Patel, Robin

Staphylococcus epidermidis is a major cause of periprosthetic joint infection (PJI); its intracellular persistence within osteoblasts may compromise therapy if that therapy is not intracellularly active. The intracellular activity of rifampin, rifapentine, and rifabutin was assessed against five rifampin-susceptible and two rifampin-resistant S. epidermidis isolates.

Background: The synovial fluid test for alpha defensin has been reported to have an excellent performance in diagnosing periprosthetic joint infection (PJI). The purpose of this study was to evaluate the performance of the lateral flow test for synovial fluid alpha defensin by using the methods of a formal diagnostic accuracy study and to compare its performance with that of the laboratory-based alpha defensin test for PJI. Methods: We conducted a diagnostic accuracy study of the index lateral flow immunoassay for synovial fluid alpha defensin relative to the reference 2013 Musculoskeletal Infection Society (MSIS) multicriteria definition of PJI. The study included a prospective multicenter cohort of outpatients with a failed hip or knee arthroplasty and a supplemental control cohort of fresh synovial fluid specimens submitted by physicians for diagnostic PJI testing. Results: Among 57 patients with PJI and 248 patients without PJI in the overall prospective patient cohort, the sensitivity and specificity of the alpha defensin lateral flow test were 89.5% (95% confidence interval [CI]: 78.5% to 96.0%) and 94.8% (95% CI: 91.2% to 97.2%), respectively. The sensitivity increased to 94.3% (95% CI: 84.3% to 98.8%) after exclusion of 17 patients with grossly bloody aspirates (>1 million red blood cells/µL). Among the supplemental control cohort of fresh synovial fluid samples, including 65 samples from patients with PJI and 397 from patients without PJI, the sensitivity and specificity of the alpha defensin lateral flow test were 98.5% (95% CI: 91.7% to 100.0%) and 98.2% (95% CI: 96.4% to 99.3%), respectively. A comparison of the sensitivity and specificity of the alpha defensin lateral flow test with those of the alpha defensin enzyme-linked immunosorbent assay (ELISA) in the combined cohort did not demonstrate a significant difference in sensitivity (94.3% [95% CI: 88.5% to 97.7%] compared with 93.0% [95% CI: 87.1% to 96.7%]) or specificity (96.9% [95% CI: 95.3% to 98.1%] compared with 97.8% [95% CI: 96.4% to 98.8%]) (both p > 0.05). Conclusions: The results of this study demonstrate the solid diagnostic performance of the alpha defensin test and have resulted in the U.S. Food and Drug Administration (FDA) authorization of the lateral-flow test with an intended use as an aid in the clinical diagnosis of PJI. Level of Evidence: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

AbstractIn this article, the editors of Clinical Infectious Diseases review some of the most important lessons they have learned about the epidemiology, clinical features, diagnosis, treatment and prevention of SARS-CoV-2 infection and identify essential questions about COVID-19 that remain to be answered.

MIC and minimum biofilm bactericidal concentration (MBBC) values of eravacycline against 185 staphylococci from periprosthetic joint infections were determined. Staphylococcus aureus had MICs of ≤0.25 μg/ml. MICs for methicillin-susceptible and -resistant Staphylococcus epidermidis were ≤1 and ≤2 μg/ml, respectively. S. aureus and S. epidermidis MBBC 50 and MBBC 90 values were 8 and 16 μg/ml for each, showing poor anti-staphylococcal biofilm activity using the method studied.

Cefiderocol (CFDC) is a siderophore cephalosporin with activity against Gram-negative bacterial species that are resistant to carbapenems and other drugs. The MICs of CFDC were determined for 610 Gram-negative bacilli, including 302 multinational Enterobacterales isolates with characterized mechanisms of beta-lactam resistance, 180 clinical isolates from the Mayo Clinic and Mayo Clinic Laboratories not characterized for specific resistance mechanisms, and 128 isolates with CFDC MICs of ≥8 μg/ml obtained from International Health Management Associates, Inc.

Shotgun metagenomic sequencing can detect nucleic acids from bacteria, fungi, viruses, and/or parasites in clinical specimens; however, little data exist to guide its optimal application to clinical practice. We retrospectively reviewed results of shotgun metagenomic sequencing testing requested on cerebrospinal fluid samples submitted to an outside reference laboratory from December 2017 through December 2019. Of the 53 samples from Mayo Clinic patients, 47 were requested by neurologists, with infectious diseases consultation in 23 cases.

Abstract Background The availability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing has rapidly increased. Current assays use a variety of technologies, measure different classes of immunoglobulin or immunoglobulin combinations, and detect antibodies directed against different portions of the virus. The overall accuracy of these tests, however, has not been well defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct best-practice guidance related to SARS-CoV-2 serologic testing. This guideline is the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. Objective IDSA’s goal was to develop evidence-based recommendations that assist clinicians, clinical laboratories, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 serologic tests in a variety of settings. We also highlight important unmet research needs pertaining to the use of anti–SARS-CoV-2 antibody tests for diagnosis, public health surveillance, vaccine development, and the selection of convalescent plasma donors. Methods A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 8 diagnostic recommendations. Conclusions Information on the clinical performance and utility of SARS-CoV-2 serologic tests is rapidly emerging. Based on available evidence, detection of anti–SARS-CoV-2 antibodies may be useful for confirming the presence of current or past infection in selected situations. The panel identified 3 potential indications for serologic testing, including (1) evaluation of patients with a high clinical suspicion for COVID-19 when molecular diagnostic testing is negative and ≥2 weeks have passed since symptom onset, (2) assessment of multisystem inflammatory syndrome in children, and (3) conducting serosurveillance studies. The certainty of available evidence supporting the use of serology for either diagnosis or epidemiology was, however, graded as very low to moderate. For the most updated version of these guidelines, please go to https://www.idsociety.org/covid19guidelines.

This study aimed to determine whether agar dilution, research-use-only disk diffusion (Mast Group Ltd., Bootle Merseyside, UK), Etest (bioMérieux, Inc., Durham, NC), and MIC test strip (MTS) (Liofilchem, Inc., Waltham, MA) methods yield equivalent results to those of broth microdilution (BMD) for imipenem-relebactam susceptibility testing using a collection of 297 Gram-negative bacilli, including members of the order Enterobacterales and Pseudomonas aeruginosa , enriched for drug resistance.

Cefiderocol (formerly S-649266) is a novel siderophore-conjugated cephalosporin with activity against a broad array of multidrug-resistant (MDR), aerobic Gram-negative bacilli. The siderophore component binds iron and uses active iron transport for drug entry into the bacterial periplasmic space. The cephalosporin moiety is the active antimicrobial component, structurally resembling a hybrid between ceftazidime and cefepime. Like other β-lactam agents, the principal bactericidal activity of cefiderocol occurs via inhibition of bacterial cell wall synthesis by binding of penicillin-binding proteins (PBPs) and inhibiting peptidoglycan synthesis, leading to cell death.