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Objectives: To investigate the susceptibility of imipenem-non-susceptible Escherichia coli (INS-EC), Klebsiella pneumoniae (INS-KP), Acinetobacter baumannii (INS-AB) and Pseudomonas aeruginosa (INS-PA) to novel antibiotics., Methods: MICs were determined using the broth microdilution method. Carbapenemase and ESBL phenotypic testing and PCR for genes encoding ESBLs, AmpCs and carbapenemases were performed., Results: Zidebactam, avibactam and relebactam increased the respective susceptibility rates to cefepime, ceftazidime and imipenem of 17 INS-EC by 58.8%, 58.8% and 70.6%, of 163 INS-KP by 77.9%, 88.3% and 76.1% and of 81 INS-PA by 45.7%, 38.3% and 85.2%, respectively. Vaborbactam increased the meropenem susceptibility of INS-EC by 41.2% and of INS-KP by 54%. Combinations of β-lactams and novel β-lactamase inhibitors or β-lactam enhancers (BLI-BLE) were inactive against 136 INS-AB. In 58 INS-EC and INS-KP with exclusively blaKPC-like genes, zidebactam, avibactam, relebactam and vaborbactam increased the susceptibility of the partner β-lactams by 100%, 96.6%, 84.5% and 75.9%, respectively. In the presence of avibactam, ceftazidime was active in an additional 85% of 20 INS-EC and INS-KP with exclusively blaOXA-48-like genes while with zidebactam, cefepime was active in an additional 75%. INS-EC and INS-KP with MBL genes were susceptible only to cefepime/zidebactam. The β-lactam/BLI-BLE combinations were active against INS-EC and INS-KP without detectable carbapenemases. For INS-EC, INS-KP and INS-AB, tigecycline was more active than omadacycline and eravacycline but eravacycline had a lower MIC distribution. Lascufloxacin and delafloxacin were active in <35% of these INS isolates., Conclusions: β-Lactam/BLI-BLE combinations were active in a higher proportion of INS-EC, INS-KP and INS-PA. The susceptibility of novel fluoroquinolones and tetracyclines was not superior to that of old ones., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sequence type (ST) 131 is a multidrug-resistant pandemic lineage of E. coli responsible for extraintestinal infections. Few surveillance data of ST131 included all antimicrobial-susceptible and -resistant isolates or focused on community-acquired urinary tract infection (UTI). From a population-based surveillance pool of 2997 outpatient urine E. coli isolates, 542 were selected for detection of ST131 based on ciprofloxacin and/or cefotaxime resistance. Pulsed-field gel electrophoresis (PFGE) was performed on all ST131 isolates to further determine their relatedness. The estimated overall ST131 prevalence in this community UTI cohort increased from 11.2% (in 2002-2004), 12.2% (in 2006-2008), 13.6% (in 2010-2012), to 17.4% in 2014-2016 ( p < 0.01). In the ciprofloxacin-resistant/cefotaxime-resistant group, ST131 increased from 33.3% in 2002-2004 to 72.1% in 2014-2016 ( p < 0.01). In the ciprofloxacin-resistant/cefotaxime-susceptible group, ST131 was found in 24.3% overall without significant increase in its prevalence over time. PFGE showed emergence of a cluster of ciprofloxacin-resistant/cefotaxime-resistant ST131 carrying Gr. 1 CTX-M ESBL in 2014-2016, especially 2016. Multivariate analysis revealed that age (≥65 y.o) and ciprofloxacin resistance were independent factors associated with ST131. This longitudinal surveillance showed that ciprofloxacin-resistant/cefotaxime-susceptible ST131 has been circulating in the community since 2002 but ciprofloxacin-resistant/cefotaxime-resistant ST131 increased rapidly in the later years.

The aim of this study is to establish an effective early intervention mechanism for construction engineering to prevent electrocution while improving labor safety and reducing the casualty risk. This study used narrative text analysis and the Haddon Matrix for data collection, and analyzed the causes from the 113 electrocution deaths among in the construction industry, the exhaustive chi-square automatic interaction detector algorithm was employed the segmentation of the correlations. Based on the theory of inventive problem solving, through IDEF0 (ICAM DEFinition) for function modeling was designed the early intervention mechanism. This study revealed the operating features related to electric shock hazards. Early intervention was introduced to reduce the relevant risks and establish safety mechanisms. The first contribution of this study is the determination of hazard correlations between operating features and conductive media, and entry point for the prevention of electrocutions. The second contribution is the suggestion of the establishment of inspection stations for electric tools, thereby ensuring that the portable power tools are safe. The final contribution is the joint application of TRIZ (Teoriya Resheniya Izobreatatelskikh Zadatch) and IDEF0, which establishing the pre-entry testing, strengthening safety mechanisms.

