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IntroductionAntimicrobial stewardship (AMS) is an important strategy to control antimicrobial resistance. Resources are available to provide guidance for design and implementation of AMS programmes, however these may have limited applicability in resource-limited settings including those in Asia. This scoping review aims to identify context-specific domains and items for the development of a healthcare facility (HCF)-level tool to guide AMS implementation in Asia.Methods and analysisThis review is the first step in a larger project to assess AMS implementation, needs and gaps in Asia. We will employ a deductive qualitative approach to identify locally appropriate domains and items of AMS implementation guided by Nilsen and Bernhardsson’s contextual dimensions. This process is also informed by discussions from a technical advisory group coordinated by the US Centers for Disease Control and Prevention to develop an AMS HCF-level assessment tool for low-income and middle-income countries. We will review English-language documents that discuss HCF-level implementation, including those describing frameworks, components/elements or recommendations for design, implementation or assessment globally and specific to Asia. We have performed the search in August–September 2021 including general electronic databases (MEDLINE, Embase, Web of Science and Google Scholar), region-specific databases, national action plans, grey literature sources and reference lists to identify eligible documents. Country-specific documents will be restricted to countries in three subregions: South Asia, East Asia and Southeast Asia. Codes and themes will be derived through a content analysis, classified following the predefined context dimensions and used for developing domains and items of the assessment tool.Ethics and disseminationResults from this review will feed into our stepwise process for developing a context-specific HCF-level assessment tool for AMS programmes to assess the implementation status, identify intervention opportunities and monitor progress over time. The process will be done in consultation with local stakeholders, the end-users of the generated knowledge.

Background There is a paucity of data regarding blood culture utilization and antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs). In addition, there has been a concern for increasing AMR infections among COVID-19 cases in LMICs. Here, we investigated epidemiology of AMR bloodstream infections (BSI) before and during the COVID-19 pandemic in the Indonesian national referral hospital. Methods We evaluated blood culture utilization rate, and proportion and incidence rate of AMR-BSI caused by WHO-defined priority bacteria using routine hospital databases from 2019 to 2020. A patient was classified as a COVID-19 case if their SARS-CoV-2 RT-PCR result was positive. The proportion of resistance was defined as the ratio of the number of patients having a positive blood culture for a WHO global priority resistant pathogen per the total number of patients having a positive blood culture for the given pathogen. Poisson regression models were used to assess changes in rate over time. Results Of 60,228 in-hospital patients, 8,175 had at least one blood culture taken (total 17,819 blood cultures), giving a blood culture utilization rate of 30.6 per 1,000 patient-days. A total of 1,311 patients were COVID-19 cases. Blood culture utilization rate had been increasing before and during the COVID-19 pandemic (both p p K. pneumoniae (23.3%), Acinetobacter spp. (13.9%) and E. coli (13.1%). The proportion of resistance for each bacterial pathogen was similar between COVID-19 and non-COVID-19 cases (all p > 0.10). Incidence rate of hospital-origin AMR-BSI increased from 130.1 cases per 100,000 patient-days in 2019 to 165.5 in 2020 (incidence rate ratio 1.016 per month, 95%CI:1.016–1.017, p p = 0.96). Conclusions In our setting, AMR-BSI incidence and etiology were similar between COVID-19 and non-COVID-19 cases. Incidence rates of hospital-origin AMR-BSI increased in 2020, which was likely due to increased blood culture utilization. We recommend increasing blood culture utilization and generating AMR surveillance reports in LMICs to inform local health care providers and policy makers.

