Abstract
BackgroundThe 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.MethodsMEDLINE, 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.ResultsFifty-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.DiscussionUsing 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.ConclusionsIAT 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1123-5) contains supplementary material, which is available to authorized users.
Highlights
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
IAT in hospitalized patients with Gram-negative infections is associated with adverse outcomes
Data sources and study selection Initial comprehensive literature searches were conducted in MEDLINE, Cochrane CENTRAL, and EMBASE databases from inception through May 2014 for Englishlanguage articles published on the use of appropriate or inappropriate empiric/initial antibiotics in patients with hospital-acquired or healthcare-associated Gram-negative bacteria
Summary
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. Gramnegative bacteria cause the four most frequent types of hospital-acquired infection: pneumonia, intraabdominal infection, urinary tract infection (UTI), and bloodstream infection. In the US from 2009 to 2010, 43 % of healthcare-associated infections, 65 % of catheter-associated UTIs, 65 % of pneumonia, and 22 % of central line-associated bloodstream infections were attributed to Gram-negative pathogens [2]. The incidence of multidrug-resistant, Gram-negative pathogens is on the rise and these organisms represent an urgent threat due to the limited availability of viable therapeutic options [3, 4]
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