The individual contributions of blaB, blaGOB and blaCME on MICs of ß-lactams in Elizabethkingia anophelis.

BACKGROUND: The blaB, blaGOB and blaCME genes are thought to confer ß-lactam resistance to Elizabethkingia anophelis, based on experiments conducted primarily on Escherichia coli. OBJECTIVES: To determine the individual contributions of ß-lactamase genes to increased MICs in E. anophelis and to assess their impact on the in vivo efficacy of carbapenem therapy. METHODS: Scarless gene deletion of one or more ß-lactamase gene(s) was performed in three clinical E. anophelis isolates. MICs were determined by broth microdilution. Hydrolytic activity and expressions of ß-lactamase genes were measured by an enzymatic assay and quantitative RT-PCR, respectively. In vivo efficacy was determined using Galleria mellonella and murine thigh infection models. RESULTS: The presence of blaB resulted in >16-fold increases, while blaGOB caused 4-16-fold increases of carbapenem MICs. Hydrolysis of carbapenems was highest in lysates of blaB-positive strains, possibly due to the constitutionally higher expression of blaB. Imipenem was ineffective against blaB-positive isolates in vivo in terms of improvement of the survival of wax moth larvae and reduction of murine bacterial load. The deletion of blaB restored the efficacy of imipenem. The blaB gene was also responsible for a >4-fold increase of ampicillin/sulbactam and piperacillin/tazobactam MICs. The presence of blaCME, but not blaB or blaGOB, increased the MICs of ceftazidime and cefepime by 8-16- and 4-8-fold, respectively. CONCLUSIONS: The constitutionally and highly expressed blaB gene in E. anophelis was responsible for increased MICs of carbapenems and led to their poor in vivo efficacy. blaCME increased the MICs of ceftazidime and cefepime.

Decrypting orphan GPCR drug discovery via multitask learning.

The drug discovery of G protein-coupled receptors (GPCRs) superfamily using computational models is often limited by the availability of protein three-dimensional (3D) structures and chemicals with experimentally measured bioactivities. Orphan GPCRs without known ligands further complicate the process. To enable drug discovery for human orphan GPCRs, multitask models were proposed for predicting half maximal effective concentrations (EC50) of the pairs of chemicals and GPCRs. Protein multiple sequence alignment features, and physicochemical properties and fingerprints of chemicals were utilized to encode the protein and chemical information, respectively. The protein features enabled the transfer of data-rich GPCRs to orphan receptors and the transferability based on the similarity of protein features. The final model was trained using both agonist and antagonist data from 200 GPCRs and showed an excellent mean squared error (MSE) of 0.24 in the validation dataset. An independent test using the orphan dataset consisting of 16 receptors associated with less than 8 bioactivities showed a reasonably good MSE of 1.51 that can be further improved to 0.53 by considering the transferability based on protein features. The informative features were identified and mapped to corresponding 3D structures to gain insights into the mechanism of GPCR-ligand interactions across the GPCR family. The proposed method provides a novel perspective on learning ligand bioactivity within the diverse human GPCR superfamily and can potentially accelerate the discovery of therapeutic agents for orphan GPCRs.

Visualizing the DNA repair process by a photolyase at atomic resolution.

Photolyases, a ubiquitous class of flavoproteins, use blue light to repair DNA photolesions. In this work, we determined the structural mechanism of the photolyase-catalyzed repair of a cyclobutane pyrimidine dimer (CPD) lesion using time-resolved serial femtosecond crystallography (TR-SFX). We obtained 18 snapshots that show time-dependent changes in four reaction loci. We used these results to create a movie that depicts the repair of CPD lesions in the picosecond-to-nanosecond range, followed by the recovery of the enzymatic moieties involved in catalysis, completing the formation of the fully reduced enzyme-product complex at 500 nanoseconds. Finally, back-flip intermediates of the thymine bases to reanneal the DNA were captured at 25 to 200 microseconds. Our data cover the complete molecular mechanism of a photolyase and, importantly, its chemistry and enzymatic catalysis at work across a wide timescale and at atomic resolution.

