Low Minimum Inhibitory Concentration of an Antibiotic Does Not Necessarily Imply a Better Antibiotic: Other Clinical and Pharmacological Factors Need Consideration for Antibiotic Selection

Sanjay Bhattacharya

Department of Microbiology, Tata Medical Center, Kolkata, West Bengal, India

Corresponding Author: Sanjay Bhattacharya, Department of Microbiology, Tata Medical Center, Kolkata, West Bengal, India, Phone: +91 9432344206, e-mail: sanjay.bhattacharya@tmckolkata.com

How to cite this article: Bhattacharya S. Low Minimum Inhibitory Concentration of an Antibiotic Does Not Necessarily Imply a Better Antibiotic: Other Clinical and Pharmacological Factors Need Consideration for Antibiotic Selection. J Acad Clin Microbiol 2024;26(1):27–28.

Source of support: Nil

Conflict of interest: None

Dear Editor,

There is a common misconception among some doctors that a lower minimum inhibitory concentration (MIC) implies a better drug (antibiotic/antifungal), and drugs should be chosen with emphasis on MICs provided in microbiology culture sensitivity reports.¹ This misconception needs to be dispelled.

Minimum inhibitory concentrations are pharmacodynamic parameters measured under strictly defined laboratory conditions. In PK/PD analysis, the MIC is the most commonly applied pharmacodynamic parameter. Other pharmacodynamic parameters include: (1) minimum bactericidal concentration (MBC), (2) mutant prevention concentration (MPC), and (3) bacterial or fungal kill rate using time-kill curves.² The MIC of an antibiotic or antifungal is the minimum concentration of the drug required to inhibit the growth of a microorganism of a particular species present at a certain fixed concentration. There are many other factors apart from MICs that are important for antimicrobial selection (Fig. 1). A low MIC does not always imply a better drug, and a high MIC may not always mean a poor therapeutic choice. A number of clinical, pharmacological, microbiological, and practical factors need consideration for antimicrobial drug selection.

Fig. 1: Factors other than MICs that are important for the selection of antimicrobial therapy; ADR, adverse drug reaction; MIC, minimum inhibitory concentration; S/I/R, sensitive/intermediate/resistant

Minimum inhibitory concentrations are important for (1) defining clinical breakpoints and epidemiological cutoff values, (2) monitoring MIC trends (MIC creep), (3) research (genotypic-phenotypic correlation of antimicrobial susceptibility), (4) identification of synergism, antagonism, additive effect, or indifference during combination therapy, and (5) pharmacokinetic-pharmacodynamic (PK-PD) studies (area under curve over MIC).

“MIC creep” is a phenomenon that describes an increase in an organism’s MICs over time. The phenomenon has been observed in many drug-bug combinations but studied extensively in Staphylococcus aureus and vancomycin. Isolates with MIC creep have been associated with therapeutic failure. MIC creep may be underestimated because of the cryopreservation effect or inaccurately estimated by automated systems. MIC creep has been reported to be lost due to cryopreservation of isolates.³

There are only a handful of clinical situations where MIC information has a direct effect on the choice of antimicrobial therapy or prognosis. These include the management of infective endocarditis (e.g., MIC of penicillin to viridans group Streptococcus), use of polymyxins in combination therapy, management of infections caused by antibiotic-resistant Streptococcus pneumoniae, and high vancomycin MIC (>2 µg/mL) associated with higher mortality in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections.⁴^-⁷

Without clinical breakpoint information, MIC data alone in microbiology reports may not help clinicians assess the likelihood of resistance development. Clinicians, clinical microbiologists, and infectious diseases specialists need appropriate training to understand the clinical significance of antibiotic susceptibility reports that include MIC values.

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