Bacterial superinfections associated with COVID-19 are common in ventilated ICU patients and impact morbidity and lethality. However, the contribution of antimicrobial resistance to the manifestation of bacterial infections in these patients has yet to be elucidated. We collected 70 Gram-negative bacterial strains, isolated from the lower respiratory tract of ventilated COVID-19 patients in Zurich, Switzerland between March and May 2020. Species identification was performed using MALDI-TOF; antibiotic susceptibility profiles were determined by EUCAST disk diffusion and CLSI broth microdilution assays. Selected Pseudomonas aeruginosa isolates were analyzed by whole-genome sequencing. Pseudomonas aeruginosa (46%) and Enterobacterales (36%) comprised the two largest etiologic groups. Drug resistance in P. aeruginosa isolates was high for piperacillin/tazobactam (65.6%), cefepime (56.3%), ceftazidime (46.9%) and meropenem (50.0%). Enterobacterales isolates showed slightly lower levels of resistance to piperacillin/tazobactam (32%), ceftriaxone (32%), and ceftazidime (36%). All P. aeruginosa isolates and 96% of Enterobacterales isolates were susceptible to aminoglycosides, with apramycin found to provide best-in-class coverage. Genotypic analysis of consecutive P. aeruginosa isolates in one patient revealed a frameshift mutation in the transcriptional regulator nalC that coincided with a phenotypic shift in susceptibility to β-lactams and quinolones. Considerable levels of antimicrobial resistance may have contributed to the manifestation of bacterial superinfections in ventilated COVID-19 patients, and may in some cases mandate consecutive adaptation of antibiotic therapy. High susceptibility to amikacin and apramycin suggests that aminoglycosides may remain an effective second-line treatment of ventilator-associated bacterial pneumonia, provided efficacious drug exposure in lungs can be achieved.

中文翻译：

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瑞士 COVID-19 患者呼吸道革兰氏阴性细菌分离株的抗菌药物敏感性模式


与 COVID-19 相关的细菌重复感染在 ICU 通气患者中很常见，会影响发病率和致死率。然而，抗菌药物耐药性对这些患者细菌感染表现的影响尚未阐明。我们收集了 2020 年 3 月至 5 月期间从瑞士苏黎世通气的 COVID-19 患者下呼吸道分离的 70 株革兰氏阴性细菌菌株。使用 MALDI-TOF 进行物种鉴定；抗生素敏感性曲线通过 EUCAST 纸片扩散和 CLSI 肉汤微量稀释测定法确定。通过全基因组测序分析选定的铜绿假单胞菌分离株。铜绿假单胞菌 (46%) 和肠杆菌 (36%) 构成了两个最大的病原菌群。铜绿假单胞菌分离株对哌拉西林/他唑巴坦 (65.6%)、头孢吡肟 (56.3%)、头孢他啶 (46.9%) 和美罗培南 (50.0%) 的耐药性较高。肠杆菌分离株对哌拉西林/他唑巴坦 (32%)、头孢曲松 (32%) 和头孢他啶 (36%) 的耐药性略低。所有铜绿假单胞菌分离株和 96% 的肠杆菌分离株均对氨基糖苷类药物敏感，其中安普霉素具有最佳的覆盖率。对一名患者的连续铜绿假单胞菌分离株进行的基因型分析揭示了转录调节因子 nalC 中的移码突变，该突变与对 β-内酰胺和喹诺酮类药物敏感性的表型转变相一致。相当程度的抗菌药物耐药性可能导致了机械通气的 COVID-19 患者出现细菌重复感染，并且在某些情况下可能需要连续调整抗生素治疗。 对阿米卡星和安普霉素的高度敏感性表明，只要能够实现肺部有效的药物暴露，氨基糖苷类药物可能仍然是呼吸机相关细菌性肺炎的有效二线治疗方法。