Clindamycin antibacterial activity

Antibacterial activity of clindamycin is found both in urine and feces after adrninistration of clindamycin. This activity is a consequence of the presence of both clindamycin and its metaboUte, de- /V-methy1c1indamycin [22431-45-4] (6, R = R = H). Unlike de-/V-methy11incomycin, the de-Ai-methyl analogue is as active in vitro as clindamycin. The analogue has been isolated from the urine of humans who had received clindamycin, and its presence in semm has been detected (65). 

When added to fermentations of Streptomjcespunipalus clindamycin is converted into de-A/-methylclindamycin (6, R = R = H). However, when clindamycin is incubated with Streptomjces armentosus clindamycin sulfoxide [68366-52-9] C gH23ClN20gS, which has low antibacterial activity, is formed... 

Lincomycins bacteriostatic activity is based on the inhibition of the bacterial proteic synthesis. Lincomycin A in particular have been largely employed in clinical therapy of infections caused by micoplasmas, Gram-positive bacteria, and cocci but it presents a lot of side effects overcome by 7-clindamycin (Fig. 21), a semi-synthetic drug with larger spectrum of action and major antibacterial activity. 

Gindamydn has antibacterial activity similar to that of erythromycin. It exerts a bacteriostatic effect mainly on gram-positive aerobic, as well as on anaerobic pathogens. Gindamycin is a semisynthetic chloro analogue of lin-comycin, which derives from a Streptomyces species. Taken orally, clindamycin is better absorbed than lincomycin, has greater antibacterial efficacy and is thus preferred. Both penetrate well into bone tissue. 

Biomodification of Clindamycin. When added to fermentations of Streptomycespunipalns, clindamycin is converted into de-iV-methylclinda-mycin. However, when clindamycin is incubated with Streptomyces armen-tosus, clindamycin sulfoxide, CuH Cl OgS, which has low antibacterial activity, is formed. Clindamycin 3-phosphate, antibactenally inactive in vitro, and the ribonucleotides clindamycin 3-(5 -cyhdylate), clindamycin 3-(5 -adenylate), clindamycin 3-(5 -undylate), and clindamycin 3-(5 -guanylate). all inactive in vitro, can be generated. All of these derivatives piotect mice infected with Staphylococcus aureus, however, presumably because of bio transformation into clindamycin. 

Macrolides e.g. erythromycin. Clindamycin, structurally a lincosamide, has a similar action and overlapping antibacterial activity. 

The low aqueous solubility of the antibiotic clindamycin hydrochloride is responsible for the pain experienced on intramuscular injection. Phosphorylation improves the aqueous solubility from 3 to >150mg/mL and avoids the pain resulting from injection of the parent clindamycin. The phosphorylated drug (Figure 41.13) possesses little or no intrinsic antibacterial activity, but, due to the enzymatic action of phosphatases, it is rapidly converted to the parent drug. The half-life for hydrolysis in vivo is approximately lOmin and only 1-2% of an intravenous dose is eliminated in the urine as unchanged prodrug. " ... 

Modification of the Carbohydrate Side Chain. The importance to the antibacterial activity of the C-7 substituents in lincosaminides has been shown not only by the increased activity of the 7(5 )-chloro-analogue, clindamycin, (1, R = H, R/ = Cl) and of the corresponding... 

One study found that the pharmacokinetics of intravenous ciprofloxacin 200 mg were not affected by intravenous clindamycin 600 mg and there is evidence that combined use may possibly enhance the antibacterial activity, particularly against S. aureus and S. pneumoniae. However, another study found that the serum bactericidal activity of ciprofloxacin against S. aureus was completely antagonised by clindamycin, if the strains were susceptible to the latter. ... 

Chloro-7-desoxylincomycin (clindeunycin) is well suited for anti-infectious treatment of infants and children . 7-Deoxy-7(R)- and -7 S)-thio-lincomycin possessed slight antibacterial activity . Microbial transformation of clindamycin produced clindamycin sulfoxide which had one fourth of the antibacterial activity of the parent antibiotic against lutea . ... 

Similar stmcture activity relationships were found in the 4 -alkyl analogues of clindamycin (87). The de- /V-methylclindamycin intermediates including de- /V-methylclindamycin itself, but unlike de-/V-methyllincomycin, are also highly active antibacterially. In addition, they are active in vivo as antknalarial agents (66—68). 

Clindamycin illustrates how a simple modification, halogenation, of a drug can have such profound effects on the biological activity of an already useful compound broadened antibacterial spectrum, increased absorption efficiency, and even a new antiprotozoal activity. 

---