Publications by authors named "Robin Patel"

433 Publications

An Integrated HOCl-Producing E-Scaffold Is Active against Monomicrobial and Polymicrobial Biofilms.

Antimicrob Agents Chemother 2021 02 17;65(3). Epub 2021 Feb 17.

Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota, USA

Oxidizing agents like hypochlorous acid (HOCl) have antimicrobial activity. We developed an integrated electrochemical scaffold, or e-scaffold, that delivers a continuous low dose of HOCl aimed at targeting microbial biofilms without exceeding concentrations toxic to humans as a prototype of a device being developed to treat wound infections in humans. In this work, we tested the device against 33 isolates of bacteria (including isolates with acquired antibiotic resistance) grown as biofilms alongside 12 combinations of dual-species biofilms. Biofilms were grown on the bottoms of 12-well plates for 24 h. An integrated e-scaffold was placed atop each biofilm and polarized at 1.5 V for 1, 2, or 4 h. HOCl was produced electrochemically by oxidizing chloride ions (Cl) in solution to chlorine (Cl); dissolved Cl spontaneously dissociates in water to produce HOCl. The cumulative concentration of HOCl produced at the working electrode in each well was estimated to be 7.89, 13.46, and 29.50 mM after 1, 2, and 4 h of polarization, respectively. Four hours of polarization caused an average reduction of 6.13 log CFU/cm (±1.99 log CFU/cm) of viable cell counts of monospecies biofilms and 5.53 log CFU/cm (±2.31 log CFU/cm) for the 12 dual-species biofilms studied. The described integrated e-scaffold reduces viable bacterial cell counts in biofilms formed by an array of antibiotic-susceptible and -resistant bacteria alone and in combination.
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http://dx.doi.org/10.1128/AAC.02007-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092506PMC
February 2021

A novel bioreactor for the stable growth of Ureaplasma parvum and Ureaplasma urealyticum.

J Microbiol Methods 2021 02 30;181:106131. Epub 2020 Dec 30.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, United States of America. Electronic address:

Ureaplasma species, including Ureaplasma parvum and Ureaplasma urealyticum, are challenging to culture and maintain. Here, we describe a novel bioreactor for growing high-titer liquid Ureaplasma cultures in a stable manner.
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http://dx.doi.org/10.1016/j.mimet.2020.106131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870580PMC
February 2021

Decrease in Enteroviral Meningitis - An Unexpected Benefit of COVID-19 Mitigation?

Clin Infect Dis 2020 Dec 23. Epub 2020 Dec 23.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

Enteroviral meningitis is seasonal, typically exhibiting a rise in prevalence in late summer/early fall. Based on clinical microbiology laboratory testing data of cerebrospinal fluid, the expected August/September/October peak in enteroviral meningitis did not occur in 2020, possibly related to COVID-19 mitigation strategies.
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http://dx.doi.org/10.1093/cid/ciaa1881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799197PMC
December 2020

Multicenter Evaluation of the Unyvero Platform for Testing Bronchoalveolar Lavage Fluid.

J Clin Microbiol 2021 02 18;59(3). Epub 2021 Feb 18.

Beaumont Hospital, Royal Oak, Section of Infectious Diseases and International Medicine, Royal Oak, Michigan, USA

Bronchoalveolar lavage (BAL) culture is a standard, though time-consuming, approach for identifying microorganisms in patients with severe lower respiratory tract (LRT) infections. The sensitivity of BAL culture is relatively low, and prior antimicrobial therapy decreases the sensitivity further, leading to overuse of empirical antibiotics. The Unyvero LRT BAL Application (Curetis GmbH, Germany) is a multiplex molecular panel that detects 19 bacteria, 10 antibiotic resistance markers, and a fungus, , in BAL fluid in ∼4.5 h. Its performance was evaluated using 1,016 prospectively collected and 392 archived specimens from 11 clinical trial sites in the United States. Overall positive and negative percent agreements with culture results for identification of bacteria that grow in routine cultures were 93.4% and 98.3%, respectively, with additional potential pathogens identified by Unyvero in 21.7% of prospectively collected specimens. For detection of , the positive percent agreement with standard testing was 87.5%. Antibiotic resistance marker results were compared to standard antibiotic susceptibility test results to determine positive predictive values (PPVs). PPVs ranged from 80 to 100%, based on the microorganism and specific resistance marker(s). The Unyvero LRT BAL Application provides accurate detection of common agents of bacterial pneumonia and of The sensitivity and rapidity of this panel suggest significant clinical value for choosing appropriate antibiotics and for antibiotic stewardship.
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http://dx.doi.org/10.1128/JCM.02497-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106704PMC
February 2021

The Impact of Surgical Strategy and Rifampin on Treatment Outcome in Cutibacterium Periprosthetic Joint Infections.

