In Vivo Evaluation of Antibacterial Chemotherapeutic Substances

Miller, A. Kathrine

doi:10.1016/s0065-2164(08)70543-4

Cited by 6 publications

(1 citation statement)

References 83 publications

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“…Mice challenged intraperitoneally are most commonly used to assess the activities of therapeutic agents against infection with this organism. To predict the clinical effectiveness of antimicrobial agents more adequately, however, it is desirable to test their activities against infections that more closely resemble the target disease (21). Although there have been numerous reports on the production and characteristics of experimental respiratory tract infections with K. pneumoniae (2,7,9,13,20,22,(27)(28)(29)31), only a few have been concerned with chemotherapeutic evaluations (2,20,28).…”

mentioning

confidence: 99%

Experimental respiratory tract infection with Klebsiella pneumoniae DT-S in mice: chemotherapy with kanamycin

Nishi¹,

Tsuchiya²

1980

Antimicrob Agents Chemother

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Such factors as suspending medium, operating pressure, exposure time, inoculum size, and strain, sex, age, and weight of the animals were examined for their effects on the development of respiratory tract infection with Klebsiella pneumoniae DT-S in mice. The suspending medium was one of the most important factors. Aerosol challenge with a 109 colony-forming units per ml resulted in deposition of 104 colony-forming units of the organisms in the lung. The numbers of organisms in the lung increased rapidly, and by 30 h, a well-developed pneumonia was apparent. All the mice died within 4 days after infection. The therapeutic effectiveness of single-dose kanamycin regimens decreased markedly with a delay in administration. The effectiveness of multi-dose kanamycin regimens was influenced by the frequency of dosage. Thus a 12-h dosage schedule was superior to a 24-h regimen. Administration of 20 mg of kanamycin per kg at 12-h intervals for 10 days, initiated 30 h after infection, provided a complete cure. The infecting organisms in the lung, trachea, and blood were eradicated by the kanamycin therapy, but those in the nasal cavity were difficult to eliminate.

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mentioning

confidence: 99%

Experimental respiratory tract infection with Klebsiella pneumoniae DT-S in mice: chemotherapy with kanamycin

Nishi¹,

Tsuchiya²

1980

Antimicrob Agents Chemother

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Antibiotica

Rehm

1980

Industrielle Mikrobiologie

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Animal models as predictors of the safety and efficacy of antibiotics

Zak

O’Reilly

1990

Eur. J. Clin. Microbiol. Infect. Dis.

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As opposed to the testing of safety, the testing of the efficacy of antibiotics in animals is not specified in any directives or guidelines and not explicitly required by regulatory authorities. There exists, however, no doubt that in the evaluation of new compounds testing of both safety and efficacy forms an essential link between in vitro tests and clinical trials. It is inconceivable that clinicians would be prepared to conduct a trial in patients without evidence of the efficacy of the antibiotic in question in an appropriate animal model of infection. Both the models for testing safety and those for testing efficacy suffer from a number of shortcomings. If investigators are aware of these deficiencies and take them into account when interpreting the results, the predictive value of the models can be significantly enhanced.

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In Vivo Evaluation of Antibacterial Chemotherapeutic Substances

Cited by 6 publications

References 83 publications

Experimental respiratory tract infection with Klebsiella pneumoniae DT-S in mice: chemotherapy with kanamycin

Experimental respiratory tract infection with Klebsiella pneumoniae DT-S in mice: chemotherapy with kanamycin

Antibiotica

Animal models as predictors of the safety and efficacy of antibiotics

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