Browsing by Author "Hsueh, Po-Ren"

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Are we ready for the global emergence of multidrug-resistant Candida auris in Taiwan?
(2018-06-01)
Lu, Po-Liang
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Liu, Wei-Lun
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Lo, Hsiu-Jung
;
Wang, Fu-Der
;
Ko, Wen-Chien
Candida auris is a recently identified multi-resistant Candida species, first reported in Japan in 2009, and poses a serious global health threat. Lack of awareness of this new Candida species and difficulties with laboratory identification have impacted significantly on outbreak detection and management, and compromised patient outcome. Accordingly, there is an urgent need to raise awareness of healthcare personnel to this emerging pathogen and determine its prevalence, impact, and challenges to the Taiwan healthcare system. Enhanced laboratory testing strategies are needed to differentiate C. auris from other Candida species to provide accurate diagnosis and implement control measures early enough to prevent hospital outbreaks. In this report, we review the key epidemiological, microbiological and clinical characteristics of C. auris and provide the results of a multicenter surveillance study of C. auris in Taiwan. We also conducted a web-based survey to determine awareness of the medical community to C. auris and the capability of Taiwanese hospital laboratories to identify this microorganism. C. auris has not yet been isolated from humans in Taiwan, but the unique features of this microorganism and its ability to reach across international boundaries justify the importance of these initiatives in Taiwan.(C) 2017, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license.
Epidemiology and trends in the antibiotic susceptibilities of Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region, 2010-2013
(2017-06-01)
Chang, Ya-Ting
;
Coombs, Geoffrey
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Ling, Thomas
;
Balaji, V.
;
Rodrigues, Camilla
This study was conducted to investigate the epidemiology and antimicrobial susceptibility patterns of Gram-negative bacilli (GNB) isolated from intra-abdominal infections (IAIs) in the Asia-Pacific region (APR) from 2010-2013. A total of 17 350 isolates were collected from 54 centres in 13 countries in the APR. The three most commonly isolated GNB were Escherichia coli (46.1%), Klebsiella pneumoniae (19.3%) and Pseudomonas aeruginosa (9.8%). Overall, the rates of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae were 38.2% and 24.3%, respectively, and they were highest in China (66.6% and 38.7%, respectively), Thailand (49.8% and 36.5%, respectively) and Vietnam (47.9% and 30.4%, respectively). During 2010-2013, the rates of ESBL-producing E. coli and K. pneumoniae isolates causing community-associated (CA) IAIs (collected <48 h after admission) were 26.0% and 13.5%, respectively, and those causing hospital-associated (HA) IAIs were 48.0% and 30.6%, respectively. Amikacin, ertapenem and imipenem were the most effective agents against ESBL-producing isolates. Piperacillin/tazobactam displayed good in vitro activity (91.4%) against CA ESBL-producing E. coli. For other commonly isolated Enterobacteriaceae, fluoroquinolones, cefepime and carbapenems exhibited better in vitro activities than third-generation cephalosporins. Amikacin possessed high in vitro activity against all GNB isolates (>80%) causing IAIs, except for Acinetobacter calcoaceticus-baumannii (ACB) complex (30.9% for HA-IAI isolates). All of the antimicrobial agents tested exhibited <45% in vitro activity against ACB complex. Antimicrobial resistance is a persistent threat in the APR and continuous monitoring of evolutionary trends in the susceptibility patterns of GNB causing IAIs in this region is mandatory. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Update on Therapeutic Options
(2019-01-30)
Sheu, Chau-Chyun
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Chang, Ya-Ting
;
Lin, Shang-Yi
;
Chen, Yen-Hsu
;
Hsueh, Po-Ren
Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with in vitro activity against CRE; and eravacycline, which is a tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new beta-lactam/beta-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE.
Management of infections caused by extended-spectrum -lactamase-producing Enterobacteriaceae: current evidence and future prospects
(2018-01-01)
Sheu, Chau-Chyun
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Lin, Shang-Yi
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Chang, Ya-Ting
;
Lee, Chun-Yuan
;
Chen, Yen-Hsu
Introduction: The spread of extended-spectrum -lactamase (ESBL)-producing Enterobacteriaceae has become a major public health threat worldwide.Area covered: A thorough systematic literature review describing the current evidence and future prospects of therapeutic options for infections caused by ESBL-producing Enterobacteriaceae.Expert commentary: The methods of detecting ESBLs have been evolving. The Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing lowered the MIC breakpoints of cephalosporins against ESBL-producing Enterobacteriaceae in 2010. Phenotypic testing for ESBLs is no longer recommended. Instead, the selection of appropriate antimicrobial agents largely depends on the report of minimum inhibitory concentrations (MICs). To date, therapeutic options for these multidrug-resistant organisms remain limited. The clinical efficacy of piperacillin/tazobactam and cefepime on in vitro-susceptible ESBL-producing Enterobacteriaceae remains a concern. Many studies found an in vitro-in vivo discordance based on current breakpoints. Carbapenems are the most reliable antibiotics for severe infections caused by ESBL-producing Enterobacteriaceae. However, their overuse has led to a serious problem of increasing drug resistance. Recently, ceftolozane/tazobactam and ceftazidime/avibactam have been approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. The introduction of these new -lactam/-lactamase inhibitor combinations offers new carbapenem-sparing options for the treatment of ESBL infections.
