Bacterial infections in COVID-19 patients, especially those caused by multidrug-resistant gram-negative strains, are associated with increased morbidity, hospital stay and mortality. However, there is limited data on the epidemiology of extended-spectrum β-lactamase (ESBL)-producing bacteria in COVID-19 patients. Here, we assessed the prevalence and the factors associated with ESBL-producing gram-negative bacterial (GNB) infections among severely ill COVID-19 patients admitted in Kenyatta National Hospital (KNH), Kenya. We adopted a descriptive cross-sectional study design for patients admitted between October 2021 and February 2022, purposively recruiting 120 SARS-CoV- 2 infected participants based on clinical presentation. Demographics and clinical characteristics data were collected using structured questionnaires and case report forms. Clinical samples were collected and analyzed by standard microbiological methods in the KNH Microbiology laboratory and the Centre for Microbiology Research, Kenya Medical Research Institute. GNB infections prevalence was 40.8%, majorly caused by ESBL—producers (67.3%) predominated by Klebsiella pneumoniae (45.5%). Generally, 73% of the ESBL producers harboured our target ESBL genes, mainly CTX-M-type (59%, 17/29) in K. pneumoniae (76.9%, 20/26). GNB harbouring TEM-type (83%, 10/12) and SHV-type (100%, 7/7) genes showed ESBLs phenotypes and inhibitor resistance, mainly involving clavulanate, but most of them remained susceptible to tazobactam (60%, 6/10). SHV-type genes carrying ESBL producers showed resistance to both cefotaxime (CTX) and ceftazidime (CAZ) (K. pneumoniae), CAZ (E. coli) or CTX (E. cloacae complex and K. pneumoniae). About 87% (20/23) of isolates encoding CTX-M-type β-lactamases displayed CTX/ceftriaxone (CRO) resistance phenotype. About 42% of isolates with CTX-M-type β-lactamases only hydrolyzed ceftazidime (CAZ). Isolates with OXA-type β-lactamases were resistant to CTX, CAZ, CRO, cefepime and aztreonam. Patients with comorbidities were 10 times more likely to have an ESBL-producing GNB infection (aOR = 9.86, 95%CI 1.30 – 74.63, p = 0.003). We report a high prevalence of ESBL-GNB infections in severely ill COVID-19 patients, predominantly due to Klebsiella pneumoniae harbouring CTX-M type ESBL genes. The patient’s underlying comorbidities increased the risk of ESBL-producing GNB infection. In COVID-19 pandemic, enhanced systematic and continuous surveillance of ESBL-producing GNB, strict adherence to infection control measures and antimicrobial stewardship policies are warranted in the current study setting.

中文翻译：

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肯尼亚国家转诊医院收治的重症 COVID-19 患者中产生超广谱 β-内酰胺酶的革兰氏阴性细菌感染

COVID-19 患者的细菌感染，尤其是由多重耐药革兰氏阴性菌株引起的细菌感染，与发病率、住院时间和死亡率增加有关。然而，关于 COVID-19 患者中产生超广谱 β-内酰胺酶 (ESBL) 的细菌的流行病学数据有限。在这里，我们评估了肯尼亚肯雅塔国家医院 (KNH) 收治的重症 COVID-19 患者中产 ESBL 革兰氏阴性细菌 (GNB) 感染的患病率和相关因素。我们对 2021 年 10 月至 2022 年 2 月期间入院的患者采用了描述性横断面研究设计，根据临床表现有意招募 120 名 SARS-CoV-2 感染参与者。使用结构化问卷和病例报告表收集人口统计和临床特征数据。在 KNH 微生物学实验室和肯尼亚医学研究所微生物学研究中心通过标准微生物学方法收集和分析临床样本。GNB 感染率为 40.8%，主要由 ESBL 产生者 (67.3%) 引起，其中以肺炎克雷伯菌 (45.5%) 为主。一般来说，73% 的 ESBL 生产者携带我们的目标 ESBL 基因，主要是肺炎克雷伯菌 (76.9%, 20/26) 中的 CTX-M 型 (59%, 17/29)。携带TEM型（83%，10/12）和SHV型（100%，7/7）基因的GNB表现出ESBLs表型和抑制剂耐药性，主要涉及克拉维酸，但大多数仍对他唑巴坦敏感（60%，6 /10）。携带 ESBL 产生者的 SHV 型基因显示出对头孢噻肟 (CTX) 和头孢他啶 (CAZ)（肺炎克雷伯菌）、CAZ（大肠杆菌）或 CTX（阴沟肠杆菌复合体和肺炎克雷伯菌）的耐药性。大约 87% (20/23) 编码 CTX-M 型 β-内酰胺酶的分离株表现出 CTX/头孢曲松 (CRO) 耐药表型。大约 42% 的 CTX-M 型 β-内酰胺酶分离株仅水解头孢他啶 (CAZ)。具有 OXA 型 β-内酰胺酶的分离株对 CTX、CAZ、CRO、头孢吡肟和氨曲南具有耐药性。患有合并症的患者发生 ESBL 产生的 GNB 感染的可能性高出 10 倍（aOR = 9.86，95% CI 1.30 – 74.63，p = 0.003）。我们报告重症 COVID-19 患者中 ESBL-GNB 感染的患病率很高，这主要是由于肺炎克雷伯菌携带 CTX-M 型 ESBL 基因。患者的潜在合并症增加了产生 ESBL 的 GNB 感染的风险。在 COVID-19 大流行中，在当前的研究环境中，有必要加强对产生 ESBL 的 GNB 的系统和持续监测，严格遵守感染控制措施和抗菌药物管理政策。