Clin Infect Dis 2021 06;72(12):e1064-e1073

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking.

Methods: In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI.

Results: We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR] = 2.15, P = .03) and antibiotic treatment over 6 weeks (adjusted HR = 0.29, P = .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment-though not statistically significant for treatment failure (adjusted HR = 0.5, P = .07) and not for relapses (adjusted HR = 0.5, P = .10).

Conclusions: We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.
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http://dx.doi.org/10.1093/cid/ciaa1839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427719PMC
June 2021

Correlation between hemolytic profile and phylotype of (formerly ) and orthopedic implant infection.

Shoulder Elbow 2020 Dec 9;12(6):390-398. Epub 2019 Aug 9.

Mayo Clinic, Rochester, USA.

Introduction: is a recognized culprit for implant-associated infections, but positive cultures do not always indicate clinically relevant infection. Studies have shown a correlation between the β-hemolytic phenotype of and its infectious capacity, but correlation with genetic phylotype has not been performed in literature. The purpose of this study is to evaluate β-hemolysis phenotype, genetic phylotype, and mid-term clinical outcomes of isolated from orthopedic surgical sites.

Methods: Fifty-four isolates previously obtained from surgical wounds of patients undergoing hip, knee, shoulder, or spine implant removal were re-cultured. There were 21 females and 33 males with an average age of 59 years (range, 18-84). Twenty-four were from clinically infected sites whereas 30 were considered contaminants. De novo β-hemolysis was analyzed and a retrospective chart review was performed to evaluate clinical outcomes at 7.1 years (range, 0.1-12.8).

Results: On agar with 5% rabbit blood, 46% of contaminant and 43% of infectious isolates were hemolytic. Type II phylotype was significantly more nonhemolytic regardless of infectious or contaminant status (p < 0.05). Type 1B correlated with a hemolytic-infectious phenotype and Type 1A with a hemolytic-contaminant phenotype but was not statistically significant.

Conclusion: The β-hemolytic profile of did not correlate with phylotype or clinically relevant orthopedic infection.
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http://dx.doi.org/10.1177/1758573219865884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689609PMC
December 2020

Leveraging Existing and Soon-to-Be-Available Novel Diagnostics for Optimizing Outpatient Antibiotic Stewardship in Patients With Respiratory Tract Infections.

Clin Infect Dis 2021 06;72(12):e1115-e1121

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Respiratory tract infections (RTIs) drive many outpatient encounters and, despite being predominantly viral, are associated with high rates of antibiotic prescriptions. With rising antibacterial resistance, optimization of prescribing of antibiotics in outpatients with RTIs is a critical need. Fortunately, this challenge arises at a time of increasing availability of novel RTI diagnostics to help discern which patients have bacterial infections warranting treatment. Effective implementation of antibiotic stewardship is needed, but optimal approaches for ambulatory settings are unknown. Future research needs are reviewed in this summary of a research summit convened by the Infectious Diseases Society of America in the fall of 2019.
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http://dx.doi.org/10.1093/cid/ciaa1815DOI Listing
June 2021

Rifampin, Rifapentine, and Rifabutin Are Active against Intracellular Periprosthetic Joint Infection-Associated Staphylococcus epidermidis.

Antimicrob Agents Chemother 2021 01 20;65(2). Epub 2021 Jan 20.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

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 isolates. Compared to no treatment, treatment resulted in a ≥2-fold log reduction of intracellular rifampin-susceptible, but not rifampin-resistant, These findings show activity of rifampin, rifapentine, and rifabutin against intraosteoblast PJI-associated .
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http://dx.doi.org/10.1128/AAC.01275-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849003PMC
January 2021

Plasmid Acquisition Alters Vancomycin Susceptibility in Clostridioides difficile.

Gastroenterology 2021 02 14;160(3):941-945.e8. Epub 2020 Nov 14.

Division of Gastroenterology and Hepatology, Department of Medicine, Rochester, Minnesota; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota. Electronic address:

The increasing incidence of primary and recurring Clostridioides difficile infections (CDI), which evade current treatment strategies, reflects the changing biology of C difficile. Here, we describe a putative plasmid-mediated mechanism potentially driving decreased sensitivity of C difficile to vancomycin treatment. We identified a broad host range transferable plasmid in a C difficile strain associated with lack of adequate response to vancomycin treatment. The transfer of this plasmid to a vancomycin-susceptible C difficile isolate decreased its susceptibility to vancomycin in vitro and resulted in more severe disease in a humanized mouse model. Our findings suggest plasmid acquisition in the gastrointestinal tract to be a possible mechanism underlying vancomycin treatment failure in patients with CDI, but further work is needed to characterize the mechanism by which plasmid genes determine vancomycin susceptibility in C difficile.
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http://dx.doi.org/10.1053/j.gastro.2020.10.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878333PMC
February 2021

Validation of the Alpha Defensin Lateral Flow Test for Periprosthetic Joint Infection.

J Bone Joint Surg Am 2021 Jan;103(2):115-122

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, and Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota.

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.
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http://dx.doi.org/10.2106/JBJS.20.00749DOI Listing
January 2021

COVID-19-Lessons Learned and Questions Remaining.

Clin Infect Dis 2021 06;72(12):2225-2240

Department of Medicine, University of California, San Diego School of Medicine, San Diego, CA, USA.

In 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.
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http://dx.doi.org/10.1093/cid/ciaa1654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797746PMC
June 2021

Planktonic and Biofilm Activity of Eravacycline against Staphylococci Isolated from Periprosthetic Joint Infections.

Antimicrob Agents Chemother 2020 11 17;64(12). Epub 2020 Nov 17.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

MIC and minimum biofilm bactericidal concentration (MBBC) values of eravacycline against 185 staphylococci from periprosthetic joint infections were determined. had MICs of ≤0.25 μg/ml. MICs for methicillin-susceptible and -resistant were ≤1 and ≤2 μg/ml, respectively. and MBBC and MBBC values were 8 and 16 μg/ml for each, showing poor anti-staphylococcal biofilm activity using the method studied.
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http://dx.doi.org/10.1128/AAC.01304-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674029PMC
November 2020

Comparison of Agar Dilution to Broth Microdilution for Testing Activity of Cefiderocol against Gram-Negative Bacilli.

J Clin Microbiol 2020 12 17;59(1). Epub 2020 Dec 17.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

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 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. (IHMA, Schaumburg, IL). Broth microdilution using standard cation-adjusted Mueller-Hinton broth (BMD) and iron-depleted cation-adjusted Mueller-Hinton broth (ID-BMD), and agar dilution (AD) using standard Mueller-Hinton agar were performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MICs were interpreted according to the investigational CLSI, FDA, and EUCAST breakpoints, and results were compared. MICs inhibiting 50 and 90% of organisms (MIC and MIC, respectively), essential agreement (EA), categorical agreement (CA), and error of different types were determined. Results showed considerable discordance between AD and ID-BMD. CFDC showed low EA and CA rates and high error rates for AD in comparison to ID-BMD. Overall, this study does not support use of standard AD for determining CFDC MICs.
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http://dx.doi.org/10.1128/JCM.00966-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771473PMC
December 2020

In vitro activity of arbekacin against multidrug-resistant gram-negative bacilli.

J Microbiol Immunol Infect 2020 Sep 9. Epub 2020 Sep 9.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Arbekacin is a broad-spectrum aminoglycoside with activity against some Gram-positive and Gram-negative bacteria.

Methods: Arbekacin minimum inhibitory concentration (MIC) values were determined for 296 drug-resistant Gram-negative bacilli, and compared to previously determined plazomicin, amikacin, gentamicin, and tobramycin MIC values.

Results: The MIC values required to inhibit 50% and 90% of isolates (MIC and MIC, respectively) were 16 and >128 μg/ml, respectively.

Conclusions: Arbekacin showed similar MIC values to amikacin and gentamicin, a lower MIC value than tobramycin, and a higher MIC value than plazomicin.
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http://dx.doi.org/10.1016/j.jmii.2020.08.018DOI Listing
September 2020

Retrospective Review of Clinical Utility of Shotgun Metagenomic Sequencing Testing of Cerebrospinal Fluid from a U.S. Tertiary Care Medical Center.

J Clin Microbiol 2020 11 18;58(12). Epub 2020 Nov 18.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

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. The majority of patients presented with difficult-to-diagnose subacute or chronic conditions. Positive results were reported for 9 (17%) Mayo Clinic patient samples, with 6 interpreted as likely contamination. Potential pathogens reported included bunyavirus, human herpesvirus 7, and enterovirus D-68, ultimately impacting care in two cases. Twenty-seven additional samples were submitted from Mayo Clinic Laboratories reference clients, with positive results reported for three (11%): two with potential pathogens (West Nile virus and ) and one with species with other bacteria below the reporting threshold (considered to represent contamination). Of 68 negative results, 10 included comments on decreased sensitivity due to high DNA background ( = 5), high RNA background ( = 1), insufficient RNA read depth ( = 3), or quality control (QC) failure with an external RNA control ( = 1). The overall positive-result rate was 15% (12/80), with 58% (7/12) of these interpreted as being inconsistent with the patient's clinical presentation. Overall, potential pathogens were found in a low percentage of cases, and positive results were often of unclear clinical significance. Testing was commonly employed in cases of diagnostic uncertainty and when immunotherapy was being considered.
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http://dx.doi.org/10.1128/JCM.01729-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685881PMC
November 2020

Molecular epidemiology of methicillin-susceptible in infants in a neonatal intensive care unit.

Infect Control Hosp Epidemiol 2020 12 16;41(12):1402-1408. Epub 2020 Sep 16.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo ClinicRochester, Minnesota.

Objective: To investigate the molecular epidemiology of methicillin-susceptible Staphylococcus aureus (MSSA) in infants in a neonatal intensive care unit (NICU) using whole-genome sequencing.

Design: Investigation of MSSA epidemiology in a NICU.

Setting: Single-center, level IV NICU.

Methods: Universal S. aureus screening was done using a single swab obtained from the anterior nares, axilla, and groin area of infants in the NICU on a weekly basis. Core genome multilocus sequence type (cgMLST) analysis was performed on MSSA isolates detected over 1 year (2018-2019).

Results: In total, 68 MSSA-colonized infants were identified, and cgMLSTs of 67 MSSA isolates were analyzed. Overall, we identified 11 cgMLST isolate groups comprising 39 isolates (58%), with group sizes ranging from 2 to 10 isolates, and 28 isolates (42%) were unrelated to each other or any of the isolate groups. Cases of infants colonized by MSSA were scattered throughout the 1-year study period, and isolates belonging to the same cgMLST group were typically detected contemporaneously, over a few weeks or a few months. Overall, 13 infants (19.7%) developed MSSA infections: bacteremia (n = 3), wound infection (n = 5), conjunctivitis (n = 4), and cellulitis (n = 1). We detected no association between these clinically manifest infections and specific cgMLST groups.

Conclusions: Although MSSA isolates in infants in a NICU showed high diversity, most were related to other isolates, albeit within small groups. cgMLST facilitates an understanding of the complex transmission dynamics of MSSA in NICUs, and these data can be used to inform better control strategies.
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http://dx.doi.org/10.1017/ice.2020.355DOI Listing
December 2020

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19:Serologic Testing.

Clin Infect Dis 2020 Sep 12. Epub 2020 Sep 12.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

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 eight diagnostic recommendations.

Conclusions: Information on the clinical performance and utility of SARS-CoV-2 serologic tests are 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 three 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 at least two weeks have passed since symptom onset; 2) assessment of multisystem inflammatory syndrome in children; and 3) for 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.
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http://dx.doi.org/10.1093/cid/ciaa1343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543294PMC
September 2020

Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis.

J Infect Dis 2020 10;222(9):1498-1504

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Rochester, Minnesota, USA.

Background: Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis.

Methods: Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively.

Results: Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group.

Conclusions: Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.
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http://dx.doi.org/10.1093/infdis/jiaa401DOI Listing
October 2020

Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections.

Nat Rev Microbiol 2021 01 19;19(1):23-36. Epub 2020 Aug 19.

