[Show abstract][Hide abstract] ABSTRACT: This study examined the efficacy of photocatalytic titanium dioxide (TiO2) coating in reducing environmental
MRSA contamination via a cross-sectional observational study in a tertiary hospital. This involved using
environmental samplings of TiO2 treated and TiO2 untreated surfaces from single rooms in intensive care unit,
open-planned intermediate care area and general ward. Planned scheduled sampling occurred up to 24 months
post TiO2 treatment. Ad hoc sampling of MRSA exposed environment occurred whenever MRSA infected or
colonized patient was admitted for >48 hours. Efficacy of TiO2 in preventing environmental contamination was
computed. Culture positive rates were compared between treated and untreated surfaces, and planned and ad
hoc sampling. 698 samples were obtained. Samples from untreated surfaces and ad hoc samples were more
likely to be culture positive (for MRSA and other bacteria) [untreated versus treated surfaces: odds ratio (OR)
2.95, 95% confidence interval (CI) 1.25 – 6.94, p=0.01; ad hoc sampling post MRSA exposure versus planned
sampling: OR 4.52, 95% CI 2.131 – 9.615, p< 0.001)] . Multivariate analysis suggests only MRSA exposure
influenced positive cultures. TiO2 did not influence positive culture results. More research is needed to evaluate
the relative lack of TiO2 efficacy in preventing contamination.
International Journal of Infection Control 09/2013; 9(3).
[Show abstract][Hide abstract] ABSTRACT: We investigated an outbreak of 47 probable and 6 confirmed cases of microsporidial keratoconjunctivitis involving participants of an international rugby tournament in Singapore in April 2012.The mode of transmission was eye contact with soil. Vittaforma corneae was identified in 4 of 6 corneal scrapings and in 1 of 12 soil water samples.
[Show abstract][Hide abstract] ABSTRACT: This work describes how to tune the amphiphilic conformation of α-mangostin, a natural compound that contains a hydrophobic xanthone scaffold, to improve its antimicrobial activity and selectivity for Gram-positive bacteria. A series of xanthone derivatives was obtained by cationic modification of the free C3 and C6 hydroxyl groups of α-mangostin with amine groups of different pKa values. Modified structures using moieties with high pKa values, such as AM-0016 (3b), exhibited potent antimicrobial properties against Gram-positive bacteria. Compound 3b also killed bacteria rapidly without inducing drug resistance and was nontoxic when applied topically. Biophysical studies and molecular dynamics simulations revealed that 3b targets the bacterial inner membrane, forming an amphiphilic conformation at the hydrophobic–water interface. In contrast, moieties with low pKa values reduced the antimicrobial activity of the parent compound when conjugated to the xanthone scaffold. This strategy provides a new way to improve “hits” for the development of membrane-active antibiotics that target drug-resistant pathogens.
Journal of Medicinal Chemistry 04/2013; · 5.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This work described how to tune the amphiphilic conformation of α-mangostin, a natural compound with a hydrophobic xanthone scaffold to improve the antimicrobial activity and selectivity for Gram-positive bacteria. A series of xanthone derivatives were obtained by cationic modification of free hydroxyl groups of α-mangostin at C3 and C6 positions with amines groups of different pKa values. Modified structures using high pKa moieties such as AM-0016 (3b) showed potent antimicrobial properties against Gram-positive bacteria. 3b also killed bacteria rapidly, did not induce drug resistance and was non-toxic when applied topically. Biophysical studies and molecular dynamic simulations revealed that 3b targeted the bacterial inner membrane, forming an amphiphilic conformation at the hydrophobic-water interface. In contrast, moieties conjugated to the xanthone scaffold with low pKa values diminished the antimicrobial activities. This strategy provides a new insight to improve "hits" in the development of new membrane-active antibiotics for drug-resistant pathogens.
Journal of Medicinal Chemistry 02/2013; · 5.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has created the need for better therapeutic options. In this study, five natural xanthones were extracted and purified from the fruit hull of Garcinia mangostana and their antimicrobial properties were investigated. α-Mangostin was identified as the most potent among them against Gram-positive pathogens (MIC=0.78-1.56μg/mL) which included two MRSA isolates. α-Mangostin also exhibited rapid in vitro bactericidal activity (3-log reduction within 5min). In a multistep (20 passage) resistance selection study using a MRSA isolated from the eye, no resistance against α-mangostin in the strains tested was observed. Biophysical studies using fluorescence probes for membrane potential and permeability, calcein encapsulated large unilamellar vesicles and scanning electron microscopy showed that α-mangostin rapidly disrupted the integrity of the cytoplasmic membrane leading to loss of intracellular components in a concentration-dependent manner. Molecular dynamic simulations revealed that isoprenyl groups were important to reduce the free energy for the burial of the hydrophobic phenyl ring of α-mangostin into the lipid bilayer of the membrane resulting in membrane breakdown and increased permeability. Thus, we suggest that direct interactions of α-mangostin with the bacterial membrane are responsible for the rapid concentration-dependent membrane disruption and bactericidal action.
