Pak-Leung Ho

The University of Hong Kong, Hong Kong, Hong Kong

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Publications (97)387.89 Total impact

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    ABSTRACT: Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanism. This study investigated the molecular epidemiology of the multidrug-resistant efflux gene oqxAB and its contribution towards nitrofurantoin resistance by using Escherichia coli isolates originating from patients with UTI (n = 205, collected in 2004-2013) and food-producing animals (n = 136, collected in 2012-2013) in Hong Kong. The oqxAB gene was highly prevalent among NIT-intermediate (11.5%-45.5%) and -resistant (39.2%-65.5%) isolates but rare (0%-1.7%) among NIT-susceptible isolates. In our isolates, the oqxAB gene was associated with IS26 and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of the oqxAB-positive E. coli were diverse. The combination of oqxAB and nfsA mutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 μg/ml to 34.3 μg/ml. In the plasmid cured variants, 20% (1/5) of isolates with nfsA mutations were NIT-S while 80% (12/15) of isolates without nfsA mutations were NIT-S (P = 0.015). The presence of plasmid-encoded oqxAB increased the mutation prevention concentration of NIT from 128 μg/ml to 256 μg/ml and facilitated development of clinically important level of nitrofurantoin resistance. In conclusion, plasmid-mediated oqxAB is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump.
    No preview · Article · Nov 2015 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Macrolide-resistant Mycoplasma pneumoniae (MRMP) is rapidly emerging in Asia, but information on the temporal relationship between the increase in macrolide resistance and changes in strain types is scarce. Between 2011 and 2014, M. pneumoniae infection was diagnosed by PCR as part of routine care in a health care region in Hong Kong. Testing was initiated by clinicians, mainly in patients with suspected M. pneumoniae pneumonia. Specimens positive for M. pneumoniae were retrospectively investigated by macrolide resistance genotyping and a four-locus (Mpn13 to -16) multilocus variable-number tandem-repeat analysis (MLVA) scheme. The overall percentage of M. pneumoniae-positive specimens was 17.9%, with annual rates ranging from 9.8% to 27.2%. The prevalence of MRMP had rapidly increased from 13.6% in 2011 to 30.7% in 2012, 36.6% in 2013, and 47.1% in 2014 (P = 0.038). Two major MLVA types, 4-5-7-2 and 3-5-6-2, accounted for 75% to 85% of the infections each year. MLVA types 4-5-7-2 and 3-5-6-2 predominated among macrolide-resistant and macrolide-sensitive groups, respectively. The increase in MRMP was mainly caused by increasing macrolide resistance in the prevalent MLVA type 4-5-7-2, changing from 25.0% in 2011 to 59.1% in 2012, to 89.7% in 2013, and to 100% in 2014 (P < 0.001). In conclusion, increasing MRMP in Hong Kong was linked to a single MLVA type, which was both prevalent and increasingly resistant to macrolides.
    No preview · Article · Sep 2015 · Journal of clinical microbiology
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    Preview · Article · Jun 2015 · Emerging Infectious Diseases
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    ABSTRACT: This study investigated 248 extended-spectrum β-lactamase-producing Escherichia coli isolates from 2012 to 2013 for hybrid blaCTX-M genes. blaCTX-M genes were detected in 228 isolates of which 14 isolates were hybrid blaCTX-M positive (6 blaCTX-M-123, 6 blaCTX-M-64, and 2 blaCTX-M-132). The 14 hybrid blaCTX-M-carrying isolates (8 from chickens, 2 each from pigs and cattle, 1 each from dog and rodent) were genetically diverse. All but 2 hybrid blaCTX-M were carried on IncI1 (5 blaCTX-M-123) and IncI2 (6 blaCTX-M-64 and one blaCTX-M-132) plasmids. Our IncI1 and IncI2 plasmids had pHNAH4-1-like and pHN1122-1-like restriction fragment length polymorphism patterns, respectively. Genetic relatedness of the plasmids to pHNAH4-1 and pHN1122-1 were confirmed by complete sequencing of 3 plasmids, pCTXM123_C0996, pCTXM64_C0967, and pCTXM132_P0421. Plasmids closely related to pHNAH4-1 and pHN1122-1 and carrying different blaCTX-M alleles have been reported from multiple geographic areas in China previously. The findings highlighted the wide dissemination of hybrid blaCTX-M variants in different parts of China. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Feb 2015 · Diagnostic microbiology and infectious disease