Background Quantifying the excess mortality attributable to antimicrobial-resistant (AMR) bacterial infections is important for assessing the potential benefit of preventive interventions and for prioritization of resources. However, there are few data from low- and middle-income countries. Methods We conducted a 2-year prospective surveillance study to estimate the excess mortality attributable to AMR infections for all types of hospital-acquired infection (HAI), and included bacterial species that were both locally relevant and included in the World Health Organization priority list. Twenty-eight-day mortality was measured. Excess mortality and population attributable fraction (PAF) of mortality caused by AMR infections compared to antimicrobial-susceptible (AMS) infections, adjusted for predefined confounders, were calculated. Results We enrolled 2043 patients with HAIs. The crude 28-day mortality of patients with AMR and AMS infections was 35.5% (491/1385) and 23.1% (152/658), respectively. After adjusting for prespecified confounders, the estimated excess mortality attributable to AMR infections was 7.7 (95% confidence interval [CI], 2.2–13.2) percentage points. This suggests that 106 (95% CI, 30–182) deaths among 1385 patients with AMR infections might have been prevented if all of the AMR infections in this study were AMS infections. The overall PAF was 16.3% (95% CI, 1.2%–29.1%). Among the bacteria under evaluation, carbapenem-resistant Acinetobacter baumannii was responsible for the largest number of excess deaths. Among all types of infection, urinary tract infections were associated with the highest number of excess deaths, followed by lower respiratory tract infections and bloodstream infections. Conclusions Estimating and monitoring excess mortality attributable to AMR infections should be included in national action plans to prioritize targets of preventive interventions. Clinical Trials Registration NCT03411538.

Melioidosis is a tropical infection caused by the soil bacterium Burkholderia pseudomallei. Despite the substantial impact of this often overlooked pathogen on both the health-care systems and economies of numerous low-income and middle-income countries around the world, melioidosis is not officially classified as a neglected tropical disease (NTD) by WHO. Melioidosis causes a higher estimated disease burden and mortality than many other recognised NTDs, with deaths primarily occurring among rural poor populations in low-income and middle-income countries. Fortunately, the impact of melioidosis in a region can be reduced once awareness is established of its known or suspected endemicity. In this Personal View, we provide evidence in support of official recognition of melioidosis as an NTD. We urge member states to request that WHO revisit their NTD list and appeal to government and philanthropic organisations to establish programmes in endemic countries to control melioidosis in order to reduce its global health burden.

Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for >50% of the patients. Here we applied metagenomic next-generation sequencing (mNGS) to characterize the human virome in 492 clinical samples (384 sera, 92 pooled nasal and throat swabs, 10 stools, and 6 cerebrospinal fluid samples) from 386 patients (213 adults and 173 children) presenting with CA sepsis who were recruited from 6 hospitals across Vietnam between 2013 and 2015., Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for >50% of the patients. Here we applied metagenomic next-generation sequencing (mNGS) to characterize the human virome in 492 clinical samples (384 sera, 92 pooled nasal and throat swabs, 10 stools, and 6 cerebrospinal fluid samples) from 386 patients (213 adults and 173 children) presenting with CA sepsis who were recruited from 6 hospitals across Vietnam between 2013 and 2015. Specific monoplex PCRs were used subsequently to confirm the presence of viral sequences detected by mNGS. We found sequences related to 47 viral species belonging to 21 families in 358 of 386 (93%) patients, including viruses known to cause human infections. After PCR confirmation, human viruses were found in 52 of 386 patients (13.4%); picornavirus (enteroviruses [n = 14], rhinovirus [n = 5], and parechovirus [n = 2]), hepatitis B virus (n = 10), cytomegalovirus (n = 9), Epstein-Barr virus (n = 5), and rotavirus A (n = 3) were the most common viruses detected. Recently discovered viruses were also found (gemycircularvirus [n = 5] and WU polyomavirus, Saffold virus, salivirus, cyclovirus-VN, and human pegivirus 2 [HPgV2] [n, 1 each]), adding to the growing literature about the geographic distribution of these novel viruses. Notably, sequences related to numerous viruses not previously reported in human tissues were also detected. To summarize, we identified 21 viral species known to be infectious to humans in 52 of 386 (13.4%) patients presenting with CA sepsis of unknown cause. The study, however, cannot directly impute sepsis causation to the viruses identified. The results highlight the fact that it remains a challenge to establish the causative agents in CA sepsis patients, especially in tropical settings such as Vietnam.

Diabetes mellitus (DM) is a serious global health problem currently affecting over 450million people worldwide. Defining its interaction with major global infections is an international public health priority. Melioidosis is caused byBurkholderia pseudomallei, an exemplar pathogen for studying intracellular bacterial infection in the context of DM due to the 12‐fold increased risk in this group. We characterized immune correlates of survival in peripheral blood of acute melioidosis patients with and without DM and highlight different immune response patterns. We demonstrate the importance of circulating NK cells and show that CX3CR1 expression on lymphocytes is a novel correlate of survival from acute melioidosis. Furthermore, excessive serum levels of IL‐15 and IL‐18BP contribute to poor outcome independent of DM comorbidity. CD8+Tcells and granzyme B expression in NK cells are important for survival of non‐DM patients, whereas high antibody titers againstB. pseudomalleiand double‐negative Tcells are linked to survival of DM patients. Recall responses support a role of γδ T‐cell‐derived IFN‐γ in the establishment of protective immunity in the DM group. Defining the hallmarks of protection in people with DM is crucial for the design of new therapies and vaccines targeting this rapidly expanding risk group.

