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Macrolides and Long-Term Survival in ICU Patients with Community-Acquired Pneumonia

July 20, 2023

Written by Seth Walsh-Blackmore

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Empiric macrolide therapy was associated with improved six and twelve-month survival among ICU patients with community-acquired pneumonia (CAP).

Macrolides: Now prolonging more than the QT interval
Most CAP patients requiring ICU-level care will have empiric antibiotics initiated in the ED. This study compares two or more days of macrolides to no macrolides in 3,775 patients aged >16y, admitted to the ICU, and receiving pneumonia-directed antibiotics within 48hrs. Data were from the MIMIC-IV database.

Macrolide therapy was associated with decreased mortality at six months: aOR 0.82 (95%CI 0.76-0.88); and 12 months: 0.84 (0.78-0.91) in a cross-validated and adjusted regression model. A similar effect was observed in a proportional hazard model: 6 month HR 0.69 (95%CI 0.60 – 0.78); 12 month HR 0.72 (0.64 – 0.81).  

Macrolide therapy was only 30.6% of the total sample, and a lower proportion of patients receiving macrolides were mechanically ventilated (32.1% vs. 42.4% p < 0.001). However, the mortality benefit remained with propensity score matching and two sensitivity analyses.

The authors also performed a targeted maximum likelihood estimation (TMLE). TMLE is an emerging machine-learning method to analyze observational data in a way that theoretically allows causal effect estimation when confounding factors exist. It still relies on model assumptions and is impacted by the initial computational parameters selected. In applying this method, the authors found an additive effect estimate of – 0.069 (95%CI -0.081, -0.036) for 12-month mortality, representing a small decrease in risk.

How will this change my practice?
These data support my preference for empiric macrolides in sick CAP patients. It’s logical, given their beta-lactam synergy and immunomodulatory properties. They are readily available, cheap, and safe, sans a few contraindications.

Another Spoonful

  • CAP is much more than macrolides. See our post on the most recent guidelines here.
  • If you nerd out on biostatistics, explore this intro to TMLE here.

Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis. Crit Care. 2023 May 31;27(1):212. doi: 10.1186/s13054-023-04466-x.

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