Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates.

Julalak C Ontong,Sarunyou Chusri,Nwabor F Ozioma,Supayang P Voravuthikunchai,Iddya Karunasagar

doi:10.1371/journal.pone.0244673

Julalak C Ontong, Sarunyou Chusri + Show 3 more

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https://doi.org/10.1371/journal.pone.0244673

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Journal: PloS one	Publication Date: Jan 6, 2021
Citations: 37	License type: CC BY 4.0

Affiliation: Thaksin University, Prince of Songkla University

Abstract

Multidrug resistant Enterobacterales have become a serious global health problem, with extended hospital stay and increased mortality. Antibiotic monotherapy has been reported ineffective against most drug resistant bacteria including Klebsiella pneumoniae, thus encouraging the use of multidrug therapies as an alternative antibacterial strategy. The present works assessed the antibacterial activity of colistin against K. pneumoniae isolates. Resistant isolates were tested against 16 conventional antibiotics alone and in combination with colistin. The results revealed that all colistin resistant isolates demonstrated multidrug resistance against the tested antibiotics except amikacin. At sub-inhibitory concentrations, combinations of colistin with amikacin, or fosfomycin showed synergism against 72.72% (8 of 11 isolates). Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens.

Highlights

The spread of multidrug resistant bacteria has become a public health emergency that threatens the continued usage of antibiotics chemotherapy
In this study K. pneumoniae isolates obtained from patients receiving treatment in tertiary hospitals were tested against colistin
The results revealed that all nine isolates from Narathiwat hospital were resistant to colistin, while one out of the three isolates from Songkhla and the only isolate from Trang were resistant to colistin

Summary

Introduction

The spread of multidrug resistant bacteria has become a public health emergency that threatens the continued usage of antibiotics chemotherapy. Infections due to carbapenemase-producing Enterobacterales are fast spreading across the globe, rendering the healthcare systems ineffective. It is estimated that infections associated with drug-resistant pathogens currently cause about 700,000 deaths annual, and if the status quo prevails could increase to 10 million annual deaths by 2050 [1]. Klebsiella pneumoniae is a Gram-negative Enterobacterales member commonly associated with hospital acquired infections. Carbapenems were used as choice drugs for the treatment of K. pneumoniae infection. With the emergence and spread of carbapenemase-producing Enterobacterales, colistin is considered a last-resort treatment option for infections caused by carbapenem resistant bacterial isolates

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