Summary: Background: In southeast Asia, antibiotic prescription in febrile patients attending primary care is common, and a probable contributor to the high burden of antimicrobial resistance. The objective of this trial was to explore whether C-reactive protein (CRP) testing at point of care could rationalise antibiotic prescription in primary care, comparing two proposed thresholds to classify CRP concentrations as low or high to guide antibiotic treatment. Methods: We did a multicentre, open-label, randomised, controlled trial in participants aged at least 1 year with a documented fever or a chief complaint of fever (regardless of previous antibiotic intake and comorbidities other than malignancies) recruited from six public primary care units in Thailand and three primary care clinics and one outpatient department in Myanmar. Individuals were randomly assigned using a computer-based randomisation system at a ratio of 1:1:1 to either the control group or one of two CRP testing groups, which used thresholds of 20 mg/L (group A) or 40 mg/L CRP (group B) to guide antibiotic prescription. Health-care providers were masked to allocation between the two intervention groups but not to the control group. The primary outcome was the prescription of any antibiotic from day 0 to day 5 and the proportion of patients who were prescribed an antibiotic when CRP concentrations were above and below the 20 mg/L or 40 mg/L thresholds. The primary outcome was analysed in the intention-to-treat and per-protocol populations. The trial is registered with ClinicalTrials.gov, number NCT02758821, and is now completed. Findings: Between June 8, 2016, and Aug 25, 2017, we recruited 2410 patients, of whom 803 patients were randomly assigned to CRP group A, 800 to CRP group B, and 807 to the control group. 598 patients in CRP group A, 593 in CRP group B, and 767 in the control group had follow-up data for both day 5 and day 14 and had been prescribed antibiotics (or not) in accordance with test results (per-protocol population). During the trial, 318 (39%) of 807 patients in the control group were prescribed an antibiotic by day 5, compared with 290 (36%) of 803 patients in CRP group A and 275 (34%) of 800 in CRP group B. The adjusted odds ratio (aOR) of 0·80 (95% CI 0·65–0·98) and risk difference of −5·0 percentage points (95% CI −9·7 to −0·3) between group B and the control group were significant, although lower than anticipated, whereas the reduction in prescribing in group A compared with the control group was not significant (aOR 0·86 [0·70–1·06]; risk difference −3·3 percentage points [–8·0 to 1·4]). Patients with high CRP concentrations in both intervention groups were more likely to be prescribed an antibiotic than in the control group (CRP ≥20 mg/L: group A vs control group, p

Melioidosis is a major neglected tropical disease with high mortality, caused by the Gram-negative bacterium Burkholderia pseudomallei (Bp). Microbiological culture remains the gold standard for diagnosis, but a simpler and more readily available test such as an antibody assay is highly desirable. In this study, we conducted a serological survey of blood donors (n = 1,060) and adult melioidosis patients (n = 200) in northeast Thailand to measure the antibody response to Bp using the indirect hemagglutination assay (IHA). We found that 38% of healthy adults (aged 17–59 years) have seropositivity (IHA titer ≥ 1:80). The seropositivity in healthy blood donors was associated with having a declared occupation of rice farmer and with residence in a nonurban area, but not with gender or age. In the melioidosis cohort, the seropositivity rate was higher in adult patients aged between 18 and 45 years (90%, 37/41) compared with those aged ≥ 45 years (68%, 108/159, P = 0.004). The seropositivity rate was significantly higher in people with diabetes (P = 0.008). Seropositivity was associated with decreased mortality on univariable analysis (P = 0.005), but not on multivariable analysis when adjusted for age, diabetes status, preexisting renal disease, and neutrophil count. This study confirms the presence of high background antibodies in an endemic region and demonstrates the limitations of using IHA during acute melioidosis in this population.

