In vitro activity of omadacycline against clinical isolates of Nocardia.

Nocardiosis typically requires a prolonged treatment duration of ≥6 months and initial combination therapy with 2-3 antibiotics. First-line regimens for nocardiosis are associated with considerable toxicity; therefore, alternative therapies are needed. Omadacycline is an aminomethylcycline with broad antimicrobial activity whose in vitro activity against Nocardia species has not been formally assessed. The in vitro potency of omadacycline was evaluated against 300 Nocardia clinical isolates by broth microdilution. The most common Nocardia species tested were N. cyriacigeorgica (21%), N. nova (20%), and N. farcinica (12%). The most common specimens were respiratory (178 isolates, 59%) and wound (57 isolates, 19%). Omadacycline minimum inhibitory concentrations (MICs) across all Nocardia species ranged from 0.06 µg/mL to 8 µg/mL, with an MIC50 of 2 µg/mL and MIC90 of 4 µg/mL. The lowest MICs were found among N. paucivorans (MIC50 = 0.25 µg/mL, MIC90 = 0.25 µg/mL), N. asiatica (MIC50 = 0.25 µg/mL, MIC90 = 1 µg/mL), N. abscessus complex (MIC50 = 0.5 µg/mL, MIC90 = 1 µg/mL), N. beijingensis (MIC50 = 0.5 µg/mL, MIC90 = 2 µg/mL), and N. otitidiscaviarum (MIC50 = 1 µg/mL, MIC90 = 2 µg/mL). The highest MICs were found among N. farcinica (MIC50 = 4 µg/mL, MIC90 = 8 µg/mL). In vitro potency differed by species among Nocardia clinical isolates. Further studies are warranted to evaluate the potential clinical utility of omadacycline for nocardiosis.

Infectious complications following CAR-t cell therapy for B cell non-Hodgkin lymphoma: a single-center experience and review of the literature.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine.

How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.

BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Analysis of the Capacity of the Fenton Process for the Treatment of Polluted Wastewater from the Leather Dyeing Industry.

In this work, the capacity of the Fenton oxidation process for the degradation of color and organic matter contained in the wastewater generated in the leather dyeing stage (WWDS) of an industrial tannery was evaluated. The wastewater characteristics included, among others, high toxicity (lethal concentration for Artemia salina, 24 h test, 50% of population = 93.71 ppm), high dye concentration (36 mg/L, yellow color), high chromium concentration (3.34 mg/L), and low biodegradability index (BOD5/COD ratio = 0.083). From an experimental design, the response surface methodology, and the multiobjective optimization analysis, the following optimal operating conditions were established: initial pH = 3.15, [Fe2+] = 0.981 mM, and [H2O2] = 5.38 mM. After 10 min of oxidation (determined from kinetic studies), it reached approximately 97% decolorization, COD reduction of approximately 82%, and TOC mineralization of approximately 92%. A synergistic effect of Fenton's reagents for TOC removal (S TOC = 0.8) and decolorization (S CN = 0.28) of the WWDS under study was confirmed experimentally. An increase in the biodegradability index, to a value of approximately 0.3, was confirmed. The cost of the treatment was estimated at 0.0112 USD/m3. Thus, the Fenton oxidation process allowed compliance with current Colombian environmental regulations and considerably improved the biodegradability and toxicity characteristics of the studied industrial effluent. It can be considered as an efficient alternative, easy to carry out on an industrial batch scale, and economically viable for the treatment of wastewater from the leather dyeing stage of an industrial tannery.

Plasma Microbial Cell-free DNA Next-generation Sequencing in the Diagnosis and Management of Febrile Neutropenia.

BACKGROUND: Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management. METHODS: This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results. RESULTS: Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases. CLINICAL TRIALS REGISTRATION: NCT02912117. CONCLUSION: KT shows promise in the diagnosis and treatment optimization of FN.

Effect of two formulations of recombinant bovine somatotropin on milk production and body condition of cattle under intensive management in Peru.

