ABSTRACT
BACKGROUND: Infections caused by extended-spectrum beta-lactamases producing Enterobacteriaceae (ESBL-E) are of major concern in clinical practice because of limited therapeutic options effective to treat them. Published studies showed that ESBL-E, widely spread in Europe, United States or Asia; are also frequent in Africa. However, the impact of ESBL-E infections is yet to be adequately determined in Sub-Saharan African countries, particularly in Senegal. The aim of our study was to estimate the incidence rate of ESBL-E infections and to assess their clinical and economic impact in Senegal. METHODS: Two retrospective cohort studies were conducted in patients hospitalized from April to October 2012. A classic retrospective cohort study comparing patients infected by an Enterobacteriaceae producer of ESBL (ESBL+) and patients infected by an Enterobacteriaceae non-producer of ESBL (ESBL-) was carried out for fatal outcomes. Besides, a retrospective parallel cohort study comparing infected patients by an ESBL+ and ESBL- versus uninfected patients was carried out for the excess LOS analyses. Multivariable regression analysis was performed to identify risk factors for fatal outcomes. A multistate model and a cost-of-illness analysis were used to estimate respectively the excess length of stay (LOS) attributable to ESBL production and costs associated. Cox proportional hazards models were used to assess the independent effect of ESBL+ and ESBL- infections on LOS. RESULTS: The incidence rate of ESBL-E infections was 3 cases/1000 patient-days (95 % CI: 2.4-3.5 cases/1000 patient-days). Case fatality rate was higher in ESBL+ than in ESBL- infections (47.3 % versus 22.4 %, p = 0.0006). Multivariable analysis indicated that risk factors for fatal outcomes were the production of ESBL (OR = 5.7, 95 % CI: 3.2-29.6, p = 0.015) or being under mechanical ventilation (OR = 5.6, 95 % CI: 2.9-57.5, p = 0.030). Newborns and patients suffering from meningitidis or cancer were patients at-risk for fatal outcomes. ESBL production increased hospital LOS (+4 days) and reduced significantly the hazard of discharge after controlling for confounders (HR = 0.3, 95 % CI:0.2-0.4). The additional cost associated with ESBL-production of 100 is substantial given the lower-middle-income status of Senegal. CONCLUSION: Our findings show an important clinical and economic impact of ESBL-E infections in Senegal and emphasize the need to implement adequate infection control measures to reduce their incidence rate. An antibiotic stewardship program is also crucial to preserve the effectiveness of our last-resort antibiotic drugs.
ABSTRACT
CONTEXT: Severe bacterial infections are not considered as a leading cause of death in young children in sub-Saharan Africa. The worldwide emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) could change the paradigm, especially in neonates who are at high risk of developing healthcare-associated infections. OBJECTIVE: To evaluate the epidemiology and the burden of ESBL-E bloodstream infections (BSI). METHODS: A case-case-control study was conducted in patients admitted in a pediatric hospital during two consecutive years. Cases were patients with Enterobacteriaceae BSI and included ESBL-positive (cases 1) and ESBL-negative BSI (cases 2). Controls were patients with no BSI. Multivariate analysis using a stepwise logistic regression was performed to identify risk factors for ESBL acquisition and for fatal outcomes. A multistate model was used to estimate the excess length of hospital stay (LOS) attributable to ESBL production while accounting for time of infection. Cox proportional hazards models were performed to assess the independent effect of ESBL-positive and negative BSI on LOS. RESULTS: The incidence rate of ESBL-E BSI was of 1.52 cases/1000 patient-days (95% CI: 1.2-5.6 cases per 1000 patient-days). Multivariate analysis showed that independent risk factors for ESBL-BSI acquisition were related to underlying comorbidities (sickle cell disease OR = 3.1 (95%CI: 2.3-4.9), malnutrition OR = 2.0 (95%CI: 1.7-2.6)) and invasive procedures (mechanical ventilation OR = 3.5 (95%CI: 2.7-5.3)). Neonates were also identified to be at risk for ESBL-E BSI. Inadequate initial antibiotic therapy was more frequent in ESBL-positive BSI than ESBL-negative BSI (94.2% versus 5.7%, p<0.0001). ESBL-positive BSI was associated with higher case-fatality rate than ESBL-negative BSI (54.8% versus 15.4%, p<0.001). Multistate modelling indicated an excess LOS attributable to ESBL production of 4.3 days. The adjusted end-of-LOS hazard ratio for ESBL-positive BSI was 0.07 (95%CI, 0.04-0.12). CONCLUSION: Control of ESBL-E spread is an emergency in pediatric populations and could be achieved with simple cost-effective measures such as hand hygiene, proper management of excreta and better stewardship of antibiotic use, especially for empirical therapy.