Infection and sepsis are leading causes of death worldwide but the epidemiology and outcomes are not well understood in resource-limited settings. We conducted a four-year prospective observational study from March 2013 to February 2017 to examine the clinical epidemiology and outcomes of adults admitted with community-acquired infection in a resource-limited tertiary-care hospital in Ubon Ratchathani province, Northeast Thailand. Hospitalized patients with infection and accompanying systemic manifestations of infection within 24 hours of admission were enrolled. Subjects were classified as having sepsis if they had a modified sequential organ failure assessment (SOFA) score ≥2 at enrollment. This study was registered with ClinicalTrials.gov, number NCT02217592. A total of 4,989 patients were analyzed. Of the cohort, 2,659 (53%) were male and the median age was 57 years (range 18-101). Of these, 1,173 (24%) patients presented primarily to the study hospital, 3,524 (71%) were transferred from 25 district hospitals or 8 smaller hospitals in the province, and 292 (6%) were transferred from one of 30 hospitals in other provinces. Three thousand seven hundred and sixteen (74%) patients were classified as having sepsis. Patients with sepsis had an older age distribution and a greater prevalence of comorbidities compared to patients without sepsis. Twenty eight-day mortality was 21% (765/3,716) in sepsis and 4% (54/1,273) in non-sepsis patients (p

Secretome (extracellular proteins) has been considered as a potential diagnostic biomarker, vaccine and therapeutic candidates for bacterial infections. In this research, secretomes of two reference Leptospira spp, namely, pathogenic L. interrogans serovar Autumnalis strain Akiyami and saprophytic L. biflexa serogroup Semaranga serovar Patoc strain P136 were evaluated for their immunogenicity to microscopic agglutination test (MAT)-positive leptospirosis patients’ sera in IgM- and IgG-ELISAs in comparison to a whole Leptospira homo-genate antigen. At a single serum dilution of 1:1,000, sensitivity of the pathogenic Leptospira secretome antigen-based IgM- and IgG-ELISAs was 90% (18/20) and 75% (15/20), respectively, when compared with that of the MAT assay. Thus, Leptospira secretome provides a potential antigen source in serodiagnosis of leptospirosis.

Background VRE bacteraemia has a high mortality and continues to defy control. Antibiotic risk factors for VRE bacteraemia have not been adequately defined. We aimed to determine the risk factors for VRE bacteraemia focusing on duration of antibiotic exposure. Methods A retrospective matched nested case-control study was conducted amongst hospitalized patients at Cambridge University Hospitals NHS Foundation Trust (CUH) from 1 January 2006 to 31 December 2012. Cases who developed a first episode of VRE bacteraemia were matched 1:1 to controls by length of stay, year, specialty and ward type. Independent risk factors for VRE bacteraemia were evaluated using conditional logistic regression. Results Two hundred and thirty-five cases were compared with 220 controls. Duration of exposure to parenteral vancomycin, fluoroquinolones and meropenem was independently associated with VRE bacteraemia. Compared with patients with no exposure to vancomycin, those who received courses of 1–3 days, 4–7 days or.7 days had a stepwise increase in risk of VRE bacteraemia [conditional OR (cOR) 1.2 (95% CI 0.4–3.8), 3.8 (95% CI 1.2–11.7) and 6.6 (95% CI 1.9–22.8), respectively]. Other risk factors were: presence of a central venous catheter (CVC) [cOR 8.7 (95% CI 2.6–29.5)]; neutropenia [cOR 15.5 (95% CI 4.2–57.0)]; hypoalbuminaemia [cOR 8.5 (95% CI 2.4–29.5)]; malignancy [cOR 4.4 (95% CI 1.6–12.0)]; gastrointestinal disease [cOR 12.4 (95% CI 4.2–36.8)]; and hepatobiliary disease [cOR 7.9 (95% CI 2.1–29.9)]. Conclusions Longer exposure to vancomycin, fluoroquinolones or meropenemwas associated with VRE bacteraemia. Antimicrobial stewardship interventions targeting high-risk antibiotics are required to complement infection control procedures against VRE bacteraemia.

