{"id":5255,"date":"2014-06-24T12:02:25","date_gmt":"2014-06-24T16:02:25","guid":{"rendered":"http:\/\/blogs.nejm.org\/?p=5255"},"modified":"2015-06-04T14:32:21","modified_gmt":"2015-06-04T18:32:21","slug":"at-long-last-some-new-antibiotics-that-might-make-a-difference","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/at-long-last-some-new-antibiotics-that-might-make-a-difference\/2014\/06\/24\/","title":{"rendered":"At Long Last, Some New Antibiotics That Might Make a Difference"},"content":{"rendered":"<p><a href=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2014\/06\/Penicillin-July-1943-Science-Pub1.gif\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-5261 size-medium\" src=\"http:\/\/blogs.nejm.org\/hiv-id-observations\/wp-content\/uploads\/sites\/2\/2014\/06\/Penicillin-July-1943-Science-Pub-300x1381.gif\" alt=\"Penicillin July 1943 Science Pub\" width=\"300\" height=\"138\" \/><\/a>Compared to HIV, HCV, and antifungal agents, development of novel antibacterial drugs has been in a bit of a funk for quite some time now.<\/p>\n<p>Here&#8217;s what&#8217;s been approved in the past 10 years, with year\u00a0of approval and a few comments:<\/p>\n<ul>\n<li><strong>Telithromycin<\/strong>\u00a0(2004): \u00a0The first ketolide antibiotic, it was supposed to overcome macrolide-resistant respiratory pathogens. But there were\u00a0<strong><a href=\"http:\/\/www.nytimes.com\/2006\/07\/19\/health\/19fda.html?ex=1169960400&amp;en=30b585a30a671f03&amp;ei=5070&amp;_r=0\">huge controversies<\/a>\u00a0<\/strong>about the clinical trials that led to its approval, and\u00a0major concerns about liver and other adverse effects. It&#8217;s still available, but no one in their right mind would use it.<\/li>\n<li><strong>Tigecycline<\/strong>\u00a0(2005): \u00a0Although this incredibly broad-spectrum tetracycline-like agent seemed like just the ticket based on its in vitro activity, clinical experience has been only fair at best. It achieves low blood levels, so isn&#8217;t suitable for bacteremia, and is associated with extremely high rates of nausea. Plus there&#8217;s this\u00a0<strong><a href=\"http:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm224370.htm\">excess death issue<\/a><\/strong>\u00a0in pooled data from several clinical trials &#8212; never a good thing!<\/li>\n<li><strong>Doripenem<\/strong>\u00a0(2007): \u00a0The most recently approved carbapenem, doripenem\u00a0was shown to be\u00a0<strong><a href=\"http:\/\/www.fda.gov\/Safety\/MedWatch\/SafetyInformation\/SafetyAlertsforHumanMedicalProducts\/ucm388328.htm\">inferior to imipenem for ventilator-associated pneumonia<\/a><\/strong>, with a lower rate of cure and a higher risk of death. (Bad.) That trial alone &#8212; sponsored by the makers of the drug, no less &#8212; should be sufficient reason never to prescribe\u00a0it.<\/li>\n<li><strong>Telavancin<\/strong>\u00a0(2009): \u00a0A relative of vancomycin, telavancin is approved for skin infections. It appears to be more nephrotoxic than vancomycin, however, and offers few advantages. I still have never prescribed it, and our ID PharmD says there has been only one patient in our hospital&#8217;s history who has received it.<\/li>\n<li><strong>Ceftaroline<\/strong>\u00a0(2010): \u00a0The first cephalosporin with anti-MRSA activity, ceftaroline has a relatively\u00a0<strong><a href=\"http:\/\/www.fda.gov\/newsevents\/newsroom\/pressannouncements\/ucm231594.htm\">narrow list of FDA-approved indications<\/a><\/strong> &#8212; namely, community-acquired pneumonia (who would use it for this?) and skin and soft tissue infections. As a result, the drug is really still trying to find itself, if I may personify Mr. C. Fosamil for a moment. What we&#8217;d really like to know is how it does for MRSA bacteremia and other severe infections, but thus far\u00a0the data for these indications are quite limited.