Lincocin (Lincomycin)

Lincomycin is an antibiotic that is structurally related to clindamycin.

Uses

Staphylococcal and Streptococcal Infections

Lincomycin is used to treat serious infections caused by susceptible strains of staphylococci, Streptococcus pneumoniae, and other streptococci. However, lincomycin is not considered the treatment of choice for infections caused by gram-positive cocci, and its use in these infections should be reserved for patients who are allergic to penicillin or for whom less toxic alternatives (for example, erythromycin) are contraindicated.

Lincomycin should not be used to treat minor bacterial infections or infections that are not caused by bacteria. Because it penetrates the central nervous system poorly, lincomycin should not be used to treat meningitis. In general, lincomycin appears to be less effective than clindamycin for infections caused by susceptible organisms because it has lower activity and is absorbed more slowly and less completely when taken by mouth. Before starting lincomycin, the causative organism should be cultured and in vitro susceptibility testing should be done. Treatment with lincomycin does not rule out surgery when needed.

Dosage and Administration

Administration

Lincomycin hydrochloride is given by mouth, by IM injection, or by slow IV infusion. Lincomycin hydrochloride has also been given by subconjunctival injection. Oral lincomycin should be taken at least 1-2 hours before or after food. Before IV administration, each gram of lincomycin should be diluted in 100 mL or more of a compatible IV solution. The appropriate dose should then be infused over at least 1 hour.

Dosage

Dosage of lincomycin hydrochloride is expressed in terms of lincomycin and depends on how severe the infection is and how susceptible the infecting organism is. The length of treatment depends on the type of infection. If lincomycin is used for infections caused by group A b-hemolytic streptococci, treatment should continue for at least 10 days. Oral Dosage The usual adult oral dose of lincomycin is 500 mg three times daily (500 mg about every 8 hours) for serious infections and 500 mg or more four times daily (500 mg or more about every 6 hours) for more severe infections.

Children older than 1 month should receive oral lincomycin at a dose of 30 mg/kg/day given in 3 or 4 equally divided doses for serious infections, or 60 mg/kg/day given in 3 or 4 equally divided doses for more severe infections.

Parenteral Dosage

The usual adult IM dose of lincomycin is 600 mg given once every 24 hours for serious infections or every 12 hours (or more often) for more severe infections. The IM dose for children older than 1 month is 10 mg/kg given once every 24 hours for serious infections or every 12 hours (or more often) for more severe infections. The usual adult IV dose of lincomycin is 600 mg to 1 g every 8-12 hours for the treatment of serious infections.

More severe infections may require a higher dose; for life-threatening infections, the adult IV dose may be increased to a maximum of 8 g daily. The IV dose of lincomycin for children older than 1 month is 10-20 mg/kg/day, depending on the severity of the infection, given in 2 or 3 equally divided doses.

Dosage in Renal and Hepatic Impairment

The manufacturer states that in Canada, patients with severe renal impairment may receive 25-30% of the usual lincomycin dose. The drug should be used with caution in these patients, and in Canadian practice serum lincomycin concentrations should be monitored during high-dose therapy.

Although the manufacturer does not make specific dosage recommendations for use of lincomycin in patients with impaired hepatic function, the drug should be used with caution in these patients, and in Canada serum lincomycin concentrations should be monitored during high-dose therapy.

Drug Interactions

Erythromycin

Because in vitro antagonism between lincomycin and erythromycin has been reported, these drugs should not be used together.

Kaolin

When used at the same time, kaolin reduces the gastrointestinal absorption of lincomycin by as much as 90%, which lowers plasma concentrations of the antibiotic. If both drugs must be used, patients should take kaolin at least 2 hours before lincomycin.

Neuromuscular Blocking Agents

Lincomycin has been shown to have neuromuscular blocking properties that may increase the neuromuscular blocking effects of other agents (for example, ether, tubocurarine, pancuronium). Lincomycin should be used with caution in patients receiving these agents.

Mechanism of Action

Lincomycin may act as either a bacteriostatic or bactericidal antibiotic, depending on the concentration of the drug reached at the site of infection and how susceptible the infecting organism is. Lincomycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; its main effect is inhibition of peptide bond formation. The site of action appears to be the same as that of clindamycin, erythromycin, chloramphenicol, oleandomycin, and troleandomycin. Spectrum Lincomycin and clindamycin have similar activity spectra; however, lincomycin is generally less active against susceptible organisms than clindamycin.

Lincomycin is active against most aerobic gram-positive cocci, including staphylococci, Streptococcus pneumoniae, and other streptococci, except Enterococcus faecalis [formerly S. faecalis].

Lincomycin is also active against several anaerobic and microaerophilic gram-negative and gram-positive organisms, including Actinomyces, Bacteroides, Eubacterium, Fusobacterium, Propionibacterium, microaerophilic streptococci, Peptococcus, Peptostreptococcus, and Veillonella. Clostridium perfringens, C. tetani, Corynebacterium diphtheriae, and Mycoplasma are also inhibited by lincomycin. Haemophilus and Neisseria are not generally inhibited by lincomycin. Lincomycin is inactive against Enterobacteriaceae, Plasmodium, fungi, and most strains of C. difficile. In vitro, lincomycin concentrations of 0.02-3.1 mcg/mL inhibit most susceptible strains of staphylococci, streptococci, Corynebacterium diphtheriae, and Actinomyces. In vitro, the minimum inhibitory concentration (MIC) of lincomycin for most susceptible anaerobic and microaerophilic bacteria is 0.1-6.2 mcg/mL.

