Prediction of incidence of neurological disorders in HIV-infected persons in Taiwan: a nested case-control study.

BACKGROUND: Neurological disorders are still prevalent in HIV-infected people. We aimed to determine the prevalence of neurological disorders and identify their risk factors in HIV-infected persons in Taiwan. METHODS: We identified 30,101 HIV-infected people between 2002 and 2016 from the National Health Insurance Research Database in Taiwan, and analyzed the incidence of neurological disorders. We applied a retrospective, nested case-control study design. The individuals with (case group) and without (control group) a neurological disorder were then matched by age, sex and time. Factors associated with neurological disorders were analyzed using a conditional logistic regression model, and a nomogram was generated to estimate the risk of developing a neurological disorder. RESULTS: The incidence of neurological disorders was 13.67 per 1000 person-years. The incidence remained stable during the observation period despite the use of early treatment and more tolerable modern anti-retroviral therapy. The conditional logistic regression model identified nine clinical factors and comorbidities that were associated with neurological disorders, namely age, substance use, traumatic brain injury, psychiatric illness, HIV-associated opportunistic infections, frequency of emergency department visits, cART adherence, urbanization, and monthly income. These factors were used to establish the nomogram. CONCLUSION: Neurological disorders are still prevalent in HIV-infected people in Taiwan. To efficiently identify those at risk, we established a nomogram with nine risk factors. This nomogram could prompt clinicians to initiate further evaluations and management of neurological disorders in this population.

Geographic distribution of the major clone of extended-spectrum beta-lactamase-producing Escherichia coli infection in a pediatric community in southern Taiwan.

BACKGROUND: The geographic distribution of the major clone of sequence type 131 (ST131) in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) infections is not known. We analyzed the clinical features, resistance mechanisms, and geographic distribution of ESBL-producing E. coli clones in 120 children. METHODS: We studied the 120 ESBL-producing E. coli strains from children younger than 18 years. A VITEK 2 automated system was used to determine bacterial identification and ESBL production. Sequence type was determined by multi-locus sequence typing (MLST). The genetic relationship of the ESBL-producing strains was studied using pulsed-field gel electrophoresis (PFGE). Phylogenetic group and blaCTX-M group was performed using polymerase chain reaction (PCR). Multiplex PCR for detecting the common group 9 variant, CTX-M-14, and group 1 variant, CTX-M-15, was also performed. The addresses of the 120 children were collected, and plotted on the Taiwan map. RESULTS: The groups in the center of Kaohsiung City lived mainly in urban areas with a population density of over 10,000 people per square kilometer, and the majority of the Kaohsiung groups on the outskirts of the city center lived in suburban areas with a population density of under 6000 people per square kilometer. There was no statistically significant difference between the city center and outskirt groups in terms of clinical presentation, laboratory, and imaging data. However, more ST131 clones, major pulsotype groups, and phylogenetic group B2 strains were found in the center of Kaohsiung than on the outskirts. CONCLUSION: ESBL-producing E. coli clones may be more challenging to treat clinically. Most infections were community-acquired, and there appeared to be major pulsotype clones, mainly in urban areas. This reinforces the necessity of environmental surveillance and sanitary procedures for ESBL-producing E. coli.

COVID-19-associated candidiasis and the emerging concern of Candida auris infections.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide. The therapeutic strategy towards CAC caused by common Candida species, such as Candida albicans, Candida tropicalis, and Candida glabrata, is similar to the pre-pandemic era. For non-critically ill patients or those with a low risk of azole resistance, fluconazole remains the drug of choice for candidemia. For critically ill patients, those with a history of recent azole exposure or with a high risk of fluconazole resistance, echinocandins are recommended as the first-line therapy. Several novel therapeutic agents alone or in combination with traditional antifungal agents for candidiasis are potential options in the future. However, for multidrug-resistant C. auris infection, only echinocandins are effective. Infection prevention and control policies, including strict isolation of the patients carrying C. auris and regular screening of non-affected patients, are suggested to prevent the spread of C. auris among patients with COVID-19. Whole-genome sequencing may be used to understand the epidemiology of healthcare-associated candidiasis and to better control and prevent these infections.

Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

The first imported case of monkeypox in Taiwan.

he first imported case of monkeypox in Taiwan was diagnosed in an Asian man with HIV-1 infection and asymptomatic COVID-19, returning from Germany. Atypical presentations included asynchronous skin lesions, anogenital lesions and prominent inguinal lymphadenopathy. Whole genomic sequence alignment indicate that the Taiwan strain clustered together with human monkeypox virus West African clade B.1, currently circulating in Europe. Prompt diagnosis and infection control measures are crucial to mitigate the spread of monkeypox.

