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Objectives: Elizabethkingia spp. are resistant to multiple antibiotics. This study aimed to determine in vitro and in vivo activities of cefiderocol against Elizabethkingia spp. and to investigate resistance mechanisms., Methods: Bloodstream isolates were collected from four hospitals. In vitro and in vivo activities were determined using broth microdilution and the wax moth model, respectively. Genome comparison and gene editing were used to confirm the contribution of target genes. Conjugation experiments and serial passage were used to determine transferability and stability, respectively. A MIC of ≤ 4 mg/L was designated as the susceptibility breakpoint., Results: Among 228 non-duplicated isolates, 226 exhibited a MIC of ≤ 4 mg/L with MIC 50/90 of 1/2 mg/L. Two isolates had a MIC of 128 mg/L; both source patients had multiple comorbidities, were ventilator-dependent, and had not received cefiderocol previously. Resistance was attributable to acquisition of bla CfxA-3 , carried by a conjugative transposon from Prevotella jejuni, and duplication of intrinsic bla CME-3 , which led to its overexpression. tetQ coexisted with bla CfxA-3 in this conjugative transposon and minocycline facilitated its transfer among E. anophelis. Antibiotics prescribed for source patients did not induce bla CME-3 duplication. The stabilities of bla CfxA-3 and double bla CME-3 were 100% and > 90%, respectively, after 10-day serial passage. Cefiderocol failed to rescue moth larvae infected with resistant strains, but removal of resistance mechanisms restored in vivo efficacy., Conclusions: Cefiderocol was in vitro and in vivo active against Elizabethkingia spp. but resistance may emerge due to the availability, transferability, and/or stability of resistance mechanisms., Competing Interests: Competing Interests All authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The use of matrix-assisted laser desorption/ionisation-time-of-flight mass spectra (MALDI-TOF MS) with machine learning (ML) has been explored for predicting antimicrobial resistance. This study evaluates the effectiveness of MALDI-TOF MS paired with various ML classifiers and establishes optimal models for predicting antimicrobial resistance and the presence of mecA gene among Staphylococcus aureus., Materials and Methods: Antimicrobial resistance against tier 1 antibiotics and MALDI-TOF MS of S. aureus were analysed using data from the Database of Resistance against Antimicrobials with MALDI-TOF Mass Spectrometry (DRIAMS) and one medical centre (CS database). Five ML classifiers were used to analyse performance metrics. The Shapley value quantified the predictive contribution of individual features., Results: The LightGBM demonstrated superior performance in predicting antimicrobial resistance for most tier 1 antibiotics among oxacillin-resistant S. aureus (ORSA) compared with all S. aureus and oxacillin-susceptible S. aureus (OSSA) in both databases. In DRIAMS, Multilayer Perceptron (MLP) was associated with excellent predictive performance, expressed as accuracy/AUROC/AUPR, for clindamycin (0.74/0.81/0.90), tetracycline (0.86/0.87/0.94), and trimethoprim-sulfamethoxazole (0.95/0.72/0.97). In the CS database, Ada and Light Gradient Boosting Machine (LightGBM) showed excellent performance for erythromycin (0.97/0.92/0.86) and tetracycline (0.68/0.79/0.86). Mass-to-charge ratio (m/z) features of 2411-2414 and 2429-2432 correlated with clindamycin resistance, whereas 5033-5036 was linked to erythromycin resistance in DRIAMS. In the CS database, overlapping features of 2423-2426, 4496-4499, and 3764-3767 simultaneously predicted the presence of mecA and oxacillin resistance., Conclusion: The predictive performance of antimicrobial resistance against S. aureus using MALDI-TOF MS depends on database characteristics and the ML algorithm selected. Specific and overlapping mass spectra features are excellent predictive markers for mecA and specific antimicrobial resistance., Competing Interests: Declarations Funding: This project was supported by Chung Shan Medical University (grant number: CSMUH No:CS1-23228). This funding source played no role in study design or conduct, data collection, analysis or interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. Competing interests: The authors declare no conflicts of interest in relation to this study. Ethical approval: CSMUH No. CS1-23228 of Chung Shan Medical University and REC112-51 of Taichung Tzu Chi Hospital). Sequence information: Not applicable., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: This study aimed to investigate the in vitro susceptibility and β-lactamase-encoding