TROVAFLOXACIN DELAYS THE ANTIBIOTIC-INDUCED INFLAMMATORY RESPONSE IN EXPERIMENTAL PNEUMOCOCCAL MENINGITIS

This study evaluates the ability of the new fluoroquinolone trovafloxa cin to attenuate the inflammatory burst known to occur after initiatio n of antibiotic treatment in pneumococcal meningitis. After exposure t o trovafloxacin or ceftriaxone for 3 h in vitro, Streptococcus pneumon iae was injected intracisternally (ic) into rabbits every 3 h over 9 h (n = 6 for each antibiotic). Ceftriaxone-treated S. pneumoniae induce d consistently higher CSF leucocyte counts (median 2568/mu L versus 54 3/mu L at 6 h; P = 0.03; 4560/mu L versus 2207/mu L at 18 h; P = 0.03) than trovafloxacin-treated bacteria. Meningitis induced in rabbits by ic injection of live S. pneumoniae was treated with equal doses of tr ovafloxacin or ceftriaxone iv (ten per group). The bactericidal rates of both antibacterial agents in CSF were almost identical. In comparis on with ceftriaxone, trovafloxacin resulted in lower tumour necrosis f actor (TNF) and interleukin 1 beta (IL-1 beta) CSF levels 2 h after th e initiation of treatment (TNF levels, median 26 U/mL versus 141 U/mL; P = 0.02; IL-1 beta levels 455 pg/mL versus 1399 pg/mL; P = 0.02). Tw elve hours after initiation of therapy, however, TNF and IL-1 beta wer e higher in trovafloxacin-treated animals (TNF, 61 U/mL versus 7 U/mL; P = 0.001; IL-1 beta, 4320 pg/mL versus 427 pg/mL; P = 0.006). The in crease 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 concl usion, S. pneumoniae treated in vitro with trovafloxacin induced less CSF leucocytosis than ceftriaxone-treated S. pneumoniae. After ic inoc ulation of live S. pneumoniae, trovafloxacin therapy delayed, but did not inhibit, the release of the proinflammatory cytokines TNF and IL-1 beta, probably by slowing the liberation of bacterial cell wall compo nents into the subarachnoid space.