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Introduction <p>Optimal minocycline dosing for <i>Acinetobacter baumannii</i> group pneumonia remains unclear. We assessed the clinical impact of high-dose (HD) versus standard-dose (SD) minocycline and explored the predictive value of susceptibility breakpoints.</p> Methods <p>In this multicenter retrospective cohort study, hospitalized adults with AB group pneumonia treated with minocycline were classified into HD (200&#xa0;mg IV q12h) or SD (100&#xa0;mg IV q12h or 200&#xa0;mg IV q24h) groups. Inverse probability of treatment weighting (IPTW) and multivariate logistic regression were applied to adjust for baseline differences. Kaplan–Meier survival and subgroup analyses were performed to evaluate dose–response effects and the utility of different minimum inhibitory concentration (MIC) breakpoints.</p> Results <p>Among 106 patients (HD: 46; SD: 60), HD therapy was associated with significantly lower in-hospital mortality (28.6% vs. 48.3%; <i>p</i> = 0.046). HD minocycline remained a protective factor in multivariate and IPTW-adjusted models. Long-term (150-day) survival favored HD therapy (log-rank test, <i>p</i> = 0.028). In 28 patients infected with MIC-confirmed isolates, HD therapy consistently trended toward lower mortality across MIC strata. Notably, the pharmacokinetic/pharmacodynamic (PK/PD)-informed breakpoint (≤ 1&#xa0;µg/ml) better discriminated survival benefit from HD therapy, whereas the Clinical and Laboratory Standards Institute (CLSI) 2024 breakpoint (≤ 4&#xa0;µg/ml) did not. These findings support dose optimization and align with the revision of CLSI breakpoints in 2025, lowering the minocycline susceptibility breakpoint for <i>Acinetobacter</i> spp. to ≤ 1&#xa0;µg/ml.</p> Conclusions <p>High-dose minocycline significantly improved in-hospital survival for <i>A. baumannii</i> group pneumonia. PK/PD-informed breakpoint may offer greater clinical relevance for guiding minocycline therapy compared to CLSI 2024 breakpoint.</p>

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High-Dose Minocycline Improves Outcomes in Acinetobacter baumannii Group Pneumonia: A Propensity-Weighted Cohort Study with MIC-Based Insights for Breakpoint Revision

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月12日

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  • Yu-Tao Tseng,
  • Yang-Chuan Chen,
  • Yi-Tzu Lee,
  • Po-Hsiang Liao,
  • Dung-Hung Chiang,
  • Po-Liang Chen,
  • Tzu-Wen Huang,
  • Yung-Chih Wang

摘要

Introduction

Optimal minocycline dosing for Acinetobacter baumannii group pneumonia remains unclear. We assessed the clinical impact of high-dose (HD) versus standard-dose (SD) minocycline and explored the predictive value of susceptibility breakpoints.

Methods

In this multicenter retrospective cohort study, hospitalized adults with AB group pneumonia treated with minocycline were classified into HD (200 mg IV q12h) or SD (100 mg IV q12h or 200 mg IV q24h) groups. Inverse probability of treatment weighting (IPTW) and multivariate logistic regression were applied to adjust for baseline differences. Kaplan–Meier survival and subgroup analyses were performed to evaluate dose–response effects and the utility of different minimum inhibitory concentration (MIC) breakpoints.

Results

Among 106 patients (HD: 46; SD: 60), HD therapy was associated with significantly lower in-hospital mortality (28.6% vs. 48.3%; p = 0.046). HD minocycline remained a protective factor in multivariate and IPTW-adjusted models. Long-term (150-day) survival favored HD therapy (log-rank test, p = 0.028). In 28 patients infected with MIC-confirmed isolates, HD therapy consistently trended toward lower mortality across MIC strata. Notably, the pharmacokinetic/pharmacodynamic (PK/PD)-informed breakpoint (≤ 1 µg/ml) better discriminated survival benefit from HD therapy, whereas the Clinical and Laboratory Standards Institute (CLSI) 2024 breakpoint (≤ 4 µg/ml) did not. These findings support dose optimization and align with the revision of CLSI breakpoints in 2025, lowering the minocycline susceptibility breakpoint for Acinetobacter spp. to ≤ 1 µg/ml.

Conclusions

High-dose minocycline significantly improved in-hospital survival for A. baumannii group pneumonia. PK/PD-informed breakpoint may offer greater clinical relevance for guiding minocycline therapy compared to CLSI 2024 breakpoint.