Abstract
BackgroundMulti-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce.MethodsA retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018.ResultsDuring this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p < 0.001 and OR 2.3, p < 0.05, respectively).The presence of each blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p < 0.001; OR 14.2, p < 0.001 and OR 1.3, p < 0.05 respectively) and being MDR (OR 1.96, p < 0.001; OR 5.9, p < 0.001 and OR 2.3, p < 0.001 respectively).ConclusionsThis study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis.
Highlights
Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns
For Acinetobacter spp., we report over 81% MDR, similar to what others have reported in ICUs in Nepal, but the ESBL prevalence we found (< 1% in Acinetobacter spp.) is much lower than what has been reported [15, 16, 29]
ESBL positivity was confirmed in 42% of K. pneumoniae and 33% of E. coli isolated from several hospitals in India [30], 40% in Enterobacteriaceae isolates from Pakistan [18] and 16% in enteric and non-enteric Gram-negative bacilli from Bangladesh [31]
Summary
Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Gram-negative bacilli, those in the bacterial family Enterobacteriaceae (e.g. Klebsiella spp. and Enterobacter spp.) and Acinetobacter spp. are common causes of serious community and hospital-acquired infections. These Gram-negative bacilli are members of the ESKAPE group of pathogens [1].These are notoriously associated with antimicrobial resistance (AMR) and frequently carry genes that induce resistance to three or more classes of antimicrobials, making them multi-drug resistant. CTX-M and TEM are the most common ESBLs, while OXA enzymes such as OXA-48, 23, 24, 51, 58 are common carbapenemases that are associated with Gramnegative bacteria that cause nosocomial infections [8, 9]
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