Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae

María M. París, Sharon Shelton, Mónica Trujillo, Sheila M. Hickey, George H. McCracken

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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 fur clindamycin-treated rabbits to develop macrolide-licosamide 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.

Original languageEnglish (US)
Pages (from-to)122-126
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume40
Issue number1
StatePublished - Jan 1996

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Investigational Therapies
Clindamycin
Cephalosporins
Streptococcus pneumoniae
Meningitis
Penicillins
Rabbits
Dexamethasone
Ceftriaxone
Cerebrospinal Fluid
Pneumococcal Meningitis
Penicillin Resistance
Macrolides

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae. / París, María M.; Shelton, Sharon; Trujillo, Mónica; Hickey, Sheila M.; McCracken, George H.

In: Antimicrobial Agents and Chemotherapy, Vol. 40, No. 1, 01.1996, p. 122-126.

Research output: Contribution to journalArticle

París, María M. ; Shelton, Sharon ; Trujillo, Mónica ; Hickey, Sheila M. ; McCracken, George H. / Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae. In: Antimicrobial Agents and Chemotherapy. 1996 ; Vol. 40, No. 1. pp. 122-126.
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