Genetic relatedness among azole-resistant Candida tropicalis clinical strains in Taiwan from 2014 to 2018.

To monitor trends in the distribution of yeast species and the susceptibilities of these species to commonly prescribed antifungal drugs, we conduct the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) every 4 years. We found that 25 of 294 Candida tropicalis isolates from TSARY 2014 and 31 of 314 C. tropicalis isolates from TSARY 2018 were resistant to fluconazole. We determined the genetic relatedness among fluconazole-resistant C. tropicalis isolates by multilocus sequence typing (MLST). Among 174 C. tropicalis isolates, including all 56 fluconazole-resistant, all 26 susceptible-dose dependent and 92 selected fluconazole-susceptible isolates, 59 diploid sequence types (DSTs) were identified. We found that 22 of the 25 fluconazole-resistant C. tropicalis from TSARY 2014 and 29 of the 31 fluconazole-resistant C. tropicalis from TSARY 2018 were genetically related and belonged to the same cluster (clade 4). A combination of mutation and overexpression of ERG11, encoding the target of azole drugs, was the major mechanism contributing to drug resistance. Approximately two-thirds of reviewed patients infected or colonised by fluconazole-resistant C. tropicalis were azole-naïve. Furthermore, there was no evidence of patient-to-patient transmission. Because the clade 4 fluconazole-resistant C. tropicalis strain persists in Taiwan, it is important to identify the source of azole-resistant C. tropicalis to prevent the spread of this resistant strain.

Methamphetamine Use Associated with Non-adherence to Antiretroviral Treatment in Men Who Have Sex with Men.

Methamphetamine is a prevalent recreational drug among men who have sex with men (MSM) living with HIV and could cause the cognitive impairment and memory loss. However, studies on the association between methamphetamine use and adherence to antiretroviral treatment (ART) are limited and had inconsistent findings. This study aimed to determine the impact of methamphetamine use on adherence to ART among MSM living with HIV. From December 2018 to October 2019, MSM living with HIV were recruited (N = 351) and non-adherence to ART was defined as a Medication Adherence Report Scale score of <23. Overall, 16.0% of the participants reported methamphetamine use in the prior three months and 13.4% of the participants had non-adherence to ART. The proportion of non-adherence to ART among HIV-positive MSM were 28.6% and 10.5% with and without methamphetamine use, respectively. After controlling for demographics, illicit drug use, and co-morbidities, methamphetamine use during the prior three months was associated with a higher risk of non-adherence to ART (adjusted odds ratio = 3.08; 95% confidence intervals: 1.24-7.69). Compared with HIV-positive MSM with non-adherence to ART, HIV-positive MSM with good adherence to ART had a higher CD4 counts and were more likely to achieve an undetectable viral load. Since poor adherence to ART is associated with an increased HIV viral load and the risk of HIV transmission to others, our study suggests that it is imperative to screen HIV-positive patients for methamphetamine use and to provide effective therapy to reduce methamphetamine use and the associated non-adherence to ART.

Human Immunodeficiency Virus Increases the Risk of Incident Heart Failure.

BACKGROUND: Although the HIV can cause myocardial inflammation, the association of HIV infection with subsequent development of heart failure (HF) has not been extensively studied. This nationwide cohort study aimed to determine the risk of incident HF in people living with HIV/AIDS (PLWHA). METHODS: We identified PLWHA using the Taiwan Centers for Disease Control and Prevention HIV Surveillance System. An age- and sex-matched control group without HIV infection was selected from the Taiwan National Health Insurance Research Database for comparison. All patients were followed up until December 2014 and were observed for a new diagnosis of HF. A time-dependent Cox proportional hazards model was used to determine the association of HIV and highly active antiretroviral therapy with incident HF, with death as a competing risk event. RESULTS: Of the 120,765 patients (24,153 PLWHA and 96,612 matched controls), 641 (0.53%) had incident HF during a mean follow-up period of 5.84 years, including 192 (0.79%) PLWHA and 449 (0.46%) controls. Time to diagnosis of incident HF was significantly shorter in PLWHA than in those without HIV infection (P < 0.001, the log-rank test). After adjusting for age, sex, and comorbidities, HIV infection was found to be an independent risk factor for incident HF (adjusted hazard ratio, 1.52; 95% confidence interval: 1.27 to 1.82). As the duration of highly active antiretroviral therapy increased, the risk of HF decreased (P = 0.014). CONCLUSIONS: HIV infection was an independent risk factor for incident HF. Clinicians need to be aware of the higher risk of HF in PLWHA.