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    ABSTRACT: Antimicrobial-resistant bacteria are either highly prevalent or increasing rapidly in Hong Kong and China. Treatment options for these bacteria are generally limited, less effective and more expensive. The emergence and dynamics of antimicrobial resistance genes in bacteria circulating between animals, the environment and humans are not entirely known. Nonetheless, selective pressure by antibiotics on the microbiomes of animal and human, and their associated environments (especially farms and healthcare institutions), sewage systems and soil are likely to confer survival advantages upon bacteria with antimicrobial-resistance genes, which may be further disseminated through plasmids or transposons with integrons. Therefore, antibiotic use must be tightly regulated to eliminate such selective pressure, including the illegalization of antibiotics as growth promoters in animal feed and regulation of antibiotic use in veterinary practice and human medicine. Heightened awareness of infection control measures to reduce the risk of acquiring resistant bacteria is essential, especially during antimicrobial use or institutionalization in healthcare facilities. The transmission cycle must be interrupted by proper hand hygiene, environmental cleaning, avoidance of undercooked or raw food and compliance with infection control measures by healthcare workers, visitors and patients, especially during treatment with antibiotics. In addition to these routine measures, proactive microbiological screening of hospitalized patients with risk factors for carrying resistant bacteria, including history of travel to endemic countries, transfer from other hospitals, and prolonged hospitalization; directly observed hand hygiene before oral intake of drugs, food and drinks; and targeted disinfection of high-touch or mutual-touch items, such as bed rails and bed curtains, are important. Transparency of surveillance data from each institute for public scrutiny provides an incentive for controlling antimicrobial resistance in healthcare settings at an administrative level.
    Preview · Article · Feb 2015 · Emerging Microbes and Infections
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    ABSTRACT: We collected nasal, axilla and groin swabs from 252 adult patients from two nephrology centers in Hong Kong. Staphylococcus lugdunensis carriage was detected in 51.6% patients(groin, 39.3%; axilla, 19.8% and nose, 17.9%). The carriage rates of methicillin-sensitive S. lugdunensis (MSSL) and methicillin-resistant S. lugdunensis (MRSL) were 46.0% and 8.3%, respectively. Independent risk factors for S. lugdunensis carriage included male sex (odds ratio [OR], 4.4), hemodialysis (OR 2.2) and aged 18–50 years (OR 2.4). The isolates belonged to ten pulsotype clusters (n = 129) and eight singletons (n = 8). All MRSL and most gentamicin and tetracycline resistant strains were found in a predominating sequence type 3 clone, designated HKU1, which accounted for 51.8% of all colonizing S. lugdunensis strains. The 21 MRSL isolates had SCCmec type V (n = 18), type IV (n = 2) and type I (n = 1). The finding highlights the potential for dissemination of multidrug resistance through successful S. lugdunensis clones.
    No preview · Article · Nov 2014 · Diagnostic Microbiology and Infectious Disease
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    ABSTRACT: Unlabelled: Secondary Streptococcus pneumoniae infection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. In the lung, lethal coinfection significantly increased virus titers and bacterial cell counts and decreased the level of virus-specific IgG, IgM, and IgA, as well as the number of B cells, CD4 T cells, and plasma cells. Lethal coinfection significantly reduced the size and weight of spleen, as well as the number of B cells along the follicular developmental lineage. In mediastinal lymph nodes, lethal coinfection significantly decreased germinal center B cells, T follicular helper cells, and plasma cells. Adoptive transfer of influenza virus-specific immune serum to coinfected mice improved survival, suggesting the protective functions of anti-influenza virus antibodies. In conclusion, coinfection reduced the B cell response to influenza virus. This study helps us to understand the modulation of the B cell response to influenza virus during a lethal coinfection. Importance: Secondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection.
    Full-text · Article · Nov 2014 · Journal of Virology
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    ABSTRACT: This study assessed pneumococcal carriage in the early periods after routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in Hong Kong. Nasopharyngeal swabs were obtained from 1110 children (<5 years) admitted with acute illness during September 2010-August 2013. Pneumococcal carriage rate was 13.5% in unvaccinated children, 14.1% in children who had ≥1 PCV dose and 15.3% in children who had ≥3 PCV doses. Nonv-PCV13 serotypes comprised 56.4% of all isolates. The most common serogroup/types were 15 (15A, 5.1%; 15B, 10.3%; 15C, 9.6%; 15F, 0.6%), 19F (17.9%), 6A (7.1%) and 6C (7.1%). Carriage of serogroup 15 was more common among vaccinated children (4.1% versus 0.6%, P = 0.033). Molecular typing revealed that expansion of several clones (clonal complex, CC63, CC199, CC1262, CC3397) was responsible for the increase in serogroup 15. Almost all CC63 and CC3397 isolates were nonsusceptible to both penicillin and erythromycin. The finding highlights the emergence of serogroup 15 following PCV13 use.
