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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 The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue).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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.

Indwelling medical devices such as catheters are a ubiquitous and indispensable component in modern medical practice for improving therapeutic outcomes for patients. Yet at the same time, they can be a cause of healthcare-associated infections contributing to patient morbidity and mortality, and healthcare costs. Other surface-related complications can also arise from interactions of the catheter with biological components in the in vivo environment. This review summarizes the progress made in the development of antimicrobial surfaces, and the application of surface modification strategies to three important classes of catheters: urinary catheters, intravascular catheters and peritoneal dialysis catheters. The review also provides a perspective on the challenges in translating favorable developments from in vitro studies into similar clinical outcomes.

Background: Streptococcus Suis (S.suis) is increasingly being recognised as a potentially preventable emerging zoonotic infection in humans with a global distribution. It is a major cause of meningitis especially among those in contact with pigs and has also been associated with a toxic shock syndrome., Case Presentations: We report the first two human cases from Sabah, Borneo, Malaysia which expands the global reach of this important pathogen. Here, we illustrate their epidemiological risk factors, clinical presentation and resulting sequelae of both patients., Conclusion: The continued public health threat of zoonotic infections such as S.suis, highlights the need for accurate epidemiological surveillance, regulation of pig farming, slaughtering and continued advocacy of best practices for pork preparation and consumption.

Background: One Health (OH) is an interdisciplinary collaborative approach to human and animal health that aims to break down conventional research and policy 'silos'. OH has been used to develop strategies for zoonotic Emerging Infectious Diseases (EID). However, the ethical case for OH as an alternative to more traditional public health approaches is largely absent from the discourse. To study the ethics of OH, we examined perceptions of the human health and ecological priorities for the management of zoonotic EID in the Southeast Asia country of Singapore., Methods: We conducted a mixed methods study using a modified Delphi technique with a panel of 32 opinion leaders and 11 semi-structured interviews with a sub-set of those experts in Singapore. Panellists rated concepts of OH and priorities for zoonotic EID preparedness planning using a series of scenarios developed through the study. Interview data were examined qualitatively using thematic analysis., Findings: We found that panellists agreed that OH is a cross-disciplinary collaboration among the veterinary, medical, and ecological sciences, as well as relevant government agencies encompassing animal, human, and environmental health. Although human health was often framed as the most important priority in zoonotic EID planning, our qualitative analysis suggested that consideration of non-human animal health and welfare was also important for an effective and ethical response. The panellists also suggested that effective pandemic planning demands regional leadership and investment from wealthier countries to better enable international cooperation., Conclusion: We argue that EID planning under an OH approach would benefit greatly from an ethical ecological framework that accounts for justice in human, animal, and environmental health., Competing Interests: One of the authors, Paul Tambyah, holds research grants from GSK, Sanofi-Pasteur, Fabentech and collects consultation fees from 3M and Johnson and Johnson, but all outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. None of the other authors have any conflicts of interest to declare.

Background: In the recent years, the data on the molecular epidemiology of influenza viruses have expanded enormously because of the availability of cutting-edge sequencing technologies. However, much of the information is from the temperate regions with few studies from tropical regions such as South-east Asia. Despite the fact that influenza has been known to transmit rapidly within semi-closed communities, such as military camps and educational institutions, data are limited from these communities., Objectives: To determine the phylogeography of influenza viruses on a university campus, we examined the spatial distribution of influenza virus on the National University of Singapore (NUS) campus., Methods: Consenting students from the NUS who sought medical attention at the UHC provided two nasopharyngeal swabs and demographic data. PCR was used for detection of influenza viruses. 34 full-genomes of pH1N1/09 viruses were successfully sequenced by Sanger method and concatenated using Geneious R7. Phylogenetic analysis was conducted using these 34 sequences and 1518 global sequences. Phylogeographic analysis was done using BaTS software and Association index and Fitch parsimony scores were determined., Results: Integrating whole genome sequencing data with epidemiological data, we found strong evidence of influenza transmission on campus as isolates from students residing on-campus were highly similar to each other (AI, P value = 0.009; PS, P value = 0.04). There was also evidence of multiple introductions from the community., Conclusions: Such data are useful in formulating pandemic preparedness plans which can use these communities as sentinel sites for detection and monitoring of emerging respiratory viral infections., Competing Interests: Dr. Paul Tambyah has received research support from Baxter, GSK, ADAMAS, Merlion Pharmaceuticals, Sanofi Pasteur, Fabentech and Inviragen. He has also received honoraria from Novartis and Astra-Zeneca. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

We report the diagnostic and therapeutic challenges in an unusually fulminant presentation of measles, presenting as severe necrotizing bronchiolitis with secondary hemophagocytic lymphohistiocytosis (HLH) in the absence of classical clinical features in an immunocompromised host on maintenance chemotherapy. Our patient had presented with features of a viral pneumonitis without the classical exanthem, in combination with HLH. Although rhinovirus-induced HLH was highly unusual, the positive rhinovirus swab result had distracted us from the eventual diagnosis. This calls for greater impetus to increase awareness and public education to improve vaccination rates and herd immunity to curb outbreaks and protect the immunocompromised patients.

Salmonella infection can cause a wide range of presentations, predominantly gastrointestinal but occasionally with cardiovascular or other extraintestinal manifestations. The diagnosis of extraintestinal salmonellosis requires a high degree of clinical suspicion and should be considered in patients with deep-seated abscesses especially if they are immunocompromised. We present a case of salmonella causing gastroenteritis complicated by an intramuscular abscess of the left leg. With prompt recognition and multidisciplinary management, the patient recovered with no serious sequela.

