Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

High rates of misidentification of uncommon Candida species causing bloodstream infections using conventional phenotypic methods.

BACKGROUND: Candidemia caused by uncommon Candida species is increasing and misidentification may compromise optimal antifungal therapy. This multicenter study aimed to evaluate the accuracy of species-level identification of uncommon Candida. METHODS: Uncommon causative species of candidemia identified in routine laboratories using CHROMagar, API-32C and VITEK-2 Yeast ID system were collected from July 2011 to June 2014. These isolates were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system and sequencing of the internal transcribed spacer and 28S rRNA gene. Susceptibility of the isolates was determined. RESULTS: Of 85 isolates evaluated, Candida guilliermondii (n = 36) was the most common, followed by Candid sake (n = 7) and Candida famata (n = 4). Using DNA-sequencing analysis as standard, none of C. sake and C. famata was correct, while VITEK MS correctly identified 10 of the 11 isolates. With the exclusion of one unspecified Candida by DNA-sequencing methods, the accuracy of conventional methods and VITEK MS was 64.3% and 86.9%, respectively (p = 0.001). Eight isolates were confirmed to be yeasts other than Candida. Compared with other Candida species, C. guilliermondii showed elevated minimal inhibitory concentration of echinocandins. CONCLUSION: Misidentification of uncommon Candida species was common using the conventional methods, especially for C. sake and C. famata. MALDI-TOF MS assisted by DNA-sequencing methods should be considered.

Early Seroreversion After 2 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Patients: Incidence and Associated Factors.

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)-positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV-positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV-positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case-control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow-up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow-up of 611 days. In a case-control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292-2.323, per 10-kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067-7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020-0.154) and 0.837 (95% CI, 0.704-0.979, per 100-cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two-dose HAV vaccination occurred in 3.9% of HIV-positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV-positive adults with predictors of early seroreversion.

Less Severe but Prolonged Course of Acute Hepatitis A in Human Immunodeficiency Virus (HIV)-Infected Patients Compared With HIV-Uninfected Patients During an Outbreak: A Multicenter Observational Study.

Background: This multicenter retrospective cohort study aimed to compare the clinical presentations and evolution of acute hepatitis A (AHA) between human immunodeficiency virus (HIV)-infected patients and HIV-uninfected counterparts during the AHA outbreak. Methods: Clinical and laboratory data were collected from the medical records of the patients with AHA at the 14 hospitals around Taiwan between May 2015 and May 2017. Results: A total of 297 adult patients with AHA were included during the study period. Their mean age was 31.4 years (range, 19.0-76.1 years); 93.4% were men and 58.6% were men who have sex with men. Of 265 patients with known HIV serostatus, 166 (62.6%) were HIV infected. Compared with HIV-uninfected patients, HIV-infected patients had a lower peak alanine aminotransferase (ALT) level (median, 1312 vs 2014 IU/L, P = .003), less coagulopathy (6.0% vs 16.2%, P = .007), and less hepatomegaly or splenomegaly on imaging studies, but a higher rate of delayed resolution of hepatitis (38.8% vs 21.3%, P = .009). HIV-infected patients with plasma RNA load <1000 copies/mL while receiving combination antiretroviral therapy (cART) had a higher peak ALT level (median, 1420 vs 978 IU/L, P = .006) and less delay in resolution of hepatitis (30.6% vs 48.8%, P = .047) than patients without cART or with plasma RNA load ≥1000 copies/mL. Conclusions: During an AHA outbreak, HIV-infected patients had a lower severity, but delayed resolution, of AHA than HIV-uninfected patients. Better viral suppression by cART alleviated the impact of HIV infection on the disease course of AHA in HIV-infected patients.

Are we ready for the global emergence of multidrug-resistant Candida auris in Taiwan?

Candida auris is a recently identified multi-resistant Candida species, first reported in Japan in 2009, and poses a serious global health threat. Lack of awareness of this new Candida species and difficulties with laboratory identification have impacted significantly on outbreak detection and management, and compromised patient outcome. Accordingly, there is an urgent need to raise awareness of healthcare personnel to this emerging pathogen and determine its prevalence, impact, and challenges to the Taiwan healthcare system. Enhanced laboratory testing strategies are needed to differentiate C. auris from other Candida species to provide accurate diagnosis and implement control measures early enough to prevent hospital outbreaks. In this report, we review the key epidemiological, microbiological and clinical characteristics of C. auris and provide the results of a multicenter surveillance study of C. auris in Taiwan. We also conducted a web-based survey to determine awareness of the medical community to C. auris and the capability of Taiwanese hospital laboratories to identify this microorganism. C. auris has not yet been isolated from humans in Taiwan, but the unique features of this microorganism and its ability to reach across international boundaries justify the importance of these initiatives in Taiwan.