The effect of recombinant somatotropin (rbST) application in cattle has been demonstrated in temperate climate but very limited studies are available in tropical regions. The objective of this study was to compare the effect of the application of two different formulations of rbST on the milk yield and body condition of dairy cattle in a commercial herd under intensive production in Peru. We evaluated the application of 500 mg of active rbST in a zinc sesame oil (ZSO-rbST; n = 44) or vitamin E lecithin (VEL-rbST; n = 45) vehicle while control cows (n = 42) did not receive any application. The application of rbST was performed by every 14 days for 12 cycles, for a total of 168 days. The application of rbST increased the milk production of primiparous and multiparous cows by 3 and 3.2 kg/day for the VEL-rbST formulation respectively when compared with control cows (p < 0.01) and no difference in milk production was observed between the ZSO-rbST formulation and the control group (p > 0.05). However, no significant difference on milk production was observed between the rbST formulations evaluated. The effect of rbST per injection cycle indicated differences in milk production and economic return for the 12 cycles between rbST and control in primiparous group, while in multiparous, no differences were found between ZSO-rbST and control (p > 0.05), but differences were observed between VEL-rbST and control in 41% of the cycles (p < 0.05). No differences in body condition were found between the two rbST formulations and the control group during the evaluation. In conclusion, the application of rbST promoted higher milk production of cattle which had a positive impact on the economic income of the farmer.

Enteric methane emissions by lactating and dry cows in the high Andes of Peru.

The objective of the study was to determine enteric methane emissions using the sulfur hexafluoride (SF6) technique and comparing with The Intergovernmental Panel on Climate Change (IPCC) methodology in lactating cows (LC) and dry cows (DC) in the Peruvian highlands. Enteric methane (CH4) emissions were measured on 5 LC and 6 DC Brown Swiss in a grazing system without concentrate. Forages samples were collected and analyzed for dry matter, crude protein, and neutral detergent fiber. Milk samples were collected and analyzed for fat, crude protein, and lactose to estimate energy-corrected milk. Animal intakes were measured using the external marker titanium dioxide (production of feces) and crude protein in feces (organic digestibility of the feed) and estimated by using performance data. The enteric methane emissions of LC were higher than methane emissions of DC (325 and 266 g CH4/cow/day for LC and DC, respectively (P < 0.001)). Methane emissions were 358.5 g CH4/day by SF6 technique and 291.6 g CH4/day by IPCC methodology for LC and 337.4 g CH4/day by SF6 technique and 195.8 g CH4/day by IPCC methodology for DC. Methane yields measured by SF6 were higher than methane yields estimated by IPCC methodology (29 g CH4/kg DM and 22 g CH4/kg DM using SF6 technique and IPCC methodology, respectively (P < 0.001)). Methane yields were differently for all expressions by physiological stage and method. The methane conversion factor (Ym) was 9.7% for LC and 9.6% for DC. Methane intensities were similar by method (P > 0.05). It was concluded that IPCC's methodology underestimate the CH4 emissions of dairy systems in the Peruvian Andes; therefore, in order to obtain precise Ym, direct measurements of enteric CH4 in the different regions of Peruvian highlands are required.

Clinical Impact of Metagenomic Next-Generation Sequencing of Plasma Cell-Free DNA for the Diagnosis of Infectious Diseases: A Multicenter Retrospective Cohort Study.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA has emerged as an attractive diagnostic modality allowing broad-range pathogen detection, noninvasive sampling, and earlier diagnosis. However, little is known about its real-world clinical impact as used in routine practice. METHODS: We performed a retrospective cohort study of all patients for whom plasma mNGS (Karius test) was performed for all indications at 5 United States institutions over 1.5 years. Comprehensive records review was performed, and standardized assessment of clinical impact of the mNGS based on the treating team's interpretation of Karius results and patient management was established. RESULTS: A total of 82 Karius tests were evaluated from 39 (47.6%) adults and 43 (52.4%) children and a total of 53 (64.6%) immunocompromised patients. Karius positivity rate was 50 of 82 (61.0%), with 25 (50.0%) showing 2 or more organisms (range, 2-8). The Karius test results led to positive impact in 6 (7.3%), negative impact in 3 (3.7%), and no impact in 71 (86.6%), and was indeterminate in 2 (2.4%). Cases with positive Karius result and clinical impact involved bacteria and/or fungi but not DNA viruses or parasites. In 10 patients who underwent 16 additional repeated tests, only 1 was associated with clinical impact. CONCLUSIONS: The real-world impact of the Karius test as currently used in routine clinical practice is limited. Further studies are needed to identify high-yield patient populations, define the complementary role of mNGS to conventional microbiological methods, and discern how best to integrate mNGS into current testing algorithms.

