New Approaches to the Optimization of Antimicrobial Therapy of Respiratory Tract Infections Using Pharmacokinetic and Pharmacodynamic Parameters

Clinical Microbiology and Antimicrobial Chemotherapy. 2004; 6(1):22-31

Type
Journal article

Abstract

To understand the relationship between drug dose and efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics need to be integrated. There are two patterns of antimicrobial activity: time-dependent killing and concentration-dependent killing. Time-dependent killing is characteristic of β-lactams and some macrolides. 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. Concentration-dependent killing is seen with aminoglycosides, quinolones, some macrolides and azalide. The major PK/PD parameter correlating with efficacy of these agents is the 24-hour area under the curve to MIC ratio, which should be ≥25 for less severe infections (≥100 in more severe infections or in immunocompromised hosts). PK/PD breakpoints for concentration-dependent agents can therefore be calculated from the formula AUC/25. For an antimicrobial to be useful empirically the MIC90 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 therapy of respiratory tract infections, where efficacy against predominant pathogens (S. pneumoniae and H. influenzae, including strains with emerging resistance) is required. PK/PD principles have been applied to recent Russian isolates of these species in this article.

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