    No preview · Article · Nov 2014 · Diagnostic Microbiology and Infectious Disease
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    ABSTRACT: We investigated differences in outcomes between 68 children hospitalized with macrolide-sensitive Mycoplasma pneumoniae pneumonia (MSMP group) and 25 children hospitalized with macrolide-resistant M. pneumoniae pneumonia (MRMP group). In the MRMP group, 19 children received macrolides and clinical failure occurred in six of which five had pneumonia progression during therapy. Copyright © 2014. Published by Elsevier B.V.
    No preview · Article · Nov 2014 · Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
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    ABSTRACT: Aminoglycoside resistance determinants among 188 aminoglycoside-resistant blood culture Escherichia coli isolates from a tertiary hospital in Hong Kong, from 2004 to 2010 were investigated. Overall, 91% had aac(3)-II, 12.2% had aac(6′)-Ib/Ib-cr, and 5.4% had the methylase genes (rmtB, armA). Aminoglycoside-resistant isolates with aac(′)-Ib/Ib-cr, rmtB, and armA often had coresistance to multiple other antibiotics.
    No preview · Article · Nov 2014 · Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
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    ABSTRACT: Background Prolonged asymptomatic carriage of vancomycin-resistant enterococci (VRE) in the gastrointestinal tract and the lack of effective decolonization regimen perpetuate the endemicity of VRE in the healthcare settings. Case presentation We report a regimen for decolonization of gastrointestinal carriage of VRE by a combination of environmental disinfection, patient isolation, bowel preparation to wash-out the fecal bacterial population using polyethylene glycol, a five-day course of oral absorbable linezolid and non-absorbable daptomycin to suppress any remaining VRE, and subsequent oral Lactobacillus rhamnosus GG to maintain the colonization resistance in four patients, including two patients with end-stage liver cirrhosis, one patient with complication post liver transplant, and one patient with complicated infective endocarditis. All patients had clearance of VRE immediately after decolonization, and 3 of them remained VRE-free for 23 to 137 days of hospitalization, despite subsequent use of intravenous broad-spectrum antibiotics without anti-VRE activity. Conclusion This strategy should be further studied in settings of low VRE endemicity with limited isolation facilities.
    Preview · Article · Sep 2014 · BMC Infectious Diseases
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    ABSTRACT: Objectives We sought to document the incidence of pediatric hospitalization for bacterial pneumonia before universal childhood conjugate pneumococcal vaccination using two different methods of diagnosis. Methods By following the World Health Organization (WHO) chest radiography (CXR) protocol, two radiologists independently read the CXRs of a cohort of systematically recruited children younger than 5 years. The children had acute respiratory infections and were admitted to one of two hospitals that care for 72.5% of all pediatric admissions on Hong Kong Island. Medical records were reviewed for clinical manifestation and to identify bacterial pneumonia diagnosed by pediatricians. Results In children younger than 5 years, the incidences of bacterial pneumonia, as diagnosed by pediatricians and by the WHO CXR standard, were 775.7 per 100,000 population [95% confidence interval (CI, 591.8–998.3)] and 439.5 per 100,000 population (95% CI, 304.6–614.5), respectively. The study period was from 2002 to 2004. Conclusion This study provided a reliable baseline estimate of the hospitalization burden of pneumococcal pneumonia in Hong Kong children before the advent of universal conjugate pneumococcal vaccination.
