Search

Background Bloodstream infection (BSI) surveillance is essential to characterize the public health threat of bacteremia. We summarize BSI epidemiology in rural Thailand over an eight year period. Methods Population-based surveillance captured clinically indicated blood cultures and associated antimicrobial susceptibility results performed in all 20 hospitals in Nakhon Phanom (NP) and Sa Kaeo (SK) provinces. BSIs were classified as community-onset (CO) when positive cultures were obtained ≤2 days after hospital admission and hospital-onset (HO) thereafter. Hospitalization denominator data were available for incidence estimates for 2009–2014. Results From 2007 to 2014 a total of 11,166 BSIs were identified from 134,441 blood cultures. Annual CO BSI incidence ranged between 89.2 and 123.5 cases per 100,000 persons in SK and NP until 2011. Afterwards, CO incidence remained stable in SK and increased in NP, reaching 155.7 in 2013. Increases in CO BSI incidence over time were limited to persons aged ≥50 years. Ten pathogens, in rank order, accounted for > 65% of CO BSIs in both provinces, all age-groups, and all years: Escherichia coli, Klebsiella pneumoniae, Burkholderia pseudomallei, Staphylococcus aureus, Salmonella non-typhi spp., Streptococcus pneumoniae, Acinetobacter spp., Streptococcus agalactiae, Streptococcus pyogenes, Pseudomonas aeruginosa. HO BSI incidence increased in NP from 0.58 cases per 1000 hospitalizations in 2009 to 0.91 in 2014, but were higher (ranging from 1.9 to 2.3) in SK throughout the study period. Extended-spectrum beta-lactamase production among E. coli isolates and multi-drug resistance among Acinetobacter spp. isolates was common (> 25% of isolates), especially among HO cases (> 50% of isolates), and became more common over time, while methicillin-resistance among S. aureus isolates (10%) showed no clear trend. Carbapenem-resistant Enterobacteriaceae were documented in 2011–2014. Conclusions Population-based surveillance documented CO BSI incidence estimates higher than previously reported from Thailand and the region, with temporal increases seen in older populations. The most commonly observed pathogens including resistance profiles were similar to leading pathogens and resistance profiles worldwide, thus; prevention strategies with demonstrated success elsewhere may prove effective in Thailand. Electronic supplementary material The online version of this article (10.1186/s12889-019-6775-4) contains supplementary material, which is available to authorized users.

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

Melioidosis incidence and mortality have reportedly been increasing in endemic areas of Thailand, but little population-based data on culture-confirmed Burkholderia pseudomallei infections exist. We provide updated estimates of melioidosis bacteremia incidence and in-hospital mortality rate using integration of two population-based surveillance databases in Nakhon Phanom, Thailand, since automated blood culture became available in 2005. From 2009 to 2013, 564 hospitalized bacteremic melioidosis patients were identified. The annual incidence of bacteremic melioidosis ranged from 14 to 17 per 100,000 persons, and average population mortality rate was 2 per 100,000 persons per year. In-hospital mortality rate declined nonsignificantly from 15% (15/102) to 13% (15/118). Of 313 (56%) bacteremic melioidosis patients who met criteria for acute lower respiratory infection and were included in the hospital-based pneumonia surveillance system, 65% (202/313) had a chest radiograph performed within 48 hours of admission; 46% (92/202) showed radiographic evidence of pneumonia. Annual incidence of bacteremic melioidosis with pneumonia was 2.4 per 100,000 persons (95% confidence intervals; 1.9–2.9). In-hospital death was more likely among bacteremic melioidosis patients with pneumonia (34%; 20/59) compared with non-pneumonia patients (18%; 59/321) (P-value = 0.007). The overall mortality could have been as high as 46% (257/564) if patients with poor clinical condition at the time of discharge had died. The continued high incidence of bacteremic melioidosis, pneumonia, and deaths in an endemic area highlights the need for early diagnosis and treatment and additional interventions for the prevention and control for melioidosis.

