Development of experimental pneumonia by infection with penicillin-insensitive Streptococcus pneumoniae in guinea pigs and their treatment with amoxicillin, cefotaxime, and meropenem

Abstract

Acute respiratory infection with penicillin-insensitive Streptococcus pneumoniae (MIC and MBC, 1 and 2 micrograms/ml, respectively) was established in guinea pigs. Intratracheal instillation of 0.5 ml of an overnight culture of S. pneumoniae concentrated 25 times (approximately 3 x 10(9) CFU) induced a bacteremic and fatal pneumonia in > 85% of untreated animals within 46 h, with a mean +/- standard deviation bacterial count of 8.83 +/- 1.11 log10 CFU in lung homogenates. This model was used to evaluate the efficacies of two doses each of amoxicillin, cefotaxime, and meropenem given 1 h after bacterial inoculation. The antibiotics were given at 8-h intervals for up to a total of four injections. The dose of 50 mg of any antibiotic per kg of body weight gave 66.6% survival, compared with 5.05% survival for untreated control animals (P < 0.001). A dose of 200 mg/kg gave a survival rate of 77.8% for meropenem and 83.3% for amoxicillin and cefotaxime, while survival for untreated controls was 11.1% (P < 0.001). Although antibiotic treatment decreased mortality compared with that in untreated controls, the antibiotics contributed to a high early (less than 9 h after bacterial inoculation) mortality, being 53.5% compared with only 6.06% for the untreated controls (P < 0.001). Quantitative cultures of the lungs of animals that died during the 46-h observation period or that were killed after this time showed a significant reduction in the numbers of organisms among treated animals compared with numbers among the control animals (P < 0.001). The described model is an appropriate system for evaluating antibiotic efficacy in invasive pulmonary infection caused by penicillin-insensitive S. pneumoniae.

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.…”

Pathogenesis of Streptococcus zooepidemicus infection after intratracheal inoculation in llamas

“…8 In other species, streptococcal bacteremia commonly is thought to develop secondary to respiratory tract infection. 9,10 In our experience, S zooepidemicus is a rare contributor to oral infections 11 and is not isolated from the distal portion of the respiratory tract of healthy camelids. 12 This suggests that camelids in North America do not commonly harbor this organism and that infection through the respiratory tract could develop.…”

Cytokine Kinetics and Other Host Factors in Response to Pneumococcal Pulmonary Infection in Mice

“…While most bacterium-induced pneumonia rodent models have been used to evaluate antibiotic pharmacokinetics and efficacy (7,8,50,59,67,84,87), various elements of the host response, including chemokines, pro-and anti-inflammatory cytokines, oxygen radicals, blood components, and immune and nonimmune cells, have also been characterized (10,25,45,74,77,81,86). Some pathogenesis studies have focused on interactions between bacterial or host factors, histological lesions, and edema (11,19,47,78).…”