Carbapenem-resistant Gram-negative bacteria, in particular the Acinetobacter baumannii-calcoaceticus complex and Enterobacteriaceae, are escalating global public health threats. We review the epidemiology and prevalence of these carbapenem-resistant Gram-negative bacteria among countries in South and Southeast Asia, where the rates of resistance are some of the highest in the world. These countries house more than a third of the world's population, and several are also major medical tourism destinations. There are significant data gaps, and the almost universal lack of comprehensive surveillance programs that include molecular epidemiologic testing has made it difficult to understand the origins and extent of the problem in depth. A complex combination of factors such as inappropriate prescription of antibiotics, overstretched health systems, and international travel (including the phenomenon of medical tourism) probably led to the rapid rise and spread of these bacteria in hospitals in South and Southeast Asia. In India, Pakistan, and Vietnam, carbapenem-resistant Enterobacteriaceae have also been found in the environment and community, likely as a consequence of poor environmental hygiene and sanitation. Considerable political will and effort, including from countries outside these regions, are vital in order to reduce the prevalence of such bacteria in South and Southeast Asia and prevent their global spread., (Copyright © 2016 American Society for Microbiology.)

Objectives: Multiresistant Gram-negative pathogens pose major healthcare concerns with a limited therapeutic armamentarium. Aminoglycosides (AG) are under-utilized due to nephrotoxicity. We aimed to evaluate AG-associated acute kidney injury (AG-AKI) in elderly inpatients, with and without shock., Methods: We examined the incidence and predictors of AG-AKI by KDIGO criteria and extended renal dysfunction (ERD) in patients aged >60 years. ERD represented a composite of hospital mortality or absence of renal recovery over 6 months following AG-AKI., Results: Two hundred and seventy-eight patients (aged 74 ± 8 years) were studied; 43% and 19% received >7 and >10 days of AG therapy, respectively, and 70% gentamicin (versus amikacin). Thirteen per cent had shock and 17% developed AG-AKI. Comparing all patients with shock versus no shock, AG-AKI developed in 33% versus 14%, respectively (P = 0.005); correspondingly among 47 patients with AG-AKI, more with shock had stage 2/3 AKI (92% versus 43%) and dialysis (50% versus 9%) (P < 0.01), but more had other strong AKI confounders than AG therapy alone (83% versus 40%, P = 0.02). Multivariate analyses identified mechanical ventilation, frusemide administration and AG therapy >10 days as predictors of AG-AKI (P < 0.05), whereas shock, pneumonia and frusemide administration predicted more severe stage 2/3 AG-AKI (P < 0.05). Hospital mortality was 30% versus 7% with AG-AKI versus none (P < 0.001). Twenty-three of 211 (11%) patients with extended analysis had ERD, with 47% experiencing renal recovery following AG-AKI. Mechanical ventilation and contrast administration during index hospitalization predicted ERD (P < 0.05)., Conclusions: AG-AKI is common in the elderly, with a significant risk of ERD, but the cause and severity are greatly influenced by critical illness and shock, more so than AG therapy alone., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Dengue is the most common arboviral illness worldwide. While most infected patients recover, a proportion of them develop severe complications or fatality. Nevertheless, the pathophysiological mechanisms which distinguish the disease severity and associated complications are not clearly understood. We studied blood profiles of dengue patients in order to identify microRNAs that could play a role in these pathophysiological mechanisms., Methods: Blood samples from 26 dengue-infected patients were collected within 0-14 days of infection. Together with samples obtained from six healthy individuals, microRNA profiles were generated to identify significantly altered microRNAs upon dengue infection. Profiles of patients with influenza were also used to determine the disease specificity of these altered microRNAs. Their discriminative power to distinguish dengue from influenza was then tested statistically., Results: Several significantly altered microRNAs were identified in patients with dengue. Twelve microRNAs were specifically altered upon acute dengue whereas 14 microRNAs exhibited similar expression between dengue and influenza. Seventeen microRNAs which could potentially distinguish dengue-related complications were also identified. Expression of miR-24-1-5p, miR-512-5p and miR-4640-3p distinguished mild dengue from those exhibiting liver complications whereas miR-383 was significantly upregulated in mild dengue compared to those diagnosed as severe dengue with fluid accumulation., Conclusions: We identified two panels of microRNAs - one specific for dengue and the other common to dengue and influenza. We also report on the differentially expressed microRNAs in patients with mild versus severe dengue, which could be the basis for the complications seen in them., (© The Author(s) 2015.)

