Association of vaccine-specific regulatory T cells with reduced antibody response to repeated influenza vaccination.

Repeated annual influenza vaccinations have been associated with reduced vaccine-induced antibody responses. This prospective study aimed to explore the role of vaccine antigen-specific regulatory T (Treg) cells in antibody response to repeated annual influenza vaccination. We analyzed pre- and postvaccination hemagglutination inhibition (HI) titers, seroconversion rates, seroprotection rates, vaccine antigen hemagglutinin (HA)-specific Treg cells, and conventional T (Tconv) cells. We compared these parameters between vaccinees with or without vaccine-induced seroconversion. Our multivariate logistic regression revealed that prior vaccination was significantly associated with a decreased likelihood of achieving seroconversion for both H1N1(adjusted OR, 0.03; 95% CI, 0.01-0.13) and H3N2 (adjusted OR, 0.09; 95% CI, 0.03-0.30). Furthermore, individuals who received repeated vaccinations had significantly higher levels of pre-existing HA-specific Treg cells than those who did not. We also found that vaccine-induced fold-increases in HI titers and seroconversion were negatively correlated with pre-existing HA-specific Treg cells and positively correlated with the ratio of Tconv to Treg cells. Overall, our findings suggest that repeated annual influenza vaccination is associated with a lower vaccine-induced antibody response and a higher frequency of vaccine-specific Treg cells. However, a lower frequency of pre-existing Treg cells correlates with a higher postvaccination antibody response.

A Randomized Clinical Trial of 1-Dose vs Accelerated 2-Dose Schedule for Hepatitis A Virus (HAV) Revaccination Among People With Human Immunodeficiency Virus Who Were Nonresponders or Had Seroreversion After Primary HAV Vaccination.

BACKGROUND: For people with human immunodeficiency virus (PWH) who have no serological responses to their primary hepatitis A virus (HAV) vaccination or have seroreversion after successful primary vaccination, the optimal revaccination strategy remains unclear. METHODS: In this open-label, randomized clinical trial, PWH who tested negative for anti-HAV antibodies after receiving a standard 2-dose series of primary HAV vaccination were enrolled and assigned in a 1:1 ratio to receive either 1 dose (the 1-dose group) or 2 doses of HAV vaccine administered 4 weeks apart (the 2-dose group). Serological response rates and anti-HAV antibody titers were compared at weeks 24 and 48. RESULTS: Of the 153 participants (77 in the 1-dose group and 76 in the 2-dose group), the overall serological response rates at week 48 after revaccination were similar between the 2 groups (2- vs 1-dose, 80.2% vs 71.4%, P = .20). However, anti-HAV antibody titers were consistently higher in the 2-dose group than in the 1-dose group. In subgroup analysis, PWH who were nonresponders to primary HAV vaccination were significantly more likely to mount a serological response after 2-dose HAV revaccination (68.4% vs 44.1%, P = .038). No severe adverse events were reported throughout the study. CONCLUSIONS: Two-dose HAV revaccination administered 4 weeks apart yielded similar serological responses as 1-dose revaccination among PWH who were nonresponders or had seroreversion after primary HAV vaccination. The 2-dose revaccination schedule generated significantly higher anti-HAV antibody titers and was more likely to elicit serological responses at week 48 among PWH who were nonresponders to primary HAV vaccination. Clinical Trials Registration. NCT03855176.

CXCL9 as a Reliable Biomarker for Discriminating Anti-IFN-γ-Autoantibody-Associated Lymphadenopathy that Mimics Lymphoma.

The diagnosis of adult-onset immunodeficiency syndrome associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents substantial challenges to clinicians and pathologists due to its nonspecific clinical presentation, absence of routine laboratory tests, and resemblance to certain lymphoma types, notably nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI). Some patients undergo lymphadenectomy for histopathological examination to rule out lymphoma, even in the absence of a preceding clinical suspicion of AIGA. This study aimed to identify reliable methods to prevent misdiagnosis of AIGA in this scenario through a retrospective case-control analysis of clinical and pathological data, along with immune gene transcriptomes using the NanoString nCounter platform, to compare AIGA and nTFHL-AI. The investigation revealed a downregulation of the C-X-C motif chemokine ligand 9 (CXCL9) gene in AIGA, prompting an exploration of its diagnostic utility. Immunohistochemistry (IHC) targeting CXCL9 was performed on lymph node specimens to assess its potential as a diagnostic biomarker. The findings exhibited a significantly lower density of CXCL9-positive cells in AIGA compared to nTFHL-AI, displaying a high diagnostic accuracy of 92.3% sensitivity and 100% specificity. Furthermore, CXCL9 IHC demonstrated its ability to differentiate AIGA from various lymphomas sharing similar characteristics. In conclusion, CXCL9 IHC emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and other similar conditions. This reliable diagnostic approach holds the potential to avert misdiagnosis of AIGA as lymphoma, providing timely and accurate diagnosis.

