"A family of bacteria has become increasingly resistant to last-resort antibiotics during the past decade, and more hospitalized patients are getting lethal infections that, in some cases, are impossible to cure.Â The findings, published today"...
Biologically inactive clindamycin phosphate is rapidly converted to active clindamycin.
By the end of short-term intravenous infusion, peak serum levels of active clindamycin are reached. Biologically inactive clindamycin phosphate disappears rapidly from the serum; the average elimination half-life is 6 minutes; however, the serum elimination half-life of active clindamycin is about 3 hours in adults and 2½ hours in pediatric patients.
After intramuscular injection of clindamycin phosphate, peak levels of active clindamycin are reached within 3 hours in adults and 1 hour in pediatric patients. Serum level curves may be constructed from IV peak serum levels as given in Table 1 by application of elimination half-lives listed above.
Serum levels of clindamycin can be maintained above the in vitro minimum inhibitory concentrations for most indicated organisms by administration of clindamycin phosphate every 8 to 12 hours in adults and every 6 to 8 hours in pediatric patients, or by continuous intravenous infusion. An equilibrium state is reached by the third dose.
The elimination half-life of clindamycin is increased slightly in patients with markedly reduced renal or hepatic function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Dosage schedules need not be modified in the presence of mild or moderate renal or hepatic disease.
Pharmacokinetic studies in elderly volunteers (61–79 years) and younger adults (18–39 years) indicate that age alone does not alter clindamycin pharmacokinetics (clearance, elimination half-life, volume of distribution, and area under the serum concentration-time curve) after IV administration of clindamycin phosphate. After oral administration of clindamycin hydrochloride, elimination half-life is increased to approximately 4.0 hours (range 3.4–5.1 h) in the elderly compared to 3.2 hours (range 2.1– 4.2 h) in younger adults. The extent of absorption, however, is not different between age groups and no dosage alteration is necessary for the elderly with normal hepatic function and normal (age-adjusted) renal function1.
Serum assays for active clindamycin require an inhibitor to prevent in vitro hydrolysis of clindamycin phosphate.
Table 1. Average Peak and Trough Serum Concentrations of
Active Clindamycin After Dosing with Clindamycin Phosphate
|Dosage Regimen||Peak mcg/mL||Trough mcg/mL|
|Healthy Adult Males (Post equilibrium)|
|600 mg IV in 30 min q6h||10.9||2.0|
|600 mg IV in 30 min q8h||10.8||1.1|
|900 mg IV in 30 min q8h||14.1||1.7|
|600 mg IM q12h*||9.|
|Pediatric Patients (first dose)*|
|5–7 mg/kg IV in 1 hour||10|
|5–7 mg/kg IM||8|
|3–5 mg/kg IM||4|
|*Data in this group from patients being treated for infection.|
Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active clindamycin.
Clindamycin has been shown to have in vitro activity against isolates of the following organisms:
Aerobic gram positive cocci, including:
- Staphylococcus aureus (penicillinase and non-penicillinase producing strains). When tested by in vitro methods, some staphylococcal strains originally resistant to erythromycin rapidly develop resistance to clindamycin.
- Staphylococcus epidermidis (penicillinase and non-penicillinase producing strains). When tested by in vitro methods, some staphylococcal strains originally resistant to erythromycin rapidly develop resistance to clindamycin.
- Streptococci (except Enterococcus faecalis)
Anaerobic gram negative bacilli, including:
- Bacteroides species (including Bacteroides fragilis group and Bacteroides melaninogenicus group)
- Fusobacterium species
Anaerobic gram positive nonsporeforming bacilli, including:
- Actinomyces species
Anaerobic and microaerophilic gram positive cocci, including:
- Peptococcus species
- Peptostreptococcus species
- Microaerophilic streptococci
Clostridia: Clostridia are more resistant than most anaerobes to clindamycin. Most Clostridium perfringens are susceptible, but other species, e.g., Clostridium sporogenes and Clostridium tertium are frequently resistant to clindamycin. Susceptibility testing should be done.
Cross resistance has been demonstrated between clindamycin and lincomycin.
Antagonism has been demonstrated between clindamycin and erythromycin.
In vitro Susceptibility Testing
Disk diffusion technique-Quantitative methods that require measurement of zone diameters give the most precise estimates of antibiotic susceptibility. One such procedure2 has been recommended for use with disks to test susceptibility to clindamycin.
Reports from a laboratory using the standardized single-disk susceptibility test1 with a 2 mcg clindamycin disk should be interpreted according to the following criteria:
Susceptible organisms produce zones of 17 mm or greater, indicating that the tested organism is likely to respond to therapy.
Organisms of intermediate susceptibility produce zones of 15–16 mm, indicating that the tested organism would be susceptible if a high dosage is used or if the infection is confined to tissues and fluids (e.g., urine), in which high antibiotic levels are attained.
Resistant organisms produce zones of 14 mm or less, indicating that other therapy should be selected.
Standardized procedures require the use of control organisms. The 2 mcg clindamycin disk should give a zone diameter between 24 and 30 mm for S. aureus ATCC 25923.
A bacterial isolate may be considered susceptible if the minimum inhibitory concentration (MIC) for clindamycin is not more than 1.6 mcg/mL. Organisms are considered moderately susceptible if the MIC is greater than 1.6 mcg/mL and less than or equal to 4.8 mcg/mL. Organisms are considered resistant if the MIC is greater than 4.8 mcg per mL.
The range of MICs for the control strains are as follows:
S. aureus ATCC 29213, 0.06 - 0.25 mcg/mL.
E. faecalis ATCC 29212, 4.0 - 16 mcg/mL.
For anaerobic bacteria the minimum inhibitory concentration (MIC) of clindamycin can be determined by agar dilution and broth dilution (including microdilution) techniques.3 If MICs are not determined routinely, the disk broth method is recommended for routine use. THE KIRBY-BAUER DISK DIFFUSION METHOD AND ITS INTERPRETIVE STANDARDS ARE NOT RECOMMENDED FOR ANAEROBES.
One year oral toxicity studies in Spartan Sprague-Dawley rats and beagle dogs at dose levels up to 300 mg/kg/day (approximately 1.1 and 3.6 times the highest recommended adult human dose based on mg/m2, respectively) have shown clindamycin to be well tolerated. No appreciable difference in pathological findings has been observed between groups of animals treated with clindamycin and comparable control groups. Rats receiving clindamycin hydrochloride at 600 mg/kg/day (approximately 2.1 times the highest recommended adult human dose based on mg/m2) for 6 months tolerated the drug well; however, dogs dosed at this level (approximately 7.2 times the highest recommended adult human dose based on mg/m2) vomited, would not eat, and lost weight.
1. Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December 1982.
2. Bauer AW, Kirby WMM, Sherris JC, Turck M; Antibiotic susceptibility testing by a standardized single disk method. Am. J. Clin. Path., 45:493-496, 1966. Standardized Disk Susceptibility Test, Federal Register, 37:20527-29, 1972.
3. National Committee for Clinical Lab. Standards. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria-Second Edition; Tentative Standard. NCCLS publication M11-T2. Villanova, PA; NCCLS; 1988.
Last reviewed on RxList: 4/3/2009
This monograph has been modified to include the generic and brand name in many instances.
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