Optimal Frequency of Hepatitis C Virus (HCV) RNA Testing for Detection of Acute HCV Infection Among At-risk People With Human Immunodeficiency Virus: A Multicenter Study.

Using 3-stage pooled-plasma hepatitis C virus (HCV) RNA testing performed quarterly among at-risk people with human immunodeficiency virus (PWH), we found that if testing had been performed every 6 or 12 months, 58.6%-91.7% of PWH who recently acquired HCV would be delayed for diagnosis and might contribute to onward HCV transmission with longer durations.

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.

Risk of non-typhoidal Salmonella vascular infections is increased with degree of atherosclerosis and inflammation: A multicenter study in southern Taiwan.

BACKGROUND: Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia. METHODS: A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center. RESULTS: Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score <1), none had vascular infections, resulting in a negative predictive value of 100%. Higher plasma concentrations of IL-1ß were detected in the cases of vascular infection than those in the control group (23.6 vs. 1.06 pg/mL, P = 0.001). CONCLUSION: Atherosclerosis of the aorta which is associated with a positive NTSVI score can predict the occurrence of vascular infections and serum IL-1ß could be a biomarker for vascular infection in patients with NTS bacteremia.

Antimicrobial treatment of monomicrobial phenotypic carbapenem-resistant Klebsiella pneumoniae bacteremia: Two are better than one.

BACKGROUNDS: Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are emerging worldwide. The optimal treatment for CRKP infections is challenging for clinicians because therapeutic agents are greatly limited. MATERIAL AND METHODS: A retrospective study of CRKP monomicrobial bacteremia was conducted at a medical center between 2010 and 2016. The use of at least one or more drugs with in vitro activity against the blood isolates was defined as appropriate combination therapy. The logistic regression model and propensity score analysis was used to assess clinical effects of therapeutic strategies. The 30-day crude mortality was the primary end point. RESULTS: Two hundred and three patients were eligible and the 30-day mortality rate was 37.9% (77 patients). As compared with monotherapy, empirical (11.6 vs. 57.3%, p < .001) or definitive (26.5% vs. 48.6%, p = .001) combination antibiotic therapy showed a lower 30-day mortality rate independently. The propensity score analysis showed that those receiving combination therapy had less clinical (p ≤ .001) or microbiological failure (p = .003) and a lower 30-day mortality rate (p < .001). Among various regimens of definitive therapy, the 30-day mortality rate was the lowest among patients with appropriate combination therapy 23.6%, (p < .001; by log rank test). The primary outcome was similar in those with definitive carbapenem-containing and carbapenem-sparing combination regimens (p = .81). The presence or absence of carbapenemase production did not affect the mortality rate (p = .26). CONCLUSION: Combination therapy, regardless of carbapenem-containing or carbapenem-sparing regimens, was associated with a favorable outcome.

Pancreaticobiliary Cancers and Aeromonas Isolates Carrying Type â ¢ Secretion System Genes ascF-ascG Are Associated With Increased Mortality: An Analysis of 164 Aeromonas Infection Episodes in Southern Taiwan.

This prospective study aimed to investigate the clinical and microbiological characteristics of different Aeromonas species. Clinical isolates of Aeromonas species between 2016 to 2018 were collected in a university hospital in southern Taiwan. The species was determined by rpoD or gyrB sequencing. A total of 222 Aeromonas isolates from 160 patients in 164 episodes were identified. The crude in-hospital mortality was 17.2%. The most frequently isolated species was Aeromonas veronii (30.6%), followed by A. caviae (24.8%), A. hydrophila (23%), and A. dhakensis (16.7%). The major clinical manifestations were primary bacteremia (31.1%), skin and soft tissue infection (22.6%), and biliary tract infection (18.3%). The most common underlying diseases were malignancy (45.1%), diabetes mellitus (27.4%), and liver cirrhosis or chronic hepatitis (26.2%). A. hydrophila and A. dhakensis predominated in the skin and soft tissue infection (p<0.0001), whereas A. vernoii and A. caviae prevailed in primary bacteremia and biliary tract infections (p=0.012). Pneumonia, malignancy, and ascF-ascG genotype were independent factors associated with mortality. Ertapenem susceptibility was decreased in A. sobria (42.9%), A. veronii (66.7%), A. dhakensis (73%), and A. hydrophila (84.3%). Cefotaxime resistance was found in 30.9% of A. caviae and 18.9% of A. dhakensis isolates, much more prevalent than the other species. The metallo-ß-lactamase blaCphA was almost invariably present in A. dhakensis, A. hydrophila, and A. veronii (100%, 100% and 89.9%, respectively). Amp-C ß-lactamases such as blaMOX and blaAQU-1 were identified in all A. caviae and 91.9% of A. dhakensis isolates. Cefepime, fluoroquinolones and tigecycline showed good in vitro activity against aeromonads.

