Treatment of experimental pneumonia due to penicillin-resistant Streptococcus pneumoniae in immunocompetent rats

Abstract

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.

Management of Infections Due to Antibiotic-Resistant Streptococcus pneumoniae

“…Animal models of pneumococcal pneumonia have been used to evaluate the efficacy of penicillin, extended-spectrum cephalosporins, carbapenems, vancomycin, and selected fluoroquinolones in the treatment of infection due to penicillinresistant strains. Different conditions such as induction of leukopenia, use of a bacterial inoculum in agar, or infection of different species of rodents were used in these studies (13,60,97,121,125,139). In general, higher doses of penicillin are superior to lower doses in clearing bacteria from the lungs and in decreasing the mortality.…”

Aerosol Infection Model of Tuberculosis in Wistar Rats

“…Rats have significantly contributed to modeling of variety of human pulmonary bacterial [8], fungal [9] and viral infections [10, 11] due to an increasing availability of rat immunological reagents. In recent years, several rat strains like Lewis, American cotton rats [12], and diabetic rat strains [13] have been successfully used to develop infection model of tuberculosis, particularly for investigating pathology and immune responses [14, 15].…”

Retention of neutralising activity by recombinant anti-pneumolysin antibody fragments

“…Streptococcus pneumoniae is a major cause of pneumonia and meningitis, is frequently isolated from immunocompromised individuals and accounts for 60–80% of all bacterial pneumonitis treated [1]. Disturbingly, the number of strains resistant to penicillin, to multiple antibiotics and cephalosporin continues to increase [2–4]. Resistant and multiresistant strains are found world‐wide and are showing an increasing geographical spread [5–7].…”