Neutralizing Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Patients With Central Nervous System and Localized Cryptococcosis: Longitudinal Follow-up and Literature Review.

BACKGROUND: Neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (AAbs) have been increasingly recognized to predispose healthy individuals to disseminated cryptococcosis. However, studies have only considered patients with central nervous system (CNS) infection. No longitudinal study has captured the disease spectrum and clinical course. METHODS: We prospectively enrolled adults without human immunodeficiency virus infection who had disseminated or unusual cryptococcosis. We compared the demographics, clinical features, kinetics of serum cryptococcal antigen (CrAg) titers, anti-GM-CSF AAb concentrations, and treatment outcomes between patients with (case patients) and without (control patients) anti-GM-CSF AAbs. Additional reports from the literature were also reviewed. RESULTS: Twenty-three patients were enrolled, of whom 6 tested positive for anti-GM-CSF AAbs. All case patients with positive fungal cultures (5/5 [100%]) were infected with Cryptococcus gattii VGII. Among them, 3 had exclusively pulmonary involvement, and 1 had only musculoskeletal lesions. Patients with CNS cryptococcosis exhibited a higher serum concentration of anti-GM-CSF AAbs than those with extraneural cryptococcosis. Case patients had higher initial and peak levels of serum CrAg and longer duration of antigenemia compared with the control patients. All case patients who had completed antifungal therapy had favorable outcomes without recurrence. CONCLUSIONS: Testing for anti-GM-CSF AAbs should be considered for not only previously healthy patients with disseminated cryptococcosis but also those with unexplained, localized cryptococcosis. Recurrence after completion of antifungal therapy was rare despite the persistence of anti-GM-CSF AAbs.

Disseminated Mycobacterium chimaera infection in a patient with adult-onset immunodeficiency syndrome: case report.

BACKGROUND: Patients with adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibodies (AIGAs) are susceptible to disseminated Mycobacterium avium complex (MAC) infections. M. chimaera, a newly identified MAC species, is distinguished from the others due to the reduced virulence. Previous cases of disseminated M. chimaera infection have been linked to cardiothoracic surgery. Reports of disseminated M. chimaera in patients without a history of cardiothoracic surgery are rare. CASE PRESENTATION: A 57-year-old Asian man, previously healthy, presented with fever, dry cough, exertional dyspnea, and decreased appetite. The delayed resolution of pneumonia despite antibiotic treatment prompted further imaging studies and biopsies from the lung and lymph node. The fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) demonstrated intense uptake in lung consolidations and diffuse lymphadenopathy. Cultures of the specimens obtained from sputum, blood, stool, lung tissue, and lymph node grew M. chimaera. Further immunological evaluation disclosed the presence of neutralizing AIGAs, which possibly led to acquired immunodeficiency and disseminated M. chimaera infection. CONCLUSIONS: We herein present the first case of adult-onset immunodeficiency due to AIGAs complicated with disseminated M. chimaera infection. Further immunological evaluation, including AIGAs, may be warranted in otherwise healthy patients who present with disseminated mycobacterial infection.

Video-assisted thoracoscopic surgery for primary pulmonary cryptococcosis.

BACKGROUND: The surgical outcome for primary pulmonary cryptococcosis remains unclear. In this study, we investigated the clinical characteristics, treatment, and outcomes of video-assisted thoracoscopic surgery (VATS) for primary pulmonary cryptococcosis. METHODS: We retrospectively reviewed the medical records of 49 patients with confirmed pulmonary cryptococcosis who underwent VATS for pulmonary nodules at the National Taiwan University Hospital between May 2013 and March 2019. Serum cryptococcal antigen (CryAg)-positive and CryAg-negative patients were compared. RESULTS: The diagnosis of pulmonary cryptococcosis was confirmed using histopathology or tissue swab culture. The mean age of the patients was 56.0 ± 12.2 years, and 27 patients (55.1%) were male. Most patients were asymptomatic (67.3%) and admitted following the detection of pulmonary lesions on a computed tomography scan of the chest. A greater proportion of patients in the CryAg-positive group (62.5%) underwent lobectomy compared with those in the CryAg-negative group (7.3%, P < 0.001). Three patients (6.1%) had neurological symptoms (headache or dizziness) and all were serum CryAg-positive. One patient with Cryptococcus gattii developed fluctuating serum CryAg titers after a 12-month antifungal treatment. No relapse occurred in the remaining 48 patients, irrespective of postoperative antifungal treatment. CONCLUSION: In patients with primary pulmonary cryptococcosis, serum CryAg detection rate is low, and VATS was an effective and safe diagnostic and therapeutic tool.