Toxoplasmosis Outbreak Associated With Toxoplasma gondii-Contaminated Venison-High Attack Rate, Unusual Clinical Presentation, and Atypical Genotype.

BACKGROUND: During 2017, in response to a physician's report, the Wisconsin Department of Health Services, Division of Public Health, began investigating an outbreak of febrile illness among attendees of a retreat where never frozen, intentionally undercooked, locally harvested venison was served. Preliminary testing tentatively identified the illness as toxoplasmosis. METHODS: Confirmatory human serology panels and testing of the venison to confirm and categorize the presence and type of Toxoplasma gondii were completed by French and American national reference laboratories. All 12 retreat attendees were interviewed; medical records were reviewed. RESULTS: All attendees were male; median age was 51 years (range: 22-75). After a median incubation period of 7 days, 9 (82%) of 11 exposed persons experienced illness lasting a median of 12 days. All 9 sought outpatient healthcare for symptoms including fever, chills, sweats, and headache (100%) and ocular disturbances (33%). Testing confirmed the illness as toxoplasmosis and venison as the infection source. Multiple laboratory results were atypical for toxoplasmosis, including transaminitis (86%), lymphocytopenia (88%), thrombocytopenia (38%), and leukopenia (63%). One exposed but asymptomatic person was seronegative; the other had immunity from prior infection. The T. gondii strain was identified as closely related to an atypical genotype (haplogroup 12, polymerase chain reaction restriction fragment length polymorphism genotype 5) common in North American wildlife but with previously uncharacterized human clinical manifestations. CONCLUSIONS: The T. gondii strain contaminating the venison might explain the unusual clinical presentations. In North America, clinicians and venison consumers should be aware of risk for severe or unusual presentations of acute toxoplasmosis after consuming undercooked game meat.

Carbon footprint in Latin American dairy systems.

The study reviewed carbon footprint (CF) analyses for milk production in Latin America from cradle to farm gate. The objective was to estimate (1) the effect of feeding management (zero-grazing, semi-confinement, and pasture), (2) cattle system (specialized dairy vs. dual-purpose), and (3) region (tropical vs. temperate) on milk production (kg/cow/day) and CF (kg CO2eq/kg fat and protein corrected milk (FPCM)). A systematic literature review was conducted, and for the final analysis, a total of 32 individual CF (from 11 studies) were used. Studies included in the final analysis allowed to calculate CF per kg FPCM, included upstream emissions calculations, and used the IPCC's tier 2 approach for enteric methane emissions. The range of the CF observed in the region was from 1.54 to 3.57 kg CO2eq/kg FPCM. Feeding management had a significant effect on milk production, but not on CF. Zero-grazing compared with pasture systems had a 140% greater milk production (20.1 vs. 8.4 kg milk/cow/day), but numerically greater CF for pasture systems (2.6 vs. 1.7 kg CO2eq/kg FPCM). Compared with specialized dairy cattle, dual-purpose cattle produced less milk (P < 0.001) and higher CF (P < 0.05). Compared with temperate regions, tropical region systems produced less milk and higher CF. In conclusion, in Latin America, the cattle system and region have a significant impact on CF, whereas the feeding management (zero-grazing, semi-confinement, and pasture) does not impact the CF of milk produced.

Parvovirus B19-induced severe anemia in heart transplant recipients: Case report and review of the literature.

