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  1. Yang SK, Yusoff K, Ajat M, Wee CY, Yap PS, Lim SH, et al.
    Front Microbiol, 2021;12:635016.
    PMID: 33815320 DOI: 10.3389/fmicb.2021.635016
    Antibiotic-adjuvant combinatory therapy serves as a viable treatment option in addressing antibiotic resistance in the clinical setting. This study was carried out to assess and characterize the adjuvant potential and mode of action of linalool against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Linalool exhibited bactericidal activity alone (11,250 μg/ml) and in combination with meropenem (5,625 μg/ml). Comparative proteomic analysis showed significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in linalool-treated KPC-KP cells. Upregulation of oxidative stress regulator proteins and downregulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that linalool increases the bacterial surface charge as well as the membrane permeability. Intracellular leakage of nucleic acid and proteins was detected upon linalool treatment. Scanning and transmission electron microscopies further revealed the breakage of bacterial membrane and loss of intracellular materials. Linalool induced oxidative stress by generating reactive oxygen species (ROS) which initiates lipid peroxidation, leading to damage of the bacterial membrane. This leads to intracellular leakage, eventually killing the KPC-KP cells. Our study demonstrated that linalool possesses great potential in future clinical applications as an adjuvant along with existing antibiotics attributed to their ability in disrupting the bacterial membrane by inducing oxidative stress. This facilitates the uptake of antibiotics into the bacterial cells, enhancing bacterial killing.
  2. Yang SK, Tan NP, Chong CW, Abushelaibi A, Lim SH, Lai KS
    Evol Bioinform Online, 2021;17:1176934320938391.
    PMID: 34017165 DOI: 10.1177/1176934320938391
    Antibiotic resistance is a major global health issue that has seen alarming rates of increase in all parts of the world over the past two decades. The surge in antibiotic resistance has resulted in longer hospital stays, higher medical costs, and elevated mortality rates. Constant attempts have been made to discover newer and more effective antimicrobials to reduce the severity of antibiotic resistance. Plant secondary metabolites, such as essential oils, have been the major focus due to their complexity and bioactive nature. However, the underlying mechanism of their antimicrobial effect remains largely unknown. Understanding the antimicrobial mode of action of essential oils is crucial in developing potential strategies for the use of essential oils in a clinical setting. Recent advances in genomics and proteomics have enhanced our understanding of the antimicrobial mode of action of essential oils. We might well be at the dawn of completing a mystery on how essential oils carry out their antimicrobial activities. Therefore, an overview of essential oils with regard to their antimicrobial activities and mode of action is discussed in this review. Recent approaches used in identifying the antimicrobial mode of action of essential oils, specifically from the perspective of genomics and proteomics, are also synthesized. Based on the information gathered from this review, we offer recommendations for future strategies and prospects for the study of essential oils and their function as antimicrobials.
  3. Yang SK, Yusoff K, Ajat M, Yap WS, Lim SE, Lai KS
    J Pharm Anal, 2021 Apr;11(2):210-219.
    PMID: 34012697 DOI: 10.1016/j.jpha.2020.05.014
    Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate (LNA) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). LNA alone exhibited bactericidal activity at 2.5% (V/V), and in combination with meropenem (MPM) at 1.25% (V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species (ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.
  4. Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, Akseer R, et al.
    PLoS One, 2019;14(4):e0214326.
    PMID: 30939149 DOI: 10.1371/journal.pone.0214326
    Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability.
  5. Yang SK, Yusoff K, Mai CW, Lim WM, Yap WS, Lim SE, et al.
    Molecules, 2017 Nov 04;22(11).
    PMID: 29113046 DOI: 10.3390/molecules22111733
    Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction.
  6. Mahizan NA, Yang SK, Moo CL, Song AA, Chong CM, Chong CW, et al.
    Molecules, 2019 Jul 19;24(14).
