Source: Pharmaceutical Benefits Scheme (AU) Revision Year: 2018 Publisher: Pfizer Australia Pty Ltd, 38-42 Wharf Road, West Ryde NSW 2114, Toll Free Number: 1800 675 229, www.pfizer.com.au
LINCOCIN is an antibiotic produced by fermentation of Streptomyces lincolnensis. LINCOCIN inhibits bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome. LINCOCIN is predominantly bacteriostatic in vitro. The antibacterial activity of LINCOCIN appears to best correlate with the length of time the concentration of active ingredient remains above the minimum inhibitory concentration (MIC) of the infecting organism.
Cross resistance between LINCOCIN and clindamycin is complete. Resistance in staphylococci and streptococci is most often due to methylation of specific nucleotides in the 23S RNA of the 50S ribosomal subunit, which can determine cross resistance to macrolides and streptogramins B (MLS B phenotype). Macrolide-resistant isolates of these organisms should be tested for inducible resistance to lincomycin/clindamycin using the D zone test
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
LINCOCIN is cross-resistant with clindamycin. A decrease in clindamycin/lincomycin susceptibility over time has been noted in particular among methicillin-resistant Staphylococcus aureus and in some species of Clostridium.
In vitro studies indicate that the following organisms are usually sensitive to concentrations achieved normally in the serum following recommended doses:
Aerobic and facultative gram-positive bacteria:
Anaerobic and microaerophilic bacteria:
Note: The drug is not active against most strains of Enterococcus faecalis, nor against Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae or other gram-negative organisms or yeasts. Some strains of Clostridium perfringens and strains of some less common human pathogens of Clostridia may be lincomycin-resistant. Depending on the sensitivity of the organism and concentration of the antibiotic, it may be either bactericidal or bacteriostatic. Cross resistance has not been demonstrated with penicillin, chloramphenicol, ampicillin, cephalosporins or the tetracyclines. Despite chemical differences, LINCOCIN exhibits antibacterial activity similar but not identical to the macrolide antibiotics (e.g. erythromycin). Some cross-resistance (with erythromycin) including a phenomenon known as dissociated cross-resistance or macrolide effect has been reported. Microorganisms have not developed resistance to LINCOCIN rapidly when tested by in vitro or in vivo methods. Staphylococci develop resistance to LINCOCIN in a slow step-wise manner based on in vitro serial subculture experiments. Studies indicated that LINCOCIN does not share antigenicity with penicillin compounds.
Susceptibility testing should be conducted using standardized laboratory methods, such as those described by the Clinical and Laboratory Standards Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Because CLSI and EUCAST have not established susceptibility breakpoints for LINCOCIN, clindamycin should be tested instead. Resistance to lincosamides may be inducible by macrolides in macrolide-resistant staphylococci, Streptococcus pneumoniae, and beta-hemolytic streptococci. Macrolide-resistant isolates of these organisms should be screened for inducible clindamycin resistance using the D-zone test or other standard methodology.
Table 1. CLSI dilution and disk diffusion susceptibility interpretive criteria for clindamycin:
| Organism | Susceptibility Interpretive Criteria | |||||
|---|---|---|---|---|---|---|
| Minimal Inhibitory Concentrations (MIC in μg/mL) | Disk Diffusion (Zone Diameters in mm) | |||||
| S | I | R | S | I | R | |
| Staphylococcus spp. | ≤0.5 | 1-2 | ≥4 | ≥21 | 15-20 | ≤14 |
| Streptococcus pneumoniae, β-hemolytic streptococci and viridans group streptococci | ≤0.25 | 0.5 | ≥1 | ≥19 | 16-18 | ≤15 |
| Anaerobic Bacteria | ≤2 | 4 | ≥8 | NA | NA | NA |
Disk content 2 μg.
MIC interpretive criteria for anaerobes are based on agar dilution.
NA = not applicable.
The validity of both the dilution and disk diffusion test methods should be verified using quality control (QC) strains, as indicated by CLSI. Acceptable limits when testing clindamycin against these organisms are listed in the table below.
Table 2. Quality control ranges for clindamycin susceptibility tests (CLSI):
| Organism | Minimum Inhibitory Concentration Range (MIC in μg/mL) | <>Disk Diffusion Range (Zone Diameters in mm) |
|---|---|---|
| Staphylococcus aureus ATCC 29213 | 0.06-0.25 | NA |
| Staphylococcus aureus ATCC 25923 | NA | 24-30 |
| Streptococcus pneumoniae ATCC 49619 | 0.03-0.12 | 19-25 |
| Bacteroides fragilis ATCC 25285 | 0.5-2 | NA |
| Bacteroides thetaiotaomicron ATCC 29741 | 2-8 | NA |
| Eggerthella lenta ATCC 43055 | 0.06-0.25 | NA |
MIC ranges for anaerobic bacteria are based on agar dilution.
