Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Jun;40(6):1520–1525. doi: 10.1128/aac.40.6.1520

Noncompromised penicillin-resistant pneumococcal pneumonia CBA/J mouse model and comparative efficacies of antibiotics in this model.

K Tateda 1, K Takashima 1, H Miyazaki 1, T Matsumoto 1, T Hatori 1, K Yamaguchi 1
PMCID: PMC163360  PMID: 8726030

Abstract

The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In this model, doses of penicillin G of 0.6 mg/kg of body weight given six times at 1-h intervals produced effective pulmonary clearance of a penicillin-susceptible strain (penicillin G MIC, 0.015 microgram/ml), while doses of 40 mg/kg given six times at 1-h intervals were required to clear a penicillin-resistant strain (penicillin G MIC, 1 microgram/ml). Imipenem (MIC, 0.25 microgram/ml) was the most active antibiotic tested against the penicillin-resistant strain, with a calculated dose of 0.42 mg/kg given six times at 1-h intervals, resulting in a 2-log decrease in the number of pulmonary bacteria. Comparable effects were seen with vancomycin (MIC, 0.5 microgram/ml), cefotaxime (MIC, 0.5 microgram/ml), and penicillin G at doses of 3.3, 5.5, and 31.0 mg/kg given six times at 1-h intervals, respectively. The pharmacokinetic profile of vancomycin in infected lungs was superior to those of the other antibiotics, especially in regard to the elimination half-life (215.4 min for vancomycin versus 15.0, 14.5, and 14.5 min for penicillin G, cefotaxime, and imipenem, respectively). Both imipenem and vancomycin allowed 90% survival when 40-mg/kg doses were administered twice a day beginning 5 days after infection. Survival rates with penicillin G (160-mg/kg doses) and cefotaxime (40-mg/kg doses) were 40 and 30%, respectively, while no saline-treated mice survived. The present study shows that the CBA/J mouse pneumonia model may be useful for evaluating antibiotic efficacies against penicillin-resistant pneumococcal pneumonia in immunocompetent individuals. Our data suggest that imipenem and vancomycin may be the most active agents against penicillin-resistant S. pneumoniae pneumonia.

