In vitro Antimicrobial Synergy Testing of Extensively Drug-Resistant Clinical Isolates at an Organ Transplant Center in Nepal

doi:10.2147/IDR.S309531

. 2021 Apr 30:14:1669-1677.

doi: 10.2147/IDR.S309531. eCollection 2021.

In vitro Antimicrobial Synergy Testing of Extensively Drug-Resistant Clinical Isolates at an Organ Transplant Center in Nepal

Rashmi Karki^#^{1

2}, Samir Lamichhane^#³, Buddha Bahadur Basnet⁴, Anuja Dahal⁵, Bal Krishna Awal^{2

6}, Shyam Kumar Mishra^#^{7

8}

Affiliations

¹ Janamaitri Foundation Institute of Health Sciences, Tribhuvan University, Nepal.
² National Public Health Laboratory, Kathmandu, Nepal.
³ Department of Pharmacology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal.
⁴ Faculty of Science, Nepal Academy of Science and Technology, Lalitpur, Nepal.
⁵ Department of Pharmacy, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal.
⁶ Shahid Dharmabhakta National Transplant Center, Bhaktapur, Nepal.
⁷ School of Optometry and Vision Science, Faculty of Medicine and Health, UNSW, Sydney, NSW, Australia.
⁸ Department of Microbiology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal.

^# Contributed equally.

PMID: 33958879
PMCID: PMC8096450
DOI: 10.2147/IDR.S309531

In vitro Antimicrobial Synergy Testing of Extensively Drug-Resistant Clinical Isolates at an Organ Transplant Center in Nepal

Rashmi Karki et al. Infect Drug Resist. 2021.

. 2021 Apr 30:14:1669-1677.

doi: 10.2147/IDR.S309531. eCollection 2021.

Authors

Rashmi Karki^#^{1

2}, Samir Lamichhane^#³, Buddha Bahadur Basnet⁴, Anuja Dahal⁵, Bal Krishna Awal^{2

6}, Shyam Kumar Mishra^#^{7

8}

Affiliations

¹ Janamaitri Foundation Institute of Health Sciences, Tribhuvan University, Nepal.
² National Public Health Laboratory, Kathmandu, Nepal.
³ Department of Pharmacology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal.
⁴ Faculty of Science, Nepal Academy of Science and Technology, Lalitpur, Nepal.
⁵ Department of Pharmacy, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal.
⁶ Shahid Dharmabhakta National Transplant Center, Bhaktapur, Nepal.
⁷ School of Optometry and Vision Science, Faculty of Medicine and Health, UNSW, Sydney, NSW, Australia.
⁸ Department of Microbiology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Nepal.

^# Contributed equally.

PMID: 33958879
PMCID: PMC8096450
DOI: 10.2147/IDR.S309531

Abstract

Purpose: 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: ESBL; MBL; MDR; XDR; antimicrobial synergy.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

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References

1. Aminov RI. A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol. 2010;1:134. doi:10.3389/fmicb.2010.00134 - DOI - PMC - PubMed
1. Gottlieb T, Nimmo GR. Antibiotic resistance is an emerging threat to public health: an urgent call to action at the Antimicrobial Resistance Summit 2011. Med J Aust. 2011;194(6):281–283. doi:10.5694/j.1326-5377.2011.tb02973.x - DOI - PubMed
1. Siegel RE. Emerging gram-negative antibiotic resistance: daunting challenges, declining sensitivities, and dire consequences. Respir Care. 2008;53(4):471–479. - PubMed
1. Roca I, Akova M, Baquero F, et al. The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect. 2015;6:22–29. doi:10.1016/j.nmni.2015.02.007 - DOI - PMC - PubMed
1. Rawat D, Extended-spectrum ND. β-lactamases in gram negative bacteria. J Glob Infect Dis. 2010;2(3):263–274. doi:10.4103/0974-777X.68531 - DOI - PMC - PubMed

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[1] Aminov RI. A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol. 2010;1:134. doi:10.3389/fmicb.2010.00134 - DOI - PMC - PubMed

[2] Aminov RI. A brief history of the antibiotic era: lessons learned and challenges for the future. Front Microbiol. 2010;1:134. doi:10.3389/fmicb.2010.00134 - DOI - PMC - PubMed

[3] Gottlieb T, Nimmo GR. Antibiotic resistance is an emerging threat to public health: an urgent call to action at the Antimicrobial Resistance Summit 2011. Med J Aust. 2011;194(6):281–283. doi:10.5694/j.1326-5377.2011.tb02973.x - DOI - PubMed

[4] Gottlieb T, Nimmo GR. Antibiotic resistance is an emerging threat to public health: an urgent call to action at the Antimicrobial Resistance Summit 2011. Med J Aust. 2011;194(6):281–283. doi:10.5694/j.1326-5377.2011.tb02973.x - DOI - PubMed

[5] Siegel RE. Emerging gram-negative antibiotic resistance: daunting challenges, declining sensitivities, and dire consequences. Respir Care. 2008;53(4):471–479. - PubMed

[6] Siegel RE. Emerging gram-negative antibiotic resistance: daunting challenges, declining sensitivities, and dire consequences. Respir Care. 2008;53(4):471–479. - PubMed

[7] Roca I, Akova M, Baquero F, et al. The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect. 2015;6:22–29. doi:10.1016/j.nmni.2015.02.007 - DOI - PMC - PubMed

[8] Roca I, Akova M, Baquero F, et al. The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect. 2015;6:22–29. doi:10.1016/j.nmni.2015.02.007 - DOI - PMC - PubMed

[9] Rawat D, Extended-spectrum ND. β-lactamases in gram negative bacteria. J Glob Infect Dis. 2010;2(3):263–274. doi:10.4103/0974-777X.68531 - DOI - PMC - PubMed

[10] Rawat D, Extended-spectrum ND. β-lactamases in gram negative bacteria. J Glob Infect Dis. 2010;2(3):263–274. doi:10.4103/0974-777X.68531 - DOI - PMC - PubMed

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In vitro Antimicrobial Synergy Testing of Extensively Drug-Resistant Clinical Isolates at an Organ Transplant Center in Nepal

Affiliations

In vitro Antimicrobial Synergy Testing of Extensively Drug-Resistant Clinical Isolates at an Organ Transplant Center in Nepal

Authors

Affiliations

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Conflict of interest statement

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