Clostridioides difficile infection: an emerging zoonosis?

INTRODUCTION: Clostridioides difficile (C. difficile) infection (CDI) is the most common cause of antibiotic-associated diarrhea and one of the common infections in healthcare facilities. In recent decades, there has been an emerging threat of community-acquired CDI (CA-CDI). Environmental transmission of C. difficile in the community setting has become a major concern, and animals are an important reservoir for C. difficile causing human diseases. AREAS COVERED: In this article, the molecular epidemiology of C. difficile in animals and recent evidences of zoonotic transfer to humans are reviewed based on an electronic search in the databases of PubMed and Google Scholar. EXPERT OPINION: C. difficile can be found in stool from diarrheal dogs and cats; therefore, household pets could be a potential source. C. difficile will threaten human health because hypervirulent C. difficile ribotype 078 strains have been found in retail chickens, pig farms, and slaughterhouses. Risk factors for fecal C. difficile carriage in animals include young age, dietary changes, and antibiotic abuse in domestic animals. With the advent of whole genome sequencing techniques, there will be more solid evidence indicating zoonotic transfer of C. difficile from animals to humans.

Morphologic Spectrum of Lymphadenopathy in Adult-onset Immunodeficiency (Anti-interferon-γ Autoantibodies).

Adult-onset immunodeficiency syndrome (AOIS) caused by anti-interferon-γ autoantibodies is an emerging disease. Affected patients present typically with systemic lymphadenopathy, fatigue, and fever. We studied 36 biopsy specimens, 31 lymph nodes, and 5 extranodal sites, of AOIS confirmed by serum autoantibody or QuantiFERON-TB Gold In-Tube assay. We describe the morphologic features and the results of ancillary studies, including special stains, immunohistochemistry, and molecular testing. The overall median age of these patients was 60.5 years (range, 41 to 83 y) with a male-to-female ratio of 20:16. All biopsy specimens showed nontuberculous mycobacterial infection, and most cases showed the following histologic features: capsular thickening with intranodal sclerosing fibrosis, irregularly distributed ill-formed granulomas or histiocytic aggregates with neutrophilic infiltration, interfollicular expansion by a polymorphic infiltrate with some Hodgkin-like cells that commonly effaces most of the nodal architecture and proliferation of high endothelial venules. In situ hybridization analysis for Epstein-Barr virus-encoded RNA showed scattered (<1%) to relatively more common (4% to 5%) positive cells in 29 of 30 (97%) tested specimens, reflecting immune dysregulation due to an interferon-γ defect. In the 31 lymph node specimens, 23 (74%) cases showed increased immunoglobulin G4-positive plasma cells (4 to 145/HPF; mean, 49.7/HPF) with focal areas of sclerosis reminiscent of immunoglobulin G4-related lymphadenopathy, 4 (13%) cases resembled, in part, nodular sclerosis Hodgkin lymphoma, and 9 (29%) cases mimicked T-cell lymphoma. Among 33 patients with available clinical follow-up, 20 (61%) showed persistent or refractory disease despite antimycobacterial therapy, and 1 patient died of the disease. We conclude that the presence of ill-defined granulomas, clusters of neutrophils adjacent to the histiocytic aggregates, and some Epstein-Barr virus-positive cells are features highly suggestive of AOIS. A high index of clinical suspicion and awareness of the morphologic features and differential diagnosis of AOIS are helpful for establishing the diagnosis.

Real-World Experience with Coformulated Ledipasvir and Sofosbuvir for HIV-Positive Patients with HCV Genotype 2 Infection: A Multicenter, Retrospective Study.

