DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

These strains would not display a blunting of inhibition on a D-test,
and clindamycin use would be appropriate. Altered metabolism occasionally
causes clindamycin resistance (Bozdogan et al., 1999).
Absorption, Distribution, and Excretion
Absorption. Clindamycin is nearly completely absorbed following
oral administration. Peak plasma concentrations of 2-3 μg/mL are
attained within 1 hour after the ingestion of 150 mg. The presence
of food in the stomach does not reduce absorption significantly. The
t 1/2
of the antibiotic is ~2.9 hours, and modest accumulation of drug
is thus expected if it is given every 6 hours.
Clindamycin palmitate, an oral preparation for pediatric use,
is an inactive prodrug that is hydrolyzed rapidly in vivo. Its rate and
extent of absorption are similar to those of clindamycin. After several
oral doses at 6-hour intervals, children attain plasma concentrations
of 2-4 μg/mL with the administration of 8-16 μg/kg.
The phosphate ester of clindamycin, which is given parenterally,
also is rapidly hydrolyzed in vivo to the active parent compound. After
intramuscular injection, peak concentrations in plasma are not attained
until 3 hours in adults and 1 hour in children; these values approximate
6 μg/mL after a 300-mg dose and 9 μg/mL after a 600-mg dose in adults.
Distribution. Clindamycin is widely distributed in many fluids and
tissues, including bone. Significant concentrations are not attained in
CSF, even when the meninges are inflamed. Concentrations sufficient to
treat cerebral toxoplasmosis are achievable (Gatti et al., 1998). The drug
readily crosses the placental barrier. Ninety percent or more of clindamycin
is bound to plasma proteins. Clindamycin accumulates in polymorphonuclear
leukocytes, alveolar macrophages, and in abscesses.
Excretion. Only ~10% of the clindamycin administered is excreted
unaltered in the urine, and small quantities are found in the feces.
However, antimicrobial activity persists in feces for ≥5 days after
parenteral therapy with clindamycin is stopped; growth of clindamycin-sensitive
microorganisms in colonic contents may be suppressed
for up to 2 weeks.
Clindamycin is inactivated by metabolism to N-demethylclindamycin
and clindamycin sulfoxide, which are excreted in the urine
and bile. Accumulation of clindamycin can occur in patients with
severe hepatic failure, and dosage adjustments thus may be required.
Therapeutic Uses and Dosage. The oral dose of clindamycin (clindamycin
hydrochloride; CLEOCIN, others) for adults is 150-300 mg every
6 hours; for severe infections, it is 300-600 mg every 6 hours. Children
should receive 8-12 mg/kg per day of clindamycin palmitate hydrochloride
(CLEOCIN PEDIATRIC) in three or four divided doses (some physicians
recommend 10-30 mg/kg per day in six divided doses) or for severe
infections, 13-25 mg/kg per day. However, children weighing ≤10 kg
should receive 1 / 2
teaspoonful of clindamycin palmitate hydrochloride
(37.5 mg) every 8 hours as a minimal dose. Clindamycin phosphate
(CLEOCIN PHOSPHATE, others) is available for intramuscular or intravenous
use. For serious infections, intravenous or intramuscular administration
is recommended in dosages of 1200-2400 mg per day, divided
into three or four equal doses for adults. Daily doses as high as 4.8 g have
been given intravenously to adults. Children should receive 15-40 mg/kg
per day in three or four divided doses; in severe infections, a minimal
daily dose of 300 mg is recommended, regardless of body weight.
Skin and Soft-Tissue Infections. Because of clindamycin’s good
activity against aerobic and anaerobic gram-positive cocci and good
oral bioavailability, it is an alternative agent for the treatment of skin
and soft-tissue infections, especially in patients with β-lactam
allergies. However, the high incidence of diarrhea and the occurrence
of pseudomembranous colitis should limit its use to infections
where it represents a clear therapeutic advantage. Clindamycin has
been employed in the treatment of necrotizing skin and soft-tissue
infections based on its potential to reduce toxin expression.
Respiratory Tract Infections. On the basis of one clinical trial which
found that clindamycin (600 mg intravenously every 8 hours) was
superior to penicillin (1 million units intravenously every 4 hours;
Levison et al., 1983), clindamycin has replaced penicillin as the
drug of choice for treatment of lung abscess and anaerobic lung and
pleural space infections. Clindamycin (600 mg intravenously every
8 hours, or 300-450 mg orally every 6 hours for less severe disease)
in combination with primaquine (15 mg of base once daily) is useful
for the treatment of mild to moderate cases of P. jiroveci pneumonia
in AIDS patients.
Other Infections. Clindamycin (600-1200 mg given intravenously
every 6 hours) in combination with pyrimethamine (a 200-mg loading
dose followed by 75 mg orally each day) and leucovorin (folinic
acid, 10 mg/day) is effective for acute treatment of encephalitis
caused by T. gondii in patients with AIDS. Clindamycin also is available
as a topical solution, gel, or lotion (CLEOCIN T, others) and as a
vaginal cream (CLEOCIN, others). It is effective topically (or orally)
for acne vulgaris and bacterial vaginosis. Clindamycin is not predictably
useful for the treatment of bacterial brain abscesses because
penetration into the CSF is poor; metronidazole, in combination with
penicillin or a third-generation cephalosporin, is preferred.
Untoward Effects.
Gastrointestinal Effects. The reported incidence of diarrhea associated
with the administration of clindamycin ranges from 2% to
20%. A number of patients (variously reported as 0.01-10%) have
developed pseudomembranous colitis caused by the toxin from the
organism C. difficile. This colitis is characterized by watery diarrhea,
fever, and elevated peripheral white blood cell counts.
Proctoscopic examination reveals white to yellow plaques on the
mucosa of the colon. This syndrome may be lethal. Discontinuation
of the drug, combined with administration of metronidazole or oral
vancomycin usually is curative, but relapses occur in up to 20% of
cases. Agents that inhibit peristalsis, such as opioids, may prolong
and worsen the condition.
Other Toxic and Irritative Effects. Skin rashes occur in ~10% of
patients treated with clindamycin and may be more common in
patients with HIV infection. Other reactions, which are uncommon,
include exudative erythema multiforme (Stevens-Johnson syndrome),
reversible elevation of aspartate aminotransferase and alanine
aminotransferase, granulocytopenia, thrombocytopenia, and
anaphylactic reactions. Local thrombophlebitis may follow intravenous
administration of the drug. Clindamycin can inhibit neuromuscular
transmission and may potentiate the effect of a
neuromuscular blocking agent administered concurrently.
STREPTOGRAMINS (QUINUPRISTIN/
DALFOPRISTIN)
Quinupristin/dalfopristin (SYNERCID) is a combination
of quinupristin, a streptogramin B, with dalfopristin, a
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CHAPTER 55
PROTEIN SYNTHESIS INHIBITORS AND MISCELLANEOUS ANTIBACTERIAL AGENTS