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: a systematic review and meta-analysis

Abstract

ObjectiveTo 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)-producingEnterobacteriaceae.DesignSystematic review and meta-analysisMethodsLiterature 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 I2statistics and metaregression.ResultsEighty-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.ConclusionsCurrent 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.

Do Probiotics During In-Hospital Antibiotic Treatment Prevent Colonization of Gut Microbiota With Multi-Drug-Resistant Bacteria? A Randomized Placebo-Controlled Trial Comparing Saccharomyces to a Mixture of Lactobacillus, Bifidobacterium, and Saccharomyces

“…Infections with multi-drug resistant bacteria (MDR) such as extended-spectrum β-lactamase (ESBL)-, AmpC β-lactamase (AmpC)-, and carbapenemase-producing Enterobacteria (CPE), vancomycin-resistant Enterococcus (VRE), or naturally resistant non-fermenting bacteria such as Pseudomonas aeruginosa are associated with a high mortality rate ( 1 – 3 ). The risk of developing an infection with MDR bacteria is relative to the abundance of fecal MDR ( 2 , 4 – 6 ).…”

Prevalence of multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli: A meta-analysis report in Ethiopia

“…ESBL-producing organisms play an important role in healthcare infections, increasing hospitalization time and morbidity and mortality rates ( 8 ). The presence of ESBL complicates antibiotic selection, especially in patients with serious infections, such as bacteremia.…”

“…The presence of ESBL complicates antibiotic selection, especially in patients with serious infections, such as bacteremia. The reason for this is that ESBL-producing bacteria are often multiresistant to various antibiotics, an interesting feature of CTX-M (CTX stands for cefotaxime and M for Munich)-producing isolates is the coresistance to various classes of antibiotics such as fluoroquinolones, aminoglycosides and co-trimoxazole due to associated resistance mechanisms, which may be either chromosomally or plasmid-encoded ( 8 , 9 , 10 , 11 ).…”

Molecular Mechanisms, Epidemiology, and Clinical Importance of β-Lactam Resistance in Enterobacteriaceae

“…In both settings, the LOS was higher and more costly for patients with bloodstream infections (BSIs) due to ESBL-Es than for patients with BSIs due to non-ESBL-E [ 172 ]. In addition, non-invasive infections caused by ESBL-E isolates were also associated with a higher mortality and prolonged LOS [ 173 ]. The increased detection of ESBL-E isolates has brought an inevitable large usage of carbapenems as a first-line therapy all over the world.…”