Extended-spectrum β-lactamase- producing gram-negative bacterial infections in severely ill COVID-19 patients admitted in a national referral hospital, Kenya (preprint)

Background: 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 bacteria (GNB) infections among severely ill laboratory-confirmed COVID-19 patients admitted at Kenyatta National Hospital (KNH), Kenya. Methods: We adopted a descriptive cross-sectional study design for patients admitted between October 2021 and February 2022, purposively recruiting 120 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, Kenya Medical Research Institute. Results: GNB infections prevalence was 40.8%, with the majority 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 the typical 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 about ten (10) times more likely to have an ESB-producing GNB infection (aOR =9.86, 95%CI: 1.30 – 74.63, p =0.003). Conclusion: 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. Enhanced systematic and continuous surveillance of ESBL-producing GNB, strict adherence to infection control measures and antimicrobial stewardship policies in the current study setting are warranted.

Multidrug resistant bacterial infections in severely ill COVID-19 patients admitted in a national referral and teaching hospital, Kenya (preprint)

Background: Bacterial infections are a common complication in patients with seasonal viral respiratory tract infections and are associated with poor prognosis, increased risk of ICU admission and 29-55% mortality. Yet, there is limited data on the burden of bacterial infections among COVID-19 patients in Africa, where underdeveloped healthcare systems are likely to play a pertinent role in the epidemiology of the COVID-19 pandemic. Here, we evaluated the etiologies, Antimicrobial Resistance profiles, risk factors, and outcomes of bacterial infections in severely ill COVID-19 patients admitted to in a tertiary national teaching and referral hospital in Kenya. Methods: A descriptive cross-sectional study design on severely ill COVID-19 patients at Kenyatta National Hospital between October and December 2021 was adopted. A structured questionnaire and case report forms were used to collect patients’ sociodemographic, clinical presentation and outcomes respectively. Blood, nasal/oropharyngeal swabs and tracheal aspirate samples were collected based on the decision of the treating physician and transported to microbiology laboratory for immediate processing following the standard bacteriological procedures. Results: At least one bacterial infection was found in 44.2% (53/120) patients sampled. A mortality rate of 31.7% (38/120) was found. The majority of pathogens were from upper respiratory tract (62.7%, 42/67), with gram-negative bacteria as the most dominant isolates (73.1%, 49/67). Male were about three times more likely to acquire bacterial infection than females (aOR = 2.61, 95% CI: 1.2 – 5.65, p = 0.015). Those aged between 25 to 40 years (aOR = 0.13, 95% CI: 0.02 – 0.6, p =0.009), vaccinated (aOR = 0.2, 95%CI: 0.05 – 0.83, p = 0.027) and admitted to the Infectious Disease Unit (IDU) ward (aOR = 3.27, 95%CI: 1.08 – 6.89, p=0.031), for those admitted for a short length of stay (0 -5 days) (aOR=14.28, 95% CI:3.25 - 62.76, p<0.001) were more likely to have a positive outcome. The majority of bacteria isolates (64.3%, 46/67) were multidrug-resistant (MDR), mostly attributable to gram negative bacteria (GNB) (69.6%, 32/46). The predominant MDR phenotypes were found in Enterococcus cloacae (42.9%, 3/7), Klebsiella pneumonia (25%, 4/16), and Escherichia coli (40%, 2/5) and mostly involved cefotaxime, ceftriaxone, gentamicin, ciprofloxacin, aztreonam and trimethoprim/sulfamethoxazole. Conclusion: Our findings highlight a high prevalence of bacterial infections in hospitalized COVID-19 patients during the peak of the pandemic, with males more likely to be infected, while those in advanced age, not vaccinated, admitted to the critical care unit, and those with prolonged length of hospital stay showing a poor hospitalization outcome. The observed high multidrug-resistant infections are unacceptably high, emphasizing the need to monitor the effectiveness of the existing infection control strategies at KNH-IDU and adherence to antimicrobial stewardship in line with local and global AMR control action plans.