Biochimica et Biophysica Acta 09/2012; · 4.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine trends and clinical and epidemiologic features of legionellosis in Singapore, we studied cases reported during 2000-2009. During this period, 238 indigenous and 33 imported cases of legionellosis were reported. Cases were reported individually and sporadically throughout each year. Although the annual incidence of indigenous cases had decreased from 0.46 cases per 100,000 population in 2003 to 0.16 cases per 100,000 in 2009, the proportion of imported cases increased correspondingly from 6.2% during 2000-2004 to 27.3% during 2005-2009 (p<0.0005). The prevalence of Legionella bacteria in cooling towers and water fountains was stable (range 12.1%-15.3%) during 2004-August 2008.
[Show abstract][Hide abstract] ABSTRACT: Because invasive fungal infections cause significant morbidity and mortality in liver transplant recipients, the use of antifungal prophylaxis, and the early empirical use of antifungal agents, is widespread on liver transplant units. The new-generation azoles such as voriconazole and the echinocandins have been welcome additions to the antifungal armamentarium. These agents have become the leading options for prophylaxis in liver transplant units, despite the absence of strong data for their efficacy in this setting.
We report two recipients of living-donor liver transplants who became infected/colonised with fungi resistant to an echinocandin and the azoles after exposure to these agents. One patient developed trichosporonosis while on caspofungin and the other became infected/ colonised with Candida glabrata that was resistant to voriconazole and posaconazole.
We report these to highlight some of the consequences of using the newer antifungal agents.
Annals of the Academy of Medicine, Singapore 06/2011; 40(6):287-90. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of Clostridium (C.) difficile infection (CDI) was on the rise from 2001 to 2006 in Singapore. Recent unpublished data suggests that its incidence had remained stable or decreased in most local public hospitals between 2006 and 2010. It is, however, not known if the polymerase chain reaction (PCR) ribotype 027 strains have been circulating, although reports suggest that this strain is emerging in Asia, with the first cases reported from Japan in 2007, as well as in Hong Kong and Australia in 2009. We initiated a culture-based surveillance to detect this epidemic strain in Singapore.
From September 2008 to December 2009, all non-duplicate toxin-positive stool samples from the three largest public hospitals in Singapore were collected for culture and further analysis.
Out of the 366 samples collected, 272 viable isolates were cultured. Of these, 240 tested toxin-positive and ten tested positive for the binary toxin gene; 35 different PCR ribotypes were found. Three isolates that tested positive for binary toxin contained the same PCR ribotyping pattern as the C. difficile 027 control strain. All three had the 18-bp deletion and single nucleotide tcdC deletion at position 117. Susceptibility testing was performed, demonstrating susceptibility to erythromycin and moxifloxacin.
We report the first three isolates of C. difficile 027 from Singapore. However, their susceptibility patterns are more consistent with the historical 027 strains. Rising CDI incidence may not be associated with the emergence of the epidemic 027 strain at this time.
Singapore medical journal 05/2011; 52(5):361-4. · 0.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper describes the epidemiological, microbiological and environmental investigations conducted during an outbreak of Salmonella gastroenteritis in Singapore.
A case-control study was undertaken to identify the vehicle of transmission. Microbiological testing was performed on faecal, food and environmental samples. Isolates of Salmonella were further characterized by phage typing and ribotyping.
There were 216 gastroenteritis cases reported from 20 November to 4 December 2007. The causative agent was identified as Salmonella enterica subspecies enterica serotype Enteritidis for 14 out of 20 cases tested. The vehicle of transmission was traced to cream cakes produced by a bakery and sold at its retail outlets (P < 0.001, OR = 143.00, 95% Cl = 27.23-759.10). More than two-thirds of the 40 Salmonella strains isolated from hospitalized cases, food samples and asymptomatic food handlers were of phage type 1; the others reacted but did not conform to any phage type. The phage types correlated well with their unique antibiograms. The ribotype patterns of 22 selected isolates tested were highly similar, indicating genetic relatedness. The dendrogram of the strains from the outbreak showed distinct clustering and correlation compared to the non-outbreak strains, confirming a common source of infection.
The cream cakes were likely contaminated by one of the ingredients used in the icing. Cross-contamination down the production line and subsequent storage of cakes at ambient temperatures for a prolonged period before consumption could have contributed to the outbreak.
