The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

The detection of pathogens associated with gastrointestinal disease may be important in certain patient populations, such as immunocompromised hosts, the critically ill, or individuals with prolonged disease that is refractory to treatment. In this study, we evaluated two commercially available multiplex panels (the FilmArray gastrointestinal [GI] panel [BioFire Diagnostics, Salt Lake City, UT] and the Luminex xTag gastrointestinal pathogen panel [GPP] [Luminex Corporation, Toronto, Canada]) using Cary-Blair stool samples (n ‫؍‬ 500) submitted to our laboratory for routine GI testing (e.g., culture, antigen testing, microscopy, and individual real-time PCR). At the time of this study, the prototype (non-FDA-cleared) FilmArray GI panel targeted 23 pathogens (14 bacterial, 5 viral, and 4 parasitic), and testing of 200 l of Cary-Blair stool was recommended. In contrast, the Luminex GPP assay was FDA cleared for the detection of 11 pathogens (7 bacterial, 2 viral, and 2 parasitic), but had the capacity to identify 4 additional pathogens using a research-use-only protocol. Importantly, the Luminex assay was FDA cleared for 100 l raw stool; however, 100 l Cary-Blair stool was tested by the Luminex assay in this study. Among 230 prospectively collected samples, routine testing was positive for one or more GI pathogens in 19 (8.3%) samples, compared to 76 (33.0%) by the FilmArray and 69 (30.3%) by the Luminex assay. Clostridium difficile (12.6 to 13.9% prevalence) and norovirus genogroup I (GI)/GII (5.7 to 13.9% prevalence) were two of the pathogens most commonly detected by both assays among prospective samples. Sapovirus was also commonly detected (5.

Background Ehrlichiosis is a clinically important, emerging zoonosis. Only Ehrlichia chaffeensis and E. ewingii have been thought to cause ehrlichiosis in humans in the United States. Patients with suspected ehrlichiosis routinely undergo testing to ensure proper diagnosis and to ascertain the cause. Methods We used molecular methods, culturing, and serologic testing to diagnose and ascertain the cause of cases of ehrlichiosis. Results On testing, four cases of ehrlichiosis in Minnesota or Wisconsin were found not to be from E. chaffeensis or E. ewingii and instead to be caused by a newly discovered ehrlichia species. All patients had fever, malaise, headache, and lymphopenia; three had thrombocytopenia; and two had elevated liver-enzyme levels. All recovered after receiving doxycycline treatment. At least 17 of 697 Ixodes scapularis ticks collected in Minnesota or Wisconsin were positive for the same ehrlichia species on polymerase-chain-reaction testing. Genetic analyses revealed that this new ehrlichia species is closely related to E. muris. Conclusions We report a new ehrlichia species in Minnesota and Wisconsin and provide supportive clinical, epidemiologic, culture, DNA-sequence, and vector data. Physicians need to be aware of this newly discovered close relative of E. muris to ensure appropriate testing, treatment, and regional surveillance. (Funded by the National Institutes of Health and the Centers for Disease Control and Prevention.)

The recent development of commercial panel-based molecular diagnostics for the rapid detection of pathogens in positive blood culture bottles, respiratory specimens, stool, and cerebrospinal fluid has resulted in a paradigm shift in clinical microbiology and clinical practice. This review focuses on U.S. Food and Drug Administration (FDA)-approved/cleared multiplex molecular panels with more than five targets designed to assist in the diagnosis of bloodstream, respiratory tract, gastrointestinal, or central nervous system infections. While these panel-based assays have the clear advantages of a rapid turnaround time and the detection of a large number of microorganisms and promise to improve health care, they present certain challenges, including cost and the definition of ideal test utilization strategies (i.e., optimal ordering) and test interpretation.

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

The coronavirus disease (COVID)-19 pandemic has placed the clinical laboratory and testing for SARS-CoV-2 front-and-center in the worldwide discussion of how to end the outbreak. Clinical laboratories have responded by developing, validating and implementing a variety of molecular and serologic assays to test for SARS-CoV-2 infection. This has played an essential role in identifying cases, informing isolation decisions and helping to curb the spread of disease. However, as the demand for COVID-19 testing has increased, laboratory professionals have faced a growing list of challenges, uncertainties and, in some situations, controversy, as they have attempted to balance the need for increasing test capacity with maintaining a high-quality laboratory operation. The emergence of this new viral pathogen has raised unique diagnostic questions for which there have not always been straightforward answers. In this commentary, the author addresses several areas of current debate, including 1) the role of molecular assays in defining the duration of isolation/quarantine, 2) whether the PCR cycle threshold value should be included on patient reports, 3) if specimen pooling and testing by research staff represent acceptable solutions to expand screening, and 4) whether testing a large percentage of the population is feasible and represents a viable strategy to end the pandemic.