There is currently an emerging outbreak of yellow fever in Angola. Cases in infected travellers have been reported in a number of other African countries, as well as in China, representing the first ever documented cases of yellow fever in Asia. There is a large Chinese workforce in Angola, many of whom may be unvaccinated, increasing the risk of ongoing importation of yellow fever into Asia via busy commercial airline routes. Large parts of the region are hyperendemic for the related Flavivirus dengue and are widely infested by Aedes aegypti, the primary mosquito vector of urban yellow fever transmission. The combination of sustained introduction of viraemic travellers, an ecology conducive to local transmission, and an unimmunized population raises the possibility of a yellow fever epidemic in Asia. This represents a major global health threat, particularly in the context of a depleted emergency vaccine stockpile and untested surveillance systems in the region. In this review, the potential for a yellow fever outbreak in Asia is discussed with reference to the ecological and historical forces that have shaped global yellow fever epidemiology. The limitations of surveillance and vector control in the region are highlighted, and priorities for outbreak preparedness and response are suggested., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The influenza virus infects millions of people each year and can result in severe complications. Understanding virus recognition and host responses to influenza infection will enable future development of more effective anti-viral therapies. Previous research has revealed diverse yet important roles for the annexin family of proteins in modulating the course of influenza A virus (IAV) infection. However, the role of Annexin-A1 (ANXA1) in IAV infection has not been addressed. Here, we show that ANXA1 deficient mice exhibit a survival advantage, and lower viral titers after infection. This was accompanied with enhanced inflammatory cell infiltration during IAV infection. ANXA1 expression is increased during influenza infection clinically, in vivo and in vitro. The presence of ANXA1 enhances viral replication, influences virus binding, and enhances endosomal trafficking of the virus to the nucleus. ANXA1 colocalizes with early and late endosomes near the nucleus, and enhances nuclear accumulation of viral nucleoprotein. In addition, ANXA1 enhances IAV-mediated apoptosis. Overall, our study demonstrates that ANXA1 plays an important role in influenza virus replication and propagation through various mechanisms and that we predict that the regulation of ANXA1 expression during IAV infection may be a viral strategy to enhance its infectivity.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a common cause of bacteraemia in endemic countries and may be associated with high mortality; carbapenems are considered the drug of choice. Limited data suggest piperacillin-tazobactam could be equally effective. We aimed to compare 30-day mortality of patients treated empirically with piperacillin-tazobactam versus a carbapenem in a multi-centre retrospective cohort study in Singapore. Only patients with active empiric monotherapy with piperacillin-tazobactam or a carbapenem were included. A propensity score for empiric carbapenem therapy was derived and an adjusted multivariate analysis of mortality was conducted. A total of 394 patients had ESBL-Escherichia.coli and ESBL-Klebsiella pneumoniae bacteraemia of which 23.1% were community acquired cases. One hundred and fifty-one received initial active monotherapy comprising piperacillin-tazobactam (n = 94) or a carbapenem (n = 57). Patients who received carbapenems were less likely to have health-care associated risk factors and have an unknown source of bacteraemia, but were more likely to have a urinary source. Thirty-day mortality was comparable between those who received empiric piperacillin-tazobactam and a carbapenem (29 [30.9%] vs. 17 [29.8%]), P = 0.89). Those who received empiric piperacillin-tazobactam had a lower 30-day acquisition of multi-drug resistant and fungal infections (7 [7.4%] vs. 14 [24.6%]), P<0.01). After adjusting for confounders, use of empiric piperacillin-tazobactam was not associated with increased 30-day mortality (OR 1.00, 95% CI; 0.45-2.17). Empiric piperacillin-tazobactam was not associated with increased 30-day mortality and may result in fewer multi-drug resistant and fungal infections when compared with a carbapenem.

Purpose: To determine the association between both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and osteomyelitis recurrence., Methods: Records of 81 males and 27 females aged 10 to 87 (median, 54) years who underwent antibiotic/ surgical treatment for primary (n=68) or recurrent (n=40) osteomyelitis that was related (n=26) or unrelated (n=82) to a prosthesis were reviewed. Of the 40 cases of osteomyelitis recurrence followed up for a median of 23.4 (range, 0.6-74.0) months, 7 and 33 were related and unrelated to a prosthesis, respectively. The cutoff points of lowest ESR and CRP for osteomyelitis recurrence were calculated. Risk factors for osteomyelitis recurrence were determined., Results: Osteomyelitis recurrence was associated with diabetes mellitus, ischaemic heart disease, non-healing wound, infection in the lower limb, and infection with methicillin-resistant Staphylococcus aureus. The cutoff points of CRP ≥5 mg/l and ESR ≥20 mm/h were used for osteomyelitis recurrence. Risk factors for osteomyelitis recurrence were ESR ≥20 mm/h, infection with methicillin-resistant S aureus, and infection in the lower limb., Conclusion: ESR was more sensitive, specific, and independently associated with osteomyelitis recurrence and should be used to guide the duration of antibiotic treatment.

Influenza is a ubiquitous infection with a spectrum ranging from mild to severe. The mystery regarding such variability in the clinical spectrum has not been fully unravelled, although a role for the complex interplay among virus characteristics, host immune response and environmental factors has been suggested. Antivirals and current vaccines have a limited role in prophylaxis and treatment because they primarily target surface glycoproteins which undergo antigenic/genetic changes under host immune pressure. Targeting conserved internal proteins could lead the way to a universal vaccine which can be used against various types/subtypes. However, this is on the distant horizon, so in the meantime, developing improved vaccines should be given high priority. In this review, we discuss where the current influenza research stands in terms of vaccines, adjuvants, and how we can better predict the vaccine strains for upcoming influenza seasons by understanding complex phenomena which drive the continuous antigenic evolution.