genes of Pseudomonas aeruginosa (P. aeruginosa) isolates with discrepant resistance to various carbapenems., Methods: Data on P. aeruginosa isolates were obtained from the Antimicrobial Testing Leadership and Surveillance program from 2012-2021. Minimum inhibitory concentrations of P. aeruginosa isolates were determined using the broth microdilution method. β-lactamase-encoding genes were identified using multiplex polymerase chain reaction assays., Results: Among the P. aeruginosa isolates that were tested, the percentages of isolates resistant to imipenem, meropenem and doripenem were 26.9% (14 447 of 53 617), 20.5% (14 098 of 68 897) and 17.5% (3660 of 20 946), respectively. Imipenem-resistant P. aeruginosa isolates were more susceptible to all tested antimicrobial agents (except colistin) than the meropenem-resistant or doripenem-resistant P. aeruginosa isolates. Carbapenemase genes were detected in 14.3% (2020 of 14 098) of meropenem-resistant P. aeruginosa isolates. Imipenem-resistant meropenem-susceptible P. aeruginosa isolates had higher susceptibility profiles, fewer carbapenemase genes (0.3% [five of 1858] vs. 4.1% [10 of 242]; P < 0.05) and a lower risk of being classified as multidrug-resistant than the imipenem-susceptible meropenem-resistant isolates (16.1% [299 of 1858] vs. 73.6% [178 of 242]; P < 0.05). Among all β-lactam combination agents, ceftazidime-avibactam and ceftolozane-tazobactam had higher susceptibility rates than meropenem-vaborbactam for meropenem-resistant P. aeruginosa (61.8% and 55.5% vs. 30.2%; P < 0.05)., Conclusion: Discrepancy in the resistance of different P. aeruginosa isolates to various carbapenems suggests their different underlying resistance mechanisms. These findings can be useful for effective resistance trend monitoring and accurate antimicrobial treatment in the future., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Stenotrophomonas maltophilia is an emerging opportunistic pathogen for which there are limited therapeutic options because of intrinsic multidrug resistance. S. maltophilia isolates were collected as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program and minimum inhibitory concentrations (MICs) were determined using broth microdilution methods. Susceptibility was interpreted according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. Isolates with tigecycline MIC ≤2 mg/L were defined as susceptible, using the United States Food and Drug Administration criteria of Enterobacterales. A total of 2330 S. maltophilia isolates were collected from 47 countries worldwide in the ATLAS program from 2004 to 2020. Most patients were hospitalized (92.3%, 2151/2330) and respiratory tract infections (47.8%, 1114/2330) were the most common source of isolates. Minocycline had the highest susceptibility rate (98.8%), followed by levofloxacin (85.0%), trimethoprim-sulfamethoxazole (TMP-SMX) (84.4%), and ceftazidime (53.7%). A total of 98.3% (2290/2330) of S. maltophilia isolates had tigecycline MIC ≤2 mg/L. Among the S. maltophilia isolates exhibiting resistance to levofloxacin and ceftazidime, 89.3% (150/168) and 97.3% (692/711), respectively, were susceptible to tigecycline. Eight countries provided more than 30 isolates and were selected for comparison. Geographical difference in antimicrobial resistance was significant for levofloxacin, minocycline, and tigecycline (all P<0.05) but not for ceftazidime (P=0.467). These in vitro data demonstrated that minocycline had a higher susceptibility rate than levofloxacin and ceftazidime, and that tigecycline could be an alternative or salvage option for the treatment of S. maltophilia infections., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: Antimicrobial resistance due to β-lactamase production is a worldwide issue, and β-lactamase inhibitors have been developed to overcome the growing problem. This study aimed to evaluate the in vitro activities of two recently introduced carbapenem/β-lactamase inhibitor combinations - imipenem/relebactam and meropenem/vaborbactam - and their comparators against Enterobacterales from patients with urinary tract infections (UTIs)., Methods: Enterobacterales isolates from patients with UTIs in Taiwan and participating in the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 2020 were included. Minimum inhibitory concentrations (MICs) for various antibiotics were determined using the broth microdilution method. Susceptibility was interpreted based on the MIC breakpoints of the Clinical and Laboratory Standards Institute 2022. Genes encoding common β-lactamases, including extended-spectrum β-lactamases, AmpC β-lactamases and carbapenemases, were detected using