High prevalence of sexually transmitted coinfections among at-risk people living with HIV.

BACKGROUND/PURPOSE: Concurrent sexually transmitted infections (STIs) are not uncommon in at-risk populations, for which control requires integrated testing, treatment and prevention. METHODS: From May, 2019 to February, 2020, multiplex real-time PCR assays were prospectively performed to detect Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) in the urine and rectal/vaginal swab specimens collected from HIV-positive patients with a history of STIs or symptoms suggestive of STIs. Patients confirmed to have acquired STIs were treated according to treatment guidelines. RESULTS: During the study period, 430 participants (99.1% men who have sex with men and median age 37 years) were included. The overall prevalence of CT, NG, and/or TV infection was 30.0%, including 24.7%, 12.1%, and 0.2% for CT, NG, and TV infection, respectively. The factors associated with CT, NG, and/or TV infection were hepatitis B surface antigen (HBsAg) seropositivity (AOR, 2.76; 95% CI, 1.22-6.26), recently acquired hepatitis C virus (HCV) infection (AOR, 5.62; 95% CI, 1.99-15.88), using mobile dating application (AOR, 2.08; 95% CI, 1.13-3.83), and oral sex (AOR, 2.12; 95% CI, 1.04-4.32). The rates of CT, NG, and/or TV infection were 50.0% in participants with recent HCV infection, 44.2% in those with HBsAg positivity, and 35.9% in those with incident syphilis. Among participants completing test-of-cure visits, the microbiological cure rate was 91.7% and 90.0% for chlamydia and gonorrhea, respectively. CONCLUSION: HIV-positive participants had a high prevalence of CT and/or NG, especially those coinfected with viral hepatitis and syphilis. Our results strongly support integrated STI services in the population.

Clonality of Fluconazole-Nonsusceptible Candida tropicalis in Bloodstream Infections, Taiwan, 2011-2017.

Candida tropicalis is the leading cause of non-C. albicans candidemia in tropical Asia and Latin America. We evaluated isolates from 344 patients with an initial episode of C. tropicalis candidemia. We found that 58 (16.9%) patients were infected by fluconazole-nonsusceptible (FNS) C. tropicalis with cross resistance to itraconazole, voriconazole, and posaconazole; 55.2% (32/58) of patients were azole-naive. Multilocus sequence typing analysis revealed FNS isolates were genetically closely related, but we did not see time- or place-clustering. Among the diploid sequence types (DSTs), we noted DST225, which has been reported from fruit in Taiwan and hospitals in Beijing, China, as well as DST376 and DST505-7, which also were reported from hospitals in Shanghai, China. Our findings suggest cross-boundary expansion of FNS C. tropicalis and highlight the importance of active surveillance of clinical isolates to detect dissemination of this pathogen and explore potential sources in the community.

In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex.

Infections caused by the difficult-to-treat bacterium Mycobacterium abscessus are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active in vitro against M. abscessus, especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. In vitro synergism between rifabutin and 10 antimicrobials was evaluated in 31 mycobacterial strains by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each rifabutin-based combination. The colony morphology was recorded. Molecular methods for determination of the M. abscessus subspecies and analysis of macrolide resistance were performed by sequencing of the secA1, rpoB, hsp65, erm(41), and rrl genes. Rifabutin yielded an MIC50 of 16 mg/liter (range, 2 to 32 mg/liter) against 26 clinical M. abscessus isolates (comprising 13 M. abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates) and 5 reference strains, including M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii BCRC 16915, M. abscessus subsp. massiliense BCRC 16916, M. chelonae ATCC 35752, and M. peregrinum ATCC 700686. Significant synergism, classified by an FICI of ≤0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin-resistant (MICs ≥ 8 mg/liter) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus isolates.

Comparing the Utilities of Different Multilocus Sequence Typing Schemes for Identifying Outbreak Strains of Mycobacterium abscessus subsp. massiliense.