Objectives: We aimed to determine susceptibilities of Elizabethkingia spp. to 25 commonly tested and 8 novel antibiotics, and to compare the performance of different susceptibility testing methods., Methods: Clinical isolates of Elizabethkingia spp., Chryseobacterium spp. and Flavobacterium spp. collected during 2002-18 (n = 210) in a nationwide surveillance programme in Taiwan were speciated by 16S rRNA sequencing. MICs were determined by broth microdilution. The broth microdilution results of 18 common antibiotics were compared with those obtained by the VITEK 2 automated system., Results: Among the Elizabethkingia spp. identified (n = 108), Elizabethkingia anophelis was the most prevalent (n = 90), followed by Elizabethkingia meningoseptica (n = 7) and Elizabethkingia miricola cluster [E. miricola (n = 6), Elizabethkingia bruuniana (n = 3) and Elizabethkingia ursingii (n = 2)]. Most isolates were recovered from respiratory or blood specimens from hospitalized, elderly patients. PFGE showed two major and several minor E. anophelis clones. All isolates were resistant to nearly all the tested β-lactams. Doxycycline, minocycline and trimethoprim/sulfamethoxazole inhibited >90% of Elizabethkingia spp. Rifampin inhibited E. meningoseptica (100%) and E. anophelis (81.1%). Fluoroquinolones and tigecycline were active against E. meningoseptica and E. miricola cluster isolates. Novel antibiotics, including imipenem/relebactam, meropenem/vaborbactam, ceftazidime/avibactam, cefepime/zidebactam, delafloxacin, eravacycline and omadacycline were ineffective but lascufloxacin inhibited half of Elizabethkingia spp. The very major discrepancy rates of VITEK 2 were >1.5% for ciprofloxacin, moxifloxacin and vancomycin. Major discrepancy rates were >3% for amikacin, tigecycline, piperacillin/tazobactam and trimethoprim/sulfamethoxazole., Conclusions: MDR, absence of standard interpretation criteria and poor intermethod concordance necessitate working guidelines to facilitate future research of emerging Elizabethkingia spp., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In Taiwan, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006 and a PCV13 national childhood catchup program was implemented in 2013. To delineate the trend of serotype distribution and antimicrobial susceptibility following vaccination programs, we investigated a total of 1845 Streptococcus pneumoniae isolates collected biennially between 2002 and 2018 over a 3-month period from 25 hospitals. The number of isolates collected over the years decreased significantly in all age groups, from a total of 320 isolates in 2002 (pre-PCV), to 196 in 2010 (post-PCV7/pre-PCV13), to 89 in 2018 (post-PCV13). Overall, PCV7/PCV13 serotypes comprised 66.9%/76.3%, 53.1%/78.1%, and 15.7%/31.5% of isolates in 2002, 2010, and 2018, respectively. The leading serotypes in the pre-PCV era were 23F, 19F, 6B, and 14, while serotype 19A predominated in the post-PCV7/pre-PCV13 era, but non-vaccine serotypes (NVT) 15A (18.0%) and 23A (15.7%) surpassed 19A (10.1%) to become the top two leading serotypes in 2018. All the major serotypes, including the emergent serotypes 15A and 23A, were multidrug-resistant with high rates of non-susceptibility to β-lactam (except serotype 3) and several non-β-lactam agents. PFGE and MLST revealed that while meropenem-susceptible serotype 15A-ST3058 isolates and a serotype 23A-ST338 clone existed in earlier years, rise and spread of meropenem-non-susceptible serotype 15A-ST63 and serotype 23A-ST166 clones occurred in recent years. We conclude that successive implementation of PCVs has led to a marked decrease in pneumococcal isolate burden, but the replacement by meropenem-non-susceptible NVT 15A and 23A highlights the need for continued local surveillance to track pneumococcal evolution in each region to help vaccine polyvalency decisions., (Copyright © 2020 Wu, Lai, Huang, Shiau, Wang and Lauderdale.)