multiplex polymerase chain reaction., Results: A total of 309 Enterobacterales isolates were included, against which both imipenem/relebactam and meropenem/vaborbactam exerted excellent efficacy (275 of 309, 95% and 288 of 309, 99.3%, respectively). Among imipenem non-susceptible isolates, 17 of 43 (39.5%) and 39 of 43 (90.7%) were susceptible to imipenem/relebactam and meropenem/vaborbactam, respectively., Conclusion: Imipenem/relebactam and meropenem/vaborbactam may be appropriate choices for treating UTIs due to Enterobacterales resistant to commonly used antibiotics. Continuous monitoring of antimicrobial resistance is crucial., Competing Interests: Competing Interests None declared., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Carbapenem-resistant Enterobacterales (CRE) are a growing threat to public health. This study was conducted to determine the prevalence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) and the associated carbapenemase genes using data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and carbapenemase genes were detected using multiplex polymerase chain reaction (PCR). Clinical and Laboratory Standards Institute breakpoints were used for interpretation of susceptibility. A total of 6753 K. pneumoniae isolates were collected from 57 countries in six regions worldwide. Of these, 1118 (16.6%) were CR-KP isolates. Among 1079 of the tested CR-KP isolates, 1017 (94.3%) had at least one of the class A (41.0%, 417/1017), B (39.3%, 400/1017), and D (38.8%, 395/1017) carbapenemase genes. The resistance patterns and associated genes differed significantly between the participating countries. India, Greece, and Argentina had the highest rates of carbapenem resistance. Susceptibility to the β-lactamase inhibitor combination, ceftazidime/avibactam was greater than that to meropenem/vaborbactam in all K. pneumoniae (93.7% vs. 90.3%, P < 0.05), CR-KP (63.3% vs. 41.5%, P < 0.05), CR-KP with genes for Klebsiella pneumoniae carbapenemase-like carbapenemase (99.5% vs. 96.0%, P < 0.05), oxacillinase-like carbapenemase (98.7% vs. 4.6%, P < 0.05), and CR-KP without carbapenemase genes (93.5% vs. 79.0%, P < 0.05). CR-KP was the only exception with class B carbapenemase, with susceptibility rates of 1.4% and 9.4% to ceftazidime/avibactam and meropenem/vaborbactam, respectively (P < 0.05). Overall, surveillance results are important for guiding empirical antimicrobial therapy in different regions and for monitoring the global transmission of CR-KP with varying resistance mechanisms., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Objectives: A total of 74 570 potentially naturally inducible chromosomal AmpC-producing (PNIC-AmpC) Enterobacterales isolates included in the Antimicrobial Testing Leadership and Surveillance Programme were obtained worldwide during 2012-2019 (22 503 from 2012-2014 and 52 067 from 2015-2019). Of these isolates, 117 and 711 obtained during 2012-2014 and 2015-2019, respectively, were carbapenem-resistant Enterobacterales (PNIC-AmpC-CRE). The MICs of ceftazidime-avibactam for these isolates were determined using the broth microdilution method., Methods: Genes encoding different Ambler classes of β-lactamases were investigated using multiplex PCR. After 97 isolates harbouring genes encoding metallo-β-lactamases (MβL) were excluded, 731 PNIC-AmpC MβL-negative CRE isolates (101 from 2012-2014 and 630 from 2015-2019) were included in this study., Results: Enterobacter cloacae (E. cloacae) complex species, Escherichia coli (E. coli) and Citrobacter freundii (C. freundii) complex species accounted for 36.3% (n = 265), 30.4% (n = 222) and 11.8% (n = 86), respectively, followed by Providencia species (n = 72), Serratia species (n = 52) and Klebsiella aerogenes (n = 34). The resistance rates to ceftazidime-avibactam for the overall PNIC-AmpC MβL-negative CRE isolates markedly differed between the two periods (35.6% vs. 63.3%; P < 0.001). Similar trends were observed for the MβL-negative-CR-E. cloacae complex species (47.4% vs. 65.2%; P = 0.046) and MβL-negative-CR-E. coli (16.2% vs. 63.8%; P < 0.001) but not for MβL-negative-CR-C. freundii complex species (40% vs. 62%; P = 0.153). Amongst the PNIC-AmpC MβL-negative CRE isolates, resistance rates to ceftazidime-avibactam worsened., Conclusions: Caution should be taken when empirically prescribing ceftazidime-avibactam for infections caused by PNIC-AmpC-CRE before susceptibility data are available., Competing Interests: Competing Interests None declared., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Increasing carbapenem resistance in Enterobacterales poses a threat to public health. In recent decades, this increase in carbapenem