Using a Knowledge-Based Clinical Decision Support System to Reduce the Time to Appropriate Antimicrobial Therapy in Hospitalized Patients With Bloodstream Infections: A Single-Center Observational Study.

Background: Inappropriate antimicrobial use is a crucial determinant of mortality in hospitalized patients with bloodstream infections. Current literature reporting on the impact of clinical decision support systems on optimizing antimicrobial prescription and reducing the time to appropriate antimicrobial therapy is limited. Methods: Kaohsiung Veterans General Hospital implemented a hospital-wide, knowledge-based, active-delivery clinical decision support system, named RAPID (Real-time Alert for antimicrobial Prescription from virtual Infectious Diseases experts), to detect whether there was an antimicrobial agent-pathogen mismatch when a blood culture result was positive. Once RAPID determines the current antimicrobials as inappropriate, an alert text message is immediately sent to the clinicians in charge. This study evaluated how RAPID impacted the time to appropriate antimicrobial therapy among patients with bloodstream infections. Results: During the study period, 633 of 11 297 recorded observations (5.6%) were determined as inappropriate antimicrobial prescriptions. The time to appropriate antimicrobial therapy was significantly shortened after the implementation of RAPID (1.65 vs 2.45 hours, P < .001), especially outside working hours (1.24 vs 6.43 hours, P < .001), in the medical wards (1.40 vs 2.14 hours, P < .001), in participants with candidemia (0.74 vs 5.36 hours, P < .001), and for bacteremia due to non-multidrug-resistant organisms (1.66 vs 2.49 hours, P < .001). Conclusions: Using a knowledge-based clinical decision support system to reduce the time to appropriate antimicrobial therapy in a real-world scenario is feasible and effective. Our results support the continued use of RAPID.

Coronavirus disease 2019 (COVID-19) associated bacterial coinfection: Incidence, diagnosis and treatment.

Coronavirus disease 2019 (COVID-19) emerged as a pandemic that spread rapidly around the world, causing nearly 500 billion infections and more than 6 million deaths to date. During the first wave of the pandemic, empirical antibiotics was prescribed in over 70% of hospitalized COVID-19 patients. However, research now shows a low incidence rate of bacterial coinfection in hospitalized COVID-19 patients, between 2.5% and 5.1%. The rate of secondary infections was 3.7% in overall, but can be as high as 41.9% in the intensive care units. Over-prescription of antibiotics to treat COVID-19 patients fueled the ongoing antimicrobial resistance globally. Diagnosis of bacterial coinfection is challenging due to indistinguishable clinical presentations with overlapping lower respiratory tract symptoms such as fever, cough and dyspnea. Other diagnostic methods include conventional culture, diagnostic syndromic testing, serology test and biomarkers. COVID-19 patients with bacterial coinfection or secondary infection have a higher in-hospital mortality and longer length of stay, timely and appropriate antibiotic use aided by accurate diagnosis is crucial to improve patient outcome and prevent antimicrobial resistance.

Trend of HIV Transmitted Drug Resistance After the Introduction of Single-Tablet Regimens in Southern Taiwan.

Background: The prevalence of transmitted drug resistance (TDR) after the universal implementation of STRs is unknown in Taiwan. Objective: This study aimed to investigate the prevalence of TDR in patients with HIV-1 infection, clarify the risk factors for pol resistance, and compare differences in HIV drug resistance before and after the implementation of STRs in Taiwan. Methods: Adult patients infected with HIV-1 were enrolled in this study from 2013 to 2021. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database edition 9. A logistic regression model was used to analyze the risk factors for pol resistance, and the differences in the prevalence of drug resistance from 2013-2016 to 2017-2021 were compared using the Mann-Whitney U-test. General linear regression was used to analyze temporal changes in the annual proportion of TDR overall and by type of antiretroviral drugs. Results: A total of 369 patients were included. The prevalence rate of pol resistance was 9.8% (36/369). The resistance rates to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 3.3%, 6.9%, 0% and 1.8%, respectively. The patients with hepatitis C infection were more likely to have pol resistance (aHR 5.767, CI 1.232-26.991, p=0.026). The prevalence rate of pol resistance did not decrease after the implementation of STRs as first-line therapy in 2017 (11.2% vs 8.7%, aHR 1.329, CI 0.667-2.645, p=0.480), and no significant temporal changes were shown in the annual proportion of TDR overall or by type of antiretroviral drug. Conclusion: Our findings showed a stable prevalence rate of transmitted drug resistance despite the implementation of STRs as the first-line therapy in June 2016.

