High-level tolerance to triclosan may play a role in Pseudomonas aeruginosa antibiotic resistance in immunocompromised hosts: evidence from outbreak investigation

Abstract

Background and methods: Pseudomonas aeruginosa is a major infectious threat to immunocompromised patients. We recently reported a fatal epidemic of multidrug-resistant P. aeruginosa in an onchoematology unit, linked to massive contamination of a triclosan-based disinfectant. The aim of this study is to evaluate the antimicrobial activity of triclosan and chlorhexidine digluconate against the epidemic strain of P. aeruginosa, to confirm the hypothesis that the soap dispenser acted as a continuous source of the infection during the outbreak, and to explore the potential role of triclosan in increasing the level of resistance to selected antibiotics.Susceptibility tests and time-kill assays for disinfectans were performed using two commercial formulations containing triclosan and chlorhexidine digluconate, respectively. Antibiotic susceptibility testing was performed by the broth microdilution method.

Findings: The P. aeruginosa epidemic strain exhibited an extremely high level of triclosan resistance (apparent MIC = 2,125 mg/L), while it was markedly susceptible to chlorhexidine digluconate (apparent MIC = 12.5 mg/L). Upon gradual adaptation to triclosan, the epidemic strain survived for a long period (> 120 h) in the presence of 3,400 mg/L (equivalent to 1.6 × MIC) of triclosan, concomitantly increasing the resistance to six antibiotics that are typical substrates of drug efflux pumps of the resistance nodulation division family. This effect was reversed by efflux pump inhibitors.

Conclusions: The epidemic P. aeruginosa strain was resistant to triclosan and its previous exposure to triclosan increases antibiotic resistance, likely through active efflux mechanisms. Since P. aeruginosa can become tolerant to elevated triclosan concentrations, the use of triclosan-based disinfectants should be avoided in those healthcare settings hosting patients at high risk for P. aeruginosa infection.

Figure 1

Time-kill kinetics of P. aeruginosa L2 in MH broth supplemented with chlorhexidine digluconate (product B, upper panel) or triclosan (product A, lower panel) at given concentrations.