Journal of Antimicrobial Chemotherapy, Vol 39, 121-127, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
A Tarasi, LL Dever and A Tomasz
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.
ORIGINAL ARTICLES
Activity of quinupristin/dalfopristin against Streptococcus pneumoniae in vitro and in vivo in the rabbit model of experimental meningitis
Rockefeller University, New York, NY 10021, USA.
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