High Rates of Antimicrobial Resistance in Rapidly Growing Mycobacterial Infections in Taiwan.

Rapidly growing mycobacteria (RGM) has gained increasing clinical importance, and treatment is challenging due to diverse drug resistance. The minimum inhibitory concentrations (MIC) of 13 antimicrobial agents using modified broth microdilution and E-test were determined for 32 clinical isolates of RGM, including Mycobacterium abscessus (22 isolates) and Mycobacterium fortuitum (10 isolates). Our results showed high rates of resistance to available antimicrobial agents. Amikacin remained highly susceptible (87.5%). Clarithromycin was active against the isolates of M. abscessus (95.5%), and M. fortuitum (50%), but 36.4% and 20% had inducible macrolide resistance, respectively. Rates of susceptibility to tigecycline were 68.2-70%, and linezolid 45.5-50%, respectively. The quinolones (ciprofloxacin and moxifloxacin) showed better in vitro activity against M. fortuitum isolates (50% susceptibility) than the M. abscessus isolates (31.8% susceptibility). The susceptibilities to other conventional anti-mycobacterial agents were poor. The MICs of E-test were higher than broth microdilution and may result in reports of false resistance. In conclusion, the implementation of the modified broth microdilution plates into the routine clinical laboratory workflow to provide antimicrobial susceptibility early, allows for the timely selection of appropriate treatment of RGM infections to improve outcome.

High Prevalence of Doravirine Resistance in HIV-1-Infected Patients with Virological Failure to an NNRTI-Based Single-Tablet Regimen.

Purpose: This study aimed to investigate the prevalence of resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-tablet regimen (STR) in Taiwanese patients and clarify the clinical implications of using doravirine in patients who fail NNRTI treatment. Patients and Methods: Taiwanese patients infected with HIV-1 who failed NNRTI-based STR treatment were enrolled in this retrospective cohort study from 2015 to 2020. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug-resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database version 9. Median values of continuous variables were compared between two groups using the Mann-Whitney U-test, and categorical variables were compared using the chi-square test or Fisher's exact test. Results: A total of 107 patients were included, of whom 29 were treatment failure to the initial STRs, and 78 failed treatment after switching to an STR. Seventy-four patients failed treatment with TDF/FTC/EFV (Atripla), 30 with TDF/FTC/RPV (Complera) and 3 with TAF/FTC/RPV (Odefsey). The prevalence rates of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were 76%, 86%, 3% and 2%, respectively. Among the 29 patients failure to the initial STRs, 62% developed doravirine resistance, compared to 64% of the 78 the patients who failed treatment after switching to an STR. There were no significant differences in the prevalence of specific NNRTI or doravirine resistance-associated mutations between these two groups. The patients with K65R mutations were more likely to have NNRTI resistance (p = 0.037) and doravirine resistance (p < 0.001). Conclusion: Our findings showed a high rate of doravirine cross-resistance in patients with NNRTI-based STR treatment failure. Doravirine should be used cautiously as a salvage regimen in patients who fail NNRTI treatment.

Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms.

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

Plasma Concentrations of sTREM-1 as Markers for Systemic Adverse Reactions in Subjects Treated With Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection.

Background: A regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for subjects with latent tuberculosis infection; however, no reliable biomarker exists for predicting systemic adverse reactions (SARs) to 3HP treatment. Methods: This prospective, multi-center study evaluated the plasma concentrations of soluble triggering receptors expressed on myeloid cells (sTREM)-1 and sTREM-2 in subjects undergoing 3HP treatment and examined the associations between these biomarkers and SARs. Results: This study enrolled 80 consecutive subjects receiving 3HP treatment, 25 of whom had SARs and 55 of whom did not. Subjects with SARs presented higher concentrations of sTREM-1 at baseline than those without SARs (240.1 ± 19.1 vs. 176.7 ± 9.4 pg/mL, P = 0.001). The area under the receiver operating characteristic curves revealed that day 1 plasma levels of sTREM-1 (0.708, 95% CI, 0.584-0.833, P = 0.003) and sTREM-2 (0.343, 95% CI, 0.227-0.459, P = 0.025) as well as the sTREM-1/sTREM-2 ratio (0.748, 95% CI, 0.638-0.858, P = 0.001) had modest discriminative power pertaining to the development of SARs. An sTREM-1 level exceeding the cut-off value (>187.4 pg/mL) (hazard ratio [HR], 6.15; 95% CI 1.67-22.70, P = 0.006) and a sTREM-2 below the cut-off value (<237.2 pg/mL) (HR, 4.46; 95% CI 1.41-14.1, P = 0.011) were independent predictors of SARs after controlling for other variables. Conclusions: Plasma sTREM-1 and sTREM-2 levels are useful biomarkers for predicting SARs during 3HP treatment. Clinical trial government: NCT04655794.

