Lincosamides clindamycin

Systemic therapy with a variety of (3-lactams, macro-lides and lincosamides (clindamycin) has been the cornerstone of skin infection therapy for many years [17]. However, topical antibiotics can play an important role in both treatment and prevention of many primary cutaneous bacterial infections commonly seen in the dermatological practice [18], Indeed, while systemic antimicrobials are needed in the complicated infections of skin and skin structure, the milder forms can be successfully treated with topical therapy alone [18], The topical agents used most often in the treatment of superficial cutaneous bacterial infections are tetracyclines, mupirocin, bacitracin, polymyxin B, and neomycin. 

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

Figure 4 Exemplar structures of various antibiotic classes that bind to either the 505 or the 305 subunit. Macrolides azithromycin (1), oxazolidinones linezolid (2), aminoglycosides Kanamycin A (3), Pleuromutilin (4), phenylpropanoids chloramphenicol (5), lincosamides clindamycin (6), Sparsomycin (7), Anisomycin (8), and tetracycline (9). See Scheme 9 for thiosptrepton (38). Not pictured streptogramins such as quinupristin/dalfopristin.

Clindamycin, a lincosamide derivative, inhibits protein biosynthesis within a unique organelle of the parasite, termed apicoplast. Its mode of action is similar to that of spiramycin. 

Lincosamides (lincomycin and clindamycin) are representatives of a very small group of drugs synthesized up of an amino acid bound to an amino sugar. Lincosamides bind with the 50 S ribosomal subunit of bacteria and inhibit protein synthesis. They also inhibit pep-tidyltransferase action. Lincosamides are bacteriostatic antibiotics however, when they reach a certain level in the plasma, they also exhibit bactericidal action against some bacteria. Lincosamides are highly active against anaerobic infections such as Peptococcus, Peptostreptococcus, Actinomyces, Propionibacterium, and Clostridium fringens, a few types of Peptococcus and Clostridium. 

Pharmacology Lincomycin and clindamycin, known collectively as lincosamides, bind exclusively to the 50 S subunit of bacterial ribosomes and suppress protein synthesis. Cross-resistance has been demonstrated between these 2 agents. Clindamycin is preferred because it is better absorbed and more potent. Pharmacokinetics Administration with food markedly impairs lincomycin (but not clindamycin) oral absorption. 

The lincosamide family of antibiotics includes lin-comycin (Lincocin) and clindamycin (Cleocin), both of which inhibit protein synthesis. They bind to the SOS ri-bosomal subunit at a binding site close to or overlapping the binding sites for chloramphenicol and erythromycin. They block peptide bond formation by interference at either the A or P site on the ribosome. Lincomycin is no longer available for human use in the United States. 

The lincosamides, lincomycin and clindamycin are active against Grampositive bacteria. Plasmid-mediated inactivation from enzymatic nucleo-tidylation occurs in some staphylococci. Plasmid-encoded enzymes can modify streptogramin A (O-acetyltransferase enzyme) and streptogramin B (hydrolase enzyme involved) in S. aureus [198, 199], There is no evidence that bacteria can circumvent the action of other antibiotics for example, mupirocin is not degraded [200]. 

Figure 13 Adenylylation of lincosamides antibiotics. Lincosamides such as clindamycin (shown) interact with the large ribosomal subunit through a complex series of interactions (A). Modification of the antibiotic by adenylylation prevents binding to the ribosome (B).

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

Clindamycin, structurally a lincosamide rather than a macrolide, binds to bacterial ribosomes to... 

The direct toxicity of the lincosamides is relatively low (SED-7, 389) (6). The adverse effects of clindamycin may be well below 1%. In a tertiary care center, adverse reactions to chndamycin were reported in 0.47% of 3896 courses, and in half of these events an effect of other medications could not be excluded (7). However, chnda-mycin has not been given in as high doses as hncomycin. 

The most prominent adverse reaction of the lincosamides is diarrhea, which varies from mildly loose bowel movements to life-threatening pseudomembranous colitis (see monograph on Beta-lactam antibiotics). Almost all antimicrobial drugs have been associated with severe diarrhea and colitis however, lincomycin and clindamycin have been particularly incriminated. The incidence of clindamycin-induced diarrhea in hospital is 23%. Diarrhea resolves promptly after withdrawal in most cases. It seems to be dose-related and may result from a direct action on the intestinal mucosa. Severe colitis due to C. difficile is not dose-related and occurs in 0.01-10% of recipients. Clustering of cases in time and place suggests the possibility of cross-infection. Even low doses of clindamycin, in some cases after topical administration, can cause marked alterations in several intestinal functions related to bowel flora (23). There was reduced susceptibility of C. difficile to clindamycin in 80% of French isolates in 1997 (24). Lincomycin was among the antibiotics that were most often associated with the development of antibiotic-associated diarrhea in a Turkish study of 154 patients other associated antibiotics were azithromycin and ampicillin (25). 