Analysis of structure-activity relationship of indol-3-yl-N-phenylcarbamic amides as potent STING inhibitors.

A structure-activity relationship (SAR) study of stimulator of interferon gene (STING) inhibition was performed using a series of indol-3-yl-N-phenylcarbamic amides and indol-2-yl-N-phenylcarbamic amides. Among these analogs, compounds 10, 13, 15, 19, and 21 inhibited the phosphorylation of STING and interferon regulatory factor 3 (IRF3) to a greater extent than the reference compound, H-151. All five analogs showed stronger STING inhibition than H-151 on the 2',3'-cyclic GMP-AMP-induced expression of interferon regulatory factors (IRFs) in a STINGR232 knock-in THP-1 reporter cell line. The half-maximal inhibitory concentration of the most potent compound, 21, was 11.5 nM. The molecular docking analysis of compound 21 and STING combined with the SAR study suggested that the meta- and para-positions of the benzene ring of the phenylcarbamic amide moiety could be structurally modified by introducing halides or alkyl substituents.

Marine diterpenoid targets STING palmitoylation in mammalian cells.

Natural products are important sources of therapeutic agents and useful drug discovery tools. The fused macrocycles and multiple stereocenters of briarane-type diterpenoids pose a major challenge to total synthesis and efforts to characterize their biological activities. Harnessing a scalable source of excavatolide B (excB) from cultured soft coral Briareum stechei, we generated analogs by late-stage diversification and performed structure-activity analysis, which was critical for the development of functional excB probes. We further used these probes in a chemoproteomic strategy to identify Stimulator of Interferon Genes (STING) as a direct target of excB in mammalian cells. We showed that the epoxylactone warhead of excB is required to covalently engage STING at its membrane-proximal Cys91, inhibiting STING palmitoylation and signaling. This study reveals a possible mechanism-of-action of excB, and expands the repertoire of covalent STING inhibitors.

A chromosome-scale genome assembly of Castanopsis hystrix provides new insights into the evolution and adaptation of Fagaceae species.

Fagaceae species dominate forests and shrublands throughout the Northern Hemisphere, and have been used as models to investigate the processes and mechanisms of adaptation and speciation. Compared with the well-studied genus Quercus, genomic data is limited for the tropical-subtropical genus Castanopsis. Castanopsis hystrix is an ecologically and economically valuable species with a wide distribution in the evergreen broad-leaved forests of tropical-subtropical Asia. Here, we present a high-quality chromosome-scale reference genome of C. hystrix, obtained using a combination of Illumina and PacBio HiFi reads with Hi-C technology. The assembled genome size is 882.6 Mb with a contig N50 of 40.9 Mb and a BUSCO estimate of 99.5%, which are higher than those of recently published Fagaceae species. Genome annotation identified 37,750 protein-coding genes, of which 97.91% were functionally annotated. Repeat sequences constituted 50.95% of the genome and LTRs were the most abundant repetitive elements. Comparative genomic analysis revealed high genome synteny between C. hystrix and other Fagaceae species, despite the long divergence time between them. Considerable gene family expansion and contraction were detected in Castanopsis species. These expanded genes were involved in multiple important biological processes and molecular functions, which may have contributed to the adaptation of the genus to a tropical-subtropical climate. In summary, the genome assembly of C. hystrix provides important genomic resources for Fagaceae genomic research communities, and improves understanding of the adaptation and evolution of forest trees.

Commelinadanxiaensis (Commelinaceae), a new species from Guangdong, China.

Commelinadanxiaensis (Commelinaceae), a remarkable new species from Mount Danxia, Guangdong Province, China, is described and illustrated. This species is similar to C.communis in inflorescences and flowers but readily distinguishable in its nearly erect stems, larger flowers, and different petal colouration.

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.

Dynamic interaction nursing intervention on functional rehabilitation and self-care ability of patients after aneurysm surgery.

