Serum level studies with a 150 mg oral dose of
clindamycin hydrochloride in 24 normal adult volunteers showed that clindamycin
was rapidly absorbed after oral administration. An average peak serum level of
2.50 mcg/mL was reached in 45 minutes; serum levels averaged 1.51 mcg/mL at 3
hours and 0.70 mcg/mL at 6 hours. Absorption of an oral dose is virtually
complete (90%), and the concomitant administration of food does not appreciably
modify the serum concentrations; serum levels have been uniform and predictable
from person to person and dose to dose. Serum level studies following multiple
doses of CLEOCIN HCl for up to 14 days show no evidence of accumulation or
altered metabolism of drug. Doses of up to 2 grams of clindamycin per day for
14 days have been well tolerated by healthy volunteers, except that the
incidence of gastrointestinal side effects is greater with the higher doses.
Concentrations of clindamycin in the serum increased
linearly with increased dose. Serum levels exceed the MIC (minimum inhibitory
concentration) for most indicated organisms for at least six hours following
administration of the usually recommended doses. Clindamycin is widely
distributed in body fluids and tissues (including bones). No significant levels
of clindamycin are attained in the cerebrospinal fluid, even in the presence of
In vitro studies in human liver and intestinal microsomes
indicated that clindamycin is predominantly metabolized by Cytochrome P450 3A4
(CYP3A4), with minor contribution from CYP3A5, to form clindamycin sulfoxide
and a minor metabolite, N-desmethylclindamycin.
The average biological half-life is 2.4 hours.
Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the
feces; the remainder is excreted as bioinactive metabolites.
Serum half-life of clindamycin is increased slightly in
patients with markedly reduced renal function. Hemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.
Use in Elderly
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.
Mechanism of Action
Clindamycin inhibits bacterial protein synthesis by
binding to the 23S RNA of the 50S subunit of the ribosome. Clindamycin is
Resistance to clindamycin is most often caused by
modification of specific bases of the 23S ribosomal RNA. Cross-resistance
between clindamycin and lincomycin is complete. Because the binding sites for
these antibacterial drugs overlap, cross-resistance is sometimes observed among
lincosamides, macrolides and streptogramin B. Macrolide-inducible resistance to
clindamycin occurs in some isolates of macrolide-resistant bacteria.
Macrolide-resistant isolates of staphylococci and beta-hemolytic streptococci should
be screened for induction of clindamycin resistance using the D-zone test.
Clindamycin has been shown to be active against most of
the isolates of the following microorganisms, both in vitro and in clinical
infections, as described in the INDICATIONS AND USAGE section.
Staphylococcus aureus (methicillin-susceptible
Streptococcus pneumoniae (penicillin-susceptible
At least 90% of the microorganisms listed below exhibit in
vitro minimum inhibitory concentrations (MICs) less than or equal to the
clindamycin susceptible MIC breakpoint for organisms of a similar type to those
shown in Table 1. However, the efficacy of clindamycin in treating clinical
infections due to these microorganisms has not been established in adequate and
well-controlled clinical trials.
Staphylococcus epidermidis (methicillin-susceptible
Finegoldia (Peptostreptococcus) magna
Micromonas (Peptostreptococcus) micros
Susceptibility Testing Methods
When available, the clinical microbiology laboratory should
provide cumulative in vitro susceptibility test results for antimicrobial drugs
used in local hospitals and practice areas to the physician as periodic reports
that describe the susceptibility profile of nosocomial and community-acquired
pathogens. These reports should aid the physician in selecting an antibacterial
drug for treatment.
Quantitative methods are used to determine antimicrobial
minimum inhibitory concentrations (MICs). These MICs provide estimates of the
susceptibility of bacteria to antimicrobial compounds. The MICs should be
determined using a standardized test method2,3 (broth and/or agar).
