Evidence that a novel quaternary compound and its organic N -chloramine derivative do not select for resistant mutants of Pseudomonas aeruginosa

• Published in: The Journal of hospital infection Vol. 91; no. 1; pp. 53 - 58
• Main Authors: De Silva, M, Ning, C, Ghanbar, S, Zhanel, G, Logsetty, S, Liu, S, Kumar, A
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2015
• Subjects: Anti-Bacterial Agents - pharmacology; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - metabolism; Chloramines - pharmacology; Cross Infection - drug therapy; Cross Infection - microbiology; Cross Infection - prevention & control; Cross-resistance; Drug Resistance, Multiple, Bacterial; Humans; Infectious Disease; Microbial Sensitivity Tests; Mutation; N-Chloramine; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - isolation & purification; Pseudomonas aeruginosa - metabolism; Quaternary ammonium compounds; Quaternary Ammonium Compounds - pharmacology; RND efflux pumps; Pseudomonas aeruginosa; Quaternary ammonium compounds; RND efflux pumps; Cross-resistance; N-Chloramine
• ISSN: 0195-6701; 1532-2939
• DOI: 10.1016/j.jhin.2015.05.009

Summary Background Pseudomonas aeruginosa is well known for causing hospital-acquired infections that are often difficult to treat because of its high intrinsic and acquired resistance to antibiotics. Resistance–nodulation–division (RND) efflux pumps are the major contributors to the intrinsic multidrug resistance (MDR) in this organism. Various biocides used in hospital settings have been shown to select for RND-pump-overexpressing mutants of P. aeruginosa that show cross-resistance to clinically relevant antibiotics. Therefore, finding biocides that do not select for multidrug-resistant mutants is important in controlling the spread of bacteria such as P. aeruginosa. Aim To evaluate the potential of a novel quaternary ammonium compound and its N -chloramine derivative in selecting for MDR mutants of P. aeruginosa. Methods P. aeruginosa PA01 was cultured in the presence of increasing concentrations of the quaternary ammonium compound and its N -chloramine derivative respectively, and one mutant each selected. Susceptibility of the mutants to both compounds as well as antibiotics was tested. Susceptibility of P. aeruginosa strains with deletions in RND pumps was also tested for both compounds to determine whether they are a substrate of these pumps. Expression of mexB , mexD , and mexY genes in the mutants was analysed using quantitative reverse transcriptase–polymerase chain reaction to determine whether the compounds can select for pump-overexpressing mutants. Findings We show that whereas both compounds can be pumped by the MexCD-OprJ pump, they neither select for mutants that overexpress RND pumps nor for mutants that display cross-resistance to antibiotics. Conclusion These compounds are promising candidates to be used as disinfectants in hospital settings.