    No preview · Article · Jul 2014 · Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
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    ABSTRACT: In Escherichia coli, fosfomycin resistance is uncommon and is mainly caused by mutations in the chromosomally encoded drug transporters (1).…
    No preview · Article · Jun 2014 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Objective To control nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in resource-limited healthcare setting with high endemicity. Methods Three phases of infection control interventions were implemented in a University-affiliated hospital between 1-January-2004 and 31-December-2012. The first phase of baseline period, defined as the first 48-months of the study period, when all MRSA patients were managed with standard precautions, followed by a second phase of 24-months, when a hospital-wide hand hygiene campaign was launched. In the third phase of 36-months, contact precautions in open cubicle, use of dedicated medical items, and 2% chlorhexidine gluconate daily bathing for MRSA-positive patients were implemented while hand hygiene campaign was continued. The changes in the incidence rates of hospital-acquired MRSA-per-1000-patient admissions, per-1000-patient-days, and per-1000-MRSA-positive-days were analyzed using segmented Poisson regression (an interrupted time series model). Usage density of broad-spectrum antibiotics was monitored. Results During the study period, 4256 MRSA-positive patients were newly diagnosed, of which 1589 (37.3%) were hospital-acquired. The reduction of hospital-acquired MRSA per 1000-patient admissions, per 1000-patient-days, and per 1000-MRSA-positive-days from phase 1 to 2 was 36.3% (p<0.001), 30.4% (p<0.001), and 19.6% (p = 0.040), while the reduction of hospital-acquired MRSA per 1000-patient admissions, per 1000-patient-days, and per 1000-MRSA-positive-days from phase 2 to 3 was 27.4% (p<0.001), 24.1% (p<0.001), and 21.9% (p = 0.041) respectively. This reduction is sustained despite that the usage density of broad-spectrum antibiotics has increased from 132.02 (phase 1) to 168.99 per 1000 patient-days (phase 3). Conclusions Nosocomial transmission of MRSA can be reduced with hand hygiene campaign, contact precautions in open cubicle, and 2% chlorhexidine gluconate daily bathing for MRSA-positive despite an increasing consumption of broad-spectrum antibiotics.
    Full-text · Article · Jun 2014 · PLoS ONE
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    ABSTRACT: The study describes a proactive infection control approach to prevent nosocomial transmission of vancomycin-resistant enterococci (VRE) and tests if this approach is effective for controlling multiple-drug resistant organisms in a nonendemic setting. In response to the increasing prevalence of VRE in Hong Kong since 2011, we adopted a multifaceted assertive approach in our health care network. This included active surveillance culture, extensive contact tracing, directly observed hand hygiene in conscious patients prior to receiving meals and medications, stringent hand hygiene and environmental cleanliness, and an immediate feedback antimicrobial stewardship program. We report the occurrence of VRE outbreaks in our hospital after institution of these measures and compared with the concurrent occurrence in other public hospitals in Hong Kong. Between July 1, 2011 and November 13, 2013, VRE was identified in 0.32% (50/15,851) of admission episodes by active surveillance culture. The risk of VRE carriage was three times higher in patients with a history of hospitalization outside our hospital networks in the past 3 months (0.56% vs. 0.17%; p = 0.001) compared with those who were not. Extensive contact tracing involving 3277 patient episodes was performed in the investigation for the 25 VRE index patients upon whom implementation of contact precautions was delayed (more than 48 hours of hospitalization). One episode of VRE outbreak was identified in our hospital network, compared with the 77 VRE outbreaks reported in the other hospital networks (controls) without these proactive infection control measures. Our multifaceted assertive proactive infection control approach can minimize the nosocomial transmission and outbreak of VRE in a nonendemic area.
    Full-text · Article · May 2014 · Journal of the Formosan Medical Association
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    ABSTRACT: We compared a novel selective medium (SSL) with routine method (blood and chocolate agars) for detection of Staphylococcus lugdunensis in 990 clinical specimens (tissue, pus or wound swabs). Significantly more S. lugdunensis were detected on SSL (34/990) than on routine media (7/990. McNemar test P=0.001).
