Vancomycin Minimum Inhibitory Concentration Is Not a Substitute for Clinical Judgment: Response to Healthcare-Associated Ventriculitis and Meningitis
Year: 2017
Type: letter
Abstract: To the Editor—We read with interest the new clinical practice guideline for healthcare-associated ventriculitis and meningitis published in Clinical Infectious Diseases [1]. The guideline recommends consideration of alternative therapies for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) meningitis and ventriculitis for isolates with a vancomycin minimum inhibitory concentration (MIC) ≥1μg/mL. We believe this recommendation places inappropriate emphasis on a single determinant of antimicrobial therapy that has uncertain clinical relevance and variable accuracy depending on the antimicrobial susceptibility testing (AST) method used. This may lead clinicians to use less well-evidenced strategies in cases likely to respond to vancomycin. AST can be performed by any of several methods, including broth microdilution (BMD), gradient diffusion (Etest), disc diffusion, and automated systems [2]. Several investigators have found that Etest methods consistently yield higher MICs than reference BMD [3–6]. Automated systems, used by most clinical laboratories, also vary in vancomycin MIC results, with VITEK 2 systems yielding lower MICs and Microscan systems higher MICs than reference BMD [4, 6]. Reports are conflicting for Phoenix systems [4, 6]. Therefore, a recommendation to change therapy on the basis of MIC testing alone leaves much in question, because the MIC result varies based on the method used. Furthermore, because clinicians are not frequently able to influence the type of testing available at their site, there is a risk of drug selection becoming more a function of laboratory testing than of clinical judgment. The threshold MIC recommended for consideration of alternative therapies by Tunkel and colleagues [1] in the new guideline, ≥1 μg/mL, is more conservative than any previous guideline; the vancomycin monitoring guideline [7] advocated that therapy change be considered only with an MIC ≥2 μg/mL, and the more recent MRSA infection guideline [8] recommended change when the MIC indicates nonsusceptibility (>2 μg/mL) or in cases of clinical failure. Presumably, the new guideline for meningitis and ventriculitis advocates a lower MIC threshold owing to lower achievable vancomycin concentrations in the cerebrospinal fluid. Prior evidence predicts achievement of the pharmacodynamic target for vancomycin, an area under the curve (AUC)/MIC ratio of ≥400, for isolates with an MIC ≤1 μg/mL, when vancomycin troughs of 15–20 mg/L are maintained for a patient of average weight and normal renal function [7]. This AUC/MIC target represents our best correlate of vancomycin clinical success in treating lower respiratory tract infections [9], but its application to meningitis and ventriculitis is unknown. There are conflicting data on the association of clinical failures with high but susceptible vancomycin MICs [10]; no specific studies for central nervous system infections are available. We agree with the authors that nosocomial MRSA meningitis and ventriculitis are commonly encountered clinical situations for which few high-quality clinical studies are available; we look forward to more data to clarify the role of newer agents. We contend that AST is one of several important considerations in determining optimal therapy for MRSA infections, but as a sole criterion it glosses over considerable nuance and uncertainty in the evidence. Therefore, we suggest that the patient’s clinical condition, response to initial therapy, and laboratory AST method should be considered along with the MIC to assess the appropriateness of an alternative therapy. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/cix552
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2626843756