Journal of Antimicrobial Chemotherapy, Vol 41, 349-355, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
H Sambatakou, EJ Giamarellos-Bourboulis, P Grecka, Z Chryssouli and H Giamarellou
Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a
semisynthetic derivative of pristinamycins IA and IIB. The following
properties of RP59500 were investigated: (i) its in-vitro activity against
164 hospital isolates of Staphylococcus aureus, 101 of which were
methicillin-resistant (MRSA); (ii) its killing effect against 24 MRSA and
seven methicillin-susceptible (MSSA) isolates; (iii) its interactions with
rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to
both rifampicin and ciprofloxacin and 12 resistant to both, at 1 x MIC, 2 x
MIC and 4 x MIC. Rifampicin and ciprofloxacin were applied at a
concentration equal to their mean serum levels in order to establish the
clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of
quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and
2 mg/L for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and
0.25 mg/L for MSSA isolates. All isolates were inhibited by
quinupristin/dalfopristin. Its killing effect varied with concentration and
time, being optimal at 4 x MIC and after 24 h growth. Strains surviving 24
h exposure to this agent had much higher MICs than the parent strain, but
only a limited number of them became resistant. Quinupristin/dalfopristin
at 2 x MIC and 4 x MIC showed in-vitro synergy with rifampicin against
highly resistant isolates mainly at 6 h and 24 h of growth involving 50-83%
of MRSA isolates, and showed synergy with ciprofloxacin at 24 h involving
42- 75% of isolates. The MIC increase in colonies surviving at 24 h was
restricted by the presence of rifampicin or ciprofloxacin. In contrast, the
above combinations acted synergically over the total number of MRSA strains
susceptible to both rifampicin and ciprofloxacin. The above findings show
that quinupristin/dalfopristin is a very potent antistaphylococcal agent,
and that its activity against MRSA isolates is enhanced when it is combined
with rifampicin or ciprofloxacin.
ORIGINAL ARTICLES
In-vitro activity and killing effect of quinupristin/dalfopristin (RP59500) on nosocomial Staphylococcus aureus and interactions with rifampicin and ciprofloxacin against methicillin-resistant isolates
First Department of Propedeutic Medicine, Athens Medical School, Greece.
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