hr-810 and Pneumonia--Pneumococcal

A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in immunocompetent rats and could be used to explore the pathophysiology and to evaluate optimal therapy of this infection in the immunocompetent host.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Cefpirome; Cephalosporins; Culture Media; Half-Life; Lung; Male; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumonia, Pneumococcal; Rats; Rats, Wistar; Streptococcus pneumoniae; Vancomycin

A new injectable cephem antibiotic, cefpirome (CPR), was evaluated clinically in children. CPR was effective in all the 17 evaluable cases with acute bacterial infections including 1 case of purulent meningitis due to Haemophilus influenzae type b. Diarrhea and elevation of serum GOT and GPT were associated with CPR therapy in 2 young infants, although they were mild and transient. The plasma T 1/2 beta of CPR was 1.17 +/- 0.22 hours after bolus injection and mostly excreted in 6 to 8 hours into urine of children with normal renal functions. The data indicate that CPR is safe and effective, when used in children with susceptible bacterial infections.

Topics: Bacterial Infections; Cefpirome; Cephalosporins; Child; Child, Preschool; Drug Evaluation; Female; Half-Life; Humans; Infant; Male; Pneumonia, Pneumococcal