Western Pacific surveillance and response journal : WPSAR. 03/2011; 2(1):23-30.
[Show abstract][Hide abstract] ABSTRACT: The rapid identification of C. albicans solely based on the presence of a pseudohyphal fringe ('spiking' colony morphology) has been descibed to give excellent sensitivity (even surpassing that of the well-established germ tube test) and specificity. We therefore evaluated the performance of this method using our standard Trypticase Soy Agar with 5% sheep blood (TSA BAP), and following overnight (18-24 hours) of incubation in a CO2 incubator, using our standard germ tube method with horse serum as the reference standard. A lower sensitivity (78.6%) than previously described was found, but the method appears to be feasible for the presumptive identification of yeasts for semi-critical and non-sterile sites. Another caveat is the possibility of Trichosporon spp. giving spiking colonial morphology, and therefore being mistaken for C. albicans.
Journal of Medical Microbiology 01/2011; 60(Pt 5):687-8. · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various studies have documented a shift in species distribution in Candida bloodstream infections (BSI), but there are little data from Southeast Asia. This study was performed to determine the species epidemiology and antifungal susceptibilities of Candida species BSI in Singapore. Candida spp. from BSI were collected from a tertiary and secondary referral hospital, and an obstetrics/paediatric hospital over a 3-year period. The most common isolates were Candida albicans (36%), Candida tropicalis (27%), Candida glabrata (16%) and Candida parapsilosis (16%). Candida parapsilosis and C. albicans were predominant in the paediatric hospital, and C. albicans and C. tropicalis predominant in the other two institutions. Candida tropicalis temporarily replaced C. albicans as the predominant strain from BSI in 2006. Overall, 87.3% of Candida isolates were susceptible to fluconazole, and 10.4% classified as susceptible-dose-dependent. Fluconazole resistance was detected in C. tropicalis (3.6%), C. parapsilosis (2.1%) and C. glabrata (4.0%). Candida albicans is the predominant species isolated from BSI in Singapore. However, non-albicans species accounted for nearly two-thirds of all cases of candidaemia and the relative increase in C. tropicalis infections deserves further investigation. Resistance to fluconazole was uncommon.
[Show abstract][Hide abstract] ABSTRACT: The antimicrobial susceptibility of Burkholderia pseudomallei isolates identified by the bacteriology laboratory at Singapore General Hospital was reviewed. Laboratory data were found to be available since 1987 and showed that ceftazidime, amoxicillin-clavulanate, chloramphenicol and tetracycline had remained effective through the years. Imipenem was added to the list of antimicrobials tested after 1989, and the isolates showed high susceptibility rates. Co-trimoxazole was found to be useful based on Etest results, but the isolates had low susceptibility rates when tested using disk diffusion.
Transactions of the Royal Society of Tropical Medicine and Hygiene 01/2009; 102 Suppl 1:S101-2. · 1.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fungaemia carries with it high mortality rates and appropriate as well as timely antifungal therapy has been shown to be life saving.
We studied the invitro activities of antifungal agents using the Etest method, against 100 Candida isolates from blood cultures, 10 Cryptococcus isolates from blood or cerebrospinal fluid and 50 mould isolates from various clinically significant sites of patients in Singapore General Hospital, from June 2004 to December 2006.
Overall, the yeasts appeared to have low minimum inhibitory concentrations (MICs) for all the 5 antifungal drugs tested except for fluconazole. The overall high MIC90 values of the moulds against the azoles were largely attributed to the non-Aspergillus moulds. Posaconazole, itraconazole, voriconazole and caspofungin appear effective against local strains of Aspergillus species, although there are no interpretive breakpoints.
The results show that the local fungal strains studied appear to be susceptible to the usual antifungal drugs recommended in the literature.
Annals of the Academy of Medicine, Singapore 11/2008; 37(10):841-6. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Worldwide, Candida albicans is the most common Candida species implicated in bloodstream infections. However, the proportion of non-albicans bloodstream infections is increasing. Fluconazole resistance is known to be more common in non-albicans species, but is also reported in C. albicans. This retrospective study was performed to determine the species epidemiology of Candida bloodstream infections in Singapore hospitals, and to perform susceptibility testing to a range of antifungal drugs.
Candida spp. isolated from bloodstream infections from October 2004 to December 2006 were collected from 3 participating hospitals: a tertiary referral hospital (Singapore General Hospital), a secondary referral hospital (Changi General Hospital) and an obstetrics/paediatric hospital [KK Women's and Children's Hospital (KKWCH)]. Isolate collection was also retrospectively extended to January 2000 for KKWCH because of the limited number of cases from this hospital. Isolates were identified by a common protocol, and antifungal susceptibility testing was performed by microbroth dilution (Sensititre One, Trek Diagnostics, United Kingdom).
The most common isolates were C. albicans (37%), C. tropicalis (27%) and C. glabrata (16%). There were differences in species distribution between institutions, with C. parapsilosis and C. albicans predominant in KKWCH, and C. albicans and C. tropicalis predominant in the other 2 institutions. Fluconazole resistance was detected in 3.2% of all Candida spp., and 85.3% were classified as susceptible. All C. albicans and C. parapsilosis were susceptible to fluconazole and voriconazole, while susceptibility to fluconazole was much more variable for C. glabrata and C. krusei.
This study shows that C. albicans remains the predominant Candida species isolated from bloodstream infections in the 3 participating hospitals. However, non-albicans species accounted for nearly two-thirds of all cases of candidaemia. Resistance to fluconazole was uncommon, and was generally confined to C. krusei and C. glabrata.
Annals of the Academy of Medicine, Singapore 11/2008; 37(10):835-40. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Campylobacter species are major enteric pathogens causing diarrhea illness in humans and animals. Immunological tests are needed for accurate and rapid identification of C. coli, in conjunction with the use of standard biochemical tests. We initiated the creation of monoclonal antibodies (MAbs) using whole C. coli cells as antigen. Four positive clones were identified, namely MAb2G6, MAb3B9, MAb4A10 and MAb5B9. Dot-blot assay and ELISA revealed that only MAb2G6 did not cross react with C. jejuni and other Campylobacter isolates. As demonstrated by dot-blot assay, MAb2G6 reacted with all 23 C. coli isolates tested but did not react with 29 isolates of C. jejuni, 3 other Campylobacter spp. isolates and 19 non-Campylobacter isolates, with the lowest detection limit was in the range of 10(3) to 10(4) bacteria. Western blots and dot blots showed that the antigen of MAb2G6 was a native protein, with immunoprecipitation assay showed that MAb2G6 bound to a protein band of approximately 43 kDa in size, corresponding to major outer membrane protein (MOMP) of C. coli revealed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). Immunofluorescence assay (IFA) showed that MOMP of C. coli was indeed the antigen of MAb2G6, with immunogold-electron microscopy demonstrated that MAb2G6 conjugated with immunogold particles bound to all over the surface of C. coli cells. MAb2G6 also showed potential usage in direct detection of C. coli in faecal samples.
Journal of Immunological Methods 10/2008; 339(1):104-13. · 2.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Campylobacter species are important enteric pathogens causing disease in humans and animals. There is a lack of a good immunological test that can be used routinely to separate Campylobacter jejuni from other Campylobacter species. We produced monoclonal antibodies (MAbs) directed against the major outer membrane protein (MOMP) of C. jejuni using recombinant MOMP as the antigen. One MAb, designated MAb5C4 and of the immunoglobulin G1 isotype, was found to be potentially specific for C. jejuni. Dot blots demonstrated that MAb5C4 reacted with all 29 isolates of C. jejuni tested but did not react with 2 C. jejuni isolates, 26 other Campylobacter spp. isolates, and 19 non-Campylobacter isolates. Western blotting showed that MAb5C4 bound to a single protein band approximately 43 kDa in size, corresponding to the expected size of C. jejuni MOMP. The detection limit of MAb5C4 in a dot blot assay was determined to be about 5 x 10(3) bacteria. The epitope on the MOMP was mapped to a region six amino acids in length with the sequence 216GGQFNP221, which is 97% conserved among C. jejuni strains but divergent in other Campylobacter spp.; a GenBank search indicated that 95% of C. jejuni isolates will be able to be detected from non-Campylobacter spp. based on the highly specific and conserved region of the GGQFNP polypeptide. The epitope is predicted to be located in a region that is exposed to the periplasm. MAb5C4 is a potentially specific and sensitive MAb that can be used for the specific detection and identification of C. jejuni.
Applied and Environmental Microbiology 03/2008; 74(3):833-9. · 3.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Singapore, an outbreak of fungal keratitis caused by members of the Fusarium solani species complex (FSSC) was identified in March 2005 to May 2006 involving 66 patients. Epidemiological investigations have indicated that improper contact lens wear and the use of specific contact lens solutions were risk factors.
We assessed the genetic diversity of the isolates using AFLP, Rep-PCR, and ERIC-PCR and compared the usefulness of these typing schemes to characterize the isolates.
AFLP was the most discriminative typing scheme and appears to group FSSC from eye infections and from other infections differently.
There was a high genomic heterogeneity among the isolates confirming that this was not a point source outbreak.