    Preview · Article · Apr 2014 · Journal of clinical microbiology
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    ABSTRACT: Few studies have described how an expanding elderly population influences the burden of antimicrobial resistance in micro-organisms. This study aimed to investigate trends in aged-stratified extended-spectrum β-lactamases (ESBL)-positive Escherichia coli metrics in relation to an aging population. The antimicrobial resistance database of E. coli from a healthcare region in Hong Kong from 2003-2012 was retrospectively reviewed. Future trends in aged-stratified ESBL metrics were predicted up to 2022. Susceptibility results of clinical E. coli isolates from patients aged 0-74 years (n=17853) and aged ≥75 years (n=17047) were analyzed. For the period 2003-2012, 23.7% of the hospital admissions were of patients aged ≥75 years. However, approximately half of the annual ESBL-positive E. coli isolates were recovered from patients aged ≥75 years, being 55.0% (233/424) in 2003 and 56.0% (639/1142) in 2012. During this period of time, the annual prevalence and cumulative incidence of ESBL-positive E. coli in patients aged ≥75 years were significantly higher than in patients aged 0-74 years. From 2012 to 2022, it is predicted that ESBL-positive E. coli prevalence among patients aged 0-74 years and ≥75 years would increase from 25.4% to 50.2% and from 30.8% to 70.0% respectively. In 2022, the predicted ESBL-positive E. coli cumulative incidence would be 63.7 per 10,000 admissions and 178.7 per 10,000 admissions among patients aged 0-74 years and ≥75 years, respectively. In conclusion, a rapidly expanding elderly population would substantially add to the burden of ESBL.
    Preview · Article · Apr 2014 · Journal of Medical Microbiology
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    ABSTRACT: To the Editor:In March 2013, a novel influenza A H7N9 virus of avian origin was reported to cause severe pneumonia in mainland China (1-3). While the great majority of patients were treated with oral oseltamivir, impaired gastrointestinal absorption in critically ill patients, the lack of virological response among patients requiring extracorporeal membrane oxygenation (ECMO) and detection of an amino acid change (arginine to lysine at residue 292 in N2) in the viral neuraminidase associated with drug resistance in two H7N9 strains are major concerns (1, 4). Here, we report a case of severe pneumonia due to avian influenza A H7N9 requiring ECMO support; there was rapid clinical and virological response following intravenous zanamivir therapy.On November 21, 2013, in Hong Kong, China, a 36-year-old Indonesian female began to have fever, malaise and cough. She had been previously healthy except for a history of vitiligo. She sought medical advice from two clinics and was given symptomatic treatment. She attended the accident and emergency department of a regional hospital in Hong Kong on November 27 when the symptoms deteriorated. Her temperature was 40.0°C, blood pressure.
    No preview · Article · Apr 2014 · European Respiratory Journal
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    ABSTRACT: Besides seasonal and pandemic influenza (1), avian influenza viruses jumping from poultries to humans can also cause significant morbidity and mortality (2).…
    Preview · Article · Mar 2014 · Journal of clinical microbiology
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    ABSTRACT: This study investigated the prevalence of IncX plasmid subtypes in commensal and pathogenic Escherichia coli isolates and the biological features of the IncX4 subtype. Two hundred twenty-five E. coli isolates from multiple sources (47 chicken, 41 pigs, 30 cattle and 107 humans), 2006-2012 were tested for presence of IncX1 to IncX5. Overall, the prevalence of IncX plasmids in chicken, pig, cattle and human isolates were 21.2% (10/47), 19.5% (8/41), 3.3% (1/30) and 4.8% (5/107) respectively. IncX4 was the most common subtype, followed by IncX1 and IncX3 while no IncX2 and IncX5 were found. Seven out of 16 (43.8%) IncX4 plasmids were found to carry blaCTX-M genes and six of them originating from different host sources (four chickens, one pig and one human) had identical or highly similar RFLP patterns. Three IncX4 carrying blaCTX-M plasmids from different host sources were investigated further. It was found that the IncX4 plasmids had little effect on bacterial host growth parameters after their introduction to J53 recipients. Conjugation experiments demonstrated that the IncX4 plasmids could be efficiently transferred at 30 -42oC at rates which were generally 102 to 105 folds higher than those for the epidemic IncFII plasmid carrying blaCTX-M (pHK01). In conclusion, the IncX plasmids are more common than previously recognized. The efficient transfer of IncX4 plasmid at different temperatures and lack of fitness burden on bacterial hosts highlight the ability of this plasmid replicon to be an important vehicle for dissemination of antimicrobial resistance.
    Full-text · Article · Mar 2014 · Journal of Medical Microbiology

Publication Stats

2k Citations
387.89 Total Impact Points

Institutions

  • 2003-2015
    • The University of Hong Kong
      • Department of Microbiology
      Hong Kong, Hong Kong
  • 2002-2015
    • Queen Mary Hospital
      Hong Kong, Hong Kong
  • 2014
    • Hong Kong SAR Government
      Hong Kong, Hong Kong
  • 2004-2014
    • Lands Department of The Government of the Hong Kong Special Administrative Region
      Hong Kong, Hong Kong