Impact of formulary interventions on the minimum inhibitory concentration of methicillin-resistant Staphylococcus aureus to mupirocin, chlorhexidine, and octenidine in a Singapore tertiary institution.

Methicillin-resistant Staphylococcus aureus (MRSA) decolonization is an effective measure to prevent clinical infection but resistance is a concern. We aim to evaluate the impact of mupirocin (MUP) ointment formulary removal, plateauing use of chlorhexidine gluconate (CHG), and hospital-wide introduction of octenidine (OCT)-based products on the minimum inhibitory concentration (MIC) of MRSA to MUP, CHG, and OCT in our hospital. A prevalence study was conducted at three time points (TP) on consecutive MRSA screening isolates to evaluate for their MICs to MUP, CHG, and OCT using broth microdilution sensititre plates and detection of the ileS-2 gene encoding high-level MUP resistance in 2013 (pre-intervention TP1; n = 160), 2016 (early post-intervention TP2; n = 99) and 2017 (late post-intervention TP3; n = 76). Statistical analyses were performed using Chi square test with reference from TP1. There was a significant improvement in MUP susceptibility (MIC < 4 mcg/ml) from 71.9% (TP1) to 86.9% (TP2; p = 0.006) to 88.2% (TP3; p = 0.007). The prevalence of MUP high-level resistance (MIC > 256 mcg/ml) reduced from 25.0% (TP1) to 12.1% (TP2; p = 0.014) to 5.3% (TP3; p = 0.001). Likewise, the prevalence of isolates harboring the ileS-2 gene decreased from 28.1% (TP1) to 18.2% (TP2; p = 0.072) to 9.2% (TP3; p = 0.002). OCT MIC range remains stable at 0.5 to 1 mcg/ml across all three TPs. The proportion of isolates with reduced CHG susceptibility (MIC ≥ 4 mcg/ml) increased over the three TPs from 23.1 to 27.2% (p = 0.45) to 42.1% (p = 0.003). Active formulary regulations have an impact on the resistance profile of MRSA and can be used as a strategy to preserve the MRSA decolonization armamentarium.

NLRP3 inflammasome pathway has a critical role in the host immunity against clinically relevant Acinetobacter baumannii pulmonary infection.

The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1ß (IL-1ß) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A. baumannii infection is unknown. Using a sublethal mouse pneumonia model, we demonstrate that an extensively drug-resistant clinical isolate (ICII) of A. baumannii exhibits reduced/delayed early pulmonary neutrophil recruitment, higher lung persistence, and, most importantly, elicits enhanced IL-1ß/IL-18 production and lung damage through NLRP3 inflammasome, in comparison with A. baumannii-type strain. A. baumannii infection-induced IL-1ß/IL-18 production is entirely dependent on NLRP3-ASC-caspase-1/caspase-11 pathway. Using Nlrp3-/- mice infection models, we further show that while NLRP3 inflammasome pathway contributes to host defense against A. baumannii clinical isolate, it is dispensable for protection against A. baumannii-type strain. Our study reveals a novel differential role for NLRP3 inflammasome pathway in the immunity against clinically relevant A. baumannii infections, and highlights inflammasome pathway as a potential immunomodulatory target.

Radium-226 levels and concentration ratios between water, vegetation, and tissues of ruffed grouse (Bonasa umbellus) from a watershed with uranium tailings near Elliot Lake, Canada.

