Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0028177
Title: Effective antibiotics in combination against extreme drug-resistant pseudomonas aeruginosa with decreased susceptibility to polymyxin B
Authors: Lim T.-P. 
Lee W.
Tan T.-Y.
Sasikala S.
Teo J.
Hsu L.-Y. 
Tan T.-T. 
Syahidah N.
Kwa A.L. 
Keywords: amikacin
levofloxacin
meropenem
metallo beta lactamase
polymyxin B
rifampicin
amikacin
antiinfective agent
beta lactamase
meropenem
ofloxacin
polymyxin B
rifampicin
thienamycin derivative
antibiotic sensitivity
article
bacterial count
bacterial strain
bactericidal activity
bacterium isolate
colony forming unit
genotype
immunocompromised patient
in vitro study
minimum inhibitory concentration
nonhuman
phenotype
phylogeny
polymerase chain reaction
Pseudomonas aeruginosa
Pseudomonas infection
public hospital
Singapore
antibiotic resistance
drug combination
drug potentiation
human
metabolism
methodology
microbiological examination
Pseudomonas infection
time
Amikacin
Anti-Bacterial Agents
beta-Lactamases
Drug Resistance, Bacterial
Drug Synergism
Drug Therapy, Combination
Humans
Microbial Sensitivity Tests
Ofloxacin
Phylogeny
Polymyxin B
Pseudomonas aeruginosa
Pseudomonas Infections
Rifampin
Thienamycins
Time Factors
Issue Date: 2011
Citation: Lim T.-P., Lee W., Tan T.-Y., Sasikala S., Teo J., Hsu L.-Y., Tan T.-T., Syahidah N., Kwa A.L. (2011). Effective antibiotics in combination against extreme drug-resistant pseudomonas aeruginosa with decreased susceptibility to polymyxin B. PLoS ONE 6 (12) : e28177. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0028177
Abstract: Objective: Extreme drug-resistant Pseudomonas aeruginosa (XDR-PA) with decreased susceptibility to polymyxin B (PB) has emerged in Singapore, causing infections in immunocompromised hosts. Combination therapy may be the only viable therapeutic option until new antibiotics become available. The objective of this study is to assess the in vitro activity of various antibiotics against local XDR-PA isolates. Methods: PA isolates from all public hospitals in Singapore were systematically collected between 2006 and 2007. MICs were determined according to CLSI guidelines. All XDR-PA isolates identified were genotyped using a PCR-based method. Time-kill studies (TKS) were performed with approximately 10 5 CFU/ml at baseline using clinically achievable unbound concentrations of amikacin (A), levofloxacin (L), meropenem (M), rifampicin (R) and PB alone and in combination. Bactericidal activity (primary endpoint) was defined as a ?3 log 10 CFU/ml decrease in the colony count from the initial inoculum at 24 hours. Results: 22 clinical XDR-PA isolates with PB MIC 2-16 ?g/ml were collected. From clonal typing, 5 clonal groups were identified and nine isolates exhibited clonal diversity. In TKS, meropenem plus PB, amikacin plus meropenem, amikacin plus rifampicin, amikacin plus PB exhibited bactericidal activity in 8/22, 3/22, 1/22 and 6/22 isolates at 24 hours respectively. Against the remaining ten isolates where none of the dual-drug combination achieved bactericidal activity against, only the triple-antibiotic combinations of ARP and AMP achieved bactericidal activity against 7/10 and 6/10 isolates respectively. Conclusion: Bactericidal activity with sustained killing effect of ?99.9% is critical for eradicating XDR-PA infections, especially in immunocompromised hosts. These findings underscore the difficulty of developing combination therapeutic options against XDR-PA, demonstrating that at least 3 antibiotics are required in combination and that efficacy is strain dependant. © 2011 Lim et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/162021
ISSN: 19326203
DOI: 10.1371/journal.pone.0028177
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