Should I Choose the Antibiotic With the Lowest MIC?

Michael J. Postelnick, BSPharm

Disclosures

August 14, 2009

Question

Given specific susceptibility information for an infectious organism, why can't you simply pick the antibiotic with the lowest minimum inhibitory concentration?

Response from Michael J. Postelnick, BSPharm
Senior Infectious Diseases Pharmacist, Clinical Coordinator, Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois

Minimum inhibitory concentrations (MICs) can be very useful in selecting the best antimicrobial agent for a given patient with known culture and susceptibility results. However, to do so effectively, one needs to understand the pharmacokinetic and pharmacodynamic properties of the antimicrobial agents in question.

Pharmacokinetics describes what the patient’s body does to the drug (absorption, distribution, metabolism, and excretion). Pharmacokinetic measures include such variables as AUC24 (area under the concentration-time curve for a 24-hour period) and peak concentration (Cmax). Pharmacodynamics describes the interaction between the antimicrobial agent and the infecting pathogen (what the drug does to the infecting organism). The most common measure used to define antimicrobial pharmacodynamics is the organism’s MIC.[1]

Research into antimicrobial pharmacokinetics and pharmacodynamics has established surrogate relationships between the 2 that correlate with outcomes such bacterial eradication or clinical cure. These relationships include the ratio of Cmax to the MIC, time above the MIC (defined as the amount of time during the dosing interval that the antimicrobial concentration in the blood or at the site of infection remains above the MIC of the organism), and the ratio of the AUC to the MIC. For concentration-dependent antimicrobial agents such as fluoroquinolones and aminoglycosides, Cmax/MIC or AUC/MIC most closely correlates with clinical and microbiological outcomes. For time-dependent antimicrobial agents such as beta-lactams, the percentage of time during the dosing interval that the drug concentration remains above the MIC of the organism is the measure that most closely predicts outcomes.[1]

Although MICs provide useful information on antimicrobial activity, they are not directly comparable and provide little information outside of the framework of the above-described constructs. For example, if an organism exhibits a 1-mg/L MIC to ciprofloxacin, this organism is probably characterized by the microbiology laboratory as being susceptible to the drug. However, ciprofloxacin as a single agent probably cannot be used to treat most serious infections with this organism because of its inability to achieve adequate concentrations at the site of infection.

In contrast, if the same organism exhibits a 4-mg/L MIC to piperacillin-tazobactam (Zosyn®), it is exquisitely susceptible and is likely to be treatable by this agent alone for even serious infections. Given the pharmacokinetics of this agent, the drug concentration probably will remain above the MIC of the organism beyond the time necessary to achieve an optimal pharmacodynamic effect.

Using our knowledge of pharmacokinetics and pharmacodynamics allows us to optimize antimicrobial choice and dose to ensure the best use of our dwindling anti-infective resources.[2]

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