Background It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. Methods We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1–59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative of the lower respiratory tract will contain smaller quantities of oropharyngeal flora and be more likely to have a predominance of potential pathogens compared to a specimen containing mainly saliva. The prevalence of potential pathogens cultured from induced sputum specimens and quantity of oropharyngeal flora were compared for different quantities of SECs and PMNs. Results Of 3772 induced sputum specimens, 2608 (69%) had 25 PMNs per LPF, measures traditionally associated with specimens from the lower respiratory tract in adults. Using isolation of low quantities of oropharyngeal flora and higher prevalence of potential pathogens as markers of higher quality, 25 PMNs per LPF) was the microscopic variable most associated with high quality of induced sputum. Conclusions Quantity of SECs may be a useful quality measure of induced sputum from young children with pneumonia.

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.

Figure S1. Community-onset (CO) BSIs caused by Gram-negative pathogens by month in Sa Kaeo and Nakhon Phanom provinces, Thailand, 2007â 2014. (PDF 156 kb)

Staphylococcus aureus infections are one of the most common bloodstream infections worldwide.1,2 Antimicrobial resistant strains, namely, methicillin-resistant S. aureus (MRSA), are associated with increased mortality, length of hospitalization, and health-care costs3–5; yet, the burden of disease is poorly understood in many countries. A 2014 World Health Organization (WHO) report emphasized the critical need for greater surveillance to more rapidly detect, respond, and control public health threats and therefore enhance global health security. World Health Organization also highlighted major gaps in surveillance in Southeast Asia.6 The few available studies suggest that S. aureus is one of the top causes of bloodstream infections in Thailand and Southeast Asia.7–13 A 2012 review found that methicillin resistance among S. aureus in Southeast Asia varied from 0–39%.14 In two cross-sectional studies in tertiary hospitals in Bangkok and northeast Thailand from 2005 and 2006, MRSA was documented in > 20% of S. aureus isolates.10,11 Since then, significant changes in the epidemiology of S. aureus and methicillin resistance in Thailand and the region may have occurred. The 2011 Jaipur Declaration emphasized the importance of antimicrobial resistance and the need for immediate regional action,15 and infection control efforts in tertiary care centers in Thailand have been intensified.16–18 A better understanding of current trends in S. aureus and MRSA bacteremia is needed to monitor trends and guide prevention and control efforts in Thailand. In 2005, the Thailand Ministry of Public Health, in collaboration with the U.S. Centers for Disease Control and Prevention (CDC), initiated population-based surveillance of bloodstream infections in two rural provinces in Thailand to create a sustainable system to monitor changes in pathogenesis and resistance patterns in rural border provinces where emerging epidemics could occur. This included implementation of automated blood culturing systems and sustained laboratory capacity building activities that were not as developed as in a metropolitan center such as Bangkok. We report incidence rates and trends in S. aureus bacteremia and methicillin resistance from 2006–2014.

Pneumonia remains a leading cause of under-five morbidity and mortality globally. Comprehensive incidence, epidemiologic and etiologic data are needed to update prevention and control strategies.We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory tract infections (ALRI) among children5 years of age in rural Thailand. ALRI cases were systematically sampled for an etiology study that tested nasopharyngeal specimens by polymerase chain reaction; children without ALRI were enrolled as controls from outpatient clinics.We identified 28,543 hospitalized ALRI cases from 2005 to 2010. Among the 49% with chest radiographs, 76% had findings consistent with pneumonia as identified by 2 study radiologists. The hospitalized ALRI incidence rate was 5772 per 100,000 child-years (95% confidence interval: 5707, 5837) and was higher in boys versus girls (incidence rate ratio 1.38, 95% confidence interval: 1.35-1.41) and in children 6-23 months of age versus other age groups (incidence rate ratio 1.76, 95% confidence interval: 1.69-1.84). Viruses most commonly detected in ALRI cases were respiratory syncytial virus (19.5%), rhinoviruses (18.7%), bocavirus (12.8%) and influenza viruses (8%). Compared with controls, ALRI cases were more likely to test positive for respiratory syncytial virus, influenza, adenovirus, human metapneumovirus and parainfluenza viruses 1 and 3 (P ≤ 0.01 for all). Bloodstream infections, most commonly Streptococcus pneumoniae and nontyphoidal Salmonella, accounted for 1.8% of cases.Our findings underscore the high burden of hospitalization for ALRI and the importance of viral pathogens among children in Thailand. Interventions targeting viral pathogens coupled with improved diagnostic approaches, especially for bacteria, are critical for better understanding of ALRI etiology, prevention and control.