We compared ChromID VRE and Brilliance VRE media for the detection of vancomycin-resistant enterococci (VRE). Using a panel of 28 enterococcal isolates, 10 vanA Enterococcus faecium and three vanA Enterococcus faecalis isolates grew as per manufacturers’ instructions whilst growth of two vanC and eight vancomycin-susceptible enterococci was inhibited on both media. Important differences were noted in the selectivity and chromogenic properties of the two media for vanA Enterococcus raffinosus and vanB E. faecium. The two media were further evaluated using 295 stool samples from nursing home residents, 34 of which grew VRE (11.5%). ChromID and Brilliance had comparable sensitivity, which was increased markedly by prolonging incubation to 48 hours (from 29% to 82%, and from 41% to 85%, respectively) and by a pre-enrichment step (to 97% and 100%, respectively). Brilliance VRE agar had higher selectivity at 48 hours, and after pre-enrichment.

Contains fulltext : 193552.pdf (Publisher’s version ) (Open Access) Background: Antimicrobial resistance (AMR) is a global health priority. Leading UK and global strategy papers to fight AMR recognise its social and behavioural dimensions, but current policy responses to improve the popular use of antimicrobials (eg, antibiotics) are limited to education and awareness-raising campaigns. In response to conceptual, methodological and empirical weaknesses of this approach, we study people's antibiotic-related health behaviour through three research questions.RQ1: What are the manifestations and determinants of problematic antibiotic use in patients' healthcare-seeking pathways?RQ2: Will people's exposure to antibiotic awareness activities entail changed behaviours that diffuse or dissipate within a network of competing healthcare practices?RQ3: Which proxy indicators facilitate the detection of problematic antibiotic behaviours across and within communities? Methods: We apply an interdisciplinary analytical framework that draws on the public health, medical anthropology, sociology and development economics literature. Our research involves social surveys of treatment-seeking behaviour among rural dwellers in northern Thailand (Chiang Rai) and southern Lao PDR (Salavan). We sample approximately 4800 adults to produce district-level representative and social network data. Additional 60 cognitive interviews facilitate survey instrument development and data interpretation. Our survey data analysis techniques include event sequence analysis (RQ1), multilevel regression (RQ1-3), social network analysis (RQ2) and latent class analysis (RQ3). Discussion: Social research in AMR is nascent, but our unprecedentedly detailed data on microlevel treatment-seeking behaviour can contribute an understanding of behaviour beyond awareness and free choice, highlighting, for example, decision-making constraints, problems of marginalisation and lacking access to healthcare and competing ideas about desirable behaviour. Trial registration number: NCT03241316; Pre-results.

Improved understanding of pathogens that cause sepsis would aid management and antimicrobial selection. In this study, we aimed to identify the causative pathogens of sepsis in southeast Asia.In this multinational multicentre cross-sectional study of community-acquired sepsis and severe sepsis, we prospectively recruited children (age ≥30 days and18 years) and adults (age ≥18 years) at 13 public hospitals in Indonesia (n=3), Thailand (n=4), and Vietnam (n=6). Hospitalised patients with suspected or documented community-acquired infection, with at least three diagnostic criteria for sepsis according to the Surviving Sepsis Campaign 2012, and within 24 h of admission were enrolled. Blood from every patient, and nasopharyngeal swab, urine, stool, and cerebrospinal fluid, if indicated, were collected for reference diagnostic tests to identify causative pathogens. We report causative pathogens of sepsis and 28-day mortality. We also estimate mortality associated with enrolment with severe sepsis. This study was registered with ClinicalTrials.gov, number NCT02157259.From Dec 16, 2013, to Dec 14, 2015, 4736 patients were screened and 1578 patients (763 children and 815 adults) were enrolled. Dengue viruses (n=122 [8%]), Leptospira spp (n=95 [6%]), rickettsial pathogens (n=96 [6%]), Escherichia coli (n=76 [5%]), and influenza viruses (n=65 [4%]) were commonly identified in both age groups; whereas Plasmodium spp (n=12 [1%]) and Salmonella enterica serovar Typhi (n=3 [0·2%]) were rarely observed. Emerging pathogens identified included hantaviruses (n=28 [2%]), non-typhoidal Salmonella spp (n=21 [1%]), Streptococcus suis (n=18 [1%]), Acinetobacter spp (n=12 [1%]), and Burkholderia pseudomallei (n=5 [1%]). 28-day mortality occurred in 14 (2%) of 731 children with known statuses and 108 (13%) of 804 adults. Severe sepsis was identified on enrolment in 194 (28%) of 731 children and 546 (68%) of 804 adults, and was associated with increased mortality (adjusted odds ratio 5·3, 95% CI 2·7-10·4; p0·001).Sepsis in southeast Asia is caused by a wide range of known and emerging pathogens, and is associated with substantial mortality.National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA, and Wellcome Trust, UK.