resistance has been caused by the global dissemination of carbapenemase-producing Enterobacterales (CPE). Carbapenemases are members of the β-lactamases that are divided into classes A, B and D based on their molecular structures. Although certain traditionally used antibiotics, such as amikacin, polymyxins, tigecycline and fosfomycin, may remain effective against some CPE, their clinical use is limited owing to adverse effects, including renal toxicity, tissue penetration or the requirement for combination treatment. Recently, several novel agents have been approved for clinical use, such as ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, eravacycline, omadacycline, meropenem/vaborbactam, imipenem/cilastatin/relebactam and plazomicin. However, the spectrum of antimicrobial activities and efficacies of novel agents vary depending on the mechanisms associated with carbapenem resistance in Enterobacterales. Therefore, it is of utmost importance to enable accurate and rapid diagnosis of CPE infection, including the determination of their antimicrobial resistance mechanisms. Here, recent advances in methods for the identification of CPE have been reviewed, including phenotypic methods (carbapenemase inactivation methods), biochemical methods [Carbapenemase Nordmann-Poirel (Carba NP) test and modified Carba NP test], immunochromatographic methods, proteomic methods [matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS)] and molecular-based methods [nucleic acid amplification technologies, hybridisation techniques (microarray) and whole-genome sequencing]. Both precise diagnosis and adequate treatment are important to combat the emerging CPE crisis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Multidrug-resistant (MDR) bacterial infections in humans are increasing worldwide. The global spread of antimicrobial resistance poses a considerable threat to human health. Phage therapy is a promising approach to combat MDR bacteria. An increasing number of reports have been published on phage therapy and the successful application of antibacterials derived using this method. Additionally, the CRISPR-Cas system has been used to develop antimicrobials with bactericidal effects in vivo. The CRISPR-Cas system can be delivered into target bacteria in various ways, with phage-based vectors being reported as an effective method. In this review, we briefly summarise the results of randomised control trials on bacteriophage therapy. Moreover, we integrated mechanisms of the CRISPR-Cas system antimicrobials in a schematic diagram and consolidated the research on phage-delivered CRISPR-Cas system antimicrobials., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

This study examined the susceptibility of carbapenem-nonsusceptible Enterobacterales (CNSE) to cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents. Non-duplicate Enterobacterales isolates from 16 Taiwanese hospitals were evaluated. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibility results were interpreted based on relevant guidelines. In total, 201 CNSE isolates were investigated, including 26 Escherichia coli isolates and 175 Klebsiella pneumoniae isolates. Carbapenemase genes were detected in 15.4% (n=4) of E. coli isolates and 47.4% (n=83) of K. pneumoniae isolates, with the most common being bla KPC (79.3%, 69/87), followed by bla OXA-48-like (13.8%, 12/87). Cefiderocol was the most active agent against CNSE; only 3.8% (n=1) of E. coli isolates and 4.6% (n=8) of K. pneumoniae isolates were not susceptible to cefiderocol. Among the carbapenem-resistant E. coli and K. pneumoniae isolates, 88.5% (n=23) and 93.7% (n=164), respectively, were susceptible to ceftazidime/avibactam. For cefepime/zidebactam, 23 (88.5%) E. coli isolates and 155 (88.6%) K. pneumoniae isolates had MICs ≤2/2 mg/L. For cefepime/enmetazobactam, 22 (84.6%) E. coli isolates and 85 (48.6%) K. pneumoniae isolates had MICs ≤2/8 mg/L. The higher MICs of K. pneumoniae against cefepime/enmetazobactam were due to only one (1.5%) of the 67 bla KPC -carrying isolates being susceptible. MICs of omadacycline were significantly higher than those of eravacycline and tigecycline. In summary, cefiderocol, ceftazidime/avibactam and cefepime/zidebactam were more effective against carbapenem-nonsusceptible E. coli and K. pneumoniae than other drugs, highlighting their potential as valuable therapeutics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Real-world experience with dolutegravir (DTG) plus boosted protease inhibitor (bPI) as a two-drug regimen is limited for highly experienced HIV-positive patients with virological failure or intolerance to antiretroviral therapy. Patients receiving