Publications by authors named "Margaret Ip"

186 Publications

Hypericin and Pheophorbide a Mediated Photodynamic Therapy Fighting MRSA Wound Infections: A Translational Study from In Vitro to In Vivo.

Pharmaceutics 2021 Sep 3;13(9). Epub 2021 Sep 3.

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong 999077, China.

High prevalence rates of methicillin-resistant (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625-10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower ( < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.
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http://dx.doi.org/10.3390/pharmaceutics13091399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472478PMC
September 2021

Longitudinal Genomic Characterization of Carbapenemase-producing Enterobacteriaceae (CPE) Reveals Changing Pattern of CPE Isolated in Hong Kong Hospitals.

Int J Antimicrob Agents 2021 Sep 12:106430. Epub 2021 Sep 12.

Department of Microbiology, the Chinese University of Hong Kong, Hong Kong, China; Prince of Wales Hospital, Hong Kong, China. Electronic address:

An active, territory-wide, CPE surveillance program implemented from 2011 showed increasing levels of carbapenemase-producing Enterobacteriaceae (CPE) isolates from patients in Hong Kong hospitals. The molecular epidemiology of 567 CPE from patients of three of seven public hospital clusters in Hong Kong are described. During a 7-year period, the incidence of CPE isolation increased from 0.05 to 9.6/100 000 patient-days. The carbapenemase genes identified were polyclonal, including bla, bla and bla, which were mainly associated with hospitalization overseas in previous years. However, increasing CPE isolation from patients without hospitalization overseas occurred in 2015, with bla (52.6%) predominant followed by bla (30.0%). Escherichia coli (46.4%) and Klebsiella spp. (38.3%) were the dominant species. Whole-genome sequencing was performed on 169 representative isolates with a combination of short and long reads using Illumina and Nanopore technology. Two distinct lineages of bla-positive Klebsiella pneumoniae (ST11 and ST258) were identified with ST11 carrying yersiniabactin gene ybt-9 on ICEKp3. ST131 E. coli producing IMP-4 was present throughout the study period. The bla and bla genes were mainly carried in IncX3 and IncN-ST7 plasmids, respectively. bla gene was carried in the IncX3 plasmid in E. coli and in the ColKP3 plasmid in K. pneumoniae. A lineage of K. pneumoniae with bla plus bla in distinct plasmids of IncF1B/IncHI1B was identified and associated with prior hospitalization overseas. This study highlights the threat of multiple types of CPE, with the predominance of bla and bla among CPE in our hospitals. Enhanced containment strategies are needed to mitigate the trend of rapidly rising CPE in healthcare settings.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106430DOI Listing
September 2021

Understanding the gut microbiota and sarcopenia: a systematic review.

J Cachexia Sarcopenia Muscle 2021 Sep 14. Epub 2021 Sep 14.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia.

Methods: A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed.

Results: A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota.

Conclusions: Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.
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http://dx.doi.org/10.1002/jcsm.12784DOI Listing
September 2021

Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM.

Lancet Infect Dis 2021 Aug 19. Epub 2021 Aug 19.

Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.
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http://dx.doi.org/10.1016/S1473-3099(21)00203-6DOI Listing
August 2021

A multi-omics study on quantifying antimicrobial resistance in European freshwater lakes.

Environ Int 2021 12 14;157:106821. Epub 2021 Aug 14.

Department of Biodiversity, University of Duisburg-Essen, Universitätsstr. 5, Essen 45141, Germany.

The surveillance of wastewater for the Covid-19 virus during this unprecedented pandemic and mapped to the distribution and magnitude of the infected in the population near real-time exemplifies the importance of tracking rapidly changing trends of pathogens or public health problems at a large scale. The rising trends of antimicrobial resistance (AMR) with multidrug-resistant pathogens from the environmental water have similarly gained much attention in recent years. Wastewater-based epidemiology from water samples has shown that a wide range of AMR-related genes is frequently detected. Albeit sewage is treated before release and thus, the abundance of pathogens should be significantly reduced or even pathogen-free, several studies indicated the contrary. Pathogens are still measurable in the released water, ultimately entering freshwaters, such as rivers and lakes. Furthermore, socio-economic and environmental factors, such as chemical industries and animal farming nearby, impact the presence of AMR. Many bacterial species from the environment are intrinsically resistant and also contribute to the resistome of freshwater lakes. This study collected the most extensive standardized freshwater data set from hundreds of European lakes and conducted a comprehensive multi-omics analysis on antimicrobial resistance from these freshwater lakes. Our research shows that genes encoding for AMR against tetracyclines, cephalosporins, and quinolones were commonly identified, while for some, such as sulfonamides, resistance was less frequently present. We provide an estimation of the characteristic resistance of AMR in European lakes, which can be used as a comprehensive resistome dataset to facilitate and monitor temporal changes in the development of AMR in European freshwater lakes.
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http://dx.doi.org/10.1016/j.envint.2021.106821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364379PMC
December 2021

Persistence of Pneumococcal Serotype 3 in Adult Pneumococcal Disease in Hong Kong.

Vaccines (Basel) 2021 Jul 7;9(7). Epub 2021 Jul 7.