Background: Outbreaks of emerging infectious diseases have led to guidelines recommending the routine use of N95 respirators for healthcare workers, many of whom are women of childbearing age. The respiratory effects of prolonged respirator use on pregnant women are unclear although there has been no definite evidence of harm from past use., Methods: We conducted a two-phase controlled clinical study on healthy pregnant women between 27 to 32 weeks gestation. In phase I, energy expenditure corresponding to the workload of routine nursing tasks was determined. In phase II, pulmonary function of 20 subjects was measured whilst at rest and exercising to the predetermined workload while breathing ambient air first, then breathing through N95-mask materials., Results: Exercising at 3 MET while breathing through N95-mask materials reduced mean tidal volume (TV) by 23.0 % (95 % CI -33.5 % to -10.5 %, p < 0.001) and lowered minute ventilation (VE) by 25.8 % (95 % CI -34.2 % to -15.8 %, p < 0.001), with no significant change in breathing frequency compared to breathing ambient air. Volumes of oxygen consumption (VO2) and carbon dioxide expired (VCO2) were also significantly reduced; VO2 by 13.8 % (95 % CI -24.2 % to -3 %, p = 0.013) and VCO2 by 17.7 %, (95 % CI -28.1 % to -8.6 %, p = 0.001). Although no changes in the inspired oxygen and carbon dioxide concentrations were demonstrated, breathing through N95-mask materials during low intensity work (3 MET) reduced expired oxygen concentration by 3.2 % (95 % CI: -4.1 % to -2.2 %, p < 0.001), and increased expired carbon dioxide by 8.9 % (95 % CI: 6.9 % to 13.1 %; p <0.001) suggesting an increase in metabolism. There were however no changes in the maternal and fetal heart rates, finger-tip capillary lactate levels and oxygen saturation and rating of perceived exertion at the work intensity investigated., Conclusions: Breathing through N95 mask materials have been shown to impede gaseous exchange and impose an additional workload on the metabolic system of pregnant healthcare workers, and this needs to be taken into consideration in guidelines for respirator use. The benefits of using N95 mask to prevent serious emerging infectious diseases should be weighed against potential respiratory consequences associated with extended N95 respirator usage., Trial Registration: The study was registered at clinicaltrials.gov, identifier NCT00265926.

Background: The seroprevalence of varicella in Southeast Asia is not well described especially in healthcare workers (HCW) in the region. We report the varicella seroprevalence among healthcare workers from a diverse range of countries working in a tertiary care hospital in Singapore., Methods: We audited the results of annual HCW health screening, which included a varicella assay, from the years 2009 to 2014. During this period, there was a change in hospital policy mandating varicella immunity for all newly employed healthcare workers. The serological data were reviewed with employment records on occupation and nationality. Seroprevalence rates were determined by standard commercial enzyme linked immunosorbent assays for each year of testing. Odds of being immune in 2014 were compared by means of multiple logistic regression., Results: A total of 10,585 samples were obtained from 6668 unique individuals over four separate cross-sections of the hospital workforce. A peak seroprevalence of 92.8 % (95 % CI 92.0-93.5) was recorded in 2014. Younger employees had a lower seroprevalence than their older colleagues. In a consolidated sample of 4875 members of the active workforce in October 2014, we identified that Indian nationals were less likely to be immune than their Singaporean national colleagues, odds ratio (OR) 0.26 (95 % CI 0.17-0.43, p < 0.001), while Chinese nationals were more likely to be immune, OR 4.34 (95 % CI 1.61-12.2, p = 0.004), after controlling for year of screening, gender, age-group and vocation. In 2014, being employed as administrative staff, OR 0.43 (95 % CI 0.29-0.64, p < 0.001) or contract service provider, OR 0.30 (95 % CI 0.19-0.47, p < 0.001), was also associated with a lower odds of being immune than being employed as a nurse., Conclusions: There remain a small number of healthcare workers who are non-immune to varicella in our tertiary hospital. A new pre-employment policy of mandatory screening and vaccination may have increased rates of immunity but more needs to be done to ensure that all of our employees are immune to varicella to protect our vulnerable patients.

Antibiotic resistance in Gram-negative uropathogens is a major global concern. Worldwide, the prevalence of Enterobacteriaceae that produce extended-spectrum β-lactamase or carbapenemase enzymes continues to increase at alarming rates. Likewise, resistance to other antimicrobial agents including aminoglycosides, sulphonamides and fluoroquinolones is also escalating rapidly. Bacterial resistance has major implications for urological practice, particularly in relation to catheter-associated urinary tract infections (UTIs) and infectious complications following transrectal-ultrasonography-guided biopsy of the prostate or urological surgery. Although some new drugs with activity against Gram-negative bacteria with highly resistant phenotypes will become available in the near future, the existence of a single agent with activity against the great diversity of resistance is unlikely. Responding to the challenges of Gram-negative resistance will require a multifaceted approach including considered use of current antimicrobial agents, improved diagnostics (including the rapid detection of resistance) and surveillance, better adherence to basic measures of infection prevention, development of new antibiotics and research into non-antibiotic treatment and preventive strategies.

Neurologic complications have long been associated with influenza. A novel strain of influenza A (H1N1) first described in humans to have outbreak potential in 2009 in Mexico went on to become the first influenza pandemic of this century. We evaluated the neurologic complications of the novel influenza A (H1N1) 2009 in children and adults admitted to all public hospitals in Singapore during the influenza A (H1N1) 2009 pandemic between May 2009 and March 2010. All patients were positive for novel H1N1 infection and presented with neurologic symptoms prior to oseltamivir treatment. Ninety-eight patients (median age 6.6 years, range 0.4-62.6) were identified; 90 % were younger than 18 years; 32 % suffered from preexisting neurological, respiratory, or cardiac disease; and 66 % presented with seizures. Of those presenting with seizures, new onset seizures were the most common manifestation (n = 40, 61.5 %), followed by breakthrough seizures (n = 18, 27.7 %) and status epilepticus (n = 7, 10.8 %). Influenza-associated encephalopathy occurred in 20 %. The majority of children (n = 88) presented with seizures (n = 63, 71.6 %), encephalopathy (n = 19, 21.6 %), and syncope (n = 4, 4.5 %). Among adults, a wider range of neurological conditions were seen, with half of them presenting with an exacerbation of their underlying neurological disease. The neurological symptoms developed at a median of 2 days after the onset of systemic symptoms. The median length of hospital stay was 3 days, and 79 % were monitored in general wards. Neurologic complications associated with the novel influenza A (H1N1) 2009 strain were generally mild and had a good outcome. They occurred more frequently in patients with underlying neurological disorders. Seizures and encephalopathy were the most common manifestations, similar to other influenza virus strains.