    PMID: 31330955 DOI: 10.3390/molecules24142631
    The evolution of antimicrobial resistance (AMR) in pathogens has prompted extensive research to find alternative therapeutics. Plants rich with natural secondary metabolites are one of the go-to reservoirs for discovery of potential resources to alleviate this problem. Terpenes and their derivatives comprising of hydrocarbons, are usually found in essential oils (EOs). They have been reported to have potent antimicrobial activity, exhibiting bacteriostatic and bactericidal effects against tested pathogens. This brief review discusses the activity of terpenes and derivatives against pathogenic bacteria, describing the potential of the activity against AMR followed by the possible mechanism exerted by each terpene class. Finally, ongoing research and possible improvisation to the usage of terpenes and terpenoids in therapeutic practice against AMR are discussed.
  7. Yang SK, Yusoff K, Thomas W, Akseer R, Alhosani MS, Abushelaibi A, et al.
    Sci Rep, 2020 01 21;10(1):819.
    PMID: 31964900 DOI: 10.1038/s41598-019-55601-0
    Misuse of antibiotics in the clinical and agricultural sectors has caused the emergence of multidrug-resistant (MDR) Klebsiella pneumoniae which contributes a threat to human health. In this study, we assessed the feasibility of lavender essential oil (LVO) as an antimicrobial agent in combinatory therapy with meropenem in suppressing the growth of carbapenemase-producing K. pneumoniae (KPC-KP). Synergistic interactions between LVO and meropenem were detected, which significantly reduce the inhibitory concentration of both LVO and meropenem by 15 and 4-fold respectively. Comparative proteomic profiling identified a disruption in the bacterial membrane via oxidative stress that was indicated by loss of membrane and cytoplasmic proteins and the upregulation of oxidative regulators. As a proof of concept, zeta potential measurements showed a change in cell surface charge while outer membrane permeability measurement indicated an increase in membrane permeability following exposure to LVO. This was indicative of a disrupted outer membrane. Ethidium bromide influx/efflux assays demonstrated no significant efflux pump inhibition by LVO, and scanning electron microscopy revealed irregularities on the cell surface after exposure to LVO. Oxidative stress was also detected with increased level of ROS and lipid peroxidation in LVO-treated cells. In conclusion, our data suggest that LVO induced oxidative stress in K. pneumoniae which oxidizes the outer membrane, enabling the influx of generated ROS, LVO and meropenem into the bacterial cells, causing damage to the cells and eventually death.
  8. Lai PJ, Ng EV, Yang SK, Moo CL, Low WY, Yap PS, et al.
    3 Biotech, 2020 Jul;10(7):313.
    PMID: 32596098 DOI: 10.1007/s13205-020-02304-3
    To better understand the synergistic antibacterial activity between piperacillin and Lavandula angustifolia essential oil (LEO) against multidrug-resistant Escherichia coli, we performed microarray transcriptomic analysis of LEO when used alone and in combination with piperacillin against the non-treated control. In total, 90 genes were differentially expressed after the combination of LEO and piperacillin treatment. Among the up-regulated genes, nfsB, nemA, fruA, nfsB, nemA are known to control microbial metabolism and nitrotoluene degradation, which were observed only in the LEO-piperacillin combinatory treatment. Four candidate genes from the microarray result, srIA, srID, waaR and nfsB, were validated by qRT-PCR as these genes showed differential expression consistently in the two methods. Biochemical pathway analysis showed that there was upregulation of genes involved in several biological processes including fructose and mannose metabolism, phosphotransferase system (PTS), lipopolysaccharide biosynthesis and nitrotoluene degradation. Genes involved in microbial metabolism in diverse environments were found both up- and down-regulated in LEO-piperacillin combinatory treatment. Our study provides new information concerning the transcriptional changes that occur during the LEO and piperacillin interaction against the multidrug-resistant bacteria and contributes to unravel the mechanisms underlying this synergism.
  9. Moo CL, Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, et al.
    Curr Drug Discov Technol, 2020;17(4):430-447.