Radionuclide levels measured in bone, muscle, kidney and liver tissues, gut contents and diet items of 47 grouse from the Serpent River drainage basin, containing uranium (U) tailings at Elliot Lake, and from control areas in Ontario, showed variation by site and tissue. The mean level of 226radium (Ra) in bones of grouse sampled from Elliot Lake (28.5 mBq g(-1)) was higher than that in bones of birds from a distant control site near Sudbury, Ontario (8.0 mBq g(-1)) but similar to the value in a local control population (28.1 mBq g(-1)). Birds from Mid- and Low-Serpent River basin populations (with 17.1 and 17.7 mBw g(-1), respectively) did not differ from local or distant control populations; muscle, liver and kidney had lower 226Ra concentrations, which did not differ significantly among populations. Levels of 226Ra in the crop contents and intestine did not differ significantly by site and were similar to those of food items consumed by the birds. Stomach content values were higher in birds sampled in Elliot Lake and at the local control site than in those taken at the distant control site; birds sampled downstream from Elliot Lake did not differ from distant controls in this regard. Levels of 232thorium (Th) and 230Th were below detection limits (0.1 microg g(-1) and 5.0 mBq g(-1), respectively) in bone, muscle and liver tissue in two grouse with elevated levels of 226Ra. Other radionuclides were measurable in some tissues: 238U in bone at 0.4 microg g(-1), in muscle to 0.2 microg g(-1), in liver to 1.0 gmg g(-1.), 228Th was found only in muscle (8.0 mBq g(-1)), 210poloniuim (Po) was found in bone, muscle and liver (maxima: 24.0, 7.0, 16.0 mBq g(-1)) with the exception of one muscle sample; 210lead (Pb) was detected in only one liver sample (50.0 mBq g(-1)). Environmental levels fell within ranges previously reported at the sites, or at similar locations elsewhere. Leaves of trembling and largetooth aspen growing in the basin had mean 226Ra levels of 14.8 and 52.7 mBq g(-1) (dry weight) respectively, and fungal material carried up to 215.4 mBq g(-1) (air-dried), with some variation by site. River and lake waters sampled near the U tailings had 118.1 mBq litre(-1) of dissolved 226Ra; at the distant control site the value was 12.1 mBq litre(-1). The concentration ratios (CR) between bone of grouse collected at the Elliot Lake sites and trembling and largetooth aspen leaves were 1.38 and 1.09 (fresh weight basis); from other diet items and to other tissues the values were less than unity. Bone tissue: water ratios, based on dissolved 226Ra levels, ranged to 30.89. People eating grouse from the study area are unlikely to consume radionuclides in excess of limits currently established by Canadian regulatory authorities.

Radionuclides (lead-210, polonium-210, thorium-230, and -232) and thorium and uranium in water, sediments, and fish from lakes near the city of Elliot Lake, Ontario, Canada.

Radionuclides (210Pb, 210Po, 230Th, and 232Th) and chemical Th and U were measured in water, sediments, and fish tissues (bone, muscle, and gut contents of laketrout, Salvelinus namaycush, whitefish, Coregonus clupeaformis and Prosopium cylindraceum) from four lakes in a watershed affected by U mining and milling operations at Elliot Lake, Ontario, and from control lakes in an adjacent, non-industrialized, watershed. Radionuclide concentration ratios between tissue levels and sediment and water levels were calculated. Annual radionuclide intakes and resulting doses were estimated for humans consuming fish from the watershed. Bone 210Pb levels were higher (186 mBq g(-1) dry wt in laketrout and 230 mBq g(-1) dry wt in one lake whitefish) than in muscle (< 50 mBq g(-1) dry wt in all cases), and generally higher in fish from study lakes than from controls, but no consistent differences were observed among fish species. Similarly, 210Po levels were higher in bone (208 +/- 33 mBq g(-1), in laketrout) than muscle (maximum 26 +/- 4 mBq g(-1), in laketrout), and in study lake populations compared to controls. Laketrout 210Po bone concentrations were higher than previously reported in Canada. Levels of 230Th, 232Th, and Th were below detection limits (20 mBq g(-1), 0.05 microg g(-1)) in body tissues in all fish species. Bone levels of U (14.6 +/- 3.0 microg g(-1), in lake whitefish) were higher than in muscle (most < 0.05 microg g(-1), except 0.12 +/- 0.04 and 0.08 +/- 0.03 microg g(-1) in lake whitefish) in fish from waters affected by industrial activity. In control lakes, bone and muscle levels were lower and not significantly different from each other. Muscle levels did not vary consistently with location. Concentration of 210Pb and U was seen from water and 'gut' material (taken as a surrogate for diet) to bone in laketrout and whitefish, and of U from water to muscle in whitefish, but in no case from sediments to tissues. Human intakes of 210Pb, 210Po, 230Th, 232Th, and U from consuming one meal of fish (375 g) per week could, in aggregate, represent an annual effective dose < 15% of the public dose limit (5 mSv). Monitoring biota living near the decommissioned Elliot Lake U operations, especially of 210Pb levels in fish muscle, with further assessment of human doses attributable to local fish and other animals in the diet, should continue. Because radionuclide effects on fish health (and on other non-human organisms) are of increasing concern, neoplasms, malformations, and reproductive anomalies in local fish deserve examination.

Radium-226 in water, sediments, and fish from lakes near the city of Elliot Lake, Ontario, Canada.

