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.

Home and Clinical Laboratory Improvement Amendments-Waived Testing for Infectious Diseases-How Do These Fit in the Testing Landscape?

Though testing for infectious diseases has long been performed in traditional clincial laboratory settings, more widespread availability of waived testing is expanding accessibility of patients to rapid test results. This is being further expanded to home testing. Nevertheless, with this greater democratization and availability of clinical testing there are important limitations that need to be balanced. In this article, we review the current test landscape for infectious diseases waived testing and opportunities for assuring optimal quality testing.

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.

Exploring the Utility of Multiplex Infectious Disease Panel Testing for Diagnosis of Infection in Different Body Sites: A Joint Report of the Association for Molecular Pathology, American Society for Microbiology, Infectious Diseases Society of America, and Pan American Society for Clinical Virology.

The use of clinical molecular diagnostic methods for detecting microbial pathogens continues to expand and, in some cases, supplant conventional identification methods in various scenarios. Analytical and clinical benefits of multiplex molecular panels for the detection of respiratory pathogens have been demonstrated in various studies. The use of these panels in managing different patient populations has been incorporated into clinical guidance documents. The Association for Molecular Pathology's Infectious Diseases Multiplex Working Group conducted a review of the current benefits and challenges to using multiplex PCR for the detection of pathogens from gastrointestinal tract, central nervous system, lower respiratory tract, and joint specimens. The Working Group also discusses future directions and novel approaches to detection of pathogens in alternate specimen types, and outlines challenges associated with implementation of these multiplex PCR panels.

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..

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.

Treatment and Epidemiology of Third-Generation Cephalosporin-Resistant Urinary Tract Infections.

BACKGROUND AND OBJECTIVES: Limited data are available on the contemporary epidemiology, clinical management, and health care utilization for pediatric urinary tract infection (UTI) due to third-generation cephalosporin-resistant Enterobacterales (G3CR) in the United States. The objective is to describe the epidemiology, antimicrobial treatment and response, and health care utilization associated with G3CR UTI. METHODS: Multisite, matched cohort-control study including children with G3CR UTI versus non-G3CR UTI. UTI was defined as per American Academy of Pediatrics guidelines, and G3CR as resistance to ceftriaxone, cefotaxime, or ceftazidime. We collected data from the acute phase of illness to 6 months thereafter. RESULTS: Among 107 children with G3CR UTI and 206 non-G3CR UTI with documented assessment of response, the proportion with significant improvement on initial therapy was similar (52% vs 57%; odds ratio [OR], 0.81; 95% confidence interval [CI], 0.44-1.50). Patients with G3CR were more frequently hospitalized at presentation (38% vs 17%; OR, 3.03; 95% CI, 1.77-5.19). In the follow-up period, more patients with G3CR had urine cultures (75% vs 53%; OR, 2.61; 95% CI, 1.33-5.24), antimicrobial treatment of any indication (53% vs 29%; OR, 2.82; 95% CI, 1.47-5.39), and subspecialty consultation (23% vs 6%; OR, 4.52; 95% CI, 2.10-10.09). In multivariate analysis, previous systemic antimicrobial therapy remained a significant risk factor for G3CR UTI (adjusted OR, 1.91; 95% CI, 1.06-3.44). CONCLUSIONS: We did not observe a significant difference in response to therapy between G3CR and susceptible UTI, but subsequent health care utilization was significantly increased.

Rapid Antigen Assays for SARS-CoV-2: Promise and Peril.

Though rapid antigen tests have historically problematic performance characteristics for the diagnosis of respiratory viral infections such as influenza, they have attained an unprecedented level of use in the context of the COVID-19 pandemic. Ease of use and scalability of rapid antigen tests has facilitated a democratization and scale of testing beyond anything reasonably achievable by traditional laboratory-based testing. In this chapter, we discuss the performance characteristics of rapid antigen testing for SARS-CoV-2 detection and their application to non-traditional uses beyond clinical diagnostic testing.

SARS-CoV-2 cycle threshold (Ct) values predict future COVID-19 cases.