BACKGROUND: Nursing practices based on the dynamic interaction model have been shown to be superior to generic nursing practices. However, whether this model is effective in patients recovering from intracranial aneurysm surgery is not well studied. AIM: To investigate the effect of nursing based on a dynamic interaction model on functional rehabilitation of patients after aneurysm surgery. METHODS: A total of 86 cases in our hospital with intracranial aneurysm from April 2019 to April 2021, were selected and divided into the study group and the control group, with 43 patients in each group. The control group received routine nursing, and the research group received nursing intervention based on a dynamic interaction model. The daily living ability (activities of daily living, ADL), cognitive function (Simple Intelligent Mental State Scale, MMSE), quality of life (Generic Quality of Life Inventory-74, GQOL-74), self-care ability (Exercise of Self-Care Agency scale), incidence of complications, and nursing satisfaction were recorded before and after intervention. RESULTS: Before intervention, ADL (52.09 ± 6.44), MMSE (18.03 ± 4.11), and GQOL-74 (53.68 ± 4.34) scores in the study group were not significantly different from those in the control group (ADL: 50.97 ± 7.32, MMSE: 17.59 ± 3.82, GQOL-74: 55.06 ± 3.98) (P > 0.05). After intervention, ADL (86.12 ± 5.07), MMSE (26.64 ± 2.66), and GQOL-74 (83.13 ± 5.67) scores in the study group were higher than those in the control group (ADL: 79.81 ± 6.35, MMSE: 24.51 ± 3.00, and GQOL-74: 77.96 ± 6.27) (P < 0.05). Before intervention, self-concept (17.46 ± 4.44), self-care skills (25.22 ± 4.20), self-care knowledge (22.35 ± 4.74), and self-care responsibility (15.06 ± 3.29) scores in the study group was similar to those in the control group (self-concept: 16.89 ± 5.53, self-care skills: 24.59 ± 4.46, self-care knowledge: 21.80 ± 3.61, and self-care responsibility: 14.83 ± 3.11) (P > 0.05). After the intervention, self-concept (26.01 ± 3.18), self-care skills (37.68 ± 6.05), self-care knowledge (45.56 ± 5.83), and self-care responsibility (22.01 ± 3.77) scores in the study group were higher than those in the control group (self-concept: 22.97 ± 3.46, self-care skills: 33.02 ± 5.65, self-care skills knowledge: 36.81 ± 5.54, and self-care responsibility: 17.97 ± 3.56 points) (P < 0.05). The incidence of complications in the study group (4.65%) was lower than that in the control group (18.60%) (P < 0.05). Nursing satisfaction in the study group (95.35%) was higher than that in the control group (81.40%) (P < 0.05). CONCLUSION: Nursing intervention based on a dynamic interaction model can improve postoperative cognitive function, daily living ability, self-care ability, quality of life, and patient satisfaction, while reducing the risk of complications.

Serial crystallography captures dynamic control of sequential electron and proton transfer events in a flavoenzyme.

Flavin coenzymes are universally found in biological redox reactions. DNA photolyases, with their flavin chromophore (FAD), utilize blue light for DNA repair and photoreduction. The latter process involves two single-electron transfers to FAD with an intermittent protonation step to prime the enzyme active for DNA repair. Here we use time-resolved serial femtosecond X-ray crystallography to describe how light-driven electron transfers trigger subsequent nanosecond-to-microsecond entanglement between FAD and its Asn/Arg-Asp redox sensor triad. We found that this key feature within the photolyase-cryptochrome family regulates FAD re-hybridization and protonation. After first electron transfer, the FAD•- isoalloxazine ring twists strongly when the arginine closes in to stabilize the negative charge. Subsequent breakage of the arginine-aspartate salt bridge allows proton transfer from arginine to FAD•-. Our molecular videos demonstrate how the protein environment of redox cofactors organizes multiple electron/proton transfer events in an ordered fashion, which could be applicable to other redox systems such as photosynthesis.

Community-Based Screening for Hepatitis B and C Infectivity Using Two Quantitative Antigens to Identify Endemic Townships.

