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. 1996 Dec;40(12):2698–2702. doi: 10.1128/aac.40.12.2698

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

C Ponte 1, A Parra 1, E Nieto 1, F Soriano 1
PMCID: PMC163606  PMID: 9124825

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.

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Selected References

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  1. Appelbaum P. C. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis. 1992 Jul;15(1):77–83. doi: 10.1093/clinids/15.1.77. [DOI] [PubMed] [Google Scholar]
  2. Azoulay-Dupuis E., Vallee E., Veber B., Bedos J. P., Bauchet J., Pocidalo J. J. In vivo efficacy of a new fluoroquinolone, sparfloxacin, against penicillin-susceptible and -resistant and multiresistant strains of Streptococcus pneumoniae in a mouse model of pneumonia. Antimicrob Agents Chemother. 1992 Dec;36(12):2698–2703. doi: 10.1128/aac.36.12.2698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Briles D. E., Crain M. J., Gray B. M., Forman C., Yother J. Strong association between capsular type and virulence for mice among human isolates of Streptococcus pneumoniae. Infect Immun. 1992 Jan;60(1):111–116. doi: 10.1128/iai.60.1.111-116.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cox A. L., Meewis J. M., Horton R. Penetration into lung tissue after intravenous administration of amoxycillin/clavulanate. J Antimicrob Chemother. 1989 Nov;24 (Suppl B):87–91. doi: 10.1093/jac/24.suppl_b.87. [DOI] [PubMed] [Google Scholar]
  5. Drusano G. L. Role of pharmacokinetics in the outcome of infections. Antimicrob Agents Chemother. 1988 Mar;32(3):289–297. doi: 10.1128/aac.32.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fitzgeorge R. B., Lever S., Baskerville A. A comparison of the efficacy of azithromycin and clarithromycin in oral therapy of experimental airborne Legionnaires' disease. J Antimicrob Chemother. 1993 Jun;31 (Suppl E):171–176. doi: 10.1093/jac/31.suppl_e.171. [DOI] [PubMed] [Google Scholar]
  7. Fukasawa M., Sumita Y., Harabe E. T., Tanio T., Nouda H., Kohzuki T., Okuda T., Matsumura H., Sunagawa M. Stability of meropenem and effect of 1 beta-methyl substitution on its stability in the presence of renal dehydropeptidase I. Antimicrob Agents Chemother. 1992 Jul;36(7):1577–1579. doi: 10.1128/aac.36.7.1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gordin F. M., Rusnak M. G., Sande M. A. Evaluation of combination chemotherapy in a lightly anesthetized animal model of Pseudomonas pneumonia. Antimicrob Agents Chemother. 1987 Mar;31(3):398–403. doi: 10.1128/aac.31.3.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Greenblatt D. J., Kock-Weser J. Drug therapy. Clinical Pharmacokinetics (first of two parts). N Engl J Med. 1975 Oct 2;293(14):702–705. doi: 10.1056/NEJM197510022931406. [DOI] [PubMed] [Google Scholar]
  10. Harrison M. P., Moss S. R., Featherstone A., Fowkes A. G., Sanders A. M., Case D. E. The disposition and metabolism of meropenem in laboratory animals and man. J Antimicrob Chemother. 1989 Sep;24 (Suppl A):265–277. doi: 10.1093/jac/24.suppl_a.265. [DOI] [PubMed] [Google Scholar]
  11. Kawana M., Kawana C., Giebink G. S. Penicillin treatment accelerates middle ear inflammation in experimental pneumococcal otitis media. Infect Immun. 1992 May;60(5):1908–1912. doi: 10.1128/iai.60.5.1908-1912.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kelly H. C., Hutchison M., Haworth S. J. A comparison of the pharmacokinetics of meropenem after administration by intravenous injection over 5 min and intravenous infusion over 30 min. J Antimicrob Chemother. 1995 Jul;36 (Suppl A):35–41. doi: 10.1093/jac/36.suppl_a.35. [DOI] [PubMed] [Google Scholar]
  13. Makhoul I. R., Merzbach D., Lichtig C., Berant M. Antibiotic treatment of experimental Pseudomonas aeruginosa pneumonia in guinea pigs: comparison of aerosol and systemic administration. J Infect Dis. 1993 Nov;168(5):1296–1299. doi: 10.1093/infdis/168.5.1296. [DOI] [PubMed] [Google Scholar]
  14. McAllister C. K., O'Donoghue J. M., Beaty H. N. Experimental pneumococcal meningitis. II. Characterization and quantitation of the inflammatory process. J Infect Dis. 1975 Oct;132(4):355–360. doi: 10.1093/infdis/132.4.355. [DOI] [PubMed] [Google Scholar]
  15. Moine P., Vallée E., Azoulay-Dupuis E., Bourget P., Bédos J. P., Bauchet J., Pocidalo J. J. In vivo efficacy of a broad-spectrum cephalosporin, ceftriaxone, against penicillin-susceptible and -resistant strains of Streptococcus pneumoniae in a mouse pneumonia model. Antimicrob Agents Chemother. 1994 Sep;38(9):1953–1958. doi: 10.1128/aac.38.9.1953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nava J. M., Bella F., Garau J., Lite J., Morera M. A., Martí C., Fontanals D., Font B., Pineda V., Uriz S. Predictive factors for invasive disease due to penicillin-resistant Streptococcus pneumoniae: a population-based study. Clin Infect Dis. 1994 Nov;19(5):884–890. doi: 10.1093/clinids/19.5.884. [DOI] [PubMed] [Google Scholar]
  17. Pallares R., Liñares J., Vadillo M., Cabellos C., Manresa F., Viladrich P. F., Martin R., Gudiol F. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med. 1995 Aug 24;333(8):474–480. doi: 10.1056/NEJM199508243330802. [DOI] [PubMed] [Google Scholar]
  18. Pennington J. E., Ehrie M. G. Pathogenesis of Pseudomonas aeruginosa pneumonia during immunosuppression. J Infect Dis. 1978 Jun;137(6):764–774. doi: 10.1093/infdis/137.6.764. [DOI] [PubMed] [Google Scholar]
  19. Sato K., Quartey M. K., Liebeler C. L., Giebink G. S. Timing of penicillin treatment influences the course of Streptococcus pneumoniae-induced middle ear inflammation. Antimicrob Agents Chemother. 1995 Aug;39(8):1896–1898. doi: 10.1128/aac.39.8.1896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smith G. M., Abbott K. H. Development of experimental respiratory infections in neutropenic rats with either penicillin-resistant Streptococcus pneumoniae or beta-lactamase-producing Haemophilus influenzae. Antimicrob Agents Chemother. 1994 Mar;38(3):608–610. doi: 10.1128/aac.38.3.608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Trnovec T., Kállay Z., Durisová M., Bezek S., Navarová J. Survival after intramuscular or inhalation administration of gentamicin in neutropenic guinea pigs infected by Klebsiella pneumoniae. J Antimicrob Chemother. 1990 Jan;25(1):127–132. doi: 10.1093/jac/25.1.127. [DOI] [PubMed] [Google Scholar]
  22. Tuomanen E., Hengstler B., Rich R., Bray M. A., Zak O., Tomasz A. Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis. J Infect Dis. 1987 May;155(5):985–990. doi: 10.1093/infdis/155.5.985. [DOI] [PubMed] [Google Scholar]
  23. Vogelman B., Gudmundsson S., Leggett J., Turnidge J., Ebert S., Craig W. A. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J Infect Dis. 1988 Oct;158(4):831–847. doi: 10.1093/infdis/158.4.831. [DOI] [PubMed] [Google Scholar]

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