Dale Fisher

Melioidosis epidemiology and risk factors from a prospective whole-population study in northern Australia

Objectives  The aims of this study were to describe the epidemiology of melioidosis in tropical northern Australia and to assess the importance of defined risk factors.

Outcomes of Patients with Melioidosis Treated with Meropenem

ABSTRACT Melioidosis, an infection due to Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. We reviewed our experience with meropenem in the treatment of severe melioidosis in 63 patients over a 6-year period. Outcomes were similar to those of ceftazidime-treated patients (n = 153) despite a deliberate selection bias to more-unwell patients receiving meropenem. The mortality among meropenem-treated patients was 19%. One patient had a possible drug fever associated with the use of meropenem. We conclude that meropenem (1 g or 25 mg/kg every 8 h intravenously for ≥14 days) is an alternative to ceftazidime and imipenem in the treatment of melioidosis. The use of meropenem may be associated with improved outcomes in patients with severe sepsis associated with melioidosis.

Ebola virus disease: An update on current prevention and management strategies

Ebola virus disease (EVD) is characterised by systemic viral replication, immuno-suppression, abnormal inflammatory responses, large volume fluid and electrolyte losses, and high mortality in under-resourced settings. There are various therapeutic strategies targeting EVD including vaccines utilizing different antigen delivery methods, antibody-based therapies and antiviral drugs. These therapies remain experimental, but received attention following their use particularly in cases treated outside West Africa during the 2014-15 outbreak, in which 20 (80%) out of 25 patients survived. Emerging data from current trials look promising and are undergoing further study, however optimised supportive care remains the key to reducing mortality from EVD.

Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial

BACKGROUND Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia. METHODS We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed. FINDINGS Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported. INTERPRETATION In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events. FUNDING National Medical Research Council, Singapore.

Ertapenem in outpatient parenteral antimicrobial therapy for complicated urinary tract infections

Background: Ertapenem is a broad-spectrum antibiotic that is increasingly being utilized. Its dosing convenience renders it suitable for outpatient therapy, and its pharmacokinetic characteristics favour its use against complicated urinary tract infections (cUTIs). Despite this, sufficient clinical data are lacking for its use against cUTIs in the outpatient setting. We assessed the microbiological and clinical cure rates associated with ertapenem treatment for cUTIs in two outpatient parenteral antimicrobial therapy (OPAT) departments. Methods: We undertook a prospective observational study of adult patients who received ertapenem for cUTIs between August 2010 and August 2014. Data on patient characteristics, clinical progress and microbiological results were collected and analysed. Results: Sixty-one patients were enrolled. The median age was 59 years (range 24, 83) and 61% were male. The most common diagnoses were pyelonephritis (39%) and prostatitis (15%). The most common causative organism was Escherichia coli (67%). Extended-spectrum β-lactamase (ESBL)-producing organisms were detected in 72% of infections. Microbiological cure was achieved in 67% overall, and was less likely in those with Klebsiella pneumoniae infection (OR = 0.21 [95%CI: 0.05 to 0.85] p = 0.029). Clinical cure was observed in 92% of patients. Conclusion: In this study of treating cUTIs with ertapenem, we have demonstrated good clinical outcomes. A lower than expected microbiological cure rate was observed in those with Klebsiella pneumoniae infection.

Spinal Implants Can be Inserted in Patients With Deep Spine Infection - Results from a Large Cohort Study.

Study Design. A retrospective, cohort study of 84 patients with deep spine infection managed at a major tertiary hospital over 14 years with a minimum follow up of 2 years. Objective. To determine the role of instrumentation in spines with deep infection. Summary of Background Data. It is often believed that implants should not be inserted in patients with deep spine infection because of the risk of persistent or recurrent infection. However, there are often concerns about spinal stability and a paucity of evidence to guide clinical practice in this field. Methods. We compared the mortality, reoperation, and reinfection rates in patients with spine infection treated with antibiotics alone, antibiotics with debridement, and antibiotics with debridement and instrumentation. Significant outcome predictors were determined using multivariable logistic regression model. Results. Forty-nine males and 35 females with a mean age was 62.0 years had spine infection affecting the lumbar spine predominantly. The most common form of infection was osteomyelitis and spondylodiscitis (69.4%). Staphylococcus aureus was the most common causative organism (61.2%). There was no difference in terms of reoperation or relapse for patients treated with antibiotics alone, antibiotics with debridement, or antibiotics with debridement and instrumentation. However, compared with antibiotics alone, the crude inhospital mortality was lower for patients treated with instrumentation (odds ratio, OR, 0.82; P = 0.01), and antibiotics with debridement (OR 0.80; P = 0.02). Conclusion. Spinal instrumentation in an infected spine is safe and not associated with higher reoperation or relapse rates. Mortality is lower for patients treated with instrumentation. Level of Evidence: 3

Outpatient parenteral antibiotic therapy (OPAT) in Asia: missing an opportunity

Objectives Healthcare facilities internationally have grown outpatient parenteral antibiotic administration services for the last few decades. The literature contains publications from dozens of countries describing systematized processes with specialist oversight and their levels of service provision and outcomes. Such descriptions are absent in the majority of Asian countries. We sought to elucidate the extent and nature of outpatient parenteral antibiotic therapy (OPAT) in Asia and to consider the ramifications and opportunities for improvement. Methods Utilizing colleagues and their personal networks, we surveyed healthcare facilities across 17 countries in Asia to ascertain the current means (if any) of providing OPAT. In that survey we also sought to explore the capacity and interest of these facilities in developing systematized OPAT services. Results Responses were received from 171 different healthcare facilities from 17 countries. Most (97/171, 57%) stated that they administer outpatient parenteral antibiotics, but only 5 of 162 facilities (3%) outside of Singapore described comprehensive services with specialist oversight. Conclusions There is very likely a large unrecognized problem of unchecked outpatient parenteral antibiotic administration in Asia. Developing comprehensive and systematized OPAT in Asia is needed as a priority in an environment in which the infectious diseases community is demanding broad stewardship approaches. There are nonetheless challenges in establishing and sustaining OPAT programmes. Local champions and leverage off identified local incentives and needs are key to regional advancement.

TO the EDITOR: Reply to the Letter: "spinal Implants Can be Inserted in Patients with Deep Spine Infection: Results from a Large Cohort Study"

Gabriel Popescu is an assistant professor in the Department of Electrical and Computer Engineering and a full-time faculty member with the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana–Champaign. He and his colleagues started the Nanobiophotonics Summer School at the Beckman Institute in 2009. The school was sponsored by the Network for Computational Nanotechnology (NCN), which is funded by the National Science Foundation.

Advances in prevention and treatment of vancomycin-resistant Enterococcus infection.

PURPOSE OF REVIEW This article reviews data, particularly from the last 2 years, addressing the prevention and treatment of vancomycin-resistant Enterococcus (VRE). We focus on infection control, particularly active screening, use of contact precautions as well as pharmacologic options for therapy. This is timely given the evolving priorities in efforts towards the prevention and treatment of multidrug-resistant organisms globally. RECENT FINDINGS Key findings include new data regarding the impact of contact precautions on the incidence of VRE colonization and bloodstream infection, new laboratory screening methods, and novel decolonization strategies and treatments. SUMMARY Additional and specific measures beyond standard precautions for infection prevention of VRE remain controversial. Horizontal measures such as chlorhexidine bathing appear beneficial, as are nontouch environmental cleaning methods. Treatment options for invasive disease have improved considerably in the last decade. Decolonization strategies require further research. Overall, the threat of VRE seems exaggerated.