Resistance

Staphylococcal resistance to lincomycin has been induced in vitro and has been shown to be acquired step by step. Natural and acquired resistance to the antibiotic has been demonstrated both in vitro and in vivo in strains of staphylococci, streptococci, and B. fragilis.

There is complete cross-resistance between clindamycin and lincomycin, and evidence of partial cross-resistance between lincomycin and erythromycin. In vitro, bacteria that are resistant to erythromycin and susceptible to lincomycin may show a dissociated type of resistance to lincomycin during susceptibility testing if erythromycin is also present.

This phenomenon may result from competition between erythromycin and lincomycin for the ribosomal binding site.

Pharmacokinetics

Absorption

About 20-30% of an oral dose of lincomycin hydrochloride is rapidly absorbed from the gastrointestinal tract. Food delays absorption and reduces the amount absorbed. Lincomycin is not inactivated by gastric acidity. After a single 500-mg oral dose of lincomycin hydrochloride is given to healthy fasting adults, peak plasma concentrations average 1.8-5.3 mcg/mL and are reached within 2-4 hours. Plasma concentrations of lincomycin average 1.4 mcg/mL at 6 hours and 0.3 mcg/mL at 12 hours.

When lincomycin hydrochloride was given by mouth to one group of children in single doses of 22-33 mg/kg, mean peak plasma concentrations of lincomycin were 4-9 mcg/mL. After IM administration of 600 mg of lincomycin hydrochloride in healthy adults, peak plasma concentrations occur within 30 minutes and range from 9.3-18. mcg/mL. Plasma concentrations range from 1.3-3.2 mcg/mL at 12 hours, and detectable concentrations may persist for up to 24 hours. After IV infusion of 600 mg of lincomycin hydrochloride over 2 hours, post-infusion plasma concentrations average 15.9-20.9 mcg/mL.

Distribution

Lincomycin is distributed into many body tissues and fluids, including peritoneal fluid, pleural fluid, synovial fluid, bone, bile, and the aqueous humour of the eye. The manufacturer states that a subconjunctival injection of 0.25 mL of a solution containing 300 mg of lincomycin per mL will produce inhibitory ocular fluid concentrations of the drug against most susceptible organisms for at least 5 hours.

The drug diffuses poorly into the CSF; however, when the meninges are inflamed, low concentrations of the drug (18% of the concurrent plasma concentration) have been reached. The concentration of lincomycin in bone is reported to be 20-33% of concurrent plasma concentrations.

Lincomycin readily crosses the placenta, and cord blood concentrations have been reported to be 25% of concurrent maternal blood concentrations. Lincomycin is distributed into milk, and milk concentrations may be equal to maternal plasma concentrations. At a plasma concentration of 5 mcg/mL, lincomycin is approximately 72% bound to plasma proteins; at a concentration of 1 mcg/mL, it is approximately 57% bound to plasma proteins.

Elimination

The plasma half-life of lincomycin is 4-6. hours in patients with normal kidney function. The plasma half-life increases in proportion to the degree of impairment in patients with reduced kidney or liver function. Plasma half-lives as high as 3 times normal have been reported in patients with severe renal impairment. Plasma concentrations of lincomycin are not appreciably affected by hemodialysis, peritoneal dialysis, or prolonged administration in patients with normal renal function.

Lincomycin is partly metabolized in the liver, and both the drug and its metabolites are excreted in urine, bile, and feces. After oral administration of 500 mg of lincomycin hydrochloride, 1-31% of the dose is excreted in urine and as much as 40% of the dose is excreted in feces. After parenteral administration of 600 mg of lincomycin hydrochloride, 1.8-30.3% of the dose is excreted in urine and 4-14% of the dose is excreted in feces.

Chemistry and Stability

Chemistry

Lincomycin is an antibiotic obtained from cultures of Streptomyces lincolnensis. Lincomycin is commercially available as the hydrochloride monohydrate. The drug occurs as a white to off-white crystalline powder that may have a faint odour and is freely soluble in water.

The pKa of lincomycin is 7.6. Lincomycin hydrochloride injection is a clear, colourless to slightly yellow solution; hydrochloric acid and/or sodium hydroxide may be added during manufacture to adjust the pH to 3-5.5.

Stability

Lincomycin hydrochloride capsules and injection should be stored at 20-25°C; avoid freezing the injection, and keep the capsules in tightly closed containers. Lincomycin hydrochloride is reported to be physically compatible for 24 hours at room temperature in the following IV infusion fluids: 5% or 10% dextrose in water or 0.9% sodium chloride, Ringer's, 1/6 M sodium lactate, 6% dextran in 0.9% sodium chloride, and Travert® 10% Electrolyte No. 1.100 Lincomycin hydrochloride has been reported to be incompatible with various drugs, but compatibility depends on several factors (for example, drug concentration, the specific diluents used, resulting pH, and temperature). Specialized references should be consulted for specific compatibility information.

Storage

Store lincomycin capsules and injection at 20-25°C (68-77°F). Keep capsules in a tightly closed container, protected from moisture. Avoid freezing the injection and protect it from excessive heat and light. Keep all medications out of reach of children.