We report a case of a 64-year-old woman who developed transfusion-dependent anemia after cardiac transplantation, the etiology of which was unknown after initial comprehensive evaluation. At the suggestion of the Transplant Infectious Diseases consultant, microbial agents with red blood cell tropism pertinent to this patient such as Parvovirus B 19 (B19V) were investigated. The B19V viral load by PCR in peripheral blood was >100 000 000 copies/ml and after treatment with intravenous immunoglobulin (IVIG), her anemia resolved. Here, we summarize the clinical and virologic characteristics, treatment, and outcome of fifteen cases of B19V-induced anemia in heart transplant recipients. Spontaneous recovery from anemia secondary to B19V has also been reported in some heart transplant recipients, possibly due to an absence of their B19V P-antigen receptor and/or reduction in their immunosuppression. Therefore, in heart transplant patients, B19V should be suspected early as a cause of severe anemia of unknown etiology. The extent that B19V-induced anemia is underdiagnosed in heart transplant recipients is unknown.

Outcomes of patients with infection related to a ventricular assist device after heart transplantation.

BACKGROUND: Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short-term survival and infectious incidence rates in the post-transplantation period and assess risk factors for infectious episodes after transplantation. METHODS: Retrospective single-center study of all consecutive adult heart transplant patients from 2008 to 2017. Survival data were estimated and summarized using the Kaplan-Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine-Gray model. The outcome of interest is the time to first infection diagnosis with post-transplant death as the competing event. RESULTS: Among 278 heart transplant patients, 74 (26.5%) underwent LVAD implantation. Twenty-one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs 27.8 kg/m2 , P = .03). Median follow-up post-transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11-3.39, P = .020) and recipient COPD (HR 2.14, [95% CI] 1.39-3.32, P = .001) when adjusted for recipient age, gender, hypertension, diabetes mellitus, and body mass index. CONCLUSIONS: Patients with LVAD-related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted.

Cut it out! Thoracic surgeon's approach to pulmonary mucormycosis and the role of surgical resection in survival.

BACKGROUND: Mucormycosis portends a poor prognosis with mortality rates ranging from 50% to 70% in pulmonary mucormycosis (PM) and up to 95% in disseminated disease. However, detailed outcomes data have been lacking. It remains unknown how to identify patients who would benefit from surgical resection. OBJECTIVES: We present our experience with patients undergoing surgical resection for PM, including an analysis of factors affecting postoperative survival. We also describe a thoracic surgeon's approach through illustrative cases. PATIENTS/METHODS: We conducted a single-centre retrospective study of all adult patients with PM who received antifungal therapy and underwent surgical resection or who received antifungal therapy alone at Stanford between January 2004 and June 2018. RESULTS: Twelve patients received antifungal therapy and underwent surgical resection and 13 patients received antifungal therapy alone. From infection onset to death (or right-censoring if still alive), patients who underwent surgical resection had a median survival of 406 days (mean, 561.3; range, 22-2510), and patients who received antifungal therapy alone had a median survival of 28 days (mean, 66.7; range, 8-447). In patients who underwent surgical resection, median postoperative survival time was 154 days (range, 11-2495), in-hospital mortality was 16.7%, and 1-year mortality was 50.0%. Age, primary disease, ASA status, extrapulmonary dissemination, laterality, multilobar involvement, number of lesions, largest lesion size, platelet count, surgical approach, type of resection or extent of resection were not significantly associated with postoperative survival. CONCLUSIONS: Surgical resection significantly increases survival and should be strongly considered for selected patients with PM.

Low Yield of FilmArray GI Panel in Hospitalized Patients with Diarrhea: an Opportunity for Diagnostic Stewardship Intervention.

The FilmArray GI panel (BioFire Diagnostics, Salt Lake City, UT) is a multiplex, on-demand, sample-to-answer, real-time PCR assay for the syndromic diagnosis of infectious gastroenteritis that has become widely adopted and, in some instances, has replaced conventional stool culture and parasite exams. Conventional testing has historically been restricted among hospitalized patients due to low diagnostic yield, but it is not known whether use of the FilmArray GI panel should be circumscribed. Cary-Blair stool samples submitted for FilmArray GI panel in adult patients admitted to an academic hospital from August 2015 to January 2017 were included in this study. Of 481 tests performed >72 h after admission, 29 (6.0%) were positive, all for a single target, excluding Clostridium difficile When follow-up tests beyond the first positive per hospitalization were excluded, 20 (4.8%) of 414 tests were positive. There was no difference in yield by immune status. Most targets detected were viral (79% of all positives [n = 23] and 70% in unique patients [n = 14]). All four cases positive for a bacterial target could not be confirmed and presentation was atypical, suggesting possible false positives. After removing potential false positives and chronic viral shedders, the yield was 3.0% (12/406). Repeat testing performed >72 h after admission and following a negative result within the first 72 h was done in 19 patients and 100% (22/22) remained negative. The FilmArray GI panel has low yield in adult patients hospitalized for >72 h, similar to conventional stool microbiology tests, and it is reasonable to restrict its use in this population.

