Relationship of minimal inhibitory concentration and bactericidal activity to efficacy of antibiotics for treatment of ventilator-associated pneumonia.

Although minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) have been used as the most popular prediction tools for antimicrobial action, they have shortcomings. The MIC and MBC do not consider time-related antimicrobial effects, such as killing rate and postantibiotic effect. In this regard, the concept of pharmacokinetic and pharmacodynamic (PK/PD) modeling has been introduced to help interpret determinations of susceptibility breakpoints. Although area under the inhibitory concentration-time curve (AUIC) can be used as a universal PK/PD parameter, target magnitudes of the parameter have to be high enough to exert rapid bactericidal activity (> 250) and to prevent selection and induction of resistance (> 100). For vancomycin used in treatment of methicillin-resistant Staphylococcus aureus pneumonia, a much higher AUIC (400) is suggested to avoid treatment failure. For resistant gram-negative bacteria, such as Pseudomonas aeruginosa, the usual dosage of fourth-generation cephalosporins, carbapenems, and fluoroquinolones cannot achieve the target AUICs. Either combination therapy or higher dosage should be administered to achieve target AUICs and prevent the potential for failure. Unresolved issues, such as influence of protein binding, PK/PD at tissue sites versus blood, the impact of the immune system, should be addressed to refine the applicability of PK/PD in antibiotic treatment.