Nipah Virus Infection.

Nipah virus, a paramyxovirus related to Hendra virus, first emerged in Malaysia in 1998. Clinical presentation ranges from asymptomatic infection to fatal encephalitis. Malaysia has had no more cases since 1999, but outbreaks continue to occur in Bangladesh and India. In the Malaysia-Singapore outbreak, transmission occurred primarily through contact with pigs, whereas in Bangladesh and India, it is associated with ingestion of contaminated date palm sap and human-to-human transmission. Bats are the main reservoir for this virus, which can cause disease in humans and animals. There are currently no effective therapeutics, and supportive care and prevention are the mainstays of management.

Local transmission and global dissemination of New Delhi Metallo-Beta-Lactamase (NDM): a whole genome analysis.

BACKGROUND: New Delhi metallo-ß-lactamase (bla NDM), a plasmid-borne carbapenemase gene associated with significant mortality and severely limited treatment options, is of global public health concern as it is found in extremely diverse Gram-negative bacterial strains. This study thus aims to genetically characterize local and global spread of bla NDM. METHODS: To investigate local transmission patterns in the context of a single hospital, whole genome sequencing data of the first 11 bla NDM-positive bacteria isolated in a local hospital were analyzed to: (1) identify and compare bla NDM-positive plasmids; and (2) study the phylogenetic relationship of the bacteria chromosomes. The global analysis was conducted by analyzing 2749 complete plasmid sequences (including 39 bla NDM-positive plasmids) in the NCBI database, where: (1) the plasmids were clustered based on their gene composition similarity; (2) phylogenetic study was conducted for each bla NDM-positive plasmid cluster to infer the phylogenetic relationship within each cluster; (3) gene transposition events introducing bla NDM into different plasmid backbones were identified; and (4) clustering pattern was correlated with the plasmids' incompatibility group and geographical distribution. RESULTS: Analysis of the first 11 bla NDM-positive isolates from a single hospital revealed very low bla NDM-positive plasmid diversity. Local transmission was characterized by clonal spread of a predominant plasmid with 2 sporadic instances of plasmid introduction. In contrast to the low diversity locally, global bla NDM spread involved marked plasmid diversity with no predominant bacterial clone. Thirty-nine (1.4 %) out of the 2749 complete plasmid sequences were bla NDM-positive, and could be resolved into 7 clusters, which were associated with plasmid incompatibility group and geographical distribution. The bla NDM gene module was witnessed to mobilize between different plasmid backbones on at least 6 independent occasions. CONCLUSIONS: Our analysis revealed the complex genetic pathways of bla NDM spread, with global dissemination characterized mainly by transposition of the bla NDM gene cassette into varied plasmids. Early local transmission following plasmid introduction is characterized by plasmid conjugation and bacterial spread. Our findings emphasize the importance of plasmid molecular epidemiology in understanding bla NDM spread.

The global spread of healthcare-associated multidrug-resistant bacteria: a perspective from Asia.

Since antibiotics were first used, each new introduced class has been followed by a global wave of emergent resistance, largely originating in Europe and North America where they were first used. Methicillin-resistant Staphylococcus aureus spread from the United Kingdom and North America across Europe and then Asia over more than a decade. Vancomycin-resistant enterococci and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae followed a similar path some 20 years later. Recently however, metallo-ß-lactamases have originated in Asia. New Delhi metallo-ß-lactamase-1 was found in almost every continent within a year of its emergence in India. Metallo-ß-lactamase enzymes are encoded on highly transmissible plasmids that spread rapidly between bacteria, rather than relying on clonal proliferation. Global air travel may have helped facilitate rapid dissemination. As the antibiotic pipeline offers little in the short term, our most important tools against the spread of antibiotic resistant organisms are intensified infection control, surveillance, and antimicrobial stewardship.

Nosocomial infections among COVID-19 patients: an analysis of intensive care unit surveillance data.

