Changing epidemiology and antimicrobial resistance of bacteria causing bacteremia in Taiwan: 2002-2020.

Bacteremia is associated with significant morbidity and mortality. The emergence of bacteria with antimicrobial resistance (AMR) has further exacerbated the poor outcomes associated with bacteremia. The Taiwan Surveillance of Antimicrobial Resistance (TSAR) program was established in 1998 to monitor bacterial epidemiology and antimicrobial resistance trends across all patient types and age groups. Between 2002 and 2020, a total of 14,539 non-duplicate bacteremia isolates were collected biennially from 29 hospitals during the months of July-September as part of the TSAR program. The three most common bacteremia agents were Escherichia coli (31%), Staphylococcus aureus (13.6%), and Klebsiella pneumoniae (12.7%) overall. However, there was a steady increase in the proportions of E. coli and Enterococcus faecium isolated from bacteremia cases (both P < 0.001), while the proportions of Acinetobacter spp. decreased. Regarding antimicrobial resistance, there was a notable increase in rates of third-generation cephalosporin and fluoroquinolone non-susceptibility among E. coli and K. pneumoniae, while the rates of carbapenem non-susceptibility were elevated but remained milder in these two species, especially in E. coli. Of concern is the alarming increase in vancomycin resistance among E. faecium, rising from 10.0% in 2004 to 47.7% in 2020. In contrast, the prevalence of methicillin-resistant S. aureus has remained stable at 51.2% overall. In conclusion, E. coli, with increasing third-generation cephalosporin and fluoroquinolone resistance, is the predominant cause of bacteremia in Taiwan during the 18-year surveillance. The escalating proportion of E. faecium in bacteremia, coupled with a concurrent upsurge in vancomycin resistance, presents a therapeutic challenge in the recent decade. IMPORTANCE: AMR surveillance not only enables the identification of regional variations but also supports the development of coordinated efforts to combat AMR on a global scale. The TSAR has been a biennial, government-endorsed, multicenter study focusing on pathogens isolated from inpatients and outpatients in Taiwan hospitals since 1998. Our report presents an 18-year comprehensive analysis on blood isolates in the 2002-2020 TSAR program. The study highlights an alarming increase in the proportion of E. faecium causing bacteremia accompanied by elevated vancomycin resistance. It is worth noting that this trend differs from the observations in the United States and China. Understanding the composition of bacteria causing bacteremia, along with their prevalence of antimicrobial resistance, holds significant importance in establishing healthcare and research priorities. Additionally, this knowledge serves as a critical factor in evaluating the effectiveness of preventive interventions.

Clonal expansion of Tn1546-like transposon-carrying vancomycin-resistant Enterococcus faecium, a nationwide study in Taiwan, 2004-2018.

OBJECTIVES: The prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased significantly in Taiwan. We investigated the molecular epidemiology of clinical VREfm isolates to increase our understanding on their spread and changes in population structure over a 14-year span. METHODS: A total of 1113 E. faecium isolates were collected biennially from 2004 to 2018 in Taiwan. MICs were determined by broth microdilution. Whole-genome sequencing (WGS) was performed on 229 VREfm isolates to characterize their genetic environment of vancomycin resistance and wgMLST was used to investigate their clonal relationship. RESULTS: Among the 229 isolates, ST17 and ST78 predominated, especially during the later years, and their prevalences increased from 14.6% (7/48) and 25.0% (12/48) in 2004-2010 to 47.5% (87/181) and 29.8% (54/181) in 2012-2018, respectively. Four types of vanA-carrying Tn1546 variants were detected, with type 1 and type 2 predominated. Type 1 Tn1546 contained an addition of IS1251, while type 2 resembled type 1 but had an addition of IS1678. wgMLST revealed several distinct clusters of ST17 and ST78 isolates, with type 1 Tn1546-harbouring ST17-Cluster 16 being the largest and most widespread clones throughout the study years. Type 2 Tn1546-carrying ST78 became a predominant clone (Cluster 21) after 2012. Isolates within these clusters are highly similar despite being from different hospitals, regions, and study year. CONCLUSION: The increase of VREfm in Taiwan was attributed to horizontal transfer of vanA-carrying Tn1546 variants between different STs and spread of persistent clones. This study highlights the importance of integrating WGS into surveillance to combat antimicrobial resistance.

Interregional mobility in different age groups is associated with COVID-19 transmission in the Taipei metropolitan area, Taiwan.

Before vaccines were introduced, mobility restriction was one of the primary control measures in the early stage of the coronavirus disease 2019 (COVID-19) pandemic. Because different age groups face disproportionate health risks, differences in their mobility changes affect the effectiveness of pandemic control measures. This study aimed to investigate the relationship between multiscale mobility patterns in different age groups and COVID-19 transmission before and after control measures implementation. Data on daily confirmed case numbers, anonymized mobile phone data, and 38 socioeconomic factors were used to construct negative binomial regression models of these relationships in the Taipei metropolitan area in May 2021. To avoid overfitting, the socioeconomic factor dimensions were reduced by principal component analysis. The results showed that inter-district mobility was a greater promoter of COVID-19 transmission than was intra-district mobility (coefficients: pre-alert, 0.52 and 0.43; post-alert, 0.41 and 0.36, respectively). Moreover, both the inter-district mobility of people aged 15-59 and ≥ 60 years were significantly related to the number of confirmed cases (coefficients: pre-alert, 0.82 and 1.05; post-alert, 0.48 and 0.66, respectively). The results can help agencies worldwide formulate public health responses to emerging infectious diseases.

High-level levofloxacin-resistant emm12 group A Streptococcus, 2012-2018: A multicenter study in Taiwan.

High-level levofloxacin-resistant group A Streptococcus emerged in Taiwan in 2012. Among the 24 isolates identified, 23 belonged to emm12/ST36, most harbored the same GyrA and ParC mutations and were highly clonal. wgMLST showed them to be closely related to the Hong Kong scarlet fever outbreak strains. Continuous surveillance is warranted.

Synthesis and characterization of new donor-acceptor type copolymers based on fluorene derivatives for photovoltaic solar cells.

In this paper, we demonstrated the successful synthesis of newly designed copolymers, C1 and C2, with donor-acceptor type structure. Both C1 and C2 copolymers contained 9,9-dioctylfluorene-2,7-bis(trimethyleneboronate) as one constructional unit to improve the solubility in common organic solvents. The other constructional unit was 2,3-bis(5-bromothiophen-2-yl)acrylonitrile (DTDBAL) for C1, while 4,7-dibromobenzo[c][1,2,5]thiadiazole unit, 5,5'-dibromo-2,2'-bithiophene unit and N1, N1-bis(4-bromophenyl)-N4,N4-bis(4-(2-phenylpropan-2-yl)phenyl)benzene-1,4-diamine are for C2. We fabricated photovoltaic devices based on the C1 and the C2 copolymers with Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) layer, PC70BM layer, TiOx layer, and aluminum (Al) electrode. The bulk heterojuntion photovoltaic devices using these copolymers as electron donor and PC70BM as the acceptor exhibited good device performances when measured at 100 mW cm-2. The power conversion efficiency (PCE) of the C1 device reached 0.45% with Voc, Jsc and FF of 0.51, 2.50 and 35%, respectively. The PCE of the C2 device reached 0.34% with Voc, Jsc, and FF of 0.56, 2.01 and 30%, respectively.

In vitro and in vivo efficacy of minocycline-based therapy for Elizabethkingia anophelis and the impact of reduced minocycline susceptibility.

