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In vivo postantibiotic effect in a thigh infection in neutropenic mice
B Vogelman1, S Gudmundsson, J Turnidge
1Medical Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.
Abstract:
The postantibiotic effect (PAE) is the suppression of bacterial growth that persists after limited exposure of organisms to antimicrobial agents. We demonstrated and standardized the in vivo PAE in a thigh infection model in neutropenic mice. Inhibitors of protein and nucleic acid synthesis induced PAEs of 1.4-7.5 h against aerobic gram-negative bacilli, whereas beta-lactam antibiotics did not induce significant PAEs. Against aerobic gram-positive cocci, cell wall-active agents and inhibitors of protein and nucleic acid synthesis induced PAEs of 1.2-7.1 h, except for penicillins, which did not induce PAEs against streptococci. With few exceptions the in vivo PAE correlated well with the PAE reported in prior in vitro studies. Residual drug in thigh tissue did not cause the PAE. Theoretically, the presence of a PAE may allow antimicrobial agents to be given more intermittently without organism regrowth after drug levels fall below the minimal inhibitory concentration.
Insights
The postantibiotic effect (PAE) was demonstrated in vivo, showing suppressed bacterial growth after antibiotic exposure. This finding supports intermittent antimicrobial dosing strategies by confirming PAE in animal models.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The postantibiotic effect (PAE) describes the lag in bacterial growth after antimicrobial exposure.
- Understanding in vivo PAE is crucial for optimizing antibiotic treatment regimens.
Purpose of the Study:
- To demonstrate and standardize the in vivo postantibiotic effect (PAE) in a murine thigh infection model.
- To evaluate the correlation between in vivo and in vitro PAE findings.
Main Methods:
- Utilized a thigh infection model in neutropenic mice to assess in vivo PAE.
- Administered various antimicrobial agents targeting protein, nucleic acid, and cell wall synthesis.
- Measured bacterial regrowth post-antibiotic exposure to determine PAE duration.
Main Results:
- Inhibitors of protein and nucleic acid synthesis induced significant PAEs (1.4-7.5 h) against Gram-negative bacilli.
- Cell wall-active agents and protein/nucleic acid synthesis inhibitors showed PAEs (1.2-7.1 h) against Gram-positive cocci, with exceptions for penicillins.
- In vivo PAE generally correlated with previously reported in vitro studies, and residual drug was not the cause of PAE.
Conclusions:
- The in vivo postantibiotic effect was successfully demonstrated and standardized in a relevant animal model.
- PAE findings in vivo largely mirrored in vitro data, validating the model's utility.
- The existence of in vivo PAE supports the potential for intermittent antimicrobial dosing to prevent bacterial regrowth.