Document Detail

Optimisation of antimicrobial therapy using pharmacokinetic and pharmacodynamic parameters.
MedLine Citation:
PMID:  11737083     Owner:  NLM     Status:  MEDLINE    
To understand the relationship between drug dose and efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics need to be integrated. Patterns of antimicrobial activity fall into one of two major patterns: time-dependent killing and concentration-dependent killing. Time-dependent killing is characteristic of many antibiotic classes, such as beta-lactams and macrolides, and seeks to optimise the duration of exposure of a pathogen to an antimicrobial. The major PK/PD parameter correlating with efficacy of time-dependent antimicrobials is the serum concentration present for 40-50% of the dosing interval, and this concentration is the susceptibility limit or breakpoint for the dosing regimen used. The second pattern, concentration-dependent killing, seeks to maximise antimicrobial concentration and is seen with aminoglycosides, quinolones and azalides. The major PK/PD parameter correlating with efficacy of these agents is the 24-h area under the curve to MIC ratio, which should be > or =25 for less severe infections or in immunocompetent hosts, and > or =100 in more severe infections or in immunocompromised hosts. PK/PD breakpoints for concentration-dependent agents can therefore be calculated from the formula AUC divided by 25. This enables development of PK/PD breakpoints based on the above parameters for time- and concentration-dependent agents for defined dosing regimens. For an antimicrobial to be useful empirically, the MIC90s of the agent against the common pathogens responsible for the disease being treated should be below the PK/PD breakpoint. This is particularly important for oral dosing regimens for treating emerging resistant respiratory tract pathogens, where efficacy against the predominant pathogens, Streptococcus pneumoniae and Haemophilus influenzae, is required.
M R Jacobs
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases     Volume:  7     ISSN:  1198-743X     ISO Abbreviation:  Clin. Microbiol. Infect.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-12-12     Completed Date:  2002-01-22     Revised Date:  2006-11-07    
Medline Journal Info:
Nlm Unique ID:  9516420     Medline TA:  Clin Microbiol Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  589-96     Citation Subset:  IM    
Department of Pathology, Case Western Reserve University, University Hospitals of Cleveland, 11100 Euclid Ave, Cleveland, OH 44106, USA.
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MeSH Terms
Anti-Bacterial Agents / pharmacokinetics*,  pharmacology*,  therapeutic use
Drug Resistance, Bacterial
Haemophilus influenzae / drug effects*,  isolation & purification
Microbial Sensitivity Tests
Respiratory Tract Infections / drug therapy*,  microbiology
Streptococcus pneumoniae / drug effects*,  isolation & purification
Reg. No./Substance:
0/Anti-Bacterial Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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