The intestinal microbiota is a complex community of bacteria, archaea, viruses, protists and fungi
. Although the composition of bacterial constituents has been linked to immune homeostasis and ...infectious susceptibility
, the role of non-bacterial constituents and cross-kingdom microbial interactions in these processes is poorly understood
. Fungi represent a major cause of infectious morbidity and mortality in immunocompromised individuals, although the relationship of intestinal fungi (that is, the mycobiota) with fungal bloodstream infections remains undefined
. We integrated an optimized bioinformatics pipeline with high-resolution mycobiota sequencing and comparative genomic analyses of fecal and blood specimens from recipients of allogeneic hematopoietic cell transplant. Patients with Candida bloodstream infection experienced a prior marked intestinal expansion of pathogenic Candida species; this expansion consisted of a complex dynamic between multiple species and subspecies with a stochastic translocation pattern into the bloodstream. The intestinal expansion of pathogenic Candida spp. was associated with a substantial loss in bacterial burden and diversity, particularly in the anaerobes. Thus, simultaneous analysis of intestinal fungi and bacteria identifies dysbiosis states across kingdoms that may promote fungal translocation and facilitate invasive disease. These findings support microbiota-driven approaches to identify patients at risk of fungal bloodstream infections for pre-emptive therapeutic intervention.
Serum (1,3)-beta-D glucan (BDG) is increasingly used to guide the management of suspected Pneumocystis pneumonia (PCP). BDG lacks specificity for PCP, and its clinical performance in high-risk cancer ...patients has not been fully assessed. Polymerase chain reaction (PCR) for PCP detection is highly sensitive, but cannot differentiate between colonization and infection. We evaluated the diagnostic performance of serum BDG in conjunction with PCP PCR on respiratory samples in patients with cancer and unexplained lung infiltrates.
We performed a retrospective analysis of adult patients evaluated for PCP at our institution from 2012 to 2015, using serum BDG and PCP PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the serum BDG at different thresholds were evaluated using PCP PCR alone or in conjunction with clinical presentation in PCP PCR-positive patients.
With PCP PCR alone as the reference method, BDG (≥80 pg/mL) had a sensitivity of 69.8%, specificity of 81.2%, PPV of 34.6%, and NPV of 95.2% for PCP. At ≥200 pg/mL in patients with a positive PCR and a compatible PCP clinical syndrome, BDG had a sensitivity of 70%, specificity of 100%, PPV of 100%, and NPV of 52.0% for PCP.
Patients negative by both BDG and PCR were unlikely to have PCP. In patients with a compatible clinical syndrome for PCP, higher BDG values (>200 pg/mL) were consistently associated with clinically-significant PCP infections among PCP PCR-positive oncology patients.
As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased ...individuals
. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer
, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19
. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.
The FilmArray Respiratory Panel (RP) (BioFire(™) Diagnostics, Inc., Salt Lake City, UT, USA) is the first multiplex molecular panel cleared by the US FDA for the detection of both bacterial and viral ...respiratory pathogens in nasopharygeal swabs. The FilmArray RP targets 20 pathogens including 17 viruses and subtypes and three bacteria, and is performed with minimal sample manipulation. The FilmArray RP has a fully automated sample-to-answer workflow with a turn-around-time of approximately 1 h. The reported sensitivity and specificity of the assay ranges from 80 to 100 and 100%, respectively, with the sensitivity for the adenovirus as low as 46%. A new version of the FilmArray RP assay (version 1.7) with improved sensitivity for the adenovirus was released in 2013. The performance characteristics and simplified workflow have allowed its implementation in a wide range of laboratories. The FilmArray RP has changed the diagnostic landscape and will have a significant impact on the care of patients with respiratory tract infection.
The ASM Awards and Prize Program recognizes outstanding achievements in basic and applied research, clinical microbiology, education, leadership, and service. This editorial briefly describes how the ...program works and highlights several awards of interest to the clinical microbiology community.
Infections remain a significant cause of morbidity and mortality in cancer patients. The differential diagnosis for these patients is often wide, and the timely selection of the right clinical tests ...can have a significant impact on their survival. However, laboratory findings with current methodologies are often negative, challenging clinicians and laboratorians to continue the search for the responsible pathogen. Novel methodologies are providing increased sensitivity and rapid turnaround time to results but also challenging our interpretation of what is a clinically significant pathogen in cancer patients. This minireview provides an overview of the most common infections in cancer patients and discusses some of the challenges and opportunities for the clinical microbiologist supporting the care of cancer patients.
•The cobas EBV test has recently been FDA-cleared for the monitoring of EBV viral loads in plasma samples of transplant patients.•Almost perfect qualitative agreement was observed between the cobas ...EBV and a EBV LDT based on Altona RealStar ASRs.•The quantitative agreement was moderate with the viral load obtained on the cobas EBV test being lower than the EBV LDT across the linear range.
Epstein–Barr Virus (EBV) viral loads in hematopoietic stem cell transplant (HSCT) recipients are typically monitored using quantitative molecular assays. The Cobas EBV test (Roche Molecular, Pleasanton, CA) has recently been FDA-cleared for the monitoring of EBV viral loads in plasma samples of transplant patients. In this study, we compared the viral loads obtained by a laboratory-developed test (EBV LDT) using Altona Analyte specific reagents (ASR) to those obtained on the Cobas EBV test.
The analytical performance of the assay was established using the EBV verification panel from Exact Diagnostics and the EBV ATCC strain B95-8. The clinical evaluation was performed using 343 plasma samples initially tested on the EBV LDT.
The analytical sensitivity (<18.8 IU/mL), precision (SD < 0.17 log) and linear range (35.0 IU/mL to 1E + 08 IU/mL) of the Cobas EBV assay established by the manufacturers were confirmed. The strength of the qualitative agreement was substantial between the cobas EBV and the EBV LDT (85.6 %; κ = 0.71) and almost perfect when discordant results were resolved (96.4 %; κ = 0.93). The quantitative agreement was moderate (82.9 %; κ = 0.53) with the viral load obtained on the Cobas EBV test being lower across the linear range of the two tests (mean log difference of 1.0). While the absolute values of the viral loads were markedly different, the overall trends observed in patients with multiple consecutive results were similar between the two tests.
The Cobas EBV test provides an accurate and valid, in vitro diagnostic (IVD) option for monitoring of EBV viral loads in transplant patients and should provide an opportunity for increased standardization and commutability of tests results across laboratories.
We performed a retrospective survey of non-Candida albicans candidemia in patients with cancer, including those with solid tumors and those with hematological malignancies as well as transplants ...patients both, solid-organ transplant recipients and hematopoietic stem cell transplant recipients. The study was performed at two healthcare centers in New York City and covered the years 2018–2022. A total of 292 patients (318 isolates) were included in the study. In order of frequency,
C. glabrata
(38%) was the most common species recovered, followed by
C. parapsilosis
(19.2%),
C. tropicalis
(12.6%),
C. krusei
(10.7%),
C. lusitaniae
(5.7%), and
C. guilliermondii
(4.4%). Micafungin was the most common antifungal treatment and 18.5% of patients were on antifungal prophylaxis. The 30-day crude mortality was 40%. 4.5% of patients had more than one non-albicans species detected. In conclusion, this study represents one of the largest surveys of non-albicans species in cancer and transplant patients and provides data on the current epidemiology of these
Candida
species in this patient population.
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