High burden of ESBL and carbapenemase-producing gram-negative bacteria in bloodstream infection patients at a tertiary care hospital in Addis Ababa, Ethiopia
Authors: Beshah Daniel , Desta Adey Feleke , Woldemichael Gurja Belay , Belachew Esmael Besufikad , Derese Solomon Gizaw , Zelelie Tizazu Zenebe , Desalegn Zelalem , Tessema Tesfaye Sisay , Gebreselasie Solomon , Abebe Tamrat 
Published: June 2023

Background
Bloodstream infection due to beta-lactamase and carbapenemase-producing gram-negative bacteria poses a substantial challenge to the effectiveness of antimicrobial treatments. Therefore, this study aimed to investigate the magnitude of beta-lactamase, carbapenemase-producing gram-negative bacteria, and associated risk factors of bloodstream infections in patients at a tertiary care hospital, in Addis Ababa, Ethiopia.

Methods
An institutional-based cross-sectional study was conducted with convenience sampling techniques from September 2018 to March 2019. Blood cultures were analyzed from 1486 bloodstream infection suspected patients across all age groups. The blood sample was collected using two BacT/ALERT blood culture bottles for each patient. Gram stain, colony characteristics, and conventional biochemical tests were used to classify the gram-negative bacteria at the species level. Antimicrobial susceptibility testing was carried out to screen beta-lactam and carbapenem drug-resistant bacteria. The E-test was conducted for extended-spectrum-beta-lactamase and AmpC-beta-lactamase-producers. A modified and EDTA-modified carbapenem inactivation method was conducted for carbapenemase and metallo-beta-lactamases producers. Data collected using structured questionnaires and medical records were reviewed, encoded, and cleaned using EpiData V3.1. software. The cleaned data were exported and analyzed using SPSS version 24 software. Descriptive statistics and multivariate logistic registration models were used to describe and assess factors associated with acquiring drug-resistant bacteria infection. A p-value <0.05 was considered statistically significant.

Result
Among 1486 samples, 231 gram-negative bacteria were identified; of these, 195(84.4%) produce drug-hydrolyzing enzymes, and 31(13.4%) produce more than one drug-hydrolyzing enzyme. We found 54.0% and 25.7% of the gram-negative bacteria to be extended-spectrum-beta-lactamase and carbapenemase-producing, respectively. The extended-spectrum-beta-lactamase plus AmpC-beta-lactamase-producing bacteria account for 6.9%. Among the different isolates Klebsiella pneumonia 83(36.7%) was the highest drug-hydrolyzing enzyme-producing bacteria. Acinetobacter spp 25(53.2%) was the most carbapenemase producer. Extended-spectrum-beta-lactamase and carbapenemase-producing bacteria were high in this study. A significant association between age groups and extended-spectrum-beta-lactamase producer bacterial infection was seen, with a high prevalence in neonates (p = <0.001). Carbapenemase showed a significant association with patients admitted to the intensive care unit (p = 0.008), general surgery (p = 0.001), and surgical intensive care unit (p = 0.007) departments. Delivery of neonates by caesarean section, and insertion of medical instruments into the body were exposing factors for carbapenem-resistant bacterial infection. Chronic illnesses were associated with an extended-spectrum-beta-lactamase-producing bacterial infection. Klebsiella pneumonia and Acinetobacter species showed the greatest rates of extensively drug-resistant (37.3%) and pan-drug-resistance (76.5%), respectively. According to the results of this study, the pan-drug-resistance prevalence was found to be alarming.

Conclusion
Gram-negative bacteria were the main pathogens responsible for drug-resistant bloodstream infections. A high percentage of extended-spectrum-beta-lactamase and carbapenemase-producer bacteria were found in this study. Neonates were more susceptible to extended-spectrum-beta-lactamase and AmpC-beta-lactamase-producer bacteria. Patients in general surgery, caesarean section delivery, and intensive care unit were more susceptible to carbapenemase-producer bacteria. The suction machines, intravenous lines, and drainage tubes play an important role in the transmission of carbapenemase and metallo-beta-lactamase-producing bacteria. The hospital management and other stakeholders should work on infection prevention protocol implementation. Moreover, special attention should be given to all types of Klebsiella pneumoniae and pan-drug resistance Acinetobacter spp transmission dynamics, drug resistance genes, and virulence factors.