1990 Fiscal Year Final Research Report Summary
Effects of Biological Response Modifiers (BRM) in the Treatment of Severe Respiratory Infections
| Project/Area Number |
01571285
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Nursing
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
KAWANE Hiroshi Department of Medicine, Kawasaki Medical School, 医学部・呼吸器内科, 助教授 (80140490)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHAMA Chikara Dpt. of Clinical Pathology, Kawasaki Meical School, 検査診断学, 講師 (50180336)
YAGI Susumu Department of Medicine, Kawasaki Medical School, 呼吸器内科, 講師 (60157956)
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| Project Period (FY) |
1989 – 1990
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| Keywords | BRM / Antibiotics / Synergistic effects / Host defense / Experimental pneumonia |
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| Research Abstract |
Infections, especially acute bacterial pneumonia, are common and major cause of morbidity and mortality in immunocompromised patients. In the past few decades a number of new antibiotics have been developed to fight gram negative bacterial infections. Excellent antibacterial activity and good clinical effects have been reported in the majority cases. But in some cases with severely depressed immune conditions, treatment often fails even when sufficient antibiotics are administered. Recently, many investigations have shown the efficacy of immunosuppresed patients. In this study, we investigated the synergistic effects of an antibiotic [cefmenoxime (CMX)] and Romultide [MDP-Lys(L18)] in the treatment of experimental Klebsiella pneumonia in mice. L18 is a newly developed derivative of MDP and has been reported to be efficacious in activating non-specific host resistance against various microbial pathogens when administered parenterally or orally prior to the infections. While about 90% of untreated animals died within a week, the mortality rate of animals treated with CMX alone at a dose of 40mg/kg/day was 60% at 7 days after the infection. When one or two doses of L18 was administered before or after the infection concomitantly with CMX, remarkable improvements of survival rates were observed. Histopathological section of the lung of mice treated with CMX and L18 showed slower progression of infection than that of mice treated with CMX alone. Significant differences were also found in quantitative cultures of viable bacteria in the lungs at 1-4 days after infection, While viable bacterial counts of the lungs of control and CMX treated groups showed rapid increase at 24-48hours after the infection, they remained less than the challenged counts (X10^4) in the lungs of mice treated with combination regimens. According to these results, we can conclude that L18 is a useful biological response modifier in the treatment of acute pulmonary bacterial infection.
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