INTRODUCTION: While coformulated ledipasvir (90 mg)/sofosbuvir (400 mg) (LDV/SOF) is approved for the treatment of hepatitis C virus (HCV) genotype 2 (GT2) infection in Taiwan, Japan, and New Zealand, data regarding its use for HIV (Human Immunodeficiency Virus)-positive patients infected with HCV GT2 are sparse. We aimed to assess the effectiveness and tolerability of LDV/SOF for HIV-positive patients with HCV GT2 coinfection. METHODS: From January 2019 to July 2020, consecutive HIV-positive Taiwanese patients infected with HCV GT2 who received LDV/SOF were retrospectively included for analysis. The effectiveness was determined by sustained virologic response 12 weeks off-therapy (SVR12). RESULTS: Of the 114 patients (mean age, 38.6 years) initiating LDV/SOF during the study period, 0.9% had liver cirrhosis and 4.4% were HCV treatment-experienced. All patients had estimated glomerular filtration rate (eGFR) > 30 ml/min/1.73 m2 and were receiving antiretroviral therapy with 98.2% having CD4 counts ≥ 200 cells/mm3 and 93.9% plasma HIV RNA load < 50 copies/ml. Antiretrovirals prescribed included tenofovir alafenamide/emtricitabine in 42.1%, tenofovir disoproxil fumarate (TDF)/emtricitabine 18.4%, other nucleoside reverse transcriptase inhibitors (NRTIs) 39.5%, non-NRTIs 12.3%, protease inhibitors 13.2%, and integrase inhibitors 74.6%. All patients had undetectable plasma HCV RNA load at the end of treatment, and 96.5% achieved SVR12 in intention-to-treat analysis. The on-treatment eGFR decline was more pronounced in those receiving TDF-containing antiretroviral therapy (mean change, - 8.33 ml/min/1.73 m2), which was reversible after discontinuation of LDV/SOF. None of the patients interrupted LDV/SOF during the 12-week treatment course. CONCLUSION: Similar to the response observed among HIV-negative patients, LDV/SOF is effective for HIV-positive patients coinfected with HCV GT2.

Clinical impact of cefepime breakpoint in patients with carbapenem-resistant Klebsiella pneumoniae bacteraemia.

The application of cefepime breakpoint for carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia has not been explored. Adult cases of monomicrobial bloodstream infection (BSI) caused by cefepime-susceptible [minimum inhibitory concentration (MIC) ≤8 mg/L] K. pneumoniae isolates with carbapenem resistance between 2010 and 2015 were reviewed. Patients treated with cefepime were compared with those treated by other active agents using a propensity score-matched analysis to assess therapeutic effectiveness. The primary endpoint was 30-day crude mortality. A total of 114 patients experienced cefepime-susceptible CRKP bacteraemia and 40 (35.1%) died during hospitalisation. A total of 33 patients (28.9%) received cefepime therapy. Fifteen patients (13.2%) had BSI due to carbapenemase-producing isolates, and 86.7% (13/15) of carbapenemase-producing isolates were classified as cefepime susceptible dose-dependent (SDD). In the multivariate logistic regression analysis, 30-day mortality was independently associated with the presence of a critical illness [adjusted odds ratio (aOR) = 12.89, 95% confidence interval (CI) 3.88-42.83; P < 0.001], pneumonia (aOR = 5.97, 95% CI 1.65-21.76; P = 0.007) and rapidly fatal underlying disease (aOR = 6.43, 95% CI 1.30-31.09; P = 0.02). In contrast, cefepime-based therapy (aOR = 0.03, 95% CI 0.003-0.38; P = 0.006) and combination therapy (aOR = 0.09, 95% CI 0.02-0.36; P = 0.001) were protective against a fatal outcome. Based on current breakpoints for Enterobacterales, cefepime therapy was not associated with an unfavourable outcome for CRKP BSI with MIC-based dosing strategies. However, the susceptibility result of SDD to cefepime should alert clinicians for possible therapeutic failure.

Anosmia and olfactory tract neuropathy in a case of COVID-19.

Coronavirus Disease-19 (COVID-19) has been in a global pandemic currently and relating symptoms were reported variously around the world. We reported a previously healthy man of COVID-19 presenting with anosmia as the obvious symptom with relevant radiological findings on brain magnetic resonance imaging.

Disseminated Mycobacterium szulgai infection in a patient with anti-interferon-gamma autoantibodies.

Incidence of nontuberculous mycobacterial infections has increased during the past decades. Disseminated infections are relatively rare and associated with immunocompromised status. We report a case of disseminated Mycobacterium szulgai infection of cervical lymphadenitis and pulmonary involvement with positive anti-interferon-gamma autoantibodies. The patient was successfully treated with rifampin, ethambutol, and clarithromycin. The case reports and series through search engines of Pubmed and Google with the keyword of disseminated infection of M. szulgai were reviewed. Fifteen patients of disseminated M. szulgai infection were reviewed and included. DisseminatedM. szulgaiinfection involves bone, skin and lymph node more common instead of pulmonary involvement, and most are associated with immunocompromised status with neoplastic hematologic disorders. In patients with disseminated M. szulgai infection, long term anti-mycobacterial agents are necessary. Most patients will respond to rifampin and ethambutol combination regimens.