Objectives: This study investigated the trend in antimicrobial resistance among group B Streptococcus (GBS) from a national surveillance programme in Taiwan and delineated characteristics of and factors associated with levofloxacin-resistant isolates., Methods: Clinical isolates of all sample types and patient groups were collected from multiple hospitals biennially between 2002 and 2012. Susceptibilities to different antibiotics were determined by broth microdilution. Molecular studies of levofloxacin-resistant isolates included serotyping, PFGE, mutations in the QRDRs and MLST., Results: A total of 1559 isolates were tested and all remained susceptible to penicillin, cephalosporins, meropenem and vancomycin. However, levofloxacin resistance increased from 2.2% (range 0%-3.3%) in 2002-06 to 6.2% (5.9%-7.5%) in 2008-12 (P = 0.016). Among the 88 levofloxacin-resistant isolates, the majority (79.5%) had the GyrA(S81L)+ParC(S79F/Y) double mutations and most (54.5%) were also resistant to clindamycin, erythromycin and tetracycline. The predominant genotype of the levofloxacin-resistant isolates was ST19/serotype III (43.2%). Four previously unreported genotypes, ST1 and its single-locus variants (ST920 and ST922)/serotype VI (28.4%) and ST1/serotype II (18.2%), were found to have circulated locally. Serotype III isolates were predominately from urine and female genital tract specimens and <65-year-old adult outpatients, while serotype II and VI isolates were mostly from respiratory and urine samples and >65-year-old inpatients. Multivariate analysis revealed that elderly age and respiratory samples were independent factors associated with levofloxacin resistance., Conclusions: Multiclonal emergence and dissemination of levofloxacin-resistant GBS isolates occurred in healthcare and community settings in Taiwan. Continuous molecular-level surveillance is important to detect new epidemic trends., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Human immuodeficency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) and community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) have increased in recent years in Taiwan. This study was undertaken to determine the prevalence of and risk factors for nasal and oral S. aureus and MRSA colonization among contemporary HIV-infected populations. Clinical variables for S. aureus and MRSA colonization among HIV-infected outpatients from three hospitals were analyzed and compared with those for oral Candida colonization. Genetic characteristics of MRSA isolates were analyzed. A total of 714 patients were screened for nasal S. aureus colonization, and a subset of 457 patients were also screened for oral S. aureus colonization. Of all patients, 79.4% were receiving HAART, and their mean CD4 count was 472 cells/mm 3 . The colonization rates in the oral cavity, nasal cavity, and at either site were 18.8%, 31.7%, and 36.8%, respectively, for S. aureus , and 3.1%, 4.4%, and 5.5%, respectively, for MRSA. These rates were all much lower than the previously reported rate of oral Candida colonization (52.4%). By multivariate analysis, a suppressed viral load (<200 copies/mL) protected against oral S. aureus , MRSA, and Candida colonization, and recent use of antibacterial agents protected against oral and nasal S. aureus colonization. Recent incarceration increased the risk of nasal MRSA colonization, while recent hospitalization, tuberculosis, older age, and intravenous drug use increased the risk of oral Candida colonization. Candida spp. did not augment S. aureus or MRSA colonization in the oral cavity. Most of the 41 MRSA isolates recovered belonged to the SCC mec IV/ pvl -negative (51.2%) and V T / pvl -positive (26.8%) ST59 local prevalent CA-MRSA clones. Distinct carriage rates demonstrated here suggested that mucosal immunity against colonization might differ in terms of microbes and sites. A decreased risk in oral carriage of MRSA and Candida might be a benefit of HAART.

The pks gene cluster encodes enzymes responsible for the synthesis of colibactin, a genotoxin that has been shown to induce DNA damage and contribute to increased virulence. The present study investigated the prevalence of pks in clinical K. pneumoniae isolates from a national surveillance program in Taiwan, and identified microbiological and molecular factors associated with pks-carriage. The pks gene cluster was detected in 67 (16.7%) of 400 isolates from various specimen types. Multivariate analysis revealed that isolates of K1, K2, K20, and K62 capsular types (p < 0.001), and those more susceptible to antimicrobial agents (p = 0.001) were independent factors strongly associated with pks-carriage. Phylogenetic studies on the sequence type (ST) and pulsed-field gel electrophoresis patterns indicated that the pks-positive isolates belong to a clonal group of ST23 in K1, a locally expanding ST65 clone in K2, a ST268-related K20 group, and a highly clonal ST36:K62 group. Carriage of rmpA, iutC, and ybtA, the genes associated with hypervirulence, was significantly higher in the pks-positive isolates than the pks-negative isolates (95.5% vs. 13.2%, p < 0.001). Further studies to determine the presence of hypervirulent pks-bearing bacterial populations in the flora of community residents and their association with different disease entities may be warranted.

Drug-resistant Klebsiella pneumoniae, especially extended-spectrum β-lactamase (ESBL)- and/or AmpC β-lactamase-producing strains, is an emerging problem worldwide. However, few data focusing on drug susceptibility of K. pneumoniae from community is available. In this study, we analyzed 1016 K. pneumoniae isolates from outpatients or those visiting emergency rooms collected during 2002-2012 from Taiwan Surveillance of Antimicrobial Resistance program. Significantly decreased susceptibilities to 3 rd generation cephalosporins and ciprofloxacin were found during the study period. By 2012, susceptibility to cefotaxime and ciprofloxacin was 83.6% and 81.6%, respectively. The prevalence of ESBL-producers increased from 4.8% in 2002 to 11.9% in 2012 (P = 0.012), while that of AmpC β-lactamase-producers increased from 0% to 9.5% in the same period (P < 0.001). Phylogenic analysis of the ESBL and AmpC-β-lactamase-producers by pulsed-field gel electrophoresis and multi-locus sequence typing revealed wide genetic diversity even among the most common sequence type 11 isolates (33.0%). By multivariate analysis, later study year, elderly, and urine isolates were associated with carriage of ESBL genes, while only urine isolates were associated with carriage of AmpC β-lactamase genes. Further studies are needed to determine which antibiotics are reasonable empirical therapy options for patients presenting with severe sepsis that might be caused by K. pneumoniae.