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

The epidemiology of hospitalised pneumococcal disease in adults following the introduction of universal childhood pneumococcal immunisation in 2009 was assessed. Culture-confirmed (SP) from adults hospitalised between 2009 to 2017 were examined. The cases were categorised into invasive pneumococcal disease (IPD) and pneumonia (bacteraemic, non-bacteraemic, and that associated with other lung conditions). The isolates were serotyped and antimicrobial susceptibilities were determined by microbroth dilution. Patient characteristics, comorbidities, and outcomes were analysed. Seven hundred and seventy-four patients (mean age, 67.7 years, SD ± 15.6) were identified, and IPD was diagnosed in 110 (14.2%). The most prevalent serotype, 19F, was replaced by serotype 3 over time. Penicillin and cefotaxime non-susceptibilities were high at 54.1% and 39.5% (meningitis breakpoints), 19.9% and 25.5% (non-meningitis breakpoints), respectively. The overall 30-day mortality rate was 7.8% and 20.4% for IPD. Age ≥ 75 years (OR:4.6, CI:1.3-17.0, < 0.02), presence of any complications (OR:4.1, CI:1.02-16.3,  < 0.05), pleural effusion (OR:6.7, CI:1.2-39.4,  < 0.03) and intensive care unit (ICU) admission (OR:9.0, CI:1.3-63.4,   0.03) were independent predictors of 30-day mortality. Pneumococcal disease by PCV 13 covered serotypes; in particular, 19F and 3 are still prominent in adults. Strengthening targeted adult vaccination may be necessary in order to reduce disease burden.
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http://dx.doi.org/10.3390/vaccines9070756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310027PMC
July 2021

Genomic Epidemiology of Multidrug-Resistant Nontyphoidal Salmonella in Young Children Hospitalized for Gastroenteritis.

Microbiol Spectr 2021 09 4;9(1):e0024821. Epub 2021 Aug 4.

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Konggrid.10784.3a, Prince of Wales Hospital, Hong Kong Special Administrative Region.

Nontyphoidal Salmonella (NTS) gastroenteritis in children remains a significant burden on health care and constitutes a majority of all admissions for Salmonella infections in public hospitals in Hong Kong. In this prospective study, 41% of 241 children hospitalized with gastroenteritis from three public hospitals during 2019 were culture confirmed to have NTS infection. These Salmonella isolates were whole-genome sequenced and predicted for their serovars/serotypes using the Salmonella Typing Resource (SISTR) and SeqSero1, and the antimicrobial resistance (AMR) genes were determined. Phylogenetic analysis revealed three major clades belonging to Salmonella enterica serovar Enteritidis sequence type 11 (ST11) (43%), multidrug-resistant (MDR) Typhimurium ST19 (12%) and its monophasic variant ST34 (25%), and mostly singletons of 15 other serovars. MDR Typhimurium and its variant were more common in infants <24 months of age and possessed genotypic resistance to five antimicrobial agents, including ampicillin (A), chloramphenicol (C), aminoglycosides (Am), sulfonamides (Su), and tetracyclines (T). Older children were more often infected with Enteritidis, which possessed distinct genotypic resistance to AAmSu and fluoroquinolones. In addition, 3% of the isolates possessed extended-spectrum beta-lactamase (ESBL) CTX-M genes, while one isolate (1%) harboring the carbapenemase gene was identified. Our findings provide a more complete genomic epidemiological insight into NTS causing gastroenteritis and identify a wider spectrum of determinants of resistance to third-generation beta-lactams and carbapenems, which are often not readily recognized. With high rates of multidrug-resistant NTS from studies in the Asia-Pacific region, the rapid and reliable determination of serovars and resistance determinants using whole-genome sequencing (WGS) is invaluable for enhancing public health interventions for infection prevention and control. Nontyphoidal Salmonella (NTS) gastroenteritis is a foodborne disease with a large global burden. Antimicrobial resistance (AMR) among foodborne pathogens is an important public health concern, and multidrug-resistant (MDR) Salmonella is prevalent in Southeast Asia and China. Using whole-genome sequencing, this study highlights the relationship of the MDR Salmonella serotypes and the diverse range of Salmonella genotypes that contaminate our food sources and contribute to disease in this locality. The findings update our understanding of Salmonella epidemiology and associated MDR determinants to enhance the tracking of foodborne pathogens for public health and food safety.
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http://dx.doi.org/10.1128/Spectrum.00248-21DOI Listing
September 2021

Formulation strategies for bacteriophages to target intracellular bacterial pathogens.

Adv Drug Deliv Rev 2021 09 13;176:113864. Epub 2021 Jul 13.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

Bacteriophages (Phages) are antibacterial viruses that are unaffected by antibiotic drug resistance. Many Phase I and Phase II phage therapy clinical trials have shown acceptable safety profiles. However, none of the completed trials could yield data supporting the promising observations noted in the experimental phage therapy. These trials have mainly focused on phage suspensions without enough attention paid to the stability of phage during processing, storage, and administration. This is important because in vivo studies have shown that the effectiveness of phage therapy greatly depends on the ratio of phage to bacterial concentrations (multiplicity of infection) at the infection site. Additionally, bacteria can evade phages through the development of phage-resistance and intracellular residence. This review focuses on the use of phage therapy against bacteria that survive within the intracellular niches. Recent research on phage behavior reveals that some phage can directly interact with, get internalized into, and get transcytosed across mammalian cells, prompting further research on the governing mechanisms of these interactions and the feasibility of harnessing therapeutic phage to target intracellular bacteria. Advances to improve the capability of phage attacking intracellular bacteria using formulation approaches such as encapsulating/conjugating phages into/with vector carriers via liposomes, polymeric particles, inorganic nanoparticles, and cell penetrating peptides, are summarized. While promising progress has been achieved, research in this area is still in its infancy and warrants further attention.
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http://dx.doi.org/10.1016/j.addr.2021.113864DOI Listing
September 2021

Correction: Li et al. Multidrug-Resistant Strains Found in Human and Fish with High Penicillin and Cefotaxime Non-Susceptibilities. 2020, , 1055.