Outbreaks of infections by Mycobacterium abscessus, particularly subspecies massiliense, are increasingly reported worldwide. Several multilocus sequence typing (MLST) protocols for grouping international outbreak strains have been developed but not yet directly compared. Using the three-gene (hsp65, rpoB, and secA1), seven-gene (argH, cya, glpK, gnd, murC, pta, and purH) and thirteen-gene (all of the preceding genes plus gdhA, pgm, and pknA) MLST schemes, we identified 22, 38, and 40 unique sequence types (STs), respectively, among a total of 139 nonduplicated M. abscessus isolates. Among subspecies massiliense, three-gene MLST not only clustered all outbreak strains together (in 100% agreement with the seven-gene and thirteen-gene schemes), but it also distinguished between two new STs that would have been grouped together by the seven-gene MLST but were distinct by the thirteen-gene MLST owing to differences in hsp65, rpoB, and pknA Here, we show that an abbreviated MLST may be useful for simultaneous identification of M. abscessus the subspecies level and screening M. abscessus subsp. massiliense isolates with outbreak potential.

The epidemiology of non-Candida yeast isolated from blood: The Asia Surveillance Study.

BACKGROUND: Current guidelines recommend echinocandins as first-line therapy for candidemia. However, several non-Candida yeast are non-susceptible to echinocandins (echinocandin non-susceptible yeast, ENSY), including Cryptococcus, Geotrichum, Malassezia, Pseudozyma, Rhodotorula, Saprochaete, Sporobolomyces and Trichosporon. In laboratories that are not equipped with rapid diagnostic tools, it often takes several days to identify yeast, and this may lead to inappropriate presumptive use of echinocandins in patients with ENSY fungemia. The aim of this study was to determine the distribution of ENSY species during a 1-year, laboratory surveillance programme in Asia. METHODS: Non-duplicate yeast isolated from blood or bone marrow cultures at 25 hospitals in China, Hong Kong, India, Singapore, Taiwan and Thailand were analysed. Isolates were considered to be duplicative if they were obtained within 7 days from the same patient. RESULTS: Of 2155 yeast isolates evaluated, 175 (8.1%) were non-Candida yeast. The majority of non-Candida yeast were ENSY (146/175, 83.4%). These included Cryptococcus (109 isolates), Trichosporon (23), Rhodotorula (10) and Malassezia (4). The proportion of ENSY isolates (146/2155, 6.7%) differed between tropical (India, Thailand and Singapore; 51/593, 8.6%) and non-tropical countries/regions (China, Hong Kong and Taiwan; 95/1562, 6.1%, P = 0.038). ENSY was common in outpatient clinics (25.0%) and emergency departments (17.8%) but rare in intensive care units (4.7%) and in haematology-oncology units (2.9%). Cryptococcus accounted for the majority of the non-Candida species in emergency departments (21/24, 87.5%) and outpatient clinics (4/5, 80.0%). CONCLUSIONS: Isolation of non-Candida yeast from blood cultures was not rare, and the frequency varied among medical units and countries.

In Vitro Evaluation of Povidone-Iodine and Chlorhexidine against Outbreak and Nonoutbreak Strains of Mycobacterium abscessus Using Standard Quantitative Suspension and Carrier Testing.

Povidone-iodine (PI) and chlorhexidine (CHX) are widely used antiseptics active against conventional Staphylococcus aureus, Enterobacteriaceae, Candida species, and viruses, but their efficacy against Mycobacterium abscessus remains unproven. We determined the in vitro potency of alcoholic PI and CHX against M. abscessus subsp. abscessus (ATCC 19977), M. abscessus subsp. bolletii (BCRC 16915), and our outbreak strain of M. abscessus subsp. massiliense (TPE 101) in reference to Staphylococcus aureus (ATCC 29213) by standard quantitative suspension and carrier methods (EN 14563). By suspension, all mycobacterial strains compared to S. aureus were significantly more resistant to CHX, but not PI. By carrier, the mean logarithmic reductions (LR) achieved by PI under clean (dirty) conditions were 6.575 (2.482), 5.540 (2.298), 4.595 (1.967), and 1.173 (0.889), while those achieved by CHX under clean (dirty) conditions were 3.164 (5.445), 5.307 (2.564), 3.844 (2.232), and 0.863 (0.389) for S. aureus, M. abscessus subsp. bolletii, M. abscessus subsp. abscessus, and M. abscessus subsp. massiliense, respectively. M. abscessus subsp. massiliense (outbreak strain) was significantly more resistant than the other tested strains to PI and CHX. By both methods, the mean LR achieved by PI was higher than for CHX for all mycobacterial strains, but under dirty conditions, neither antiseptic was effectively mycobactericidal (LR < 5). These preliminary findings caution against the universal replacement of PI with CHX as the first-line skin antiseptic, since all M. abscessus isolates were resistant to CHX. More studies are needed to establish the best practice for skin antisepsis if mycobacterial infections are also to be prevented.

