US Food and Drug Administration Perspectives on Clinical Mass Spectrometry.

Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and Drug Administration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders.

Failure to recognize nontuberculous mycobacteria leads to misdiagnosis of chronic pulmonary tuberculosis.

Background: Nontuberculous mycobacterial (NTM) infections cause morbidity worldwide. They are difficult to diagnose in resource-limited regions, and most patients receive empiric treatment for tuberculosis (TB). Our objective here is to evaluate the potential impact of NTM diseases among patients treated presumptively for tuberculosis in Mali.

Geosmithia argillacea: an emerging cause of invasive mycosis in human chronic granulomatous disease.

Background: Chronic granulomatous disease (CGD) is an inherited disorder of the nicotinamide adenine dinucleotide phosphate oxidase that leads to defective production of microbicidal superoxide and other oxidative radicals, resulting in increased susceptibility to invasive infections, especially those due to fungi.

Methods: Geosmithia argillacea was identified from cultured isolates by genomic sequencing of the internal transcribed spacer region. Isolates previously identified as Paecilomyces variotii, a filamentous fungus closely resembling G.

Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of clinically important yeast species.

We evaluated the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for the rapid identification of yeast species. Using Bruker Daltonics MALDI BioTyper software, we created a spectral database library with m/z ratios of 2,000 to 20,000 Da for 109 type and reference strains of yeast (44 species in 8 genera). The database was tested for accuracy by use of 194 clinical isolates (23 species in 6 genera).

Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems.

Rationale: Single-site clinic-based studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease, but systematic data are lacking.

Objectives: To describe prevalence and trends for NTM lung disease at four geographically diverse integrated heath care delivery systems in the United States.

Methods: We abstracted mycobacterial culture results from electronic laboratory databases and linked to other datasets containing clinical and demographic information.

Pharmacokinetics of liposomal amphotericin B in pleural fluid.

We report the penetration of liposomal amphotericin B into the pleural fluid of a patient with pulmonary zygomycosis and empyema. The ratio of area under the concentration-versus-time curve in pleural fluid (AUC(pleural fluid)) to that in serum (AUC(serum)) for liposomal amphotericin B over 24 h was 9.4%, with pleural fluid concentrations of 2.

Fusarium proliferatum soft tissue infection at the site of a puncture by a plant: recovery, isolation, and direct molecular identification.

After allogeneic stem cell transplantation, a 49-year-old man developed fever and inflammation at the site of a plant puncture on a finger. A hyalohyphomycete was recovered by incubating the plant spine fragment following surgery. Amplification of the internal transcribed spacer region and 5.

Chronic invasive aspergillosis caused by Aspergillus viridinutans.

Aspergillus viridinutans, a mold phenotypically resembling A. fumigatus, was identified by gene sequence analyses from 2 patients. Disease was distinct from typical aspergillosis, being chronic and spreading in a contiguous manner across anatomical planes.

Pulmonary nontuberculous mycobacterial infections in hyper-IgE syndrome.

Patients with Hyper Immunoglobulin E Syndrome are predisposed to infections with nontuberculous mycobacteria (NTM) as bronchiectasis develops. Pulmonary NTM infection should be aggressively looked for and treated in these patients.

Invasive aspergillosis due to Neosartorya udagawae.

Background: Invasive aspergillosis (IA) is most commonly caused by the morphospecies Aspergillus fumigatus. However, genetic-based methods indicate that organisms phenotypically identified as A. fumigatus actually constitute a mold complex, designated Aspergillus section fumigati subgenus fumigati.

Cohort study of molecular identification and typing of Mycobacterium abscessus, Mycobacterium massiliense, and Mycobacterium bolletii.

Mycobacterium abscessus is the most common cause of rapidly growing mycobacterial chronic lung disease. Recently, two new M. abscessus-related species, M.