Presence of cytomegalovirus DNA in leucocytes is associated with increased oxidative stress and subclinical atherosclerosis in healthy adults.

OBJECTIVE: Investigate the latent cytomegalovirus (CMV) infection as a biomarker of oxidative stress and atherosclerosis. METHODS: Latent CMV infection was diagnosed in healthy individuals with PCR-evidence of CMV DNA in peripheral leucocytes. Oxidative stress and atherosclerosis were measured by mitochondrial DNA oxidative damage index (mtDNA(ΔCT)) and intima media thickness (IMT). RESULTS: The CMV DNA positive subjects had a higher mean mtDNA(ΔCT) and greater IMT than subjects in the control group. CONCLUSIONS: Presence of CMV DNA in leucocytes, as a marker of latent CMV infection, was associated with increased levels of oxidative stress and subclinical atherosclerosis in healthy adults.

Antituberculosis treatment and hepatotoxicity in patients with chronic viral hepatitis.

BACKGROUND: Whether antituberculosis (anti-TB) treatment in patients with chronic viral hepatitis affects the incidence and onset time of drug-induced hepatotoxicity (DIH) is still controversial. The aim of this retrospective study was to find out whether chronic viral hepatitis affects the incidence and onset time of DIH. METHODS: All patients diagnosed with active TB and being treated at a tertiary referral hospital between 2002 and 2009 were identified from medical records, from which 553 patients were enrolled in the study. The incidence and onset of DIH in patients with and without chronic viral hepatitis (controls) were compared. RESULTS: The incidence of DIH was similar in patients with and without chronic hepatitis (8 % [32/392] vs. 7 % [11/161], P > 0.05). The incidence of transient liver function impairment (TLI) was significantly lower in controls than in chronic hepatitis patients (2 % [9/392] vs. 12 % [20/161], P < 0.001. The mean onset times of DIH in the control, hepatitis B virus (HBV), and hepatitis C virus (HCV) groups were not significantly different (40, 39, and 67 days, respectively, all P > 0.05). The mean onset times of TLI in the control, HBV, and HCV groups were significantly different (23, 48, and 68 days, respectively, all P < 0.05). CONCLUSIONS: Liver function impairment during anti-TB therapy in patients with chronic viral hepatitis was due to mostly TLI, with TLI occurring later than in controls. Chronic viral hepatitis had no significant effect on the incidence of DIH.

Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018-2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. METHODS: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and ß-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). RESULTS: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC ß-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel ß-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam. CONCLUSIONS: The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Efficacy of copper-silver ionization for controlling fungal colonization in water distribution systems.

The purpose of this study was to identify the prevalence of fungal colonization in water systems and to evaluate the effect of decreasing fungal colonization by a copper-silver ionization system. Environmental samples were collected for fungal culture prospectively during a 1-year period (2011-2012) at the study hospital. A total of 392 water samples were examined from five buildings on March 1, 2011 and February 29, 2012. Fungi were isolated in 13 (3.4%) of 392 water samples from five buildings. The prevalence of fungal colonization in buildings was decreased from 4.76% (9/189) to 1.97% (4/203), a reduction of more than 40%, in pre-ionization and post-ionization treatment (p < 0.001). Thirteen (3.4%) of 392 water samples yielded fungi including Fusarium species (n = 7), Penicillium species (n = 2), Scedosporium species (n = 2), Aspergillus species (n = 1), and one unidentifiable mold. The number of isolated Fusarium species in ionized water samples (0.5% (1/203)) was statistically lower than those in nonionized (3.2% (6/189)) (p = 0.003). Our finding may determine if this ionization method can be applied for control of waterborne fungi colonization in hospital water systems.

Zoonotic atypical pneumonia due to Chlamydophila psittaci: first reported psittacosis case in Taiwan.

Human psittacosis caused by Chlamydophila psittaci is one of the most common zoonotic atypical pneumonias featuring pulmonary as well as extrapulmonary infections. Most of the cases involve avian contact history especially with psittacine birds. Herein we report a 44-year-old male patient displaying atypical pneumonia symptoms of intermittent fever, dry cough, chest pain, dyspnea, headache, hepatitis, and hyponatremia. He had two sick cockatiels, one of which had died a month previously. A microimmunofluorescence test was performed to check the serum antibody levels against Chlamydophila psittaci. The serum IgM titer showed positive titer of 1:256, 1:256, and 1:128 on Days 11, 23, and 43 after disease onset, respectively. His fever subsided soon and clinical symptoms improved after minocycline was administrated on Day 12. The psittacosis case was confirmed by history of psittacine bird contact, clinical symptoms, treatment response, and positive IgM titer. To our knowledge, this is the first report of a psittacosis case in Taiwan.

