Brenda Ang

Outbreak of Nipah-virus infection among abattoir workers in Singapore

BACKGROUND In March 1999, an outbreak of encephalitis and pneumonia occurred in workers at an abattoir in Singapore. We describe the clinical presentation and the results of investigations in these patients. METHODS Clinical and laboratory data were collected by systemic review of the case records. Serum and cerebrospinal fluid (CSF) samples were tested for IgM antibodies to Nipah virus with an IgM capture ELISA. Reverse-transcriptase PCR was done on the CSF and tissue samples from one patient who died. FINDINGS Eleven patients were confirmed to have acute Nipah-virus infection based on raised IgM in serum. Nipah virus was identified by reverse transcriptase PCR in the CSF and tissue of the patient who died. The patients were all men, with a median age of 44 years. The commonest presenting symptoms were fever, headache, and drowsiness. Eight patients presented with signs of encephalitis (decreased level of consciousness or focal neurological signs). Three patients presented with atypical pneumonia, but one later developed hallucinations and had evidence of encephalitis on CSF examination. Abnormal laboratory findings included a low lymphocyte count (nine patients), low platelet count, low serum sodium, and high aspartate aminostransferase concentration (each observed in five patients). The CSF protein was high in eight patients and white-blood-cell count was high in seven. Chest radiography showed mild interstitial shadowing in eight patients. Magnetic resonance imaging (MRI) showed focal areas of increased signal intensity in the cortical white marker in all eight patients who were scanned. The nine patients with encephalitis received empirical treatment with intravenous aciclovir and eight survived. INTERPRETATION Infection with Nipah virus caused an encephalitis illness with characteristic focal areas of increased intensity seen on MRI. Lung involvement was also common, and the disease may present as an atypical pneumonia.

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-β-lactamases have originated in Asia. New Delhi metallo-β-lactamase-1 was found in almost every continent within a year of its emergence in India. Metallo-β-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.

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.

Cerebral melioidosis in Singapore: a review of five cases

A variety of neurological manifestations of infection with Burkholderia pseudomallei have been described including cerebral abscesses, which are a well-recognized form of neurological melioidosis. The optimal antibiotic therapy for this condition has not been defined; however, combinations of intravenous antibiotics are frequently used in the early stages. Five cases of melioidosis involving brain abscesses are described which presented in Singapore over the past 3 years (1997-2000), 4 of which cases had evidence of disseminated infection. Despite profound neurological deficits and low Glasgow Coma Scale scores at presentation in 3 of these cases, all survived after surgical drainage and prolonged courses of intravenous ceftazidime or imipenem, and only 2 of whom had residual neurological impairment. One incidental finding on computed tomography (CT) or magnetic resonance imaging (MRI) scans not described before as an association with cerebral melioidosis was sinusitis in 4 out of the 5 cases.

Nonconcordance with Surgical Site Infection Prevention Guidelines and Rates of Surgical Site Infections for General Surgical, Neurological, and Orthopedic Procedures

ABSTRACT Surgical site infection (SSI) is a common and preventable complication of surgery, but the relative importance of individual measures recommended by guidelines has not been determined. Elective general surgical, neurological, and orthopedic procedures requiring antibiotic prophylaxis from a 3-month period were retrospectively studied to determine concordance with SSI prevention guidelines and to identify factors which predicted the development of SSIs. A total of 216 surgeries were reviewed, with 18 SSIs (8.3%). A mean of 1.4 antibiotic prophylaxis errors per surgery were identified, with correct antibiotic type identified for 64%, antibiotic timing for 83%, supplemental antibiotic dosing for 34%, and antibiotic duration of less than 24 h for 44%. Normothermia was present in 79% of surgeries, and normoglycemia was present in 17%. Univariate analysis of the SSI rate identified four significant factors. Antibiotic prophylaxis for less than 24 h postoperatively (odds ratio [OR], 0.213; 95% confidence interval [95% CI]0.060 to 0.757) and neurosurgery (OR, 0.118; 95% CI, 0.15 to 0.903) correlated with a reduced risk of SSI. The mean number of prophylaxis errors (OR, 1.6; 95% CI, 1.02 to 2.4) and a duration of surgical drainage for more than 3 days (OR, 2.679; 95% CI, 1.009 to 7.113) predicted SSI. By multivariate analysis, errors in individual antibiotic prophylaxis measures were not significantly associated with SSI; however, the presence of more than two errors was significant (OR, 4.030; 95% CI, 1.018 to 15.96). A strong correlation was identified between the degree of concordance to SSI prevention guidelines and the SSI rate (P = 0.001, Mantel-Haenszel linear-by-linear association chi-square test).