NA = Not applicable
ATCC is a registered trademark of the American Type Culture Collection
Table 3. EUCAST dilution and disk diffusion susceptibility interpretive criteria for clindamycin:
| Organism | Minimal Inhibitory Concentrations (MIC in μg/mL) | Disk Diffusion (Zone Diameters in mm) | ||
|---|---|---|---|---|
| S | R | S | R | |
| Staphylococcus spp. | ≤ 0.25 | >0.5 | ≥22 | <19 |
| Streptococcus groups A, B, C, G | ≤0.5 | >0.5 | ≥17 | <17 |
| Streptococcus pneumoniae | ≤0.5 | >0.5 | ≥19 | <19 |
| Viridans group streptococci | ≤0.5 | >0.5 | ≥19 | <19 |
| Gram-positive anaerobes (except Clostridium difficile) | ≤4 | -- | NA | NA |
| Gram-negative anaerobes | ≤4 | -- | NA | NA |
Disk content 2 μg.
MIC interpretive criteria for anaerobes are based on agar dilution.
NA = not applicable.
Table 4. Quality control ranges for clindamycin susceptibility tests (EUCAST):
| Organism | Minimum Inhibitory Concentration Range (MIC in μg/mL) | Disk Diffusion Range (Zone Diameters in mm) |
|---|---|---|
| Staphylococcus aureus ATCC 29213 | 0.06–0.25 | 23-29 |
| Streptococcus pneumoniae ATCC 49619 | 0.03–0.12 | 22-28 |
No data available.
LINCOCIN is absorbed rapidly after a 500 mg oral dose in the fasting state, producing an average peak serum level of 5.3 micrograms/mL at 2 hours post dose. Doubling the dose increases but does not double the peak serum levels. Food in the stomach reduces total absorption as well as peak serum levels.
Significant levels have been demonstrated in the majority of body tissues. Although lincomycin appears to diffuse into cerebrospinal fluid (CSF), levels of lincomycin in the CSF appear inadequate for the treatment of meningitis.
Tissue level studies indicate that bile is an important route of excretion. The excretion of lincomycin in urine and bile does not account for all of the administered dose and a substantial proportion of the drug appears to be inactivated in the body, presumably in the liver.
The biological half-life, after, intramuscular administration is approximately 5hours.
Urinary recovery of drug in a 24-hour period ranges from 1.0% to 31% (mean: 4.0%) after a single oral dose of 500 mg. Bile is an important route of excretion.
Intramuscular administration of a single dose of 600 mg of lincomycin produces an average peak serum level of 11.6 micrograms/mL at 60 minutes and maintains therapeutic levels for 17 to 20 hours for most susceptible gram-positive organisms. Urinary excretion after this dose ranges from 1.8% to 24.8% (mean: 10.3%).
The intravenous infusion over a 2-hour interval of 600 mg of lincomycin achieves average peak serum levels of 15.9 μg/mL and yields therapeutic levels for 14 hours for most susceptible gram-positive organisms. Urinary excretion ranges from 4.9% to 23.3% (mean: 15.1%).
Haemodialysis and peritoneal dialysis do not effectively remove lincomycin from the blood.
The serum half-life of LINCOCIN may be prolonged in patients with severe impairment of renal function compared to patients with normal renal function.
In patients with abnormal hepatic function, serum half-life may be two-fold longer than in patients with normal hepatic function.
Lincomycin was not genotoxic in various in vitro and in vivo genotoxicity studies including bacterial reverse mutation assays, gene mutation assays in mammalian cells and Drosophila melanogaster germ cells, chromosomal aberration assays in human lymphocytes, and in vivo micronucleus assays. It induced DNA damage in one unscheduled DNA synthesis (UDS) assay in primary rat hepatocytes, but it was negative in another UDS assay in rat hepatocytes and in a UDS assay in Chinese hamster lung fibroblasts.
Lincomycin was not carcinogenic in rats at up to 100 mg/kg/day administered in the diet for 26 months.
No effects on fertility were observed in rats administered lincomycin at oral doses up to 1000 mg/kg/day.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
