Quinupristin/dalfopristin attenuates the inflammatory response and reducesthe concentration of neuron-specific enolase in the cerebrospinal fluid ofrabbits with experimental Streptococcus pneumoniae meningitis

The inflammatory response following initiation of antibiotic therapy and pa rameters of neuronal damage were compared during intravenous treatment with quinupristin/dalfopristin (100 mg/kg as either a short or a continuous inf usion) and ceftriaxone (10 mg/kg/h) in a rabbit model of Streptococcus pneu moniae meningitis. With both modes of administration, quinupristin/dalfopri stin was less bactericidal than ceftriaxone. However, the concentration of proinflammatory cell wall components (lipoteichoic acid (LTA) and teichoic acid (TA)) and the activity of tumour necrosis factor (TNF) in cerebrospina l fluid (CSF) were significantly lower in the two quinupristin/dalfopristin groups than in ceftriaxone-treated rabbits. The median LTA/TA concentratio ns (25th/75th percentiles) were as follows: (i) 14 h after infection: 133 ( 72/155) ng/mL for continuous infusion of quinupristin/dalfopristin and 193 (91/308) ng/mL for short duration infusion, compared with 455 (274/2042) ng /mL for ceftriaxone (P = 0.002 and 0.02 respectively); (ii) 17 h after infe ction: 116 (60/368) ng/mL for continuous infusion of quinupristin/dalfopris tin and 117 (41/247) ng/mL for short duration infusion, compared with 694 ( 156/2173) ng/mL for ceftriaxone (P = 0.04 and 0.03 respectively). Fourteen hours after infection the median TNF activity (25th/75th percentiles) was 0 .2 (0.1/1.9) U/mL for continuous infusion of quinupristin/dalfopristin and 0.1 (0.01/3.5) U/mL for short duration infusion, compared with 30 (4.6/180) U/mL for ceftriaxone (P = 0.02 for each comparison); 17 h after infection the TNF activity was 2.8 (0.2/11) U/mL (continuous infusion of quinupristin /dalfopristin) and 0.1 (0.04/6.1) U/mL (short duration infusion), compared with 48.6 (18/169) U/mL for ceftriaxone (P = 0.002 and 0.001). The concentr ation of neuron-specific enolase (NSE) 24 h after infection was significant ly lower in animals treated with quinupristin/dalfopristin: 4.6 (3.3/5.7) m u g/L (continuous infusion) and 3.6 (2.9/4.7) mu g/L (short duration infusi on) than in those treated with ceftriaxone (17.7 (8.8/78.2) mu g/L) (P = 0. 03 and 0.009 respectively). in conclusion, antibiotic treatment with quinup ristin/dalfopristin attenuated the inflammatory response within the subarac hnoid space after initiation of antibiotic therapy. The concentration of NS E in the CSF, taken as a measure of neuronal damage, was lower in quinupris tin/dalfopristin-treated rabbits than in ceftriaxone-treated rabbits.