Association between empiric combination therapy using antipseudomonal agents and in-hospital mortality among patients with sepsis in intensive care units in Japan: A propensity score-matched analysis

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Abstract
Sepsis mortality due to drug-resistant organisms remains high. However, the effectiveness of empiric combination therapy for sepsis caused by potential drug-resistant gram‑negative bacilli remains debated. This was a nested case-control study using Japanese nationwide data from a medical reimbursement system between 2010 and 2017. The eligibility criteria were adult patients who were admitted to the intensive care unit, with new-onset sepsis at or after admission. We enrolled patients with combination therapy and monotherapy by propensity score matching using their baseline characteristics. We developed a logistic regression model including combination therapy, severity of organ dysfunction, and interaction terms as the adjusting variables. Overall, 7084 patients were included in this study, 3542 and 3542 of whom were enrolled in the combination therapy and monotherapy groups, respectively. The logistic regression model revealed combination therapy and moderate and severe organ dysfunction were significantly associated with in-hospital mortality (odds ratio [OR] 95% confidence interval [CI]: 1.52 [1.20–1.91], OR [95% CI]: 1.78 [1.43–2.23], and OR [95% CI]: 4.22 [2.61–6.81], respectively). Interaction between combination therapy and severe organ dysfunction was statistically significant (OR [95% CI]: 0.41 [0.21–0.80], P for interaction = .009). However, adjusted in-hospital mortality based on the model was not significantly different between the combination therapy and monotherapy groups among patients with severe organ dysfunction (44% [95% CI: 38–51] vs 47% [95% CI: 41–54]). Our results did not reveal any specific effectiveness of combination therapy; however, the significant interaction between combination therapy and severe organ dysfunction may indicate the possible survival benefit of combination therapy for severe sepsis subset.

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