DTG plus bPI between September 2016 and June 2019 at 15 designated hospitals for HIV care in Taiwan were retrospectively included in this study. A standardised case record form was used to collect clinical data. The primary endpoint was virological response, defined as achieving or maintaining plasma HIV-RNA <50 copies/mL at Week 48. A total of 77 patients were included; 58 (75.3%) had documented genotypic resistance to 1-4 antiretroviral classes. The most commonly used PI was darunavir (87.0%; 67/77). Seven patients (9.1%) had no virological data at Week 48, including three with loss to follow-up, one severe hyperlipidaemia, one renal failure and cardiovascular disease, one superimposed HBV infection and one death from anal cancer. The virological response rate increased from 59.7% at baseline to 90.9% at Week 24 and 85.7% at Week 48. The only patient (1.3%) with virological failure at Week 48 had poor adherence and baseline low-level resistance to darunavir with resistance-associated mutations at M46L, I50V and V82A. Compared with baseline, mean total cholesterol increased by 20.1 mg/dL and weight by 2.8 kg at Week 48, while the estimated glomerular filtration rate decreased by 14.4 mL/min/1.73m 2 (both P < 0.05). We conclude that a two-drug regimen containing DTG plus bPI was effective in highly-experienced HIV-positive patients, but metabolic impact and weight gain should be closely monitored., (Copyright © 2021. Published by Elsevier Ltd.)

Multicenter surveillance of antimicrobial susceptibility was performed for 235 vancomycin-resistant Enterococcus faecium (VREfm) isolates from 18 Taiwanese hospitals. The minimum inhibitory concentrations (MICs) of eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics were determined using the broth microdilution method. Nearly all isolates of VREfm were not susceptible to teicoplanin, dalbavancin, and telavancin, with susceptibility rates of 0.5%, 1.7% and 0.5%, respectively. Tigecycline and eravacycline were active against 93.2% and 89.7% of the VREfm isolates, respectively. Moreover, the susceptibility rates of quinupristin/dalfopristin, tedizolid, and linezolid were 59.1%, 84.2%, and 77.4%, respectively. Additionally, 94% of the VREfm isolates were classified as susceptible to daptomycin, and the MICs of omadacycline required to inhibit VREfm growth by 50% and 90% were 0.12 and 0.5 mg/L, respectively. Susceptibility rates of VREfm isolates to synthetic tetracyclines and daptomycin were slightly lower and to oxazolidinone-class antibiotics were much lower in Taiwan than those in other parts of the world. Continuous monitoring of VREfm resistance to novel antibiotics, including synthetic tetracyclines, oxazolidinone-class antibiotics, and daptomycin, is needed in Taiwan., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Multicentre surveillance of antimicrobial susceptibility of clinically important Gram-negative bacteria (GNB) from 16 Taiwanese hospitals was performed. Escherichia coli (n = 398), Klebsiella pneumoniae (n = 346), Pseudomonas aeruginosa (n = 252) and Acinetobacter baumannii complex (ABC) (n = 188) bloodstream isolates, non-typhoidal Salmonella (n = 230) and Shigella flexneri (n = 18) from various sources were collected. Antimicrobial MICs were determined using broth microdilution. Genes encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase (VIM), OXA-48-like carbapenemase (OXA-48) as well as mcr-1-5 genes were detected by molecular methods. Rates of carbapenem non-susceptibility were 2.8%, 9.0%, 0.4%, 0%, 10.3% and 48.8% for E. coli, K. pneumoniae, Salmonella, Shigella, P. aeruginosa and ABC, respectively. For carbapenemases, one (0.3%) E. coli harboured bla NDM-1 . Fifteen (4.3%), two (0.6%) and two (0.6%) K. pneumoniae contained bla KPC , bla OXA-48 and bla VIM , respectively. Two (0.5%) E. coli and fourteen (4.0%) K. pneumoniae were non-wild-type according to the colistin MIC. Among Enterobacteriaceae with a colistin MIC ≥ 2 mg/L, mcr-1 was detected in one E. coli, two K. pneumoniae and three Salmonella spp. All three mcr-1-positive Salmonella isolates were collected from community-acquired infections; none of the six mcr-1-positive Enterobacteriaceae were carbapenem-resistant. Carbapenem resistance has increased among clinically important GNB, especially among hospital-acquired infections. bla KPC , especially the bla KPC-2 variant, was detected in approximately one-half of the carbapenem-resistant K. pneumoniae isolates in this study. Although resistance rates to colistin remained low among Enterobacteriaceae, the finding of mcr-1 from different species raises concern of potential dissemination., (Copyright © 2019. Published by Elsevier B.V.)

