{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:11:24Z","timestamp":1791234684709,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    An effective regimen for treatment of tuberculosis (TB) is comprised of multiple drugs that inhibit a range of essential cellular activities in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n                    . The effectiveness of a regimen is further enhanced if constituent drugs act with synergy. Here, we report that faropenem (a penem) or biapenem, doripenem, or meropenem (carbapenems), which belong to the \u03b2-lactam class of antibiotics, and rifampin, one of the drugs that forms the backbone of TB treatment, act with synergy when combined. One of the reasons (carba)penems are seldom used for treatment of TB is the high dosage levels required, often at the therapeutic limits. The synergistic combination of rifampin and these (carba)penems indicates that (carba)penems can be administered at dosages that are therapeutically relevant. The combination of faropenem and rifampin also limits the frequency of resistant mutants, as we were unable to obtain spontaneous mutants in the presence of these two drugs. The combinations of rifampin and (carba)penems were effective not only against drug-sensitive\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n                    but also against drug-resistant clinical isolates that are otherwise resistant to rifampin. A combination of doripenem or biapenem and rifampin also exhibited synergistic activity against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium abscessus<\/jats:named-content>\n                    . Although the MICs of these three drugs alone against\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. abscessus<\/jats:named-content>\n                    are too high to be of clinical relevance, their concentrations in combinations are therapeutically relevant; therefore, they warrant further evaluation for clinical utility to treat\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium abscessus<\/jats:named-content>\n                    infection, especially in cystic fibrosis patients.\n                  <\/jats:p>","DOI":"10.1128\/aac.01158-15","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T22:20:26Z","timestamp":1439245226000},"page":"6561-6567","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":127,"title":["Carbapenems and Rifampin Exhibit Synergy against Mycobacterium tuberculosis and Mycobacterium abscessus"],"prefix":"10.1128","volume":"59","author":[{"given":"Amit","family":"Kaushik","sequence":"first","affiliation":[{"name":"Taskforce to Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayani","family":"Makkar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Parrish","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urvashi","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyanu","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Taskforce to Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27629-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi701506h"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi8001055"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00296-11"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1167498"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08199.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00023-13"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/jac\/dks395","article-title":"Is there a place for beta-lactams in the treatment of multidrug-resistant\/extensively drug-resistant tuberculosis? Synergy between meropenem and amoxicillin\/clavulanate","volume":"68","author":"Gonzalo X","year":"2013","unstructured":"Gonzalo X, Drobniewski F. 2013. Is there a place for beta-lactams in the treatment of multidrug-resistant\/extensively drug-resistant tuberculosis? Synergy between meropenem and amoxicillin\/clavulanate. J Antimicrob Chemother 68:366\u2013369.","journal-title":"J Antimicrob Chemother"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03539-14"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200207-678OC"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt410"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/ajcp\/53.6.880","article-title":"A microdilution method for antibiotic susceptibility testing: an evaluation","volume":"53","author":"Gavan TL","year":"1970","unstructured":"Gavan TL, Town MA. 1970. A microdilution method for antibiotic susceptibility testing: an evaluation. Am J Clin Pathol 53:880\u2013885.","journal-title":"Am J Clin Pathol"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.2.462"},{"key":"e_1_3_3_15_2","volume-title":"Approved standard M24-A2","author":"Clinical and Laboratory Standards Institute","year":"2011","unstructured":"Clinical and Laboratory Standards Institute. 2011. Susceptibility testing of mycobacteria, nocardiae and other aerobic actinomycetes. Approved standard M24-A2. 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