Infection and Drug Resistance (Apr 2021)
In vitro Antimicrobial Synergy Testing of Extensively Drug-Resistant Clinical Isolates at an Organ Transplant Center in Nepal
Abstract
Rashmi Karki,1,2,* Samir Lamichhane,3,* Buddha Bahadur Basnet,4 Anuja Dahal,5 Bal Krishna Awal,2,6 Shyam Kumar Mishra7,8,* 1Janamaitri Foundation Institute of Health Sciences, Tribhuvan University, Nepal; 2National Public Health Laboratory, Kathmandu, Nepal; 3Department of Pharmacology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal; 4Faculty of Science, Nepal Academy of Science and Technology, Lalitpur, Nepal; 5Department of Pharmacy, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal; 6Shahid Dharmabhakta National Transplant Center, Bhaktapur, Nepal; 7School of Optometry and Vision Science, Faculty of Medicine and Health, UNSW, Sydney, NSW, Australia; 8Department of Microbiology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal*These authors contributed equally to this workCorrespondence: Shyam Kumar MishraSchool of Optometry and Vision Science, UNSW, Sydney, NSW, AustraliaTel +61415538329Email [email protected]: Inappropriate use of broad-spectrum antibiotics contributes to the emergence of multidrug-resistant (MDR) bacteria. Finding novel antimicrobial agents and strategies based on synergistic combinations are essential to combat MDR infections. This study was designed to determine in vitro synergy of different antimicrobials against extensively drug-resistant (XDR) Gram-negative clinical isolates.Methods: A descriptive, cross-sectional study was conducted at Human Organ Transplant Center, Nepal, for five months. Clinical isolates were checked for their drug-resistance properties including extended-spectrum beta-lactamase- (ESBL-) and metallo-beta-lactamase- (MBL-) production. The XDR isolates were further tested for antimicrobial synergy, and the results were interpreted as synergistic, additive, indifferent or antagonistic determining fractional inhibitory concentration of the antibiotics.Results: Out of total 1155 clinical samples, 308 showed significant growth. Escherichia coli was the most common isolate (n=142) followed by Klebsiella pneumoniae, Acinetobacter calcoaceticus baumannii (Acb) complex, Pseudomonas aeruginosa and miscellaneous bacteria. Out of the culture positive isolates, 21.4% were MDR and 10.06% were XDR. The XDR population comprised K. pneumoniae (18.42%), E. coli (9.86%), Acb complex (7.41%) and P. aeruginosa (4.17%). Among the culture positive isolates, 4.5% and 5.8% were ESBL- and MBL-producers, respectively. Colistin, polymyxin B, and tigecycline were the antibiotics effective in majority of MDR isolates as compared to carbapenems. The combination of antibiotics – meropenem and colistin showed the highest proportion of “synergy” among all XDR E. coli whereas the combination of amikacin and colistin showed synergistic effect in XDR K. pneumoniae.Conclusion: A significant proportion of isolates were MDR among which a large fraction was XDR. The combination of meropenem, amikacin and colistin with one another in pair showed beneficial activity in vitro. Such combinations can be utilized as effective therapy for XDR infections. Further studies are required to confirm these findings, and accordingly treatment protocols should be developed in the management of such infections.Keywords: antimicrobial synergy, ESBL, MBL, MDR, XDR
