Plasmodium vivax Infections among Immigrants from China Traveling to the United States.

Beginning in 2023, we observed increased Plasmodium vivax malaria cases at an institution in Los Angeles, California, USA. Most cases were among migrants from China who traveled to the United States through South and Central America. US clinicians should be aware of possible P. vivax malaria among immigrants from China.

Point-Counterpoint: What's in a Name? Clinical Microbiology Laboratories Should Use Nomenclature Based on Current Taxonomy.

INTRODUCTION The mnemonic SPICE (Serratia, Pseudomonas, indole-positive Proteus, Citrobacter, and Enterobacter) has served as a reminder to consider when a Gram-negative organism may carry a chromosomal copy of blaampC, with the associated risk of developing resistance to first-, second-, and third-generation cephalosporins. However, in 2017, there was a well-founded proposal to rename Enterobacter aerogenes to Klebsiella aerogenes, based on whole-genome sequencing (WGS), and the SPICE mnemonic lost its relevance. With the increased use of WGS for taxonomy, it seems like bacteria and fungi are undergoing constant name changes. These changes create unique challenges for clinical microbiology laboratories, who would like to issue reports that are readily understood and that help clinicians determine empirical antibiotic therapy, interpret antimicrobial resistance, and understand clinical significance. In this Point-Counterpoint, Drs. Karen Carroll and Erik Munson discuss the pros of updating bacterial taxonomy and why clinical labs must continue to update reporting, while Drs. Susan Butler-Wu and Sheila Patrick argue for caution in adopting new names for microorganisms.

Comparative Evaluation of Current Biochemical-, Sequencing-, and Proteomic-Based Identification Methods for the Streptococcus bovis Group.

The Streptococcus bovis group (previously group D streptococci) consists of seven distinct species and subspecies. Definitive identification within the group is important, as certain organisms have been associated with gastrointestinal carcinoma, bacteremia, infective endocarditis, meningitis, biliary tract disease, and carcinoma, among others. Definitive identification, however, remains elusive due to limitations and inconsistencies across commonly used identification platforms in the United States. Here, we compared the performance of standard biochemical (Trek Gram-positive identification [GPID] plate, Vitek 2 GPID), sequencing (16S rDNA, sodA) databases (NCBI, RDP, CDC MicrobeNet), and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) platforms (Vitek MS, Bruker Biotyper MS) using a set of eight type strains representing all seven strains within the S. bovis group. Despite the evaluation of contemporary methods, no single platform was able to definitively identify all type strains within the S. bovis group. Vitek MS (85.7%, 7/8) provided the most accurate definitive identifications, followed by sodA sequencing (75%, 6/8). Vitek 2 and Bruker Biotyper RUO platforms performed the next best (62.5%, 5/8). All remaining platforms failed to adequately differentiate type strains within the S. bovis group (range, 0 to 37.5%). Laboratorians and clinicians should be aware of the identification limitations of routine testing algorithms and incorporate reflex testing, when appropriate, to platforms such as Vitek MS and/or sodA sequencing that are more able to definitively identify S. bovis group organisms. Further clinical evaluation was conducted using 65 clinical isolates from three geographically distinct U.S. institutions. Future improvements in identification platforms may reveal new clinical and epidemiological trends for members of the S. bovis group.

Multicenter evaluation of the BIOFIRE Joint Infection Panel for the detection of bacteria, yeast, and AMR genes in synovial fluid samples.

The bioMérieux BIOFIRE Joint Infection (JI) Panel is a multiplex in vitro diagnostic test for the simultaneous and rapid (~1 h) detection of 39 potential pathogens and antimicrobial resistance (AMR) genes directly from synovial fluid (SF) samples. Thirty-one species or groups of microorganisms are included in the kit, as well as several AMR genes. This study, performed to evaluate the BIOFIRE JI Panel for regulatory clearance, provides data from a multicenter evaluation of 1,544 prospectively collected residual SF samples with performance compared to standard-of-care (SOC) culture for organisms or polymerase chain reaction (PCR) and sequencing for AMR genes. The BIOFIRE JI Panel demonstrated a sensitivity of 90.9% or greater for all but six organisms and a positive percent agreement (PPA) of 100% for all AMR genes. The BIOFIRE JI Panel demonstrated a specificity of 98.5% or greater for detection of all organisms and a negative percent agreement (NPA) of 95.7% or greater for all AMR genes. The BIOFIRE JI Panel provides an improvement over SOC culture, with a substantially shorter time to result for both organisms and AMR genes with excellent sensitivity/PPA and specificity/NPA, and is anticipated to provide timely and actionable diagnostic information for joint infections in a variety of clinical scenarios.

Classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (HL) is rare disease, with an incidence of approximately 85,000 patients globally per year and a predilection for adolescents and young adults (ages 15-39). Since the introduction of combination chemotherapy in the 1960's and radiation dating back to the early 1900's, therapeutic options and by extension, clinical outcomes have improved dramatically with 5-year overall survival (OS) approaching 90% today. [1](#ref-0001) Advances in understanding HL biology have additionally facilitated development of targeted agents and immunotherapy which have further improved short and long-term outcomes. Despite continued improvements in up-front and salvage therapy, long-term survivors of HL experience several treatment-associated late toxicities, thus, along with efforts to improve therapeutic efficacy, efforts to reduce late effects remain a high-priority in the field.

Multimodal Management of Cervical Insufficiency Complicated by Intra-amniotic Candida albicans Infection.

INTRODUCTION: Bacteria are the most common pathogens implicated in ascending infections in patients with cervical insufficiency. However, Candida albicans is a rare and serious cause of intra-amniotic infection that should be considered on the differential diagnosis. Upon diagnosis following cerclage placement, patients are generally advised to undergo immediate cerclage removal and discontinuation of the pregnancy due to the high risk of maternal and fetal morbidity. However, some patients decline and instead elect to continue the pregnancy with or without treatment. Limited data exist to guide management of these high-risk patients. CASE PRESENTATION: We describe a case of previable intra-amniotic C. albicans infection diagnosed following physical examination-indicated cerclage placement. The patient declined pregnancy termination and subsequently underwent systemic antifungal therapy as well as serial intra-amniotic fluconazole instillations. Fetal blood sampling confirmed transplacental transfer of maternal systemic antifungal therapy. The fetus delivered preterm and without evidence of fungemia, despite persistently positive amniotic fluid cultures. CONCLUSION: In a well-counseled patient with culture-proven intra-amniotic C. albicans infection declining termination of pregnancy, multimodal antifungal therapy in the form of systemic and intra-amniotic fluconazole administration may prevent subsequent fetal or neonatal fungemia and improve postnatal outcomes. KEY POINTS: · Candida is an uncommon cause of intra-amniotic infection in the setting of cervical insufficiency.. · Multimodal antifungal therapy may prevent fetal fungemia related to intra-amniotic Candida infection.. · Fetal blood sampling confirmed transplacental passage of fluconazole after maternal administration..

New Perspectives on Antimicrobial Agents: Long-Acting Lipoglycopeptides.

The long-acting lipoglycopeptides (LGPs) dalbavancin and oritavancin are semisynthetic antimicrobials with broad and potent activity against Gram-positive bacterial pathogens. While they are approved by the Food and Drug Administration for acute bacterial skin and soft tissue infections, their pharmacological properties suggest a potential role of these agents for the treatment of deep-seated and severe infections, such as bloodstream and bone and joint infections. The use of these antimicrobials is particularly appealing when prolonged therapy, early discharge, and avoidance of long-term intravascular catheter access are desirable or when multidrug-resistant bacteria are suspected. This review describes the current evidence for the use of oritavancin and dalbavancin in the treatment of invasive infections, as well as the hurdles that are preventing their optimal use. Moreover, this review discusses the current knowledge gaps that need to be filled to understand the potential role of LGPs in highly needed clinical scenarios and the ongoing clinical studies that aim to address these voids in the upcoming years.

Prevalence and Characterization of the Cefazolin Inoculum Effect in North American Methicillin-Susceptible Staphylococcus aureus Isolates.