Longitudinal nationwide surveillance data on antimicrobial non-susceptibility and prevalence of extended-spectrum β-lactamases (ESBLs) as well as AmpC β-lactamases producers among Escherichia coli from different sources in the community settings are limited. Such data may impact treatment practice. The present study investigated E. coli from outpatients and patients visiting emergency rooms collected by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program. A total of 3481 E. coli isolates were studied, including 2153 (61.9%) from urine and 1125 (32.3%) from blood samples. These isolates were collected biennially between 2002 and 2012 from a total of 28 hospitals located in different geographic regions of Taiwan. Minimum inhibitory concentrations (MIC) were determined using methods recommended by the Clinical Laboratory Standards Institute (CLSI). The prevalence and factors associated with the presence of ESBL and AmpC β-lactamase-producers were determined. Significant increases in non-susceptibility to most β-lactams and ciprofloxacin occurred during the study period. By 2012, non-susceptibility to cefotaxime and ciprofloxacin reached 21.1% and 26.9%, respectively. The prevalence of ESBL- and AmpC- producers also increased from 4.0% and 5.3%, respectively, in 2002-2004, to 10.7% for both in 2010-2012 (P < 0.001). The predominant ESBL and AmpC β-lactamase genes were CTX-M and CMY-types, respectively. Non-susceptibility of urine isolates to nitrofurantoin remained at around 8% and to fosfomycin was low (0.7%) but to cefazolin (based on the 2014 CLSI urine criteria) increased from 11.5% in 2002-2004 to 23.9% in 2010-2012 (P <0.001). Non-susceptibility of isolates from different specimen types was generally similar, but isolates from elderly patients were significantly more resistant to most antimicrobial agents and associated with the presence of ESBL- and AmpC- β-lactamases. An additional concern is that decreased ciprofloxacin susceptibility (MIC 0.12-1 mg/L) was as high as 25% in isolates from all age groups, including those from pediatric patients. Our data indicated that there is a need to re-evaluate appropriate treatment selection for community-acquired infections in Taiwan. Identification of community reservoirs of multidrug-resistant E. coli is also warranted.

Background: Longitudinal nationwide data on antimicrobial susceptibility in Proteus mirabilis from different sources are rare. The effects of the revised Clinical and Laboratory Standards Institute (CLSI) β-lactam breakpoints on susceptibility rates and on detecting extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase-producers in this species are also seldom evaluated. The present study analyzed data from the Taiwan Surveillance of Antimicrobial Resistance program to address these issues., Methods: Isolates were collected biennially between 2002 and 2012 from 25 to 28 hospitals in Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. All isolates with aztreonam, ceftazidime, or cefotaxime MIC ≥ 2 mg/L were checked for the presence of ESBL by CLSI confirmatory test and subjected to ESBL and AmpC β-lactamases gene detection by PCR. Univariate and multivariate analyses were performed., Results: Between 2002 and 2012, a total of 1157 P. mirabilis were studied. Susceptibility to cefotaxime, ceftazidime, and ciprofloxacin decreased significantly during the past decade, from 92.6% to 81.7%, 100% to 95.2%, and 80.1% to 53.8%, respectively (P < 0.01). The revised CLSI breakpoints had significant impact on susceptibility to cefazolin (2009 vs. current breakpoints, 71.9% vs. 0.9%) and imipenem (99.8% vs. 55.1%) (P < 0.001 for both). However, using the 2014 cefazolin breakpoints for urinary tract infections, 81.2% of the urine isolates were susceptible. Susceptibilities of isolates from different specimen types were mostly similar but outpatient isolates were more susceptible than inpatient isolates. The overall prevalence of ESBL- and AmpC- producers was 8.2% and 4.7%, respectively, but AmpC carriage increased significantly over the years (from 0 to 7.0%, P < 0.001). ESBL and AmpC β-lactamase-producers were more likely to be found in elderly and ICU patients. The predominant ESBL and AmpC β-lactamase genes were CTX-M- and CMY- types, respectively., Conclusions: A significant decrease in susceptibility to 3rd-generation cephalosporins and ciprofloxacin occurred in P. mirabilis from Taiwan in the past decade. The prevalence of ESBL remained stable but AmpC β-lactamase-producing P. mirabilis increased significantly. Cefotaxime was a better surrogate than ceftazidime for predicting the presence of these β-lactamases. Continuous surveillance on antimicrobial resistance and associated resistance mechanisms in P. mirabilis is warranted.

Levofloxacin resistance in Haemophilus influenzae has increased significantly in Taiwan, from 2.0% in 2004 to 24.3% in 2010 (p<0.001). Clinical and molecular investigations of 182 levofloxacin-resistant isolates revealed that the increase was mainly the result of the spread of several clones in the elderly population in different regions.

