virginiamycin and Meningitis--Pneumococcal

The inflammatory response following initiation of antibiotic therapy and parameters of neuronal damage were compared during intravenous treatment with quinupristin/dalfopristin (100 mg/kg as either a short or a continuous infusion) and ceftriaxone (10 mg/kg/h) in a rabbit model of Streptococcus pneumoniae meningitis. With both modes of administration, quinupristin/dalfopristin 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 cerebrospinal fluid (CSF) were significantly lower in the two quinupristin/dalfopristin groups than in ceftriaxone-treated rabbits. The median LTA/TA concentrations (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 infection: 116 (60/368) ng/mL for continuous infusion of quinupristin/dalfopristin 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 concentration of neuron-specific enolase (NSE) 24 h after infection was significantly lower in animals treated with quinupristin/dalfopristin: 4.6 (3.3/5.7) microg/L (continuous infusion) and 3.6 (2.9/4.7) microg/L (short duration infusion) than in those treated with ceftriaxone (17.7 (8.8/78.2) microg/L) (P = 0.03 and 0.009 respectively). In conclusion, antibiotic treatment with quinupristin/dalfopristin attenuated the inflammatory response within the subarachnoid space after initiation of antibiotic therapy. The concentration of NSE in the CSF, taken as a measure of neuronal damage, was lower in quinupristin/dalfopristin-treated rabbits than in ceftriaxone-treated rabbits.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Cerebrospinal Fluid Proteins; Disease Models, Animal; Inflammation; Lactic Acid; Lipopolysaccharides; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Neurons; Phosphopyruvate Hydratase; Rabbits; Streptococcus pneumoniae; Subarachnoid Space; Teichoic Acids; Tumor Necrosis Factor-alpha; Virginiamycin

In the rabbit model of Streptococcus pneumoniae meningitis, treatment with rifabutin, quinupristin-dalfopristin, moxifloxacin and trovafloxacin led to smaller increases of the CSF concentrations of the pro-inflammatory cell wall components lipoteichoic and teichoic acids (LTA and TA) than did treatment with ceftriaxone. Low doses of moxifloxacin were associated with higher LTA and TA concentrations in CSF than were high doses.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Aza Compounds; Ceftriaxone; Cephalosporins; Disease Models, Animal; Fluoroquinolones; Immunoenzyme Techniques; Lipopolysaccharides; Meningitis, Pneumococcal; Moxifloxacin; Naphthyridines; Polysaccharides, Bacterial; Quinolines; Rabbits; Reference Values; Rifabutin; Teichoic Acids; Virginiamycin

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.

Topics: Animals; Anti-Bacterial Agents; Chinchilla; Colony Count, Microbial; Disease Models, Animal; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Rabbits; Streptococcus pneumoniae; Virginiamycin

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Meningitis, Pneumococcal; Rabbits; Streptococcus pneumoniae; Virginiamycin