Full Text

The Full Text of this article is available as a PDF (821.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Austrian R. Pneumococcal pneumonia. Diagnostic, epidemiologic, therapeutic and prophylactic considerations. Chest. 1986 Nov;90(5):738–743. doi: 10.1378/chest.90.5.738. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Barakett V., Lesage D., Delisle F., Richard G., Petit J. C. Killing kinetics of imipenem against penicillin-resistant Streptococcus pneumoniae. J Antimicrob Chemother. 1994 May;33(5):1025–1028. doi: 10.1093/jac/33.5.1025. [DOI] [PubMed] [Google Scholar]
  5. Barry B., Muffat-Joly M., Gehanno P., Pocidalo J. J. Effect of increased dosages of amoxicillin in treatment of experimental middle ear otitis due to penicillin-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother. 1993 Aug;37(8):1599–1603. doi: 10.1128/aac.37.8.1599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bingen E., Doit C., Farinotti R., Lambert-Zechovsky N. Killing kinetics of cefuroxime against Streptococcus pneumoniae in an in vitro model simulating serum concentration profiles after intramuscular administration. Eur J Clin Microbiol Infect Dis. 1993 Apr;12(4):297–299. doi: 10.1007/BF01967263. [DOI] [PubMed] [Google Scholar]
  7. Caputo G. M., Appelbaum P. C., Liu H. H. Infections due to penicillin-resistant pneumococci. Clinical, epidemiologic, and microbiologic features. Arch Intern Med. 1993 Jun 14;153(11):1301–1310. [PubMed] [Google Scholar]
  8. Catalán M. J., Fernández J. M., Vazquez A., Varela de Seijas E., Suárez A., Bernaldo de Quirós J. C. Failure of cefotaxime in the treatment of meningitis due to relatively resistant Streptococcus pneumoniae. Clin Infect Dis. 1994 May;18(5):766–769. doi: 10.1093/clinids/18.5.766. [DOI] [PubMed] [Google Scholar]
  9. Doit C. P., Bonacorsi S. P., Fremaux A. J., Sissia G., Cohen R., Geslin P. L., Bingen E. H. In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis. Antimicrob Agents Chemother. 1994 Nov;38(11):2655–2659. doi: 10.1128/aac.38.11.2655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ducharme M. P., Slaughter R. L., Edwards D. J. Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight. Ther Drug Monit. 1994 Oct;16(5):513–518. doi: 10.1097/00007691-199410000-00013. [DOI] [PubMed] [Google Scholar]
  11. Feldman C., Kallenbach J. M., Miller S. D., Thorburn J. R., Koornhof H. J. Community-acquired pneumonia due to penicillin-resistant pneumococci. N Engl J Med. 1985 Sep 5;313(10):615–617. doi: 10.1056/NEJM198509053131006. [DOI] [PubMed] [Google Scholar]
  12. Friedland I. R., Paris M., Shelton S., McCracken G. H. Time-kill studies of antibiotic combinations against penicillin-resistant and -susceptible Streptococcus pneumoniae. J Antimicrob Chemother. 1994 Aug;34(2):231–237. doi: 10.1093/jac/34.2.231. [DOI] [PubMed] [Google Scholar]
  13. Gray B. M., Dillon H. C., Jr Clinical and epidemiologic studies of pneumococcal infection in children. Pediatr Infect Dis. 1986 Mar-Apr;5(2):201–207. doi: 10.1097/00006454-198603000-00009. [DOI] [PubMed] [Google Scholar]
  14. Heikkilä A. M., Erkkola R. U. The need for adjustment of dosage regimen of penicillin V during pregnancy. Obstet Gynecol. 1993 Jun;81(6):919–921. [PubMed] [Google Scholar]
  15. Knudsen J. D., Frimodt-Møller N., Espersen F. Experimental Streptococcus pneumoniae infection in mice for studying correlation of in vitro and in vivo activities of penicillin against pneumococci with various susceptibilities to penicillin. Antimicrob Agents Chemother. 1995 Jun;39(6):1253–1258. doi: 10.1128/aac.39.6.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Loo V. G., Lavellée J., McAlear D., Robson H. G. The in-vitro susceptibilities of 326 Streptococcus pneumoniae isolates to nine antimicrobial agents including penicillin and newer quinolones. J Antimicrob Chemother. 1994 Mar;33(3):641–645. doi: 10.1093/jac/33.3.641. [DOI] [PubMed] [Google Scholar]
  17. Macfarlane J. T., Finch R. G., Ward M. J., Macrae A. D. Hospital study of adult community-acquired pneumonia. Lancet. 1982 Jul 31;2(8292):255–258. doi: 10.1016/s0140-6736(82)90334-8. [DOI] [PubMed] [Google Scholar]
  18. McCracken G. H., Jr, Sakata Y. Antimicrobial therapy of experimental meningitis caused by Streptococcus pneumoniae strains with different susceptibilities to penicillin. Antimicrob Agents Chemother. 1985 Feb;27(2):141–145. doi: 10.1128/aac.27.2.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Mouton J. W., van den Anker J. N. Meropenem clinical pharmacokinetics. Clin Pharmacokinet. 1995 Apr;28(4):275–286. doi: 10.2165/00003088-199528040-00002. [DOI] [PubMed] [Google Scholar]
  21. Pallares R., Gudiol F., Liñares J., Ariza J., Rufi G., Murgui L., Dorca J., Viladrich P. F. Risk factors and response to antibiotic therapy in adults with bacteremic pneumonia caused by penicillin-resistant pneumococci. N Engl J Med. 1987 Jul 2;317(1):18–22. doi: 10.1056/NEJM198707023170104. [DOI] [PubMed] [Google Scholar]
  22. París M. M., Hickey S. M., Uscher M. I., Shelton S., Olsen K. D., McCracken G. H., Jr Effect of dexamethasone on therapy of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother. 1994 Jun;38(6):1320–1324. doi: 10.1128/aac.38.6.1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rondanelli R., Dionigi R. V., Calvi M., Dell'Antonio M., Corsico G., Mapelli A. Cefotaxime therapy of lower respiratory tract infections in intensive-care patients. Int J Clin Pharmacol Res. 1987;7(1):73–76. [PubMed] [Google Scholar]
  24. Spika J. S., Facklam R. R., Plikaytis B. D., Oxtoby M. J. Antimicrobial resistance of Streptococcus pneumoniae in the United States, 1979-1987. The Pneumococcal Surveillance Working Group. J Infect Dis. 1991 Jun;163(6):1273–1278. doi: 10.1093/infdis/163.6.1273. [DOI] [PubMed] [Google Scholar]
  25. Woodhead M. A., Macfarlane J. T., McCracken J. S., Rose D. H., Finch R. G. Prospective study of the aetiology and outcome of pneumonia in the community. Lancet. 1987 Mar 21;1(8534):671–674. doi: 10.1016/s0140-6736(87)90430-2. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES