title: In vitro activity of CXA-101 plus tazobactam (CXA-201) against CTX-M-14- and CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae.
abstract: CXA-101, a novel cephalosporin with good antipseudomonal activity, was evaluated against a consecutive and polyclonal collection of extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli (n = 149) and Klebsiella pneumoniae (n = 20), mainly CTX-M-15- (69%) or CTX-M-14 producing (22%). A total of 41% of the E. coli isolates belonged to the international clone O25b-ST131. Broth microdilution versus CXA-101, CXA-tazobactam 4 and 8 mg/L (CXA-201), ceftazidime-tazobactam (CAT), ceftazidime-clavulanate (CAC), piperacillin-tazobactam (TZP), amoxicillin-clavulanate (ACL), ampicillin-sulbactam (ASU), and other comparators was performed, using EUCAST methodology and breakpoints. Susceptibility to CXA-201 was 96% (tazobactam 8 mg/L, tentative breakpoint S ≤ 1 mg/L), CAT 93%, CAC 95%, ACL 24%, ASU 2%, TZP 58%, ciprofloxacin 25%, levofloxacin 30%, gentamicin 54%, tobramycin 34%, amikacin 90%, and tigecycline 98%. Ninety-four percent of the TZP-resistant and all ACL-resistant isolates were CXA-201 susceptible. CXA-201 has good in vitro activity against ESBL-producing Enterobacteriaceae and might be a future therapeutic option for infections caused by TZP- and ACL-resistant isolates.
authors.affiliation: Division of Medicine, Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden. emilia.titelman@karolinska.se
authors.forename: Emilia
authors.initials: E
authors.lastname: Titelman
authors.forename: Inga M
authors.initials: IM
authors.lastname: Karlsson
authors.forename: Yigong
authors.initials: Y
authors.lastname: Ge
authors.forename: Christian G
authors.initials: CG
authors.lastname: Giske
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D002511:Cephalosporins / Q000494:pharmacology*; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004927:Escherichia coli Infections / Q000382:microbiology; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078142:Tazobactam; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C519491:ceftolozane; D010397:Penicillanic Acid; C456080:beta-lactamase CTX-M-14; C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases; D000078142:Tazobactam