In Vitro Activity of NXL104 in Combination with β-Lactams against Klebsiella pneumoniae Isolates Producing KPC Carbapenemases

作者：Andrea Endimiani, Yuvraj Choudhary, Robert A. Bonomo · 发表于：Antimicrobial Agents and Chemotherapy · 年份：2009 · DOI：10.1128/aac.00641-09 · 被引用次数：133 · 研究领域：Antibiotic Resistance in Bacteria、Antibiotics Pharmacokinetics and Efficacy、Pharmaceutical and Antibiotic Environmental Impacts

Klebsiella pneumoniae isolates producing class A KPC carbapenemases (KPC-Kp) are spreading at an alarming rate around the world (8, 10, 11). These isolates are highly resistant to penicillins, cephalosporins, and commercially available β-lactam/β-lactamase inhibitor combinations and show reduced susceptibility to carbapenems. KPC-Kp are also commonly resistant to quinolones, aminoglycosides, and occasionally to colistin (3, 7, 10). Therefore, our antibiotic choices for the treatment of infections due to KPC-Kp isolates are extremely limited. Developing novel β-lactamase inhibitors that are active against different classes of carbapenemases is an important goal (1). NXL104 (Novexel SA, Romainville, France) is a new β-lactamase inhibitor currently in clinical trials (http://clinicaltrials.gov/) and active against class A (e.g., TEM-, SHV-, and CTX-M-types) and class C β-lactamases (2, 9). However, data regarding its in vitro activity in combination with β-lactams against KPC-Kp isolates are very limited (9). In the present work, we analyzed the in vitro activity of NXL104 in combination with different β-lactams against a collection of 42 well-characterized KPC-Kp clinical isolates collected in the United States (6, 7). In a previous analysis, we demonstrated that (i) these strains possessed a complex β-lactamase background (i.e., three or more bla genes per isolate) and that (ii) clavulanate or tazobactam were unable to lower the MICs of β-lactams to susceptibility ranges...