novobiocin and Pneumococcal-Infections

Topics: Acute Disease; Anti-Bacterial Agents; Bacitracin; Bronchitis; Chloramphenicol; Chronic Disease; Ear Diseases; Humans; Labyrinth Diseases; Laryngitis; Neomycin; Novobiocin; Otitis Externa; Otitis Media; Penicillins; Pneumococcal Infections; Polymyxins; Respiratory Tract Infections; Staphylococcal Infections; Streptococcal Infections; Streptomycin; Tetracycline; Tonsillitis; Tracheal Diseases

Therapeutic alternatives are needed against infections caused by highly multidrug-resistant Streptococcus pneumoniae. Novobiocin, an old antibiotic, was tested in vitro and in a murine sepsis model against one amoxicillin-susceptible and three amoxicillin-resistant strains [minimum inhibitory concentrations (MICs) 8-64 mg/L]. Novobiocin MICs for all strains were 0.25-0.5 mg/L. In sepsis, novobiocin and amoxicillin were evaluated at 25, 50, 100 and 200 mg/kg given at 1, 5, 24 and 48 h post bacterial challenge. The most effective regimens in animals infected with the amoxicillin-susceptible strain were 200 mg/kg novobiocin and 25 mg/kg amoxicillin, achieving 100% survival and undetectable organisms in the peritoneum. Among mice infected with amoxicillin-resistant S. pneumoniae, 200 mg/kg novobiocin gave the highest protection (90-100% survivors), followed by 200mg/kg amoxicillin (60-100%), 100 mg/kg novobiocin (50-87.5%) and 50 mg/kg amoxicillin (14.3-25%). The killing effect of antibiotics in the peritoneum (mean Deltalog(10) colony-forming units/mL between treated and control mice) was as follows: 200 mg/kg novobiocin (-6.6)>200 mg/kg amoxicillin (-5.6)>100 mg/kg novobiocin (-3.7) > 50 mg/kg amoxicillin (-0.7). Total plasma and ultrafiltrate pharmacokinetics of novobiocin (200 mg/kg, single dose) in non-infected mice showed, respectively, half-lives of 151 min and 215 min, area under the concentration-time curves (AUCs) of 945.0 mgh/L and 136.6 mgh/L and maximal concentrations of 147 mg/L and 18 mg/L. Novobiocin may be a promising agent for therapy of highly beta-lactam-resistant pneumococcal infections.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; beta-Lactams; Colony Count, Microbial; Drug Resistance, Bacterial; Female; Mice; Microbial Sensitivity Tests; Microbial Viability; Novobiocin; Peritoneum; Pneumococcal Infections; Sepsis; Streptococcus pneumoniae; Survival Analysis; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacitracin; Child; Child, Preschool; Chloramphenicol; Drug Therapy, Combination; Erythromycin; Eye Diseases; Female; Gentamicins; Humans; Infant; Male; Methicillin; Methods; Middle Aged; Neomycin; Nitrofurantoin; Novobiocin; Penicillin G; Penicillin Resistance; Pneumococcal Infections; Polymyxins; Streptococcus pneumoniae; Streptomycin; Tetracycline; Virulence

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Chloramphenicol; Chlortetracycline; Dihydrostreptomycin Sulfate; Drug Stability; Erythromycin; Gastric Juice; Hydrogen-Ion Concentration; Kanamycin; Male; Mice; Microbial Sensitivity Tests; Novobiocin; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rifampin; Solutions; Staphylococcal Infections; Staphylococcus; Streptococcal Infections

Topics: Anti-Bacterial Agents; Bronchitis; Chloramphenicol; Erythromycin; Haemophilus influenzae; Novobiocin; Penicillins; Pneumococcal Infections; Pneumonia; Scotland; Staphylococcal Infections; Statistics as Topic; Streptomycin; Tetracycline; Virus Diseases

Topics: Anti-Bacterial Agents; Bacitracin; Child; Chloramphenicol; Chlortetracycline; Drainage; Empyema; Erythromycin; Escherichia coli Infections; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Kanamycin; Novobiocin; Oleandomycin; Pediatrics; Penicillins; Pneumococcal Infections; Pneumothorax; Staphylococcal Infections; Streptococcal Infections; Sulfonamides; Surgical Procedures, Operative; Tetracycline; Vancomycin

Topics: Anti-Bacterial Agents; Bacitracin; Chloramphenicol; Drug Resistance, Microbial; Epidemiology; Erythromycin; Genetics; Kanamycin; Neomycin; Novobiocin; Oleandomycin; Penicillin Resistance; Pharmacology; Pneumococcal Infections; Research; Streptococcus pneumoniae; Streptomycin; Tetracycline