Changing hepatitis D virus epidemiology in a hepatitis B virus endemic area with a national vaccination program.

UNLABELLED: The emergence of hepatitis D virus (HDV) infection in the era of widespread HBV vaccination has not been described before. We aimed to investigate the changing epidemiology of HDV infection among high- and low-risk populations after an outbreak of human immunodeficiency virus (HIV) infection among injection drug users (IDUs) in Taiwan. A prospective, multicenter, cohort study of 2,562 hepatitis B surface antigen (HBsAg)-positive individuals was conducted to determine the prevalence, genotype, and risk factors of HDV infection from 2001 through 2012. The prevalence rates of HDV infection were 74.9%, 43.9%, 11.4%, 11.1%, and 4.4% among HIV-infected IDUs, HIV-uninfected IDUs, HIV-infected men who have sex with men, HIV-infected heterosexuals, and the general population of HBsAg-positive subjects, respectively. A significant increase in the trend of HDV prevalence from 38.5% to 89.8% was observed in HIV-infected IDUs (odds ratio = 3.06; 95% confidence interval: 1.68-5.56; P = 0.0002). In multivariate analysis, injection drug use, hepatitis C virus infection, HIV infection, serum HBsAg level ≧250 IU/mL, duration of drug use, and older age were significant factors associated with HDV infection. HDV genotype IV (72.2%) was the prevalent genotype circulating among IDUs, whereas genotype II was predominant in the non-IDU populations (73.3%). In the HIV cohort born after 1987 who were HBsAg negative, over half (52.9%) had antibody to hepatitis B surface antigen antibody levels of <10 mIU/mL and there was a significantly higher HBsAg seroprevalence in the HIV cohort, compared to the control group (8.1% vs. 0.0%; P = 0.02). CONCLUSION: In the era of HBV vaccination, IDUs and HIV-infected individuals have emerged as high-risk groups and a reservoir for HDV infection. Effective strategies are needed to curb the reemerging epidemic of HDV infection in these high-risk groups.

Patients infected with CRF07_BC have significantly lower viral loads than patients with HIV-1 subtype B: mechanism and impact on disease progression.

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.

Epidemiology and staphylococcal cassette chromosome mec typing of methicillin-resistant Staphylococcus aureus isolates in Taiwan: A multicenter study.

BACKGROUND/PURPOSE: After community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was identified, new community-onset, healthcare-associated MRSA (HA-MRSA-CO) infections have been noticed as MRSA infection in patients with community-onset infection who have underlying conditions resulting in frequent exposure to the healthcare system. However, previous studies have not thoroughly investigated whether HA-MRSA-CO has characteristics resembling those of CA-MRSA or hospital-onset, healthcare-associated MRSA (HA-MRSA-HO) infection. METHODS: A multicenter, retrospective study was conducted to analyze the clinical and microbiological data of patients with clinical isolates of MRSA from nine hospitals in Taiwan. RESULTS: In total, 203 patients with MRSA isolates, including 27 patients with CA-MRSA (13.3%), 59 with HA-MRSA-CO (29.1%), and 117 with HA-MRSA-HO (57.6%), were studied. Compared to HA-MRSA-HO isolates, the CA-MRSA and HA-MRSA-CO isolates were associated with a higher proportion of skin and soft tissue infections (81.8% and 65.3% vs. 40.5%, p=0.001 and p=0.002) as well as lesser rate of resistance to ciprofloxacin (33.3% and 50.9% vs. 74.4%, p<0.001 and p=0.002), gentamicin (44.4% and 64.4% vs. 84.6%, p<0.001 and p=0.002), and trimethoprim/sulfamethoxazole (33.3% and 42.4% vs. 58.1%, p=0.02 and p=0.048), and a lower 30-day all-cause mortality rate (7.4% and 0% vs. 20.9%, p<0.001). Most of the CA-MRSA isolates were classified as staphylococcal cassette chromosome mec (SCCmec) type VT (11/27, 40.7%), whereas most HA-MRSA-HO isolates were classified as SCCmec type III (66/117, 56.4%). CONCLUSION: The CA-MRSA, HA-MRSA-CO, and HA-MRSA-HO clinical isolates significantly differed in their clinical presentations and molecular characteristics.

Latent tuberculosis among injection drug users in a methadone maintenance treatment program, Taipei, Taiwan: TSPOT.TB versus tuberculin skin test.

BACKGROUND: Taiwan has a growing HIV/AIDS epidemic that has recently shifted to an increase among injection drug users (IDUs). IDUs co-infected with HIV and tuberculosis (TB) have a high risk of progression from latent tuberculosis infection (LTBI) to active TB. METHODS: This study aimed to determine the prevalence and correlates of LTBI among IDUs by TSPOT.TB and tuberculin skin test (TST), in a large methadone program in Taipei, Taiwan. Consenting participants were interviewed by a trained worker regarding sociodemographics, substance use history, and health factors. RESULTS: Multivariate analysis was used to determine risks associated with each test outcome. Of 287 participants, 165 (58.7%) tested TSPOT.TB-positive and 244 (85.0%) tested TST-positive. The mean age was 44 y, and 7.3% were HIV-infected. Kappa statistics indicated slight concordance between TSPOT.TB and TST. In multivariate analysis, after controlling for potential confounders, TSPOT.TB positivity was significantly associated with age ≥ 50 y (reference, 20-34 y). A history of ever having had contact with a TB-infected person was associated with TST positivity, whereas HIV infection was inversely associated with TSPOT.TB positivity and TST positivity. CONCLUSIONS: This study shows a high prevalence of LTBI in individuals at risk for HIV infection in Taipei, Taiwan. Future TB prevention programs should particularly focus on IDUs.

Early experience of the pandemic influenza H1N1 2009 epidemic in Taiwan.

BACKGROUND: A novel influenza H1N1 began in March 2009, rapidly spread, and then became a pandemic outbreak. Diagnosis by polymerase chain reaction result was not always available because of a surge in workload and therefore clinical diagnosis became important. However, clinical differences between the patients infected by the novel H1N1 virus and those infected by the influenza-like non-novel H1N1 have not been reported. This study was conducted to compare the demographic background, clinical manifestations, and laboratory findings between novel H1N1 influenza infections and other non-novel H1N1 infections. METHODS: At an early stage of H1N1 spread, cases presenting with influenza-like symptom and travel or contact history were quarantined into infection disease-designated hospitals in Taiwan. Data on consecutive patients under investigation for infection with novel influenza A (H1N1) were collected between April 29 and June 19, 2009. The data set consisted of clinical manifestations, plain chest radiography, hematological results, and biochemical findings. Testing of nasopharyngeal swab samples by reverse transcription polymerase chain reaction was used to detect H1N1. RESULTS: Overall, 166 cases were collected. Among these individuals, there were 14 confirmed H1N1 cases. The clinical manifestations of the H1N1 cases included fever in 13 patients (92.9%), followed by cough, rhinorrhea, a sore throat, myalgia, headache, malaise, abdominal tenderness, and diarrhea. Leukopenia was present in nine patients (64.2%) and lymphocytopenia was present in five (35.7%). The duration of virus shedding was 7.0 ± 1.8 days. When compared with the non-H1N1 cases by multiple logistic regression analysis, cases infected by the novel H1N1 virus were more likely to be younger than 20 years [Odds ratio (OR) = 27.7, 95% confidence interval (CI) = 1.3-597.8, p = 0.034), have traveled from the US (OR = 14.5, 95% CI = 2.1-101.4, p = 0.007) or Thailand (OR = 56.7, 95% CI = 4.6-700.6, p = 0.002) and to have presented with myalgia (OR = 8.5, 95% CI = 1.4-52.0, p = 0.021) or leukopenia (OR = 17.4, 95% CI = 3.4-90.5, p = 0.001). CONCLUSION: When a patient presents with influenza-like acute febrile respiratory illness symptoms and is young in age, has a travel history involving an affected area, and is suffering from myalgia or leukopenia, physicians should be alerted to the possibility of novel H1N1 virus infection.