Department of Chemistry, University of Massachusetts Amherst, Amherst, MA, USA.

Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative 'outside of the box' therapeutics. Nanomaterial-based therapies are promising tools to combat bacterial infections that are difficult to treat, featuring the capacity to evade existing mechanisms associated with acquired drug resistance. In addition, the unique size and physical properties of nanomaterials give them the capability to target biofilms, overcoming recalcitrant infections. In this Review, we highlight the general mechanisms by which nanomaterials can be used to target bacterial infections associated with acquired antibiotic resistance and biofilms. We emphasize design elements and properties of nanomaterials that can be engineered to enhance potency. Lastly, we present recent progress and remaining challenges for widespread clinical implementation of nanomaterials as antimicrobial therapeutics.
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http://dx.doi.org/10.1038/s41579-020-0420-1DOI Listing
January 2021

Clinical predictors and timing of cessation of viral RNA shedding in patients with COVID-19.

J Clin Virol 2020 Sep 5;130:104577. Epub 2020 Aug 5.

Division of Infectious Diseases, Rochester, MN, USA; Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN, USA.

Background: Molecular detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is key in the diagnosis of coronavirus disease 2019 (COVID-19) and has been widely used for followup of cases as a proxy for contagiousness. The persistence of SARS-CoV-2 RNA shedding in the context of clinical features and comorbidities is understudied.

Methods: We retrospectively reviewed laboratory-confirmed COVID-19 adult symptomatic cases at Mayo Clinic, eventually achieving cessation of viral RNA shedding (CVS), defined as two consecutive negative SARS-CoV-2 PCR results on nasopharyngeal swabs collected at least 24 h apart.

Results: A total of 251 patients were included, median age was 53 years and 59 % female. The most common symptoms at diagnosis were cough, myalgia, dyspnea, fever and chills. Myalgia, cough, anosmia, ageusia and sore throat were common at CVS, but fever and dyspnea were not observed. The median time from symptom onset to CVS was 23 days, and did not differ by symptoms. The weekly cumulative CVS rate was 2, 14, 44, 73, 91 and 95 % at 1-6 weeks from symptom onset, respectively. Cough and fever were associated with a positive PCR test if tested within 2 weeks of symptoms (P < 0.05). Patients with asthma or immunosuppression were less likely to achieve CVS if tested 3 weeks into symptoms (P < 0.04).

Conclusions: The cumulative CVS rate at 3 weeks from symptom-onset is 44 % in our entire cohort. The findings of our study highlight the low yield of repeating a SARS-CoV-2 NP PCR test within 21 days of a laboratoryconfirmed COVID-19 diagnosis.
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http://dx.doi.org/10.1016/j.jcv.2020.104577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405830PMC
September 2020

Seasonality of Coronavirus 229E, HKU1, NL63, and OC43 From 2014 to 2020.

Mayo Clin Proc 2020 08 6;95(8):1701-1703. Epub 2020 Jun 6.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

The possibility of seasonality of COVID-19 is being discussed; we show clinical microbiology laboratory data illustrating seasonality of coronaviruses 229E, HKU1, NL63, and OC43. The data shown are specific to the 4 studied coronaviruses and may or may not generalize to COVID-19.
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http://dx.doi.org/10.1016/j.mayocp.2020.05.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275147PMC
August 2020

Imipenem-Relebactam Susceptibility Testing of Gram-Negative Bacilli by Agar Dilution, Disk Diffusion, and Gradient Strip Methods Compared with Broth Microdilution.

J Clin Microbiol 2020 09 22;58(10). Epub 2020 Sep 22.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

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 and , enriched for drug resistance. MIC and disk diameter results were interpreted using United States Food and Drug Administration breakpoints. Overall, 76.8% of the isolates tested were susceptible to imipenem-relebactam by BMD. MIC values for agar dilution, Etest, and MTS were not significantly different from that for BMD, although they tended to be 1 to 2 dilutions higher. Essential agreement was 95.6% for agar dilution, 90.6% for Etest, and 85.2% for MTS. Categorical agreement was 98.0% for agar dilution, 73.1% for disk diffusion, 96.3% for Etest, and 96.6% for MTS. In conclusion, agar dilution and Etest yielded comparable results to BMD for imipenem-relebactam.
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http://dx.doi.org/10.1128/JCM.00695-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512178PMC
September 2020

Cefiderocol Antimicrobial Susceptibility Testing Considerations: the Achilles' Heel of the Trojan Horse?

J Clin Microbiol 2020 12 17;59(1). Epub 2020 Dec 17.

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

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. Iron concentrations need to be taken into consideration when antimicrobial susceptibility to cefiderocol is determined. Broth microdilution (BMD) and disk diffusion methods have been developed to determine activity of cefiderocol. For BMD, cation-adjusted Mueller-Hinton broth (CAMHB) requires iron depletion to provide MICs predictive of activity. A method to prepare iron-depleted CAMHB (ID-CAMHB) has been described by the Clinical and Laboratory Standards Institute (CLSI). For disk diffusion, standard Mueller-Hinton agar is recommended, presumably because iron is bound in the medium. Currently, clinical FDA and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and investigational (research-use-only) CLSI breakpoints exist for interpreting cefiderocol susceptibility results for certain Gram-negative bacilli. Cefiderocol does not have clinically relevant activity against Gram-positive or anaerobic organisms. FDA or EUCAST breakpoints should be applied to interpret results for , , and complex for patient care until the investigational status has been removed from CLSI breakpoints. Further clinical outcome data are required to assess the effectiveness of cefiderocol for treatment of other species (non- complex) and at this time, and, as such, antimicrobial susceptibility testing of these organisms should be limited to research use in the scenario of limited treatment options.
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http://dx.doi.org/10.1128/JCM.00951-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771437PMC
December 2020

Characteristics and Risk Factors of Post-Infection Irritable Bowel Syndrome After Campylobacter Enteritis.

Clin Gastroenterol Hepatol 2021 09 23;19(9):1855-1863.e1. Epub 2020 Jul 23.

Division of Gastroenterology and Hepatology. Electronic address:

Background & Aims: Campylobacter is the leading cause of bacterial gastroenteritis in the United States. We investigated the prevalence of postinfection irritable bowel syndrome (PI-IBS) in a cohort with culture-confirmed Campylobacter cases; risk factors for PI-IBS based on clinical factors; and shifts in IBS patterns postinfection in patients with pre-existing IBS.

Methods: The Minnesota Department of Health collects data on symptoms and exposures upon notification of Campylobacter cases. From 2011 through 2019, we sent surveys (the Rome III and IBS symptom severity surveys) to 3586 patients 6 to 9 months after Campylobacter infection. The prevalence of PI-IBS was estimated and risk factors were assessed using multivariable logistic regression.

Results: There were 1667 responders to the survey, 249 of whom had pre-existing IBS. Of the 1418 responders without pre-existing IBS, 301 (21%) subsequently developed IBS. Most of these individuals had IBS-mixed (54%), followed by IBS-diarrhea (38%), and IBS-constipation (6%). The mean IBS symptom severity score was 218 (indicating moderate severity). Female sex, younger age, bloody stools, abdominal cramps, and hospitalization during acute enteritis were associated with increased risk, whereas fever was protective for the development of PI-IBS. Antibiotic use and exposure patterns were similar between PI-IBS and control groups. Among patients with IBS-mixed or IBS-diarrhea before infection, 78% retained their subtypes after infection. In contrast, only 50% of patients with IBS-constipation retained that subtype after infection, whereas 40% transitioned to IBS-mixed. Of patients with pre-existing IBS, 38% had increased frequency of abdominal pain after Campylobacter infection.

Conclusions: In a cohort of patients with Campylobacter infection in Minnesota, 21% developed PI-IBS; most cases reported mixed IBS or diarrhea of moderate severity. Demographic and clinical factors during acute enterocolitis are associated with PI-IBS development. Campylobacter infection also can result in a switch of a pre-existing IBS phenotype.
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http://dx.doi.org/10.1016/j.cgh.2020.07.033DOI Listing
September 2021

Phage Therapy for Limb-threatening Prosthetic Knee Klebsiella pneumoniae Infection: Case Report and In Vitro Characterization of Anti-biofilm Activity.

Clin Infect Dis 2021 07;73(1):e144-e151

Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, USA.