Microorganisms 2021 Jun 1;9(6). Epub 2021 Jun 1.

Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), Hong Kong, China.

The authors would like to make the following correction to the published paper [...].
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http://dx.doi.org/10.3390/microorganisms9061198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229236PMC
June 2021

Is there a role of faecal microbiota transplantation in reducing antibiotic resistance burden in gut? A systematic review and Meta-analysis.

Ann Med 2021 12;53(1):662-681

Faculty of Medicine, Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, China.

Objectives: The aim of current systematic review and meta-analysis is to provide insight into the therapeutic efficacy of fecal microbiota transplantation (FMT) for the decolonization of antimicrobial-resistant (AMR) bacteria from the gut.

Methods: The protocol for this Systematic Review was prospectively registered with PROSPERO (CRD42020203634). Four databases (EMBASE, MEDLINE, SCOPUS, and WEB of SCIENCE) were consulted up until September 2020. A total of fourteen studies [ ( = 2), case reports ( = 7), case series without control arm ( = 3), randomized clinical trials (RCT,  = 2)], were reviewed. Data were synthesized narratively for the case reports, along with a proportion meta-analysis for the case series studies ( = 102 subjects) without a control arm followed by another meta-analysis for case series studies with a defined control arm ( = 111 subjects) for their primary outcomes.

Results: Overall, seven non-duplicate case reports ( = 9 participants) were narratively reviewed and found to have broad AMR remission events at the 1-month time point. Proportion meta-analysis of case series studies showed an overall 0.58 (95% CI: 0.42-0.74) AMR remission. Additionally, a significant difference in AMR remission was observed in FMT vs treatment naïve (RR = 0.44; 95% CI: 0.20-0.99) and moderate heterogeneity (=65%). A subgroup analysis of RCTs ( = 2) revealed FMT with further benefits of AMR remission with low statistical heterogeneity (RR = 0.37; 95% CI: 0.18-0.79; =23%).

Conclusion: More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.KEY MESSAGEExisting studies in this subject are limited and of low quality with moderate heterogeneity, and do not allow definitive conclusions to be drawn.More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.
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http://dx.doi.org/10.1080/07853890.2021.1927170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238059PMC
December 2021

Colonization with selected antibiotic resistant bacteria among a cohort of Sri Lankan university students.

BMC Infect Dis 2021 Jun 15;21(1):578. Epub 2021 Jun 15.

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.

Background: Antibiotic Resistance is an imminent global public health threat. Antibiotic resistance emerged in healthcare settings and has now moved on to the community settings. This study was conducted to identify the rates of asymptomatic colonization with selected antibiotic resistant organisms, (Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli and Klebsiella spp and carbapenem resistant E.coli and Klebsiella spp) - among a group of university students in Sri Lanka. Identification of genetic determinants of MRSA and ESBL was an additional objective of the study.

Methods: A self - collected nasal swab and a peri-rectal swab collected after passing stools were obtained. Routine microbiological methods were used for the isolation S.aureus from the nasal swab and E.coli and Klebsiella species from the peri-rectal swab. Antibiotic sensitivity testing was performed as recommended by clinical and laboratory standard institute (CLSI). Three (3) genes that are responsible for ESBL production; bla, bla, and bla were tested using previously described primers and PCR procedures. Identification of MecA and PVL genes attributed to MRSA was also done with PCR.

Results: A total of 322 participants between 21 and 28 years were recruited representing 5 different faculties of study. Seventy one (22.0%) were colonized with S.aureus and 14 among them with MRSA, making the MRSA colonization rate of 4.3%. Forty five (15%) of the participants were colonized with an ESBL producing E.coli or Klebsiella spp. No one was colonized with carbapenem resistant E.coli or Klebsiella species. Of the 45 ESBL producers the commonest genetic determinant identified was bla (n = 36), while 16 isolates had bla and 7 had bla Similarly, of the 14 isolates identified as MRSA, 3 (21.4%) were found to be PVL positive while 11 (78.6%) were MecA positive.

Conclusions: A high rate of colonization with ESBL producing E.coli and Klebsiella species was noted in our study group.
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http://dx.doi.org/10.1186/s12879-021-06289-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207576PMC
June 2021

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

Lancet Digit Health 2021 06;3(6):e360-e370

Irish Meningitis and Sepsis Reference Laboratory, Children's Health Ireland at Temple Street, Dublin, Ireland; Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

Background: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic.

Methods: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed.

Findings: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded.

Interpretation: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

Funding: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).
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http://dx.doi.org/10.1016/S2589-7500(21)00077-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166576PMC
June 2021

The role of gut microbiota in bone homeostasis.

Bone Joint Res 2021 Jan;10(1):51-59

Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Aims: The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

Methods: Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted.