Clonal Diversification and Changes in Lipid Traits and Colony Morphology in Mycobacterium abscessus Clinical Isolates.

The smooth-to-rough colony morphology shift in Mycobacterium abscessus has been implicated in loss of glycopeptidolipid (GPL), increased pathogenicity, and clinical decline in cystic fibrosis (CF) patients. However, the evolutionary phenotypic and genetic changes remain obscure. Serial isolates from nine non-CF patients with persistent M. abscessus infection were characterized by colony morphology, lipid profile via thin-layer chromatography and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), sequencing of eight genes in the GPL locus, and expression level of fadD23, a key gene involved in the biosynthesis of complex lipids. All 50 isolates were typed as M. abscessus subspecies abscessus and were clonally related within each patient. Rough isolates, all lacking GPL, predominated at later disease stages, some showing variation within rough morphology. While most (77%) rough isolates harbored detrimental mutations in mps1 and mps2, 13% displayed previously unreported mutations in mmpL4a and mmpS4, the latter yielding a putative GPL precursor. Two isolates showed no deleterious mutations in any of the eight genes sequenced. Mixed populations harboring different GPL locus mutations were detected in 5 patients, demonstrating clonal diversification, which was likely overlooked by conventional acid-fast bacillus (AFB) culture methods. Our work highlights applications of MALDI-TOF MS beyond identification, focusing on mycobacterial lipids relevant in virulence and adaptation. Later isolates displayed accumulation of triacylglycerol and reduced expression of fadD23, sometimes preceding rough colony onset. Our results indicate that clonal diversification and a shift in lipid metabolism, including the loss of GPL, occur during chronic lung infection with M. abscessus. GPL loss alone may not account for all traits associated with rough morphology.

Prevalence of carbapenemase-producing Enterobacteriaceae and its impact on clinical outcomes at a teaching hospital in Taiwan.

Among 15,174 non-duplicated Enterobacteriaceae isolates, the prevalence of carbapenem-nonsusceptible Enterobacteriaceae (CNSE) was about 2.5% at a teaching hospital in Taiwan during 2010. Among 117 available isolates of CNSE, 8.6% carried genes encoding carbapenemases. Tigecycline and colistin were the most active agents against carbapenemase-producing and non-producing isolates. Patients infected with CNSE had an all-cause in-hospital mortality of 37.3%, and mortality was similar for infections from carbapenemase producers and non-producers (14-day mortality rates: 22.2% and 21.5%; 30-day mortality rates: 22.2% and 32.3%, respectively). Continuous surveillance of CNSE is recommended in Taiwan.

A difficult-to-treat pleuropulmonary histoplasmosis in a patient with rheumatoid arthritis in Taiwan.

Amphotericin B and itraconazole are the primary agents for treating histoplasmosis. Newer azoles are alternatives for patients refractory to or intolerant of standard therapy. We report an 83-year-old woman with rheumatoid arthritis complicated with pleuropulmonary histoplasmosis who responded to liposomal amphotericin B, but progressed under voriconazole and posaconazole maintenance therapy.

Simultaneous determination of triazole antifungal drugs in human plasma by sweeping-micellar electrokinetic chromatography.

The number of cases of invasive fungal infections (IFIs) has risen significantly in recent years; therefore, this study developed a sensitive and effective sweeping-micellar electrokinetic chromatography (MEKC) method for the simultaneous determination of the three most frequently used triazole antifungal drugs for the treatment of IFIs, which included voriconazole, itraconazole, and posaconazole. Due to the diverse lipophilicity of the tested drugs, the analytical conditions that resulted in good resolution between itraconazole and posaconazole caused the peak for voriconazole to split. The splitting phenomenon was resolved by incorporating a high-salt stacking mechanism into the sweeping-MEKC method. The optimum background electrolyte was composed of 25 mM phosphoric acid solution (pH 2.2), 100 mM sodium dodecyl sulfate, 13 % acetonitrile, and 13 % tetrahydrofuran. The best peak shape of voriconazole was obtained when the conductivity ratio between the sample matrix and background electrolyte was 2.3. Compared to the conventional MEKC mode, the enhancement factor of the sweeping-MEKC method was 66 for itraconazole, 55 for posaconazole, and 43 for voriconazole. The sweeping-MEKC method was validated in terms of precision, accuracy, linearity, specificity, selectivity, and sensitivity. The linearity ranges of the method covered the commonly used therapeutic ranges of the three drugs. The developed sweeping-MEKC method was successfully applied to the analysis of clinical samples, thus demonstrating its applicability for clinical use.