Ra-226 was measured by alpha-emission spectroscopy in water, sediments, and fish (tissues and gut contents), from five lakes in a watershed containing U mining and milling operations at Elliot Lake, Ontario, and from control lakes in an adjacent non-industrialized watershed. Ra-226 transfer parameters from lake water and sediments to fish tissues, and annual intakes by humans consuming fish, were estimated. Mean dissolved 226Ra levels ranged from approximately 76 mBq litre(-1) in water of the most affected lake, to < 10 mBq litre(-1) in control lakes. Levels in summer were consistently higher than in fall or winter; no consistent variation with depth was noted. Sediment levels ranged from approximately 3000 mBq g(-1) dry wt in one study lake to < 100 mBq g(-1) dry wt of sediment in control lakes. Bone 226Ra concentrations were higher than in muscle. The lake trout (Salvelinus namaycush), a predatory secondary consumer, had bone 226Ra levels (< 20 mBq g(-1) dry wt) that did not show significant site variation. In contrast, bottom feeding whitefish had significantly more 226Ra in bone tissue (to 38 mBq g(-1) dry wt in the lake whitefish, Coregonus clupeaformis, and 76 mBq g(-1) in round whitefish, Prosopium cylindraceum) in study lakes than in controls (< 20 mBq g(-1) dry wt). Ra-226 levels in lake trout muscle were low and showed erratic variation among lakes whereas levels in whitefish muscle did not vary significantly among study and control sites. Lake herring (= cisco, Coregonus artedii), a planktivorous fish taken only from Quirke Lake, had mean 226Ra levels of 18 and 1.4 mBq g(-1) dry wt in bone and muscle, respectively. Gut 226Ra levels, highest in lake trout from McCabe and Quirke Lakes (126 +/- 53, 64 +/- 44 mBq g(-1) dry wt, respectively), and just detectable in McCabe and Elliot Lake whitefish (24 +/- 2, 36 +/- 14 mBq g(-1) dry wt, respectively), were below detection in lake trout and whitefish from other lakes. Concentration ratios (CRs) of 226Ra from water to muscle ranged from 8 to 14 in lake trout, 7 to 14 in whitefish, and 4 to 6 in lake herring. The water to bone CRs varied from 81 to 142, 314 to 548, and 126 to 272 in the same species. CRs were always < 1 between sediments and fish tissues. Annual intake of 226Ra by human consumers of these fish was estimated to provide an effective dose of 0.003 mSv year(-1). This represents a small fraction of both natural background (> 2 mSv year(-1)) and the public dose limit (5 mSv year(-1)).

226Ra and other radionuclides in water, vegetation, and tissues of beavers (Castor canadensis) from a watershed containing U tailings near Elliot Lake, Canada.

Radionuclide levels were measured in tissues, gut contents, diet items, and water at site of capture, of adult beavers from the Serpent River drainage basin which contains U tailings at Elliot Lake, Ontario, and from nearby control sites. Levels of (226)Ra in beaver bone, muscle and kidney were highest in animals from locations close to U tailings; liver levels did not vary by site. Environmental (226)Ra levels were within ranges previously reported at these or similar locations elsewhere; levels in beaver gut contents reflected levels in diet items. Concentration ratios exceeded unity only between some vegetation items and beaver bone at the Elliot Lake site and were less than 0.19 between vegetation and other tissues. In two beavers with tissue levels of (226)Ra higher than other sampled, neither (232)Th nor (230)Th were detected in bone, muscle or liver tissues. U-238 was measurable in bone, muscle and liver, (228)Th in bone, (210)Po bone, muscle and liver; and (210)Pb was measurable only in bone. Estimated yearly intakes of radionuclides by people eating beavers were calculated to be below current allowable levels set by the Canadian regulatory authorities.

Radium-226 in cattails, Typha latifolia, and bone of muskrat, Ondatra zibethica (L.), from a watershed with uranium tailings near the city of Elliot Lake, Canada.