<\/li>\n<li><strong>Fidaxomicin<\/strong>\u00a0(2011): \u00a0This novel treatment for C. diff may\u00a0be\u00a0<strong><a href=\"http:\/\/cid.oxfordjournals.org\/content\/53\/5\/440.short\">slightly more effective than vancomycin<\/a><\/strong>, at least in certain populations. It is extremely expensive &#8212; it&#8217;s the current winner in the\u00a0<strong><a href=\"https:\/\/www.optumrx.com\/RxSolWeb\/mvc\/discountDrugPricing.do?ndcLabelName=DIFICID+TAB+200MG&amp;ndc=52015008001&amp;event=drugDetail\">&#8220;Most Expensive Oral Antibiotic&#8221; competition<\/a><\/strong> &#8212; so anecdotally it&#8217;s almost always used as a second-line or salvage therapy. In addition, FMT and other microbiome-restoring treatments may ultimately make use of antibiotics for C. diff of limited use.<\/li>\n<\/ul>\n<p>I&#8217;ve probably left\u00a0some antibacterial out from the above list (did it by memory, except for the FDA approval dates &#8212; always risky), but think this pretty much covers the decade. Aside\u00a0from ceftaroline &#8212; which again, is still kind of in a transitional phase as we gather more data &#8212; it&#8217;s not a particularly impressive group of drugs.<\/p>\n<p>Hence\u00a0the recent approvals of\u00a0<a href=\"http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm398724.htm\">dalbavancin<\/a>\u00a0and\u00a0<a href=\"http:\/\/www.fda.gov\/NewsEvents\/Newsroom\/PressAnnouncements\/ucm402174.htm\">tedizolid<\/a>, and the likely upcoming approvals of oritavancin, ceftazidime\/avibactam and ceftolozane\/tazobactam, all give ample reason for hope. <a href=\"http:\/\/www.pewtrusts.org\/en\/research-and-analysis\/issue-briefs\/2013\/11\/07\/gain-how-a-new-law-is-stimulating-the-development-of-antibiotics\">These incentives<\/a> seem to be working!<\/p>\n<p>Dalbavancin and oritavancin, with their prolonged half-lives and infrequent administration, could &#8220;profoundly affect how skin and soft tissue\u00a0infections are managed, by reducing or in some cases eliminating costs and risks of hospitalization,&#8221; to quote\u00a0<a href=\"http:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMe1405078\">this nice editorial in the <em>New England Journal of Medicine<\/em><\/a>.<\/p>\n<p>Tedizolid is (finally) an alternative to linezolid, with once-daily dosing and likely\u00a0<a href=\"http:\/\/cid.oxfordjournals.org\/content\/58\/suppl_1\/S51.full\">a better safety profile.<\/a><\/p>\n<p>And the two new cephalosporin\/beta-lactamase inhibitor combos could provide much-needed options for highly resistant gram negative infections, which we hope would\u00a0obviate or at least reduce the use\u00a0of tigecycline and colistin.<\/p>\n<p>Sure, we still need to see these drugs in the &#8220;real world&#8221; before we know about effectiveness, tolerability, safety, and price. But I&#8217;m cautiously optimistic.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Compared to HIV, HCV, and antifungal agents, development of novel antibacterial drugs has been in a bit of a funk for quite some time now. Here&#8217;s what&#8217;s been approved in the past 10 years, with year\u00a0of approval and a few comments: Telithromycin\u00a0(2004): \u00a0The first ketolide antibiotic, it was supposed to overcome macrolide-resistant respiratory pathogens. But [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5,8],"tags":[],"class_list":["post-5255","post","type-post","status-publish","format-standard","hentry","category-health-care","category-infectious-diseases","category-patient-care"],"post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/5255","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/comments?post=5255"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/posts\/5255\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/media?parent=5255"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/categories?post=5255"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/hiv-id-observations\/index.php\/wp-json\/wp\/v2\/tags?post=5255"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}