Antistaphylococcal penicillins and cefazolin remain the primary treatments for infections with methicillin-susceptible Staphylococcus aureus (MSSA). The cefazolin inoculum effect (CzIE) causes the cefazolin MIC to be elevated in proportion to the number of bacteria in the inoculum. The objective of this multicenter study was to evaluate the prevalence of the CzIE in North American MSSA isolates. Clinical MSSA isolates from six microbiology laboratories in the United States and one microbiology laboratory in Canada were screened for the CzIE by broth microdilution at a standard inoculum (~5 × 105 CFU/mL) and a high inoculum (~5 × 107 CFU/mL). Genome sequencing was performed to further characterize the MSSA isolates. The CzIE was present in 57/305 (18.6%) MSSA isolates, ranging from 0% to 27.9% across study sites. More of the CzIE-positive isolates (29.8%) had standard inoculum cefazolin MICs of 1.0 µg/mL than the CzIE-negative isolates did (3.2%) (P < 0.0001). Conversely, more CzIE-negative isolates (39.5%) had standard inoculum MICs of 0.25 µg/mL than the CzIE positive isolates did (5.3%) (P < 0.0001). The most common BlaZ ß-lactamase types found in the CzIE-positive strains were type C (53.7%) and type A (44.4%). ST8 and ST30 were the most common sequence types among CzIE-positive isolates and correlated with BlaZ type C and A, respectively. The CzIE was present in up to a quarter of clinical MSSA isolates from North American clinical laboratories. Further studies to determine the impact of the presence of the CzIE on clinical outcomes are needed.

Active DNA demethylation: many roads lead to Rome.

DNA methylation is one of the best-characterized epigenetic modifications and has been implicated in numerous biological processes, including transposable element silencing, genomic imprinting and X chromosome inactivation. Compared with other epigenetic modifications, DNA methylation is thought to be relatively stable. Despite its role in long-term silencing, DNA methylation is more dynamic than originally thought as active DNA demethylation has been observed during specific stages of development. In the past decade, many enzymes have been proposed to carry out active DNA demethylation and growing evidence suggests that, depending on the context, this process may be achieved by multiple mechanisms. Insight into how DNA methylation is dynamically regulated will broaden our understanding of epigenetic regulation and have great implications in somatic cell reprogramming and regenerative medicine.

Central Nervous System Prophylaxis and Treatment in Acute Leukemias.

OPINION STATEMENT: Improvements in systemic therapy in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) have improved patient outcomes and reduced the incidence of CNS relapse. However, management of patients with CNS disease remains challenging, and relapses in the CNS can be difficult to salvage. In addition to treatment with CNS-penetrant systemic therapy (high-dose methotrexate and cytarabine), intrathecal prophylaxis is indicated in all patients with ALL, however is not uniformly administered in patients with AML without high-risk features. There is a limited role for radiation treatment in CNS prophylaxis; however, radiation should be considered for consolidative treatment in patients with CNS disease, or as an option for palliation of symptoms. Re-examining the role of established treatment paradigms and investigating the role of radiation as bridging therapy in the era of cellular therapy, particularly in chemotherapy refractory patients, is warranted.

Reducing Catheter-associated Urinary Tract Infections via Cost-saving Diagnostic Stewardship.

We conducted a quality improvement project at our large, public, tertiary-care, academic hospital to reduce the standardized infection ratio (SIR) of hospital-acquired catheter-associated urinary tract infections (CAUTIs). Our diagnostic stewardship program, based on education and audit and feedback, significantly reduced inpatient urine culture orders and CAUTI SIR.

Is the Patient Infected with SARS-CoV-2?

The U.S. Food and Drug Administration currently uses the nasopharyngeal swab specimen as the reference standard for evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. We propose that the patient-infected status algorithm is a superior way to classify whether an individual is infected or not infected.

Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV Test.

With the approach of respiratory virus season in the Northern Hemisphere, clinical microbiology and public health laboratories will need rapid diagnostic assays to distinguish severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from influenza virus and respiratory syncytial virus (RSV) infections for diagnosis and surveillance. In this study, the clinical performance of the Xpert Xpress SARS-CoV-2/Flu/RSV test (Cepheid, Sunnyvale, CA, USA) for nasopharyngeal swab specimens was evaluated in four centers: Johns Hopkins Medical Microbiology Laboratory, Northwell Health Laboratories, NYC Public Health Laboratory, and Los Angeles County/University of Southern California (LAC+USC) Medical Center. A total of 319 nasopharyngeal swab specimens, positive for SARS-CoV-2 (n = 75), influenza A virus (n = 65), influenza B virus (n = 50), or RSV (n = 38) or negative (n = 91) by the standard-of-care nucleic acid amplification tests at each site, were tested using the Cepheid panel test. The overall positive percent agreement for the SARS-CoV-2 target was 98.7% (n = 74/75), and the negative agreement was 100% (n = 91), with all other analytes showing 100% total agreement (n = 153). Standard-of-care tests to which the Cepheid panel was compared included the Cepheid Xpert Xpress SARS-CoV-2, Cepheid Xpert Xpress Flu/RSV, GenMark ePlex respiratory panel, BioFire respiratory panel 2.1 and v1.7, DiaSorin Simplexa COVID-19 Direct, and Hologic Panther Fusion SARS-CoV-2 assays. The Xpert Xpress SARS-CoV-2/Flu/RSV test showed high sensitivity and accuracy for all analytes included in the test. This test will provide a valuable clinical diagnostic and public health solution for detecting and differentiating SARS-CoV-2, influenza A and B virus, and RSV infections during the current respiratory virus season.