Retinal hemorrhages in 4 patients with dengue fever.

We report 4 patients with retinal hemorrhages that developed during hospitalization for dengue fever. Onset of symptoms coincided with resolution of fever and the nadir of thrombocytopenia. Retinal hemorrhages may reflect the rising incidence of dengue in Singapore or may be caused by changes in the predominant serotype of the dengue virus.

Safety and clinical outcomes of carbapenem de-escalation as part of an antimicrobial stewardship programme in an ESBL-endemic setting

OBJECTIVES To evaluate the safety and clinical outcomes of patients who received carbapenem de-escalation as guided by an antimicrobial stewardship programme (ASP) in a setting where ESBL-producing Enterobacteriaceae are endemic. METHODS Patients receiving meropenem or imipenem underwent a prospective ASP review for eligibility for de-escalation according to defined institutional guidelines. Patients in whom carbapenem was de-escalated or not de-escalated, representing the acceptance and rejection of the ASP recommendation, respectively, were compared. The primary outcome was the clinical success rate; secondary outcomes included the 30 day readmission and mortality rates, the duration of carbapenem therapy, the incidence of adverse drug reactions due to antimicrobials, the acquisition of carbapenem-resistant Gram-negative bacteria and the occurrence of Clostridium difficile-associated diarrhoea (CDAD). RESULTS The de-escalation recommendations for 300 patients were evaluated; 204 (68.0%) were accepted. The patient demographics and disease severity were similar. The clinical success rates were similar [de-escalated versus not de-escalated, 183/204 (89.7%) versus 85/96 (88.5%), P=0.84], as was the survival at hospital discharge [173/204 (84.8%) versus 79/96 (82.3%), P=0.58]. In the de-escalated group, the duration of carbapenem therapy was shorter (6 versus 8 days, P<0.001), the rate of adverse drug reactions was lower [11/204 (5.4%) versus 12/96 (12.5%), P=0.037], there was less diarrhoea [9/204 (4.4%) versus 12/96 (12.5%), P=0.015], there was a lower incidence of carbapenem-resistant Acinetobacter baumannii acquisition [4/204 (2.0%) versus 7/96 (7.3%), P=0.042] and there was a lower incidence of CDAD [2/204 (1.0%) versus 4/96 (4.2%), P=0.081]. CONCLUSIONS This study suggests that the ASP-guided de-escalation of carbapenems led to comparable clinical success, fewer adverse effects and a lower incidence of the development of resistance. This approach is safe and practicable, and should be a key component of an ASP.

Surgical Masks for Protection of Health Care Personnel against Pandemic Novel Swine-Origin Influenza A (H1N1)-2009: Results from an Observational Study

There is ongoing debate about the efficacy of surgical masks versus N95 respirators for protection against pandemic novel swine-origin influenza A (H1N1)-2009. Our hospital, which is designated to manage outbreaks of emerging infection, has robust surveillance systems to detect infection in staff. The incidence of pandemic H1N1-2009 remained low in staff with use of surgical masks.