AIM: Anticipating local surges in COVID-19 cases has predominantly been based on observation of increasing cases. We sought to determine if temporal trends in SARS-CoV-2 Cycle threshold (Ct) values from clinical testing were predictive of future cases. METHODS: Data were collected from a large, safety-net hospital in Los Angeles, California. Ct values for all SARS-CoV-2 detections by the GeneXpert system (Cepheid) between October 2020 to March 2021 were analyzed. RESULTS: A total of 2,114 SARS-CoV-2-positive samples were included. Cases increased dramatically in December 2020, peaking the first week of January, before returning to pre-surge numbers by mid-February. Ct values fell during this same period, with values in December and January (25.6 ± 7.8 and 27±7.9, respectively) significantly lower than those of the other months (30±9.3 to 37.7 ± 6.3). Average weekly Ct values for all patients negatively correlated with the number of tests run two weeks in the future (r= -0.74, p<0.0001), whereas Ct values for asymptomatic patients negatively correlated most strongly with total number of tests performed one month later (r= -0.88, p<0.0001). Predictive modeling using these Ct values correctly predicted whether cases would increase or decrease 65% of the time for a subsequent surge (May-July 2021). CONCLUSIONS: During the largest COVID-19 surge in Los Angeles to date, we observed significantly lower Ct values (representing higher levels of viral RNA) suggesting that increased transmission of COVID-19 was temporarily associated with higher viral loads. Decreasing Ct values appear to be a leading indicator for predicting future COVID-19 cases, which can facilitate improved hospital-level surge planning.

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.

Fosfomycin vs Ertapenem for Outpatient Treatment of Complicated Urinary Tract Infections: A Multicenter, Retrospective Cohort Study.

BACKGROUND: We sought to determine the comparative efficacy of fosfomycin vs ertapenem for outpatient treatment of complicated urinary tract infections (cUTIs). METHODS: We conducted a multicenter, retrospective cohort study involving patients with cUTI treated with outpatient oral fosfomycin vs intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis. RESULTS: We identified 322 patients with cUTI treated with fosfomycin (n = 110) or ertapenem (n = 212) meeting study criteria. The study arms had similar demographics, although patients treated with ertapenem more frequently had pyelonephritis or bacteremia while fosfomycin-treated patients had more retained catheters, nephrolithiasis, or urinary obstruction. Most infections were due to extended-spectrum ß-lactamase-producing E. coli and Klebsiella pneumoniae, 80%-90% of which were resistant to other oral options. Adjusted odds ratios for clinical success at 30 days, clinical success at last follow-up, and relapse were 1.21 (95% CI, 0.68-2.16), 0.84 (95% CI, 0.46-1.52), and 0.94 (95% CI, 0.52-1.70) for fosfomycin vs ertapenem, respectively. Patients treated with fosfomycin had significant reductions in length of hospital stay and length of antimicrobial therapy and fewer adverse events (1 vs 10). Fosfomycin outcomes were similar irrespective of duration of lead-in intravenous (IV) therapy or fosfomycin dosing interval (daily, every other day, every third day). CONCLUSIONS: These results would support the conduct of a randomized controlled trial to verify efficacy. In the meantime, they suggest that fosfomycin may be a reasonable stepdown from IV antibiotics for cUTI.

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.

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.

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.

A needle in the haystack? Assessing the significance of envelope (E) gene-negative, nucleocapsid (N2) gene-positive SARS-CoV-2 detection by the Cepheid Xpert Xpress SARS-COV-2 assay.

The clinical significance of high crossing threshold (Ct) detection of SARS-CoV-2 by RT-PCR is inadequately defined. In the course of universal admission screening with the Cepheid Xpert Xpress SARS-CoV-2 assay at our institution, we observed that 3.9 % (44/1123) of SARS-CoV-2 positive results were negative for the envelope (E) gene target but positive for the nucleocapsid (N2) target. The overall SARS-CoV-2 positivity rate during the three-month study period was 15.4 % (1123/7285), spanning April-June 2020. The majority of patients with E-negative, N2-positive results were asymptomatic, with 29.5 % of patients symptomatic for COVID-19 at the time of presentation. Asymptomatic patients with E-negative, N2-positive results were significantly younger than symptomatic patients with the same results (average 37.6 vs. 58.4, p = 0.003). Similar proportions of prior SARS-CoV-2 positivity were noted among symptomatic and asymptomatic individuals (38.5 % vs. 33.3 %, p = 0.82). Among the 16 asymptomatic patients with radiographic imaging performed, four (25 %) had chest radiographic findings concerning for viral pneumonia. Interestingly, we observed an E-negative, N2-positive result in one patient with a previous SARS-CoV-2 by the Xpert Xpress that occurred 71 days prior. Critically, E-negative, N2-positive results were observed in 8 symptomatic patients with a new diagnosis of COVID-19. Thus, though concerns remain about extended SARS-CoV-2 RT-PCR positivity in some patients, the ability of clinical laboratories to detect patients with high Ct values (including E-negative, N2-positive results) is vital for retaining maximal sensitivity for diagnostic purposes. Our data show that a finding of E-positive, N2-negative SARS-CoV-2 should not be used to rule out the presence of subclinical infection.

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.

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.