Acute respiratory infections in hospitalised infants with congenital heart disease.

OBJECTIVES: To assess the overall burden and outcomes of acute respiratory infections in paediatric inpatients with congenital heart disease (CHD). METHODS: This is a retrospective cross-sectional study of non-neonates <1 year with CHD in the Kid's Inpatient Database from 2012. We compared demographics, clinical characteristics, cost, length of stay, and mortality rate for those with and without respiratory infections. We also compared those with respiratory infections who had critical CHD versus non-critical CHD. Multi-variable regression analyses were done to look for associations between respiratory infections and mortality, length of stay, and cost. RESULTS: Of the 28,696 infants with CHD in our sample, 26% had respiratory infections. Respiratory infection-associated hospitalisations accounted for $440 million in costs (32%) for all CHD patients. After adjusting for confounders including severity, mortality was higher for those with respiratory infections (OR 1.5, p = 0.003), estimated mean length of stay was longer (14.7 versus 12.2 days, p < 0.001), and estimated mean costs were higher ($53,760 versus $46,526, p < 0.001). Compared to infants with respiratory infections and non-critical CHD, infants with respiratory infections and critical CHD had higher mortality (4.5 versus 2.3%, p < 0.001), longer mean length of stay (20.1 versus 15.5 days, p < 0.001), and higher mean costs ($94,284 versus $52,585, p < 0.001). CONCLUSION: Acute respiratory infections are a significant burden on infant inpatients with CHD and are associated with higher mortality, costs, and longer length of stay; particularly in those with critical CHD. Future interventions should focus on reducing the burden of respiratory infections in this population.

Clinical Significance of Low Serum Cryptococcal Antigen Titers by Lateral Flow Assay in Immunocompromised Patients: a Retrospective Case-Control Study.

Cryptococcus species are associated with invasive fungal infections in immunosuppressed individuals. The clinical significance of low-titer cryptococcal antigen (CrAg) by lateral flow assay is frequently uncertain. We investigated the correlation of low CrAg titers with disease in an immunocompromised patient population. Patients with first-time positive CrAg results with low serum titers (≤1:10) at two medical centers (Los Angeles, CA) from April 2014 to July 2018 were included. Age-matched controls with high (≥1:20) and negative titers were selected. We extracted medical records for pertinent clinical, radiologic, and laboratory data for cryptococcal disease. From 2,196 serum samples submitted for CrAg testing, 96 cases were included (32 each in low-titer, high-titer, and negative-titer groups). One or more immunocompromising condition was identified in 95% of patients, including HIV infection (45%), solid organ transplant (26%), and cirrhosis (22%). Pulmonary cryptococcosis was diagnosed in 9 (28%) low-titer and 8 (25%) high-titer patients (P = 1.00). Disseminated cryptococcosis occurred in 7 (22%) low-titer and 15 (47%) high-titers cases (P = 0.064). Titers ≤1:10 more frequently represented isolated antigenemia in HIV-positive than non-HIV, immunocompromised patients (P < 0.001). Follow-up testing in patients with ≤1:5 titers (n = 21) showed persistently low titers in 6 of 12 instances and increased titers in 2 cases. Twenty-seven patients with low CrAg titers were treated with antifungal therapy and 22 (81%) responded well clinically. Low-serum CrAg titers (≤1:10) correlated with cryptococcal disease in a substantial proportion of non-HIV immunocompromised patients and should prompt careful clinical workup for cryptococcal infection.

When Should Asymptomatic Persons Be Tested for COVID-19?

On 24 August 2020, the Centers for Disease Control and Prevention (CDC) updated its website to highlight that asymptomatic individuals, even those with exposure to a COVID-19-positive contact, do not necessarily need to be tested unless they have medical conditions associated with increased risk of severe illness from COVID-19. The CDC subsequently updated its guidance on 19 September 2020 to support testing of asymptomatic persons, including close contacts of persons with documented SARS-CoV-2 infection. In this editorial, the American Society for Microbiology Clinical and Public Health Microbiology Committee's Subcommittee on Laboratory Practices comments on testing of asymptomatic individuals relative to current medical knowledge of the virus and mitigation measures. Specific points are provided concerning such testing when undertaking contact tracing and routine surveillance. Limitations to consider when testing asymptomatic persons are covered, including the need to prioritize testing of contacts of positive COVID-19 cases. We urge the CDC to consult with primary stakeholders of COVID-19 testing when making such impactful changes in testing guidance.