High sensitivity and specificity of acid-fast microscopy for diagnosis of pulmonary tuberculosis in an African population with a high prevalence of human immunodeficiency virus.

Laboratories in low-income countries report that acid-fast microscopy is insensitive and nonspecific. We demonstrate that for a Ugandan population with high prevalences of tuberculosis and human immunodeficiency virus infection, acid-fast microscopy is highly sensitive (93.1%) and specific (100%) when performed by trained technologists in a carefully controlled manner using established techniques.

"Mycobacterium tilburgii," a newly described, uncultivated opportunistic pathogen.

Molecular methods are increasingly used to identify pathogens that are difficult to cultivate. We report a case of disseminated infection with "Mycobacterium tilburgii," a proposed species that has never been cultivated. The case illustrates the diagnostic utility of sequence analysis of the 16S rRNA gene directly from clinical specimens.

Polymerase chain reaction of secA1 on sputum or oral wash samples for the diagnosis of pulmonary tuberculosis.

Background: Nucleic acid amplification tests are sensitive and specific for identifying Mycobacterium tuberculosis in sputum smear-positive populations, but they are less sensitive in sputum smear-negative populations. Few studies have assessed their performance among patients infected with HIV, and no studies have assessed their performance with oral wash specimens, which may be easier to obtain than sputum samples.

Methods: We performed a prospective study involving 127 adults from 2 populations who were undergoing evaluation for respiratory complaints at Mulago Hospital in Kampala, Uganda.

Mycobacterium abscessus and M. avium trigger Toll-like receptor 2 and distinct cytokine response in human cells.

Mycobacterium avium (MAV) and M. abscessus (MAB) are ubiquitous environmental organisms increasingly recognized to cause chronic lung disease in patients with apparently normal immune function. Little is yet known about their human pathophysiology.

Emericella quadrilineata as cause of invasive aspergillosis.

We noted a cluster of 4 cases of infection or colonization by Emericella spp., identified by sequence-based analysis as E. quadrilineata.

Infections caused by Scedosporium spp.

Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp.

Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease.

Background: Chronic granulomatous disease (CGD) is associated with multiple and recurrent infections. In patients with CGD, invasive pulmonary infection with Aspergillus species remains the greatest cause of mortality and is typically insidious in onset. Acute fulminant presentations of fungal pneumonia are catastrophic.

Relationship between metabolism and biomass of medically important zygomycetes.

Little is known about the relationships between metabolic activity and fungal biomass or time of incubation for medically important fungal pathogens. Understanding these relationships may be especially relevant for rapidly growing organisms, such as zygomycetes. A range of inocula of five clinical isolates of zygomycetes (one each of Rhizopus oryzae,Rhizopus microsporus, Cunninghamella bertholletiae, Mucor circinelloides and Absidia corymbifera) were incubated for 6, 8, 12, 24 and 48 h, after which hyphal mass was assessed spectrophotometrically and metabolic activity was measured using various concentrations of XTT and menadione.

Characterization and comparison of galactomannan enzyme immunoassay and quantitative real-time PCR assay for detection of Aspergillus fumigatus in bronchoalveolar lavage fluid from experimental invasive pulmonary aspergillosis.

Bronchoalveolar lavage (BAL) is widely used for evaluation of patients with suspected invasive pulmonary aspergillosis (IPA). However, the diagnostic yield of BAL for detection of IPA by culture and direct examination is limited. Earlier diagnosis may be facilitated by assays that can detect Aspergillus galactomannan antigen or DNA in BAL fluid.

Identification of Mycobacterium species by secA1 sequences.

We describe a novel molecular method for the differentiation and identification of 29 mycobacterial species. The target is the secA1 gene that codes for the essential protein SecA1, a key component of the major pathway of protein secretion across the cytoplasmic membrane. A 700-bp region of the secA1 gene was amplified and sequenced from 47 American Type Culture Collection strains of 29 Mycobacterium species as well as from 59 clinical isolates.