Our multicenter nationwide surveillance data indicated that erythromycin (ERY) resistance among group A Streptococcus (GAS) isolates in Taiwan declined from 53.1% in 1998 and 2000 to 14.6% in 2002 and 2004 and 10.7% in 2006 to 2010 (P < 0.01). The present study aimed to assess the epidemiology of GAS in Taiwan and identify factors associated with ERY resistance. All 127 ERY-resistant (ERY(r)) isolates and 128 randomly selected ERY-susceptible (ERY(s)) isolates recovered from 1998 to 2010 were emm typed. ERY(r) isolates were also characterized by ERY resistance phenotype and mechanisms and pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing was performed on selected ERY(r) isolates. The predominant emm types in ERY(r) isolates were emm22 (n = 33, 26.0%), emm12 (n = 24, 18.9%), emm4 (n = 21, 16.5%), and emm106 (n = 15, 11.8%). In ERY(s) isolates, emm12 (n = 27, 21.9%), emm1 (n = 18, 14.1%), emm106 (n = 16, 12.5%), and emm11 (n = 9, 7.1%) predominated. The most common ERY resistance phenotype was the M phenotype (resistant to macrolides) (70.9%), with all but one isolate carrying mef(A), followed by the constitutive macrolide-lincosamide-streptogramin B resistance (cMLSB) phenotype (26.8%), with isolates carrying erm(B) or erm(TR). ERY(r) isolates of the emm12-sequence type 36 (ST36) lineage with the cMLSB phenotype were mostly present before 2004, while those of the emm22-ST46 lineage with the M phenotype predominated in later years. Recovery from respiratory (throat swab) specimens was an independent factor associated with ERY resistance. emm1 and emm11 GAS isolates were significantly associated with ERY(s), while emm22 was detected only in ERY(r) GAS. In addition, emm106 isolates were prevalent among the abscess/pus isolates, whereas emm12 isolates were strongly associated with a respiratory (throat) origin. In addition to identifying factors associated with ERY resistance in GAS, our study provides helpful information on the changing GAS epidemiology in Taiwan.

We consider a single-machine two-agent problem where the objective is to minimize a weighted combination of the total completion time and the total tardiness of jobs from the first agent given that no tardy jobs are allowed for the second agent. A branch-and-bound algorithm is developed to derive the optimal sequence and two simulated annealing heuristic algorithms are proposed to search for the near-optimal solutions. Computational experiments are also conducted to evaluate the proposed branch-and-bound and simulated annealing algorithms.

Longitudinal national data on resistance in Enterococcus faecalis and E. faecium from different sources in Taiwan are rare. The present study analyzed data from the Taiwan Surveillance of Antimicrobial Resistance program to address this issue. Between 2002 and 2010, a total of 1696 E. faecalis and 452 E. faecium isolates were studied. Although these 2 species together comprised similar percentages of all enterococci in each study year (94.1-97.2%, P = 0.19), the proportion of E. faecium increased from 12.4% in 2002 to 27.3% in 2010 (P < 0.001). The most noteworthy change in susceptibilities of these 2 species was vancomycin resistance in E. faecium (VREfm), which increased from 0.3% in 2004 to 24.9% in 2010 (P < 0.001). VREfm prevalence differed significantly between geographic regions, patient age groups, and locations. Multidrug resistance was very common in both species even in isolates from outpatients (82.7% for E. faecalis and 98.1% for E. faecium), at rates similar to those from intensive care unit (ICU) and non-ICU patients (80.5-80.9% in E. faecalis and 97.2-98.6% in E. faecium). Nonsusceptibility to linezolid was <0.5% in both species. All tested isolates were susceptible to daptomycin. Continuous surveillance of VRE prevalence and survey of community reservoirs of multidrug-resistant enterococci are warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Acinetobacter baumannii complex (ABC) has emerged as an important pathogen causing a variety of infections. Longitudinal multicenter surveillance data on ABC from different sources in Taiwan have not been published. Using data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) conducted biennially, we investigated the secular change in resistance of 1640 ABC from 2002 to 2010 (TSAR period III to VII) to different antimicrobial agents and identified factors associated with imipenem-resistant and extensively drug-resistant ABC (IRABC and XDRABC)., Methods: Isolates were collected by TSAR from the same 26 hospitals located in all 4 regions of Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. Isolates nonsusceptible to all tested aminoglycosides, fluoroquinolones, β-lactam, β-lactam/β-lactam inhibitors, and carbapenems were defined as extensively drug-resistant (XDR). Multivariate logistic regression analysis was performed to assess the relationship between predictor variables among patients with resistant ABC and patients with non-resistant ABC., Results: The prevalence of IRABC increased from 3.4% in 2002 to 58.7% in 2010 (P < 0.001; odds ratio [OR], 2.138; 95% confidence interval [CI], 1.947 to 2.347) and that of XDRABC increased from 1.3% in 2002 to 41.0% in 2010 (P < 0.001; OR, 1.970; 95% CI, 1.773-2.189). The rates of non-susceptibility to other antimicrobial agents remained high (>55%) over the years with some fluctuations before and after TSAR V (2006) on some agents. Multivariate analysis revealed that recovery from elderly patients, origins other than blood, from ICU settings, or geographic regions are independent factors associated with IRABC and XDRABC. Although the prevalence of XDRABC increased in all four regions of Taiwan over the years, central Taiwan had higher prevalence of XDRABC starting in 2008. Susceptibility to polymyxin remained high (99.8%)., Conclusions: This longitudinal multicenter surveillance program revealed significant increase and nationwide emergence of IRABC and XDRABC in Taiwan over the years. This study also identified factors associated with IRABC and XDRABC to help guide empirical therapy and at-risk groups requiring more intense interventional infection control measures with focused surveillance efforts.

