Determinants of Recurrent Melioidosis

Recurrent melioidosis represents relapse following failure to eradicate bacteria responsible for the primary infection or re-infection with a new strain. The first results chapter (chapter 3) evaluates the proportion of recurrent melioidosis due to relapse versus re-infection. Isolates from the same patient with an identical genotype were considered as relapse and those with a different genotype as re-infection. Three quarters of recurrent cases were due to relapse and one quarter were due to re-infection. There are two ways in which this approach could be confounded. First, ‘re-infection’ could actually represent relapse if primary infection was caused by simultaneous infection with multiple B. pseudomallei strains, followed by chance selection of different strains from the two episodes for genotyping. The chance of this mistake occurring is based on the rate of polyclonal B. pseudomallei infection. Chapter 4 describes the rate of polyclonal infection in a large group of unselected patients in northeast Thailand, which was very low (2/133 cases, 1.5%). Second, ‘relapse’ could actually represent reinfection in the event that re-infection was caused by a B. pseudomallei strain that was by chance identical to the primary strain. The probability of this happening is based on the degree of genetic diversity of B. pseudomallei in the environment. Chapter 5 demonstrates that the population of B. pseudomallei in even a small sampling site is extremely diverse. Thus, it is unlikely that the assessment of the causes of recurrent melioidosis contained significant errors due to polyclonal infection or low genetic diversity of the organism. Chapter 6 examines specific risk factors of relapse and reinfection. Duration and choices of antibiotics used for the primary episode were major determinants of relapse. Chapter 7 compares the clinical manifestations of relapse and re-infection and develops a simple scoring index to predict relapse or re-infection in patients presenting with recurrent melioidosis

Association between activities related to routes of infection and clinical manifestations of melioidosis.

We sought associations between route of infection by Burkholderia pseudomallei and clinical manifestations in 330 cases of melioidosis in northeast Thailand using bivariate multivariable logistic regression models. Activities related to skin inoculation were negatively associated with bacteraemia, activities related to ingestion were associated with bacteraemia, and activities related to inhalation were associated with pneumonia. Our study suggests that route of infection is one of the factors related to clinical manifestations of melioidosis

Fragmentation pathways of [Re₂(μ-OR)₃(CO)₆]– (R = H, Me) and ligand exchange reactions with oxygen donor ligands, investigated by electrospray mass spectrometry

The rhenium hydroxy and methoxy carbonyl complexes [Re₂(μOR)₃(CO)₆]⁻ (R = H or Me) have been studied by negative-ion electrospray mass spectrometry (ESMS). The complexes undergo facile exchange reactions with protic compounds, including alcohols and phenols. With dimethyl malonate, ester hydrolysis occurs giving carboxylate-containing complexes, and with H₂O₂ or ButOOH, oxidation to ReO₄⁻occurs. The feasibility and extent of these reactions can conveniently, rapidly, and unambiguously be determined by electrospray mass spectrometry, and is dependent on the acidity and steric bulk of the protic compound. The results also suggest that the complexes can be used as versatile starting materials for the synthesis of a wide range of analogous [Re₂(μ-OR)₃(CO)₆]⁻ complexes by simple reaction with an excess of the appropriate alcohol. By varying the applied cone voltage the fragmentation pathways have been investigated; the hydroxy complex undergoes dehydration followed by CO loss, whereas for the methoxy complex -hydride elimination (and CO loss) is observed, with confirmation provided by deuterium labelling studies. Under ESMS conditions, the neutral complexes [Re₂(μ-OR)₂(μ-dppf )(CO)₆] [R = H or Me; dppf = 1,1 -bis(diphenylphosphino)ferrocene] undergo substantial solvolysis and hydrolysis to give mainly mononuclear species; simple parent ions (e.g. [M + H]⁺) are not formed in appreciable abundance, probably due to the lack of an efficient ionisation pathway

Impact of low blood culture usage on rates of antimicrobial resistance

Abstract Objectives The magnitude of impact caused by low blood culture utilization on estimates of the proportions and incidence rates of antimicrobial-resistant (AMR) bacterial infections is largely unknown. Methods We used routine electronic databases of microbiology, hospital admission and drug prescription at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand, from 2011 to 2015, and bootstrap simulations. Results The proportions of Escherichia coli and Klebsiella pneumoniae bacteraemias caused by 3rd generation cephalosporin resistant isolates (3GCREC and 3GCRKP) were estimated to increase by 13 and 24 percentage points (from 44% to 57% and from 51% to 75%), respectively, if blood culture utilization rate was reduced from 82 to 26 blood culture specimens per 1,000 patient-days. Among patients with hospital-origin bloodstream infections, the proportion of 3GCREC and 3GCRKP whose first positive blood culture was taken within ±1 calendar day of the start of a parenteral antibiotic at the study hospital was substantially lower than those whose first positive blood culture was taken later into parenteral antibiotic treatment (30% versus 79%, p<0.001; and 37% versus 86%, p<0.001). Similar effects were observed for methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter spp. and carbapenem-resistant Pseudomonas aeruginosa. Conclusion Impacts of low blood culture utilization rate on the estimated proportions and incidence rates of AMR infections could be high. We recommend that AMR surveillance reports should additionally include blood culture utilization rate and stratification by exposure to a parenteral antibiotic at the hospital

Repeat Blood Culture Positive for B. pseudomallei Indicates an Increased Risk of Death from Melioidosis

Melioidosis, a bacterial infection caused by Burkholderia pseudomallei, is notoriously difficult to cure despite appropriate antimicrobial therapy and has a mortality rate of up to 40%. We demonstrate that a blood culture positive for B. pseudomallei taken at the end of the first and/or second week after hospitalization for melioidosis is a strong prognostic factor for death (adjusted odds ratio = 4.2, 95% confidence interval = 2.1–8.7, P < 0.001 and adjusted odds ratio = 2.6, 95% confidence interval = 1.1–6.0, P = 0.03, respectively). However, repeat cultures of respiratory secretions, urine, throat swabs, or pus/surface swabs provide no prognostic information. This finding highlights the need for follow-up blood cultures in patients with melioidosis

Strategies to Reduce Mortality from Bacterial Sepsis in Adults in Developing Countries

Sharon Peacock and colleagues discuss management of adult patients with sepsis in low- and middle-income settings, with a particular emphasis on tropical regions

Global Burden and Challenges of Melioidosis

This is a reprint of articles from the Special Issue published online in the open access journal Tropical Medicine and Infectious Disease (ISSN 2414-6366) from 2018 to 2019 (available at: https://www. mdpi.com/journal/tropicalmed/special issues/melioidosis

Burkholderia pseudomallei and melioidosis

Burkholderia pseudomallei, the causative agent of melioidosis, is found in soil and water of tropical and subtropical regions globally. Modelled estimates of the global burden predict that melioidosis remains vastly under-reported, and a call has been made for it to be recognized as a neglected tropical disease by the World Health Organization. Severe weather events and environmental disturbance are associated with increased case numbers, and it is anticipated that, in some regions, cases will increase in association with climate change. Genomic epidemiological investigations have confirmed B. pseudomallei endemicity in newly recognized regions, including the southern United States. Melioidosis follows environmental exposure to B. pseudomallei and is associated with comorbidities that affect the immune response, such as diabetes, and with socioeconomic disadvantage. Several vaccine candidates are ready for phase I clinical trials. In this Review, we explore the global burden, epidemiology and pathophysiology of B. pseudomallei as well as current diagnostics, treatment recommendations and preventive measures, highlighting research needs and priorities