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The postantibiotic effect: a review of in vitro and in vivo data
G G Zhanel1, D J Hoban, G K Harding
1Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Abstract:
The term postantibiotic effect (PAE) refers to a period of time after complete removal of an antibiotic during which there is no growth of the target organism. The PAE appears to be a feature of most antimicrobial agents and has been documented with a variety of common bacterial pathogens. Several factors influence the presence or duration of the PAE including the type of organism, type of antimicrobial, concentration of antimicrobial, duration of antimicrobial exposure, and antimicrobial combinations. In vitro, beta-lactam antimicrobials demonstrate a PAE against gram-positive cocci but fail to produce a PAE with gram-negative bacilli. Antimicrobials that inhibit RNA or protein synthesis produce an in vitro PAE against gram positive cocci and also produce a PAE against gram-negative bacilli. In vitro methods used to determine the PAE include colony counts, optical density, and measurement of adenosine triphosphate in bacteria. The exact mechanisms by which antimicrobials induce the PAE have not been clearly delineated. Animal studies reveal in vivo PAEs in accordance with PAEs obtained in vitro for most organism/antimicrobial combinations. The clinical relevance of the PAE is probably most important when designing dosage regimens. The presence of a long PAE allows aminoglycosides to be dosed infrequently; the lack of an in vivo PAE suggests that beta-lactam antimicrobials require frequent or continuous dosing. Important questions remain to be answered concerning the PAE.
Insights
The postantibiotic effect (PAE) is a crucial period where bacteria don't grow after antibiotic removal. Understanding PAE helps optimize antimicrobial drug dosing for better treatment outcomes.
Area of Science:
- Microbiology
- Pharmacology
Background:
- The postantibiotic effect (PAE) describes the suppressed microbial growth following antibiotic exposure.
- PAE is observed with various antimicrobial agents and bacterial pathogens.
- Factors influencing PAE include organism type, antimicrobial agent, concentration, exposure duration, and combinations.
Purpose of the Study:
- To review the characteristics and implications of the postantibiotic effect (PAE).
- To explore the in vitro and in vivo findings related to PAE.
- To discuss the clinical relevance of PAE in antimicrobial therapy.
Main Methods:
- Literature review of studies investigating the postantibiotic effect.
- Analysis of in vitro data using methods like colony counts, optical density, and ATP measurement.
- Examination of in vivo animal studies and their correlation with in vitro findings.
Main Results:
- Beta-lactams show PAE against Gram-positive cocci but not Gram-negative bacilli in vitro.
- RNA or protein synthesis inhibitors exhibit PAE against both Gram-positive and Gram-negative bacteria in vitro.
- In vivo PAE generally aligns with in vitro observations.
Conclusions:
- PAE is a significant factor in designing antimicrobial dosage regimens.
- Long PAE of aminoglycosides permits infrequent dosing.
- Lack of in vivo PAE for beta-lactams suggests frequent or continuous administration is necessary.