Abstract

BackgroundInfectious diseases are among the leading causes of death in many low-income countries, such as Ethiopia. Without reliable local data concerning causative pathogens and antimicrobial resistance, empiric treatment is suboptimal. The objective of this study was to characterize gram-negative bacteria (GNB) as pathogens and their resistance pattern in hospitalized patients with infections in central Ethiopia.MethodsPatients ≥ 1 year of age with fever admitted to the Asella Referral and Teaching Hospital from April 2016 to June 2018 were included. Blood and other appropriate clinical specimens were collected and cultured on appropriate media. Antibiotic susceptibility testing (AST) was performed using the Kirby–Bauer method and VITEK® 2. Species identification and detection of resistance genes were conducted using MALDI-ToF MS (VITEK® MS) and PCR, respectively.ResultsAmong the 684 study participants, 54.2% were male, and the median age was 22.0 (IQR: 14–35) years. Blood cultures were positive in 5.4% (n = 37) of cases. Among other clinical samples, 60.6% (20/33), 20.8% (5/24), and 37.5% (3/8) of swabs/pus, urine and other body fluid cultures, respectively, were positive. Among 66 pathogenic isolates, 57.6% (n = 38) were GNB, 39.4% (n = 26) were gram-positive, and 3.0% (n = 2) were Candida species. Among the isolated GNB, 42.1% (16/38) were Escherichia coli, 23.7% (9/38) Klebsiella pneumoniae and 10.5% (4/38) Pseudomonas aeruginosa.In total, 27/38 gram-negative isolates were available for further analysis. Resistance rates were as follows: ampicillin/sulbactam, 92.6% (n = 25); cefotaxime, 88.9% (n = 24); ceftazidime, 74.1% (n = 20); cefepime, 74.1% (n = 20); gentamicin, 55.6% (n = 15); piperacillin/tazobactam, 48.1% (n = 13); meropenem, 7.4% (n = 2); and amikacin, 3.7% (n = 1). The blaNDM-1 gene was detected in one K. pneumoniae and one Acinetobacter baumannii isolate, which carried an additional blaOXA-51 gene. The ESBL enzymes were detected in 81.5% (n = 22) of isolates as follows: TEM, 77.2% (n = 17); CTX-M-1 group, 68.2% (n = 15); SHV group, 27.3% (n = 6); and CTX-M-9 group, 9.1% (n = 2). Based on the in vitro antimicrobial susceptibility results, empiric treatment initiated in 13 of 18 (72.2%) patients was likely ineffective.ConclusionWe report a high prevalence of ESBL-producing bacteria (81.5%) and carbapenem resistance (7.4%), with more than half of GNB carrying two or more ESBL enzymes resulting in suboptimal empiric antibiotic therapy. These findings indicate a need for local and national antimicrobial resistance surveillance and the strengthening of antimicrobial stewardship programs.

Highlights

  • Infectious diseases are among the leading causes of morbidity and mortality in many low-income countries, such as Ethiopia [1]

  • We report a high prevalence of Extended-spectrum β-lactamase (ESBL)-producing bacteria (81.5%) and carbapenem resistance (7.4%), with more than half of gram-negative bacteria (GNB) carrying two or more ESBL enzymes resulting in suboptimal empiric antibiotic therapy

  • These findings indicate a need for local and national antimicrobial resistance surveillance and the strengthening of antimicrobial stewardship programs

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Summary

Introduction

Infectious diseases are among the leading causes of morbidity and mortality in many low-income countries, such as Ethiopia [1]. A major driver of resistance in GNB is the horizontal transfer of mobile genetic elements carrying genes for extended-spectrum β-lactamases (ESBL) and/or carbapenemases [4]. These enzymes hydrolyze penicillins, third-generation cephalosporins (3GCs) and carbapenems. The most prevalent carbapenemases are oxacillinases (OXA), namely, OXA23, OXA-24/40, OXA-48, OXA-51, OXA-58, OXA-143, and OXA-235; Klebsiella pneumoniae carbapenemase (KPC); metallo-beta-lactamases (MBL), such as the New Delhi metallo-β-lactamase (NDM); imipenemase (IMP); and Verona imipenemase (VIM) These enzymes confer resistance to cephalosporins and carbapenems [5, 6]. The objective of this study was to characterize gram-negative bacteria (GNB) as pathogens and their resistance pattern in hospitalized patients with infections in central Ethiopia

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