Radium-226 concentrations were measured in the main food plants (cattails, Typha latifolia) and bone of adult muskrats (Ondatra zibethica (L.)), taken from a study area near Quirke Lake in the Serpent River drainage basin. This watershed receives drainage containing radionuclides from the U tailings near the City of Elliot Lake, Ontario, Canada. Two control sites (one local, one 130 km distant) were also sampled. Radium-226 levels in cattails varied by plant part and place of collection. Roots sampled in the study area had the highest mean (226)Ra level (1135.0 mBq g(-1)), stems and leaves had 284.2 and 275.9 mBq g(-1), respectively (dry-weight basis, n = 6 in all cases). Local and distant control cattails carried much lower (226)Ra levels (20.2 and 15.2 mBq g(-1) dry weight, respectively, using pooled equal portions of all plant parts, n = 3 in both cases). Muskrats from waters with mean total (226)Ra levels in the period, 1984-1987 greater than 75.0 mBq litre(-1) ('study-high' sites), near U tailings within 10 km of Quirke Lake, had a mean (geometric) bone level of (226)Ra of 344.9 mBq g(-1) (dry-weight basis, n = 36); those from nearby waters, containing < 75.0 mBq litre(-1) of (226)Ra ('study-low' sites), had a mean bone level (80.3 mBq g(-1), n = 9) similar to animals taken in unaffected local control areas 20 km from the tailings (79.1 mBq g(-1), n = 12); animals from the distant control area, near Sudbury, Ontario, had the lowest mean burden (11.5 mBq g(-1), n = 24). Levels were unrelated to age or sex of the animals. Dry-weight based (226)Ra concentration ratios (bone concentration/plant tissue concentration) were calculated to range from 0.3-1.4 in the study-high area to 2.4-6.3 in the local control area. Wet-weight based concentration ratios were about 4.3 times higher. Concentration ratios were similar to values calculated for other species and in general agreement with values calculated for humans. The muskrat is judged to be a useful indicator (biomonitor) of environmental (226)Ra levels as there is a highly significant positive correlation coefficient (r = 0.74) between bone and ambient (water) concentrations of the radionuclide (F79 = 95.04, P < 0.0001) Estimated yearly (226)Ra intake by people eating muskrats was calculated to be below the current allowable level set by Canadian regulatory authorities.

U- and Th-series radionuclides in snowshoe hare (Lepus americanus) taken near U mill tailings close to Elliot Lake, Ontario, Canada.

Snowshoe hare (Lepus americanus) trapped near U tailings had higher concentrations of (226)Ra in their bones (250 +/- 94 mBq g(-1) dry wt) than those from local control sites 3-15 km from the tailings (20-30 mBq g(-1) dry wt) and those from a distant control site 880 km away from the U mining area, which were below the detection limit (DL) (3.7 mBq g(-1) dry wt). Most chyme (stomach content) samples contained 226Ra below DL. Concentration ratios of 226Ra from tissues of local plants, considered important in the hare's diet, to bone ranged from 0.22 to 8.60. Concentrations of 210Pb and 210Po (95-245 mBq g(-1) dry wt) were not significantly different among tailings and control site populations. Disequilibrium between these isotopes and their precursors was noted. No significant accumulation of U and Th was noted at any site. Higher concentrations of 228Th compared to 232Th are attributed to accumulation of 228Ra in a manner similar to that of 226Ra. Based on bone 226Ra and 210Po contents, the maximum internal dose rates to the skeleton and the maximum life-time dose of hare living near tailings were 3.9 x 10(-5) Gy d(-1) and 4.2 x 10(-2) Gy, respectively. These rates were below the threshold required to produce osteosarcoma in other mammals and were considered unlikely to adversely affect hare during their lifetime. Radionuclide uptake by the animals was concluded to have no environmental significance in the transport of radionuclides from tailings to other locations.

Cost-effectiveness analysis of medical and surgical treatment for duodenal ulcer in Singapore.

A mathematical model involving transitions between possible states of duodenal ulcer was used to calculate the costs of various treatments, medical and surgical, which are available for the long-term management of duodenal ulcer. Costs of medical and surgical treatment were based on costs incurred at the National University Hospital, Singapore as at 1990. Elective surgery incurs a high cost, both financial and in terms of mortality, at the outset with minimal additional costs subsequently. The various medical options cost less initially but their costs are cumulative and eventually overtake the costs of surgical treatment. These calculations are based on the use of a proprietary preparation of a histamine-2-blocker. If a generic preparation is used, medical treatment becomes considerably cheaper over a 15 year period.

Uptake of 226Ra by established vegetation and black cutworm larvae, Agrotis ipsilon (class Insecta: order Lepidoptera), on U mill tailings at Elliot Lake, Canada.

