Chemother 58: 3991; 2014<\/p>\n","protected":false},"excerpt":{"rendered":"
After a single high dose of (8 or 10 mg\/kg BW) of daptomycin IV, bone levels were measured in plasma and trabecular bone obtained during hip or knee surgery of 16 patients.[1] At the time of surgery, mean concentrations in plasma and synovial fluid were 39 and 22 \u00b5g\/mL, respectively.\u00a0 Continue reading Adequate Penetration of Daptomycin Into Bone Tissue<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"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":[19,227,18],"tags":[403,230,229,92,66,85,228,233,91,71,234,67,232,231,1371],"class_list":["post-439","post","type-post","status-publish","format-standard","hentry","category-qidp_antibiotic","category-recent_literature","category-the_viewpoint","tag-antibiotic-blog","tag-bone-penetration","tag-cubicin","tag-cubist","tag-dalbavancin","tag-dalvance","tag-daptomycin","tag-endocarditis","tag-francis-tally","tag-lipoglycopeptide","tag-orbactiv","tag-oritavancin","tag-osteomyelitis","tag-prosthetic-joint-infection","tag-qidp"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-75","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":1693,"url":"https:\/\/allphasepharma.com\/dir\/2015\/07\/10\/1693\/brilacidin-qidp-drug-at-a-critical-juncture\/","url_meta":{"origin":439,"position":0},"title":"Brilacidin – QIDP Drug At a Critical Juncture","author":"Harald","date":"July 10, 2015","format":false,"excerpt":"At around this time (July 2015), Cellceutix is\u00a0expected to hammer out a Phase 3 program for brilacidin, its defensin-mimetic and host-defense protein (HDP) mimic structurally similar to magainin, with FDA. Brilacidin is certainly an interesting novel compound, coming from a new class, with a unique mode of action.\u00a0 It has\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"brilacidin - slider2 copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/brilacidin-slider2-copy1.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/brilacidin-slider2-copy1.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/07\/brilacidin-slider2-copy1.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1408,"url":"https:\/\/allphasepharma.com\/dir\/2015\/05\/07\/1408\/no-such-thing-as-a-free-ride\/","url_meta":{"origin":439,"position":1},"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 "QIDP Antibiotics"","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":3116,"url":"https:\/\/allphasepharma.com\/dir\/2017\/01\/30\/3116\/txa-709-kid-qidp-block\/","url_meta":{"origin":439,"position":2},"title":"TXA-709 –\u00a0 New Kid on the Block","author":"Harald","date":"January 30, 2017","format":false,"excerpt":"When searching for FtsZ inhibitors on PubMed, there are 187 hits. When narrowing down the search looking for clinical trials only, there are none. Taxis Pharmaceuticals obtained QIDP status for its candidate drug TXA-709 in late 2016 and it is still in preclinical testing. The drug\u2019s target, bacterial replication machinery\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\/01\/FtsZ-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/FtsZ-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/FtsZ-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2802,"url":"https:\/\/allphasepharma.com\/dir\/2016\/10\/18\/2802\/qidp-drug-update-part-1-an-updated-who-is-who\/","url_meta":{"origin":439,"position":3},"title":"QIDP Drug Update \u2013 Part 1: An Updated Who Is Who","author":"Harald","date":"October 18, 2016","format":false,"excerpt":"It is time for a new look at the field of QIDP drugs. Today we\u00a0are providing an updated searchable database which now has 57 entries. (Status: 10\/18\/16) Despite best efforts to provide accurate\u00a0information,\u00a0errors may have crept in. Please let us know\u00a0if you detect mistakes. We will make corrections or post\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"qidp-slider-5","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-slider-5.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-slider-5.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-slider-5.jpg?resize=525%2C300 1.5x"},"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":439,"position":4},"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":2061,"url":"https:\/\/allphasepharma.com\/dir\/2015\/10\/20\/2061\/polyphor-pol7080-and-the-journey-to-the-land-of-pyocyanea-part-2\/","url_meta":{"origin":439,"position":5},"title":"Polyphor POL7080 And The Journey to The Land of Pyocyanea\u00a0 (Part 2)","author":"Harald","date":"October 20, 2015","format":false,"excerpt":"Roche\u2019s current Phase 2 program is strangely ambiguous. RG-7929 has not made it into www.clinicaltrials.gov yet, only POL7080 is listed. An uncontrolled open label study in \u201cpatients with non-CF acute exacerbation of bronchiectasis due to P. aeruginosa requiring IV treatment\u201d is enrolling. Well, good luck finding those patients! At best,\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"bridge Pyocyanea-P2","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-P2.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-P2.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/10\/bridge-Pyocyanea-P2.jpg?resize=525%2C300 1.5x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/439","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=439"}],"version-history":[{"count":7,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/439\/revisions"}],"predecessor-version":[{"id":2018,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/439\/revisions\/2018"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=439"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=439"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=439"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
![\"daptomycin\"](\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/07\/daptomycin.jpg?ssl=1\")
<\/a>