Background: Prosthetic joint infection (PJI) is a potentially limb-threatening complication of total knee arthroplasty. Phage therapy is a promising strategy to manage such infections including those involving antibiotic-resistant microbes, and to target microbial biofilms. Experience with phage therapy for infections associated with retained hardware is limited. A 62-year-old diabetic man with a history of right total knee arthroplasty 11 years prior who had suffered multiple episodes of prosthetic knee infection despite numerous surgeries and prolonged courses of antibiotics, with progressive clinical worsening and development of severe allergies to antibiotics, had been offered limb amputation for persistent right prosthetic knee infection due to Klebsiella pneumoniae complex. Intravenous phage therapy was initiated as a limb-salvaging intervention.

Methods: The patient received 40 intravenous doses of a single phage (KpJH46Φ2) targeting his bacterial isolate, alongside continued minocycline (which he had been receiving when he developed increasing pain, swelling, and erythema prior to initiation of phage therapy). Serial cytokine and biomarker measurements were performed before, during, and after treatment. The in vitro anti-biofilm activity of KpJH46Φ2, minocycline and the combination thereof was evaluated against a preformed biofilm of the patient's isolate and determined by safranin staining.

Results: Phage therapy resulted in resolution of local symptoms and signs of infection and recovery of function. The patient did not experience treatment-related adverse effects and remained asymptomatic 34 weeks after completing treatment while still receiving minocycline. A trend in biofilm biomass reduction was noted 22 hours after exposure to KpJH46Φ2 (P = .063). The addition of phage was associated with a satisfactory outcome in this case of intractable biofilm-associated prosthetic knee infection. Pending further studies to assess its efficacy and safety, phage therapy holds promise for treatment of device-associated infections.
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http://dx.doi.org/10.1093/cid/ciaa705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246933PMC
July 2021

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19.

Clin Infect Dis 2020 Jun 16. Epub 2020 Jun 16.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Background: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance.

Objective: The IDSA's goal was to develop an evidence-based diagnostic guideline to assists clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings, and highlight important unmet research needs in the COVID-19 diagnostic testing space.

Methods: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. 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 15 diagnostic recommendations.

Conclusions: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered low to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.
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http://dx.doi.org/10.1093/cid/ciaa760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337674PMC
June 2020

Comparative analysis of 23 synovial fluid biomarkers for hip and knee periprosthetic joint infection detection.

J Orthop Res 2020 12 19;38(12):2664-2674. Epub 2020 Jun 19.

Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota.

There is interest in novel synovial fluid biomarkers for the detection of periprosthetic joint infection (PJI). Here, we assessed the diagnostic accuracy of 23 simple or sophisticated synovial fluid biomarkers for periprosthetic hip or knee infection detection. One hundred seven subjects were studied, 57 of whom had aseptic failure (AF) and 50 PJI. The following synovial fluid biomarkers were tested using spectrophotometric assays, immunoassays, lateral flow tests, or test strips: leukocyte count, monocyte percentage, lymphocyte percentage, neutrophil percentage, C-reactive protein (CRP), glucose, lactate, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, tumor necrosis factor-α, α-defensin, and leukocyte esterase. The best-performing synovial fluid biomarkers to differentiate PJI from AF-that is, those with highest area under the curve compared to all other biomarkers-were leukocyte count, percent neutrophils and percent monocytes, CRP, and α-defensin (P < .0001).
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http://dx.doi.org/10.1002/jor.24766DOI Listing
December 2020

Proposed Plasma Ammonia Reference Intervals in a Reference Group of Hospitalized Term and Preterm Neonates.

J Appl Lab Med 2020 03;5(2):363-369

Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

Background: Plasma ammonia is commonly measured in the diagnostic evaluation of hospitalized newborns, but reference values are not well defined.

Methods: We prospectively enrolled newborns admitted to the level III/IV neonatal intensive care unit and level II intermediate special care nursery from January 2017 to January 2018. Infants with inborn errors of metabolism or liver disease were excluded. Plasma ammonia concentrations were measured once within the first week of life and evaluated by sex, gestational age, timing of the draw, blood collection method, and type of nutrition. Reference intervals were calculated.

Results: 127 neonates were included; one third (34%) were term infants born at ≥37 weeks gestation, and two thirds (66%) were born preterm at <37 weeks gestation. Median plasma ammonia concentrations were 32 μmol/L (range <10 to 86 μmol/L). Median ammonia concentrations were higher among preterm compared to term infants (35 vs. 28 μmol/L, p = 0.0119), and term female compared to term male infants (34 vs. 26 μmol/L, p = 0.0228). There was no difference in median ammonia concentrations between female and male preterm infants, based on gestational age within the preterm group, timing of the blood draw, presence of hyperbilirubinemia, blood collection method, or type of nutritional intake.

Conclusions: Plasma ammonia concentrations among newborns are higher than the expected adult concentrations and may vary by gestational age and sex. Blood collection method, type of nutrition, hyperbilirubinemia, and timing of the draw do not impact concentrations. We propose a reference limit of ≤82 μmol/L for newborns less than one week of age.
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http://dx.doi.org/10.1093/jalm/jfz001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055669PMC
March 2020

Staphylococcus aureus whole genome sequence-based susceptibility and resistance prediction using a clinically amenable workflow.

Diagn Microbiol Infect Dis 2020 Jul 11;97(3):115060. Epub 2020 Apr 11.

Division of Clinical Microbiology, Mayo Clinic, Rochester, MN; Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN. Electronic address:

We used graphical user interface-based automated analytical tools from Next Gen Diagnostics (Mountain View, CA) and 1928 Diagnostics (Gothenburg, Sweden) to analyze whole genome sequence (WGS) data from 102 unique blood culture isolates of Staphylococcus aureus to predict antimicrobial susceptibly, with results compared to those of phenotypic susceptibility testing. Of 916 isolate/antibiotic combinations analyzed using the Next Gen Diagnostics tool, there were 9 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 8 for clindamycin and 1 for minocycline. Of 612 isolate/antibiotic combinations analyzed using the 1928 Diagnostics tool, there were 13 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 9 for clindamycin, 3 for trimethoprim-sulfamethoxazole, and 1 for rifampin. Trimethoprim-sulfamethoxazole was not assessed by Next Gen Diagnostics, and minocycline was not assessed by 1928 Diagnostics. There was complete concordance between phenotypic susceptibility/resistance and genotypic prediction of susceptibility/resistance using both analytical platforms for oxacillin, vancomycin, and mupirocin, as well as by the Next Gen Diagnostics analytical tool for levofloxacin (the 1928 Diagnostics tool did not assess levofloxacin). These results suggest that, from a performance standpoint, with some caveats, automatic bioinformatics tools may be acceptable to predict susceptibility and resistance to a panel of antibiotics for S. aureus.
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http://dx.doi.org/10.1016/j.diagmicrobio.2020.115060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094441PMC
July 2020

Randomized Trial Evaluating Clinical Impact of RAPid IDentification and Susceptibility Testing for Gram-negative Bacteremia: RAPIDS-GN.

Clin Infect Dis 2021 07;73(1):e39-e46

Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota, USA.

Background: Rapid blood culture diagnostics are of unclear benefit for patients with gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, randomized, controlled trial comparing outcomes of patients with GNB BSIs who had blood culture testing with standard-of-care (SOC) culture and antimicrobial susceptibility testing (AST) vs rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (RAPID).

Methods: Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship (AS) review or RAPID with AS. The primary outcome was time to first antibiotic modification within 72 hours of randomization.

Results: Of 500 randomized patients, 448 were included (226 SOC, 222 RAPID). Mean (standard deviation) time to results was faster for RAPID than SOC for organism ID (2.7 [1.2] vs 11.7 [10.5] hours; P < .001) and AST (13.5 [56] vs 44.9 [12.1] hours; P < .001). Median (interquartile range [IQR]) time to first antibiotic modification was faster in the RAPID arm vs the SOC arm for overall antibiotics (8.6 [2.6-27.6] vs 14.9 [3.3-41.1] hours; P = .02) and gram-negative antibiotics (17.3 [4.9-72] vs 42.1 [10.1-72] hours; P < .001). Median (IQR) time to antibiotic escalation was faster in the RAPID arm vs the SOC arm for antimicrobial-resistant BSIs (18.4 [5.8-72] vs 61.7 [30.4-72] hours; P = .01). There were no differences between the arms in patient outcomes.

Conclusions: Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for gram-negative BSIs.

Clinical Trials Registration: NCT03218397.
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http://dx.doi.org/10.1093/cid/ciaa528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246790PMC
July 2021
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