Understanding, Verifying, and Implementing Emergency Use Authorization Molecular Diagnostics for the Detection of SARS-CoV-2 RNA.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought a new wave of challenges to health care, particularly in the area of rapid diagnostic test development and implementation. The diagnosis of acute coronavirus disease 2019 (COVID-19) is critically dependent on the detection of SARS-CoV-2 RNA from clinical specimens (e.g., nasopharyngeal swabs). While laboratory-developed testing for SARS-CoV-2 is an essential component of diagnostic testing for this virus, the majority of clinical microbiology laboratories are dependent on commercially available SARS-CoV-2 molecular assays. In contrast to assays approved or cleared by the U.S. Food and Drug Administration (FDA) for in vitro diagnostic use, assays for the detection of SARS-CoV-2 nucleic acids have emergency use authorization (EUA) from the FDA. Outside of highly specialized academic and commercial laboratory settings, clinical microbiology laboratories are likely unfamiliar with the EUA classification, and thus, assay verification can be daunting. Further compounding anxiety for laboratories are major issues with the supply chain that are dramatically affecting the availability of test reagents and requiring laboratories to implement multiple commercial EUA tests. Here, we describe guidance for the verification of assays with EUA for the detection of SARS-CoV-2 nucleic acid from clinical specimens.

Application, Verification, and Implementation of SARS-CoV-2 Serologic Assays with Emergency Use Authorization.

Interest continues to grow regarding the role of serologic assays for the detection of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The U.S. Food and Drug Administration (FDA) has granted emergency use authorization (EUA) status to many SARS-CoV-2 serologic assays. In this document, expert recommendations from clinical microbiologist members of the American Society for Microbiology (ASM) concerning detailed verification strategies for SARS-CoV-2 serologic assays with FDA EUA are provided, as are insights into assay limitations and reporting considerations for laboratories. Assessments concerning single-antibody and multiantibody isotype detection assays, which may provide either differentiated or nondifferentiated (i.e., total antibody) antibody class results, are addressed. Additional considerations prior to assay implementation are also discussed, including biosafety, quality control, and proficiency testing strategies. As the landscape of SARS-CoV-2 serologic testing is rapidly changing, this document provides updated guidance for laboratorians on application of these assays.

Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Test.

Nucleic acid amplification tests (NAATs) are the primary means of identifying acute infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accurate and fast test results may permit more efficient use of protective and isolation resources and allow rapid therapeutic interventions. We evaluated the analytical and clinical performance characteristics of the Xpert Xpress SARS-CoV-2 (Xpert) test, a rapid, automated molecular test for SARS-CoV-2. Analytical sensitivity and specificity/interference were assessed with infectious SARS-CoV-2; other infectious coronavirus species, including SARS-CoV; and 85 nasopharyngeal swab specimens positive for other respiratory viruses, including endemic human coronaviruses (hCoVs). Clinical performance was assessed using 483 remnant upper- and lower-respiratory-tract specimens previously analyzed by standard-of-care (SOC) NAATs. The limit of detection of the Xpert test was 0.01 PFU/ml. Other hCoVs, including Middle East respiratory syndrome coronavirus, were not detected by the Xpert test. SARS-CoV, a closely related species in the subgenus Sarbecovirus, was detected by a broad-range target (E) but was distinguished from SARS-CoV-2 (SARS-CoV-2-specific N2 target). Compared to SOC NAATs, the positive agreement of the Xpert test was 219/220 (99.5%), and the negative agreement was 250/261 (95.8%). A third tie-breaker NAAT resolved all but three of the discordant results in favor the Xpert test. The Xpert test provided sensitive and accurate detection of SARS-CoV-2 in a variety of upper- and lower-respiratory-tract specimens. The high sensitivity and short time to results of approximately 45 min may impact patient management.

Correction: A Year of Infection in the Intensive Care Unit: Prospective Whole Genome Sequencing of Bacterial Clinical Isolates Reveals Cryptic Transmissions and Novel Microbiota.

[This corrects the article DOI: 10.1371/journal.pgen.1005413.].