{"id":2313,"date":"2016-03-03T06:44:49","date_gmt":"2016-03-03T11:44:49","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2313"},"modified":"2017-03-31T16:42:49","modified_gmt":"2017-03-31T20:42:49","slug":"iv-fosfomycin-to-the-rescue-and-to-a-place-near-you","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2016\/03\/03\/2313\/iv-fosfomycin-to-the-rescue-and-to-a-place-near-you\/","title":{"rendered":"IV Fosfomycin To The Rescue \u2013 And To a Place Near You"},"content":{"rendered":"

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

A recent letter to the Editor by Simkins et al. is worth reviewing [1]<\/a>. The authors describe the complicated course of a patient who suffered graft rejection after liver transplantation, received broad-spectrum antibiotics during prolonged hospitalization and eventually had a bloodstream infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) which was resistant to colistin and tigecycline. The organism, however, was fosfomycin-sensitive. The team obtained IV fosfomycin from a European source which cleared the infection once treatment was\u00a0initiated.<\/p>\n

However, here is the rub: it took 10 (ten!) days to get IV fosfomycin to the bedside, as the drug is not approved in the US and had to be imported. In such cases, an emergency IND is required which involves paperwork and contact with the FDA. This process has been streamlined in 2015 and should not be too burdensome anymore [2]<\/a>. Nonetheless, shipment of drugs not approved in\u00a0the US can easily get stuck in customs – as in this case, for 3 days \u2013 creating all kinds of bureaucratic issues which take an inordinate amount of time and effort\u00a0to get resolved [3]<\/a>.<\/p>\n

This should give pause for reflection. These days we are clamoring for new drugs with activity against CRE. We could have the foresight to stockpile fosfomycin at CDC or another location to make access faster and easier. Fosfomycin PO is already approved in the US as a UTI agent, however, fosfomycin IV is not, for reasons unclear. Probably there was no sponsor for this old drug.<\/p>\n

It sounds too good to be true: here is an antibiotic which has not been used much and has retained excellent activity against some of the most difficult-to-treat pathogens. Fosfomycin has a remarkably broad spectrum of activity, very favorable PK, a cidal mode of action, no significant DDI, and a decent\u00a0safety profile. Importantly, several recent publications have remarked on fosfomycin\u2019s good activity against CRE [4]<\/a>.<\/p>\n

There is no need for lengthy Phase 3 trials, no need to study PK\/PD, ADME and dose finding, or to conduct studies in hepatic and renal impairment, for QTc effects\u00a0etc, etc as all this data is already available. Fosfomycin has a novel cell wall targeting MoA (murA inhibition), represents a molecular class distinctly different from other antibacterials, does not result in cross-resistance\u00a0with other antibiotics, and has moderate risk for clinical resistance development. Approved and used in Europe for many years, it is a well-known entity listed in several pharmacopoeias. It is not an \u2018investigational\u2019 drug under development for which little more is known other than preclinical data.<\/p>\n

A good review of the microbiology, PK and clinical data situation has been published by Michalopoulos [5]<\/a>.<\/p>\n

Antibiotics like fosfomycin should be available expeditiously and with minimal paperwork. They\u00a0should be accessible from within<\/span> the USA. An international pharmacy could be set up in close cooperation with FDA or CDC to provide this and similar drugs which are already approved in other jurisdictions.<\/p>\n

Physicians should not have to deal with customs issues; our\u00a0gate keepers, i.e., FDA and US CBP (Customs and Border Protection), should take on the responsibility for a smooth delay-free shipment process for an emergency IND drug shipment. The current situation is unnecessarily difficult and really should\u00a0be streamlined.<\/p>\n

References:
\n<\/strong>[1]<\/a> J Simkins. Intravenous Fosfomycin Treatment for Carbapenem-Resistant Klebsiella pneumoniae in the United States.\u00a0 Ann Pharmacother 2015; 49:1177
\n[2]<\/a> FDA Guidance for Industry. Individual Patient Expanded Access Applications: Form FDA 3926. http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM432717.pdf
\n[3]<\/a> https:\/\/help.cbp.gov\/app\/answers\/detail\/a_id\/320\/~\/purchasing-medications-from-a-supplier-outside-the-u.s.
\n[4]<\/a> K Linsenmeyer. Activity of Fosfomycin against Extended-Spectrum-b-Lactamase Producing Uropathogens in Patients in the Community and Hospitalized Patients. Antimicrob Agents Chemother 60:1134, 2016
\n[5]<\/a> A Michalopoulos.\u00a0 The revival of fosfomycin. Internat J Infect Dis 15 (2011): e732<\/p>\n","protected":false},"excerpt":{"rendered":"

