LINCOMYCIN INJECTION

Indications

• Bacterial infections caused by Gram-positive cocci and bacilli
• Skin and soft tissue infections
• Bone infections
• Respiratory tract infections
• Infections in penicillin-allergic patients

Dosage

Adults: Refer to the BNF for

Mechanism of action

Lincomycin functions as a structural analogue of the 3' end of L-Pro-Met-tRNA and deacylated-tRNA, allowing it to interact with the 23S rRNA of the 50S bacterial ribosomal subunit. This interaction inhibits protein synthesis by preventing the translocation of peptides on the ribosome. Lincomycin may exhibit both bacteriostatic and bactericidal effects, depending on the concentration achieved at the site of infection and the susceptibility of the bacteria.

Pharmacodynamics

Lincomycin is primarily effective against Gram-positive cocci and bacilli, with notable activity against Staphylococcus and Streptococcus species. It also has some efficacy against certain Gram-negative cocci and anaerobic bacteria, though clindamycin is generally more potent in the latter category. Caution is advised due to the risk of severe hypersensitivity reactions and the potential for inducing Clostridium difficile-associated diarrhea, especially in vulnerable populations such as the elderly or those with a history of gastrointestinal disorders.

Pharmacokinetics

Lincomycin is well-absorbed orally and can be administered intravenously. It is distributed widely in body tissues and fluids, including bone and abscesses. The drug is metabolized in the liver and excreted primarily in urine, with a half-life that allows for effective dosing intervals. Its pharmacokinetics can be influenced by factors such as renal function and the presence of other medical conditions.

Contra-indications

• Hypersensitivity to lincomycin or any of its components
• History of severe gastrointestinal disease, including colitis
• Concurrent use with other agents that may cause colitis

Adverse effects

• Severe cutaneous hypersensitivity reactions
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Erythema multiforme
• Acute generalized exanthematous pustulosis
• Clostridium difficile associated diarrhea (CDAD)
• Nausea
• Vomiting
• Abdominal pain

Interactions

• May enhance the effects of neuromuscular blocking agents
• Potential interaction with other antibiotics affecting the gut flora

Precautions

• Use with caution in elderly patients
• Patients with a history of gastrointestinal disease
• Patients with a history of asthma or significant allergies
• Monitor for signs of Clostridium difficile infection during treatment

Pregnancy

Lincomycin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. It is not recommended as a first-line treatment.

Breast-feeding

Lincomycin is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Capsules
• Oral solution
• Injection

Mechanism of action

Lincomycin contains the unusual amino acid moiety propyl hygric acid linked to the sugar moiety α-methylthiolincosamine (α-MTL) that, like other lincosamides, functions as a structural analogue of the 3' end of L-Pro-Met-tRNA and deacylated-tRNA to interact with the 23S rRNA of the 50S bacterial ribosomal subunit. Detailed investigations into the mechanism of the related lincosamide [clindamycin] suggested a two-phase binding, instantaneously to the A-site with a shift in equilibrium towards the P-site over several seconds. This shift appears to be due to rotation of the propyl hygric acid moiety, while the α-MTL remains relatively stationary. Recent crystal structures of lincomycin in complex with the 50S ribosomal subunit of _Staphylococcus aureus_ show that the α-MTL moiety forms hydrogen bonds with C2611, A2058, G2505, A2059, and G2503 of the 23S rRNA while the propyl hygric acid moiety interacts only through van der Waals contacts, suggesting it may be free to rotate similar to [clindamycin]. This mechanism is supported by the observation that the most common resistance mechanism, which also affects macrolides and streptogramin B (MSLB resistance) involves methylation of A2058; other resistance mechanisms similarly target residues such as A2058, A2059, and C2611. Lincomycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Lincomycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of clindamycin, erythromycin, and chloramphenicol. /The authors/ ... investigated the inhibition of peptide bond formation by the antibiotic lincomycin, at 150 mM NH4Cl. /The authors/ ... used an in vitro system in which a ribosomal ternary complex, the acetyl[3H] phenylalanine-tRNA-70 S ribosome-poly(U) complex (complex C), reacts with puromycin, forming peptide bonds. Complex C can be considered an analog of the elongating ribosomal complex and puromycin an analog of aminoacyl-tRNA. In a previous study /the authors/ ... reported on the kinetics of inhibition by lincomycin at 100 mM NH4Cl. In the present investigation, /the authors/ ... find that an increase of the ammonium ion concentration to 150 mM causes profound changes in the kinetic behavior of the system, which can be summarized as follows. First, the association rate for complex C and lincomycin is increased. At a lincomycin concentration of 10 uM the apparent equilibration rate constant is 4.3 min-1 at 100 mM NH4Cl, whereas it becomes 6.7 min-1 at 150 mM. Second, at 150 mM NH4Cl, with increasing concentrations of lincomycin, there is a transition from competitive to mixed-noncompetitive inhibition. The prevailing notion is that lincomycin acts at the ribosomal A-site, a mechanism that agrees only with competitive kinetics (mutually exclusive binding between puromycin and lincomycin). At the molecular level, the change in the kinetics of inhibition that we observe may mean that the mutually exclusive binding between aminoacyl-tRNA and lincomycin is converted to simultaneous binding, as a result of conformational changes occurring in the elongating ribosomal complex.

Pharmacodynamics

Lincomycin is a lincosamide antibiotic derived as a natural fermentation product from _Streptomyces lincolnensis_. Like [clindamycin], lincomycin is active against Gram-positive cocci and bacilli as well as Gram-negative cocci and some other organisms such as _Haemophilus_ spp. It is also effective against anaerobic bacteria, though in this regard [clindamycin] is generally more potent. Prescribing information highlights that the range of clinically confirmed effectiveness is largely limited to _Staphylococcus_ spp. and _Streptococcus_ spp., with additional activity noted _in vitro_. Lincomycin should be used with caution due to its association with severe cutaneous hypersensitivity reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and acute generalized exanthematous pustulosis, and its potential to precipitate _Clostridium difficile_ associated diarrhea (CDAD), which may lead to fatal colitis. Special care should therefore be exercised when used in elderly patients, individuals with a history of gastrointestinal disease, and those with a history of asthma or significant allergies. Lincomycin for injection may contain benzyl alcohol as a preservative, which has been associated with gasping syndrome in pediatric patients. The serum half-life is extended in patients with hepatic/renal impairment and may require dose adjustments and additional monitoring. Like all antibiotics, lincomycin use may cause overgrowth of non-susceptible organisms, which should be considered.