Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

BACKGROUND: Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified. METHODS: We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in Escherichia coli and Klebsiella pneumoniae BSI. We matched each bacteraemic patient to two uninfected patients. We compared outcomes between 3GC-susceptible and 3GC-resistant BSI and their respective uninfected controls using Cox regression models. RESULTS: For 1431 E. coli BSI patients, we matched 1152 (81%) 3GC-susceptible and 279 (19%) 3GC-resistant cases to 2263 and 546 uninfected inpatient controls. For 1368 K. pneumoniae BSI patients, we matched 502 (37%) 3GC-susceptible and 866 (63%) 3GC-resistant cases to 982 and 1656 uninfected inpatient controls. We found that 3GC-resistant E. coli had similar hazard ratios (HRs) for in-hospital mortality over their matched controls as compared to susceptible infections over their controls (ratio of HRs 1.03, 95% CI 0.73-1.46). Similarly, 3GC-resistance in K. pneumoniae BSI was not associated with mortality (ratio of HR 1.10, 95% CI 0.80-1.52). Estimates of mortality impact varied by site without a consistent pattern. CONCLUSIONS: In a retrospective analysis, including the use of matched uninfected patients, there did not appear to be an impact of 3GC-resistance on mortality in E. coli or K. pneumoniae BSI in African hospitals, as compared with susceptible BSI with equivalent species. Better information on the actual use of antibiotics in treating infections in African hospitals would improve these impact estimates.

Erratum to: Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study.

[This corrects the article DOI: 10.1093/jacamr/dlaa130.].

Bacterial Infections in Neonates, Madagascar, 2012-2014.

Severe bacterial infections are a leading cause of death among neonates in low-income countries, which harbor several factors leading to emergence and spread of multidrug-resistant bacteria. Low-income countries should prioritize interventions to decrease neonatal infections; however, data are scarce, specifically from the community. To assess incidence, etiologies, and antimicrobial drug-resistance patterns of neonatal infections, during 2012-2014, we conducted a community-based prospective investigation of 981 newborns in rural and urban areas of Madagascar. The incidence of culture-confirmed severe neonatal infections was high: 17.7 cases/1,000 live births. Most (75%) occurred during the first week of life. The most common (81%) bacteria isolated were gram-negative. The incidence rate for multidrug-resistant neonatal infection was 7.7 cases/1,000 live births. In Madagascar, interventions to improve prevention, early diagnosis, and management of bacterial infections in neonates should be prioritized.

Acquisition of extended spectrum beta-lactamase-producing enterobacteriaceae in neonates: A community based cohort in Madagascar.

In low and middle income countries (LMICs), where the burden of neonatal sepsis is the highest, the spread of extended spectrum beta-lactamase-producing enterobacteriaceae (ESBL-PE) in the community, potentially contributing to the neonatal mortality, is a public health concern. Data regarding the acquisition of ESBL-PE during the neonatal period are scarce. The routes of transmission are not well defined and particularly the possible key role played by pregnant women. This study aimed to understand the neonatal acquisition of ESBL-PE in the community in Madagascar. The study was conducted in urban and semi-rural areas. Newborns were included at birth and followed-up during their first month of life. Maternal stool samples at delivery and six stool samples in each infant were collected to screen for ESBL-PE. A Cox proportional hazards model was performed to identify factors associated with the first ESBL-PE acquisition. The incidence rate of ESBL-PE acquisition was 10.4 cases/1000 newborn-days [95% CI: 8.0-13.4 cases per 1000 newborn-days]. Of the 83 ESBL-PE isolates identified, Escherichia coli was the most frequent species (n = 28, 34.1%), followed by Klebsiella pneumoniae (n = 20, 24.4%). Cox multivariate analysis showed that independent risk factors for ESBL-PE acquisition were low birth weight (adjusted Hazard-ratio (aHR) = 2.7, 95% CI [1.2; 5.9]), cesarean-section, (aHR = 3.4, 95% CI [1.7; 7.1]) and maternal use of antibiotics at delivery (aHR = 2.2, 95% CI [1.1; 4.5]). Our results confirm that mothers play a significant role in the neonatal acquisition of ESBL-PE. In LMICs, public health interventions during pregnancy should be reinforced to avoid unnecessary caesarean section, unnecessary antibiotic use at delivery and low birth weight newborns.

Combating Global Antibiotic Resistance: Emerging One Health Concerns in Lower- and Middle-Income Countries.

Antibiotic misuse in lower- and middle-income countries (LMICs) contributes to the development of antibiotic resistance that can disseminate globally. Strategies specific to LMICs that seek to reduce antibiotic misuse by humans, but simultaneously improve antibiotic access, have been proposed. However, most approaches to date have not considered the growing impact of animal and environmental reservoirs of antibiotic resistance, which threaten to exacerbate the antibiotic resistance crisis in LMICs. In particular, current strategies do not prioritize the impacts of increased antibiotic use for terrestrial food-animal and aquaculture production, inadequate food safety, and widespread environmental pollution. Here, we propose new approaches that address emerging, One Health challenges.

A community survey of antibiotic consumption among children in Madagascar and Senegal: the importance of healthcare access and care quality.

BACKGROUND: Antibiotic resistance is growing in low-income countries (LICs). Children in LICs are particularly at risk. Information on antibiotic consumption is needed to control the development and spread of resistant bacteria. METHODS: To measure antibiotic consumption and related factors, a community survey was undertaken in two sites in Madagascar (Antananarivo and Moramanga) and in Senegal (Guediawaye) among children under 2. Face-to-face interviews were conducted with parents or caregivers of eligible children. Regression analysis was used to determine variables associated with reported antibiotic consumption. Availability of health structures and health policies were also investigated. RESULTS: Population estimates for antibiotic consumption in the last 3 months were 37.2% (95% CI 33.4%-41.2%) in Guediawaye, 29.3% (95% CI 25.0%-34.1%) in Antananarivo and 24.6% (95% CI 20.6%-29.1%) in Moramanga. In all sites, the large majority of antibiotics were taken with a prescription (92.2%, 87.0% and 92.0% for Antananarivo, Moramanga and Guediawaye, respectively) and purchased in pharmacies (89.4%, 73.5% and 78.5%, respectively). Living in houses without flushing toilets and baby age were significantly associated with any antibiotic consumption after adjusting for site. A higher density of public health structures was associated with lower antibiotic consumption levels, while a higher density of private pharmacies was associated with higher levels across sites. CONCLUSIONS: These data are crucial for the implementation of local programmes aimed at optimizing antibiotic consumption. Factors such as density of healthcare facilities, prescriber training and national policy must be taken into account when developing strategies to optimize antibiotic consumption in LICs.

Infections caused by extended-spectrum beta-lactamases producing Enterobacteriaceae: clinical and economic impact in patients hospitalized in 2 teaching hospitals in Dakar, Senegal.

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.

Epidemiology and Burden of Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae in a Pediatric Hospital in Senegal.

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.