Reduced Susceptibility of Proteus mirabilis to Triclosan

Abstract

Clinical isolates of Proteus mirabilis causing catheter encrustation and blockage are susceptible to the biocide triclosan (MICs of 0.2 mg/liter). Studies with laboratory models of the bladder have demonstrated that the inflation of catheter retention balloons with triclosan solutions rather than water results in the diffusion of triclosan from the balloons into the surrounding urine and the inhibition of catheter encrustation by P. mirabilis. The aim of this study was to test whether the exposure of P. mirabilis to triclosan under laboratory conditions resulted in the selection of strains with reduced susceptibilities to this biocide. Exposure to triclosan in agar was shown to select mutants with MICs elevated from 0.2 mg/liter up to 80 mg/liter. In a selection of 14 of these strains, the decreased susceptibility was found to be stable and not associated with increased resistance to antibiotics. Experiments with the laboratory models demonstrated that inflation of the catheter balloons with triclosan (10 mg/ml) prevented encrustation and blockage by the parent strain P. mirabilis B2 (MIC, 0.2 mg/liter) and the mutant strain M48 (MIC, 2.0 mg/liter) but had no effect on crystalline biofilm formation by strain M55 (MIC, 40 mg/liter). These results suggest that, in any clinical trial or subsequent clinical use of the strategy, it will be important to monitor the urinary flora of the catheterized patients for P. mirabilis strains with reduced susceptibility to triclosan. The emergence of these strains could undermine the ability of the triclosan strategy to control catheter encrustation.Several studies have reported that the care of half of the many patients undergoing long-term bladder catheterization is compromised when the flow of urine through the catheter is blocked by encrustation (11,13,27). The problem stems from infection by urease-producing bacteria, particularly Proteus mirabilis (7,12,19). These organisms colonize catheters, producing biofilm communities embedded in a polysaccharide gel matrix. The urease they produce hydrolyzes urea to ammonia, elevating the pH of the urine and the biofilm. Under the resulting alkaline conditions, crystals of calcium and magnesium phosphates form in the urine and a crystalline biofilm develops on the catheter (20). This material can block the eyehole and lumen of the catheter, preventing the flow of urine from the bladder and putting the health and welfare of the patient at risk. All types of urinary catheters are vulnerable to encrustation, and currently there are no effective methods available to clinical staff to control the problem (13, 21).Strains of P. mirabilis causing catheter encrustation have been shown to be very sensitive to the biocide triclosan, with MICs of 0.2 mg/liter (9). A strategy to control catheter encrustation has been developed in which triclosan can be delivered directly into the residual urine in the catheterized bladder (25). Laboratory studies with models of the catheterized bladder inoculated with P. mirabilis demonstrated that when the rete...

Biomaterial modification of urinary catheters with antimicrobials to give long-term broadspectrum antibiofilm activity

“…Concerns regarding resistance strains appearing as a result of use of antimicrobial catheters are entirely justified and this is why we used these combinations of antimicrobials, which according to the Dual Drug Principle [29] would significantly reduce the likelihood of mutational resistance. Also, when much higher inocula of P. mirabilis (~10 8 cfu/mL) have been exposed to triclosan alone on agar surfaces they have shown evidence of mutational resistance, as expected [30]. However, those mutants showing MICs of 2 mg/L were still prevented from colonizing urinary catheters in a laboratory model [30].…”

In Vitro Study of the Effect of Cationic Biocides on Bacterial Population Dynamics and Susceptibility

“…Other investigators have subsequently repeated this observation (23). These reports have raised the possibility that biocides other than TCS might contribute to the emergence of resistance (2,12,43). While the interaction of TCS with a specific target (the enoyl acyl carrier protein reductase) of E. coli may be unique, it is possible to generate clones of some species with decreased QAC susceptibility in pure culture training experiments whereby bacteria are passaged on escalating concentrations of the microbial (8,17,19,20,26,39).…”

“…Since multidrug efflux pump expression has been associated with changes in the MICs of therapeutically important antibiotics, there is the potential for decreases in CB susceptibility, accompanied by reductions in the effectiveness of antibiotics (13,14) or other biocides (2,18). A number of studies, however, have questioned such associations (25,43). Since the 1970s there have been sporadic reports of bacteria with reduced susceptibility within clinical environments that would normally receive long-term exposure to these biocides (7,10,42).…”

Antimicrobial Potential of Momordica charantia L. against Multiresistant Standard Species and Clinical Isolates

“…5 Its spread in hospitals is a worrying condition, representing the main risk factor for isolated infections toward the use of antibiotics in large quantities; 5 and is also considered an important source of bacteremia and a predominant cause of morbidity and mortality in patients, for example, with cystic fibrosis. 2 The P. mirabilis and P. rettgeri are Gram-negative bacteria, commonly associated with urinary-tract infections in hospitalized patients from the intensive care unit and is associated with the use of urinary catheters, 35,36 being one of the main etiological agents responsible for much of nosocomial infections affecting the urinary tract, a special concern when we consider the reports of antibiotic JcDP resistance. 6 The extract of M. charantia L. also showed a strong antimicrobial activity potential against S. aureus and E. coli.…”