[Nursing Experience of Caring for a Patient With COVID-19 During Isolation].

The ongoing coronavirus disease-2019 (COVID-19) epidemic continues to have a global impact. This article describes the author's experience providing nursing care to a female patient who was diagnosed with COVID-19 after returning to Taiwan from overseas. During the patient's period of isolation (February 5th to February 29th, 2020), the author used Roy's adaptation model to perform first-level holistic physical, psychological, and social nursing assessments and collected health-problem information using face-to-face interviews, telephone interviews, and observations via a remote monitoring system. A second level of assessment confirmed that the problems faced by the patient included (1) existing infections related to COVID-19 and (2) anxiety related to uncertainties about disease prognosis, forgiveness from the family, and potential violations of personal privacy by the media. Due to the special nature of the isolation ward, the author used a remote physiological monitoring system to monitor the vital signs, fever, and shortness of breath status of the patient to quickly decrease her physical discomfort and to improve her self-care ability during hospitalization. Environmental cleanliness was strictly maintained to reduce the risk of cross-infection and ensure patient safety. To alleviate patient anxiety, the author established a good therapeutic interpersonal relationship with the patient by making 10-60 minutes of caring calls to her each day, by providing individual care measures, and by using the Internet to play audio and video to teach mindfulness meditation. Caring for COVID-19 cases is a completely new experience. The author hopes that this experience may be used as a reference for caregivers.

A case of COVID-19 and pneumonia returning from Macau in Taiwan: Clinical course and anti-SARS-CoV-2 IgG dynamic.

A 46-year-old woman presented to the emergency department with 2-day fever and cough at seven days after returning from Macau. COVID-19 and pneumonia was diagnosed based on the positive real-time RT-PCR tests for oropharyngeal swab samples and the presence of anti-SARS-COV-2 IgG starting from the illness day 11 and post-exposure 18-21 days.

Recommendations and guidelines for the treatment of Clostridioides difficile infection in Taiwan.

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided.

Treatment Outcome of Bacteremia Due to Non-Carbapenemase-producing Carbapenem-Resistant Klebsiella pneumoniae Bacteremia: Role of Carbapenem Combination Therapy.

PURPOSE: Infections caused by carbapenemase-producing Klebsiella pneumoniae are emerging causes of morbidity and mortality worldwide. Optimal treatment for non-carbapenemase-producing carbapenem-resistant K pneumoniae (nCP-CRKP) bacteremia remains undefined. The goal of this study was to assess the clinical outcome, predictors of mortality, and therapeutic strategy of carbapenems for nCP-CRKP bacteremia. METHODS: A retrospective study of monomicrobial bacteremia caused by nCP-CRKP, at a medical center between 2010 and 2015 was conducted. CRKP which was defined as a minimum inhibitory concentration (MIC) of ≥ 2 for ertapenem or ≥ 4 mg/L for meropenem, or imipenem. Multiplex polymerase chain was applied to detect carbapenemase genes. The patients definitively treated with combination therapy were compared with monotherapy using a propensity score-matched analysis to assess therapeutic effectiveness. The primary end point was the 30-day crude mortality and clinical prognostic factors were assessed. FINDINGS: Overall 171 patients met criteria were eligible for the study and their overall 30-day mortality rate was 38.6%. The multivariate logistic regression analysis showed that combination therapy was associated with a lower 30-day mortality rate (adjusted odds ratio [aOR], 0.11; 95% CI, 0.03-0.43; P = 0.001) and less clinical (aOR, 0.21; 95% CI, 0.08-0.58; P = 0.003) and microbiologic (aOR, 0.36; 95% CI, 0.19-0.71; P = 0.003) failure. However, the 30-day mortality rate in the cases infected by a pathogen with a meropenem MIC ≤8 mg/L receiving carbapenem-containing or carbapenem-sparing combination regimens was similar (15 of 58 [25.9%] vs 5 of 20 [23.3%]; P = 1.0). IMPLICATIONS: Combination therapy, regardless of carbapenem-containing or carbapenem-sparing, with one or more active agents improved survival more than monotherapy and was more effective in patients with critical illness. (Clin Ther. 2020; 42:XXX-XXX) © 2020 Elsevier HS Journals, Inc.

Bloodstream infections in hospitalized adults with dengue fever: Clinical characteristics and recommended empirical therapy.

BACKGROUND: Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed. METHODS: Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected. RESULTS: Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week. CONCLUSIONS: BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.