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Antimicrobial resistance issues of the future
1Department of Medicine, William S. Middleton Memorial VA Hospital, Madison, Wisconsin 53705, USA.
Diagnostic Microbiology and Infectious Disease
|August 1, 1996
Summary
Antimicrobial resistance impacts oral drug effectiveness. Achieving optimal bactericidal activity requires maintaining drug concentrations above the minimum inhibitory concentration (MIC) for a specific duration, especially for beta-lactams against resistant pathogens.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Increasing antimicrobial resistance in respiratory pathogens threatens the efficacy of standard oral drug regimens.
- Maximizing bactericidal activity is the primary goal of antimicrobial therapy.
- Pharmacokinetic/pharmacodynamic (PK/PD) parameters, specifically the duration of time serum concentrations exceed the minimum inhibitory concentration (MIC), are crucial for determining drug efficacy.
Purpose of the Study:
- To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) targets for optimizing antimicrobial therapy against respiratory pathogens.
- To identify oral beta-lactams that achieve sufficient serum concentrations above the MIC for effective treatment of infections caused by penicillin-resistant Streptococcus pneumoniae and Haemophilus influenzae.
Main Methods:
- Review of animal models and clinical studies in children with acute otitis media to establish PK/PD targets.
- Analysis of serum drug concentrations and their duration above the MIC for various oral beta-lactams against specific pathogens.
- Assessment of antimicrobial resistance patterns for Streptococcus pneumoniae and Haemophilus influenzae.
Main Results:
- Serum concentrations of beta-lactams need to exceed the MIC for approximately 40-50% of the dosing interval to achieve maximum antimicrobial efficacy and bacteriologic cure.
- Amoxicillin and amoxicillin/clavulanate are effective oral beta-lactams against penicillin-resistant Streptococcus pneumoniae, achieving the required duration above MIC.
- Cefixime, cefpodoxime, and amoxicillin/clavulanate provide the longest durations of serum concentrations above the MIC for Haemophilus influenzae.
Conclusions:
- Optimizing antimicrobial therapy requires achieving specific PK/PD targets, particularly maintaining drug concentrations above the MIC for a defined period.
- Amoxicillin and amoxicillin/clavulanate are key oral beta-lactams for treating infections with penicillin-resistant Streptococcus pneumoniae.
- Addressing antimicrobial resistance necessitates the development of new antimicrobials, optimized dosing regimens, and robust resistance control strategies including prudent use, infection control, and vaccination.