{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:56:55Z","timestamp":1790251015725,"version":"4.1.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"The Supporting Project from Yongchuan Hospital, Chongqing Medical University","award":["YJSCI201304"],"award-info":[{"award-number":["YJSCI201304"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The combination of \u03b2-lactams and \u03b2-lactamase inhibitors has been shown to have potent\n            <jats:italic>in vitro<\/jats:italic>\n            activity against multidrug-resistant tuberculosis (MDR-TB) isolates. In order to identify the most potent \u03b2-lactam\u2013\u03b2-lactamase inhibitor combination against MDR-TB, we selected nine \u03b2-lactams and three \u03b2-lactamase inhibitors, which belong to different subgroups. A total of 121 MDR-TB strains were included in this study. Out of the \u03b2-lactams used herein, biapenem was the most effective against MDR-TB and had an MIC\n            <jats:sub>50<\/jats:sub>\n            value of 8 \u03bcg\/ml. However, after the addition of clavulanate or sulbactam, meropenem exhibited the most potent anti-MDR-TB activity with an MIC\n            <jats:sub>50<\/jats:sub>\n            value of 4 \u03bcg\/ml. For meropenem, 76 (62.8%), 41 (33.9%), and 22 (18.2%) of the 121 MDR-TB strains were subjected to a synergistic effect when the drug was combined with sulbactam, tazobactam, or clavulanate, respectively. Further statistical analysis revealed that significantly more strains experienced a synergistic effect when exposed to the combination of meropenem with sulbactam than when exposed to meropenem in combination with tazobactam or clavulanate, respectively (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01). In addition, a total of 10.7% (13\/121) of isolates harbored mutations in the\n            <jats:italic>blaC<\/jats:italic>\n            gene, with two different nucleotide substitutions: AGT333AGG and ATC786ATT. For the strains with a Ser111Arg substitution in BlaC, a better synergistic effect was observed in the meropenem-clavulanate and in the amoxicillin-clavulanate combinations than that in a synonymous single nucleotide polymorphism (SNP) group. In conclusion, our findings demonstrate that the combination of meropenem and sulbactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg substitution of BlaC may be associated with an increased susceptibility of MDR-TB isolates to meropenem and amoxicillin in the presence of clavulanate.\n          <\/jats:p>","DOI":"10.1128\/aac.01035-15","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T01:35:21Z","timestamp":1446514521000},"page":"393-399","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["<i>In Vitro<\/i>\n            Activity of \u03b2-Lactams in Combination with \u03b2-Lactamase Inhibitors against Multidrug-Resistant Mycobacterium tuberculosis Isolates"],"prefix":"10.1128","volume":"60","author":[{"given":"Dan","family":"Zhang","sequence":"first","affiliation":[{"name":"Yongchuan Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Wang","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Beijing Pediatric Research Institute, Beijing Children's Hospital affiliated to Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Pang","sequence":"additional","affiliation":[{"name":"National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report","author":"World Health Organization","year":"2013","unstructured":"World Health Organization. 2013. Global tuberculosis report. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2013.12.007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108789"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis128"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70041-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-014-0632-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir858"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09657"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1167498"},{"key":"e_1_3_3_11_2","first-page":"366","article-title":"Is there a place for \u03b2-lactams in the treatment of multidrug-resistant\/extensively drug-resistant tuberculosis?","volume":"68","author":"Gonzalo X","year":"2013","unstructured":"Gonzalo X, Drobniewski F. 2013. Is there a place for \u03b2-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":"Synergy between meropenem and amoxicillin\/clavulanate. 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