In vitro susceptibilities of Stenotrophomonas maltophilia isolates to antimicrobial agents commonly used for related infections: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2004-2020.

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

Seroprevalence of varicella-zoster virus antibody and immunogenicity of live attenuated varicella vaccine in healthcare workers in Taiwan.

BACKGROUND: Healthcare workers (HCWs) without evidence of immunity to varicella-zoster virus (VZV) are recommended to undergo varicella vaccination. Immunogenicity of live attenuated varicella vaccine has rarely been investigated among HCWs in Taiwan. METHODS: Anti-VZV immunoglobulin G (IgG) titer was checked for all HCWs at Changhua Christian Hospital from 2011 to 2017. One-dose and two-dose (separated by 4-8 weeks) vaccines were administered to HCWs with equivocal and negative anti-varicella IgG results, respectively. Follow-up anti-VZV IgG was determined at least 4 weeks after completion of vaccination. Factors associated with seroconversion to varicella vaccination were analyzed. RESULTS: Among 2406 included HCWs, the anti-VZV IgG serostatus was tested positive, equivocal and negative in 1924 (79.9%), 117 (4.9%) and 365 (15.2%), respectively. The seroprevalence had decreased from 88.0% (235/267) in 2011 to 72.2% (270/374) in 2017 (p for trend <0.05). A total of 67.8% (327/482) HCWs completed scheduled vaccination and serological follow-up. The seroconversion rates for HCWs with baseline equivocal and negative anti-VZV IgG results were 100% (80/80) and 79.4% (196/247) after one- and two-dose vaccination, respectively. In multivariate analysis, obesity (adjusted odds ratio, 0.308; 95% confidence interval [CI], 0.11-0.94, p = 0.039) was the only factor statistically significantly associated with seroconversion to vaccination. CONCLUSION: Decreasing trends of seroprevalence of VZV were observed among HCWs from 2011 to 2017. HCWs who were obese were less likely to respond to varicella vaccination.

Switching to coformulated bictegravir, emtricitabine, and tenofovir alafenamide maintained viral suppression in adults with historical virological failures and K65N/R mutation.

OBJECTIVES: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. METHODS: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) <200 copies/ml for ≥3 months. PLWH were excluded if integrase inhibitor resistance-associated mutations were detected. The primary end point was losing virologic control (PVL >50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. RESULTS: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL <50 copies/ml before switching. After a median observation of 98.6 weeks (interquartile range 77.9-120.3), 94.4% (n = 68) continued BIC/FTC/TAF. At week 48, the rate of losing virologic control was 2.8% (2/72). M184V/I was not associated with viral rebound. CONCLUSION: Despite the emergence of K65N/R +/- M184V/I after virologic failures, BIC/FTC/TAF could be an option for simplification after viral suppression.

A new collaborative care approach toward hepatitis C elimination in marginalized populations.

BACKGROUND: Treating marginalized populations with HCV infection for elimination is faced with the challenge for the integration of HCV screening service offered for patients often moving across multiple settings. We envisaged a novel collaborative care approach to identify to what extent HCV patients overlapped between and within these multiple institutions and reported the findings of treatment coverage of these marginalized populations after HCV care cascades. METHODS: We enrolled 7765 patients residing in the Changhua County, Taiwan offered with HCV screening from correctional institutions, HIV clinics, methadone clinics, and the existing HIV surveillance program (four subgroups including police-arrested people, probationers, non-injection drug user, and high-risk behavior people) between 2019 and 2020. The collaborative care and information were integrated through a teamwork of gastroenterologists, psychologists, infectious disease specialists, and nursing coordinators under the auspices of local health authority. RESULTS: The overall participation rate in HCV screening was 92.65% (7194/7765). The prevalence rate was the highest in methadone clinics (90.17%) followed by correctional institutions (37.67%), HIV clinics (34.60%), and the surveillance program (18.14%). We found 25.41% (77/303) of methadone clinic patients, 17.65% (129/731) of HIV clinic patients, and various proportions for 44.09% (41/93) of deferred prosecuted or probationers under surveillance program were also recruited into other settings. Individuals' patient flow within setting was more frequent than that between setting. After calibrating the overlap of patient flow, a total of 1700 anti-HCV positives out of 4074 after screening were traced with available follow-up information to complete 92.52% treatment coverage of 1177 RNA-positives (77.23%) diagnosed from 1524 undergoing RNA testing with similar findings across multiple settings. CONCLUSION: A new collaborative integrated care was adopted for elucidating patient flow between and within multiple settings in order to calibrate the accurate demand for HCV care cascades and enhance HCV treatment coverage in marginalized populations.

Week 96 Results of Switching from Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide among HIV/Hepatitis B Virus-Coinfected Patients.

Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of <50 copies/mL with tenofovir disoproxil fumarate (TDF)-containing ART and switched to elvitegravir/cobicistat/emtricitabine/TAF were prospectively enrolled. Serial plasma HIV and HBV viral loads, HBV and hepatitis D virus (HDV) serology, renal parameters, metabolic profiles, and bone mineral density (BMD) were assessed through 96 weeks. At baseline and weeks 48, 72, and 96, 5.8%, 5.1%, 5.8%, and 5.1% of the participants had plasma HBV DNA of ≥20 IU/mL, and 0%, 0.7%, 1.5%, and 2.2% had HIV RNA of ≥50 copies/mL, respectively. Hepatitis B surface antigen (HBsAg) loss occurred in 1.5% of 274 participants, and hepatitis B e-antigen (HBeAg) loss or seroconversion occurred in 14.3% of 35 HBeAg-positive participants. Compared with baseline, the median urine protein-to-creatinine ratio (79 versus 63 mg/g, P < 0.001) and ß2-microglobulin-to-creatinine ratio (165 versus 83 µg/g, P < 0.001) continued to decrease at week 96. BMD of the spine and hip slightly increased (mean change, +0.9% and +0.5%, respectively). The median triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol increased from baseline to week 96 (116 versus 141, 166 versus 190, 99 versus 117, and 42 versus 47 mg/dL, respectively; all P < 0.001), and most of the increases occurred in the first 48 weeks of the switch. Our study showed that switching from TDF-containing ART to elvitegravir/cobicistat/emtricitabine/TAF maintained HBV and HIV viral suppression through 96 weeks among HIV/HBV-coinfected patients. Proteinuria continued to improve, while fasting lipids increased and BMD stabilized at 96 weeks after the switch. IMPORTANCE Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide as a maintenance therapy showed durable and high rates of viral suppression for HIV/HBV-coinfected patients, with only 5.1% and 2.2% of patients having HBV DNA of ≥20 IU/mL and HIV RNA of ≥50 copies/mL, respectively, at 96 weeks. Our study fills the data gap on the long-term clinical effectiveness of tenofovir alafenamide-containing antiretroviral therapy in people living with HIV who have HBV coinfection.

Whole-genome sequencing and identification of Morganella morganii KT pathogenicity-related genes.

BACKGROUND: The opportunistic enterobacterium, Morganella morganii, which can cause bacteraemia, is the ninth most prevalent cause of clinical infections in patients at Changhua Christian Hospital, Taiwan. The KT strain of M. morganii was isolated during postoperative care of a cancer patient with a gallbladder stone who developed sepsis caused by bacteraemia. M. morganii is sometimes encountered in nosocomial settings and has been causally linked to catheter-associated bacteriuria, complex infections of the urinary and/or hepatobiliary tracts, wound infection, and septicaemia. M. morganii infection is associated with a high mortality rate, although most patients respond well to appropriate antibiotic therapy. To obtain insights into the genome biology of M. morganii and the mechanisms underlying its pathogenicity, we used Illumina technology to sequence the genome of the KT strain and compared its sequence with the genome sequences of related bacteria. RESULTS: The 3,826,919-bp sequence contained in 58 contigs has a GC content of 51.15% and includes 3,565 protein-coding sequences, 72 tRNA genes, and 10 rRNA genes. The pathogenicity-related genes encode determinants of drug resistance, fimbrial adhesins, an IgA protease, haemolysins, ureases, and insecticidal and apoptotic toxins as well as proteins found in flagellae, the iron acquisition system, a type-3 secretion system (T3SS), and several two-component systems. Comparison with 14 genome sequences from other members of Enterobacteriaceae revealed different degrees of similarity to several systems found in M. morganii. The most striking similarities were found in the IS4 family of transposases, insecticidal toxins, T3SS components, and proteins required for ethanolamine use (eut operon) and cobalamin (vitamin B12) biosynthesis. The eut operon and the gene cluster for cobalamin biosynthesis are not present in the other Proteeae genomes analysed. Moreover, organisation of the 19 genes of the eut operon differs from that found in the other non-Proteeae enterobacterial genomes. CONCLUSIONS: This is the first genome sequence of M. morganii, which is a clinically relevant pathogen. Comparative genome analysis revealed several pathogenicity-related genes and novel genes not found in the genomes of other members of Proteeae. Thus, the genome sequence of M. morganii provides important information concerning virulence and determinants of fitness in this pathogen.

Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 µg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Trends in susceptibility of vancomycin-resistant Enterococcus faecium to tigecycline, daptomycin, and linezolid and molecular epidemiology of the isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006 to 2010.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC(90)s) from 2006-2007 (0.06 µg/ml) to 2008-2010 (0.12 µg/ml). The MIC(90)s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.