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Appropriate initial antibiotic therapy in hospitalized patients with gram-negative infections: systematic review and
Gowri Raman1,2, Esther Avendano3, Samantha Berger4
1Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA, 02111, USA. graman@tuftsmedicalcenter.org.
Background:
The rapid global spread of multi-resistant bacteria and loss of antibiotic effectiveness increases the risk of initial inappropriate antibiotic therapy (IAT) and poses a serious threat to patient safety. We conducted a systematic review and meta-analysis of published studies to summarize the effect of appropriate antibiotic therapy (AAT) or IAT against gram-negative bacterial infections in the hospital setting.
Methods:
MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched until May 2014 to identify English-language studies examining use of AAT or IAT in hospitalized patients with Gram-negative pathogens. Outcomes of interest included mortality, clinical cure, cost, and length of stay. Citations and eligible full-text articles were screened in duplicate. Random effect models meta-analysis was used.
Results:
Fifty-seven studies in 60 publications were eligible. AAT was associated with lower risk of mortality (unadjusted summary odds ratio [OR] 0.38, 95 % confidence interval [CI] 0.30-0.47, 39 studies, 5809 patients) and treatment failure (OR 0.22, 95 % CI 0.14-0.35; 3 studies, 283 patients). Conversely, IAT increased risk of mortality (unadjusted summary OR 2.66, 95 % CI 2.12-3.35; 39 studies, 5809 patients). In meta-analyses of adjusted data, AAT was associated with lower risk of mortality (adjusted summary OR 0.43, 95 % CI 0.23-0.83; 6 studies, 1409 patients). Conversely, IAT increased risk of mortality (adjusted summary OR 3.30, 95 % CI 2.42-4.49; 16 studies, 2493 patients). A limited number of studies suggested higher cost and longer hospital stay with IAT. There was considerable heterogeneity in the definition of AAT or IAT, pathogens studied, and outcomes assessed.
Discussion:
Using a large set of studies we found that IAT is associated with a number of serious consequences,including an increased risk of hospital mortality. Infections caused by drug-resistant, Gram-negative organisms represent a considerable financial burden to healthcare systems due to the increased costs associated with the resources required to manage the infection, particularly longer hospital stays. However, there were insufficient data that evaluated AAT for the outcome of costs among patients with nosocomialGram-negative infections.
Conclusions:
IAT in hospitalized patients with Gram-negative infections is associated with adverse outcomes. Technological advances for rapid diagnostics to facilitate AAT along with antimicrobial stewardship, surveillance, infection control, and prevention is needed.
Insights
Inappropriate antibiotic therapy (IAT) for Gram-negative infections significantly increases hospital mortality risk. Appropriate antibiotic therapy (AAT) is crucial for patient safety and reducing adverse outcomes in hospitalized patients.
Area of Science:
- Infectious Diseases
- Clinical Pharmacy
- Public Health
Background:
- The rise of multi-resistant bacteria and declining antibiotic effectiveness heighten the risk of inappropriate antibiotic therapy (IAT).
- IAT poses a significant threat to patient safety in hospital settings.
- Gram-negative bacterial infections are a growing concern in healthcare.
Purpose of the Study:
- To systematically review and meta-analyze studies on the impact of appropriate antibiotic therapy (AAT) versus IAT.
- To summarize the effects of AAT and IAT on mortality, clinical cure, cost, and length of stay for Gram-negative infections.
- To assess the patient safety implications of antibiotic prescribing in hospitals.
Main Methods:
- Systematic search of MEDLINE, EMBASE, and Cochrane CENTRAL databases up to May 2014.
- Inclusion of English-language studies on hospitalized patients with Gram-negative pathogens.
- Random effects models meta-analysis to synthesize data on mortality and treatment failure.
Main Results:
- AAT was associated with significantly lower mortality (unadjusted OR 0.38; adjusted OR 0.43) and treatment failure.
- IAT was linked to increased mortality risk (unadjusted OR 2.66; adjusted OR 3.30).
- Limited evidence suggested higher costs and longer hospital stays with IAT.
Conclusions:
- IAT in hospitalized patients with Gram-negative infections leads to adverse outcomes, including increased mortality.
- Drug-resistant Gram-negative infections impose a substantial financial burden on healthcare systems.
- Rapid diagnostics, antimicrobial stewardship, and infection control are essential to promote AAT.
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