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Clindamycin has been shown to have in vitro activity against isolates of the following organisms; Anaerobic gram positive non spore forming bacilli, including: Propionibacterium acnes.
Pharmacodynamic effects: Efficacy is related to the time period that the agent level is above the minimum inhibitory concentration (MIC) of the pathogen (%T/MIC).
Resistance: Resistance to clindamycin in Propionibacterium acnes can be caused by mutations at the rRNA antibiotic binding site or by methylation of specific nucleotides in the 23S RNA of the 50S ribosomal subunit. These alterations can determine cross resistance to macrolides and streptogramins B (MLSB phenotype). Macrolide-resistant isolates should be tested for inducible resistance to clindamycin using the D-zone test. Cross-resistance has been demonstrated between clindamycin and lincomycin.
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. Particularly in severe infections or therapy failure microbiological diagnosis with verification of the pathogen and its susceptibility to clindamycin is recommended.
Resistance is usually defined by susceptibility interpretive criteria (breakpoints) established by regulatory agencies, CLSI or EUCAST for systemically administered antibiotics. These breakpoints may be less relevant for topically administered clindamycin. Although clindamycin is not specifically cited, EUCAST has suggested that, for topically applied antimicrobials, resistance might be better defined by epidemiological cut-off values (ECOFFS) rather than the clinical breakpoints determined for systemic administration. However, MIC distributions and ECOFFS have not been published by EUCAST for P. acnes. Based on correlations between clinical results in acne patients and the clindamycin MICs for their P. acnes isolates, values as high as 256 mg/L are considered susceptible for topically administered clindamycin.
CLSI has published MIC ranges for a limited number (58) of unique clinical isolates of P. acnes collected in 2010-2012 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 isolates of P. acnes, had reported a resistance rate of 15% to clindamycin. However, this study used a breakpoint of 0.12 mg/L; using the current breakpoint of 4 mg/L, there were no resistant isolates.
Breakpoints: CLSI and EUCAST breakpoints for Gram-positive anaerobes are listed as follows. Although the two institutions report the values differently, the resistance breakpoint is the same, because CLSI recognized a category of intermediate susceptibility (4 mg/L). As previously indicated, these breakpoints are based on use in systemic infections. (See Tables 1 and 2.)
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Click on icon to see table/diagram/imagePharmacokinetics: Clindamycin activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of clindamycin (10 mg/mL) in an isopropyl alcohol and water solution for 4 weeks was 597 mcg/g of comedonal material (range 0-1490 mcg/g). Clindamycin in vitro inhibits all Propionibacterium acnes cultures tested (MICs 0.4 mcg/mL). Free fatty acids on the skin surface have been decreased from approximately 14% to 2% following application of clindamycin.
Lotion: Following multiple topical applications of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per mL in an isopropyl alcohol and water solution, very low levels of clindamycin are present in the serum (0-3 ng/mL) and less than 0.2% of the dose is recovered in urine as clindamycin.
Topical gel: Following multiple topical application of clindamycin phosphate at a concentration equivalent to 10 mg clindamycin per gram in the gel formulation, 0.053% (morning) and 0.070% (evening) of the administered dose was recovered in the urine as clindamycin. Average absolute bioavailability was 1.6% and 2.2% after morning and evening doses, respectively.
Geriatric Use: Clinical studies for topical clindamycin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Toxicology: Preclinical Safety Data: Carcinogenesis: Long term studies in animals have not been performed with clindamycin to evaluate carcinogenic potential.
Mutagenesis: Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.
Impairment of Fertility: Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 1.1 times the highest recommended adult human dose based on mg/m2) revealed no effects on fertility or mating ability.
In oral embryo fetal development studies in rats and subcutaneous embryo fetal development studies in rats and rabbits, no developmental toxicity was observed except at doses that produced maternal toxicity.