Candida tropicalis is the second most common Candida species causing fungaemia in Taiwan, and decreased susceptibility to fluconazole has been reported. This study analysed the clinical characteristics of adult patients with C. tropicalis fungaemia and the antifungal susceptibilities of isolates at five tertiary hospitals in Taiwan (1 July 2011 to 30 June 2014). A standardised case record form was used retrospectively to collect demographic, clinical and microbiological characteristics, antifungal treatment and outcomes. MICs of non-duplicate isolates were determined using Sensititre TM YeastOne TM and were interpreted using cut-off values recommended by the CLSI. A total 248 patients were diagnosed over the study period; 30-day crude mortality was 52.0%. Multivariate analysis showed that high Charlson comorbidity index ≥4 (OR = 2.09, 95% CI 1.22-3.59; P = 0.008), neutropenia (OR = 4.61, 95% CI 1.42-15.00; P = 0.011) and treatment with an azole-based regimen (OR = 0.39, 95% CI 0.17-0.90; P = 0.028) were significantly associated with 30-day mortality. A total of 33.9% of isolates were non-susceptible to fluconazole (MIC 50 , 2 mg/L; MIC 90 , 16 mg/L; MIC range, 0.25 to >256 mg/L), whilst 56.9% to voriconazole (MIC 50 , 0.25 mg/L; MIC 90 , 1 mg/L; MIC range, 0.015 to >8 mg/L) according to CLSI clinical breakpoints. There was no significant correlation between overall mortality and MICs of fluconazole or voriconazole. This study showed high mortality in patients with C. tropicalis fungaemia, and azole-based antifungal treatment could improve outcomes regardless of fluconazole MICs of infecting isolates compared with patients without any treatment within 48 h., (Copyright © 2018. Published by Elsevier B.V.)

In 2009, the Study for Monitoring Antimicrobial Resistance Trends (SMART) was expanded to include surveillance of Gram-negative pathogens causing urinary tract infections (UTIs) in the Asia-Pacific region. A total of 1762 isolates were collected from 38 centers in 11 countries from patients with UTIs in 2009 and 2010. In vitro susceptibilities were determined by the broth microdilution method and susceptibility profiles were determined using minimum inhibitory concentration (MIC) interpretive criteria, as recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2010 (M100-S20), in 2011 (M100-S21), and in 2012 (M100-S22). Enterobacteriaceae comprised 86.0% of the isolates, of which Escherichia coli (56.5%) and Klebsiella pneumoniae (13.8%) were the two most common species. Amikacin was the most effective antibiotic (91.7%), followed by ertapenem (86.9%), imipenem (86.6%), and piperacillin-tazobactam (84.9%). Rates of susceptibility were 50.3% for cefoxitin and ranged from 50.3% to 74.2% for the third- and fourth-generation cephalosporins. For ciprofloxacin and levofloxacin, the susceptibility rates were 51.4% and 54.4%, respectively. Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae comprised 28.2% of all isolates. We also found a high rate of resistance to carbapenems among Acinetobacter baumannii and Pseudomonas aeruginosa causing UTI. Interestingly, according to 2012 CLSI breakpoints, approximately 33.4% of ESBL producers were still susceptible to ceftazidime. However, this in vitro efficacy of ceftazidime needs to be validated in vivo by clinical data. The lowered CLSI interpretive breakpoints for piperacillin-tazobactam, carbapenems, and some cephalosporins in 2011-2012 for Enterobacteriaceae resulted in an approximate 5% drop in susceptibility rates for each drug, with the exception of imipenem for which the susceptibility rate dropped from 99.4% according to 2010 criteria to 91.2% according to 2011 criteria. With the updated CLSI criteria, the antimicrobial resistance threat from UTI pathogens in the Asia Pacific area was revealed to be more prominent., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We investigated the trend in resistance to carbapenems among isolates of Enterobacteriaceae that had been collected from patients with intra-abdominal infections at five medical centers in Taiwan from 2006 to 2010 and evaluated the correlation between resistance to carbapenems and consumption of said agents as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, the usage of ertapenem and that of total carbapenems (ertapenem, imipenem, and meropenem) increased significantly from 6.13 to 13.38 defined daily doses per 1000 patient-days for ertapenem and from 20.43 to 34.25 defined daily doses per 1000 patient-days for total carbapenems. The most common species were Escherichia coli (n = 1095), Klebsiella spp. (n = 663), and Enterobacter spp. (n = 202). The susceptibility of all isolates to ertapenem and to imipenem varied during the study period. For ertapenem, the rates of nonsusceptibility ranged from 3.5% to 10.3% and those for imipenem ranged from 3.5% to 10.7%. Although the use of carbapenems increased during the study period, there was no marked increase in resistance to carbapenems. Continuous monitoring of resistance trends is necessary so that antimicrobial prescription policies can be adjusted and infection control intervention programs can be implemented., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This study examined the rates of susceptibility to third-generation cephalosporins and carbapenems among Enterobacteriaceae isolates that had been obtained from patients with intraabdominal infections in the Asia-Pacific region as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Susceptibility profiles obtained using 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints were compared with those obtained using the 2011 CLSI breakpoints. From 2002 to 2010, Escherichia coli and Klebsiella pneumoniae together accounted for more than 60% of the 13714 Enterobacteriaceae isolates analyzed during the study period. Extended-spectrum β-lactamase (ESBL) producers comprised 28.2% of E. coli isolates and 22.1% of K. pneumoniae isolates in the Asia-Pacific region, with China (55.6% and 33.7%, respectively) and Thailand (43.1% and 40.7%, respectively) having the highest proportions of ESBL producers. Based on the 2011 CLSI criteria, 77.2% of the Enterobacteriaceae isolates, 40.4% of ESBL-producing E. coli, and 25.2% of ESBL-producing K. pneumoniae isolates were susceptible to ceftazidime. Carbapenems showed in vitro activity against >90% of Enterobacteriaceae isolates in all participating countries, except for ertapenem in South Korea (susceptibility rate 82.2%). Marked differences (>5%) in susceptibility of ESBL-producing E. coli and K. pneumoniae isolates to carbapenems were noted between the profiles obtained using the 2009 CLSI criteria and those using the 2011 CLSI criteria. Continuous monitoring of antimicrobial resistance is necessary in the Asia-Pacific region., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide surveillance program designed to longitudinally monitor the in vitro activity of antimicrobial agents against pathogens that cause intra-abdominal infections (IAIs). In this study, trends in antimicrobial resistance during the period 2006 to 2010 were analyzed at five tertiary-care hospitals in Taiwan. Enterobacteriaceae accounted for the majority (80.9%) of the 2417 Gram-negative isolates, and the two most common species were Escherichia coli (38.8%) and Klebsiella pneumoniae (23.5%). The rates of susceptibility of Enterobacteriaceae isolates to cephalosporins decreased during the study period. Although carbapenems, fluoroquinolones, piperacillin-tazobactam, and amikacin were active in vitro against more than 80% of the Enterobacteriaceae isolates, the activity of carbapenems declined during the study period. Extended-spectrum β-lactamase (ESBL) production in E. coli was steady, but that in K. pneumoniae decreased during the study period. The rate of ESBL-producing species was three-fold higher among patients with nosocomial IAIs than among patients with community-acquired IAIs. The majority of isolates from liver were K. pneumoniae (69%) and very few of those isolates were ESBL producers (0.9%). Pseudomonas aeruginosa (9.3%) and Acinetobacter baumannii (3.8%) were the two most common non-Enterobacteriaceae. P. aeruginosa showed improved susceptibility, whereas A. baumannii showed a rapid development of resistance during the study period. There was marked geographic variation in resistance patterns of the isolates obtained during the study period. Northern Taiwan had the highest rate of ESBL producers and the highest rate of ceftazidime resistance among P. aeruginosa isolates. Central Taiwan had the lowest rate of ESBL producers but the highest rates of carbapenem resistance among P. aeruginosa and A. baumannii isolates. Continuous monitoring and regular updates of epidemiological data are needed to guide appropriate empiric antimicrobial therapy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We investigated the trends in antimicrobial resistance among species of Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan during the period 2006-2010 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, 1032 isolates of Gram-negative bacilli that had been collected from patients with hepatobiliary infections