Screening and linkage to care are essential to achieve viral hepatitis elimination before 2030. The accurate identification of endemic areas is important for controlling diseases with geographic aggregation. Viral activity drives prognosis of chronic hepatitis B and hepatitis C virus infection. This screening was conducted in Chiayi County from 2018-2019. All residents aged 30 years or older were invited to participate in quantitative HBsAg (qHBsAg) and HCV Ag screening. Among the 4010 participants (male:female = 1630:2380), the prevalence of qHBsAg and HCV Ag was 9.9% (396/4010) and 4.1% (163/4010), respectively. High-prevalence townships were identified, three for qHBsAg > 15% and two for HCV Ag > 10%. The age-specific prevalence of qHBsAg was distributed in an inverse U-shape with a peak (16.0%, 68/424) for subjects in their 40 s; for HCV, prevalence increased with age. Concentrations of qHBsAg < 200 IU/mL were found in 54% (214/396) of carriers. The rate of oral antiviral treatment for HCV was 75.5% (114/151), with subjects younger than 75 years tending to undergo treatment (85.6% vs. 57.4%, p < 0.001). QHBsAg and HCV Ag core antigens can reflect the concentration of the viral load, which serves as a feasible screening tool. Using quantitative antigen screening for hepatitis B and C in community-based screening, two hyperendemic townships were identified from an endemic county.

In vitro and in vivo comparison of eravacycline- and tigecycline-based combination therapies for tigecycline-resistant Acinetobacter baumannii.

Several antimicrobial combination therapies are used to treat multiple drug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii infections. A novel antibiotic, eravacycline, shows a higher potency than tigecycline. The efficacies of eravacycline-based therapies have not yet been evaluated. We demonstrated the effectiveness of eravacycline- and tigecycline-based combination therapies in XDR and especially tigecycline resistant A. baumannii. Thirteen eligible isolates were selected from 642 non-duplicate Acinetobacter blood isolates from four medical centres in 2010-2014. Tigecycline/imipenem and eravacycline/imipenem combinations were simultaneously effective against some isolates in vitro with fractional inhibitory concentration index of 0.5. In contrast, eravacycline- and tigecycline-based combination therapies provided no additional benefits in mouse survival compared to those for monotherapy. In summary, colistin is still the final resort for XDR-A. baumannii treatment according to the sensitivities. Owning to rapid development of resistance in A. baumannii, novel antibiotics are urgently needed.

Outcomes of hepatitis B immunoglobulin and hepatitis B vaccination in high-risk newborns born to HBeAg-positive mothers.

BACKGROUND: To evaluate the protective efficacy of a hepatitis B (HB) vaccination program in Taiwan among high-risk children. METHODS: Children born to HBeAg-positive mothers from 2001 to 2010 were invited back. Blood samples for hepatitis B virus (HBV) seromarkers were taken and the children underwent hepatobiliary ultrasonography. Perinatal factors including delivery mode and vaccination history were collected from their medical records. According to the results of HBV serological markers, the children were initially classified into five groups: HBV naïve, HB vaccine responder, HBsAg carrier, recovered from HBV infection, and anti-HBc-positive alone. Children in the HBV naïve and anti-HBc-positive alone groups who presented with an anamnestic response after a booster HB vaccine were re-assigned to the vaccine responder and recovered from infection groups, respectively. RESULTS: All of the 196 enrolled children received postnatal hepatitis B immunoglobulin (HBIG) and HB vaccinations, of whom one was HBV naïve (0.5%), 109 were vaccine responders (55.6%), 21 were carriers (10.7%), and 65 recovered from infection (33.2%). Among the 21 carriers, 14 (66.7%) presented in the immunotolerant phase. Cesarean section was the only significant perinatal factor between the carriers (5.3%) and those who recovered from infection (37.7%) (p = 0.007). CONCLUSION: In this study, there was a 43.9% HBV infection rate and 10.7% HBsAg carrier rate in high-risk Taiwanese children even after receiving HBIG and HB vaccinations. C-section may protect newborns from becoming HBsAg carriers, while HBV genotype and time of HBIG injection did not contribute to the HBV carrier rate.