Results: A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss.

Conclusion: Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article:  2021;10(1):51-59.
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http://dx.doi.org/10.1302/2046-3758.101.BJR-2020-0273.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845471PMC
January 2021

A Novel Dicationic Boron Dipyrromethene-based Photosensitizer for Antimicrobial Photodynamic Therapy against Methicillin-Resistant Staphylococcus aureus.

Curr Med Chem 2021 ;28(21):4283-4294

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong.

Background: We report herein the synthesis of a novel dicationic boron dipyrromethene derivative (compound 3) which is symmetrically substituted with two trimethylammonium styryl groups.

Methods: The antibacterial photodynamic activity of compound 3 was determined against sixteen methicillin-resistant Staphylococcus aureus (MRSA) strains, including four ATCC type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two mutant strains [AAC(6')-APH(2") and RN4220/pUL5054], and ten nonduplicate clinical strains of hospital- and community-associated MRSA. Upon light irradiation, the minimum bactericidal concentrations of compound 3 were in the range of 1.56-50 μM against all the sixteen MRSA strains. Interestingly, compound 3 was not only more active than an analogue in which the ammonium groups are not directly connected to the n-conjugated system (compound 4), but also showed significantly higher (p < 0.05) antibacterial potency than the clinically approved photosensitizer methylene blue. The skin irritation of compound 3 during topical application was tested on human 3-D skin constructs and proven to be non-irritant in vivo at concentrations below 1.250 mM. In the murine MRSA infected wound study, the colony forming unit reduction of compound 3 + PDT group showed significantly (p < 0.05) higher value (>2.5 log) compared to other test groups except for the positive control.

Conclusion: In conclusion, the present study provides a scientific basis for future development of compound 3 as a potent photosensitizer for photodynamic therapy for MRSA wound infection.
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http://dx.doi.org/10.2174/0929867328666201208095105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287893PMC
July 2021

Baicalein-modified hydroxyapatite nanoparticles and coatings with antibacterial and antioxidant properties.

Mater Sci Eng C Mater Biol Appl 2021 Jan 22;118:111537. Epub 2020 Sep 22.

Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface (LRS), 4 place Jussieu, 75005 Paris, France. Electronic address:

Aseptic loosening and bacterial infections are the two main causes of failure for metallic implants used for joint replacement. A coating that is both bioactive and possesses antimicrobial properties may address such shortcomings and improve the performance of the implant. We have sought to study the properties of combining hydroxyapatite-based nanoparticles or coatings with baicalein, a plant-extracted molecule with both antibacterial and antioxidant properties. (B-type) carbonated hydroxyapatite nanoparticles prepared by a chemical wet method could subsequently adsorbed by soaking in a baicalein solution. The amount of adsorbed baicalein was determined to be 63 mg.g by thermogravimetric measurements. In a second approach, baicalein was adsorbed on a biomimetic calcium-deficient hydroxyapatite planar coating (12 μm thick) deposited on Ti6Al4V alloy from an aqueous solution of calcium, phosphate, sodium and magnesium salts. Soaking of the hydroxyapatite coated on titanium alloy in a baicalein solution induced partial dissolution/remodeling of the upper surface of the coating. However, the observed remodeling of the surface was much more pronounced in the presence of a baicalein solution, compared to pure water. The presence of adsorbed baicalein on the HAp layer, although it could not be precisely quantified, was assessed by XPS and fluorescence analysis. Planar coatings exhibited significant antibacterial properties against Staphylococcus epidermidis. Baicalein-modified nanoparticles exhibited significant antioxidant properties. These results illustrate the potential of hydroxyapatite used as a carrier for natural biologically-active molecules and also discuss the challenges associated with their applications as antibacterial agents.
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http://dx.doi.org/10.1016/j.msec.2020.111537DOI Listing
January 2021

Multidrug-Resistant Strains Found in Human and Fish with High Penicillin and Cefotaxime Non-Susceptibilities.

Microorganisms 2020 Jul 16;8(7). Epub 2020 Jul 16.

Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), Hong Kong, China.

Penicillin non-susceptible (PEN-NS GBS) has been increasingly reported, with multidrug-resistant (MDR) GBS documented in Japan. Here we identified two PEN-NS GBS strains during our surveillance studies: one from a patient's wound and the other from a tilapia. The patient's GBS (H21) and fish GBS (F49) were serotyped and tested for antibiotic susceptibility. Whole-genome sequencing was performed to find the sequence type, antimicrobial resistance genes, and mutations in penicillin-binding proteins (PBPs) and fluoroquinolone (FQ) resistance genes. H21 and F49 belonged to ST651, serotype Ib, and ST7, serotype Ia, respectively. H21 showed PEN and cefotaxime minimum inhibitory concentrations (MICs) of 2.0 mg/L. F49 showed PEN MIC 0.5 mg/L. H21 was MDR with , , , , , and antimicrobial resistance genes observed. Alignment of PBPs showed the combination of PBP1B (A95D) and 2B mutations (V80A, S147A, S160A) in H21 and a novel mutation in F49 at N192S in PBP2B. Alignment of FQ-resistant determinants revealed mutation sites on gyrA, gyrB, and parC and E in H21. To our knowledge, this is the first report of GBS isolates with such high penicillin and cefotaxime MICs. This raises the concern of emergence of MDR and PEN-NS GBS in and beyond healthcare facilities.
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http://dx.doi.org/10.3390/microorganisms8071055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409034PMC
July 2020

Discovery of Antibacterials That Inhibit Bacterial RNA Polymerase Interactions with Sigma Factors.

J Med Chem 2020 07 7;63(14):7695-7720. Epub 2020 Jul 7.

State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, People's Republic of China.

Formation of a bacterial RNA polymerase (RNAP) holoenzyme by a catalytic core RNAP and a sigma (σ) initiation factor is essential for bacterial viability. As the primary binding site for the housekeeping σ factors, the RNAP clamp helix domain represents an attractive target for novel antimicrobial agent discovery. Previously, we designed a pharmacophore model based on the essential amino acids of the clamp helix, such as R278, R281, and I291 ( numbering), and identified hit compounds with antimicrobial activity that interfered with the core-σ interactions. In this work, we rationally designed and synthesized a class of triaryl derivatives of one hit compound and succeeded in drastically improving the antimicrobial activity against , with the minimum inhibitory concentration reduced from 256 to 1 μg/mL. Additional characterization of antimicrobial activity, inhibition of transcription, in vitro pharmacological properties, and cytotoxicity of the optimized compounds demonstrated their potential for further development.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091929PMC
July 2020

Monosubstituted tricationic Zn(II) phthalocyanine enhances antimicrobial photodynamic inactivation (aPDI) of methicillin-resistant (MRSA) and cytotoxicity evaluation for topical applications: and study.

Emerg Microbes Infect 2020 Dec;9(1):1628-1637

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong (SAR), People's Republic of China.

Antimicrobial photodynamic therapy (aPDT) is an innovative approach to combat multi-drug resistant bacteria. It is known that cationic Zn(II) phthalocyanines (ZnPc) are effective in mediating aPDT against methicillin-resistant (MRSA). Here we used ZnPc-based photosensitizer named ZnPcE previously reported by our research group to evaluate its aPDT efficacy against broad spectrum of clinically relevant MRSAs. Remarkably, anti-MRSA activity was achieved using near-infrared (NIR, >610 nm) light with minimal bactericidal concentrations ranging <0.019-0.156 µM against the panel of MRSAs. ZnPcE was not only significantly ( < .05) more potent than methylene blue, which is a clinically approved photosensitizer but also demonstrated low cytotoxicity against human fibroblasts cell line (Hs-27) and human immortalized keratinocytes cell line (HaCaT). The toxicity was further evaluated on human 3-D skin constructs and found ZnPcE did not manifest skin irritation at ≤7.8 µM concentration. In the murine MRSA wound model, ZnPcE with PDT group demonstrated > 4 log CFU reduction and the value is significantly higher ( < .05) than all test groups except positive control. To conclude, results of present study provide a scientific basis for future clinical evaluation of ZnPcE-PDT on MRSA wound infection.
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http://dx.doi.org/10.1080/22221751.2020.1790305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473158PMC
December 2020

Facilitators and barriers to completing recommended doses of pneumococcal vaccination among community-living individuals aged ≥65 years in Hong Kong - a population-based study.

Hum Vaccin Immunother 2021 02 2;17(2):527-536. Epub 2020 Jul 2.

Centre for Health Behaviours Research, JC School of Public Health and Primary Care, The Chinese University of Hong Kong , Hong Kong, China.

Individuals aged ≥65 y are recommended to receive pneumococcal vaccination (PV). PV completion is defined as receiving two doses of PV among those with at least one high-risk condition for severe invasive pneumococcal diseases (IPD) or receiving one dose of PV among those without any high-risk conditions. This study investigated factors associated with PV completion among a random sample of community-living older adults in Hong Kong, China. In addition, factors associated with receiving a single dose of PV among older adults with at least one high-risk condition were also investigated. A total of 750 community-living Chinese-speaking individuals aged ≥65 y in Hong Kong (response rate: 63.4%) completed a random telephone survey from May to July 2019. PV completion was 10% among all participants. Among participants with high-risk condition(s) for severe IPD, 11.4% received a single dose of PV. After adjustment for significant background variables, several Health Belief Model constructs were significantly associated with both dependent variables: (1) perceived risk of contracting pneumococcal diseases, (2) perceived benefits of PV for protecting themselves or others, (3) perceived barriers to PV uptake, (4) being suggested by significant others to take up PV (cue to action), and (5) confidence to take up PV (perceived self-efficacy). In addition, being knowledgeable about pneumococcal diseases and vaccination, and knowing at least one peer of similar age who had taken up PV were also positively associated with both dependent variables. Targeted, theory-based health promotion efforts are needed to increase PV coverage among elderly in Hong Kong.
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http://dx.doi.org/10.1080/21645515.2020.1776545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899695PMC
February 2021

Swine methicillin-resistant carrying toxic-shock syndrome toxin gene in Hong Kong, China.

Emerg Microbes Infect 2020 Dec;9(1):1534-1536

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong (SAR), People's Republic of China.

We report a SCC II, ST39 methicillin-resistant isolate from pigs that harboured toxic-shock syndrome toxin gene (1). The gene was located in a rare pathogenicity island SaPI68111, which also carried enterotoxin genes that can cause fatal infections. Pigs may potentially serve as a reservoir for MRSA dissemination.
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http://dx.doi.org/10.1080/22221751.2020.1785335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473289PMC
December 2020

Contemporary approaches and future perspectives of antibacterial photodynamic therapy (aPDT) against methicillin-resistant Staphylococcus aureus (MRSA): A systematic review.

Eur J Med Chem 2020 Aug 13;200:112341. Epub 2020 May 13.

Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (SAR), China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. Electronic address:

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections in both the community and healthcare settings challenges the limited options of effective antibiotics and motivates the search for alternative therapeutic solutions, such as antibacterial photodynamic therapy (aPDT). While many publications have described the promising anti-bacterial activities of PDT in vitro, its applications in vivo and in the clinic have been very limited. This limited availability may in part be due to variabilities in the selected photosensitizing agents (PS), the variable testing conditions used to examine anti-bacterial activities and their effectiveness in treating MRSA infections. We thus sought to systematically review and examine the evidence from existing studies on aPDT associated with MRSA and to critically appraise its current state of development and areas to be addressed in future studies. In 2018, we developed and registered a review protocol in the International Prospective Register of Systematic Reviews (PROSPERO) with registration No: CRD42018086736. Three bibliographical databases were consulted (PUBMED, MEDLINE, and EMBASE), and a total of 113 studies were included in this systematic review based on our eligibility criteria. Many variables, such as the use of a wide range of solvents, pre-irradiation times, irradiation times, light sources and light doses, have been used in the methods reported by researchers, which significantly affect the inter-study comparability and results. On another note, new approaches of linking immunoglobulin G (IgG), antibodies, efflux pump inhibitors, and bacteriophages with photosensitizers (PSs) and the incorporation of PSs into nano-scale delivery systems exert a direct effect on improving aPDT. Enhanced activities have also been achieved by optimizing the physicochemical properties of the PSs, such as the introduction of highly lipophilic, poly-cationic and site-specific modifications of the compounds. However, few in vivo studies (n = 17) have been conducted to translate aPDT into preclinical studies. We anticipate that further standardization of the experimental conditions and assessing the efficacy in vivo would allow this technology to be further applied in preclinical trials, so that aPDT would develop to become a sustainable, alternative therapeutic option against MRSA infection in the future.
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http://dx.doi.org/10.1016/j.ejmech.2020.112341DOI Listing
August 2020

Synthesis and In Vitro Photodynamic Activity of Cationic Boron Dipyrromethene-Based Photosensitizers against Methicillin-Resistant .

Biomedicines 2020 May 29;8(6). Epub 2020 May 29.

Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.

A series of cationic boron dipyrromethene (BODIPY) derivatives were synthesized and characterized with various spectroscopic methods. Having the ability to generate singlet oxygen upon irradiation, these compounds could potentially serve as photosensitizers for antimicrobial photodynamic therapy. Of the five BODIPYs being examined, the dicationic aza-BODIPY analogue (compound ) demonstrated the highest potency against a broad spectrum of clinically relevant methicillin-resistant (MRSA), including four ATCC-type strains (ATCC 43300, ATCC BAA-42, ATCC BAA-43, and ATCC BAA-44), two strains carrying specific antibiotic resistance mechanisms [-AAC(6')-APH(2") and RN4220/pUL5054], and ten non-duplicate clinical strains from hospital- and community-associated MRSAs of the important clonal types ST239, ST30, and ST59, which have previously been documented to be prevalent in Hong Kong and its neighboring countries. The anti-MRSA activity of compound was achieved upon irradiation with near-infrared light (>610 nm) with minimal bactericidal concentrations (MBCs) ranging from 12.5 to 25 µM against the whole panel of MRSAs, except the hospital-associated MRSAs for which the MBCs were in the range of 50-100 µM. Compound was significantly ( < 0.05) more potent than methylene blue, which is a clinically approved photosensitizer, indicating that it is a promising antimicrobial agent that is worthy of further investigation.
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http://dx.doi.org/10.3390/biomedicines8060140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344895PMC
May 2020

A simple, rapid typing method for Streptococcus agalactiae based on ribosomal subunit proteins by MALDI-TOF MS.

Sci Rep 2020 05 29;10(1):8788. Epub 2020 May 29.

Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong.

Streptococcus agalactiae (Group B Streptococcus, GBS), is a frequent human colonizer and a leading cause of neonatal meningitis as well as an emerging pathogen in non-pregnant adults. GBS possesses a broad animal host spectrum, and recent studies proved atypical GBS genotypes can cause human invasive diseases through animal sources as food-borne zoonotic infections. We applied a MALDI-TOF MS typing method, based on molecular weight variations of predefined 28 ribosomal subunit proteins (rsp) to classify GBS strains of varying serotypes into major phylogenetic lineages. A total of 249 GBS isolates of representative and varying capsular serotypes from patients and animal food sources (fish and pig) collected during 2016-2018 in Hong Kong were analysed. Over 84% (143/171) noninvasive carriage GBS strains from patients were readily typed into 5 globally dominant rsp-profiles. Among GBS strains from food animals, over 90% (57/63) of fish and 13% (2/15) of pig GBS matched with existing rsp-profiles, while the remainder were classified into two novel rsp-profiles and we failed to assign a fish strain into any cluster. MALDI-TOF MS allowed for high-throughput screening and simultaneous detection of novel, so far not well described GBS genotypes. The method shown here is rapid, simple, readily transferable and adapted for use in a diagnostic microbiology laboratory with potential for the surveillance of emerging GBS genotypes with zoonotic potential.
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http://dx.doi.org/10.1038/s41598-020-65707-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260235PMC
May 2020

Adherence to Treatment Guideline Improves Patient Outcomes in a Prospective Cohort of Adults Hospitalized for Community-Acquired Pneumonia.

Open Forum Infect Dis 2020 May 24;7(5):ofaa146. Epub 2020 Apr 24.

Department of Microbiology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

Background: Understanding local epidemiology and etiologies of community-acquired pneumonia in hospitalized patients is crucial for determining the appropriateness of treatment guidelines. We aim to determine the etiologies, severity, and outcomes in adults hospitalized for community-acquired pneumonia and to study the impact of empirical antibiotic therapy on patient outcomes.

Methods: We performed a prospective observational cohort study involving adults hospitalized for community-acquired pneumonia in Hong Kong. Sputum, nasopharyngeal aspirate, blood, and urine were collected for bacterial culture, molecular tests for detection of viruses and atypical pathogens, and antigen tests. Multivariable logistic regression model and Cox proportional hazard models were performed to determine independent factors associated with prolonged hospitalization and mortality.

Results: From February 2017 to July 2018, 258 patients were enrolled. The median age was 73 (interquartile range, 61-80) years, 66% were male, 57% had underlying chronic illnesses, 13% had CURB-65 score ≥3, and 10% had higher 1-year mortality. Pathogens were identified in 45% of patients; 20% had viral, 15% had bacterial, and 9% had polymicrobial pneumonia. (12%), influenza virus (12%), and (1.2%) were the most common bacterial, viral, and atypical pathogens, respectively. Nonadherence to local empirical antibiotic treatment guidelines (primarily recommending beta-lactam and doxycycline) was observed in 25% and was independently associated with prolonged hospitalization (≥7 days) and higher mortality, after adjustment for age, underlying chronic illness, and disease severity.

Conclusions: Adherence to treatment guidelines was associated with shorter hospitalization and improved survival. We provided evidence for the use of doxycycline for coverage of atypical pathogens in nonsevere pneumonia.
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http://dx.doi.org/10.1093/ofid/ofaa146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243378PMC
May 2020

Prevalence and associated factors for carriage of Enterobacteriaceae producing ESBLs or carbapenemase and methicillin-resistant Staphylococcus aureus in Hong Kong community.

J Infect 2020 08 21;81(2):242-247. Epub 2020 May 21.

Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China.

Objectives: We conducted a cross-sectional study in Hong Kong community to estimate the carriage prevalence, associated factors and genotypes of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Enterobacteriaceae (CPE).

Methods: Seemingly healthy subjects were asked to provide nasal, handprint and stool samples from March to April 2017. Isolates were characterized by molecular methods. We used multivariable logistic regression models within a generalized estimating equation framework to identify risk factors for ESBL-E carriage. Characteristics of MRSA/CPE carriage were summarized.

Results: The prevalence of ESBL-E, MRSA and CPE were 52.8% (104/197), 2.5% (5/197) and 0.5% (1/197) respectively. Most ESBL-E isolates were E. coli (85.6%; 113/132). Most ESBL genes belonged to bla (68.9%) and bla (53.0%) types. Self-reported antibiotic consumption (≥2 courses) in the past six months was associated with ESBL-E carriage (adjusted odds ratio: 4.71-5.47).

Conclusions: Abundance of ESBL-E in the community are causes of concern, and antibiotic use is associated with its carriage. Presence of MRSA and CPE in community members without clear healthcare exposure hints on a change in their epidemiology. This study establishes a baseline to formulate infection control policies and future studies in combating antimicrobial resistance.
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http://dx.doi.org/10.1016/j.jinf.2020.05.033DOI Listing
August 2020

A systematic review on current osteosynthesis-associated infection animal fracture models.

J Orthop Translat 2020 Jul 30;23:8-20. Epub 2020 Mar 30.

Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.

Objective: Osteosynthesis-associated infection is a challenging complication post fracture fixation, burdening the patients and the orthopaedic surgeons alike. A clinically relevant animal model is critical in devising new therapeutic strategies. Our aim was to perform a systematic review to evaluate existing preclinical models and identify their applications in aspects of animal selection, bacterial induction, fracture fixation and complications.

Methods: A systematic literature research was conducted in PubMed and Embase up to February 2020. A total of 31 studies were included. Information on the animal, bacterial induction, fracture fixation, healing result and complications were extracted.

Results: Animals selected included murine (23), rabbit (6), ewe (1) and goat (1). Larger animals had enabled the use of human-sized implant, however small animals were more economical and easier in handling. was the most frequently chosen bacteria for induction. Bacterial inoculation dose ranged from 10 ​CFU. Consistent and replicable infections were observed from 10 ​CFU in general. Methods of inoculation included injections of bacterial suspension (20), placement of foreign objects (8) and pretreatment of implants with established biofilm (3). Intramedullary implants (13), plates and screws (18) were used in most models. Radiological (29) and histological evaluations (24) in osseous healing were performed. Complications such as instability of fracture fixation (7), unexpected surgical death (5), sepsis (1) and persistent lameness (1) were encountered.

Conclusion: The most common animal model is the infected open fracture internally fixated. Replicable infections were mainly from 10 ​CFU of bacteria. However, with the increase in antibiotic resistance, future directions should explore polymicrobial and antibiotic resistant strains, as these will no doubt play a major role in bone infection. Currently, there is also a lack of osteoporotic bone infection models and the pathophysiology is unexplored, which would be important with our aging population.

The Translational Potential Of This Article: This systematic review provides an updated overview and compares the currently available animal models of osteosynthesis-associated infections. A discussion on future research directions and suggestion of animal model settings were made, which is expected to advance the research in this field.
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http://dx.doi.org/10.1016/j.jot.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231979PMC
July 2020

Prevalence and Characteristics of Extended-Spectrum-β-Lactamase-Producing and Carbapenemase-Producing from Freshwater Fish and Pork in Wet Markets of Hong Kong.

mSphere 2020 04 15;5(2). Epub 2020 Apr 15.

Department of Microbiology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin, Hong Kong, SAR

This study identified and characterized extended-spectrum-β-lactamase-producing (ESBL-E) and carbapenemase-producing (CPE) from farmed freshwater fish and pig offal procured from the wet markets across Hong Kong. During March 2018 to January 2019, 730 food animal samples, namely, 213 snakehead fish, 198 black carp, and 339 pig organs, were examined. ESBL-E and CPE were isolated from the homogenized samples plated on selective media and identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). All ESBL-E and CPE strains were tested for antimicrobial susceptibilities. ESBL-E and CPE gene groups were detected by multiplex PCR and group strains were Sanger sequenced for CTX-M types. All CPE isolates were whole-genome sequenced. Isolation of ESBL-E from pig small (52.4%) and large (50%) intestines and tongues (25.1%) was significantly ( < 0.05) more frequent than from snakehead (0.94%) and black carp (0.5%) fish. ESBL-E isolates ( = 171) revealed resistance rates of 16.3%, 29.8%, 35.6%, 53.2%, 55.0%, and 100% to piperacillin-tazobactam, amoxicillin-clavulanate, cefepime, gentamicin, ciprofloxacin, and ampicillin, respectively, whereas CPE ( = 28) were resistant to almost all the antibiotics tested except gentamicin, ciprofloxacin, and fosfomycin. The predominant ESBL gene groups in fishes and pig offals were , where was the major subtype in the group (64.4% of isolates in the group). was the major genotype in the group (32.2%). All CPE strains possessed genes. High rates of ESBL-E and CPE were identified in food animals from wet markets of Hong Kong, which may serve as a potential reservoir of antimicrobial-resistant genes and increase the challenges in tackling antimicrobial resistance beyond health care settings. Extended-spectrum-β-lactamase-producing (ESBL-E) and carbapenemase-producing (CPE) are of global health importance, yet there is a paucity of surveillance studies on food animals in Hong Kong. Here, we report a high prevalence of ESBL-E (ranging from 0.5% to 52.4%) and CPE (0% to 9.9%) from various food animal samples procured from wet markets across Hong Kong. All CPE strains were characterized by whole-genome sequencing and possessed NDM-1 and -5 genes and other resistance determinants. Given the increased resistance profile of these strains, this study highlights the emerging threat of ESBL-E and CPE disseminated in farmed animals. Furthermore, our data enriched our understanding of antibiotic resistance reservoirs from a One Health perspective that can widely spread across various niches, beyond health care settings.
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http://dx.doi.org/10.1128/mSphere.00107-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160683PMC
April 2020

Biological characteristics associated with virulence in ribotype 002 in Hong Kong.

Emerg Microbes Infect 2020 17;9(1):631-638. Epub 2020 Mar 17.

Institute of Digestive Disease, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR.

infection (CDI) is a common cause of nosocomial diarrhea and can sometimes lead to pseudo-membranous colitis and toxic megacolon. We previously reported that the PCR ribotype 002 was a common ribotype in Hong Kong that was associated with increased mortality. In this study, we assessed bacteriological characteristics and virulence of ribotype 002 compared to other common ribotypes, including ribotypes 012, 014 and 046. We observed significantly higher toxin A ( 0.05) and toxin B (< 0.05) production, sporulation ( 0.001) and germination rates (< 0.0001) in ribotype 002 than other common ribotypes. In a murine model of infection, ribotype 002 caused significantly more weight loss ( < 0.001) and histological damage ( < 0.001) than other common ribotypes. These findings may have contributed to the higher prevalence and mortality observed, and provided mechanistic insights that can help public surveillance and develop novel therapeutics to combat against this infection.
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http://dx.doi.org/10.1080/22221751.2020.1739564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144233PMC
March 2020

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia.

Genome Med 2020 01 16;12(1):11. Epub 2020 Jan 16.

Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria, 3004, Australia.

Background: Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide.

Methods: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool.

Results: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae.

Conclusions: K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.
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http://dx.doi.org/10.1186/s13073-019-0706-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966826PMC
January 2020

Systematic review of human gut resistome studies revealed variable definitions and approaches.

Gut Microbes 2020 11 16;12(1):1700755. Epub 2020 Jan 16.

Department of Microbiology, The Chinese University of Hong Kong , Hong Kong SAR, China.

In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.
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http://dx.doi.org/10.1080/19490976.2019.1700755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524153PMC
November 2020
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