Mendes Rodrigo E, Castanheira Mariana, Woosley Leah N, Stone Gregory G, Bradford Patricia A, Flamm Robert K
JMI Laboratories, North Liberty, Iowa, USA
JMI Laboratories, North Liberty, Iowa, USA.
Antimicrob Agents Chemother. 2017 May 24;61(6). doi: 10.1128/AAC.02447-16. Print 2017 Jun.
The correlation of the clinical efficacy of ceftazidime-avibactam (plus metronidazole) with that of meropenem was evaluated in subjects infected with Gram-negative isolates having characterized β-lactam resistance mechanisms from the complicated intra-abdominal infection (cIAI) phase 3 clinical trials. isolates displaying ceftriaxone and/or ceftazidime MIC values of ≥2 μg/ml and isolates with ceftazidime MIC values of ≥16 μg/ml were characterized for extended-spectrum-β-lactamase (ESBL) content. and isolates with imipenem and meropenem MIC values of ≥2 and ≥8 μg/ml, respectively, were tested for carbapenemase genes. The primary efficacy endpoint was clinical cure at test of cure (TOC) among the members of the microbiologically modified intention-to-treat (mMITT) population. A total of 14.5% (56/387) and 18.8% (74/394) of patients in the ceftazidime-avibactam and meropenem arms had isolates that met the MIC screening criteria at the baseline visit, respectively. CTX-M variants alone (29.7%; 41/138) or in combination with OXA-1/30 (35.5%; 49/138), most commonly, group 1 variants (79/90; 87.8%), represented the β-lactamases most frequently observed among isolates. Among the patients infected with pathogens that did not meet the screening criteria, 82.2% showed clinical cure in the ceftazidime-avibactam group versus 85.9% in the meropenem group. Among patients infected with any pathogens that met the MIC screening criteria, clinical cure rates at TOC were 87.5% and 86.5% for the ceftazidime-avibactam and meropenem groups, respectively. Ceftazidime-avibactam had clinical cure rates of 92.5% to 90.5% among patients infected with ESBL- and/or carbapenemase-producing strains at the baseline visit, while meropenem showed rates of 84.9% to 85.4%. The ceftazidime-avibactam and meropenem groups had cure rates of 75.0% and 86.7%, respectively, among patients having any pathogens producing AmpC enzymes. The efficacy of ceftazidime-avibactam was similar to that of meropenem for treatment of cIAI caused by ESBL-producing organisms. (This study has been registered at ClinicalTrials.gov under registration no. NCT01499290 and NCT01500239.).
在复杂腹腔内感染（cIAI）3期临床试验中，对感染具有特定β-内酰胺耐药机制的革兰氏阴性菌的受试者，评估了头孢他啶-阿维巴坦（加甲硝唑）与美罗培南的临床疗效相关性。对头孢曲松和/或头孢他啶MIC值≥2μg/ml的菌株以及头孢他啶MIC值≥16μg/ml的菌株进行超广谱β-内酰胺酶（ESBL）含量鉴定。对亚胺培南MIC值≥2μg/ml和美罗培南MIC值≥8μg/ml的菌株检测碳青霉烯酶基因。主要疗效终点是微生物学改良意向性治疗（mMITT）人群中治疗结束时（TOC）的临床治愈。头孢他啶-阿维巴坦组和美罗培南组分别有14.5%（56/387）和18.8%（74/394）的患者在基线访视时其分离株符合MIC筛选标准。单独的CTX-M变体（29.7%；41/138）或与OXA-1/30联合（35.5%；49/138），最常见的是1组变体（79/90；87.8%），是在分离株中最常观察到的β-内酰胺酶。在感染不符合筛选标准病原体的患者中，头孢他啶-阿维巴坦组的临床治愈率为82.2%，而美罗培南组为85.9%。在感染任何符合MIC筛选标准病原体的患者中，头孢他啶-阿维巴坦组和美罗培南组在TOC时的临床治愈率分别为87.5%和86.5%。在基线访视时感染产ESBL和/或碳青霉烯酶菌株的患者中，头孢他啶-阿维巴坦的临床治愈率为92.5%至90.5%，而美罗培南为84.9%至85.4%。在有任何产AmpC酶病原体的患者中，头孢他啶-阿维巴坦组和美罗培南组的治愈率分别为75.0%和86.7%。头孢他啶-阿维巴坦治疗由产ESBL生物体引起的cIAI的疗效与美罗培南相似。（本研究已在ClinicalTrials.gov注册，注册号为NCT01499290和NCT01500239。）