The MIC values should be interpreted according to the criteria provided in
Quantitative methods that require the measurement of zone
diameters can also provide reproducible estimates of the susceptibility of
bacteria to antimicrobial compounds. The zone size should be determined using a
standardized method2,5. This procedure uses paper disks impregnated
with 2 mcg of clindamycin to test the susceptibility of bacteria to
clindamycin. The disk diffusion breakpoints are provided in Table 1.
For anaerobic bacteria, the susceptibility to clindamycin
can be determined by a standardized test method2,4. The MIC values
obtained should be interpreted according to the criteria provided in Table 1.
Table 1: Susceptibility Test Interpretive Criteria for
||Minimal Inhibitory Concentrations (MIC in mcg/mL)
||Disk Diffusion (Zone Diameters in mm)
|| ≤ 0.5
|| ≥ 4
|| ≥ 21
|| ≤ 14
|Streptococcus pneumoniae and other Streptococcus spp.
|| ≤ 0.25
|| ≥ 1
|| ≥ 19
|| ≤ 15
|| ≤ 2
|| ≥ 8
A report of Susceptible (S ) indicates
that the antimicrobial drug is likely to inhibit growth of the pathogen if the
antimicrobial drug reaches the concentration usually achievable at the site of
infection. A report of Intermediate (I) indicates that the result should be
considered equivocal, and, if the microorganism is not fully susceptible to
alternative, clinically feasible drugs, the test should be repeated. This
category implies possible clinical applicability in body sites where the drug
is physiologically concentrated or in situations where high dosage of drug can
be used. This category also provides a buffer zone that prevents small,
uncontrolled technical factors from causing major discrepancies in
interpretation. A report of Resistant (R) indicates that the antimicrobial drug
is not likely to inhibit growth of the pathogen if the antimicrobial drug
reaches the concentration usually achievable at the infection site; other
therapy should be selected.
Standardized susceptibility test procedures require the
use of laboratory controls to monitor and ensure the accuracy and precision of
the supplies and reagents used in the assay, and the techniques of the
individuals performing the test.2,3,4,5 Standard clindamycin powder
should provide the MIC ranges in Table 2. For the disk diffusion technique
using the 2 mcg clindamycin disk the criteria provided in Table 2 should be
Table 2: Acceptable Quality Control Ranges for
||Acceptable Quality Control Ranges
|Minimum Inhibitory Concentration Range (mcg/mL)
||Disk Diffusion Range (Zone Diameters in mm)
|Enterococcus faecalis1 ATCC 29212
|Staphylococcus aureus ATCC 29213
|Staphylococcus aureus ATCC 25923
|Streptococcus pneumoniae ATCC 49619
|Bacteroides fragilis ATCC 25285
|Bacteroides thetaiotaomicron ATCC 29741
|Clostridium difficile2 ATCC 700057
|Eggerthella lenta ATCC 43055
|1Enterococcus faecalis has been
included in this table for quality control purposes only.
2Quality control for C. difficle is performed using the agar
dilution method only, all other obligate
anaerobes may be tested by either
broth microdilution or agar dilution methods. NA=Not applicable ATCC® is a
registered trademark of the American Type Culture Collection
1. Smith RB, Phillips JP: Evaluation of CLEOCIN HCl and
CLEOCIN Phosphate in an Aged Population. Upjohn TR 8147-82-9122-021, December
2. CLSI. Performance Standards for Antimicrobial
Susceptibility Testing: 26th ed. CLSI supplement M100S. Wayne, PA: Clinical and
Laboratory Standards Institute; 2016.
3. CLSI. Methods for Dilution Antimicrobial
Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard -
Tenth Edition. CLSI document M07-A10. Wayne, PA: Clinical and Laboratory
Standards Institute; 2015.
4. CLSI. Methods for Antimicrobial Susceptibility Testing
of Anaerobic Bacteria; Approved Standard-Eighth Edition. CLSI document M11-A8.
Wayne, PA: Clinical and Laboratory Standards Institute; 2012.
5. CLSI. Performance Standards for Antimicrobial Disk
Susceptibility Tests; Approved Standard -Twelfth Edition. CLSI document
M02-A12. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.