Variation of effect estimates in the analysis of mortality and length of hospital stay in patients with infections caused by bacteria-producing extended-spectrum beta-lactamases

TY - JOUR

T1 - Variation of effect estimates in the analysis of mortality and length of hospital stay in patients with infections caused by bacteria-producing extended-spectrum beta-lactamases

T2 - a systematic review and meta-analysis

AU - Shamsrizi, Parichehr

AU - Gladstone, Beryl Primrose

AU - Carrara, Elena

AU - Luise, Dora

AU - Cona, Andrea

AU - Bovo, Chiara

AU - Tacconelli, Evelina

N1 - © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2020/1/20

Y1 - 2020/1/20

N2 - OBJECTIVE: To assess the variation of effect estimates in the analysis of mortality and length of stay (LOS) in patients with infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.DESIGN: Systematic review and meta-analysis METHODS: Literature search for clinical studies from 1 January 1960 to 1 October 2018 was conducted in PubMed. Primary outcomes were risk ratios (RRs) of all-cause and attributable mortality and weighted mean differences (WMDs) in LOS in patients with bloodstream infections (BSIs) and non-invasive infections. Any change in the effect estimates was assessed by grouping studies according to design, setting, economy-based country classification, reporting period, microbiological aetiology, infection type and adjustment for appropriateness of empirical treatment. The impact of ESBL production was calculated using random-effect meta-analysis and heterogeneity was evaluated by I2 statistics and metaregression.RESULTS: Eighty-four studies including 22 030 patients and 149 outcome measures were included in the meta-analysis. Most studies were retrospective cohorts from high-income countries, providing unadjusted estimates. ESBL production in patients with BSIs (56 studies) increased the RR for all-cause mortality by a factor of 1.70 (95% CI 1.52 to 1.90; p<0.001), attributable mortality (16 studies) by 1.75 (95% CI 1.448 to 2.108; p<0.001) and WMD in the intensive care unit by 3.07 days (95% CI 1.61 to 4.54; p<0.001). WMD in hospital LOS was significantly higher in BSIs (4.41 days; 95% CI 3.37 to 5.46; p<0.001) and non-invasive (2.19 days; 95% CI 1.56 to 2.81; p<0.001). Subgroup analyses showed variation of estimates by study design, population, strain and assessment of appropriateness of empiric treatment. High heterogeneity was observed in all analyses.CONCLUSIONS: Current evidence of the clinical burden of infections caused by ESBL-producing bacteria is highly heterogeneous and based mainly on unadjusted estimates derived from retrospective studies. Despite these limitations, ESBL production in strains causing BSIs seems associated with higher all-cause and attributable mortality and longer hospitalisation.

AB - OBJECTIVE: To assess the variation of effect estimates in the analysis of mortality and length of stay (LOS) in patients with infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.DESIGN: Systematic review and meta-analysis METHODS: Literature search for clinical studies from 1 January 1960 to 1 October 2018 was conducted in PubMed. Primary outcomes were risk ratios (RRs) of all-cause and attributable mortality and weighted mean differences (WMDs) in LOS in patients with bloodstream infections (BSIs) and non-invasive infections. Any change in the effect estimates was assessed by grouping studies according to design, setting, economy-based country classification, reporting period, microbiological aetiology, infection type and adjustment for appropriateness of empirical treatment. The impact of ESBL production was calculated using random-effect meta-analysis and heterogeneity was evaluated by I2 statistics and metaregression.RESULTS: Eighty-four studies including 22 030 patients and 149 outcome measures were included in the meta-analysis. Most studies were retrospective cohorts from high-income countries, providing unadjusted estimates. ESBL production in patients with BSIs (56 studies) increased the RR for all-cause mortality by a factor of 1.70 (95% CI 1.52 to 1.90; p<0.001), attributable mortality (16 studies) by 1.75 (95% CI 1.448 to 2.108; p<0.001) and WMD in the intensive care unit by 3.07 days (95% CI 1.61 to 4.54; p<0.001). WMD in hospital LOS was significantly higher in BSIs (4.41 days; 95% CI 3.37 to 5.46; p<0.001) and non-invasive (2.19 days; 95% CI 1.56 to 2.81; p<0.001). Subgroup analyses showed variation of estimates by study design, population, strain and assessment of appropriateness of empiric treatment. High heterogeneity was observed in all analyses.CONCLUSIONS: Current evidence of the clinical burden of infections caused by ESBL-producing bacteria is highly heterogeneous and based mainly on unadjusted estimates derived from retrospective studies. Despite these limitations, ESBL production in strains causing BSIs seems associated with higher all-cause and attributable mortality and longer hospitalisation.

KW - Cross Infection/microbiology

KW - Enterobacteriaceae/enzymology

KW - Enterobacteriaceae Infections/microbiology

KW - Humans

KW - Length of Stay/statistics & numerical data

KW - beta-Lactamases/biosynthesis

U2 - 10.1136/bmjopen-2019-030266

DO - 10.1136/bmjopen-2019-030266

M3 - SCORING: Journal article

C2 - 31964661

VL - 10

SP - e030266

JO - BMJ OPEN

JF - BMJ OPEN

SN - 2044-6055

IS - 1

ER -