In vitro and in vivo activity of miltefosine against penicillin-sensitive and -resistant Streptococcus pneumoniae strains.
The in vitro and in vivo activity of miltefosine against penicillin-sensitive and penicillin-resistant pneumococcal strains was studied. The minimum inhibitory concentrations (MICs) of miltefosine were determined in cation-adjusted Mueller Hinton plus 2% lysed horse blood (CAMHB) and in Todd-Hewitt (TH) broth. The respective MICs were higher using CAMHB (128 and 64 mg/L) than using TH broth (4 and 8 mg/L). The in vivo activity was studied in a murine peritonitis-sepsis model. Miltefosine was orally administered at doses of 15 and 30 mg/kg/day after, at the time of, and before bacterial challenge for 3-5 days. All control and 16 out of the 17 (94.1%) miltefosine-treated animals that were inoculated with the penicillin-sensitive strain died. No survival was observed among control and miltefosine-treated animals inoculated with the penicillin-resistant pneumococcal strain. The in vivo unresponsiveness of miltefosine in this sepsis model could be attributed to some inhibitory effect of blood, inadequate pharmacokinetics and/or the extracellular localization of the pneumococcus.
Huelves
L
L
Department of Medical Microbiology and Antimicrobial Chemotherapy, Fundaćion Jiménez Díaz, Madrid, Spain. lhuelves@fjd.es <lhuelves@fjd.es>
Del Prado
G
G
Gracia
M
M
Rodríguez-Cerrato
V
V
Ponte
C
C
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001431:Bacteriological Techniques; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D010538:Peritonitis / Q000188:drug therapy; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D010767:Phosphorylcholine; C039128:miltefosine