Background Several vaccines are now clinically available under emergency use authorization in the United States and have demonstrated efficacy against symptomatic COVID-19. The impact of vaccines on asymptomatic SARS-CoV-2 infection is largely unknown. Methods We conducted a retrospective cohort study of consecutive, asymptomatic adult patients (n = 39,156) within a large United States healthcare system who underwent 48,333 pre-procedural SARS-CoV-2 molecular screening tests between December 17, 2020 and February 8, 2021. The primary exposure of interest was vaccination with at least one dose of an mRNA COVID-19 vaccine. The primary outcome was relative risk of a positive SARS-CoV-2 molecular test among those asymptomatic persons who had received at least one dose of vaccine, as compared to persons who had not received vaccine during the same time period. Relative risk was adjusted for age, sex, race/ethnicity, patient residence relative to the hospital (local vs. non-local), healthcare system regions, and repeated screenings among patients using mixed effects log-binomial regression. Results Positive molecular tests in asymptomatic individuals were reported in 42 (1.4%) of 3,006 tests performed on vaccinated patients and 1,436 (3.2%) of 45,327 tests performed on unvaccinated patients (RR=0.44 95% CI: 0.33-0.60; p<.0001). Compared to unvaccinated patients, the risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after 1 st dose (RR=0.21; 95% CI: 0.12-0.37; p<.0001) and >0 days after 2 nd dose (RR=0.20; 95% CI: 0.09-0.44; p<.0001) in the adjusted analysis. Conclusions COVID-19 vaccination with an mRNA-based vaccine showed a significant association with a reduced risk of asymptomatic SARS-CoV-2 infection as measured during pre-procedural molecular screening. The results of this study demonstrate the impact of the vaccines on reduction in asymptomatic infections supplementing the randomized trial results on symptomatic patients.

Gastrointestinal disease is a major cause of morbidity and mortality worldwide, especially among young children and immunocompromised patients. Diarrhea may result from infection with a variety of microbial pathogens, including bacteria, viruses, or parasites. Historically, the diagnosis of infectious diarrhea has been made using microscopy, antigen tests, culture, and real-time PCR. A combination of these traditional tests is often required due to the inability to distinguish between infectious etiologies based on the clinical presentation alone. Recently, several multiplex molecular assays have been developed for the detection of gastrointestinal pathogens directly from clinical stool samples. These panels allow for the detection and identification of up to 20 pathogens in as little as 1 h. This review will focus on the multiplex molecular panels that have received clearance from the FDA for the diagnosis of diarrheal disease and will highlight issues related to test performance, result interpretation, and cost-effectiveness of these new molecular diagnostic tools. Diarrheal disease remains a significant global health concern, with the World Health Organization estimating that there are ϳ1.7 billion total cases each year, resulting in Ͼ750,000 deaths among children younger than 5 years old (1). Gastrointestinal (GI) infection with bacteria (e.g., Clostridium difficile, Escherichia coli, Shigella), viruses (e.g., norovirus, rotavirus), or parasites (e.g., Cryptosporidium, Giardia) is a major cause of diarrheal illness worldwide, often resulting from contaminated food/water and poor sanitation. Rapid and accurate detection of GI pathogens is important so that appropriate therapy can be initiated and proper infection control and epidemiologic measures can be taken to help reduce or prevent the spread of disease (2, 3). Traditionally, the laboratory diagnosis of GI infections has relied on a combination of conventional techniques, including microscopy, culture, antigen detection, and individual real-time PCR assays. These methods have demonstrated good performance (4-6), but they are labor intensive, are time consuming, and require health care providers to select the appropriate tests, as a result of clinically indistinguishable illness caused by many infectious agents (7). Recently, there has been substantial interest in the development of multiplex molecular assays for the detection and identification of infectious diseases, including pathogens responsible for causing diarrhea. These syndromic panels allow health care providers to cast a broad net and achieve a timely diagnosis, which may be important in certain patient populations, such as immunocompromised hosts (ICH) and the critically ill (8). This review highlights three commercial multiplex panels (FilmArray GI panel [BioFire Diagnostics, Salt Lake City, UT], Luminex xTag GI pathogen panel [GPP] [Luminex Corporation, Toronto, Canada], and Nanosphere Verigene enteric pathogen [EP] test [Nanosphere, Inc., Northbrook, IL]) that have been cleared by the Food ...