RESUMEN
Clindamycin, which is usually used in combination with pyrimethamine, has been proven effective in the treatment of cerebral toxoplasmosis in human immunodeficiency virus-infected patients. However, it is not known if clindamycin achieves inhibitory concentrations at the site of infection. Also, it has been hypothesized that the activity of clindamycin against Toxoplasma gondii may be due, at least in part, to a metabolite. We evaluated the penetration of clindamycin and its major metabolite, N-demethylclindamycin (NDC), into cerebrospinal fluid (CSF) of AIDS patients undergoing lumbar puncture for diagnostic purposes. A single, 1,200-mg dose of clindamycin was administered as a 45-min intravenous infusion beginning at 1.5 or 2.5 h before CSF sampling. The concentrations of clindamycin in CSF ranged from 0.091 to 0.429 mg/liter at 1.5 h and from 0.120 to 0.283 mg/liter at 2.5 h following the beginning of the infusion. The concentrations of clindamycin in CSF were well above the 50% inhibitory concentration of 0.001 mg/liter and the parasiticidal concentration of 0.006 mg/liter. NDC was undetectable both in plasma and in CSF. Our study provides a pharmacokinetic rationale for the clinical efficacy of clindamycin in the treatment of cerebral toxoplasmosis.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/metabolismo , Clindamicina/metabolismo , Adulto , Barrera Hematoencefálica , Clindamicina/administración & dosificación , Clindamicina/líquido cefalorraquídeo , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Toxoplasmosis Cerebral/tratamiento farmacológicoRESUMEN
Although penicillin resistance among Streptococcus pneumoniae strains is increasing in many areas, resistance to clindamycin remains low. In our well-characterized rabbit meningitis model, we conducted experiments to evaluate the bacteriologic efficacy of clindamycin after a penicillin- and cephalosporin-resistant S. pneumoniae strain was intracisternally inoculated. Animals received a loading intravenous dose of 30 mg of clindamycin per kg of body weight and then two doses of 20 mg/kg given 5 h apart. In addition to clindamycin, some animals received dexamethasone (DXM) with or without ceftriaxone. The concentrations of clindamycin in cerebrospinal fluid were from 8.9 to 12.8% of the concomitant concentrations in serum and were unaffected by DXM administration. Mean changes in CFU (log10 per milliliter) at 10 and 24 h were -3.7 and -6.1, respectively, for clindamycin-treated rabbits, -3.6 and -6.3 for clindamycin-DXM-treated rabbits, -3.9 and -5.8, respectively, for clindamycin-ceftriaxone-treated rabbits, and -5.0 and -6.7, respectively, for clindamycin-ceftriaxone-DXM-treated rabbits. By 24 h all but one of the cultures of cerebrospinal fluid (that from a clindamycin-DXM-treated rabbit) were sterile. Because of the potential risk for clindamycin-treated rabbits to develop macrolide-lincosamide resistance, we attempted, unsuccessfully, to induce clindamycin resistance in vitro in two S. pneumoniae strains. Although clindamycin therapy might be effective in selected patients with multiple-drug-resistant pneumococcal meningitis who have failed conventional treatments, clinical experience is necessary before it can be recommended.
Asunto(s)
Antibacterianos/uso terapéutico , Resistencia a las Cefalosporinas , Clindamicina/uso terapéutico , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/microbiología , Resistencia a las Penicilinas , Streptococcus pneumoniae/efectos de los fármacos , Animales , Antibacterianos/líquido cefalorraquídeo , Antibacterianos/farmacología , Resistencia a las Cefalosporinas/genética , Clindamicina/líquido cefalorraquídeo , Clindamicina/farmacología , Humanos , Masculino , Meningitis Neumocócica/líquido cefalorraquídeo , Pruebas de Sensibilidad Microbiana , Mutación/efectos de los fármacos , Resistencia a las Penicilinas/genética , Conejos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/crecimiento & desarrollo , Factores de TiempoRESUMEN
The authors measured levels of clindamycin, a drug well established as useful in the treatment of various soft-tissue and parenchymal bacterial infections, in serum, cerebrospinal fluid, and brain tissue of 14 rhesus monkeys. Penetration into brain tissue was erratic and concentrations detected were not significant. Cerebrospinal fluid levels, however, averaged 20.5% of paired serum concentrations and were higher than concentrations needed to inhibit most Gram-positive bacteria. Further studies in humans are indicated before this antibiotic may be used routinely.