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234 Hermsen and Rotschaferdisulfiram-like properties of metronidazole when given concomitantly with ethanol(32), and this reaction has also been disputed by others (33).SummaryAfter more than 40 years of clinical use, metronidazole remains a mainstay in thetreatment of anaerobic infections. Metronidazole has an excellent pharmacokineticprofile, with low protein binding, good oral bioavailability, and a long half-life.Although metronidazole has been in use for many years, resistance of anaerobesto metronidazole remains under 5%, which further cements metronidazole’s rolein the treatment of infections due to anaerobes. The dosing regimens of metronidazolewere formulated before pharmacodynamics emerged as a science, butmetronidazole’s concentration-dependent bactericidal activity, prolonged PAE,and favorable pharmacokinetic and safety profiles allow for dosing manipulationtoward more convenient regimens (e.g., 1500 mg every 24 hours).CLINDAMYCINPharmacologyClindamycin (7-chloro-7-deoxylincomycin), a lincosamide antibiotic, has been usedclinically for over 30 years. Clindamycin exerts an antibacterial effect through theinhibition of protein synthesis by binding to the 50S ribosomal subunit. Clindamycinis used for various gram-positive and anaerobic infections, and is an option forpatients who are allergic to b-lactams. Clindamycin’s use in anaerobic infections isthe focus of this chapter. As in the case of metronidazole, a plethora of informationregarding basic knowledge about clindamycin exist, although pharmacodynamicdata are sparse.Antimicrobial SpectrumClindamycin exhibits antimicrobial activity versus various aerobic gram-positiveorganisms as well as gram-positive and gram-negative anaerobic bacteria (34).Similar to metronidazole, clindamycin is effective against the clinically importantanaerobe, Bacteroides spp. Additionally, clindamycin possesses antibacterial activityagainst Peptostreptococcus, Fusobacterium spp., Propionibacterium spp., Eubacteriumspp., Actinomyces spp., and most strains of C. perfringens among others.PharmacokineticsWhen given orally, clindamycin is well absorbed, with a bioavailability of approximately90%. Clindamycin is highly protein bound (>90%), and the steady statevolume of distribution in adults is approximately 0.79 L/kg (35). The eliminationhalf-life of clindamycin is approximately 2 to 2.4 hours (34,35). Moreover, clindamycinundergoes metabolism in the liver to form active metabolites (34). Althoughthe use of clindamycin in AIDS patients is not discussed in this chapter, one shouldrecognize that the pharmacokinetic parameters are significantly different in AIDSpatients, for both intravenous and oral administration (35).ResistanceResistance is the primary concern with the use of clindamycin. A study evaluatingthe susceptibility of 186 C. difficile isolates to clindamycin reported that 66.7% of theisolates were resistant and 24.7% were intermediately resistant (6). Moreover,approximately 22% of B. fragilis group spp. are considered to be resistant to