General Properties

Lincosamides are derivatives of an amino acid and a sulfur-containing octose. They are monobasic and more stable in salt forms (hydrochlorides and phosphates).

Antimicrobial Activity

Mode of Action

Lincomycin and clindamycin bind exclusively to the 50S subunit of bacterial ribosomes and suppress protein synthesis. Lincosamides, macrolides, and chloramphenicol, although not structurally related, seem to act at this same site. The lincosamides are bacteriostatic or bactericidal depending on the concentration. Activity is enhanced at an alkaline pH.

Bacterial Resistance

Resistance to lincosamides appears slowly, perhaps as a result of chromosomal mutation. Plasmid-mediated resistance has been found in strains of Bacteroides fragilis. Resistance appears to be due to an alteration in the 50S ribosomal subunit. Cross-resistance with other antibiotics has been shown in vitro but not in vivo with erythromycin.

Antimicrobial Spectra

Lincomycin has a limited spectrum against aerobic pathogens but a fairly broad spectrum against anaerobes. Clindamycin is a more active analog with somewhat different pharmacokinetic patterns. Many gram-positive cocci are inhibited by lincosamides, but most gram-negative organisms are resistant, as are most mycoplasmas. Bacteroides spp and other anaerobes are usually susceptible. Clostridium difficile strains appear to be regularly resistant.

Pharmacokinetic Features

Absorption

Lincomycin is incompletely absorbed from the GI tract, especially if administered soon after feeding; plasma concentrations peak within 2–4 hr. Absorption from IM injection sites is good; plasma concentrations peak in 1–2 hr. About 90% of an oral dose of clindamycin is absorbed, and effective plasma concentrations are achieved more rapidly than with lincomycin. Absorption is not significantly affected by the ingestion of food. Clindamycin palmitate is used PO, and clindamycin phosphate IM; the latter reaches peak plasma concentration in 1–3 hr.

Distribution

Lincosamides are widely distributed in many fluids and tissues, including bone, but significant concentrations are not attained in the CSF even when the meninges are inflamed. They diffuse across the placenta in many species. About 90% of clindamycin is bound to plasma proteins. It also accumulates in polymorphonuclear WBC and alveolar macrophages such that concentrations exceed those of plasma 50-fold. Clindamycin is able to penetrate glycocalyx, such as that associated with dental tartar.

Biotransformation

After administration PO, ~50% of a dose of lincomycin and 80–90% of a dose of clindamycin are metabolically altered in the liver. Metabolites often retain activity. Liver disease impairs the biotransformation of lincosamides.

Excretion

Unchanged antibiotic and several metabolites may be excreted in bile and urine. The proportions depend on the route of administration. Concentrations remain high in the feces for some days, and growth of sensitive microorganisms in the large intestine may be suppressed for up to 2 wk. Milk is also an important excretory route.

Pharmacokinetics

The elimination half-life of lincosamides is frequently >3 hr, and the apparent volume of distribution is >1 L/kg. They are usually administered bid. In dogs, clindamycin has an elimination half-life of 3.9 hr and a volume of distribution of 1.4 L/kg.

Therapeutic Indications and Dose Rates

The lincosamides are indicated for infections caused by susceptible gram-positive organisms, particularly streptococci and staphylococci, and for those caused by an-aerobic pathogens.

A selection of general dosages for some lincosamides is listed in see Antibacterial Agents: Dosages of Lincosamides. The dose rate and frequency should be adjusted as needed for the individual animal.

Table 24
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Dosages of Lincosamides Lincosamide Species Dosage, Route, and Frequency Lincomycin Cattle 10 mg/kg, IM, bid Pigs 10 mg/kg, IM, bid 7 mg/kg, in-feed Dogs 20 mg/kg, PO, sid Cats 10 mg/kg, IM, bid 25 mg/kg, PO, bid Clindamycin Dogs, cats 5–10 mg/kg, PO, bid

Special Clinical Concerns

Adverse Effects and Toxicity

No serious organ toxicity has been reported, but GI disturbances do occur. Clindamycin-induced pseudomembranous enterocolitis (caused by toxigenic Clostridium difficile) is a serious adverse reaction seen in humans. Lincosamides are contraindicated in horses because severe and even fatal colitis may develop. Skeletal muscle paralysis may be seen at high concentrations. Hypersensitivity reactions occasionally are seen. Lincosamides should not be used in neonates because of their limited ability to metabolize drugs.

Interactions

Lincosamides have additive neuromuscular effects with anesthetic agents and skeletal muscle relaxants. Kaolinpectin prevents their absorption from the GI tract. They should not be combined with bactericidal agents or with the macrolides.

Effects on Laboratory Tests

Alkaline phosphatase, AST, and ALT may be increased.

Drug Withdrawal Times

In several countries, there is a 2-day withdrawal time for pigs.

Last full review/revision March 2012 by Dawn Merton Boothe, DVM, PhD, DACVIM, DACVCP