Journal of Antimicrobial Chemotherapy, Vol 39, 781-788, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
R Nau, G Zysk, H Schmidt, FR Fischer, AK Stringaris, K Stuertz and W Bruck
This study evaluates the ability of the new fluoroquinolone trovafloxacin
to attenuate the inflammatory burst known to occur after initiation of
antibiotic treatment in pneumococcal meningitis. After exposure to
trovafloxacin or ceftriaxone for 3 h in vitro, Streptococcus pneumoniae was
injected intracisternally (i.c.) into rabbits every 3 h over 9 h (n = 6 for
each antibiotic). Ceftriaxone- treated S. pneumoniae induced consistently
higher CSF leucocyte counts (median 2568/microL versus 543/microL at 6 h; P
= 0.03; 4560/microL versus 2207/microL at 18 h; P = 0.03) than
trovafloxacin-treated bacteria. Meningitis induced in rabbits by i.c.
injection of live S. pneumoniae was treated with equal doses of
trovafloxacin or ceftriaxone i.v. (ten per group). The bactericidal rates
of both antibacterial agents in CSF were almost identical. In comparison
with ceftriaxone, trovafloxacin resulted in lower tumour necrosis factor
(TNF) and interleukin 1beta (IL-1beta) CSF levels 2 h after the initiation
of treatment (TNF levels, median 26 U/mL versus 141 U/mL; P = 0.02; IL-
1beta levels 455 pg/mL versus 1399 pg/mL; P = 0.02). Twelve hours after
initiation of therapy, however, TNF and IL-1beta were higher in
trovafloxacin-treated animals (TNF, 61 U/mL versus 7 U/mL; P = 0.001;
IL-1beta, 4320 pg/mL versus 427 pg/mL; P = 0.006). The increase in CSF
lactate was less during trovafloxacin therapy than with ceftriaxone
(median: 2.0 mmol/L versus 4.0 mmol/L; P = 0.03). In conclusion, S.
pneumoniae treated in vitro with trovafloxacin induced less CSF
leucocytosis than ceftriaxone-treated S. pneumoniae. After i.c. inoculation
of live S. pneumoniae, trovafloxacin therapy delayed, but did not inhibit,
the release of the proinflammatory cytokines TNF and IL-1beta, probably by
slowing the liberation of bacterial cell wall components into the
subarachnoid space.
JOURNAL ARTICLE
Trovafloxacin delays the antibiotic-induced inflammatory response in experimental pneumococcal meningitis
Department of Neurology, University of Gottingen, Germany.
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