P-1348. Impact of Minocycline Minimum Inhibitory Concentrations on Clinical Outcomes in Stenotrophomonas maltophilia Respiratory and Bloodstream Infections

TL;DR

This study found no significant difference in treatment outcomes for Stenotrophomonas maltophilia infections based on minocycline MIC levels, suggesting the current breakpoint may not reliably predict clinical success.

Contribution

The study provides clinical data evaluating the impact of updated minocycline MIC breakpoints for S. maltophilia, which had previously been based on a single PK/PD study.

Findings

Treatment failure rates were 48% for MIC ≤ 1 mg/L and 65% for MIC 2-4 mg/L, but the difference was not statistically significant.

Higher Pitt Bacteremia Scores and ICU admission were associated with treatment failure, but MIC group was not independently predictive.

More data with larger sample sizes are needed to confirm the clinical relevance of the updated MIC breakpoint.

Abstract

The Clinical & Laboratory Standards Institute (CLSI) recently lowered the minocycline breakpoint for Stenotrophomonas maltophilia infections from ≤ 4 to ≤ 1 mg/L due to results from one PK/PD study, however clinical data are lacking. This study assessed clinical outcomes between minocycline MICs (≤ 1 mg/L vs 2-4 mg/L) for S. maltophilia respiratory and bloodstream infections.

This was a retrospective, cohort study of patients ≥ 18 years of age hospitalized at NYP/CUIMC who received ≥ 48 hrs of minocycline for S. maltophilia infection. Primary outcome was frequency of treatment failure. Secondary outcomes include isolation of S. maltophilia on follow-up cultures, development of minocycline resistance, and 30-day in-hospital mortality. Characteristics were compared between groups and between those with success/failure to construct a multivariable analysis for clinical failure considering all factors with a p-value < 0.2 and including MIC group.

80 patients were included: 63 with MIC of ≤ 1 and 17 with MIC of 2-4 mg/L. Majority (91%) were respiratory infections with 48 (60%) of patients being mechanically ventilated, 50 (63%) in the ICU at time of infection, and 35 (44%) were immunosuppressed. There was no difference in characteristics between groups and the Pitt Bacteremia Score was 3 in the MIC ≤ 1 group compared to 4 in the MIC 2-4 group (p=0.938). Treatment failure occurred in 41 (51%): 30 (48%) in the MIC ≤ 1 group and 11 (65%) in the MIC 2-4 group (p=0.328). Mechanical ventilation [30 (73%) vs. 18 (46%); p=0.025], ICU [31 (76%) vs. 19 (49%); p=0.024], and higher median PITT bacteremia score [5 vs. 2; p=0.001] were more common in those who failed compared to those with success. In the multivariable model, MIC 2-4 mg/L was not independently associated with treatment failure [OR 2.26 (95% CI 0.615-8.40; p=0.226).

In patients who received minocycline for S. maltophilia respiratory and bloodstream infections, treatment failure did not differ between patients who had minocycline MIC of ≤ 1 mg/L compared to 2-4 mg/L. Although the results were not statistically significant, numerically there was a higher percentage of patients who failed treatment that had an MIC of 2-4 mg/L. More data with a larger sample size are needed.

Nicholas Demenagas, PharmD, Ferring Pharmaceuticals: Advisory Board