A recent letter to the Editor by Simkins et al. is worth reviewing [1]. The authors describe the complicated course of a patient who suffered graft rejection after liver transplantation, received broad-spectrum antibiotics during prolonged hospitalization and eventually had a bloodstream infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) which was resistant Continue reading IV Fosfomycin To The Rescue \u2013 And To a Place Near You<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2315,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":true,"_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},"jetpack_post_was_ever_published":false},"categories":[227,3,18],"tags":[1271,403,1537,177,363,1892,1535,1534,1890,1893,99,1583,1538,1533,1894,1536,43,1889],"class_list":["post-2313","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","category-the_viewpoint","tag-allphase-pharma-consulting","tag-antibiotic-blog","tag-carbapenem-resistant-klebsiella","tag-colistin","tag-cre","tag-crkp","tag-drug-importation","tag-emergency-ind","tag-eu","tag-expanded-access-application","tag-fda-guidance","tag-harald-reinhart","tag-importation-delays-for-ind-drugs","tag-iv-fosfomycin","tag-mura-inhibitor","tag-po-fosfomycin","tag-tigecycline","tag-usa"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/02\/Fosfomycin-slider-copy.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-Bj","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":3071,"url":"https:\/\/allphasepharma.com\/dir\/2017\/01\/19\/3071\/cdc-report-pan-resistant-ndm-klebsiella-nevada-sad-tale\/","url_meta":{"origin":2313,"position":0},"title":"CDC Report on Pan-Resistant NDM Klebsiella in Nevada\u2013 A Sad Tale","author":"Harald","date":"January 19, 2017","format":false,"excerpt":"During the past few weeks the case of a patient with MDR Klebsiella infection has made the news. We are told that this particular pathogen is \u201cresistant to 26 antibiotics\u201d. We were informed that the patient had multiple prior hospitalizations in India, supposedly the origin of the uncontrolled untreatable infection.\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/CDC-KP-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/CDC-KP-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/CDC-KP-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1401,"url":"https:\/\/allphasepharma.com\/dir\/2015\/04\/30\/1401\/a-renaissance-for-old-drugs-fosfomycin-and-colistin\/","url_meta":{"origin":2313,"position":1},"title":"A Renaissance for Old Drugs: Fosfomycin and Colistin","author":"Harald","date":"April 30, 2015","format":false,"excerpt":"Fosfomycin Who would have thought that a drug that has been around since 1969 [2] could become eligible for QIDP status in 2015? Well, Zavante Therapeutics recently garnered the coveted QIDP designation for fosfomycin IV. This formulation has been available in Europe for a quite some\u00a0time but not in the\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2186,"url":"https:\/\/allphasepharma.com\/dir\/2015\/12\/19\/2186\/aztreonam-plus-avibactam-a-new-bright-star-in-the-night-sky\/","url_meta":{"origin":2313,"position":2},"title":"Aztreonam PLUS Avibactam \u2013 A New Bright Star in the Night Sky","author":"Harald","date":"December 19, 2015","format":false,"excerpt":"Looking at the molecular structure of ceftazidime (CTAZ) and aztreonam (ATM), the differences are clear, and so are the similarities: ATM does not have the cephem ring structure of CTAZ, only the 4-member beta-lactam ring.\u00a0 However, the side chains are identical in both CTAZ and ATM which explains the overlapping\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"Avibactam - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/Avibactam-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/Avibactam-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/Avibactam-slider.jpg?resize=525%2C300 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/Avibactam-slider.jpg?resize=700%2C400 2x"},"classes":[]},{"id":3100,"url":"https:\/\/allphasepharma.com\/dir\/2017\/01\/24\/3100\/kill-mocking-bug-cre-crab-variety\/","url_meta":{"origin":2313,"position":3},"title":"To Kill A Mocking Bug – of the CRKP or CRAB Variety","author":"Harald","date":"January 24, 2017","format":false,"excerpt":"Meropenem stands out as an antibiotic to be used first in ESBL and MDR infections, given its efficacy profile and safety record (see earlier blog). It also would seem to be appropriate to use relatively high doses or prolonged infusion times \u2013 or both - to improve T>MIC for the\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Mero-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Mero-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Mero-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1629,"url":"https:\/\/allphasepharma.com\/dir\/2015\/06\/29\/1629\/nitrofurantoin-an-old-drug-resurrected-needs-prospective-scrutiny\/","url_meta":{"origin":2313,"position":4},"title":"Nitrofurantoin \u2013 An Old Drug Resurrected Needs Prospective Scrutiny","author":"Harald","date":"June 29, 2015","format":false,"excerpt":"When older drugs get reintroduced into clinical practice because pathogens have developed resistance to newer agents, it comes at the price of uncertainty. Often, older drugs were approved based on rather limited\u00a0data, often considered incomplete by today\u2019s standards.\u00a0 Take colistin as an example: approved in the early 60ies, we still\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"UTI - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/UTI-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/UTI-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/06\/UTI-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":6499,"url":"https:\/\/allphasepharma.com\/dir\/2026\/04\/10\/6499\/treating-serious-crab-infections\/","url_meta":{"origin":2313,"position":5},"title":"Treating Serious CRAB Infections","author":"Harald","date":"April 10, 2026","format":false,"excerpt":"There are MDR pathogens, and there is carbapenem-resistant A. baumannii, aka CRAB. This surely must be one of the most formidable bacterial organisms. It has resistance mechanisms second to none.\u00a0 When found in patients, it is very difficult to eradicate and extremely difficult to get rid off, once established in\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/03\/CRAB.jpg?fit=1200%2C338&ssl=1&resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/03\/CRAB.jpg?fit=1200%2C338&ssl=1&resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/03\/CRAB.jpg?fit=1200%2C338&ssl=1&resize=525%2C300 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/03\/CRAB.jpg?fit=1200%2C338&ssl=1&resize=700%2C400 2x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2026\/03\/CRAB.jpg?fit=1200%2C338&ssl=1&resize=1050%2C600 3x"},"classes":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2313","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=2313"}],"version-history":[{"count":11,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2313\/revisions"}],"predecessor-version":[{"id":3280,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2313\/revisions\/3280"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/2315"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=2313"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=2313"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=2313"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}