(484) Incidence of Clinical Treatment Failure in MRSA Pneumonia Treated With Linezolid With Elevated MICs

Introduction: The Infectious Disease Society of America (IDSA) guidelines recommend vancomycin, linezolid, or clindamycin for patients with MRSA pneumonia. When vancomycin has a minimum inhibitory concentration (MIC) of 2 or greater, it is unlikely that pharmacokinetic targets can be achieved without being toxic to the patient. When this occurs, linezolid is often used. There have been recent studies evaluating the pharmacokinetics of linezolid among different patient populations and infections, including pneumonia, when the MIC is ≤ 2 μg/mL. These studies describe that the pharmacokinetic targets were not met and suggest the need for therapeutic drug monitoring to ensure therapeutic levels are reached, however, linezolid with an MIC of 4 μg/mL is not often addressed. In the absence of widespread access to therapeutic drug monitoring, it is important to evaluate clinical outcomes in linezolid with higher MICs.

Methods: A retrospective chart review was utilized to evaluate adult patients from July 2015 to July 2022 with MRSA pneumonia treated with linezolid. The primary outcome was clinical deterioration within 96 hours of definitive antibiotic initiation resulting in one or more of the following: development or worsening of hemodynamic instability, appearance of respiratory failure, radiographical progression, persistence or reappearance of fever > 38oC, or clinician determination of treatment failure defined as a change in antibiotics. Secondary outcomes included ICU mortality and length of stay.

Results: A total of 40 patients were included, 25 in the MIC ≤ 2 μg/mL group and 15 patients in the MIC of 4 μg/mL group. Baseline characteristics were similar between groups. The composite endpoint of clinical deterioration occurred in 64% of patients in the MIC ≤ 2 μg/mL group and in 67% of patients in the MIC of 4 μg/mL group (p=0.864). Mean length of stay was 30 days in the MIC of ≤ 2 μg/mL group and 23 days in the MIC of 4 μg/mL group (p=0.417). ICU mortality occurred in 16% of patients that in the MIC of ≤ 2 μg/mL group and 27% of patients in the MIC of 4 μg/mL group (p=1.000).

Conclusions: There was no identified association between MIC of linezolid and clinical treatment failure.