were tested for susceptibility to 12 antimicrobial agents in accordance with the Clinical and Laboratory Standards Institute guidelines. Enterobacteriaceae accounted for the majority (n = 874, 84.7%) of isolates and Escherichia coli was the most common pathogen (n = 323, 31.3%). There were significantly more E. coli (P = 0.001) and Proteus mirabilis (P = 0.031) isolates collected from patients who had been hospitalized for less than 48 h and significantly more Serratia marcescens (P = 0.035) and Pseudomonas aeruginosa (P = 0.008) isolates collected from patients who had been hospitalized for 48 h or longer. The prevalence of extended-spectrum β-lactamase (ESBL)-producing pathogens was low. The decline in susceptibility rates with time was remarkable for ceftazidime (P = 0.036), ciprofloxacin (P = 0.029), and levofloxacin (P = 0.018). The most effective antibiotics, i.e., those that were active against more than 90% of Enterobacteriaceae, were amikacin, cefepime, imipenem, ertapenem, and piperacillin-tazobactam. Susceptibility of P. aeruginosa to anti-pseudomonal agents was greater than 80%. In this study, we found an overall increase in resistance to antimicrobial agents among Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan. Surveillance of antimicrobial susceptibility and updates of treatment guidelines are recommended to help achieve optimal therapy for patients with hepatobiliary infections., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance study designed to monitor resistance trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from intra-abdominal infections. During 2003-2010, a total of 20710 GNB isolates were collected at medical centers in China, Hong Kong, Korea, New Zealand, and Taiwan. The susceptibility profiles of 2252 isolates of non-Enterobacteriaceae GNB were determined. At least 10 isolates of a given organism were required for that organism to be included in the analysis. Pseudomonas aeruginosa was the leading organism (49.2% of non-Enterobacteriaceae GNB), followed by Acinetobacter baumannii (21.5%), Aeromonas spp. (11.6%), and Stenotrophomonas maltophilia (9.1%). All the other species/genera made up less than 2%. The rates of susceptibility of the four major organisms were examined for two different time periods and according to whether the isolates had been obtained <48 h after hospitalization or ≥ 48 h after hospital admission. P. aeruginosa, Aeromonas spp., and S. maltophilia showed sustained levels of susceptibility to several antimicrobial agents in the two time periods, whereas A. baumannii exhibited very high rates of resistance to most antimicrobial agents including imipenem. Nosocomial P. aeruginosa and A. baumannii were more resistant than community-acquired pathogens, although this was not the case for Aeromonas spp. and S. maltophilia. Worldwide and regional surveillance is necessary to guide empirical antimicrobial therapy for infections due to non-Enterobacteriaceae GNB., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Integrons, efflux pumps, phosphoglucomutase (SpgM), and melanin and biofilm formation were investigated in 40 multidrug-resistant (MDR) and 30 non-MDR Stenotrophomonas maltophilia isolates recovered from patients treated at National Taiwan University Hospital (Taipei, Taiwan). Class 1 integrons were clearly associated with multidrug resistance. Sequencing data revealed that aminoglycoside-modifying genes occurred most frequently in the integron and disclosed a new bla(IMP-8)/aac6-II/aadA5 gene cassette. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was performed to assess the expression of Sme efflux pumps and SpgM in S. maltophilia. MDR isolates exhibited hyperexpression of SmeABC, and SmeDEF and SpgM were more frequently found in MDR isolates than non-MDR isolates. In addition, the ability of MDR isolates to form melanin-like pigment and biofilm was also greater than that of the non-MDR isolates. The SmeABC or SmeDEF pump was shown to be associated with resistance to all agents tested. The presence of an integron as well as production of pigment and biofilm was also responsible for resistance against eight, six and six of the tested agents, respectively. High SpgM expression was associated with resistance to only three of the tested agents. These findings define the important roles of integrons, efflux pumps, and melanin-like pigment and biofilm formation in the multidrug resistance of S. maltophilia. MDR isolates possessed more resistance mechanisms than susceptible strains., (Copyright 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)