High Baseline C-Reactive Protein Level Can Predict the Occurrence of the Jarisch-Herxheimer Reaction in Patients with Active Syphilis.

BACKGROUND: The Jarisch-Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis. METHODS: This prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal-Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment. RESULTS: Twenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986-19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033-26,150 ng/mL] vs 3489 ng/mL [IQR 924-160,640] ng/mL, p = 0.0059, 95% CI 4002-17,098 ng/mL, area under the curve 0.799, 95% CI 0.632-0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL). CONCLUSION: A high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.

Longitudinal non-cystic fibrosis trends of pulmonary Mycobacterium abscessus disease from 2010 to 2017: spread of the "globally successful clone" in Asia.

BACKGROUND: Mycobacterium abscessus (MAB) has emerged as the predominant pulmonary non-tuberculous mycobacterial pathogen in parts of Asia, including Taiwan. The reasons for the significant increase in MAB infections in the non-cystic fibrosis (CF) populations are poorly understood. The study aimed to elucidate whether this increase is related to the spread of the globally successful clone of MAB. METHODS: We performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010-2017 at seven hospitals across Taiwan. RESULTS: In total, 183 (49.3%) isolates were M. abscessus subsp. abscessus (MAB-a), 187 (50.4%) were M. abscessus subsp. massiliense (MAB-m), and 1 (0.3%) was M. abscessus subsp. bolletii (MAB-b). MAB-a sequence type (ST)1 (23.7%) and ST127 (3.8%), followed by MAB-m ST48 (16.2%), ST117 (15.1%), ST23 (8.6%) were most common overall. Of MAB-a strains, 50 (27.3%) belonged to novel STs and 38 (10.2%) were singleton strains, while of MAB-m strains, only 10 (5.3%) were novel and 8 (2.2%) were singletons. From 2010 to 2017, the frequency of the historically dominant ST1 declined from 28.6% to 22.5%, whereas the recently emerged globally successful clonal cluster 3, ST23 and ST48, increased from 14.3% to 40.0%. CONCLUSIONS: The dominance of ST1 particularly in the last 2 years of this study appears to be declining, while ST23, reported in outbreaks among CF and post-surgical cohorts across the Americas and Europe, alongside the closely related ST48, is present among non-CF populations in Taiwan. These trends need to be confirmed with further ongoing studies to track the molecular epidemiology of clinical MAB isolates worldwide.

Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Patients with Liver Cirrhosis.

BACKGROUND: This study aimed to investigate the frequency of sequence type (ST) 131 strains and outcome of cirrhotic patients with bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase-producing Escherichia coli (ESBLEC) and non-extended-spectrum beta-lactamase-producing Escherichia coli (NESBLEC). METHODS: The incidence of ST 131 strains, hospital stay, and 30-day re-admission/mortality were compared between 51 ESBLEC and 51 NESBLEC bacteremic patients with cirrhosis. RESULTS: ST 131 strains were found in 35.3% of the ESBLEC group and 0% of the NESBLEC group (p < 0.001). Mean hospital stay was 26.5 days in the ESBLEC group and 17.1 days in the NESBLEC group (p = 0.006). Thirty-day re-admission rates were 11.8% in the ESBLEC group and 5.9% in the NESBLEC group (p = 0.5). ST 131 strains were associated with 30-day re-admission (odds ratio: 4.5, 95% confidence interval: 1.1-18.9). Thirty-day mortality rate was 31.4% in the ESBLEC group and 23.5% in the NESBLEC group (p = 0.4). CONCLUSION: In patients with cirrhosis, the ESBLEC BSIs group had a higher frequency of ST 131 strains and longer hospital stay than the NESBLEC BSIs group with similar 30-day re-admission/mortality. ST 131 strains were associated with 30-day re-admission.

Identifying predictors for bacterial and fungal coinfection on chest computed tomography in patients with Pneumocystis pneumonia.

BACKGROUND: Pneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality. METHODS: This is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis. RESULTS: A total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03-19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27-10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72-22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44-19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure. CONCLUSION: Early identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.