OBJECTIVES: Elizabethkingia anophelis is inherently resistant to multiple antibiotics, except minocycline. This study aimed to determine the in vitro and in vivo efficacy of minocycline monotherapy and combination therapy against susceptible strains and the impact of reduced minocycline susceptibility. METHODS: Three clinical isolates and one laboratory-induced mutant with reduced minocycline susceptibility were included. Time-kill and checkerboard assays were used to assess in vitro efficacy and synergy, respectively. Galleria mellonella infection and mouse pneumonia models were used to assess in vivo efficacy, and a mouse thigh infection model was used to determine the bacterial load. RESULTS: Minocycline monotherapy exerted a modest inhibitory effect on three clinical minocycline-susceptible E. anophelis isolates in vitro, but delayed G. mellonella death and improved infected mouse survival; it also significantly reduced the in vivo bacterial load. Minocycline had decreased efficacy on G. mellonella and mice infected by the mutant with reduced minocycline susceptibility. Genome comparison revealed several spontaneous mutations associated with reduced minocycline susceptibility. Among eight antibiotics tested in combination with minocycline, rifampin consistently showed in vitro synergy. The addition of rifampin (1 mg/L) reduced the mutant prevention concentration of minocycline from 2-4 mg/L to < 0.5 mg/L. However, compared with monotherapy, the combination of rifampin and minocycline did not further reduce the bacterial load or improve the survival of G. mellonella or mice. CONCLUSION: Minocycline monotherapy was in vivo effective against susceptible E. anophelis. Reduced minocycline susceptibility due to spontaneous mutation decreased its therapeutic efficacy. In combination with rifampin, it prevented the in vitro emergence of reduced susceptibility but did not provide additional in vivo survival benefit.

The epidemiology and etiologies of respiratory tract infection in Northern Taiwan during the early phase of coronavirus disease 2019 (COVID-19) outbreak.

BACKGROUND: Coronavirus disease 2019 (COVID-19) manifests symptoms as common etiologies of respiratory tract infections (RTIs). During the pandemic of COVID-19, identifying the etiologies correctly from patients with RTI symptoms was crucial in not only disease control but preventing healthcare system from collapsing. By applying sensitive PCR-based molecular assays, we detected the etiologic agents and delineated the epidemiologic picture of RTIs in the early phase of COVID-19 pandemic. METHODS: From December 2019 to February 2020, we screened patients presented with RTIs using multiplex PCR-based diagnostic assays. Data from pediatric and adult patients were compared with different months and units in the hospital. RESULTS: Of all 1631 patients including 1445 adult and 186 pediatric patients screened, 8 viruses and 4 bacteria were identified. Positive rates were 25% in December, 37% in January, and 20% in February, with pediatric patients having higher positive rates than adults (Ps < 0.001). In pediatric patients, RhV/EnV was the most commonly detected, followed by parainfluenza viruses. Most Mycoplasma pneumoniae infection occurred in pediatric patients. RhV/EnV was the most commonly detected agent in pediatric patients admitted to intensive care units (ICUs), while influenza accounted for the majority of adult cases with critical illness. Noticeably, seasonal coronavirus ranked second in both adult and pediatric patients with ICU admission. CONCLUSION: While we focused on the pandemic of COVID-19, common etiologies still accounted for the majority of RTIs and lead to severe diseases, including other seasonal coronaviruses.

Evaluation of Carbon Dioxide-Based Urethane Acrylate Composites for Sealers of Root Canal Obturation.

A new root canal sealer was developed based on urethane acrylates using polycarbonate polyol (PCPO), a macrodiol prepared in the consumption of carbon dioxide as feedstock. The superior mechanical properties and biostability nature of PCPO-based urethane acrylates were then co-crosslinked with a difunctional monomer of tripropylene glycol diarylate (TPGDA) as sealers for resin matrix. Moreover, nanoscale silicate platelets (NSPs) immobilized with silver nanoparticles (AgNPs) and/or zinc oxide nanoparticles (ZnONPs) were introduced to enhance the antibacterial effect for the sealers. The biocompatibility and the antibacterial effect were investigated by Alamar blue assay and LDH assay. In addition, the antibacterial efficiency was performed by using Enterococcus faecalis (E. faecalis) as microbial response evaluation. These results demonstrate that the PCPO-based urethane acrylates with 50 ppm of both AgNP and ZnONP immobilized on silicate platelets, i.e., Ag/ZnO@NSP, exhibited great potential as an antibacterial composite for the sealer of root canal obturation.

