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Published on: April 18, 2019
Combination therapy for treatment of infections with gram-negative bacteria
Pranita D Tamma1, Sara E Cosgrove, Lisa L Maragakis
1The Johns Hopkins Medical Institutions, Department of Medicine, Division of Pediatric Infectious Diseases, Baltimore, Maryland, USA. ptamma1@jhmi.edu
Abstract:
Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria.
Insights
Combination antibiotic therapy is beneficial for empiric treatment of Gram-negative infections, especially with rising multidrug-resistant organisms. Its value diminishes once susceptibility data is known.
Area of Science:
- Infectious Diseases
- Pharmacology
- Critical Care Medicine
Background:
- Combination antibiotic therapy is common for severe Gram-negative infections.
- Rising multidrug-resistant Gram-negative organisms support empiric combination use.
- The benefit of continued combination therapy post-susceptibility testing is debated.
Purpose of the Study:
- To review evidence comparing monotherapy and combination therapy for Gram-negative infections.
- To evaluate the role of combination therapy in empiric versus definitive treatment.
Main Methods:
- Systematic review of existing literature.
- Comparison of outcomes between monotherapy and combination therapy groups.
- Analysis of data regarding empiric and targeted treatment strategies.
Main Results:
- Combination therapy increases the likelihood of effective empiric treatment.
- Evidence for in vitro synergy or resistance prevention during definitive treatment is limited.
- Greatest benefit observed during the empiric phase of treatment.
Conclusions:
- Combination antibiotic therapy is most advantageous during the empiric treatment of Gram-negative infections.
- Continued combination therapy after susceptibility results is controversial.
- Focus on effective empiric agent selection is key.
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