Development of experimental pneumonia by infection with penicillin-insensitive Streptococcus pneumoniae in guinea pigs and their treatment with amoxicillin, cefotaxime, and meropenem.
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.
Ponte
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Department of Medical Microbiology, Fundación Jiménez Díaz, Madrid, Spain.
Parra
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Nieto
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Soriano
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D000658:Amoxicillin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D002439:Cefotaxime / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000382:microbiology; D000077731:Meropenem; D010403:Penicillin Resistance; D010406:Penicillins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013845:Thienamycins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
D002511:Cephalosporins; D010406:Penicillins; D013845:Thienamycins; D000658:Amoxicillin; D000077731:Meropenem; D002439:Cefotaxime