Humoral immunity against capsule polysaccharide protects the host from magA+ Klebsiella pneumoniae-induced lethal disease by evading Toll-like receptor 4 signaling.

Klebsiella pneumoniae magA (for mucoviscosity-associated gene A) is linked to the pathogenesis of primary pyogenic liver abscess, but the underlying mechanism by which magA increases pathogenicity is not well elucidated. In this study, we investigated the role of the capsular polysaccharides (CPS) in the pathogenesis of magA(+) K. pneumoniae by comparing host immunity to magA(+) K. pneumoniae and a DeltamagA mutant. We found that Toll-like receptor 4 recognition by magA(+) K. pneumoniae was hampered by the mucoviscosity of the magA(+) K. pneumoniae CPS. Interestingly, monoclonal antibodies (MAbs) against magA(+) K. pneumoniae CPS recognized all of the K1 strains tested but not the DeltamagA and non-K1 strains. Moreover, the anti-CPS MAbs protected mice from magA(+) K. pneumoniae-induced liver abscess formation and lethality. This indicates that the K1 epitope is a promising target for vaccine development, and anti-CPS MAbs has great potential to protect host from K1 strain-induced mortality and morbidity in diabetic and other immunocompromised patients in the future.

A prospective etiologic study of community-acquired pneumonia in Taiwan.

BACKGROUND AND PURPOSE: The treatment of community-acquired pneumonia (CAP) is complicated by the growing threat of antimicrobial resistance and the tendency to rely on empirical therapy. This study investigated the etiologic agents of adult CAP in Taiwan and the susceptibility of Streptococcus pneumoniae isolates from these patients. METHODS: A collaborative group was established in the emergency department to conduct a prospective study of the etiology of adult CAP. The etiologic agent was determined by a combination of microscopic, culture, serologic and antigen detection methods. Pneumococcal susceptibility testing was performed to determine the extent of penicillin resistance. RESULTS: A total of 100 consecutive cases of mild to moderate adult CAP prior to the severe acute respiratory syndrome epidemic were enrolled. The etiologic agent was determined in 72% of cases. The 5 most common causative pathogens were S. pneumoniae (26%), Mycoplasma pneumoniae (20%), Chlamydia pneumoniae (13%), Haemophilus influenzae (9%), and Klebsiella pneumoniae (5%). Atypical pathogens accounted for 40% of CAP. Bacteremic pneumonia was diagnosed in 6.2% of cases. Co-infections with 2 or more pathogens were found in 16% of the cases. Among the 20 isolates of S. pneumoniae, 85% (17/20) were susceptible to penicillin, 3 (15%) were intermediate, and none were resistant to penicillin. CONCLUSION: S. pneumoniae, M. pneumoniae and C. pneumoniae were the 3 leading causes of mild to moderate CAP in Taiwan. This study indicates that penicillin-resistant S. pneumoniae play a very limited role in this condition in adults.

Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital.