Introduction The prevalence of bacteremia caused by Gram negative non-fermentative (GNNF) bacteria has been increasing globally over the past decade. Many studies have investigated their epidemiology but focus on the common GNNF including Pseudomonas aeruginosa and Acinetobacter baumannii. Knowledge of the uncommon GNNF bacteremias is very limited. This study explores invasive bloodstream infection GNNF isolates that were initially unidentified after testing with standard microbiological techniques. All isolations were made during laboratory-based surveillance activities in two rural provinces of Thailand between 2006 and 2014. Methods A subset of GNNF clinical isolates (204/947), not identified by standard manual biochemical methodologies were run on the BD Phoenix automated identification and susceptibility testing system. If an organism was not identified (12/204) DNA was extracted for whole genome sequencing (WGS) on a MiSeq platform and data analysis performed using 3 web-based platforms: Taxonomer, CGE KmerFinder and One Codex. Results The BD Phoenix automated identification system recognized 92% (187/204) of the GNNF isolates, and because of their taxonomic complexity and high phenotypic similarity 37% (69/187) were only identified to the genus level. Five isolates grew too slowly for identification. Antimicrobial sensitivity (AST) data was not obtained for 93/187 (50%) identified isolates either because of their slow growth or their taxa were not in the AST database associated with the instrument. WGS identified the 12 remaining unknowns, four to genus level only. Conclusion The GNNF bacteria are of increasing concern in the clinical setting, and our inability to identify these organisms and determine their AST profiles will impede treatment. Databases for automated identification systems and sequencing annotation need to be improved so that opportunistic organisms are better covered., Author summary Infections caused by Gram negative non fermentative bacteria (GNNF), other than the more commonly described Pseudomonas aeruginosa and Acinetobacter baumannii, constitute an emerging problem. They are not only isolated in nosocomial settings, mainly affecting immunocomprised hosts, but also are opportunistic infections causing invasive disease in rural communities. GNNF bacteria are ubiquitously distributed in the environment and have a high propensity for antimicrobial resistance. Thus, their accurate identification to the species level is important for appropriate patient management. These bacteria are taxonomically heterogeneous, and many isolates are not satisfactorily identified by the standard biochemical assays because of overlapping phenotypic characteristics. In this study we explored using the BD Phoenix automated identification system to improve the identification of GNNF isolates and recognized 92% (187/204) of the previously unidentified isolates; 117 of which were to the species level. Antimicrobial resistance profiles were identified for 50% (94/187) of the isolates identified by the BD Phoenix system. For the remaining 12 unidentified organisms whole genome sequencing was performed. Three web-based programs were used for organism identification and results varied because of differences in the underlying databases used.