Comparison of clinical characteristics of bacteremia from Elizabethkingia meningoseptica and other carbapenem-resistant, non-fermenting Gram-negative bacilli at a tertiary medical center.

BACKGROUND: Acquired carbapenem resistance among non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB complex), is a serious problem in nosocomial infections. We previously reported that patients infected with the intrinsically carbapenem-resistant Elizabethkingia meningoseptica were associated with high mortality. However, little information is available regarding the clinical outcome of E. meningoseptica bacteremia when compared to that of other carbapenem-resistant NFGNB. METHODS: We conducted an observational study that included consecutive patients with E. meningoseptica, carbapenem-resistant ACB complex, carbapenem-resistant P. aeruginosa, and Stenotrophomonas maltophilia bacteremia at a Taiwanese medical center in 2015. We compared the clinical characteristics and outcomes between patients with E. meningoseptica bacteremia and those with other carbapenem-resistant NFGNB bacteremia. RESULTS: We identified 30 patients with E. meningoseptica, 71 with carbapenem-resistant ACB complex, 25 with S. maltophilia, and 17 with carbapenem-resistant P. aeruginosa bacteremia. The clinical characteristics, disease severity, and previous antibiotic exposures were similar between patients with bacteremia either due to E. meningoseptica or other carbapenem-resistant NFGNB. Patients with E. meningoseptica bacteremia had a higher rate of appropriate empirical antibiotics than those with other carbapenem-resistant NFGNB and was less associated with central venous catheterization. The 28-day mortality rates were similar between patients with E. meningoseptica and the other carbapenem-resistant NFGNB bacteremia (46.7% vs 46%, p = 0.949). CONCLUSION: The mortality rate of E. meningoseptica bacteremia was as high as other carbapenem-resistant NFGNB infections. The emerging E. meningoseptica infection calls for active surveillance and continued awareness from clinical physicians for this serious carbapenem-resistant infection.

Comparison of the therapeutic efficacy of fluoroquinolone and non-fluoroquinolone treatment in patients with Elizabethkingia meningoseptica bacteraemia.

Elizabethkingia meningoseptica is a non-fermentative Gram-negative bacillus that has emerged as an important pathogen in nosocomial infections and is usually associated with high mortality. E. meningoseptica is inherently resistant to many broad-spectrum antibiotics, and appropriate antibiotic selection is crucial for survival. Data about the therapeutic efficacy of fluoroquinolone in E. meningoseptica bacteraemia are limited. We retrospectively enrolled patients with E. meningoseptica bacteraemia who were treated with a single antimicrobial agent with in vitro activity against E. meningoseptica for at least 48 hours in a Taiwanese medical centre between January 2011 and June 2016. We compared the therapeutic efficacy of fluoroquinolone and non-fluoroquinolone treatment. A logistic regression and a propensity score-adjusted model were used to evaluate the risk factors for 14-day mortality. A total of 66 patients were identified, 24 who received fluoroquinolone treatment (ciprofloxacin, n = 9; levofloxacin, n = 15) and 42 who received non-fluoroquinolone treatment (piperacillin/tazobactam, n = 26; trimethoprim/sulfamethoxazole, n = 15; minocycline, n = 1). The fluoroquinolone group had significantly lower 14-day mortality than the non-fluoroquinolone group (8.3% vs. 33.3%, P = 0.023). The APACHE II score was significantly higher in the non-fluoroquinolone group than in the fluoroquinolone group. In a propensity-adjusted analysis, fluoroquinolone use was an independent factor associated with 14-day survival. After stratification using the APACHE II score, treatment with fluoroquinolone was associated with 14-day survival, but did not reach statistical significance in both groups with greater and lesser severity. Therefore, fluoroquinolone is a suitable antimicrobial agent for treating E. meningoseptica bacteraemia.

