title: Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: University of Texas Southwestern Medical Center at Dallas, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: París
authors.forename: S
authors.initials: S
authors.lastname: Shelton
authors.forename: M
authors.initials: M
authors.lastname: Trujillo
authors.forename: S M
authors.initials: SM
authors.lastname: Hickey
authors.forename: G H
authors.initials: GH
authors.lastname: McCracken
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use*; D018550:Cephalosporin Resistance / Q000235:genetics; D002981:Clindamycin / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000187:drug effects; D010403:Penicillin Resistance / Q000235:genetics; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin