Ai Ling Tan

Singapore General Hospital, Tumasik, Singapore

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Publications (31)80.81 Total impact

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    ABSTRACT: Colonization of patients occurs before development into invasive candidiasis. There is a need to determine the incidences of Candida colonization and infection in SICU patients, and evaluate the usefulness of beta-D-glucan (BDG) assay in diagnosing invasive candidiasis when patients are colonized. Clinical data and fungal surveillance cultures in 28 patients were recorded from November 2010, and January to February 2011. Susceptibilities of Candida isolates to fluconazole, voriconazole, amphotericin B, micafungin, caspofungin and anidulafungin were tested via Etest. The utilities of BDG, Candida score and colonization index for candidiasis diagnosis were compared via ROC. 30 BDG assays were performed in 28 patients. Four assay cases had concurrent colonization and infection; 23 had concurrent colonization and no infection; three had no concurrent colonization and infection. Of 136 surveillance swabs, 52 (38.24 %) were positive for Candida spp, with C. albicans being the commonest. Azole resistance was detected in C. albicans (7 %). C. glabrata and C. tropicalis were, respectively, 100 and 7 % SDD to fluconazole. All 3 tests showed high sensitivity of 75-100 % but poor specificity ranging 15.38-38.46 %. BDG performed the best (AUC of 0.89). Despite that positive BDG is common in surgical patients with Candida spp colonization, BDG performed the best when compared to CI and CS.
    No preview · Article · Dec 2015 · BMC Infectious Diseases
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    ABSTRACT: Introduction: We present a case of cutaneous penicilliosis in a paediatric patient with acute myeloid leukaemia (AML). Case report: A 2-year-old boy with AML first developed probable pulmonary aspergillosis during induction chemotherapy in an overseas centre in May 2013, and was treated with AmBisome and voriconazole. When he was admitted to our centre with relapsed AML in October 2013, he was given a fifth course of chemotherapy, and treated with AmBisome for probable pulmonary aspergillosis in view of pulmonary nodular opacities on computed tomography. He thereafter developed an erythematous skin lesion with central eschar on his right hand and left calf. Serum and bronchoalveolar lavage galactomannan antigen (GM Ag) indices increased to a value of .10. AmBisome was changed to voriconazole, and caspofungin was added for 10 days. The left calf skin biopsy showed abundant fungal hyphae with septations. A skin culture grew Penicillium citrinum with MICs (mg ml21) of: caspofungin 0.016, itraconazole 0.5, amphotericin 1.5 and voriconazole .256.Caspofungin and itraconazole were commenced, and voriconazole was discontinued. The skin lesions and serial GM Ag indices improved. The patient later developed increasing GM Ag indices to a value of .10, which was attributed to Aspergillus flavus left pulmonary mycetoma, which was surgically resected. He eventually succumbed to relapsed AML after a bone-marrow transplant. Conclusion: To the best of our knowledge, this is the first paediatric case of P. citrinum infection. Rising GM Ag indices were attributed to cross-reactivity of Penicillium spp. with GM Ag enzyme immunoassays. Keywords: Pencillium citrinum; Penicilliosis; Galactomannan.
    Full-text · Article · Aug 2015
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    ABSTRACT: Treating infections caused by multidrug-resistant Gram-negative pathogens is challenging, and there is concern regarding the toxicity of the most effective antimicrobials for Gram-negative pathogens. We hypothesized that conjugating a fatty acid moiety onto a peptide dimer could maximize the interaction with lipopolysaccharide (LPS) and facilitate the permeabilization of the LPS barrier, thereby improving potency against Gram-negative pathogens. We systematically designed a series of N-lipidated peptide dimers that are active against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). The optimized lipid length was 6-10 carbons. At these lipid lengths, the N-lipidated peptide dimers exhibited strong LPS permeabilization. Compound 23 exhibited synergy with select antibiotics in most of the combinations tested. 23 and 32 also displayed rapid bactericidal activity. Importantly, 23 and 32 were non-hemolytic at 10 mg/mL, with no cellular or in vivo toxicity. These characteristics suggest that these compounds can overcome the limitations of current Gram-negative-targeted antimicrobials such as polymyxin B.
    No preview · Article · Jul 2015 · Journal of Medicinal Chemistry
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    Full-text · Article · Jul 2015 · Annals of the Academy of Medicine, Singapore

  • No preview · Article · Jul 2015 · The Breast Journal
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    ABSTRACT: The epidemiology of candidaemia varies between hospitals and geographic regions. Although there are many studies from Asia, a large-scale cross-sectional study across Asia has not been performed. We conducted a 12-month, laboratory-based surveillance of candidaemia at 25 hospitals from China, Hong Kong, India, Singapore, Taiwan and Thailand. The incidence and species distribution of candidaemia were determined. There were 1,601 episodes of candidaemia among 1.2 million discharges. The overall incidence was 1.22 episodes per 1,000 discharges and varied among the hospitals (range, 0.16-4.53 per 1,000 discharges) and countries (range, 0.25-2.93 per 1,000 discharges). The number of Candida blood isolates and the total number of fungal isolates were highly correlated among the 6 countries (R²=0.87) and 25 hospitals (R²=0.77). There was a moderate correlation between incidence of candidaemia and the ICU/total bed ratio (R²=0.47), although ICUs contributed to only 23% of candidaemia cases. Of 1,910 blood isolates evaluated, C. albicans was most frequently isolated (41.3%), followed by C. tropicalis (25.4%), C. glabrata (13.9%) and C. parapsilosis (12.1%). The proportion of C. tropicalis among blood isolates was higher in haemato-oncology wards than others wards (33.7% vs 24.5%, p=0.0058) and was more likely to be isolated from tropical countries than other Asian countries (46.2% vs 18.9%, p=0.04). In conclusion, the ICU settings contribute, at least in part, to the incidence variation among hospitals. The species distribution is different from Western countries. Both geographic and healthcare factors contribute to the variation of species distribution. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jun 2015 · Clinical Microbiology and Infection
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    ABSTRACT: Background: In view of high mortality and morbidity rates associated with vascular access-associated bloodstream infection (VAABSI) in hemodialysis patients, clinical practice guidelines recommend empiric antibiotic therapy for suspected vascular access-related infections. We aim to describe the microbiology of confirmed VAABSI and evaluate the choice of empiric antibiotics, and whether they are prescribed in concordance with the in-house antibiotic guidelines. Methods: This was a single-center, retrospective, observational study conducted in a tertiary hospital. All adult hemodialysis patients aged 21 years and above who had confirmed VAABSI with positive blood culture results dated from January 2011 to June 2012 were recruited. Relevant information was retrieved electronically from the hospital patient online database, SCM 5.5 Sunrise Enterprise Gateway. Results: A total of 144 episodes of VAABSI were recorded from 118 patients. Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) accounted for 64.2% (68/106) of the gram-positive infections. Gram-negative organisms grew in 26.4% (38/144) of blood cultures and Pseudomonas aeruginosa was the most common organism isolated. The recommended in-house guideline was used as empiric therapy in 24 episodes of VAABSI (16.7%). Five patients died due to VAABSI and none were prescribed antibiotics in concordance with in-house guidelines. Conclusions: Empiric antibiotics against MSSA and MRSA, as well as gram-negative organisms, especially P. aeruginosa, should be used in patients with suspected vascular access-related infections in our institution. Monitoring of microbiological profile is necessary to guide timely administration of appropriate empiric antibiotics. Further studies are necessary to evaluate the relationship between adherence to in-house guidelines and patients' outcomes.
    Full-text · Article · Feb 2015
  • CY Chan · AL Tan · Ban Hock Tan
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    ABSTRACT: An infective aetiology, including fungal infection, should be considered in the differential diagnosis of immunocompromised patients presenting with skin lesions. Dematiaceous fungi are recognised as pathogens in organ transplant recipients. Herein, we describe a rare case of a chronic necrotising granulomatous skin lesion caused by Pyrenochaeta romeroiin a renal transplant recipient, and review the existing literature on the topic. To the best of our knowledge, this is the first report of such a case in Singapore. Recognition of infections caused by dematiaceous fungi is important because some strains are difficult to identify and require special molecular diagnostic techniques. Treatment involves surgical excision and long-term antifungal therapy. Data on the optimal antifungal regimen in such a diagnosis is limited.
    No preview · Article · Apr 2014 · Singapore medical journal
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    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.
    Full-text · Article · Sep 2013 · International Journal of Infection Control
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    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.
    Full-text · Article · Sep 2013 · Emerging Infectious Diseases
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    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.
    No preview · Article · Apr 2013 · Journal of Medicinal Chemistry
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    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.
    No preview · Article · Feb 2013 · Journal of Medicinal Chemistry
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    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.
    Preview · Article · Sep 2012 · Biochimica et Biophysica Acta
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    ABSTRACT: The success of membrane-based, cell-encapsulating microcapsules depends on the membrane permselectivity that provides efficient inward transport of nutrients, therapeutic protein egress, and complete exclusion of immunoglobulins. Microcapsules with a calcium crosslinked alginate core and a genipin-crosslinked chitosan alginate (GCA) were prepared with good control over size, membrane thickness and density. Importantly, in this study, we report a novel approach of using three relevant biomolecules and investigating the effects of the membrane characteristics (thickness and density) and microcapsule size on biomolecular mass transport across the GCA microcapsules using mathematical models based on a balance of the chemical potential. Scaling analysis was used to interrelate the membrane thickness, chitosan–alginate reaction rate constant, and diffusion coefficient. The resistance to diffusion of the three biomolecules increased with membrane density and thickness. Interestingly, swelling in the large microcapsules resulted in an increase in permeability, allowing larger biomolecules (immunoglobulin and carbonic anhydrase) to diffuse more readily. In the case of the smaller biomolecule, vitamin B12, a shorter diffusion path length in smaller microcapsules allowed better ingress. When compared with other microcapsules, the GCA microcapsules possess improved permselectivity for them to allow diffusion of small nutrient molecules and proteins, whereas completely excluding antibodies. Also, these results elucidate the importance of membrane properties and microcapsule size to realize favorable transport of biomolecules. © 2011 American Institute of Chemical Engineers AIChE J, 2011
    No preview · Article · Nov 2011 · AIChE Journal
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    Meng Chon Lam · Li Wei Ang · Ai Ling Tan · Lyn James · Kee Tai Goh
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    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.
    Full-text · Article · Jul 2011 · Emerging Infectious Diseases
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    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.
    Full-text · Article · Jun 2011 · Annals of the Academy of Medicine, Singapore
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    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.
    Full-text · Article · May 2011 · Singapore medical journal
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    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.
    No preview · Article · Apr 2011 · Journal of Medical Microbiology
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    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.
    Preview · Article · Mar 2011
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    ABSTRACT: Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. In 2007 and 2008, this Gonococcal Antimicrobial Surveillance Programme (GASP) was enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres within the WPR. Approximately 17,450 N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea by external quality controlled methods in 24 reporting centres in 20 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR, but much lower rates of penicillin resistance and little quinolone resistance was present in most of the Pacific Island countries. The proportion of gonococci reported as 'resistant', 'less susceptible' or 'non-susceptible' gonococci to the third-generation cephalosporin antibiotic ceftriaxone lay in a wide range, but no major changes were evident in cephalosporin minimal inhibitory concentration (MIC) patterns in 2007-2008. Altered cephalosporin susceptibility was associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit a form of plasmid mediated high level resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR supports the need for gonococcal antimicrobial resistance surveillance programs such as GASP to be maintained and potentially expanded.
    No preview · Article · Mar 2010 · Communicable diseases intelligence