    PMID: 30836923 DOI: 10.2174/1570163816666190304122219
    Antimicrobials are useful compounds intended to eradicate or stop the growth of harmful microorganisms. The sustained increase in the rates of antimicrobial resistance (AMR) worldwide is worrying and poses a major public health threat. The development of new antimicrobial agents is one of the critical approaches to overcome AMR. However, in the race towards developing alternative approaches to combat AMR, it appears that the scientific community is falling behind when pitched against the evolutionary capacity of multi-drug resistant (MDR) bacteria. Although the "pioneering strategy" of discovering completely new drugs is a rational approach, the time and effort taken are considerable, the process of drug development could instead be expedited if efforts were concentrated on enhancing the efficacy of existing antimicrobials through: combination therapies; bacteriophage therapy; antimicrobial adjuvants therapy or the application of nanotechnology. This review will briefly detail the causes and mechanisms of AMR as background, and then provide insights into a novel, future emerging or evolving strategies that are currently being evaluated and which may be developed in the future to tackle the progression of AMR.
  10. Song HK, Lee KM, Jung SA, Hong SN, Han DS, Yang SK, et al.
    Intest Res, 2016 Jul;14(3):240-7.
    PMID: 27433146 DOI: 10.5217/ir.2016.14.3.240
    The quality of care in inflammatory bowel disease (IBD) has not been systematically estimated. The aim of this study was to investigate the current status of quality of IBD care in Asian countries.
  11. Moo CL, Yang SK, Osman MA, Yuswan MH, Loh JY, Lim WM, et al.
    Pol J Microbiol, 2020;69:1-6.
    PMID: 32162852 DOI: 10.33073/pjm-2020-007
    Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism of β-caryophyllene, a compound that can be found in various EOs, against Bacillus cereus. The minimum inhibitory concentration of β-caryophyllene against B. cereus was 2.5% (v/v), whereas killing kinetics of β-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to -3.98 mV, compared to untreated cells (-5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity of B. cereus via the ethidium bromide influx/efflux activity. The results revealed that β-caryophyllene was able to alter membrane permeability and integrity of B. cereus, leading to membrane damage and intracellular content leakage, which eventually caused cell death.

    Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism of β-caryophyllene, a compound that can be found in various EOs, against Bacillus cereus. The minimum inhibitory concentration of β-caryophyllene against B. cereus was 2.5% (v/v), whereas killing kinetics of β-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to –3.98 mV, compared to untreated cells (–5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity of B. cereus via the ethidium bromide influx/efflux activity. The results revealed that β-caryophyllene was able to alter membrane permeability and integrity of B. cereus, leading to membrane damage and intracellular content leakage, which eventually caused cell death.

  12. Moo CL, Osman MA, Yang SK, Yap WS, Ismail S, Lim SH, et al.
    Sci Rep, 2021 10 21;11(1):20824.
    PMID: 34675255 DOI: 10.1038/s41598-021-00249-y
    Antimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death.
  13. Ran Z, Wu K, Matsuoka K, Jeen YT, Wei SC, Ahuja V, et al.
    J Gastroenterol Hepatol, 2021 Mar;36(3):637-645.
    PMID: 32672839 DOI: 10.1111/jgh.15185
    Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.
  14. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):30-36.
    PMID: 29024102 DOI: 10.1111/jgh.14018
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  15. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):20-29.
    PMID: 29023903 DOI: 10.1111/jgh.14019
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  16. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    Intest Res, 2018 Jan;16(1):17-25.
    PMID: 29422794 DOI: 10.5217/ir.2018.16.1.17
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised 3 parts: management of latent TB in preparation for anti-TNF therapy, monitoring during anti-TNF therapy, and management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  17. Park DI, Hisamatsu T, Chen M, Ng SC, Ooi CJ, Wei SC, et al.
    Intest Res, 2018 Jan;16(1):4-16.
    PMID: 29422793 DOI: 10.5217/ir.2018.16.1.4
    Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from 9 Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised 2 parts: risk of TB infection Recommendaduring anti-TNF therapy, and screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.
  18. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    Intest Res, 2019 Jul;17(3):285-310.
    PMID: 31146509 DOI: 10.5217/ir.2019.00026
    The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
  19. Ooi CJ, Hilmi I, Banerjee R, Chuah SW, Ng SC, Wei SC, et al.
    J Gastroenterol Hepatol, 2019 Aug;34(8):1296-1315.
    PMID: 30848854 DOI: 10.1111/jgh.14648
    The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
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