Castanheira Mariana, Mills Janet C, Costello Sarah E, Jones Ronald N, Sader Helio S
JMI Laboratories, North Liberty, Iowa, USA
JMI Laboratories, North Liberty, Iowa, USA.
Antimicrob Agents Chemother. 2015;59(6):3509-17. doi: 10.1128/AAC.00163-15. Epub 2015 Apr 6.
Ceftazidime-avibactam (MIC50/90, 0.12/0.25 μg/ml) inhibited 99.9% (20,698/20,709) of Enterobacteriaceae isolates at ≤8 μg/ml. This compound was active against resistant subsets, including ceftazidime-nonsusceptible Enterobacter cloacae (MIC50/90, 0.25/0.5 μg/ml) and extended-spectrum β-lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4% (1,696/13,692 isolates from targeted species) of the isolates, including 776 Escherichia coli (12.0% for this species; MIC50/90, 0.12/0.25 μg/ml), 721 Klebsiella pneumoniae (16.3%; MIC50/90, 0.12/0.25 μg/ml), 119 Klebsiella oxytoca (10.3%; MIC50/90, 0.06/0.25 μg/ml), and 80 Proteus mirabilis (4.9%; MIC50/90, 0.06/0.12 μg/ml) isolates. The most common enzymes detected among ESBL phenotype isolates from 2013 (n = 743) screened using a microarray-based assay were CTX-M-15-like (n = 307), KPC (n = 120), SHV ESBLs (n = 118), and CTX-M-14-like (n = 110). KPC producers were highly resistant to comparators, and ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml) and tigecycline (MIC50/90, 0.5/1 μg/ml; 98.3% susceptible) were the most active agents against these strains. Meropenem (MIC50/90, ≤0.06/≤0.06 μg/ml) and ceftazidime-avibactam (MIC50/90, 0.12/0.25 μg/ml) were active against CTX-M-producing isolates. Other enzymes were also observed, and ceftazidime-avibactam displayed good activity against the isolates producing less common enzymes. Among 11 isolates displaying ceftazidime-avibactam MIC values of >8 μg/ml, three were K. pneumoniae strains producing metallo-β-lactamases (all ceftazidime-avibactam MICs, >32 μg/ml), with two NDM-1 producers and one K. pneumoniae strain carrying the bla(KPC-2) and bla(VIM-4) genes. Therapeutic options for isolates producing β-lactamases may be limited, and ceftazidime-avibactam, which displayed good activity against strains, including those producing KPC enzymes, merits further study in infections where such organisms occur.
头孢他啶-阿维巴坦（MIC50/90为0.12/0.25μg/ml）在≤8μg/ml时可抑制99.9%（20,698/20,709）的肠杆菌科分离株。该化合物对耐药亚组具有活性，包括对头孢他啶不敏感的阴沟肠杆菌（MIC50/90为0.25/0.5μg/ml）和产超广谱β-内酰胺酶（ESBL）表型的分离株。在12.4%（1,696/13,692株来自目标菌种的分离株）的分离株中发现了ESBL表型，其中包括776株大肠埃希菌（该菌种的12.0%；MIC50/90为0.12/0.25μg/ml）、721株肺炎克雷伯菌（16.3%；MIC50/90为0.12/0.25μg/ml）、119株产酸克雷伯菌（10.3%；MIC50/90为0.06/0.25μg/ml）和80株奇异变形杆菌（4.9%；MIC50/90为0.06/0.12μg/ml）分离株。使用基于微阵列的检测方法对2013年（n = 743）的ESBL表型分离株进行筛查，检测到的最常见酶为CTX-M-15样酶（n = 307）、KPC酶（n = 120）、SHV型ESBL（n = 118）和CTX-M-14样酶（n = 110）。产KPC酶的菌株对对照药物高度耐药，头孢他啶-阿维巴坦（MIC50/90为0.5/2μg/ml）和替加环素（MIC50/90为0.5/1μg/ml；98.3%敏感）是针对这些菌株活性最强的药物。美罗培南（MIC50/90≤0.06/≤0.06μg/ml）和头孢他啶-阿维巴坦（MIC50/90为0.12/0.25μg/ml）对产CTX-M酶的分离株具有活性。还观察到了其他酶，头孢他啶-阿维巴坦对产生较少见酶的分离株显示出良好活性。在11株头孢他啶-阿维巴坦MIC值>8μg/ml的分离株中，3株为产金属β-内酰胺酶的肺炎克雷伯菌菌株（所有头孢他啶-阿维巴坦MIC值均>32μg/ml），其中2株为NDM-1产酶株，1株肺炎克雷伯菌菌株携带bla(KPC-2)和bla(VIM-4)基因。产β-内酰胺酶分离株的治疗选择可能有限，头孢他啶-阿维巴坦对包括产KPC酶菌株在内的多种菌株显示出良好活性，在这类微生物引起感染的治疗中值得进一步研究。
