title: Activity of quinupristin/dalfopristin against Streptococcus pneumoniae in vitro and in vivo in the rabbit model of experimental meningitis.
abstract: We tested the efficacy of quinupristin/dalfopristin, an antibiotic made up of dalfopristin (70%) and quinupristin (30%) against a large panel of Streptococcus pneumoniae strains. The pneumococcal isolates (217) included 200 penicillin-resistant and 17 penicillin-susceptible clinical isolates. Eighty-nine of the 200 resistant bacteria showed an intermediate level and 111/200 showed a high level of resistance to penicillin. Of the highly resistant strains, 56/111 belonged to the multidrug-resistant Spanish/USA epidemic clone of S. pneumoniae, as defined by appropriate genetic techniques. The resistant panel also included six isolates of another multidrug-resistant epidemic clone: isolates with capsular type 6B belonging to the Spanish/Icelandic clone of S. pneumoniae. Quinupristin/dalfopristin had a uniform mean MIC of 0.25 mg/L against all pneumococcal isolates, including 37 strains representing a wide spectrum of erythromycin MICs, from 0.03 up to 8.0 mg/L. Quinupristin/dalfopristin showed powerful bactericidal activity against a penicillin-susceptible test strain in vitro and against representatives of both the Spanish/USA and the Spanish/Icelandic multidrug-resistant clones. The rate of bactericidal activity was independent of drug concentration between 2.5 x and 10 x MIC. Quinupristin/dalfopristin was also tested in a rabbit model of experimental meningitis using 50 mg/kg i.v. bolus injections and a penicillin-susceptible capsular type 3 S. pneumoniae strain as the test organism. Quinupristin/dalfopristin had no effect on the intracisternal growth of bacteria when the drug was injected before CSF inflammation, whereas it caused a 2 log kill in 2 h, after which bacterial growth in the CSF resumed, when injected i.v. at a time of inflammation. When a second dose was given 2 h later, this produced a 3 log loss of viability after 4 h. A single injection of ampicillin 50 mg/kg i.v. caused a similar 3 log kill after 4 h under comparable conditions.
authors.affiliation: Rockefeller University, New York, NY 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tarasi
authors.forename: L L
authors.initials: LL
authors.lastname: Dever
authors.forename: A
authors.initials: A
authors.lastname: Tomasz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002682:Chinchilla; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D008297:Male; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development; D014769:Virginiamycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014769:Virginiamycin; C062940:quinupristin-dalfopristin