Evaluation of antimicrobial agents using an experimental pulmonary superinfection model with Aspergillus fumigatus and Pseudomonas aeruginosa in leukopenic mice
| Autor: | Shinzaburo Minami, Keizo Yamaguchi, Yasuo Watanabe, Kazuo Kizawa, Junichi Mitsuyama |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Microbiology (medical) Microbial Sensitivity Tests Biology medicine.disease_cause Microbiology Aspergillus fumigatus Mice Anti-Infective Agents Amphotericin B medicine Animals Aspergillosis Pseudomonas Infections Pharmacology (medical) Mycosis Antibacterial agent Mice Inbred ICR Lung Diseases Fungal Cilastatin Pseudomonas aeruginosa Leukopenia bacterial infections and mycoses medicine.disease biology.organism_classification Disease Models Animal Infectious Diseases Viable count Superinfection Drug Therapy Combination medicine.drug |
| Zdroj: | Journal of Infection and Chemotherapy. 9:144-150 |
| ISSN: | 1341-321X |
| DOI: | 10.1007/s10156-003-0234-x |
| Popis: | The therapeutic efficacy of amphotericin B (AmB), imipenem/cilastatin (IPM/CS), pazufloxacin (PZFX) mesilate, and combinations of these, was evaluated using an experimental pulmonary superinfection model in mice caused by Pseudomonas aeruginosa and Aspergillus fumigatus. The superinfected mice died within 3 days. Although the viable cell count of P. aeruginosa increased markedly from 10(3) to 10(8) CFU/lung on day 2 after infection, that of A. fumigatus decreased from 10(3) to 10(2) CFU/lung on that day, showing that P. aeruginosa facilitated the mortality in the superinfection. Extensive necrosis in the lung parenchyma and moderate hyphae proliferation of A. fumigatus were observed on day 2 after infection. Mice treated with PZFX mesilate (50 mg/kg per day) and the combination of PZFX mesilate (50 mg/kg per day) - AmB (2.5 mg/kg per day) showed prolonged survival in comparison to untreated control mice ( P0.05). In the PZFX mesilate-treated group, no significant necrosis was observed, but necrosis due to the hyphae proliferation of A. fumigatus was still observed in the lung parenchyma on day 6 after infection. However, neither significant necrosis nor hyphae proliferation of A. fumigatus was observed in mice treated with the combination of PZFX mesilate - AmB. On the other hand, the survival rates of mice treated with AmB (2.5 mg/kg per day), IPM/CS (50 mg/kg per day), and the IPM/CS-AmB combination were all less than 10%. The viable cell count of P. aeruginosa decreased in PZFX mesilate-alone group and in the combination of PZFX mesilate - AmB group, but no significant decrease in this count was observed in the IPM/CS and combination of IPM/CS-AmB group. The viable count of A. fumigatus was increased in the IPM/CS, PZFX mesilate-alone, and combination of IPM/CS-AmB groups, but the count was suppressed in the AmB-alone and the combination of PZFX mesilate - AmB group. In conclusion, this superinfection model would be useful to evaluate the therapeutic potential of combinations of antibacterial and antifungal agents, and the scheduling of drug administration in terminal infections caused by P. aeruginosa and A. fumigatus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect