Focused Research Theme – Antimicrobial Resistance and Antibiotic Stewardship

Focused Research Theme – Antimicrobial Resistance and Antibiotic Stewardship

Introduction

Antimicrobial resistance and the emergence of multi-drug-resistant organisms (MDROs) in the healthcare setting and in the community is a global concern worldwide. A multidisciplinary research group was formed in early 2000s, initially in response to the emergence of Methicillin-resistant Staphylococcus aureus (MRSA), which became endemic in many hospitals in Asia Pacific region. In recent years, community-acquired MRSA as well as a number of MDROs which are resistant to virtually all currently available drugs are becoming prevalent. The CUHK Department of Microbiology has a strong interest in understanding the mechanisms of spread of these resistant organisms and their resistance determinants, and exploring new strategies to combat antimicrobial resistance.

Theme Leader
Prof. Margaret Ip
Members:
Ms. Coral Lee
Dr. Carmen Li
Dr Nilakshi Barua
Mr. Jun Yang
Ongoing research topics:
Mechanisms of resistance determinants and spread of these determinants.
Use of animal models to study pathogenicity of bacteria.
Bacterial genomics and transcriptomes to study phylogenetics and evolution of MRSA, regulatory mechanisms of resistance and virulence.
Molecular typing methods for MRSA and other MDROs.
New and alternative treatment options.
Research on Gram positive bacteria:
Methicillin-resistance Staphylococcus aureus & One Health
Streptococcus pneumoniae and other Streptococci
Recent Publications

  1. Qiu Y, Chu AJ, Tsang TF, Zheng Y, Lam NM, Li KSL, Ip M, Yang X, Ma C. Synthesis and biological evaluation of nusbiarylin derivatives as bacterial rRNA synthesis inhibitor with potent antimicrobial activity against MRSA and VRSA. Bioorg Chem. 2022 Jul;124:105863.
  2. Barua N, Huang L, Li C, Yang Y, Luo M, Wei WI, Wong KT, Lo NWS, Kwok KO, Ip M. Comparative Study of Two-Dimensional (2D) vs. Three-Dimensional (3D) Organotypic Kertatinocyte-Fibroblast Skin Models for Staphylococcus aureus (MRSA) Infection. Int J Mol Sci. 2021 Dec 28;23(1):299.
  3. Barua N, Yang Y, Huang L, Ip M. VraSR Regulatory System Contributes to the Virulence of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in a 3D-Skin Model and Skin Infection of Humanized Mouse Model. Biomedicines. 2021 Dec 24;10(1):35.
  4. Chan BCL, Dharmaratne P, Wang B, Lau KM, Lee CC, Cheung DWS, Chan JYW, Yue GGL, Lau CBS, Wong CK, Fung KP, Ip M. 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):1399.
  5. Munasinghe T, Vidanapathirana G, Kuthubdeen S, Ekanayake A, Angulmaduwa S, De Silva K, Subhasinghe S, Kalupahana R, Liyanapathirana V, Ip M. Colonization with selected antibiotic resistant bacteria among a cohort of Sri Lankan university students. BMC Infect Dis. 2021 Jun 15;21(1):578.
  6. Dharmaratne P, Yu L, Wong RC, Chan BC, Lau KM, Wang B, Lau CBS, Fung KP, Ng DK, Ip M. A Novel Dicationic Boron Dipyrromethene-based Photosensitizer for Antimicrobial Photodynamic Therapy against Methicillin-Resistant Staphylococcus aureus. Curr Med Chem. 2021;28(21):4283-4294.
  7. Dharmaratne P, Wang B, Wong RCH, Chan BCL, Lau KM, Ke MR, Lau CBS, Ng DKP, Fung KP, Ip M. Monosubstituted tricationic Zn(II) phthalocyanine enhances antimicrobial photodynamic inactivation (aPDI) of methicillin-resistant Staphylococcus aureus (MRSA) and cytotoxicity evaluation for topical applications: in vitro and in vivo study. Emerg Microbes Infect. 2020 Dec;9(1):1628-1637. doi: 10.1080/22221751.2020.1790305. PMID: 32619386; PMCID: PMC7473158.
  8. Dharmaratne P, Sapugahawatte DN, Wang B, Chan CL, Lau KM, Lau CB, Fung KP, Ng DK, Ip M. 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 15;200:112341.
  9. Dharmaratne P, Wong RCH, Wang J, Lo PC, Wang B, Chan BCL, Lau KM, Lau CBS, Fung KP, Ip M, Ng DKP. Synthesis and In Vitro Photodynamic Activity of Cationic Boron Dipyrromethene-Based Photosensitizers against Methicillin-Resistant Staphylococcus aureus. Biomedicines. 2020 May 29;8(6):140.
  10. Leung B, Dharmaratne P, Yan W, Chan BCL, Lau CBS, Fung KP, Ip M, Leung SSY. Development of thermosensitive hydrogel containing methylene blue for topical antimicrobial photodynamic therapy. J Photochem Photobiol B. 2020 Jan;203:111776.
  11. Steinig EJ, Duchene S, Robinson DA, Monecke S, Yokoyama M, Laabei M, Slickers P, Andersson P, Williamson D, Kearns A, Goering RV, Dickson E, Ehricht R, Ip M, O’Sullivan MVN, Coombs GW, Petersen A, Brennan G, Shore AC, Coleman DC, Pantosti A, de Lencastre H, Westh H, Kobayashi N, Heffernan H, Strommenger B, Layer F, Weber S, Aamot HV, Skakni L, Peacock SJ, Sarovich D, Harris S, Parkhill J, Massey RC, Holden MTG, Bentley SD, Tong SYC. Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent. mBio. 2019 Nov 26;10(6):e01105-19
  12. Qiu Y, Chan ST, Lin L, Shek TL, Tsang TF, Barua N, Zhang Y, Ip M, Chan PK, Blanchard N, Hanquet G, Zuo Z, Yang X, Ma C. Design, synthesis and biological evaluation of antimicrobial diarylimine and -amine compounds targeting the interaction between the bacterial NusB and NusE proteins. Eur J Med Chem. 2019 Sep 15;178:214-231.
  13. Chan BCL, Ip M, Gong HS, Lui SL, See RH,  Jolivalt C, Fung KP, Leung PC, Reiner NE,  Lau CBS. Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase” has been accepted by Phytomedicine (2013, in press).
  14. You JHS, Chan CY, Wong MY, Ip M. Active Surveillance and Decolonization of Methicillin-resistant Staphylococcus aureus on Admission to Neonatal Intensive Care Unit in Hong Kong- A Cost-effectiveness Analysis Infect Cont Hosp Epid 2012;33:1024-30. Epub 2012 Aug 27. PMID:22961022.
  15. Hon KL, Wang SS, Lee KK, Lee VW, Leung TF, Ip M. Combined antibiotic/corticosteroid cream in the empirical treatment of moderate-to-severe eczema: friend or foe? J Drugs Dermatol 2012;11:861-4.
  16. Chan BCL, Yu H, Wong CW, Lui SL Jolivalt C, Ganem-Elbaz C, Paris JM, Morleo B, Litaudon M, Lau CBS, Ip M, Fung KP, Leung PC, Han QB. Quick identification of kuraridin, a noncytotoxic anti-MRSA (methicillin-resistant Staphylococcus aureus) agent from Sophora flavescens using high-speed counter-current chromatography. J Chromatography B Analyt Technol Biomed Life Sci  2012, 880:157-162. Epub 2011 Dec 2.
  17. Chan BCL, Ip M , Lau CBS, Lui SL, Jolivalt C, Ganem-Elbaze C, Litaudon M, Reiner NE, Gong HS, See RH, Fung KP, Leung PC. Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase. J Ethnopharmacology, 2011;137:767-773.  doi:10.1016/j.jep.2011.06.039.
  18. Monecke S, Akpaka P, Borg M, Chow H, Coleman DC , Coombs G, Ip M, Jatzwauk L, Jones D, Kadlec K, Kearns A, Laurent F, O’Brien FG , Pearson J, Ruppelt A, Schwarz S, Scicluna E, Shore A, Slickers P, Ta HL, Weber S, Ehricht R. A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS One 2011;6:e17936.
  19. You JHS, Mak MMW, To LYT, Ip M*. Complicated Infections with Meticillin-Resistant Staphylococcus aureus In Hong Kong. J Hosp Infect 2011;78:71-2. Epub 2011 Feb 12.
  20. You JHS, Chow SSL, Lui JWW, Ip M. New target concentrations for vancomycin in Hong Kong. Int J Antimicrob Agents 2011;37:83-4. Epub 2010 Nov 11.
  21. Ip M*, Chau SSL, Lui SL, Leung E, Ling T. Vancomycin MICs for MRSA in Hong Kong. IntJ Antimicrob Agents, 2010;36:383-384.
  22. Nübel U, Roumagnac P , Feldkamp M , Song JH, Ko KS, Huang YC, Coombs G, Ip M, Westh H, Skov R, Struelens MJ, Goering RV, Strommenger B, Weller A, Witte W, Achtman M. Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus. Proc Nat Acad Sci, USA 2008;105: 14130-14135.
  23. You JHS, Ip DNC, Wong CTN, Ling T, Lee N, Ip M*.MRSA Bacteremia in Hong Kong. J Hosp Infect 2008;70:379-381.
  24. Hon KLE, Leung AKC, Kong AYF, Leung TF, Ip M. Atopic Dermatitis complicated by methicillin-resistant Staphylococcus aureus Infection. J Nat Med Asso 2008; 100:797-800.
  25. Lee N, Cockram CS, Lui G, Lam R, Lam E, Lai R, Ip M*.  A Community Case of Methicillin-Resistant Staphylococcus aureus Infection. Emerging Infect Dis 2006; 12: 172-174.
  26. Hon KLE, MCA Lam, TF Leung, WYC Kam, MCA Li, Ip M, TF Fok. Clinical features associated with nasal Staphylococcus aureus colonization in Chinese children with moderate-to-severe atopic dermatitis. Annals Academy of Medicine Singapore, 2005; 34: 602-605.
  27. Ip M*, Yung RWH, Ng TK, Luk WK, Tse C, Hung P, Enright M, Lyon DJ. Contemporary Methicillin-resistant Staphylococcus aureus (MRSA) clones in Hong Kong. J Clin Microbiol, 2005;43: 5069-5073.
  28. Ip M*, Lyon DJ, Chio F, Cheng AFB. Longitudinal analysis of methicillin-resistant Staphylococcus aureus (MRSA) in a Hong Kong Teaching Hospital. Infection Control and Hospital Epidemiology, 2004, 25:126-129.
  29. Ip M*, Lyon DJ, Chio F, Enright M, Cheng AF. Characterization of Hong Kong isolates of Methicillin-Resistant Staphylococcus aureus (MRSA) by Phage Typing, Pulsed-field Gel Electrophoresis (PFGE) and Fluorescent amplified-fragment length polymorphism analysis (FAFLP). J Clin Microbiol 2003, 41: 4980-4985.
  30. Ip M*. Review: Update on Bacterial Skin Infections – Community acquired Methicillin resistant Staphylococcus aureus (CA-MRSA). Hong Kong Journal of Dermatology & Venereology, 2007.
  1. Karlowsky JA, Lob SH, Khan TK, Chen WT, Woo PCY, Seto WH, Ip M, Leung SWM, Wong QW, Chau RWY, DeRyke CA, Young K, Motyl MR, Sahm DF. Carbapenem resistance among Gram-negative isolates collected from patients in ICU and non-ICU hospital wards in Hong Kong: SMART 2017-2020. J Glob Antimicrob Resist. 2023 Jun;33:260-266.
  2. Pan M, Barua N, Ip M. Mucin-degrading gut commensals isolated from healthy faecal donor suppress intestinal epithelial inflammation and regulate tight junction barrier function. Front Immunol. 2022 Oct 12;13:1021094.
  3. Karlowsky JA, Lob SH, Khan A, Chen WT, Woo PCY, Seto WH, Ip M, Leung S, Wong QW, Chau RWY, DeRyke CA, Young K, Motyl MR, Sahm DF. Activity of ceftolozane/tazobactam against Gram-negative isolates among different infections in Hong Kong: SMART 2017-2019. J Med Microbiol. 2022 Apr;71(4).
  4. Zhu C, Li C, Lai CKC, Ng R, Chau KY, Wong KT, Lo NWS, Barua N, Yang Y, Liyanapathirana V, Hui M, Lai RW, Fung KSC, Tsang DN, Ip M. Longitudinal Genomic Characterization of Carbapenemase-producing Enterobacteriaceae (CPE) Reveals Changing Pattern of CPE Isolated in Hong Kong Hospitals. Int J Antimicrob Agents. 2021 Nov;58(5):106430.
  5. Woh PY, Yeung MPS, Goggins WB 3rd, Lo N, Wong KT, Chow V, Chau KY, Fung K, Chen Z, Ip M. Genomic Epidemiology of Multidrug-Resistant Nontyphoidal Salmonella in Young Children Hospitalized for Gastroenteritis. Microbiol Spectr. 2021 Sep 3;9(1):e0024821
  6. Munasinghe T, Vidanapathirana G, Kuthubdeen S, Ekanayake A, Angulmaduwa S, De Silva K, Subhasinghe S, Kalupahana R, Liyanapathirana V, Ip M. Colonization with selected antibiotic resistant bacteria among a cohort of Sri Lankan university students. BMC Infect Dis. 2021 Jun 15;21(1):578
  7. Kwok KO, Chan E, Chung PH, Tang A, Wei WI, Zhu C, Riley S, Ip M. Prevalence and associated factors for carriage of Enterobacteriaceae producing ESBLs or carbapenemase and methicillin-resistant Staphylococcus aureus in Hong Kong community. J Infect. 2020 Aug;81(2):242-247
  8. Sapugahawatte DN, Li C, Zhu C, Dharmaratne P, Wong KT, Lo N, Ip M. Prevalence and Characteristics of Extended Spectrum-β-Lactamase-Producing and Carbapenemase-Producing Enterobacteriaceae from Freshwater Fish and Pork in Wet Markets of Hong Kong. mSphere. 2020 Apr 15;5(2):e00107-20.
  9. Wyres KL, Nguyen TNT, Lam MMC, Judd LM, van Vinh Chau N, Dance DAB, Ip M, Karkey A, Ling CL, Miliya T, Newton PN, Lan NPH, Sengduangphachanh A, Turner P, Veeraraghavan B, Vinh PV, Vongsouvath M, Thomson NR, Baker S, Holt KE. Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia. Genome Med. 2020 Jan 16;12(1):11.
  10. Clinical and economic outcomes of Klebsiella pneumoniae bacteraemia in Hong Kong. J Hosp Infect (2013, submitted).
  11. Lee CC, Lui G, Ip M, Ling TKW, Lee N. Frequent Detection of Plasmid-mediated Quinolone Resistance (qnr) Genes in Multidrug-resistant Enterobacteriaceae Blood Isolates, Hong Kong. EurJ Clin Microbiol & InfectDis 2012;31:3183-9. doi: 10.1007/s10096-012-1683-x. Epub 2012 Jun 29.
  12. Siu LK, Fung CP, Chang FY, Lee N, Yeh KM, Koh TH*, Ip M*. Molecular typing and virulence analysis among serotype K1 Klebsiella pneumoniae isolated from liver abscess patients and stool carriage from non-infectious subjects in Hong Kong, Singapore and Taiwan. J Clin Microbiol 2011;49:3761-3765. doi: 10.1128/JCM.00977-11
  13. Lam PKN, Tian Q, Ip M, Gomersall CD. .Effect of Pre-exposure on In vitro Adsorption of Amikacin by Polyacrylonitrile Hemofilter. Antimicrob Agents Chemother 2011;55:3641.
  14. Hui D, Ip M, Ling T, Chang, S-C; Liao CH, Yoo C-G, Udompanich V, Muttalif R, Roa C,  Soepandi P, Mangunnegoro H, Liu H, Kim DK, Yoon HI, Mogmeud S, Salleh A, Mendoza M, Fajardo-Ang C, Isbaniah F, Burhan E. A multicentre surveillance study on the characteristics, bacterial etiologies and in-vitro antibiotic susceptibilities in patients with acute exacerbations of COPD. Respirology 2011;16:532-539.
  15. KJ, Ip M, Ker HB, Mendoza M, Hsu L, Kiratisin P, Chongthaleong A, Redjeki IS, Quintana A, Flamm R, Garcia J, Cassettari M, Cooper D, Okolo P, Morrissey I. In vitro activity of doripenem and other carbapenems against contemporary gram-negative pathogens isolated from hospitalised patients in the Asia-Pacific Region: Results of the COMPACT Asia Pacific Study. Int J Antimicrob Agents 2010; 36:501-6.
  16. Wong GKC, Ip M, Poon WS, Mak CWK, Ng RY. Antibiotics-impregnated ventricular catheter versus Systemic antibiotics for prevention of nosocomial cerebrospinal Fluid (CSF) and non-CSF infections: A prospective randomized clinical trial. Neurology, Neurosurgery & Psychiatry, 2010;81:1064-7.
  17. You JHS, Chow TCP, Yeung AWC, Lee N, Ip M*. Acinetobacter baumannii bacteraemia in Hong Kong. J Hosp Infect 2010;75:81. Epub 2010 Mar 29.
  18. Lam PKN, Tian Q, Ip M, Gomersall CD.. In vitro adsorption of gentamicin and netilmicin by polyacrylonitrile and polyamide hemofiltration filters. Antimicrob Agents Chemother 2010;54:963 – 965.
  19. Broughton EI, Ip M, Coles CL, Walker DG. Hospital costs and lengths of stay associated with fluoroquinolone-resistant salmonella infections in Hong Kong. J Public Health 2010;32:165-72.
  20. You JHS, Mok SSM, Chang CCM, Lee N, Ip M*. Bacteraemia with Extended-Spectrum Beta-Lactamases-producing Escherichia coli in Hong Kong. Int J AntimicrobAgents. 2009;34:605-616.
  21. Tian Q, Gomersall CD, Ip M, Tan PE, Joynt GM, Choi GYS. Adsorption of amikacin: a significant mechanism of elimination by hemofiltration. Antimicrobial Agents & Chemother 2008;52:1009-13.
  22. You JHS, Kei HW, Lau WC, Wong KY, Marasinghe T, Lee N, Ip M*. Are beta-lactams related to higher morbidity and mortality in urinary tract infections caused by extended-spectrum B-lactamases-producing Escherichia coli? J HospInfect, 2008;68:181-3.
  23. You JHS, Lo LPY, Chung IYK, Marasinghe T, Lee N, Ip M*, Effect of an Antimicrobial Stewardship Programme on the use of Carbapenems in a Hong Kong Teaching Hospital – A Pilot Study. J Hosp Infect 2007,65:378-9.
  24. M*, Lui SL, Chau SSL, Lung I, Burd A. The Prevalence of Resistance to Silver in a Burns Unit. J Hosp Infect 2006; 63: 342-344.
  25. Ip M*, Lui SL, Poon VKM,
  26. Lung I,  Burd A. Antimicrobial Activities of Silver Dressings – an In Vitro Comparison.  J Med Microbiol 2006; 55(Pt  1): 59-63.
  27. Ip M, Au C, Cheung SW, Chan CY and Cheng AFB. A rapid high performance liquid chromatographic assay for the new B-lactams. Journal of Antimicrobial Chemotherapy 1998;42:121-3.
  28. Li PKT, M Ip, MC Law, CC Szeto, CB Leung, TYH Wong, KKL Ho, AYM Wang, SF Lui, AWY Yu, DJ Lyon, AFB Cheng, KN Lai. Use of intraperitoneal cefepime as monotherapy in treatment of CAPD peritonitis. Peritoneal Dialysis International; 2000; 20: 232-241.
  29. Ip M. Antimicrobial Resistance – The Challenge Ahead. Topical Update – The Hong Kong College of Pathologists, Newsletter 2009;1:4-7.
  30. Ip M. Antibiotic Resistance: the Local Scenario. Bulletin of the Hong Kong Society for Infectious Diseases, 2007: Mar, vol.11.No.1 .
  31. Ip M. Moxifloxacin. Medical Progress 2001; 28: 45-48.
  32. Ip M. ABCs of Antimicrobial Resistance. Hong Kong Medical Diary 2003; 8: 8-11.
Chapter title: “Role of medicinal herbs in treatment against methicillin-resistant Staphylococus aureus (MRSA) infections.” Chan BCL, Ip M, Lau CBS, Han QB, Jolivalt C, Paris JM, Reiner NE, See RH, Fung KP, Leung PC. Book title: Recent Progress in Medicinal Plants; vol. 34, 2012. (http://star-bk.com/pic/pdf/1933699248.pdf).

Chapter title: “Chinese medicinal herbs against antibiotic-resistant bacterial pathogens.” Book title: “Science against microbial pathogens: communicating current research and technological advances” Chan BCL, Lau CBS, Jolivalt C, Lui SL, Ganem-Elbaz C, Paris JM, Litaudon M, Fung KP, Leung PC and Ip M *. 2012, Publisher: Formatex Research Center (http://www.formatex.org/microbiology3/chapters2.html).

Chapter 16: Antimicrobial Dressings. Ip M*. Book title: “Advanced Wound Repair Therapies “  Woodhead Publishing – Edited by David Farrar & Bryan Greener, 2012.