Background: We aimed to study patients with prosthetic valve endocarditis (PVE) and analyse factors associated with in-hospital adverse events., Methods: A review of all patients who underwent echocardiography at a local university hospital with definite PVE (modified Duke's criteria) was performed. Adverse events of in-hospital mortality and redo valve surgery were identified., Results: There were 23 patients with PVE (median age 53 years (IQR:38-66), 12 males (52%)). Twelve adverse events occurred including seven (30%) in-hospital mortalities and five (21%) redo valve surgery. Factors associated with in-hospital mortality include Staphylococcus aureus-PVE (86% vs 31%, p=0.027), presence of shock (86% vs 19%, p=0.005) and intensive care unit admission (72% vs 19%, p=0.026). Factors associated with the need for redo valve surgery include a younger median age (37 vs 61 years, p=0.012), longer median length of stay (58 vs 17 days, p=0.004), history of intravenous drug abuse (IVDA) (60% vs 6%, p=0.021) and right-sided valvular involvement (40% vs 0%, p=0.040). Using a composite endpoint of both outcomes, factors associated with in-hospital adverse events were a history of IVDA (36% vs 0%, p=0.037) and presence of shock (64% vs 17%, p=0.036)., Conclusion: PVE carries a high risk of poor clinical outcome in terms of in-hospital mortality and the need for redo surgery., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.

Background: Blood-borne infections remain a risk of blood transfusions. While routine screening of donated blood products has greatly reduced the risk of human immunodeficiency virus, hepatitis B, and hepatitis C transmission, arboviruses such as dengue, chikungunya, and the West Nile virus remain significant risks especially during outbreaks., Case Report: We report a rare case of dengue documented to be acquired through a blood transfusion, which resulted in severe thrombocytopenia prolonging admission in hospital in a neurosurgical patient., Results: The donor of one of the units of red blood cells presented with dengue fever 2 days after donating. Sanger sequencing confirmed DENV-2 (dengue virus, Serotype 2) in both the donor and the patient samples and showed 100% nucleotide sequence identity between the two viruses, confirming transfusion-transmitted dengue infection., Conclusion: This case highlights the importance of arboviral screening of donor blood, especially for populations in endemic areas during outbreaks., (© 2015 AABB.)

Background: In response to global concerns about the largest Ebola virus disease (EVD), outbreak to-date in West Africa documented healthcare associated transmission and the risk of global spread, the International Society of Chemotherapy (ISC) Infection Control Working Group created an Ebola Infection Control Readiness Checklist to assess the preparedness of institutions around the globe. We report data from the electronic checklist that was disseminated to medical professionals from October to December 2014 and identify action needed towards better preparedness levels., Findings: Data from 192 medical professionals (one third from Africa) representing 125 hospitals in 45 countries around the globe were obtained through a specifically developed electronic survey. The survey contained 76 specific questions in 7 major sections: Administrative/operational support; Communications; Education and audit; Human resources, Supplies, Infection Prevention and Control practices and Clinical management of patients. The majority of respondents were infectious disease specialists/infection control consultants/clinical microbiologists (75; 39 %), followed by infection control professionals (59; 31 %) and medical doctors of other specialties (17; 9 %). Nearly all (149; 92 %) were directly involved in Ebola preparedness activities. Whilst, 54 % indicated that their hospital would need to handle suspected and proven Ebola cases, the others would subsequently transfer suspected cases to a specialized centre., Conclusion: The results from our survey reveal that the general preparedness levels for management of potentially suspected cases of Ebola virus disease is only partially adequate in hospitals. Hospitals designated for admitting EVD suspected and proven patients had more frequently implemented Infection Control preparedness activities than hospitals that would subsequently transfer potential EVD cases to other centres. Results from this first international survey provide a framework for future efforts to improve hospital preparedness worldwide.

Background: Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae., Methods: All adult patients with a BSI caused by cefotaxime non-susceptible E. coli or K. pneumoniae were included from May 2012-May 2013. We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI., Results: There were 92 BSIs that fulfilled the microbiological inclusion criteria. 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy died (adjusted HR for survival 0.91, 95% CI 0.13 to 6.28; p = 0.92). The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97). The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26). There were no significant differences in subsequent isolation of carbapenem resistant organisms (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed BSI (0% vs. 2%, p = 0.23)., Conclusions: BLBLIs appear to have a similar efficacy to carbapenems in the treatment of cefotaxime-resistant E. coli and K. pneumoniae bloodstream infections. Directed therapy with a BLBLI, when susceptibility is proven, may represent an appropriate carbapenem-sparing option.

