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Escherichia coli and Klebsiella pneumoniae are two of the most common causes of bloodstream infections (BSIs) worldwide.1,2 β-Lactam antibiotics are the preferred treatment because of their selective toxicity, broad spectrum of activity, and low cost.3,4 However, E. coli and K. pneumoniae, and other Enterobacteriaceae, have developed extended-spectrum β-lactamase (ESBL)–producing capability and can hydrolyze penicillins, cephalosporins, and monobactams, rendering them clinically ineffective.5 Extended-spectrum β-lactamase–producing E. coli and K. pneumoniae are increasingly reported worldwide in hospital and community settings, resulting in prolonged and more expensive hospitalizations and increased morbidity and mortality.6,7 Prompt identification is essential for appropriate treatment and improved patient outcomes.8,9 Extended-spectrum β-lactamase–producing E. coli have been identified throughout Thailand,10–13 with the first documented case in 1994,14 and a prevalence among different clinical specimens ranging from 22% to 59%, and evidence that they are becoming more common.10–13,15 However, representative estimates of the incidence of ESBL-producing E. coli and K. pneumoniae and longitudinal trends in antimicrobial resistance are currently limited in Southeast Asia. This study aimed to expand our understanding of ESBL-producing pathogen disease burden by estimating trends in population-based E. coli and K. pneumoniae bacteremia incidence, changes over time in the proportion of these cases due to ESBL-producing organisms, susceptibility profiles to other antibiotics, and the probability of recurrent infections. This study used the same well-established surveillance database that was previously used to estimate the incidence and susceptibility profiles of several other pathogens in rural Thailand.16–19

The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed comprehensive quality indicator, data query, and monitoring reports. Among the approximately 9000 cases and controls, analyzable laboratory results were available for ≥96% of core specimens collected. Selected approaches to data management in PERCH may be extended to the planning and organization of international studies of similar scope and complexity.

Bloodstream infection surveillance conducted from 2008 to 2014 in all 20 hospitals in Sa Kaeo and Nakhon Phanom provinces, Thailand, allowed us to look at disease burden, antibiotic susceptibilities, and recurrent infections caused by extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella pneumoniae. Of 97,832 blood specimens, 3,338 were positive for E. coli and 1,086 for K. pneumoniae. The proportion of E. coli isolates producing ESBL significantly increased from 19% to 22% in 2008–2010 to approximately 30% from 2011 to 2014 (P-value for trend = 0.02), whereas ESBL production among K. pneumoniae cases was 27.4% with no significant trend over time. Incidence of community-onset ESBL-producing E. coli increased from 5.4 per 100,000 population in 2008 to 12.8 in 2014, with the highest rates among persons aged ≥ 70 years at 79 cases per 100,000 persons in 2014. From 2008 to 2014, community-onset ESBL-producing K. pneumoniae incidence was 2.7 per 100,000, with a rate of 12.9 among those aged ≥ 70 years. Although most (93.6% of E. coli and 87.6% of K. pneumoniae) infections were community-onset, hospital-onset infections were twice as likely to be ESBL. Population-based surveillance, as described, is vital to accurately monitor emergence and trends in antimicrobial resistance, and in guiding the development of rational antimicrobial therapy recommendations.

Results In total 65,078 patients were enrolled into 213 clinical trials of artemisinin-containing regimens with 413 treatment arms containing either an artemisinin derivative alone (n=26) or in combination with a partner drug (n=387). The proportion of patients remaining parasitaemic at 24, 48 and 72 hours was documented in 115 (28%), 167 (40%) and 153 (37%) treatment arms, respectively. Excluding resistance studies in Cambodia, the median proportion of patients still parasitaemic was 53.8% [range 3-95, IQR=30.5-69.2] at 24 hours, 6% [range 0-65.9, IQR=2-11.5] at 48 hours and 0 [range 012.6, IQR=0-2] at 72 hours. Comparing studies from 2000-2005 and 2006-2011, the median proportion of patients remaining parasitaemic at 72 hours decreased in Africa (1.6% vs. 0, p=0.0004), but increased in Asia (0.8% vs. 1.2%, p=