Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.

The gut microbiome is now considered an organ unto itself and plays an important role in health maintenance and recovery from critical illness. The commensal organisms responsible for the framework of the gut microbiome are valuable in protection against disease and various physiological tasks. Critical illness and the associated interventions have a detrimental impact on the microbiome. While antimicrobials are one of the fundamental and often life-saving modalities in septic patients, they can also pave the way for subsequent harm because of the resulting damage to the gut microbiome. Contributing to many of the non-specific signs and symptoms of sepsis, the balance between the overuse of antimicrobials and the clinical need in these situations is often difficult to delineate. Given the potency of antimicrobials utilized to treat septic patients, the effects on the gut microbiome are often rapid and long-lasting, in which case full recovery may never be observed. The overgrowth of opportunistic pathogens is of significant concern as they can lead to infections that become increasingly difficult to treat. Continued research to understand the disturbances within the gut microbiome of critically ill patients and their outcomes is essential to help develop future therapies to circumvent damage to, or restore, the microbiome. In this review, we discuss the impact of the antimicrobials often used for the treatment of sepsis on the gut microbiota.

Background Melioidosis, caused by the environmental bacterium Burkholderia pseudomallei, is an oftenfatal infectious disease with a high prevalence across tropical areas. Clinical presentation can vary from abscess formation to pneumonia and septicaemia. We assessed the global burden of melioidosis, expressed in disability-adjusted life years (DALYs), for the year 2015. Methods A systematic review of the peer-reviewed literature for human melioidosis cases between 1990 and 2015 was performed. Using a broad search strategy, no language restrictions and combinations of search terms, Burkholderia spp. and disease names, all relevant articles were screened on title, abstract, and full text. Quantitative data from cases including mortality, age, sex, infectious and post-infectious sequelae, antibiotic treatment and symptom duration were extracted. This information was then combined with established disability weights and expert panel discussions to construct an incidence-based disease model. The disease model was integrated with established global incidence and mortality estimates to calculate global melioidosis DALYs. Findings 2 888 articles were screened, of which 475 eligible studies containing quantitative information were retained. Sepsis/septic shock and pneumonia were the most common outcomes, occurring in 18.0% (1526/8469), 12.1% (1004/8298) and 35.7% (3633/10175) of patients respectively. The male to female ratio of infection was 2:1. We estimate that in 2015, the global burden of melioidosis was 4•6 million DALYs (UI 3•2-6•6) or 84•3 per 100 000 people (UI 57•5-120•0). Years of life lost (YLL) accounted for 98•9% (UI 97•7-99•5) of the total DALYs. Interpretation Our estimates enable comparison with other tropical diseases which are already recognised as neglected and give policy makers the information necessary to reconsider melioidosis as a major neglected tropical disease.

AbstractMelioidosis, caused by the facultative intracellular gram-negative pathogen Burkholderia pseudomallei, is an emerging cause of community-acquired pneumonia across the tropics. The majority of patients present with pneumonia with or without sepsis, but localized and asymptomatic infection is also well recognized. Recent modeling and epidemiological studies have demonstrated the widespread presence of B. pseudomallei in otherwise unrecognized regions with a predicted mortality of 90,000 deaths worldwide. Innovative environmental studies are also uncovering how hydrodynamic, pedology, fauna, and weather events influence geographic distribution and incidence of melioidosis cases. Of concern is the changes associated with global warming, which will be conducive to B. pseudomallei in combination with the global diabetes pandemic. In fact, over 80% of patient developing melioidosis have underlying comorbidities. For this great mimicker, culture remains the mainstay of diagnosis and despite availability of other assays, challenges still remain in reducing time to diagnosis and avoiding misdiagnosis. With institution of timely antimicrobials such as ceftazidime and supportive intensive care, overall mortality can be reduced to 10%, although this can still be as high as 50% in poorly resourced areas. Promise is on the horizon with the first human vaccine trials being planned for 2021. Meanwhile new multiomics techniques are giving us a better understanding of the role of virulence and host–pathogen interactions on patient outcomes.

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We read with interest the paper by Evans 1 in which the author demonstrated that a noticeable drop in leucocyte count and temperature over the first 48-h of medical management predicted early discharge on oral antibiotics. We recently undertook an audit of all patients with acute sigmoid diverticulitis, over a 4-month period, which supported these findings.Our audit reviewed all admissions to the surgical admissions unit of our district general Trust to improve surgical practice and thereby patient care, focussing on management and length of stay. Of all 33 patients admitted, none developed any complications or required surgical interventions. Further, neither intolerance of oral intake, nor opioid need, precluded discharge -despite this, however, mean length of stay was 3 days.It has been shown that 70-85% of episodes of sigmoid diverticulitis resolve with medical management, 1 and, further, Broderick-Villa et al.2 have shown that the risk of recurrent diverticulitis after initial non-operative management was significantly lower than previous reports. Therefore, this study has important implications for current surgical practice.There are currently no published guidelines in the UK, and other studies have shown, as has our audit, that there is no consensus between practitioners regarding management. 3Combining the results of Evans' study, current ASCRS guidelines 4 and our audit, we have written a local guideline to encourage best practice and a reduction in unnecessary inpatient stay. If admission is necessary, then decreasing inflammatory markers within 48-h is an indication for discharge, as complications appearing after this have now been shown to be unlikely.A 48-h rule should have a significant impact on length of stay of patients with acute sigmoid diverticulitis, with consequent benefits for the patient and substantial financial savings for our Trust.