Village-to-village screening for hepatitis B and C using quantitative HBsAg and anti-HCV testing with reflex HCV core antigen tests in the remote communities of a resource-rich setting: a population-based prospective cohort study.

OBJECTIVES: Community-based screening for hepatitis B virus (HBV) and hepatitis C virus (HCV) is essential for hepatitis elimination. This study attempted to increase screening accessibility and efficacy by using alternative tools. DESIGN: Population-based prospective cohort study. SETTING: Hepatitis elimination program at Yunlin County, Taiwan. PARTICIPANTS: All 4552 individuals participated in 60 screening sessions of a community-based HBV and HCV screening project in five rural townships with approximately 95 000 inhabitants in central-western Taiwan. INTERVENTIONS: To increase accessibility, 60 outreach screening sessions were conducted in 41 disseminative sites. Quantitative HBV surface antigen (qHBsAg) and anti-HCV testing with reflex HCV core antigen (HCV Ag) tests were employed as alternative screening tools. MAIN OUTCOME MEASURES: Calculate village-specific prevalence of HBsAg, anti-HCV and HCV Ag and establish patient allocation strategies according to levels of qHBsAg HCV Ag and alanine aminotransferase (ALT). RESULTS: Of 4552 participants, 553, 697 and 290 were positive for HBsAg, anti-HCV and HCV Ag, respectively; 75 of them had both HBsAg and anti-HCV positivity. The average (range) number of participants in each screening session was 98 (31-150). The prevalence rates (range) of HBsAg, anti-HCV and HCV Ag were 12.1% (4.3%-19.4%), 15.3% (2.6%-52.3%) and 6.4% (0%-30.2%), respectively. The HCV Ag positivity rate among anti-HCV-positive participants was 42% (0%-100%). Using cut-off values of >200 IU/mL for qHBsAg, >3 fmol/L for HCV Ag and >40 IU/mL for ALT as criteria for patient referral, we noted an 80.2% reduction in referral burden. Three villages had high anti-HCV prevalences of 52.3%, 53.8% and 63.4% with corresponding viraemic prevalences of 23.2%, 30.1% and 22% and thus constituted newly identified HCV-hyperendemic villages. CONCLUSION: Outreach hepatitis screening increases accessibility for residents in rural communities. Screening HBV and HCV through qHBsAg and HCV Ag tests provides information concerning viral activities, which might be conducive to precise patient allocation in remote communities.

In vitro activity of imipenem/relebactam, meropenem/vaborbactam, ceftazidime/avibactam, cefepime/zidebactam and other novel antibiotics against imipenem-non-susceptible Gram-negative bacilli from Taiwan.

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 ß-lactams and novel ß-lactamase inhibitors or ß-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 ß-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 ß-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: ß-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.

Usefulness of quantitative hepatitis B surface antigen testing in hepatitis B community-based screening.

BACKGROUND/PURPOSE: Low viral load (LVL) of hepatitis B virus (HBV) is a predictor of chronic HBV infection. However, the usefulness of quantitative hepatitis B surface antigen (qHBsAg) in predicting LVL in community-based screening has not been well studied. We aimed to measure the prevalence of LVL in HBV carriers and validate the efficacy of qHBsAg in predicting LVL. METHODS: This community-based screening study was conducted in Taiwan. HBV DNA was assayed in HBsAg carriers. Participants were randomized to training and validation sets to determine the ability of qHBsAg to predict LVL. Receiver operating characteristic curves were used to identify the best cutoff values in the training set. RESULTS: Among the 2919 participants, 359 (12.2%) were HBsAg carriers. There were 132 and 137 carriers in the training and validation sets, respectively. Significant correlations were found between qHBsAg and HBV DNA in both training and validation sets. Thirty and 29 participants with qHBsAg <8 IU/mL in the training and validation sets, respectively, had LVL. Using 8 IU/mL as the cutoff, negative predictive value (NPV) of qHBsAg for HBV DNA levels >2000 IU/mL was 100%. The best cutoff level of qHBsAg to predict HBV LVL was 200 IU/mL, with a sensitivity, specificity, and accuracy of 75.0%, 76.1%, and 75.8%, respectively, in the training set. The positive predictive value and NPV were 70.0% and 77.9%, respectively, in the validation set. CONCLUSION: Approximately 60% of HBsAg carriers had HBV LVL, and qHBsAg <8 IU/mL accurately predicts LVL. This quantitative test provides additional information for community-based screening.

