Susceptibility of antibiotic-resistant Gram-negative bacteria to biocides: a perspective from the study of catheter biofilms.

Bacteria resistant to both the agents deployed to prevent infections and those used to treat infections would be formidable nosocomial pathogens. The aim of this paper is to review the evidence that Gram-negative bacteria resistant to antibiotics and biocides have emerged and been responsible for catheter-associated urinary tract infection. A study of patients undergoing intermittent bladder catheterization revealed that the frequent application of the antiseptic chlorhexidine to the perineal skin prior to the insertion of the catheter was effective against the normal Gram-positive skin flora but not against the Gram-negative organisms that subsequently colonized this site. Organisms such as Providencia stuartii, Pseudomonas aeruginosa and Proteus mirabilis were repeatedly isolated from the skin of these patients and inevitably went on to cause urinary infections. The minimum inhibitory concentration (MIC) of chlorhexidine for many of these strains proved to be 200-800 microg ml(-1) compared with the 10-50 microg ml(-1) recorded for reference strains of Gram-negative species. A subsequent survey of over 800 Gram-negative isolates from urinary tract infections in patients from both hospitals and the community revealed that chlorhexidine resistance was not a widespread phenomenon, but was restricted to these species and to units where the care of catheterized patients involved the extensive use of chlorhexidine. Analysis of the antibiotic resistance patterns revealed that the chlorhexidine-resistant strains were also multidrug resistant. Other clinical studies also reported catheter-associated infections with chlorhexidine- and multidrug-resistant strains of Pr. mirabilis when chlorhexidine was being used extensively. This species poses particular problems to the catheterized patient. Chlorhexidine thus proved counterproductive in the care of catheters and its use in this context has been largely abandoned. Suggestions of reintroducing this agent in the form of biocide-impregnated catheters should be resisted.