Antimicrobial Combination Therapy in Septic Patients: A Systematic Review and Meta-Analysis
CCCF ePoster library. Vazquez-Grande G. Nov 8, 2018; 233362; 81 Disclosure(s): I have no disclosures
Dr. Gloria Vazquez-Grande
Dr. Gloria Vazquez-Grande
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Introduction: Sepsis is the major cause of infection-associated mortality and remains among the leading causes of death in intensive care units (ICUs) worldwide.

Objectives:  To evaluate the efficacy and safety of antimicrobial combination therapy (defined as at least two antimicrobials of different mechanistic classes) in patients with sepsis.

Data Sources:  Randomized controlled trials from PubMed, EMBASE, CENTRAL, Scopus (inception to February 2017), reference lists of relevant articles, grey literature.

Selection criteria: Two reviewers independently identified randomized controlled trials comparing antimicrobial monotherapy with combination therapy in critically ill patients with sepsis or septic shock.

Data collection:  Two reviewers independently extracted trial-level data including patient characteristics, interventions, outcomes, and funding source. Risk of bias of included studies was assessed using the Cochrane Risk of Bias tool.

Main results:  The literature search identified 2725 citations, of which 36 were deemed to be potentially relevant. Ten publications met the inclusion criteria and were included in the meta-analysis. All the included trials had high risk of bias (no blinding). Combination therapy showed no significant difference in mortality compared to monotherapy (RR 1.04, CI 95% 0.89 to 1.20, I2 0%; 9 trials; 2206 participants). None of the subgroup analyses or secondary outcomes showed significant differences between groups. Drug reported adverse events were significantly higher in the combination therapy arm (RR 0.75, CI 95% 0.60 to 0.93, I2 15%; 7 trials; 1609 participants).

Conclusions: Combination therapy may not have a benefit over monotherapy in septic patients. At this time the available evidence doesn’t support or recommend combination therapy for the treatment of sepsis or septic shock. As we were unable to discriminate based on severity of illness, a meta-regression adjusting by risk of death is needed to indicate whether patients may benefit from combination therapy. Large randomized controlled trials looking at patient-related outcomes are required to further explore the benefits and harms of this intervention.



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