Chlorhexidine Linked to Colistin Resistance

Lara C. Pullen, PhD

November 02, 2016

Scientists have identified chlorhexidine-resistant clinical isolates of Klebsiella pneumoniae that are also cross-resistant to colistin, a last-resort antibiotic. The finding is alarming, as chlorhexidine is commonly used in disinfectants used in the home and in healthcare settings. The new research suggests that exposure to the chlorhexidine is associated with stable resistance to the antibiotic colistin.

Colistin stands as an antibiotic of last resort for multidrug-resistant infections, so the discovery has clinical implications for both infection prevention procedures and treatment of multidrug resistance. The new discovery raises concern that disinfectant use represents a novel path for bacteria to develop resistance to all existing antibiotics.

Matthew E. Wand, PhD, senior project team leader at Public Health England in Wiltshire, and colleagues published the results of their analysis of clinical K pneumoniae isolates online October 31 in Antimicrobial Agents and Chemotherapy.

They examined the ability of K pneumoniae to survive exposure to increased concentrations of chlorhexidine and found that although some strains died on exposure to chlorhexidine, others gained the ability to survive much higher concentrations of the antiseptic.

The surviving K pneumoniae isolates first adapted to chlorhexidine and then developed cross-resistance to colistin. When the investigators examined the mechanism behind this resistance, they found that an efflux pump (smvA/R) appeared to play a critical role. They also noted that this same efflux pump is found in a number of different species.

The results add to the steady stream of reports from around the world of bacteria impervious to the last-resort antibiotic colistin.

"Chlorhexidine is a critical part of current infection control practices, and the development of increased resistance to this compound has potential implications for our ability to prevent infections during routine and emergency surgery, and during admission to hospitals," coauthor J. Mark Sutton, PhD, scientific leader at Public Health England, said in a news release.

Metabolic Pathway

The investigators observed that K pneumoniae isolates that do not possess homologs to smvA/R are highly susceptible to chlorhexidine. This suggests that smvA is an important efflux pump in chlorhexidine resistance, a conclusion that was reinforced by the results of experiments using an uncoupling agent that affects these efflux pumps.

For their detailed study, the researchers performed genome analysis of chlorhexidine-adapted strains and identified mutations in the two-component regulator phoPQ and/or a putative Tet-repressor gene smvR. Although the phoPQ mutations arose through chlorhexidine adaptation, the mutations were also associated with colistin resistance.

The authors explain that they cannot be certain the phoPQ mutations cause colistin resistance. It is possible that additional factors are important in mediating resistance to chlorhexidine and that the phoPQ mutations are compensatory and enable the resistant strain to recover its fitness after development of biocide resistance.

The authors have disclosed no relevant financial relationships.

Antimicrob Agents Chemother. Published online October 31, 2016. Abstract

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