Ertapenem Versus Meropenem for the Treatment of Extended Spectrum Beta-Lactamase-Producing Enterobacterales Bacteremia in Critically Ill Patients.

BACKGROUND: The preferred carbapenem for treatment of infections caused by extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in critically ill patients is debated. OBJECTIVE: The purpose of this study was to evaluate the difference in clinical failure between ertapenem and meropenem for treatment of ESBL-E bacteremia in critically ill patients. Of concern is ertapenem use in hypoalbuminemia given the potential for higher drug clearance. METHODS: This retrospective, matched cohort study compared critically ill patients treated with ertapenem or meropenem for ESBL-E bacteremia between October 2016 and August 2022. Patients were matched on age, sex, lowest albumin, and in a 1:2 ratio of ertapenem to meropenem. The primary outcome, clinical failure, was a composite of 30-day mortality, antibiotic escalation, and microbiological failure. Secondary outcomes included all-cause readmission and development of superinfection. RESULTS: Of 54 patients, 18 received ertapenem and 36 meropenem. Most had a urinary infection source (55.6% vs 41.7%, P = 0.393). There was no difference in clinical failure (50.0% vs 38.9%, P = 0.436). Ertapenem patients had antibiotic escalation more often (33.3% vs 2.8%, P = 0.002). There was no difference in 30-day mortality (11.1% vs 27.8%, P = 0.298), microbiological failure (27.8% vs 11.1%, P = 0.142), all-cause readmission (22.2% vs 13.9%, P = 0.461), or development of superinfection (11.1% vs 13.9%, P = 1.000). CONCLUSION AND RELEVANCE: There was no difference in clinical failure in a small, retrospective cohort of critically ill patients receiving ertapenem or meropenem for ESBL-E bacteremia. Ertapenem may be appropriate in some critically ill and hypoalbuminemic patients, though additional data are needed.

Automated versus physician assignment of cause of death for verbal autopsies: randomized trial of 9374 deaths in 117 villages in India.

BACKGROUND: Verbal autopsies with physician assignment of cause of death (COD) are commonly used in settings where medical certification of deaths is uncommon. It remains unanswered if automated algorithms can replace physician assignment. METHODS: We randomized verbal autopsy interviews for deaths in 117 villages in rural India to either physician or automated COD assignment. Twenty-four trained lay (non-medical) surveyors applied the allocated method using a laptop-based electronic system. Two of 25 physicians were allocated randomly to independently code the deaths in the physician assignment arm. Six algorithms (Naïve Bayes Classifier (NBC), King-Lu, InSilicoVA, InSilicoVA-NT, InterVA-4, and SmartVA) coded each death in the automated arm. The primary outcome was concordance with the COD distribution in the standard physician-assigned arm. Four thousand six hundred fifty-one (4651) deaths were allocated to physician (standard), and 4723 to automated arms. RESULTS: The two arms were nearly identical in demographics and key symptom patterns. The average concordances of automated algorithms with the standard were 62%, 56%, and 59% for adult, child, and neonatal deaths, respectively. Automated algorithms showed inconsistent results, even for causes that are relatively easy to identify such as road traffic injuries. Automated algorithms underestimated the number of cancer and suicide deaths in adults and overestimated other injuries in adults and children. Across all ages, average weighted concordance with the standard was 62% (range 79-45%) with the best to worst ranking automated algorithms being InterVA-4, InSilicoVA-NT, InSilicoVA, SmartVA, NBC, and King-Lu. Individual-level sensitivity for causes of adult deaths in the automated arm was low between the algorithms but high between two independent physicians in the physician arm. CONCLUSIONS: While desirable, automated algorithms require further development and rigorous evaluation. Lay reporting of deaths paired with physician COD assignment of verbal autopsies, despite some limitations, remains a practicable method to document the patterns of mortality reliably for unattended deaths. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02810366. Submitted on 11 April 2016.

Epidemiology of dengue virus infections in Nepal, 2006-2019.

BACKGROUND: Dengue is one of the newest emerging diseases in Nepal with increasing burden and geographic spread over the years. The main objective of this study was to explore the epidemiological patterns of dengue since its first outbreak (2006) to 2019 in Nepal. METHODS: This study is a retrospective analysis that covers the last 14 years (2006-2019) of reported dengue cases from Epidemiology Diseases Control Division (EDCD), Ministry of Health and Population, Government of Nepal. Reported cases were plotted over time and maps of reported case incidence were generated (from 2016 through 2019). An ecological analysis of environmental predictors of case incidence was conducted using negative binomial regression. RESULTS: While endemic dengue has been reported in Nepal since 2006, the case load has increased over time and in 2019 a total of 17 992 dengue cases were reported from 68 districts (from all seven provinces). Compared to the case incidence in 2016, incidence was approximately five times higher in 2018 [incidence rate ratio (IRR): 4.8; 95% confidence interval (CI) 1.5-15.3] and over 140 times higher in 2019 (IRR: 141.6; 95% CI 45.8-438.4). A one standard deviation increase in elevation was associated with a 90% decrease in reported case incidence (IRR: 0.10; 95% CI 0.01-0.20). However, the association between elevation and reported cases varied across the years. In 2018 there was a cluster of cases reported from high elevation Kaski District of Gandaki Province. Our results suggest that dengue infections are increasing in magnitude and expanding out of the lowland areas to higher elevations over time. CONCLUSIONS: There is a high risk of dengue outbreak in the lowland Terai region, with increasing spread towards the mid-mountains and beyond as seen over the last 14 years. Urgent measures are required to increase the availability of diagnostics and resources to mitigate future dengue epidemics.