Prevalence of HIV-1 Integrase Strand Transfer Inhibitor Resistance in Treatment-Naïve Voluntary Counselling and Testing Clients by Population Sequencing and Illumina Next-Generation Sequencing in Taiwan.

PURPOSE: Integrase strand transfer inhibitors (INSTIs) are used as first-line therapy for HIV-1-infected patients. Next-generation sequencing (NGS) can detect low-frequency mutants; however, the clinical value of NGS to detect resistance variants is unknown. This study aimed to evaluate the prevalence of INSTI resistance in southern Taiwan and determine the clinical implications of using NGS to detect integrase region low-level resistant variants. PATIENTS AND METHODS: This retrospective cohort study included antiretroviral therapy-naïve HIV-1-infected individuals at Kaohsiung Veterans General Hospital, Taiwan, from 2013 to 2017. Drug-resistance mutations were determined, and an in-house polymerase chain reaction was used for genotyping INSTI resistance. NGS was used to assess INSTI resistance (≧1%), and the results were compared with those from population sequencing. Drug resistance-associated mutations were defined according to the 2019 IAS-USA HIV drug resistance-associated mutations list, and accessory mutations by a Stanford HIVdb score ≥10 to at least one INSTI. RESULTS: A total of 224 patients were included. Subtype B HIV-1 strains were found in 96% of the individuals and subtype CRF01_AE in 4%. The prevalence rates for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and INSTI resistance were 4%, 5.8%, 0.4% and 0.9%, respectively. The most common INSTI resistance-associated mutations were G163K (0.4%) and E138A (0.4%). Of the 38 patients diagnosed in 2017 who had both NGS and population sequencing data, none had INSTI resistance-associated mutations by population sequencing; however, NGS detected four more INSTI resistance-associated mutations with low frequencies (G163R 3.25%, S153F 3.21%, S153Y 1.36% and Y143H 2.06%). Two patients with S153F and S153Y low frequencies mutations started INSTI-based highly active antiretroviral therapy, and none had virological failure by week 48. CONCLUSION: Our findings showed a low rate of HIV drug resistance to INSTIs (0.9%) in treatment-naïve patients. NGS detected more INSTI resistance-associated mutations at a low frequency. Low-level drug resistance-associated mutations to INSTIs identified by NGS did not have an impact on the treatment response to INSTI-based first-line therapy.

Treatment for Mycobacterium abscessus complex-lung disease.

Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant pathogens capable of a wide spectrum of infections, with 50% of infections involving the lungs. The decision to commence treatment is determined according to the severity of the disease, risk of progressive disease, presence of comorbidities, and goals of treatment. MABC is resistant to standard antituberculous agents and has variable drug susceptibility across different geographical locations, therefore, antibiotic susceptibility testing of all clinically significant isolates is crucial for selecting a treatment strategy. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. Despite the introduction of new drugs for treatment, treatment outcomes remain unsatisfactory. The combination of surgical resection of limited lung disease regions with a multidrug, macrolide-based therapy offers the optimal chance of achieving clinical cure of the disease. This review focuses on medical treatment of MABC-lung disease and the efficacy of new agents, such as clofazimine, amikacin inhalation therapy, tigecycline and linezolid, for treating MABC-lung disease.

Safety and treatment completion of latent tuberculosis infection treatment in the elderly population-A prospective observational study in Taiwan.

BACKGROUND: The detection and treatment of latent tuberculosis infection (LTBI) is a key step in eliminating tuberculosis (TB), but information on safety and on treatment interruption in elderly LTBI patients remains limited. METHODS: This multicenter prospective observational study included individuals with LTBI who underwent preventive therapy. Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (<60 years old) were analyzed. RESULTS: A total of 406 LTBI patients, comprising 167 elderly and 239 young patients, were included in the analyses. The incidence of SARs was similar in the elderly group (18%) and the young group (15.1%). Being middle-aged (35-59 years), body mass index <23 kg/m2, a regimen of 3 months of once-weekly rifapentine plus isoniazid, and end-stage renal disease were independent factors associated with SARs. The treatment interruption rate was similar between the elderly group (21.6%) and the young group (15.9%). LTBI patients aged ≥80 years with SARs had the highest risk of treatment interruption. CONCLUSIONS: The occurrence of SARs was similar in the elderly (≥60 years old) and young (<60 years old) LTBI patients receiving preventive therapy. Extremely old (≥80 years old) LTBI patients had a higher treatment interruption rate, especially when they had SARs.