The environmental bacterium $\textit{Burkholderia pseudomallei}$ causes an estimated 165,000 cases of human melioidosis per year worldwide and is also classified as a biothreat agent. We used whole genome sequences of 469 $\textit{B. pseudomallei}$isolates from 30 countries collected over 79 years to explore its geographic transmission. Our data point to Australia as an early reservoir, with transmission to Southeast Asia followed by onward transmission to South Asia and East Asia. Repeated reintroductions were observed within the Malay Peninsula and between countries bordered by the Mekong River. Our data support an African origin of the Central and South American isolates with introduction of B. pseudomallei into the Americas between 1650 and 1850, providing a temporal link with the slave trade. We also identified geographically distinct genes/variants in Australasian or Southeast Asian isolates alone, with virulence-associated genes being among those over-represented. This provides a potential explanation for clinical manifestations of melioidosis that are geographically restricted.

Burkholderia pseudomallei is a soil-dwelling bacterium and the cause of melioidosis, which kills an estimated 89,000 people per year worldwide. Agricultural workers are at high risk of infection due to repeated exposure. Little is known about soil physicochemical properties associated with presence or absence of the organism. Here, we evaluated the soil physicochemical properties and presence of B. pseudomallei in 6,100 soil samples collected from 61 rice fields in Thailand. The presence of B. pseudomallei was negatively associated with the proportion of clay, proportion of moisture, level of salinity, percentage of organic matter, presence of cadmium, and nutrient levels (phosphorous, potassium, calcium, magnesium and iron). The presence of B. pseudomallei was not associated with the level of soil acidity (p=0.54). In a multivariable logistic regression model, presence of B. pseudomallei was negatively associated with the percentage of organic matter (OR=0.06; 95%CI 0.01-0.47, p=0.007), level of salinity (OR=0.06; 95%CI 0.01-0.74, p=0.03), and percentage of soil moisture (OR=0.81; 95%CI 0.66-1.00, p=0.05). Our study suggests that in rice fields, B. pseudomallei thrives in those that are nutrient-depleted. Some agricultural practices result in a decline in soil nutrients, which may impact on the presence and amount of B. pseudomallei in affected areas. IMPORTANCE: Burkholderia pseudomallei is an environmental Gram-negative bacillus and the cause of melioidosis. Humans acquire the disease following skin inoculation, inhalation or ingestion of the bacterium in the environment. The presence of B. pseudomallei in soil defines geographic regions where humans and livestock are at risk of melioidosis, yet little is known about soil properties associated with presence of the organism. We evaluated the soil properties and presence of B. pseudomallei in 61 rice fields in East, Central and Northeast Thailand. We demonstrated that the organism was more commonly found in soils with lower levels of organic matter and nutrients including phosphorus, potassium, calcium, magnesium and iron. We also demonstrated that crop residue burning after harvest, which can reduce soil nutrients, was not uncommon. Some agricultural practices result in a decline in soil nutrients, which may impact on the presence and amount of B. pseudomallei in affected areas.

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, has a wide range of clinical manifestations. Here, we describe rheumatological melioidosis (involving one or more of joint, bone or muscle), and compare features and outcome with patients without rheumatological involvement. A retrospective study of patients with culture-confirmed melioidosis admitted to Sappasithiprasong Hospital, Ubon Ratchathani during 2002 and 2005 identified 679 patients with melioidosis, of whom 98 (14.4%) had rheumatological melioidosis involving joint (n=52), bone (n = 5), or muscle (n = 12), or a combination of these (n=29). Females were over-represented in the rheumatological group, and diabetes and thalassemia were independent risk factors for rheumatological involvement (OR; 2.49 and 9.56, respectively). Patients with rheumatological involvement had a more chronic course, as reflected by a longer fever clearance time (13 vs 7 days, p = 0.06) and hospitalization (22 vs 14 days, p < 0.001), but lower mortality (28% vs 44%, p = 0.005). Patients with signs and symptoms of septic arthritis for longer than 2 weeks were more likely to have extensive infection of adjacent bone and muscle, particularly in diabetic patients. Surgical intervention was associated with a survival benefit, bur not a shortening of the course of infection.

