Abstract
Carbapenem-resistant gram-negative bacteria are an increasingly significant clinical threat globally. This risk may be underestimated in Kenya as only four carbapenemase genes in three bacterial species have been described. The study aimed to understand the antibiotic resistance profiles, genes, sequence types, and distribution of carbapenem-resistant gram-negative bacteria from patients in six hospitals across five Kenyan counties by bacterial culture, antibiotic susceptibility testing, and whole-genome sequence analysis. Forty-eight, non-duplicate, carbapenem non-susceptible, clinical isolates were identified across the five counties (predominantly in Nairobi and Kisii): twenty-seven Acinetobacter baumannii, fourteen Pseudomonas aeruginosa, three Escherichia coli, two Enterobacter cloacae, and two Klebsiella pneumoniae. All isolates were non-susceptible to β-lactam drugs with variable susceptibility to tigecycline (66%), minocycline (52.9%), tetracycline (29.4%), and levofloxacin (22.9%). Thirteen P. aeruginosa isolates were resistant to all antibiotics tested. Eleven carbapenemase genes were identified: blaNDM-1, blaOXA-23, -58, -66, -69, and -91 in A. baumannii (STs 1, 2, 164 and a novel ST1475), blaNDM-1 in E. cloacae (STs 25,182), blaNDM-1, blaVIM-1and -6, blaOXA-50 in P. aeruginosa (STs 316, 357, 654, and1203), blaOXA-181, blaNDM-1 in K. pneumoniae (STs 147 and 219), and blaNDM-5 in E. coli (ST164). Five A. baumannii isolates had two carbapenemases, blaNDM-1, and either blaOXA-23 (4) or blaOXA-58 (1). AmpC genes were detected in A. baumannii (blaADC-25), E. cloacae (blaDHA-1 and blaACT-6, 16), and K. pneumoniae (blaCMY). Significant multiple-drug resistant genes were the pan-aminoglycoside resistance16srRNA methyltransferase armA, rmtB, rmtC, and rmtF genes. This study is the first to report blaOXA-420, -58, -181, VIM-6, and blaNDM-5 in Kenyan isolates. High-risk STs of A. baumannii (ST1475, ST2), E. cloacae ST182, K. pneumoniae ST147, P. aeruginosa (ST357, 654), and E. coli ST167, ST648 were identified which present considerable therapeutic danger. The study recommends urgent carbapenem use regulation and containment of high-risk carbapenem-resistant bacteria.
Highlights
Multidrug resistance among clinically significant gram-negative bacteria (GNB)
Patient data and the antimicrobial susceptibility (AS) data for each isolate extracted from the automated platforms were compiled in a Microsoft Access database. These compiled data were transferred to Microsoft Excel for descriptive statistical analysis with frequency distributions and the results summarized in tables
69% of the isolates were from male subjects, 87% were inpatient, and 64% were healthcare-associated infections (HAI) per the CDC/NHSN Surveillance Definition of Healthcare-Associated Infection [34]
Summary
Multidrug resistance among clinically significant gram-negative bacteria (GNB) Pseudomonas aeruginosa, and Acinetobacter baumannii) has led to increased morbidity and an estimated 40% mortality in developing countries [1, 2]. These adverse outcomes are due to treatment options being limited to expensive, often unavailable, last-line drugs such as tigecycline. Carbapenems are an important βlactam drug class used to treat serious multidrug-resistant bacterial infections. The global increase in carbapenem resistance (CR) has been recognized as a severe health threat [3]. Secondary mechanisms for CR are the constitutive over-production of AmpC and changes in permeability due to loss or down-regulation of porins [5]
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