The spread of extended-spectrum β-lactamase (ESBL) genes in Enterobacteriaceae such as Escherichia coli or Klebsiella spp is a major challenge to modern medical practice. Carbapenems are the treatment of choice for serious infections caused by ESBL producers; however, carbapenem resistance has increased globally. ESBL producers might be susceptible to β-lactam-β-lactamase inhibitor (BLBLI) combination antibiotics such piperacillin-tazobactam or amoxicillin-clavulanate. These drugs are frequently avoided in serious infections caused by ESBL producers because of the inoculum effect in-vitro (especially for piperacillin-tazobactam), animal data suggesting inferior efficacy when compared with carbapenems, concerns about pharmacokinetic-pharmacodynamic drug target attainment with standard doses, and poor outcomes shown in some observational studies. Prospective cohort data and a meta-analysis suggest that BLBLIs are non-inferior to carbapenems in the treatment of bloodstream infections caused by ESBL producers. We examine why BLBLIs are perceived as inferior in the treatment of infection with ESBL producers, and discuss data that suggest these concerns might not be strongly supported by clinical evidence., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Urinary tract infections constitute a large proportion of nosocomial infections, and the urinary catheter is the most important predisposing factor. Encrustation induced by urease-producing uropathogens like Proteus mirabilis causes further complications. In the present work, a strategy for controllable and sustained release of silver over several weeks has been developed for combating bacterial infection and encrustation in urinary devices. Silver nanoparticles (AgNPs) were first immobilized on polydopamine (PDA) pre-treated silicone catheter surface and this was followed by another PDA coating. The number of AgNP-PDA bilayers could be manipulated to control the amount of silver loaded and its subsequent release. Poly(sulfobetaine methacrylate-co-acrylamide) was then grafted to provide an antifouling outer layer, and to ensure free diffusion of Ag from the surface. The micron-scale combination of an antifouling coating with AgNP-PDA bilayers reduced colonization of the urinary catheter by uropathogens by approximately two orders of magnitude. With one and two AgNP-PDA bilayers, the coated catheter could resist encrustation for 12 and 45 days, respectively, compared with approximately 6 days with the Dover™ silver-coated catheter. Such anti-infective and anti-encrustation catheters can potentially have a large impact on reducing patient morbidity and healthcare expenditure., (© 2014 Wiley Periodicals, Inc.)

Background: Southeast Asia is a potential locus for the emergence of novel influenza strains. However, information on influenza within the region is limited., Objectives: This study was to determine the proportion of influenza-like illness (ILI) caused by influenza A and B viruses in a university cohort in Singapore, identify important distinctive clinical features of influenza infection and potential factors associated with influenza infection compared with other causes of ILI., Methodology: A surveillance study was conducted from 2007 to 2009, at the University Health and Wellness Centre, National University of Singapore (NUS). Basic demographic information and nasopharyngeal swabs were collected from consenting students and staff with ILI, with Influenza A and B identified by both culture and molecular methods., Results: Proportions of influenza A and B virus infections in subjects with ILI were 153/500 (30.6%) and 11/500 (2.2%) respectively. The predominant subtype was A/H1N1, including both the seasonal strain (20/153) and the pandemic strain (72/153). The clinical symptom of fever was more common in subjects with laboratory confirmed influenza than other ILIs. On-campus hostel residence and being a student (compared with staff) were associated with increased risk of laboratory confirmed influenza A/H1N1 2009 infection., Conclusions: This study provides a baseline prevalence of influenza infection within young adults in Singapore in a university setting. Potential risk factors, such as hostel residence, were identified, allowing for more targeted infection control measures in the event of a future influenza pandemic.

