Dataset Information

In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae.

ABSTRACT: Objectives:Colistin is still a "last-resort" antibiotic used to manage human infections due to multidrug-resistant (MDR) Klebsiella pneumoniae. However, colistin-resistant K. pneumoniae (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate the genetic data of CR-Kp and identify the antibacterial activity of fosfomycin (FM) alone and in combination with amikacin (AMK) or colistin (COL) against CR-Kp in vitro. Methods:Three clinical CR-Kp isolates from three patients were collected. Whole-genome sequencing and bioinformatics analysis were performed. The Pharmacokinetics Auto Simulation System 400, by simulating human pharmacokinetics in vitro, was employed to simulate FM, AMK, and COL alone and in combination. Different pharmacodynamic parameters were calculated for determining the antimicrobial effect. Results:Whole-genome sequencing revealed that none of the three isolates contain mcr gene and that no insertion was found in pmrAB, phoPQ, or mgrB genes. We found the antibacterial activity of AMK alone was more efficient than FM or COL against CR-Kp. The area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was higher than 170 LogCFU/mL·h-1. In addition, the area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with COL (75,000 IU/kg every12 hours) was higher than that of monotherapies (>100 LogCFU/mL·h-1 vs <80 LogCFU/mL·h-1). Conclusion:FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was effective at maximizing bacterial killing against CR-Kp.

SUBMITTER: Yu W

PROVIDER: S-EPMC5926077 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant <i>Klebsiella pneumoniae</i>.

Yu Wei W Luo Qixia Q Shi Qingyi Q Huang Chen C Yu Xiao X Niu Tianshui T Zhou Kai K Zhang Jiajie J Xiao Yonghong Y

Infection and drug resistance 20180424

<h4>Objectives</h4>Colistin is still a "last-resort" antibiotic used to manage human infections due to multidrug-resistant (MDR) <i>Klebsiella pneumoniae</i>. However, colistin-resistant <i>K. pneumoniae</i> (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate the genetic data of CR-Kp and identify the antibacterial activity of fosfomycin (FM) alone and in combination with amikacin (AMK) or colistin (COL) against CR-Kp in vitro.<h4>Met ...[more]

PMID: 29731646

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Project description:The emergence and dissemination of carbapenemases, bacterial enzymes able to inactivate most ?-lactam antibiotics, in Enterobacteriaceae is of increasing concern. The concurrent spread of resistance against colistin, an antibiotic of last resort, further compounds this challenge further. Whole-genome sequencing (WGS) can play a significant role in the rapid and accurate detection/characterization of existing and emergent resistance determinants, an essential aspect of public health surveillance and response activities to combat the spread of antimicrobial resistant bacteria. In the current study, WGS data was used to characterize the genomic content of antimicrobial resistance genes, including those encoding carbapenemases, in 10 multidrug-resistant Klebsiella pneumoniae isolates from Pakistan. These clinical isolates represented five sequence types: ST11 (n = 3 isolates), ST14 (n = 3), ST15 (n = 1), ST101 (n = 2), and ST307 (n = 1). Resistance profiles against 25 clinically-relevant antimicrobials were determined by broth microdilution; resistant phenotypes were observed for at least 15 of the 25 antibiotics tested in all isolates except one. Specifically, 8/10 isolates were carbapenem-resistant and 7/10 isolates were colistin-resistant. The blaNDM-1 and blaOXA-48 carbapenemase genes were present in 7/10 and 5/10 isolates, respectively; including 2 isolates carrying both genes. No plasmid-mediated determinants for colistin resistance (e.g. mcr) were detected, but disruptions and mutations in chromosomal loci (i.e. mgrB and pmrB) previously reported to confer colistin resistance were observed. A blaOXA-48-carrying IncL/M-type plasmid was found in all blaOXA-48-positive isolates. The application of WGS to molecular epidemiology and surveillance studies, as exemplified here, will provide both a more complete understanding of the global distribution of MDR isolates and a robust surveillance tool useful for detecting emerging threats to public health.

Dataset Information

In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant Klebsiella pneumoniae.

Publications

In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant <i>Klebsiella pneumoniae</i>.

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