Determination of the Mutant Prevention Concentration and the Mutant Selection Window of Topical Antimicrobial Agents against <b><i>Propionibacterium acnes</i></b>

Abstract

Determination of the mutant prevention concentration (MPC) and the mutant selection window (MSW) of antimicrobial agents used to treat pathogenic bacteria is important in order to apply effective antimicrobial therapies. Here, we determined the MPCs of the major topical antimicrobial agents against Propionibacterium acnes and Staphylococcus aureus which cause skin infections and compared their MSWs. Among the MPCs of nadifloxacin and clindamycin, the clindamycin MPC was determined to be the lowest against P. acnes. In contrast, the nadifloxacin MPC was the lowest against S. aureus. Calculations based on the minimum inhibitory concentrations and MPCs showed that clindamycin has the lowest MSW against both P. acnes and S. aureus. Nadifloxacin MSWs were 4-fold higher against P. acnes than against S. aureus. It is more likely for P. acnes to acquire resistance to fluoroquinolones than S. aureus. Therefore, topical application of clindamycin contributes very little to the emergence of resistant P. acnes and S. aureus strains.

Relationship between quinolone use and resistance of Staphylococcus epidermidis in patients with acne vulgaris

“…We previously reported that C. acnes is more likely to acquire resistance to quinolones in comparison with S. aureus . However, the detection rate of quinolone‐resistant C. acnes strains was significantly lower than that of quinolone‐resistant S. epidermidis strains in this study.…”

“…However, skin bacteria are also exposed to oral quinolones administrated for systemic infections. We previously reported that the risk of inducing the development of antimicrobial‐resistant bacteria by oral antimicrobial agents is higher than with topical agents because a lower antimicrobial concentration is distributed over the skin with the latter . Therefore, antimicrobial treatment of acne vulgaris will promote the development of antimicrobial‐resistant S. epidermidis , which is a common skin inhabitant and generally an off‐target bacterium.…”

Long‐term administration of oral macrolides for acne treatment increases macrolide‐resistant Propionibacterium acnes

“…Resistant mutants are generally selected for by higher antimicrobial concentrations (MIC or higher) . We suggest that they are also selected by pre‐incubation in low concentration antimicrobials, because the mutants were obtained on agar plates with up to 32 μg/mL of clarithromycin and clindamycin, a much higher MPC than shown by the parental strain (MPC of clarithromycin, 0.25 μg/mL; clindamycin, 0.125 μg/mL) …”

“…Propionibacterium acnes was incubated in modified Gifu Anaerobic Broth (GAM Broth; Nissui Pharmaceutical, Tokyo, Japan) for 48 h in anaerobic conditions. The resulting suspension was concentrated to 10 10 colony-forming units/mL, following the method described by Nakase et al 14 Our "direct selection method" used modified GAM broth without antimicrobials. Our "pre-antimicrobial exposed selection method" used the broth with 0.03 lg/mL of either clarithromycin or clindamycin.…”

“…21 We suggest that they are also selected by pre-incubation in low concentration antimicrobials, because the mutants were obtained on agar plates with up to 32 lg/mL of clarithromycin and clindamycin, a much higher MPC than shown by the parental strain (MPC of clarithromycin, 0.25 lg/mL; clindamycin, 0.125 lg/mL). 14 The characteristic of slow growth in P. acnes as an anaerobic bacterium was considered to affect the emergence frequency of resistant mutants. In the pre-clarithromycin-exposed experiment, the resistant mutants grew relatively slowly during pre-incubation.…”