Digital Memory Characteristics of Aromatic Polyimides Based on Pyridine and Its Derivatives.

Soluble aromatic polyimides and polyvinyls were prepared by incorporating pyridine moiety and its derivatives in the backbone and the side groups, respectively: 6F-Py-i polymers based on the polyimide backbone (6F-Py-1 to 6F-Py-7) and PVPy-i polymers based on the polyvinyl backbone (PVPy-1 to PVPy-4). All polymers were found to be amorphous. The 6F-Py-i polymers were thermally stable up to 511-545 °C; the PVPy-i polymers were stable up to 362-376 °C. Their glass transitions, thin film densities, molecular orbitals, and band gaps were determined. The electrical devices fabricated with the polymers in an electrode/polymer/electrode structure revealed p-type unipolar write-once-read-many times (namely, permanent) or dynamic random access memory or dielectric behavior, depending on the substituents of the pyridine unit and the film thicknesses. In particular, such digital memory characteristics were found to originate from the pyridine moieties possessing a high charge affinity in the polymers. However, the pyridine moieties were found to still need at least two or more aromatic substituents to get enough power to stabilize charges via utilizing the resonance effects provided by the substituents. Overall, this study demonstrated that the pyridine unit conjugated with two or more aromatic substituents is a very useful component to design and synthesize digital memory materials based on thermally stable polyimides and other high performance polymers. The 6F-Py-i polymers have potential for the low-cost mass production of high-performance programmable unipolar permanent memory devices with very low power consumption.

Sorption behavior of polyaramides in relation to isolation of nucleic acids and proteins.

The effect of chemical composition and morphology of the surface layers of new polyaramide-containing sorbents on the mechanism of selective sorption of nucleic acids and proteins was investigated as compared to the previously studied sorbents modified with fluoropolymers and polyaniline (high-throughput materials providing one-step isolation of DNA from biological mixtures). A series of silica-based sorbents modified with polyaramides having consistently varying structure and containing the set of "key" structural elements (aromatic units and nitrogen atoms in the backbone, fluorinated groups), and various donor and acceptor moieties was prepared. The chemical composition of the polymer coatings was evaluated by X-ray photoelectron spectroscopy. The surface morphology was studied by scanning probe microscopy. The sorption properties were investigated by passing the mixtures containing DNA, RNA and proteins of different nature through the cartridges containing the obtained sorbents. All the investigated materials weakly retain double-stranded DNA but effectively retain RNA and proteins. The sorption capacity of the sorbents depends on the protein nature. The observed sorption behavior was shown to be determined by the chemical structure and not by the morphology of the polymer coating. It was proposed that similarity of the sorption properties of the series of chemically different polymers could be determined by similar total input of different sorption mechanisms.

A bifunctional copolymer additive to utilize photoenergy transfer and to improve hole mobility for organic ternary bulk-heterojunction solar cell.

To realize the high efficiency organic photovoltaics (OPVs), two critical requirements have to be fulfilled: (1) increasing the photon energy absorption range of the active layer, and (2) improving charge separation and transport in the active layer. This study reports the utilization of THC8, a novel fluorescence-based polymer containing propeller-shaped di-triarylamine and fluorene moieties in the active layer consisting of poly-3-hexylthiophene and [6,6]-phenyl-C61-butyric acid methyl ester to form a ternary bulk heterojunction. The results showed that the high absorbance and strong fluorescence of THC8 at 420 and 510 nm, respectively, broadened the spectral absorption of the OPV, possibly through Förster resonance energy transfer. In addition, the morphology of the device active layer was improved with the addition of a suitable amount of THC8. Consequently, the charge transport property of the active layer was improved. The best power conversion efficiency (PCE) of the device with THC8 was 3.88%, a 25% increase compared to the PCE of a pristine OPV.