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Pharmacokinetic contributions to postantibiotic effects. Focus on aminoglycosides
1Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Abstract:
The postantibiotic effect (PAE) refers to a period of time after complete removal of an antimicrobial 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. Various factors influence the presence or duration of the PAE including the type of organism, type of antimicrobial, concentration of antimicrobial, duration of antimicrobial exposure, antimicrobial combinations, and inoculum and medium used. beta-Lactams demonstrate a PAE against Gram-positive cocci, but produce only a short PAE with Gram-negative bacilli. Antimicrobial agents that inhibit RNA or protein synthesis have a PAE against Gram-positive cocci and Gram-negative bacilli. In vivo studies of aminoglycosides suggest that area under the plasma concentration-time curve is the pharmacokinetic parameter that best correlates with clinical efficacy. This is thought to be due to the concentration-dependent killing and PAE possessed by these antimicrobials. Animal and human studies have reported that once-daily administration of aminoglycoside is as effective as, or more effective than, and possibly less toxic than traditional multiple daily administration.
Insights
The postantibiotic effect (PAE) is a crucial factor in antimicrobial efficacy. Understanding PAE and optimizing antimicrobial dosing, like with aminoglycosides, enhances treatment outcomes.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The postantibiotic effect (PAE) is the delay in microbial regrowth after antimicrobial exposure.
- PAE is observed with most antimicrobial agents against various bacterial pathogens.
- Factors influencing PAE include organism type, antimicrobial agent, concentration, exposure duration, combinations, and media.
Purpose of the Study:
- To review the characteristics and influencing factors of the postantibiotic effect (PAE).
- To discuss the PAE of different antimicrobial classes, including beta-lactams and protein/RNA synthesis inhibitors.
- To explore the role of PAE and pharmacokinetic parameters in aminoglycoside efficacy and dosing.
Main Methods:
- Literature review of studies investigating the postantibiotic effect (PAE).
- Analysis of factors affecting PAE duration and presence.
- Examination of in vivo data correlating pharmacokinetic parameters with clinical outcomes for aminoglycosides.
Main Results:
- Beta-lactams show a significant PAE against Gram-positive cocci but a short PAE against Gram-negative bacilli.
- Antimicrobials inhibiting RNA or protein synthesis exhibit PAE against both Gram-positive cocci and Gram-negative bacilli.
- Area under the plasma concentration-time curve is the key pharmacokinetic parameter for aminoglycoside efficacy, linked to their concentration-dependent killing and PAE.
Conclusions:
- The postantibiotic effect (PAE) is a significant pharmacodynamic property influencing antimicrobial effectiveness.
- Aminoglycosides demonstrate concentration-dependent killing and a notable PAE, supporting once-daily dosing strategies.
- Once-daily aminoglycoside administration in vivo appears as effective or more effective, and potentially less toxic, than multiple daily doses.