Introduction Invasive salmonellosis is a common cause of bloodstream infection in Southeast Asia. Limited epidemiologic and antimicrobial resistance data are available from the region. Methods Blood cultures performed in all 20 hospitals in the northeastern province of Nakhon Phanom (NP) and eastern province of Sa Kaeo (SK), Thailand were captured in a bloodstream infection surveillance system. Cultures were performed as clinically indicated in hospitalized patients; patients with multiple positive cultures had only the first included. Bottles were incubated using the BacT/Alert system (bioMérieux, Thailand) and isolates were identified using standard microbiological techniques; all Salmonella isolates were classified to at least the serogroup level. Antimicrobial resistance was assessed using disk diffusion. Results Salmonella was the fifth most common pathogen identified in 147,535 cultures with 525 cases (211 in Nakhon Phanom (NP) and 314 in Sa Kaeo (SK)). The overall adjusted iNTS incidence rate in NP was 4.0 cases/100,000 person-years (95% CI 3.5–4.5) and in SK 6.4 cases/100,000 person-years (95% CI 5.7–7.1; p = 0.001). The most common serogroups were C (39.4%), D (35.0%) and B (9.9%). Serogroup D predominated in NP (103/211) with 59.2% of this serogroup being Salmonella serovar Enteritidis. Serogroup C predominated in SK (166/314) with 84.3% of this serogroup being Salmonella serovar Choleraesuis. Antibiotic resistance was 68.2% (343/503) for ampicillin, 1.2% (6/482) for ciprofloxacin (or 58.1% (280/482) if both intermediate and resistant phenotypes are considered), 17.0% (87/512) for trimethoprim-sulfamethoxazole, and 12.2% (59/484) for third-generation cephalosporins (cefotaxime or ceftazidime). Multidrug resistance was seen in 99/516 isolates (19.2%). Conclusions The NTS isolates causing bloodstream infections in rural Thailand are commonly resistant to ampicillin, cefotaxime, and TMP-SMX. Observed differences between NP and SK indicate that serogroup distribution and antibiotic resistance may substantially differ throughout Thailand and the region., Author summary Invasive strains of non-typhoidal salmonella (iNTS) are a common cause of bloodstream infection in Southeast Asia, however limited epidemiologic and antimicrobial resistance data are available and no population-based studies have been published from the region. We use nine years of bloodstream infections data from surveillance conducted in two Thai border provinces to report on the incidence, serotype distribution and antimicrobial resistance patterns. Incidence of iNTS was 5.1 cases/100,000 population (95% CI 4.7–5.6), likely an under estimate of the true burden of disease as we only used hospitalized cases and less sensitive blood culture for bacterial isolation. Levels of drug non-susceptibility were high among isolates, especially for fluoroquinolones such as ciprofloxacin (~60%) and third-generation cephalosporins such as cefotaxime or ceftazidime (~15%) that are commonly prescribed to provide empirical coverage against these pathogens. Multidrug resistance was widespread at 20% of isolates. Our data emphasizes the need for increased microbiological surveillance, and support the need for rational antibiotic therapy and the development of treatment guidelines.

No studies have quantified the impact of pre-culture antibiotic use on the recovery of individual blood- borne pathogens or on population-level incidence estimates for Streptococcus pneumoniae . We conducted bloodstream infection surveillance in Thailand during November 2005-June 2008. Pre-culture antibiotic use was assessed by reported use and by serum antimicrobial activity. Of 35,639 patient blood cultures, 27% had reported pre-culture antibiotic use and 24% (of 24,538 tested) had serum antimicrobial activity. Pathogen isolation was half as common in patients with versus without antibiotic use; S. pneumoniae isolation was 4- to 9-fold less common (0.09% versus 0.37% by reported antibiotic use; 0.05% versus 0.45% by serum antimicrobial activity, P < 0.01). Pre-culture antibiotic use by serum antimicrobial activ- ity reduced pneumococcal bacteremia incidence by 32% overall and 39% in children < 5 years of age. Our findings high- light the limitations of culture-based detection methods to estimate invasive pneumococcal disease incidence in settings where pre-culture antibiotic use is common.

Community-acquired bloodstream infections cause substantial morbidity and mortality worldwide, but microbiology capacity and surveillance limitations have challenged good descriptions of pathogen distribution in many regions, including Southeast Asia. Active surveillance for bloodstream infections has been conducted in two rural Thailand provinces for >7 years. Blood specimens were divided into two culture bottles, one optimized for aerobic growth (F bottle) and a second for enhanced growth of mycobacteria (MB bottle), and processed with the BactT/Alert 3D system. Because the routine use of MB culture bottles is resource intensive (expensive and requires prolonged incubation), we assessed the added yield of MB bottles by comparing the proportion of pathogens detected by MB versus that by F bottles from 2005 to 2012. Of 63,066 blood cultures, 7,296 (12%) were positive for at least one pathogen; the most common pathogens were Escherichia coli (28%), Burkholderia pseudomallei (11%), Klebsiella pneumoniae (9%), and Staphylococcus aureus (6%). Two bottles improved the yield overall, but the added yield attributable to the MB bottles was limited to a few pathogens. In addition to the detection of mycobacteria and some fungi, MB bottles improved the detection of B. pseudomallei (27% [MB] versus 8% [F]; P < 0.0001), with added benefit if therapy was initiated prior to the blood culture. The targeted use of MB bottles is warranted for patients at risk for mycobacterial and fungal infections and for infection with B. pseudomallei , a common cause of septicemia in Thailand.