Catheter-associated urinary tract infections (CAUTIs) are the most common hospital-acquired infections worldwide, aggravating the problem of antimicrobial resistance and patient morbidity. There is a need for a potent and robust antimicrobial coating for catheters to prevent these infections. An ideal coating agent should possess high antimicrobial efficacy and be easily and economically conjugated to the catheter surface. In this study, we report a simple yet effective immobilization strategy to tether a potent synthetic antimicrobial peptide, CWR11, onto catheter-relevant surfaces. Polydopamine (PD) was deposited as a thin adherent film onto a polydimethylsiloxane (PDMS) surface to facilitate attachment of CWR11 onto the PD-functionalized polymer. Surface characterization of the CWR11-tethered surfaces confirmed the successful immobilization of peptides onto the PD-coated PDMS. The CWR11-immobilized PDMS slides displayed excellent antimicrobial (significant inhibition of 5×10(4) colony-forming units of CAUTI-relevant microbes) and antibiofilm (∼92% enhanced antibacterial adherence) properties. To assess its clinical relevance, the PD-based immobilization platform was translated onto commercial silicone-coated Foley catheters. The CWR11-impregnated catheter displayed potent bactericidal properties against both Gram-positive and Gram-negative bacteria, and retained its antimicrobial functionality for at least 21days, showing negligible cytotoxicity against human erythrocyte and uroepithelial cells. The outcome of this study demonstrates the proof-of-concept potential of a polydopamine-CWR11-functionalized catheter to combat CAUTIs., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Human infection with the avian influenza A H5N1 virus results in disease with a high fatality rate, against which antiviral treatments have limited efficacy. We aimed to investigate the safety, pharmacokinetics, and therapeutic potential of specific polyclonal immunoglobulin equine F(ab')₂ fragments raised against influenza A/Vietnam/1194/2004 virus (H5N1 subtype) in healthy volunteers., Methods: We did a randomised, double-blind, placebo-controlled, single-centre phase 1 study. In stage 1 (one infusion) and stage 2 (five infusions) of the trial, we randomly assigned healthy male volunteers to receive once-daily intravenous infusions of 0·85 U/kg body weight of F(ab')₂ or once-daily saline placebo. Randomisation was done centrally, with one block of four patients and one block for substitutes (three actives, one placebo) in stage 1, and two blocks of six patients (five actives and one placebo) and the same block for substitutes in stage 2. The primary objective was assessment of the clinical and laboratory safety of F(ab')₂, which was monitored for 22 days in the group that received one dose (assessments on days 0-2, 4, 8, 15, and 22) and 33 days in the group that received five doses (days 0-6, 8, 10, 12, 19, 26, and 33). A final post-study safety assessment was done at 120 days. We also assessed pharmacokinetic outcomes, and assayed haemagglutination and seroneutralisation activity. Analysis was done according to intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02295813., Findings: We enrolled 16 healthy Asian men between Sept 28 and Dec 28, 2012, and randomly assigned 13 to one or five doses of F(ab')₂ and three to placebo. F(ab')₂ was well tolerated, and no deaths or serious adverse events occurred. Three patients had mild adverse events (one each of blepharospasm, sinusitis, and pyrexia). The pyrexia (38°C) was regarded as probably related to the infusion, and resolved after 37 min. Our laboratory assessments of blood and urine samples and physical examinations of heart rate, electrocardiogram readings, and weight showed no clinically significant safety issues. Mean peak plasma concentrations were 19·3 μg/mL (SD 3·5) with the one dose schedule and 23·0 μg/mL (4·5) with the five-dose schedule. F(ab')₂ were still detectable in plasma on average up to 5 days after five doses. Haemagglutination inhibition was only increased after the third dose, but in-vitro seroneutralisation activity was transiently increased after each of the five doses to concentrations regarded as clinically beneficial in infected patients., Interpretation: F(ab')₂ showed good safety, tolerability, and therapeutic potential for managing of H5N1 exposed patients., Funding: Fab'entech., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Infections due to multi-drug resistant gram negative bacilli (RGNB) in critically ill patients have been reported to be associated with increased morbidity and costs and only a few studies have been done in Asia. We examined the financial impact of nosocomial RGNB infections among critically ill patients in Singapore., Methods: A nested case control study was done for patients at medical and surgical ICUs of a tertiary university hospital (August 2007-December 2011) matched by propensity scores. Two groups of propensity-matched controls were selected for each case patient with nosocomial drug resistant gram negative infection: at-risk patients with no gram negative infection or colonization (Control A) and patients with ICU acquired susceptible gram negative infection (SGNB) (Control B). The costs of the hospital stay, laboratory tests and antibiotics prescribed as well as length of stay were compared using the Wilcoxon matched-pairs signed rank test., Results: Of the 1539 patients included in the analysis, 76 and 65 patients had ICU acquired RGNB and SGNB infection respectively. The median(range) total hospital bill per day for patients with RGNB infection was 1.5 times higher than at-risk patients without GNB infection [Singapore dollars 2637.8 (458.7-20610.3) vs. 1757.4 (179.9-6107.4), p0.0001]. The same trend was observed when compared with SGNB infected patients. The median costs per day of antibiotics and laboratory investigations were also found to be significantly higher for patients with RGNB infection. The length of stay post infection was not found to be different between those infected with RGNB and SGNB., Conclusion: The economic burden of RGNB infections to the patients and the hospital is considerable. Efforts need to be taken to prevent their occurrence by cost effective infection control practices.

Of the ≈400 cases of avian influenza (H7N9) diagnosed in China since 2003, the only travel-related cases have been in Hong Kong and Taiwan. Detection of a case in a Chinese tourist in Sabah, Malaysia, highlights the ease with which emerging viral respiratory infections can travel globally.

Elizabethkingia meningoseptica is a nosocomial non-fermenting gram-negative bacillus that has an increasing prevalence in health care settings, especially in intensive care environments. While it has long been recognized as a rare but serious cause of neonatal meningitis and sepsis, its role as a cause of ocular pathology is not well-known. We report the first case of E. meningoseptica endogenous endophthalmitis caused by bacteraemia by the same organism. In view of its aggressiveness and virulence in the eye, and the high rate of misdiagnosis or missed diagnosis of endogenous endophthalmitis especially given its low incidence, we may wish to consider screening all cases of E. menigoseptica bloodstream infections for endophthalmitis in future, similar to how it has become routine to refer all patients with Klebsiella bacteraemia to ophthalmologists for screening for endophthalmitis in our local hospitals.