Although the presence of mecA is the genotypic determinant of methicillin-resistant Staphylococcus aureus (MRSA), certain MRSA strains, especially community-associated MRSA (C-MRSA), can display an oxacillin MIC in the Clinical and Laboratory Standards Institute susceptible breakpoint range (≤ 2 μg/ml). Among 91 and 180 isolates thought to be methicillin-susceptible S. aureus (MSSA) with oxacillin MICs of 2 and 1 μg/ml as determined by the Sensititre broth microdilution test initially, 52 (57.1%) and 6 (3.3%), respectively, were mecA positive. These mecA-positive low-oxacillin-MIC isolates belong to the dominant Taiwan C-MRSA clone (clonal complex [CC] 59), 56 of which carried SCCmec type V and were pvl positive, and 43 of which belonged to spa CC t437. All 271 isolates were retested by Sensititre, as well as by Vitek II and disk diffusion (DD). Based on the oxacillin results, the sensitivities of the Sensititre, Vitek II, and DD methods were 48.3% (28/58), 46.6% (27/58), and 89.6% (52/58), respectively. Although cefoxitin was better at detecting these isolates, 12.1, 10.4, and 5.2% of these isolates were still misidentified as MSSA by Sensititre, Vitek II, and DD, respectively. These results highlight the difficulty in the accurate identification of MRSA with borderline oxacillin MICs in the CC59:SCCmec V clone, which likely has contributed to its spread in the health care and community settings. Since this clone has now been detected in other countries, and since other C-MRSA lineages have also been found to have low-level β-lactam resistance, the findings of the present study may be relevant to other regions. Further studies are warranted to determine the extent and clinical impact of such misidentification.

Background: Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in debilitated hosts. Clinical management of S. maltophilia is challenging due to its intrinsic resistance to a variety of antibiotics. This study investigated the trend and prevalence of antimicrobial resistance in S. maltophilia from a nationwide surveillance study in Taiwan., Methods: S. maltophilia isolates were collected biennially between 1998 and 2008 as part of the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program from medical centers and regional hospitals throughout Taiwan. Minimal inhibitory concentrations (MIC) were determined using the Clinical and Laboratory Standards Institute reference broth microdilution method., Results: A total of 377 non-duplicate S. maltophilia isolates were collected from 38 hospitals. The majority of the isolates were from the respiratory tract (256, 67.9%), followed by blood (48, 12.7%). Overall, 376 (99.7%) isolates were susceptible to minocycline, 362 (96%) to tigecycline, 311 (82.5%) to trimethoprim/sulfamethoxazole (TMP-SMX), 300 (79.6%) to levofloxacin, 92 (24.4%) to ceftazidime, and 70 (18.6%) to ticarcillin-clavulanic acid. The MIC(50)/MIC(90) of minocycline, tigecycline, TMP-SMX, levofloxacin, ceftazidime, and ticarcillin-clavulanic acid, were ≤0.5/1 μg/mL, 0.25/1 μg/mL, ≤0.25/8 μg/mL, 1/4 μg/mL, 32/128 μg/mL, and 64/128 μg/mL, respectively. A trend of increased non-susceptibility to levofloxacin (p=0.014) was observed over the 10-year study period. Compared to TMP-SMX-susceptible isolates, TMP-SMX-resistant isolates were less susceptible to levofloxacin (54.5% vs. 84.9%, p<0.001)., Conclusion: In this 10-year study, minocycline and TMP-SMX remained the two antimicrobials with better in vitro activities against S. maltophilia than ceftazidime, levofloxacin, and ticarcillin-clavulanic acid. The activity of levofloxacin against S. maltophilia in Taiwan declined during the past 10 years., (Copyright © 2011. Published by Elsevier B.V.)

The in vitro antibacterial activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, against 770 clinical isolates were investigated. Nemonoxacin (tested as its malate salt, TG-875649) showed better in vitro activity than ciprofloxacin and levofloxacin against different species of staphylococci, streptococci, and enterococci, Neisseria gonorrhoeae, and Haemophilus influenzae. The in vitro activity of TG-875649 was also comparable to or better than that of moxifloxacin against these pathogens, which included ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus and levofloxacin-resistant Streptococcus pneumoniae.

Nosocomial infections caused by antibiotic-resistant Klebsiella pneumoniae are emerging as a major health problem worldwide, while community-acquired K. pneumoniae infections present with a range of diverse clinical pictures in different geographic areas. In particular, an invasive form of K. pneumoniae that causes liver abscesses was first observed in Asia and then was found worldwide. We are interested in how differences in gene content of the same species result in different diseases. Thus, we sequenced the whole genome of K. pneumoniae NTUH-K2044, which was isolated from a patient with liver abscess and meningitis, and analyzed differences compared to strain MGH 78578, which was isolated from a patient with pneumonia. Six major types of differences were found in gene clusters that included an integrative and conjugative element, clusters involved in citrate fermentation, lipopolysaccharide synthesis, and capsular polysaccharide synthesis, phage-related insertions, and a cluster containing fimbria-related genes. We also conducted comparative genomic hybridization with 15 K. pneumoniae isolates obtained from community-acquired or nosocomial infections using tiling probes for the NTUH-K2044 genome. Hierarchical clustering revealed three major groups of genomic insertion-deletion patterns that correlate with the strains' clinical features, antimicrobial susceptibilities, and virulence phenotypes with mice. Here we report the whole-genome sequence of K. pneumoniae NTUH-K2044 and describe evidence showing significant genomic diversity and sequence acquisition among K. pneumoniae pathogenic strains. Our findings support the hypothesis that these factors are responsible for the changes that have occurred in the disease profile over time.