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions.

SUMMARYAcinetobacteris a well-recognized nosocomial pathogen. Previous reports of community-associatedAcinetobacterinfections have lacked clear case definitions and assessment of healthcare-associated (HCA) risk factors. We identifiedAcinetobacterbacteraemia cases from blood cultures obtained Acinetobactercases, 32 (44%) had no HCA risk factors. Compared to HCA infections, non-HCA infections were more often caused byAcinetobacterspecies other thancalcoaceticus–baumanniicomplex species and by antibiotic-susceptible organisms. Despite similar symptoms, the case-fatality proportion was lower in non-HCA than HCA cases (9%vs. 45%,P Acinetobacteras a potential cause of community-associated infections in Thailand; prospective studies are needed to improve understanding of associated risk factors and disease burden.

Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in northeastern Thailand. Population-based disease burden estimates are lacking and limited data on melioidosis exist from other regions of the country. Using active, population-based surveillance, we measured the incidence of bacteremic melioidosis in the provinces of Sa Kaeo (eastern Thailand) and Nakhon Phanom (northeastern Thailand) during 2006–2008. The average annual incidence in Sa Kaeo and Nakhon Phanom per 100,000 persons was 4.9 (95% confidence interval [CI] = 3.9–6.1) and 14.9 (95% CI = 13.3–16.6). The respective population mortality rates were 1.9 (95% CI = 1.3–2.8) and 4.4 (95% CI = 3.6–5.3) per 100,000. The case-fatality proportion was 36% among those with known outcome. Our findings document a high incidence and case fatality proportion of bacteremic melioidosis in Thailand, including a region not traditionally considered highly endemic, and have potential implications for clinical management and health policy.

Background. Population-based estimates of the incidence of invasive pneumococcal disease are unavailable for Thailand and other countries in Southeast Asia. We estimated the incidence of pneumococcal bacteremia cases requiring hospitalization in rural Thailand. Methods. Blood cultures were performed on samples from hospitalized patients in 2 rural provinces where active, population-based surveillance of community-acquired pneumonia is conducted. Blood cultures were performed at clinician discretion and were encouraged for all patients with suspected pneumonia and all children aged

BACKGROUNDStreptococcus pneumoniae is an important cause of morbidity and mortality in Southeast Asia, but regional data is limited. Updated burden estimates are critical as pneumococcal conjugate vaccine (PCV) is highly effective, but not yet included in the Expanded Program on Immunization of Thailand or neighboring countries.METHODSWe implemented automated blood culture systems in two rural Thailand provinces as part of population-based surveillance for bacteremia. Blood cultures were collected from hospitalized patients as clinically indicated.RESULTSFrom May 2005- March 2010, 196 cases of pneumococcal bacteremia were confirmed in hospitalized patients. Of these, 57% had clinical pneumonia, 20% required mechanical ventilation, and 23% (n = 46) died. Antibiotic use before blood culture was confirmed in 25% of those with blood culture. Annual incidence of hospitalized pneumococcal bacteremia was 3.6 per 100,000 person-years; rates were higher among children aged CONCLUSIONSWe demonstrated a high pneumococcal bacteremia burden, yet underestimated incidence because we captured only hospitalized cases, and because pre-culture antibiotics were frequently used. Our findings together with prior research indicate that PCV would likely have high serotype coverage in Thailand. These findings will complement ongoing cost effectiveness analyses and support vaccine policy evaluation in Thailand and the region.