Background: The widespread use of empiric broad spectrum antibiotics has contributed to the global increase of Resistant Gram-Negative Bacilli (RGNB) infections in intensive care units (ICU). The aim of this study was to develop a tool to predict nosocomial RGNB infections among ICU patients for targeted therapy., Methods: We conducted a prospective observational study from August'07 to December'11. All adult patients who were admitted and stayed for more than 24 hours at the medical and surgical ICU's were included. All patients who developed nosocomial RGNB infections 48 hours after ICU admission were identified. A prediction score was formulated by using independent risk factors obtained from logistic regression analysis. This was prospectively validated with a subsequent cohort of patients admitted to the ICUs during the following time period of January-September 2012., Results: Seventy-six patients with nosocomial RGNB Infection (31bacteremia) were compared with 1398 patients with Systemic Inflammatory Response Syndrome (SIRS) without any gram negative bacterial infection/colonization admitted to the ICUs during the study period. The following independent risk factors were obtained by a multivariable logistic regression analysis - prior isolation of Gram negative organism (coeff: 1.1, 95% CI 0.5-1.7); Surgery during current admission (coeff: 0.69, 95% CI 0.2-1.2); prior Dialysis with end stage renal disease (coeff: 0.7, 95% CI 0.1-1.1); prior use of Carbapenems (coeff: 1.3, 95% CI 0.3-2.3) and Stay in the ICU for more than 5 days (coeff: 2.4, 95% CI 1.6-3.2). It was validated prospectively in a subsequent cohort (n = 408) and the area-under-the-curve (AUC) of the GSDCS score for predicting nosocomial ICU acquired RGNB infection and bacteremia was 0.77 (95% CI 0.68-0.89 and 0.78 (95% CI 0.69-0.89) respectively. The GSDCS (0-4.3) score clearly differentiated the low (0-1.3), medium (1.4-2.3) and high (2.4-4.3) risk patients, both for RGNB infection (p:0.003) and bacteremia (p:0.009)., Conclusion: GSDCS is a simple bedside clinical score which predicts RGNB infection and bacteremia with high predictive value and differentiates low versus high risk patients. This score will help clinicians to choose appropriate, timely targeted antibiotic therapy and avoid exposure to unnecessary treatment for patients at low risk of nosocomial RGNB infection. This will reduce the selection pressure and help to contain antibiotic resistance in ICUs.

The rapid development of antimicrobial resistance among micro-organisms is a serious public health concern. Moreover, the dissemination of antibiotic-resistant bacteria makes this issue a global problem, and Asia is no exception. For example, since New Delhi metallo-β-lactamase (NDM)-producing Enterobacteriaceae were identified in India, further spread of NDM has become a worldwide threat. However, the epidemiology of antibiotic-resistant bacteria in Asia may be different to other regions, and clinical condition may be worse than in western countries. Antibiotic-resistant bacteria, including community-acquired and hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant enterococci, macrolide- and penicillin-resistant Streptococcus pneumoniae, extend-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp., are becoming prevalent in many countries in Asia. Moreover, the prevalence of each antibiotic-resistant bacterium in each country is not identical. This review provides useful information regarding the critical condition of antibiotic resistance in Asia and emphasises the importance of continuous surveillance of resistance data., (Copyright © 2014 International Society for Chemotherapy of Infection and Cancer. All rights reserved.)

Healthcare associated infections (HAI) are among the major complications of modern medical therapy. The most important HAIs are those related to invasive devices: central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated pneumonia (VAP) as well as surgical site infections (SSI). HAIs are associated with significant mortality, morbidities and increasing healthcare cost. The cited case-fatality rate ranges from 2.3% to 14.4% depending on the type of infection. In this mini-review, we shed light on these aspects as well as drivers to decrease HAIs., (Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Antibiotic resistance in Gram-negative bacteria, especially Enterobacteriaceae, can be conferred by a large number of different acquired resistance genes, although it appears that relatively few dominate. A previous survey of Escherichia coli and Klebsiella pneumoniae isolates from Sydney, Australia, revealed that a limited set of genes could reliably predict resistance to third-generation cephalosporins (3GCs) and aminoglycosides. Here we tested E. coli and K. pneumoniae isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration of ≥ 2 μg/mL from China and Singapore, with significantly higher resistance rates than Australia, as well as the USA. Few targets were needed to predict non-susceptibility to 3GCs (95/95; 100%) and gentamicin (47/51; 92%). The gene types detected here are consistent with previous surveys in similar countries with similar resistance rates, where the majority of 3GC resistance can be explained by blaCTX-M genes. This study identified a limited set of genes capable of predicting resistance to 3GC and aminoglycoside antibiotics and implies a restriction in the global resistance gene pool that can be exploited for diagnostic purposes., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: Staphylococcus aureus bacteremia is a common infection associated with significant morbidity and mortality. Telavancin is a bactericidal lipoglycopeptide active against Gram-positive pathogens, including methicillin-resistant S. aureus (MRSA). We conducted a randomized, double-blind, Phase 2 trial in patients with uncomplicated S. aureus bacteremia., Methods: Patients were randomized to either telavancin or standard therapy (vancomycin or anti-staphylococcal penicillin) for 14 days. Continuation criteria were set to avoid complicated S. aureus bacteremia. The primary end point was clinical cure at 84 days., Results: In total, 60 patients were randomized and 58 received ≥1 study medication dose (all-treated), 31 patients fulfilled inclusion/exclusion and continuation criteria (all-treated target [ATT]) (telavancin 15, standard therapy 16), and 17 patients were clinically evaluable (CE) (telavancin 8, standard therapy 9). Mean age (ATT) was 60 years. Intravenous catheters were the most common source of S. aureus bacteremia and ~50% of patients had MRSA. A similar proportion of CE patients were cured in the telavancin (88%) and standard therapy (89%) groups. All patients with MRSA bacteremia were cured and one patient with MSSA bacteremia failed study treatment in each group. Although adverse events (AEs) were more common in the telavancin ATT group (90% vs. 72%), AEs leading to drug discontinuation were similar (7%) in both treatment arms. Potentially clinically significant increases in serum creatinine (≥1.5 mg/dl and at least 50% greater than baseline) were more common in the telavancin group (20% vs. 7%)., Conclusions: This study suggests that telavancin may have utility for treatment of uncomplicated S. aureus bacteremia; additional studies are warranted. (Telavancin for Treatment of Uncomplicated Staphylococcus Aureus Bacteremia (ASSURE); NCT00062647).

Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into consideration in order to make meaningful public policy recommendations.