Clindamycin

Pharmacotherapeutic group: anti-acne preparations, anti-infectives for treatment of acne, ATC code: D10AF01 Mechanism of action Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis. It binds to the 50S ribosomal subunit and affects ribosome assembly as well as the translational process. Although clindamycin phosphate is inactive *in vitro*, rapid *in vivo* hydrolysis converts this compound to clindamycin, which has antibacterial activity. Clindamycin has demonstrated *in vitro* activity against isolates of the following microorganisms: Anaerobic Gram-positive non-spore-forming bacteria, including: *Propionibacterium acnes*. Pharmacodynamic effects Efficacy is related to the period of time during which the drug level exceeds the minimum inhibitory concentration (MIC) of the pathogen (%T/MIC). Resistance Resistance to clindamycin in *Propionibacterium acnes* may be caused by mutations at the antibiotic binding site of rRNA or by methylation of specific nucleotides in the 23S RNA of the 50S ribosomal subunit. These alterations may confer cross-resistance to macrolides and streptogramins B (MLSB phenotype). Macrolide-resistant isolates should be tested for inducible clindamycin resistance using the D-test. Cross-resistance between clindamycin and lincomycin has been demonstrated. The prevalence of acquired resistance may vary by geographical location and over time for selected species, and local information on resistance should be obtained, particularly when treating severe infections. Where necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the product in at least some types of infection is questionable. In particular, for severe infections or treatment failure, microbiological diagnosis with confirmation of the pathogen and its susceptibility to clindamycin is recommended. Resistance is generally defined on the basis of susceptibility interpretive criteria (breakpoints) established by regulatory agencies; CLSI (Clinical and Laboratory Standards Institute) or EUCAST (European Committee on Antimicrobial Susceptibility Testing) for systemically administered antibiotics. These breakpoints may be less relevant for topically administered clindamycin. Although clindamycin is not specifically mentioned, EUCAST suggests that resistance to topically administered antimicrobial agents be defined using epidemiological cut-off values (ECOFFs) rather than the clinical breakpoints established for systemic administration. However, MIC distributions and ECOFFs for *P. acnes* have not been published by EUCAST. Based on correlations between clinical outcomes in patients with acne and the clindamycin MIC for their *P. acnes* isolates, values of ≤ 256 mg/l are considered susceptible for topical clindamycin administration. CLSI has published MIC ranges for a limited number (58) of unique clinical *P. acnes* isolates collected between 2010 and 2012 in US hospitals. 91% of these isolates were susceptible to clindamycin (MIC ≤ 8 mg/l). A recent Belgian surveillance study (2011–2012) of anaerobic bacteria included 22 *P. acnes* isolates. 95.5% were susceptible to clindamycin. An earlier European surveillance study, which included 304 *P. acnes* isolates, reported a 15% clindamycin resistance rate. However, that study used a breakpoint of 0.12 mg/l. Had the current breakpoint of 4 mg/l been applied, no isolates would have been resistant. Breakpoints CLSI and EUCAST breakpoints for Gram-positive anaerobic bacteria are listed below. Although the two organisations have reported different values, the resistance breakpoint is the same because CLSI recognises an intermediate susceptibility category (4 mg/ml). As noted above, the breakpoints are based on use in systemic infections. EUCAST breakpoints for systemically administered clindamycin Pathogen Susceptible Resistant Gram-positive anaerobic bacteria (except *Clostridium difficile*) ≤ 4 mg/l > 4 mg/l CLSI breakpoints for systemically administered clindamycin Pathogen Susceptible Resistant Anaerobes ≤ 2 mg/l > 8 mg/l