Instituto Central, Hospital das Clínicas, Universidade de São Paulo, São Paulo, Brazil
School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Antimicrob Agents Chemother. 2019 Sep 23;63(10). doi: 10.1128/AAC.00528-19. Print 2019 Oct.
In this article, we report a case series of patients with infections caused by coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC, 1 μg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant .
在这篇文章中，我们报告了一系列对碳青霉烯类和多黏菌素类药物耐药的感染患者，他们根据同情用药方案接受了头孢他啶/阿维巴坦（CAZ-AVI）挽救治疗。我们在 3 家中心招募了 29 名成人患者，这些患者因耐药微生物感染且现有治疗方法被认为无效而接受 CAZ-AVI 治疗，并在治疗结束时评估临床和微生物学治愈率以及 14 天和 30 天的全因死亡率。使用肉汤微量稀释法测定抗菌药物敏感性谱，并用全基因组 DNA 测序。12 名（41.4%）患者有菌血症，48.3%（14/29）的感染采用联合治疗。所有菌株均为 KPC-2 产酶株，对 CAZ-AVI 敏感（MIC，1μg/ml）。临床治愈率很高（29/24 [82.7%]；95%置信区间，64.2%至 94.2%），甚至对菌血症病例也是如此（75%）。14 天和 30 天死亡率分别为 29/9（31%）和 29/15（51.7%）。肺炎的 14 天死亡率与血流感染相同（33.3%），虽然没有统计学意义，但我们发现接受 CAZ-AVI 调整剂量治疗的肾功能损害患者死亡率较高（9/4 [44%]； = 0.22）。我们得出结论，CAZ-AVI 是治疗因治疗困难而导致的严重耐药感染的一种选择。