Clinical and molecular characterization of Acinetobacter seifertii in Taiwan.

OBJECTIVES: Acinetobacter seifertii, a new member of the Acinetobacter baumannii group, has emerged as a cause of severe infections in humans. We investigated the clinical and molecular characteristics of A. seifertii. PATIENTS AND METHODS: This retrospective study enrolled 80 adults with A. seifertii bloodstream infection (BSI) at four medical centres over an 8 year period. Species identification was confirmed by MALDI-TOF MS, rpoB sequencing and WGS. Molecular typing was performed by MLST. Clinical information, antimicrobial susceptibility and the mechanisms of carbapenem and colistin resistance were analysed. Transmissibility of the carbapenem-resistance determinants was examined by conjugation experiments. RESULTS: The main source of A. seifertii BSI was the respiratory tract (46.3%). The 28 day and in-hospital mortality rates of A. seifertii BSI were 18.8% and 30.0%, respectively. High APACHE II scores and immunosuppressant therapy were independent risk factors for 28 day mortality. The most common MLST type was ST553 (58.8%). Most A. seifertii isolates were susceptible to levofloxacin (86.2%), and only 37.5% were susceptible to colistin. Carbapenem resistance was observed in 16.3% of isolates, mostly caused by the plasmid-borne ISAba1-blaOXA-51-like genetic structure. A. seifertii could transfer various carbapenem-resistance determinants to A. baumannii, Acinetobacter nosocomialis and other A. seifertii isolates. Variations of pmrCAB and lpxCAD genes were not associated with colistin resistance of A. seifertii. CONCLUSIONS: Levofloxacin and carbapenems, but not colistin, have the potential to be the drug of choice for A. seifertii infections. A. seifertii can transfer carbapenem-resistance determinants to other species of the A. baumannii group and warrants close monitoring.

Feasibility of anti-HCV reflex HCV Ag screening strategy in an HCV endemic community.

BACKGROUND/PURPOSE: The HCV core antigen (HCV Ag) assay displays high sensitivity and strong correlation with HCV RNA. However, the feasibility of anti-HCV reflex HCV Ag screening in a community-wide setting is rarely discussed. METHODS: We performed a two-phase community-based hepatitis C screen in an HCV-prone area of central Taiwan. During the training phase, all participants were test for anti-HCV, HCV Ag and HCV RNA to validate sensitivity, specificity, and accuracy of HCV Ag. During the validation phase, an anti-HCV reflex HCV Ag screen was conducted based on the results of training phase. Outcomes of the study were presented as positive and negative predictive values (PPV and NPV). RESULTS: Of 935 training phase participants, the rate of positive anti-HCV and HCV Ag were 175 (18.7%) and 78 (8.3%), respectively. Test sensitivity, specificity, and accuracy of HCV Ag were 97.1%, 98.6%, and 97.8%, respectively. During validation phase, only anti-HCV-positive serum samples were tested for HCV Ag. Of 1932 participant, 285 (14.8%) were anti-HCV-positive. 133 (46.7%) of the 285 anti-HCV-positive samples were HCV Ag-positive. PPV and NPV were 98.4% and 99.3%, respectively. Across the entire participant sample, a significant linear correlation between HCV Ag and HCV RNA concentration was noted (r2 = 0.93, p-value<0.001) following log-log transformation. CONCLUSION: Anti-HCV reflex HCV Ag screening is a feasible strategy for aiding HCV-prone communities.