Benzalkonium chloride lowers fluoroquinolone MPC

June 1, 2008

In vitro testing shows that the mutant prevention concentration for gatifloxacin against fluoroquinolone-sensitive methicillin-resistant Staphylococcus aureus is significantly lowered by the addition of benzalkonium chloride.

Key Points

Chicago-Results of an in vitro study show that the combination of gatifloxacin and benzalkonium chloride (BAK) affords significantly greater activity against methicillin-resistant Staphylococcus aureus (MRSA) than either compound alone, including a lower propensity to select for resistant organisms, said Joseph R. Blondeau, PhD.

In a poster at the annual meeting of the American Society of Cataract and Refractive Surgery, Dr. Blondeau and Christine Hesje, BSc, presented their research in which they determined that the mutant prevention concentration (MPC) of gatifloxacin with BAK for fluoroquinolone-sensitive MRSA was significantly lower than the MPCs for gatifloxacin and BAK alone.

"The relevance of this finding is that it suggests [0.3% gatifloxacin] (Zymar, Allergan), the commercially available ophthalmic solution of gatifloxacin that is formulated with BAK, may have a reduced propensity to select for fluoroquinolone-resistant MRSA compared with a formulation containing a fluoroquinolone alone," said Dr. Blondeau, adjunct professor of microbiology and immunology, and clinical associate professor of pathology, University of Saskatchewan, Saskatoon.

In their laboratory, Dr. Blondeau and coworkers have been conducting studies to differentiate among antibacterial compounds regarding their propensity to select for bacterial resistance. To that end, they have moved beyond testing that determines only MIC values and have been defining the MPC, which represents the antimicrobial drug concentration required to inhibit growth of the least susceptible cell present in high-density bacterial populations.

"MIC testing evaluates the lowest drug concentration that prevents microbial growth using an inoculum of 105 or 106 colony forming units/ml (CFU/ml). However, a paper we published in 2001 suggested such an approach may be flawed considering infection is associated with a higher density of organisms, and in that situation, there is an increased likelihood that spontaneously resistant organisms are present," Dr. Blondeau explained.

"MPC testing is performed using an inoculum containing 1010 CFU/ml but with the usual range of antibacterial concentrations," he said. "Through this research we have found that two compounds with a similar MIC may differ in their probability for selecting for resistant mutants."

In the present study, the MIC90 and MPC values of gatifloxacin, BAK, and gatifloxacin-BAK were evaluated for a total of 17 clinical isolates of fluoroquinolone-sensitive MRSA. The results were consistent with previous research that showed the antimicrobial activity of gatifloxacin against MRSA, based on MIC testing, was increased by the presence of BAK. In the present study, the MIC90 concentration of the gatifloxacin-BAK combination was <0.004 μg/ml, which was more than 30-fold lower than the MIC90 for gatifloxacin (0.125 μg/ml) and more than 775-fold lower than the MIC for BAK alone (3.1 μg/ml).

In the MPC testing, the gatifloxacin-BAK combination had an MPC value of <0.004 μg/ml, which represented a more than 1,000-fold reduction compared with the MPC for gatifloxacin (≥4 μg/ml) and a more than 1,500-fold reduction compared with the MPC for BAK alone (6 to 10 μg/ml).

Consumer financing program launched

FROM STAFF REPORTS

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