Increasing Incidence of Clostridium difficile-associated Disease, Singapore

To the Editor: Clostridium difficile–associated disease (CDAD) has increased in incidence across North America and Europe (1). Recent reports document the emergence of an epidemic strain of C. difficile, NAP1/BI/027, associated with increased virulence (2,3). However, less information is available regarding CDAD epidemiology in Asia. We examined the incidence of C. difficile among hospitalized patients in Singapore from 2001 through 2006 and conducted a case–control study to evaluate risk factors for testing positive for C. difficile toxin (CDT) in our population. Tan Tock Seng Hospital (TTSH) is a 1,200-bed, acute-care general hospital in Singapore that serves an urban population of 4 million. We calculated CDAD incidence using the number of patients testing positive for CDT per 10,000 patient days from 2001 through 2006. We used this calculation because CDT testing would have been ordered for clinical indications. CDT testing was performed by using the same ELISA (Premier Toxins AB Meridian Bioscience, Inc., Cincinnati, OH, USA) throughout the entire period of investigation. Case-patients and controls were selected from patients hospitalized at TTSH from January 1 through December 31, 2004. Microbiology laboratory records were used to define 3 groups. Case-patients were defined as CDT-positive inpatients (group 1). Two sets of negative controls were defined: the first (group 2) consisted of patients who tested negative for CDT. However, because false-negatives could nullify differences between groups 1 and 2, we defined a second set of negative controls (group 3) from among 18,000 inpatients not tested for CDT. Seventy patients were selected from each group by using a random number generator program. Forty-eight, 61, and 56 records were retrieved for groups 1, 2, and 3, respectively. Standardized forms were used to extract data from hospital medical records. Demographic data and hospitalization details, including ward type (6-bed, 4-bed, or single room), were collected. We examined antimicrobial drug use within 30 days of admission and within 30 days of CDT testing. We also evaluated the use of proton pump inhibitors (PPIs) and H2 blockers because these have been reported as risk factors (1,4–6). Outcomes ascertained included the time to discharge after CDT testing, and death within 30 days after CDT testing. The study was approved by the institutional ethics review board. Characteristics of case-patients and controls were compared by using the Wilcoxon rank sum test for continuous variables and the Fisher exact test for categorical variables. Variables significantly associated with CDT in the univariate analysis were selected for inclusion in the multivariate regression model. A 2-sided p value <0.05 was considered significant for all comparisons. CDAD incidence rose sharply from 1.49 cases per 10,000 patient-days in 2001 to 6.64 cases per 10,000 patient-days in 2006 (Figure). During the same period, the percentage of CDT-positive samples increased from 7% to 11%, while the number of samples tested increased from 906 to 3,508. Figure Clostridium difficile–associated disease incidence, Singapore, 2001–2006. Comparing group 1 (CDT positive) with group 2 (CDT negative), a CDT-positive result was more likely to occur in those with prolonged hospital admissions (>14 days) than in those who had shorter hospital stays (<7 days; odds ratio [OR] 2.59, 95% confidence interval [CI] 1.01–6.63). Of the 19 CDT-positive patients on PPIs and the 34 CDT-negative patients on PPIs, the median exposures were 14 and 7 days, respectively (p = 0.01). In multivariate analysis, exposure to broad-spectrum antimicrobial drugs was a borderline significant risk factor (adjusted OR 2.24, 95% CI 1.00–5.02, p = 0.05). When group 1 (CDT positive) was compared with group 3 (not tested for CDT), quinolones (OR 6.67, 95% CI 1.85–24.03), anti-anaerobic antimicrobial agents (OR 7.29, 95% CI 2.39–22.26), and stay in a 6-bed ward (OR 3.15, 95% CI 1.01–9.82) were significant risk factors in multivariate analysis. Case-patients were more likely than controls to have a longer hospital stay after testing positive. The median hospital stay after CDT testing was 16 days for case-patients versus 11 days for controls (p = 0.03). This study documents a 4-fold rise in CDAD incidence among hospitalized patients in Singapore from 2001 through 2006. The current incidence, 6.64 per 10,000 patient-days, is comparable to that reported by large hospitals in Canada (7), which indicates that CDAD has emerged as an important nosocomial infection in Singapore. This incidence rate, based on the number of patients (rather than the number of isolates) who had positive CDT test results, and the rise in sample positivity from 7% to 11% suggests that the higher rates are due to a true increased occurrence rather than merely more testing. Possible factors driving the rise in CDAD include increased use of antimicrobial agents or changes in use patterns. The volume of quinolones and broad-spectrum antimicrobial drugs used at TTSH doubled between 2002 and 2005, consistent with other studies implicating quinolones as a risk factor in CDAD (4). Rising incidence or virulence could herald the geographic spread of new C. difficile strains. Given the spread of NAP1/BI/027 strains in other parts of the world, this increased incidence in Singapore should heighten vigilance for the introduction of outbreak strains into Asia. The findings from this study have implications for hospital management and infection control. Environmental contamination has been described as a mode of transmission (1). Potential crowding in 6-bed wards may increase spread of CDAD and may be particularly relevant in busy healthcare facilities in Asia. CDAD is estimated to cost the healthcare system in the United States

Risk factors for pandemic (H1N1) 2009 virus seroconversion among hospital staff, Singapore.

3.2 billion annually (8). With longer hospitalization for persons after they test positive for CDT, as seen in our study, rising CDAD rates could increase hospital occupancy and result in excess healthcare expenditures. CDAD in Asia is an emerging challenge that needs to be recognized. Its control will ultimately depend on priority being given to epidemiologic surveillance, infection control, and stewardship of antimicrobial agents.