Factors associated with development of complications among adults with influenza: a 3-year prospective analysis.

BACKGROUND/PURPOSE: This prospective study aimed to describe the clinical features, as well as outcomes, of adult patients with influenza of different severity, and to determine the predictors for development of complications. METHODS: From December 2006 to March 2009, four types of diagnostic tests were given to both in- and outpatients with influenza-like illness (ILI). Confirmed cases were categorized into three groups (uncomplicated, moderately complicated, and severely complicated) for analysis using a proportional odds logistic regression model. RESULTS: A total of 206 laboratory-confirmed cases of influenza were identified out of 360 enrolled patients with ILI. Among 30 patients (14.6%) classified as complicated cases due to development of pneumonia (n=28) and viral encephalopathy (n=2), 16 were hospitalized in general wards (moderately complicated) and 14 required admission to intensive care units (severely complicated). Complicated patients were less likely to have classic symptoms of ILI than uncomplicated patients. By multivariate analysis, the presence of coronary artery disease, systemic corticosteroid use, impaired renal function and delayed hospital visit were independently associated with development of complications. CONCLUSION: Our study results may help clinicians to identify patients at high risk for complicated influenza, to provide timely antiviral therapy and optimal clinical care.

Cutaneous presentation of disseminated cytomegalovirus infection in a non-transplant patient with hematological malignancy: A case report.

RATIONALE: Cytomegalovirus (CMV) disease is relatively uncommon in nontransplant hematological patients. Moreover, cutaneous manifestations of CMV diseases have scarcely been reported and are probably under-recognized. PATIENT CONCERNS: We describe a patient with large B-cell lymphoma who developed a band-form, erythematous lesion over his left abdomen soon after the second course of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone chemotherapy. DIAGNOSES: The lesion was initially mistaken for bacterial cellulitis or herpes zoster and was histologically confirmed as cutaneous CMV infection. Subsequent work-up also detected CMV viremia and the presence of CMV meningoencephalitis. INTERVENTIONS: The patient was treated with ganciclovir plus CMV immune globulin followed by foscarnet. OUTCOMES: Although the patient's cutaneous lesion resolved, his cognitive impairment did not recover, and he developed a fatal multi-organ failure 1 month later. LESSONS: Cutaneous CMV disease can herald multisystem involvement and an unfavorable prognosis in immunocompromised hosts. It should be ruled out with biopsy in patients with hematological malignancy who have cutaneous lesions refractory to antibacterial therapy.

Mycobacterium abscessus and Mycobacterium massiliense exhibit distinct host and organ specificity: a cross-sectional study.

PURPOSE: Precise subspeciation of Mycobacterium abscessus complex (MAB) is crucial for predicting antibiotic susceptibilities and patient outcomes. However, routine clinical microbiology laboratories have limited diagnostic tools for the differentiation of the subspecies. Thus, we investigated the predictors for MAB subspecies to actuate rapid differentiation and the optimal treatment plans. METHODS: We retrospectively identified stored clinical isolates of MAB and reviewed patient medical records to compare clinical characteristics, sites of infection, and outcomes among patients infected with M. abscessus subsp. abscessus (M. abscessus) and M. abscessus subsp. massiliense (M. massiliense). MAB subspecies were characterised by multilocus sequence analysis with 3-locus sequence (hsp65, rpoB, and secA1) and pulsed-field gel electrophoresis. RESULTS: After outbreak and duplicated cases were excluded, 56 and 36 patients with infection caused by M. abscessus and M. massiliense, respectively, were included in the analysis. Patients with either cardiovascular disease or risk factors for cardiovascular disease (male gender and age ≥55 years) were 4.5 times more likely to harbour M. abscessus (P = 0.002), whereas M. massiliense was 4.8 times more frequently recovered from cutaneous and surgical wounds (P = 0.04). CONCLUSION: Distinct host and organ specificity were observed among patients infected with M. abscessus and those with M. massiliense. These differences may provide clinically significant clues to optimise treatment strategies.