OBJECTIVES: To describe the immunological responses and clinical outcome of coronavirus (SARS) infected healthcare workers (HCW) who had been administered with convalescent plasma as a treatment. METHODS: Convalescent plasma (500 mL) was obtained from each of three SARS patients and transfused into the three infected HCW. Donors were blood type O and seronegative for hepatitis B and C, HIV, syphilis and human T-cell lymphotropic virus types I and II (HTLV-I and -II). Serum antibody (IgG) titre was >640. Apharesis was performed with a CS 3000 plus cell separator followed by the forming of the convalescent phase plasma. As part of the routine check with donated plasma, the convalescent plasma was confirmed free of residual SARS-CoV by RT-PCR. Serial serum samples obtained from the recipients of the convalescent plasma were collected to undertake real-time quantitative RT-PCR for SARS-CoV for direct measurement of viral concentration. Specific immunoglobulin IgM and IgG concentrations were titrated using an antigen microarray developed in-house. RESULTS: Viral load dropped from 495 x 10(3), 76 x 10(3) or 650 x 10(3) copies/mL to zero or 1 copy/mL one day after transfusion. Anti-SARS-CoV IgM and IgG also increased in a time-dependent manner following transfusion. All three patients survived. One HCW became pregnant subsequently, delivering 13 months after discharge. Positive anti-SARS-CoV IgG was detected in the newborn. Passive transfer of anti-SARS-CoV antibody from the mother was considered as a possibility. CONCLUSIONS: All infected HCW whose condition had progressed severely and who had failed to respond to the available treatment, survived after transfusion with convalescent plasma.

Clinical and genetic analysis of invasive and non-invasive group A streptococcal infections in central Taiwan.

To evaluate the clinical, bacteriologic, and genetic relatedness between invasive and non-invasive infections caused by group A Streptococcus (GAS), we retrospectively analyzed the GAS isolates in our hospital from the past decade. A total of 70 GAS-infected cases were enrolled in our study from the period 1993 to 2002. Twenty one cases had invasive disease, and 49 were non-invasive. Their medical records were reviewed, and demographic data were collected for analysis. Antimicrobial susceptibility testing was conducted according to the National Committee for Clinical Laboratory Standards for Streptococcus spp. Isolates were subjected to chromosomal SmaI (Invitrogen) digestion of pulsed-field gel electrophoresis (PFGE), and emm typing was also performed. The mean age of the invasive group was 41.1 +/- 22.4 years compared with 13.0 +/- 16.6 years for the non-invasive group (p<0.05). Eighty one percent of the invasive group had underlying diseases. Diabetes and malignancy were the 2 most common medical conditions. All isolates were susceptible to penicillin. The resistance rate was 42.8% and 55.1% for erythromycin in the invasive and non-invasive groups, respectively. A total of 51 different PFGE types were identified among the GAS isolates without particular genotypes. Serotype M12 was the most common one (28.4%), followed by M4 (19.4%). Our study demonstrated that the patients in the invasive group were older, with more underlying diseases, and with a higher mortality rate. Antimicrobial susceptibility of the isolates was the same in both groups. There was no epidemic strain, nor did PFGE reveal a more invasive clone.

Haemophilus parainfluenzae and Fusobacterium necrophorum liver abscess: a case report.

Liver abscess is a potentially life-threatening disease. The clinical features of pyogenic liver abscess are variable and probably correlate with a variety of pathogenic microorganisms and underlying diseases that may be involved. The most common pathogen of liver abscess in Taiwan is Klebsiella pneumoniae. Diabetes mellitus and hepatobiliary calculus are major diseases associated with liver abscess. Haemophilus parainfluenzae is a commensal of the upper respiratory tract, but is an uncommon isolate in liver abscess. We describe a 44-year-old man with liver abscess caused by mixed H. parainfluenzae and Fusobacterium necrophorum infection. He received percutaneous liver abscess drainage and intravenous antibiotic therapy for 3 weeks and fully recovered. No recurrence occurred during the follow-up period of 4 months.