Since the lincosamides are eliminated by biliary excretion, toxicity would be expected in patients with liver disease. High doses of clindamycin may be hepatotoxic (34). Abnormal liver function tests during treatment with hn-comycin are rare, and only in patients who had taken large doses (over 4 g/day) for more than 3 weeks (6). In another series, intravenous lincomycin 4—18 g/day was not associated with renal or hepatic toxicity (SED-7, 388). 

Clindamycin and hncomycin potentiate the action of nondepolarizing neuromuscular blocking drugs, such as pancuronium and D-tubocurarine. The lincosamide-induced block cannot be reliably reversed pharmacologically (71). 

The macrolide antibiotics include erythromycin, clarithromycin, azithromycin, tylosin, tilmicosin and tiamulin. Clindamycin and lincomycin are related lincosamides. Susceptible bacteria include staphylococci, streptococci, Campylobacter jejunii, Clostridium spp., R. equi, Mycoplasma pneumoniae and Chlamydia spp. Drugs in this group are only effective against a few Gram-negative bacteria in cattle, namely some strains of Pasteurella and Haemophilus spp. Macrolides and lincosamides are associated with causing colitis in horses, so their use is usually restricted to p.o. erythromycin for the treatment of R. equi infections in foals. Subantimicrobial doses of erythromycin are administered i.v. to horses for gastrointestinal prokinetic action. 

Examples of antibiotics that attack bacteria by inhibiting protein synthesis at the ribosomal level include the following tetracycline antibiotics (e.g. chlortetracycline) aminoglycoside antibiotics (e.g. neomycin, streptomycin) macrolide antibiotics (e.g. erythromycin, clarithromycin, azithromycin) also chloramphenicol, fusidic acid and lincosamides (e.g. clindamycin). 

Erythromycin estolate in conjunction with rifampin (both drugs administered orally) can be recommended for the treatment of Rhodococcus equi pneumonia in foals. Early diagnosis of the infection and prompt initiation of therapy considerably increase the effectiveness of treatment. Apart from this specific indication, macrolide antibiotics (including erythromycin) and lincosamides (lincomycin and clindamycin) are contra-indicated in horses. Antimicrobial agents in these classes can cause severe disturbance of the balance between commensal bacterial flora in the colon of the horse. 

Clindamycin is an antibiotic/antiinfective/lincosamide, which suppresses bacterial protein synthesis. It is indicated in the treatment of serious infections caused by susceptible strains of anaerobes, streptococci, staphylococci, and pneumococci treatment of acne vulgaris (topical use) treatment of bacterial vaginosis (vaginal use) in nonpregnant women and second- or third-trimester pregnant women (Cleocin and ClindaMax only). 

This chaj)ter discusses three groups of broad-spectrum antibiotics the tetracyclines, tlie macrolid, and the lincosamides. Example of the tetracycline include doxycycline (Vibramycin), minocycline (Minocin), and tetracycline (Sumycin). Examples of the macrohde include azithromycin (Zitliromax), clarithromycin (Biaxin), and erytliromycin (E-Mycin). The lincosamides include clindamycin (Cleocin) and lin-comycin (Lincocin). The Summary Drug Table Tetracyclines, Macrolide, and Lincosamide describe the lyi es of broad-spectrum antibiotics discussed in tliis chapter. 

A. Classification and Pharmacokinetics The lincosamides lincomycin and clindamycin inhibit bacterial protein synthesis via a mechanism similar to that of the macrolides, though they are not chemically related. Mechanisms of resistance include methylation of the binding site on the 50S ribosomal subunit and enzymatic inactivation. Cross-resistance between lincosamides and macrolides is common. Good tissue penetration occurs after oral absorption. The lincosamides are eliminated partly by metabolism and partly by biliary and renal excretion. 

Lincomycin (Lincocin) has been used in the past to treat serious streptococci, pneumococci, and staphylococci infections but has generally been replaced by safer and more effective antibiotics. Clindamycin (Cleocin) is a semisynthetic derivative of lincomycin and has a similar mechanism but is more effective. It is indicated for the treatment of bone and joint infections, pelvic (female) and intraabdominal infections, bacterial septicemia, pneumonia, and skin and soft tissue infections. In a normal dose, lincosamides prevent the growth of bacteria (bacteriostatic). In larger doses, it kills bacteria (bacteriocidal). 

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