AstraZeneca Pharmaceuticals, 35 Gatehouse Drive, Waltham, MA 02451, USA.
AstraZeneca Global Medicines Development, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523. doi: 10.1093/jac/dky204.
This analysis evaluated the clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa isolates pooled from the adult Phase III clinical trials in patients with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI) or nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP).
Baseline isolates from five Phase III randomized controlled trials of ceftazidime/avibactam versus predominantly carbapenem comparators in patients with cIAI (RECLAIM 1 and 2; NCT01499290 and RECLAIM 3; NCT01726023), cUTI (RECAPTURE 1 and 2; NCT01595438 and NCT01599806), NP including VAP (REPROVE; NCT01808092) and cIAI or cUTI caused by ceftazidime-non-susceptible Gram-negative pathogens (REPRISE; NCT01644643) were tested for MDR status and susceptibility to ceftazidime/avibactam and carbapenem-based comparators using CLSI broth microdilution methodology. Microbiological and clinical responses for patients with ≥1 MDR Enterobacteriaceae or P. aeruginosa isolate were assessed at the test-of-cure (TOC) visit.
In the pooled microbiologically modified ITT population, 1051 patients with MDR Enterobacteriaceae and 95 patients with MDR P. aeruginosa isolates were identified. Favourable microbiological response rates at TOC for all MDR Enterobacteriaceae and MDR P. aeruginosa were 78.4% and 57.1%, respectively, for ceftazidime/avibactam and 71.6% and 53.8%, respectively, for comparators. The proportions of patients with ≥1 MDR isolate who were clinically cured at TOC were similar in the ceftazidime/avibactam (85.4%) and comparator (87.9%) arms.
Ceftazidime/avibactam demonstrated similar clinical efficacy to predominantly carbapenem comparators against MDR Enterobacteriaceae and P. aeruginosa, and may be a suitable alternative to carbapenem-based therapies for cIAI, cUTI and NP/VAP caused by MDR Gram-negative pathogens.
本分析评估了头孢他啶/阿维巴坦对来自复杂性腹腔内感染（cIAI）、复杂性尿路感染（cUTI）或医院获得性肺炎（NP）包括呼吸机相关性肺炎（VAP）成人三期临床研究中分离的耐多药肠杆菌科和铜绿假单胞菌的临床活性。
对五项头孢他啶/阿维巴坦与主要碳青霉烯类对照药物治疗 cIAI（RECLAIM 1 和 2；NCT01499290 和 RECLAIM 3；NCT01726023）、cUTI（RECAPTURE 1 和 2；NCT01595438 和 NCT01599806）、NP 包括 VAP（REPROVE；NCT01808092）和头孢他啶不敏感革兰阴性病原体引起的 cIAI 或 cUTI（REPRISE；NCT01644643）的患者的基线分离株进行了多药耐药状态检测，并采用 CLSI 肉汤微量稀释法检测了对头孢他啶/阿维巴坦和碳青霉烯类对照药物的敏感性。在治疗期结束时（TOC）评估了至少有 1 株耐多药肠杆菌科或铜绿假单胞菌分离株的患者的微生物学和临床反应。
在合并的微生物学改良意向治疗人群中，确定了 1051 例耐多药肠杆菌科和 95 例耐多药铜绿假单胞菌分离株患者。所有耐多药肠杆菌科和耐多药铜绿假单胞菌的 TOC 时良好的微生物学反应率分别为头孢他啶/阿维巴坦 78.4%和对照药物 71.6%，头孢他啶/阿维巴坦分别为 57.1%和对照药物 53.8%。在 TOC 时，至少有 1 株耐多药分离株的患者中，头孢他啶/阿维巴坦（85.4%）和对照药物（87.9%）组的临床治愈率相似。
头孢他啶/阿维巴坦对耐多药肠杆菌科和铜绿假单胞菌的临床疗效与主要碳青霉烯类对照药物相似，对于耐多药革兰阴性病原体引起的 cIAI、cUTI 和 NP/VAP，可能是碳青霉烯类治疗的替代药物。