New drugs for the treatment of complicated intra-abdominal infections in the era of increasing antimicrobial resistance
(2016-04)
Syue, Ling-Shan
;
Chen, Yen-Hsu
;
Ko, Wen-Chien
;
Hsueh, Po-Ren
;
生醫工程研究所
The continuing increase in multidrug-resistant organisms (MDROs) worldwide has created new challenges in treating complicated intra-abdominal infections (cIAIs). A number of novel antimicrobial agents have been developed against resistant pathogens. To target extended-spectrum beta-lactamase (ESBL)-producing pathogens, novel beta-lactam antibiotics, such as ceftolozane/tazobactam, ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and S-649266, are antimicrobial alternatives for cIAIs. Two new drugs, eravacycline and plazomicin, have activity against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, carbapenem-resistant Acinetobacter baumannii and ESBL-producers. New lipoglycopeptides and oxazolidinones provide feasible options against resistant Gram-positive pathogens. These novel antimicrobials may play a role in improving the clinical outcomes of cIAIs caused by MDROs. (C) 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Overexpression of an Outer Membrane Protein Associated with Decreased Susceptibility to Carbapenems in Proteus mirabilis
(2015-03-10)
Tsai, Yi-Lin
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Wang, Min-Cheng
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Hsueh, Po-Ren
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Liu, Ming-Che
;
Hu, Rouh-Mei
Proteus mirabilis isolates commonly have decreased susceptibility to imipenem. Previously, we found P. mirabilis hfq mutant was more resistant to imipenem and an outer membrane protein (OMP) could be involved. Therefore, we investigated the role of this OMP in carbapenem susceptibility. By SDS-PAGE we found this OMP (named ImpR) was increased in hfq mutant and LC-MS/MS revealed it to be the homologue of Salmonella YbfM, which is a porin for chitobiose and subject to MicM (a small RNA) regulation. We demonstrated that ImpR overexpression resulted in increased carbapenem MICs in the laboratory strain and clinical isolates. Chitobiose induced expression of chb (a chitobiose utilization operon). Real-time RT-PCR and SDS-PAGE were performed to elucidate the relationship of hfq, impR, chb and MicM in P. mirabilis. We found MicM RNA was decreased in hfq mutant and chbBC-intergenic region (chbBC-IGR) overexpression strain (chbIGRov), while impR mRNA was increased in hfq mutant, micM mutant and chbIGRov strain. In addition, mutation of hfq or micM and overexpression of chbBC-IGR increased ImpR protein level. Accordingly, chitobiose made wild-type have higher levels of ImpR protein and are more resistant to carbapenems. Hfq- and MicM-complemented strains restored wild-type MICs. Mutation of both impR and hfq eliminated the increase in carbapenem MICs observed in hfq mutant and ImpR-complementation of hfq/impR double mutant resulted in MICs as hfq mutant, indicating that the ImpR-dependent decreased carbapenem susceptibility of hfq mutant. These indicate MicM was antisense to impR mRNA and was negatively-regulated by chbBC-IGR. Together, overexpression of ImpR contributed to the decreased carbapenem susceptibility in P. mirabilis.
Preferential induction of transforming growth factor-beta production in gastric epithelial cells and monocytes by Helicobacter pylori soluble proteins
(2007-11-01)
Wu, Ming-Shiang
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Lin, Jaw-Town
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Hsu, Ping-Ning
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Lin, Ching-Yi
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Hsieh, Yuan-Ting
Background. The cytokines induced by Helicobacter pylori, as well as the intricate balance of proinflammatory and anti-inflammatory cytokines, are relevant to the outcomes of H. pylori infection. Transforming growth factor (TGF)-beta and interleukin (IL)-10 are 2 vital anti-inflammatory cytokines that regulate mucosal immunity in various inflammatory and infectious diseases. Methods. To elucidate whether host-bacteria interaction can influence TGF-beta and IL-10 production, we investigated the expression of TGF-beta and IL-10 in various mammalian cell lines preincubated with H. pylori and other enteric bacteria. Results. The amount of TGF-beta protein, but not IL-10, was significantly increased after stimulation with H. pylori, but other enteric bacteria did not induce TGF-beta production. Different H. pylori strains isolated from patients with gastritis, peptic ulcer, gastric cancer and strains with cagA or vacA isogenic mutations showed similar effects on TGF-beta induction, indicating that this effect was a constitutional characteristic of H. pylori and independent of cagA and vacA status. Conclusion. The results imply the presence of a protein factor ( termed "TGF-beta-inducing protein") that induces production of TGF-beta. In view of the multiple effects of TGF-beta, we conclude the TGF-beta-inducing protein of H. pylori might mediate the immune response and contribute to the pathogenesis of H. pylori infection.