Surveillance of nosocomial infections, like catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection, possible ventilator-associated pneumonia and secondary bloodstream infections were observed to study the impact of COVID-19 outbreak in ICUs from Tan Tock Seng Hospital and National Centre for Infectious Diseases, Singapore between February and June 2020. Higher nosocomial infection rates were observed in COVID-19 patients, although it was not statistically significant. Moreover, COVID-19 patients seem to be more predisposed to CAUTI despite a higher proportion of non-COVID-19 patients having urinary catheters. Thus, continued vigilance to ensure adherence to IPC measures is needed.

Optical coherence tomography patterns as predictors of visual outcome in dengue-related maculopathy.

PURPOSE: The purpose of this study was to characterize the presentations, long-term outcomes, and visual prognostic factors in dengue-related maculopathy of 41 patients with dengue fever and impaired vision from dengue-related maculopathy in a retrospective noninterventional and observational series. METHODS: The medical records of patients with dengue-related maculopathy diagnosed over 18 months between July 2004 and December 2005 at The Eye Institute, Tan Tock Seng Hospital and Communicable Disease Center, Singapore, were reviewed and followed up for 24 months. Visual acuity and symptoms (presence of scotoma on automated visual fields and Amsler grid) were correlated with optical coherence tomography evaluation. RESULTS: Mean age was 28.7 years and there were more men (53.7%). The most common visual complaints were blurring of vision (51.2%) and central scotoma (34.1%). Most patients recovered best-corrected visual acuity >20/40. Optical coherence tomography showed 3 patterns of maculopathy: 1) diffuse retinal thickening; 2) cystoid macular edema; and 3) foveolitis. The visual outcome was independent of the extent of edema, but scotomata persisted longest in patients with foveolitis and shortest with those with diffuse retinal thickening. CONCLUSION: Dengue-associated ocular inflammation is an emerging ophthalmic condition and often involves the posterior segment. Prognosis is variable. Patients usually regain good vision but may retain persistent scotomata even at 2 years despite clinical resolution of the disease. Optical coherence tomography patterns in dengue maculopathy are useful for characterization, monitoring, and prognostication of the visual defect.

Review of human infections with avian influenza H5N1 and proposed local clinical management guideline.

INTRODUCTION: The current avian and human H5N1 influenza epidemic has been in resurgence since 2004. We decided to evaluate published evidence in relation to epidemiology, clinical features and course, laboratory diagnosis, treatment and outcome of human H5N1 influenza, and develop institutional clinical management guidelines. METHODS: A search of PubMed was conducted for all English language articles with search terms "avian", "influenza" and "H5N1". The bibliography of articles was searched for other references of interest. RESULTS: Published case series from Hong Kong in 1997, and Thailand and Vietnam since 2004 have indicated a rapidly progressive primary viral pneumonia resulting in acute respiratory distress syndrome. The majority of human H5N1 infections can be linked to poultry exposure. Hitherto there has been no evidence of efficient human-to-human transmission. Case fatality rates have varied from 71% in Thailand to 100% in Cambodia. Oseltamivir appears to be the only potentially effective antiviral therapy. H5N1 isolates in Vietnam have become resistant to oseltamivir, resulting in persistent viral replication and death. There is as yet no effective human H5N1 vaccine. CONCLUSIONS: National and international preparedness plans are well advised. Clinical trials to evaluate higher dose oseltamivir therapy and immunomodulatory treatment are urgently needed.

Clinical impact of non-antibiotic recommendations by a multi-disciplinary antimicrobial stewardship team.

INTRODUCTION: The multi-disciplinary antimicrobial stewardship team at the study hospital conducts prospective review and feedback on all inpatient orders of piperacillin-tazobactam and carbapenems. In addition, the team provides non-antibiotic recommendations (i.e. additional investigations and infectious disease reviews). This study aimed to describe the impact of these recommendations on patient outcomes. METHODS: Patients on carbapenem and piperacillin-tazobactam who received at least one non-antibiotic recommendation between January 2012 and August 2014 were included in this study. Acceptance and rejection of non-antibiotic recommendations by the managing physician were compared. The primary outcome was 30-d mortality. RESULTS: Non-antibiotic recommendations were made in 166 patients. There were no differences in baseline characteristics between patients for whom recommendations were accepted and patients for whom recommendations were rejected. Thirty-day mortality (18.0% vs. 34.5%, P = 0.02) was significantly lower in patients who had at least one non-antibiotic recommendation accepted. Multi-variate analysis found that Charlson's comorbidity score [odds ratio (OR) 1.20, 95% confidence interval (CI) 1.03-1.42, P = 0.03], APACHE II score (OR 1.10, 95% CI 1.01-1.19, P < 0.01), hepatobiliary source of infection (OR 10.19, 95% CI 1.44-72.13, P = 0.02) and acceptance of at least one non-antibiotic recommendation (OR 0.39, 95% CI 0.17-0.88, P = 0.02) were independently associated with 30-d mortality. CONCLUSIONS: During prospective review and feedback of piperacillin-tazobactam and carbapenems, acceptance of non-antibiotic recommendations was found to be associated with a reduction in 30-d mortality.