Radium-226 levels in samples from an inactive U tailings site at Elliot Lake, Ontario, Canada, were: 9,140 +/- 500 mBq g-1 dry weight in the substrate; 62 +/- 1 mBq g-1 dry weight in rye, Secale cereale, and less than 3.7 mBq g-1 dry weight in oats, Avena sativa, the dominant species established by revegetation of the tailings; and 117 +/- 7 mBq g-1 dry weight in washed and unwashed black cutworm larvae. Concentration ratios were: vegetation to tailings 0.001-0.007; black cutworms to vegetation 3.6 and black cutworms to tailings 0.01. The values are considered too low to be considered a hazard to herring gulls, Larus argentatus, which occasionally feed on cutworms.

Transfer coefficient of 226Ra from vegetation to meadow voles, Microtus pennsylvanicus, on U mill tailings.

The 226Ra level in vegetation growing on U mine tailings in Elliot Lake, Ontario, Canada, was 211 + 22 mBq g-1 (dry weight) compared to less than 7 mBq g-1 (dry weight) in material from a control site. Skeletons of meadow voles (Microtus pennsylvanicus) established on the tailings had concentrations of 226Ra of 6,083 +/- 673 mBq per animal in winter; 7,163 +/- 1,077 mBq per animal in spring; 1,506 +/- 625 mBq per animal in summer; and 703 +/- 59 mBq per animal in fall, compared to less than 7 mBq per animal in controls. The 226Ra transfer coefficient from vegetation to voles (defined as total millibecquerels of 226Ra in adult vole per total millibecquerels of 226Ra consumed by the vole in its lifetime) was calculated as 4.6 +/- 2.9 X 10(-2) in summer and 2.8 +/- 0.6 X 10(-2) in fall.

The effect of test duration on the sensitivity and specificity of ultra-rapid urease test for the detection of Helicobacter pylori infection.

BACKGROUND: 'Home made' ultra-rapid urease tests are used extensively in the Asia Pacific region. Data on the reliability of these 'home made' tests are limited. AIMS: To evaluate the effect of test duration on the sensitivity and specificity of a self-prepared biopsy urease test for the detection of Helicobacter pylori. METHODS: Using histology as the 'gold standard', the effect of test duration on the sensitivity and specificity of a self prepared urease test for the detection of H. pylori was evaluated in 411 consecutive patients undergoing upper gastrointestinal endoscopy. RESULTS: Histology was positive for H. pylori in 217 of the 411 patients (52.8%). Within 24 hours of retrieving the specimen, 189 (87.1%) of the histology positives and 174 (89.7%) of the histology negatives were correctly identified by the urease test. Of the H. pylori positives, 72.0%, 81.0%, 89.9% and 100% were detected by the urease test within one minute, five minutes, three hours and 24 hours respectively. Thus, sensitivities of the urease test at one minute, five minutes, three hours and 24 hours were 62.7%, 70.5%, 78.3% and 87.1% respectively. Corresponding figures for the specificity were 93.8%, 93.3%, 92.3% and 89.7% respectively. Using a receiver-operating characteristic curve, an optimal combination of sensitivity and specificity was obtained when the urease test was read at 24 hours. CONCLUSIONS: While the biopsy urease test was positive in most cases within a minute, better results could be obtained if the test continued to be read over a 24 hour period.

Racial differences in Helicobacter pylori seroprevalence in Singapore: correlation with differences in peptic ulcer frequency.

The aim of this study was to determine, first, whether racial differences exist in the seroprevalence of Helicobacter pylori infection in Singapore, and second, whether these differences correlate with racial differences in peptic ulcer frequency. A commercial serological test for immunoglobulin (Ig)G antibody to H. pylori which was 90% sensitive and 83% specific in our population was used to screen 403 adult blood donors of Chinese, Malay and Indian origin, aged between 15-60 years. Serum specimens from 84 paediatric patients admitted to the Paediatrics Department, National University of Singapore, with non-gastroenterological illnesses were also tested. In all three races, seroprevalence of H. pylori increased with age. Indians have the highest prevalence of infection followed by Chinese and Malays. Peptic ulcer prevalences are known to be highest in Chinese, followed by Indians and Malays. The Malays have the lowest prevalence of H. pylori and peptic ulcer among the three races in Singapore. Indians have a higher prevalence of H. pylori antibodies but a lower frequency of peptic ulcer than the Chinese. Racial differences in peptic ulcer frequency between Chinese and Indians are not explained by the prevalence of H. pylori infection; other environmental or genetic factors may be involved.