TY - JOUR
T1 - Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae
AU - París, María M.
AU - Shelton, Sharon
AU - Trujillo, Mónica
AU - Hickey, Sheila M.
AU - McCracken, George H.
PY - 1996/1
Y1 - 1996/1
N2 - 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.
AB - 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.
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U2 - 10.1128/aac.40.1.122
DO - 10.1128/aac.40.1.122
M3 - Article
C2 - 8787892
AN - SCOPUS:0030049980
SN - 0066-4804
VL - 40
SP - 122
EP - 126
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 1
ER -