The outbreak of SARS at Tan Tock Seng Hospital--relating epidemiology to control.

INTRODUCTION: The outbreak of severe acute respiratory syndrome (SARS) began after the index case was admitted on 1 March 2003. We profile the cases suspected to have acquired the infection in Tan Tock Seng Hospital (TTSH), focussing on major transmission foci, and also describe and discuss the impact of our outbreak control measures. MATERIALS AND METHODS: Using the World Health Organization (WHO) case definitions for probable SARS adapted to the local context, we studied all cases documented to have passed through TTSH less than 10 days prior to the onset of fever. Key data were collected in liaison with clinicians and through a team of onsite epidemiologists. RESULTS: There were 105 secondary cases in TTSH. Healthcare staff (57.1%) formed the majority, followed by visitors (30.5%) and inpatients (12.4%). The earliest case had onset of fever on 4 March 2003, and the last case, on 5 April 2003. Eighty-nine per cent had exposures to 7 wards which had cases of SARS that were not isolated on admission. In 3 of these wards, major outbreaks resulted, each with more than 20 secondary cases. Attack rates amongst ward-based staff ranged from 0% to 32.5%. Of 13 inpatients infected, only 4 (30.8%) had been in the same room or cubicle as the index case for the ward. CONCLUSIONS: The outbreak of SARS at TTSH showed the challenges of dealing with an emerging infectious disease with efficient nosocomial spread. Super-spreading events and initial delays in outbreak response led to widespread dissemination of the outbreak to multiple wards.

Safety and effectiveness of improving carbapenem use via prospective review and feedback in a multidisciplinary antimicrobial stewardship programme.

INTRODUCTION: Antimicrobial stewardship programmes (ASP) can reduce antibiotic use but patient safety concerns exist. We evaluated the safety of prospective carbapenem review and feedback and its impact on carbapenem use and patient outcomes. MATERIALS AND METHODS: After 3 months implementation of our ASP, we compared patients with and without acceptance of ASP recommendations on the use of carbapenems. Primary outcome was 30-day mortality. Secondary outcomes included duration of carbapenem use, length of hospitalisation, clinical response, microbiological clearance, 30-day readmission and mortality at discharge. RESULTS: Of 226 recommendations for 183 patients, 59.3% was accepted. De-escalation, switching to oral antibiotics and antibiotic cessation comprised 72% of recommendations. Patients with acceptance of ASP recommendations had lower 30-day mortality and higher end-of-therapy clinical response despite shorter carbapenem duration (P <0.05). Predictors of 30-day mortality were Pitt bacteraemia score (adjusted odds ratio [aOR] 1.39, 95% confidence interval [CI], 1.11 to 1.74; P = 0.004) and non-acceptance of ASP recommendations (aOR 2.84, 95% CI, 1.21 to 6.64; P = 0.016). CONCLUSION: Our prospective carbapenem review and feedback mainly comprising of reducing carbapenem use is safe.

Severe varicella infection occurring after herpes zoster reactivation in a patient with AIDS.

Herpes zoster reactivation occurs in patients who had primary varicella infection, afflicting mainly the elderly and the immunocompromised. However, it is rare that varicella infection develop after zoster reactivation. We report on a patient with underlying HIV/AIDS who had two previous episodes of herpes zoster and still developed varicella infection, complicated by pneumonitis and polyradiculitis. We also review the relevant literature.