A 269-kilobase conjugative plasmid, pK29, from a Klebsiella pneumoniae strain was sequenced. The plasmid harbors multiple antimicrobial resistance genes, including those encoding CMY-8 AmpC-type and CTX-M-3 extended-spectrum beta-lactamases in the common backbone of IncHI2 plasmids. Mechanisms for dissemination of the resistance genes are highlighted in comparative genomic analyses.

Avoparcin, a vancomycin analogue, was banned as a feed additive in Taiwan in 2000. A nationwide surveillance was conducted to study the prevalence of vancomycin-resistant enterococci (VRE) on chicken farms between 2000 and 2003. Among the 1021 E. faecalis and 967 E. faecium isolates studied, resistance to tetracycline, erythromycin, high-level aminoglycosides, ciprofloxacin and chloramphenicol either increased or remained high except vancomycin. The proportion of VRE decreased, between 2000 and 2003, from 13.7% (22/161) to 3.7% (11/299) for E. faecalis, and 3.4% (4/119) to 0% (0/300) for E. faecium. Only 8.8% (7/80) of the chicken farms surveyed harboured VRE in 2003 compared with 25% (15/60) in 2000. All VRE were resistant to tetracycline and erythromycin. All VRE possess the vanA gene but nearly all (79 of 83 isolates) were susceptible to teicoplanin, indicating VanB phenotype. Some clones were detected from different farms in various regions over the years. We conclude that the frequency of VRE in chicken farms decreased in association with a ban on avoparcin; and the continued presence of VRE may be due to the ability of some strains to persist in the farms, transfer of vancomycin resistance determinants or co-selection by the continued use of other antibiotics.

A plasmid containing the qnrS quinolone resistance determinant and the gene encoding the SHV-2 beta-lactamase has been discovered from a clinical Klebsiella pneumoniae strain isolated in Taiwan. The complete 98-kb sequence of this plasmid, designated pK245, was determined by using a whole-genome shotgun approach. Transfer of pK245 conferred low-level resistance to fluoroquinolones in electroporant Escherichia coli epi300. The sequence of the immediate region surrounding qnrS in pK245 is nearly identical (>99% identity) to those of pAH0376 from Shigella flexneri and pINF5 from Salmonella enterica serovar Infantis, the two other qnrS-carrying plasmids reported to date, indicating a potential common origin. Other genes conferring resistance to aminoglycosides (aacC2, strA, and strB), chloramphenicol (catA2), sulfonamides (sul2), tetracycline (tetD), and trimethoprim (dfrA14) were also detected in pK245. The dfrA14 gene is carried on a class I integron. Several features of this plasmid, including three separate regions containing putative replicons, a partitioning-control system, and a type II restriction modification system, suggest that it may be able to replicate and adapt in a variety of hosts. Although no critical conjugative genes were detected, multiple insertion sequence elements were found scattered throughout pK245, and these may facilitate the dissemination of the antimicrobial resistance determinants. We conclude that pK245 is a chimera which acquired its multiple antimicrobial resistance determinants horizontally from different sources. The identification of pK245 plasmid expands the repertoire of the coexistence of quinolone and extended-spectrum-beta-lactam resistance determinants in plasmids carried by various species of the family Enterobacteriaceae in different countries.

Of the 798 clinical Salmonella isolates collected from multiple hospitals in Taiwan, resistance to ampicillin (48.5%), chloramphenicol (55.3%), streptomycin (59.0%), sulfamethoxazole (68.0%), and tetracycline (67.8%) was high, whereas resistance to all 5 antimicrobials (ACSSuT R-type) comprised 327 (41%) and was highly prevalent in Salmonella enterica serotype Typhimurium (72.7%, 176/242), the most common serotype. Additional resistance to trimethoprim was present in 155 (19.4% overall) of the ACSSuT R-type isolates from several serotypes. Reduced susceptibility to fluoroquinolone (FQ) (ciprofloxacin MIC >0.125-1 microg/mL and nalidixic acid-resistant) was detected in 223 (27.9%) isolates including 117 (14.7% overall) that were also ACSSuT-resistant. Full resistance to FQ was detected in Salmonella Choleraesuis (35.5%, 6/17) and Salmonella Schwarzengrund (16.7%, 10/60); both serotypes were also multiresistant to other antimicrobials. Studies are needed to determine the sources of different multidrug-resistant serotypes. Continued national surveillance is underway to monitor changes in resistance trends and to detect further emergence of resistant Salmonella serotypes in Taiwan.