Recent developments in antibiotic agents for the treatment of complicated intra-abdominal infections
(2016-02-11)
Lin, Shang-Yi
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Huang, Chung-Hao
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Ko, Wen-Chien
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Chen, Yen-Hsu
;
Hsueh, Po-Ren
Introduction: Treatment of complicated intra-abdominal infections (cIAIs) is becoming increasingly difficult because of the widespread emergence of multidrug-resistant organisms.Areas covered: In this review, we discuss the effectiveness of several new antibiotics for the treatment of cIAIs, including new -lactamase inhibitor combinations (BLICs) and tetracycline-class drugs, recently developed aminoglycosides and quinolones, and novel lipoglycopeptides and oxazolidinones.Expert opinion: Of the new BLICs, ceftolozane/tazobactam is associated with adequate clinical cure rates in patients with cIAIs. Currently, two new -lactamase inhibitors, namely avibactam and MK-7655, are under development for clinical use in the treatment of cIAIs. Eravacycline, a novel, fully synthetic tetracycline-class drug, has been shown in Phase II and III clinical trials to be more potent than tigecycline against a significant number of multidrug-resistant organisms causing cIAIs. Plazomicin, a next-generation aminoglycoside, is a promising agent for treatment of cIAIs due to multidrug-resistant pathogens. Of the recently developed quinolones, delafloxacin and finafloxacin have been shown to be effective against pathogens that survive and multiply in mildly acidic environments, although further clinical studies examining their clinical utility in the treatment of cIAIs are warranted. Oritavancin, a new semisynthetic lipoglycopeptide agent, has been demonstrated to be a potent antibiotic in the treatment of cIAIs due to drug-resistant Gram-positive organisms. Several other new antibiotics in development also show promise and will hopefully broaden the possibilities for treatment of complicated intra-abdominal infections due to MDR pathogens.
Role of rifampin for the treatment of bacterial infections other than mycobacteriosis
(2017-11-01)
Lee, Chun-Yuan
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Huang, Chung-Hao
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Lu, Po-Liang
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Ko, Wen-Chien
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Chen, Yen-Hsu
Objectives: Rifampin was initially approved for the treatment of tuberculosis. Because of its low toxicity, broad-spectrum activity, and good bioavailability, rifampin is now commonly administered as combination antimicrobial therapy for the treatment of various infections caused by organisms other than mycobacteria. This review summarizes the most recent clinical studies on the use of rifampin combinations for treating four common non-mycobacterial infections: acute bacterial meningitis, infective endocarditis and bacteraemia, pneumonia, and biofilm-related infections. Methods: We performed a literature search of clinical studies published in English from January 2005 to June 2016 using the PubMed database with the search terms "rifampin" with "meningitis" or "infective endocarditis and bacteraemia" or "pneumonia" or "prosthetic joint infections. Results: Current evidence to support a rifampin combination therapy as a treatment for non-mycobacterial infections was largely based on in vitro/in vivo studies and non-comparable retrospective case series. Additionally, controlled clinical trials that directly compared outcomes resulting from rifampin treatment versus treatment without rifampin were limited. Conclusions: Rifampin combination therapy appears promising for the treatment of non-mycobacterial infections. However, further definitive clinical trials are necessary to validate its use because the risk of adverse drug-drug interactions and of the emergence of rifampin resistance during treatment may outweigh the potential benefits. (C) 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Update on infections caused by Stenotrophomonas maltophilia with particular attention to resistance mechanisms and therapeutic options
(2015-09-02)
Chang, Ya-Ting
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Lin, Chun-Yu
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Chen, Yen-Hsu
;
Hsueh, Po-Ren
;
生醫工程研究所
Stenotrophomonas maltophilia is a Gram-negative, biofilm-forming bacterium. Although generally regarded as an organism of low virulence, S. maltophilia is an emerging multi-drug resistant opportunistic pathogen in hospital and community settings, especially among immunocompromised hosts. Risk factors associated with S. maltophilia infection include underlying malignancy, cystic fibrosis, corticosteroid or immunosuppressant therapy, the presence of an indwelling central venous catheter and exposure to broad spectrum antibiotics. In this review, we provide a synthesis of information on current global trends in S. maltophilia pathogenicity as well as updated information on the molecular mechanisms contributing to its resistance to an array of antimicrobial agents. The prevalence of S. maltophilia infection in the general population increased from 0.8-1.4% during 1997-2003 to 1.3-1.68% during 2007-2012. The most important molecular mechanisms contributing to its resistance to antibiotics include beta-lactamase production, the expression of Qnr genes, and the presence of class 1 integrons and efflux pumps. Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial drug of choice. Although a few studies have reported increased resistance to TMP/SMX, the majority of studies worldwide show that S. maltophilia continues to be highly susceptible. Drugs with historically good susceptibility results include ceftazidime, ticarcillin-clavulanate, and fluoroquinolones; however, a number of studies show an alarming trend in resistance to those agents. Tetracyclines such as tigecycline, minocycline, and doxycycline are also effective agents and consistently display good activity against S. maltophilia in various geographic regions and across different time periods. Combination therapies, novel agents, and aerosolized forms of antimicrobial drugs are currently being tested for their ability to treat infections caused by this multi-drug resistant organism.