Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Malawi-Liverpool Wellcome Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi; Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK.
Lancet Microbe. 2022 Dec;3(12):e922-e930. doi: 10.1016/S2666-5247(22)00282-8. Epub 2022 Nov 3.
The burden of antimicrobial resistance is a major threat to global health; however, prospective clinical outcome data from Africa are scarce. In Malawi, third-generation cephalosporins are the antibiotics of choice in patients admitted to hospital despite a rapid proliferation of resistance to these drugs. We aimed to quantify the effect of resistance to third-generation cephalosporins on mortality and length of hospital stay among patients with bloodstream infections.
We did a prospective cohort study of patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Patients of all ages who had positive blood cultures for Enterobacterales were included, with the exception of those from the genus Salmonella, and were followed up for 180 days. We characterised blood culture isolates using whole-genome sequencing and used Cox regression models to estimate the effect of resistance to third-generation cephalosporins on length of hospital stay, in-hospital mortality, and survival.
Between Jan 31, 2018, and Jan 13, 2020, we recruited 326 patients, from whom 220 (68%) of 326 isolates were resistant to third-generation cephalosporins. The case fatality proportion was 45% (99 of 220) in patients with bloodstream infections that were resistant to third-generation cephalosporins, and 34% (36 of 106) in patients with bloodstream infections that were sensitive to third-generation cephalosporins. Resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1·44, 95% CI 1·02-2·04), longer hospital stays (1·5 days, 1·0-2·0) and decreased probability of discharge alive (HR 0·31, 0·22-0·45). Whole-genome sequencing showed a high diversity of sequence types of both Escherichia coli and Klebsiella pneumoniae. Although isolates associated with death were distributed across clades, we identified three E coli clades (ST410, ST617, and ST648) that were isolated from 14 patients who all died.
Resistance to third-generation cephalosporins is associated with increased mortality and longer hospital stays in patients with bloodstream infections in Malawi. These data show the urgent need for allocation of resources towards antimicrobial resistance mitigation strategies in Africa.
Wellcome Trust and Wellcome Asia and Africa Programme.
抗生素耐药性的负担是对全球健康的主要威胁；然而，来自非洲的前瞻性临床结果数据仍然很少。在马拉维，尽管这些药物的耐药性迅速增加，但第三代头孢菌素仍然是住院患者的首选抗生素。我们旨在量化第三代头孢菌素耐药性对血流感染患者死亡率和住院时间的影响。
我们对马拉维布兰太尔伊丽莎白女王中央医院的住院患者进行了前瞻性队列研究。除了沙门氏菌属之外，所有年龄的血培养阳性肠杆菌科患者都被纳入研究，并随访 180 天。我们使用全基因组测序对血培养分离株进行了特征描述，并使用 Cox 回归模型估计第三代头孢菌素耐药性对住院时间、院内死亡率和生存率的影响。
在 2018 年 1 月 31 日至 2020 年 1 月 13 日期间，我们共招募了 326 名患者，其中 220 名（68%）的 326 个分离株对第三代头孢菌素耐药。第三代头孢菌素耐药的血流感染患者的病死率比例为 45%（99/220），而第三代头孢菌素敏感的血流感染患者的病死率比例为 34%（36/106）。第三代头孢菌素耐药与院内死亡率增加相关（风险比[HR]1.44，95%CI1.02-2.04），住院时间延长（1.5 天，1.0-2.0），存活出院的可能性降低（HR0.31，0.22-0.45）。全基因组测序显示，大肠杆菌和肺炎克雷伯菌的序列类型多样性很高。虽然与死亡相关的分离株分布在不同的分支中，但我们确定了三个大肠杆菌分支（ST410、ST617 和 ST648），它们均从 14 名死亡患者中分离出来。
第三代头孢菌素耐药与马拉维血流感染患者的死亡率增加和住院时间延长相关。这些数据表明，迫切需要在非洲分配资源，以实施缓解抗生素耐药性的策略。
惠康信托基金会和惠康非洲和亚洲计划。