Melioidosis is an infectious disease endemic to northern Australia and Southeast Asia. In response to clinical confusion regarding the appropriate dose of amoxicillin-clavulanate, we have developed guidelines for the appropriate dosing of this second-line agent. For eradication therapy for melioidosis, we recommend 20/5 mg/kg orally, three times daily. Copyright © 2008 by The American Society of Tropical Medicine and Hygiene.

BACKGROUND: The term 'zero tolerance' has recently been applied to healthcare-associated infections, implying that such events are always preventable. This may not be the case for healthcare-associated infections such as methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. METHODS: We combined information from an epidemiological investigation and bacterial whole-genome sequencing to evaluate a cluster of five MRSA bacteraemia episodes in four patients in a specialist hepatology unit. RESULTS: The five MRSA bacteraemia isolates were highly related by multilocus sequence type (ST) (four isolates were ST22 and one isolate was a single-locus variant, ST2046). Whole-genome sequencing demonstrated unequivocally that the bacteraemia cases were unrelated. Placing the MRSA bacteraemia isolates within a local and global phylogenetic tree of MRSA ST22 genomes demonstrated that the five bacteraemia isolates were highly diverse. This was consistent with the acquisition and importation of MRSA from the wider referral network. Analysis of MRSA carriage and disease in patients within the hepatology service demonstrated a higher risk of both initial MRSA acquisition compared with the nephrology service and a higher risk of progression from MRSA carriage to bacteraemia, compared with patients in nephrology or geriatric services. A root cause analysis failed to reveal any mechanism by which three of five MRSA bacteraemia episodes could have been prevented. CONCLUSIONS: This study illustrates the complex nature of MRSA carriage and bacteraemia in patients in a specialized hepatology unit. Despite numerous ongoing interventions to prevent MRSA bacteraemia in healthcare settings, these are unlikely to result in a zero incidence in referral centres that treat highly complex patients.

Melioidosis, an infectious disease caused by the environmental bacterium Burkholderia pseudomallei, has remained in the shadows for far too long. Described over 100 years ago by Alfred Whitmore in Rangoon, the disease is so neglected that it is not even on any of the lists of neglected tropical diseases, despite the fact that it probably kills more people each year than diseases that are much better known, such as leptospirosis and dengue. We aim to set the record straight.

OBJECTIVES: Infectious diseases consultation (IDC) in adults with Staphylococcus aureus bacteraemia (SAB) has been shown to improve management and outcome. The aim of this study was to evaluate the impact of IDC on the management of SAB in children. STUDY DESIGN: Observational cohort study of children with SAB. SETTING: Cambridge University Hospitals National Health Service (NHS) Foundation Trust, a large acute NHS Trust in the UK. PARTICIPANTS: All children with SAB admitted to the Cambridge University Hospitals NHS Foundation Trust between 16 July 2006 and 31 December 2012. METHODS: Children with SAB between 2006 and 31 October 2009 were managed by routine clinical care (pre-IDC group) and data were collected retrospectively by case notes review. An IDC service for SAB was introduced in November 2009. All children with SAB were reviewed regularly and data were collected prospectively (IDC group) until 31 December 2012. Baseline characteristics, quality metrics and outcome were compared between the pre-IDC group and IDC group. RESULTS: There were 66 episodes of SAB in 63 children-28 patients (30 episodes) in the pre-IDC group, and 35 patients (36 episodes) in the IDC group. The median age was 3.4 years (IQR 0.2-10.7 years). Patients in the IDC group were more likely to have echocardiography performed, a removable focus of infection identified and to receive a longer course of intravenous antimicrobial therapy. There were no differences in total duration of antibiotic therapy, duration of hospital admission or outcome at 30 or 90 days following onset of SAB. CONCLUSIONS: IDC resulted in improvements in the investigation and management of SAB in children.

Cerebrospinal fluid fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated cryptococcal meningitis. The identification of factors associated with mortality informs strategies to improve outcomes., Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0–1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4–11.1), high peripheral white blood cell count (>10 × 109 cells/L; OR, 8.7; 95% CI, 2.5–30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin

[This corrects the article on p. e1488 in vol. 6.].