We found a virulent closely related clone (Panton-Valentine leukocidin-positive, SCCmec V:ST59) of methicillin-resistant Staphylococcus aureus in inpatients and outpatients in Taiwan. The isolates were found mostly in wounds but were also detected in blood, ear, respiratory, and other specimens; all were susceptible to ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole.

In the Taiwan Surveillance of Antimicrobial Resistance programme, isolates were collected from 21 hospitals over a 3-month period in 2000 (TSAR II) and rates of resistance in Gram-positive pathogens were determined. Resistance rates were high including oxacillin resistance in Staphylococcus aureus (60%) and coagulase-negative staphylococci (80%), high-level gentamicin resistance (HLGR) in Enterococcus faecalis (60%) and penicillin non-susceptibility in Streptococcus pneumoniae (69%). Oxacillin resistance had increased from 1998 (TSAR I) and may be spreading into outpatient settings. In contrast, less than 2% enterococci were vancomycin-resistant. No linezolid resistance was found in either staphylococci or enterococci.

In a nationwide surveillance of antimicrobial resistance (Taiwan Surveillance of Antimicrobial Resistance, TSAR), isolates were collected from 21 medical centers and regional hospitals throughout Taiwan over a three-month period in 2000 (TSAR II). This report summarizes susceptibility data of 7 common Gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii) in the TSAR II collection and compared selected key forms of resistance by epidemiologic factors and with isolates collected in 1998 (TSAR I) as well as with data from international surveillance studies. Resistance of the 5 Enterobacteriaceae species to most of the commonly prescribed "first-line" antimicrobials in Taiwan, such as ampicillin (78% in E. coli, 68% in P. mirabilis), gentamicin (19% in K. pneumonia to 66% in S. marcescens), and trimethoprim/sulfamethoxazole (29% in K. pneumoniae to 70% in P. mirabilis), was high, several of which are higher than other countries. Resistance to certain broad-spectrum antimicrobials is also more acute in Taiwan than most Western countries, such as ceftazidime resistant A. baumannii (73%) and ciprofloxacin resistant E. coli (12%). Differences in geographic regions and specimen types were associated with certain forms of resistance in TSAR II; however, the resistance problem is prevalent among both inpatients and outpatients of not only medical centers but also regional hospitals throughout Taiwan.

Vancomycin resistant enterococci (VRE) with VanB phenotype-vanA genotype incongruence were found in all 39 VRE isolated from chicken carcasses and four human VRE isolates in Taiwan. Three identical mutations in the vanS gene were found in the VanB phenotype-vanA genotype VRE sequenced. This finding indicates possible transmission of glycopeptide resistance among different hosts.

For the first national surveillance of antibiotic resistance in Taiwan, we collected in 1998 from 22 hospitals (6 medical centers, 15 regional hospitals, and 1 local hospital) 3,211 isolates in all parts of the country. Besides 50 random successive isolates from inpatients, each hospital was requested to collect 25 isolates each from positive blood cultures, hospital-acquired infections, outpatients and the pediatric department. We re-speciated all the submitted specimens and determined their antibiotic susceptibility patterns. The most common isolates were Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae), Staphylococcus aureus, and Pseudomonas aeruginosa. Among hospital-acquired infections, Acinetobacter spp. were among those which accounted for over 10% of the isolates. The oxacillin resistance of S. aureus was 82% in isolates from hospital-acquired infections, and 40% from outpatients. Among Enterococcus spp., 85% were either E. faecalis or E. faecium. They were 14% resistant to vancomycin. Among gram-negative bacteria, K. pneumoniae and Acinetobacter baumanii were hospital-acquired isolates that were most clearly more resistant than community acquired isolates. This difference was less apparent in the case of Enterobacter cloacae, Serratia marcescens, and P. aeruginosa. These bacteria were generally more resistant from all sources. Fifty-one percent of Salmonella were resistant to ampicillin; however, these were all sensitive to ciprofloxacin. Isolates from the East were least resistant. Plotting the disc zone diameters of antibiotics within the susceptible range, we identified subpopulations with smaller diameters in the case of vancomycin against S. aureus, ciprofloxacin against E. coli, and ciprofloxacin against Salmonella spp. These findings represent one of the purposes of this surveillance as they may portend developing resistances which bear careful watching in the future.

A 64-year-old man with hepatic actinomycosis presented with several months of weight loss and poor appetite. However, no fever was noted before admission. Findings on abdominal sonography and computed tomography scan were suggestive of hepatocellular carcinoma. A sono-guided percutaneous liver biopsy specimen demonstrated only chronic fibrosing inflammation. Therefore, laparotomy was performed and the diagnosis of hepatic actinomycosis was established after surgical resection. The patient was then successfully treated. The fact that hepatic actinomycosis may be very similar to hepatocellular carcinoma should be highly suspected. The hospital course of this patient concerning this condition and a brief review of the literature are presented to illustrate the diagnostic difficulties which may be encountered in such cases.