Prevention of infectious diseases in patients with Good syndrome.

PURPOSE OF REVIEW: Good syndrome is a profoundly immunocompromising condition with heterogeneous immune deficits characterized by the presence of thymoma, low-to-absent B-lymphocyte counts, hypogammaglobulinemia, and impaired cell-mediated immunity. Opportunistic infectious diseases associated with Good syndrome represent a diagnostic and therapeutic challenge, given their protean clinical manifestations. Although these infectious complications have been reviewed in prior publications, recommendations regarding their prevention have been lacking. RECENT FINDINGS: Good syndrome usually occurs in adult patients between the ages of 40 and 70 years. Immunologically, it is characterized by low or absent peripheral blood B lymphocytes, hypogammaglobulinemia, and variable defects in cell-mediated immunity including low CD4 T counts, inverted CD4:CD8 T-lymphocyte ratio, and reduced T-lymphocyte mitogen proliferative responses. Patients with Good syndrome are susceptible to a variety of infectious diseases, of which the most common are recurrent bacterial sinopulmonary infections, mucocutaneous candidiasis, and CMV tissue-invasive disease. Preventive guidelines including targeted antimicrobial prophylaxis and vaccination strategies can mitigate infectious complications in patients with Good syndrome. SUMMARY: Immunological deficits and infectious complications in Good syndrome have been described for over 60 years. Further research is needed to elucidate its exact pathogenesis and define the mechanistic relationship between thymoma and hypogammaglobulinemia. However, tailored prophylactic strategies can be recommended for patients with Good syndrome.

Performance of Targeted Fungal Sequencing for Culture-Independent Diagnosis of Invasive Fungal Disease.

BACKGROUND: Identification of fungi causing invasive fungal disease (IFD) is critical for guiding antifungal therapy. We describe the performance and clinical impact of a targeted panfungal polymerase chain reaction (PCR) amplicon sequencing assay for culture-independent diagnosis of IFD. METHODS: Between January 2009 and September 2016, 233 specimens, consisting of fresh and formalin-fixed, paraffin-embedded (FFPE) tissues and sterile body fluids with known diagnosis of IFD based on reference method results (n = 117), and specimens with negative fungal culture, but with microscopic and ancillary findings indicative of IFD (n = 116), were included. PCR amplicons from the internal transcribed spacer 2 and the D2 region of 28S ribosomal RNA gene were sequenced and fungi identified. RESULTS: Sensitivity and specificity of fungal sequencing in specimens with known diagnosis were 96.6% (95% confidence interval [CI], 87.4%-99.4%; 58/60) and 98.2% (95% CI, 89.4%-99.9%; 56/57). In patients with suspected IFD, the diagnostic yield of fungal sequencing was 62.9% (73/116) overall and 71.3% (57/80) in patients classified with proven IFD based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and Mycoses Study Group (EORTC/MSG) criteria. Samples obtained by open biopsy had a significantly higher diagnostic yield (71.5% [40/56]) compared with core-needle biopsy (50% [17/34] P = .04) and fine needle aspiration (0% [0/2]; P = .009). Additionally, D2 sequencing diagnosed 5 cases of invasive protozoal infections due to Toxoplasma gondii (n = 3), Trypanosoma cruzi, and Leishmania species. Sequencing results altered patient management in the majority of suspected cases. CONCLUSIONS: The targeted fungal sequencing assay allowed accurate identification of fungi causing IFD and additionally provided partial-protozoal coverage. The diagnostic yield was dependent on the amount of tissue available for testing.