Search

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio, Akagera, Aridis, Roche, grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from Infectious Diseases of America for his service as Associate Editor of Clinical Infectious Diseases, and a patent sepsis diagnostics pending; support for meetings and/or travel from Contrafect. J. T. T. reports being a Scientific Advisor for Resonantia Diagnostics, Inc, and grants or contracts from NIH and CDC. C. A. A. received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics, Harris County Public Health, NIH; support for meetings and/or travel from Infectious Diseases Society of America, American Society for Microbiology, Society of Hospital Epidemiology of America, European Society for Clinical Microbiology and Infectious Diseases, Merieux Foundation, Sociedad Argentina d Infectologia, Sociedad Chilena de Infectologia, Sociedad Colombiana de Infectologia, Panamerican Society for Infectious Diseases, Brazilian Society for Infectious Diseases; participation on the World Health Organization, Antibacterial Pipeline Advisory Group, NIH Grant Review Study Sections, Editor-in-Chief of Antimicrobial Agents and Chemotherapy. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood., Methods: We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (pulsed-field gel electrophoresis [PFGE] and whole-genome sequencing [WGS]) was used to determine whether episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors for recurrence., Results: Of the 1423 patients with GNB-BSI in this study, 60 (4%) had recurrent GNB-BSI. Non-White race (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38-4.01; P = .002), admission to a surgical service (OR, 2.18; 95% CI, 1.26-3.75; P = .005), and indwelling cardiac device (OR, 2.73; 95% CI, 1.21-5.58; P = .009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30 of 48) and 38% were due to reinfection (18 of 48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47 of 48) of cases. Median time to relapse and reinfection was similar (113 days; interquartile range [IQR], 35-222 vs 174 days; IQR, 69-599; P = .13). Presence of a cardiac device was associated with relapse (relapse: 7 of 27, 26%; nonrelapse: 65 of 988, 7%; P = .002)., Conclusions: In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Cardiac device was a risk factor for relapse., Competing Interests: Potential conflicts of interest. V. G. F. reports personal fees from Novartis, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co, Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Basilea, Affinergy, Janssen, xBiotech, Contrafect, Regeneron, Basilea, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, Armata, Valnbio, Akagera, Aridis, Roche, Pfizer, and C3J; grants from NIH, MedImmune, Cerexa/Forest/Actavis/Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Cubist/Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Basilea, Janssen, Green Cross, Cubist, Cerexa, Durata, Theravance, and Debiopharm; royalties from UpToDate; a patent pending in sepsis diagnostics; support from Contrafect to present phase 2 data at 2019 European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); serving as associate editor, Clinical Infectious Diseases; and stock or stock options to self from ArcBio and Valanbio. J. T. T. is a scientific advisor for Resonantia, Inc. C. A. A. reports grant support from Merck Pharmaceuticals, Entasis Pharmaceuticals and MeMed Diagnostics, and Harris County Public Health; payments made to the institution during the conduct of this study from NIH/NIAID ARLG UM1AI104681, NIH/NIAID T32 AI141349, NIH/NIAID U19 AI144297, NIH/NIAID R01 AI150685, and NIH/NIAID R21 AI151536; royalties or licenses from UpToDate paid to self; reimbursements to attend IDWeek as speaker and part of the organizing committee from the Infectious Diseases Society of America, to attend ASMMicrobe as speaker from American Society for Microbiology, to attend the Society for Healthcare Epidemiology of America (SHEA) Conference as speaker from Society of Hospital Epidemiology of America, to attend ECCMID as speaker from the European Society for Clinical Microbiology and Infectious Diseases, to attend the Interdisciplinary Course on Antibiotics and Resistance (ICARE) course as faculty from Merieux Foundation, and to attend annual meeting as speaker from Sociedad Argentina de Infectologia, Sociedad Chilena de Infectologia, Sociedad Colombiana de Infectologia, Panamerican Society for Infectious Diseases, and Brazilian Society for Infectious Diseases; participation on the World Health Organization’s Antibacterial Pipeline Advisory Group (received no financial compensation, no travel, meetings have all been virtual); payment made to self from NIH Grant Review Study Section; a voluntary position, no compensation, payment for travel and accommodation for board meetings as member of the Infectious Diseases Society of America Board of the Directors; and payment made to self as editor in chief, Antimicrobial Agents and Chemotherapy. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We conducted a longitudinal study to evaluate changes in the clinical presentation and epidemiology of Staphylococcus aureus bacteremia (SAB) in an academic, US medical center., Methods: Consecutive patients with monomicrobial SAB were enrolled from January 1995 to December 2015. Each person's initial bloodstream S. aureus isolate was genotyped using spa typing. Clonal complexes (CCs) were assigned using Ridom StaphType software. Changes over time in both the patient and bacterial characteristics were estimated with linear regression. Associations between genotypes or clinical characteristics and complications were estimated using multivariable regression models., Results: Among the 2348 eligible participants, 54.2% had an implantable, foreign body of some type. This proportion increased significantly during the 21-year study period, by 0.96% annually (P = .002), as did comorbid conditions and acquisition outside of the hospital. Rates of any metastatic complication also significantly increased, by 0.94% annually (P = .019). Among the corresponding bloodstream S. aureus isolates, spa-CC012 (multi-locus sequence type [MLST] CC30), -CC004 (MLST CC45), -CC189 (MLST CC1), and -CC084 (MLST CC15) all significantly declined during the study period, while spa-CC008 (MLST CC8) significantly increased. Patients with SAB due to spa-CC008 were significantly more likely to develop metastatic complications in general, and abscesses, septic emboli, and persistent bacteremia in particular. After adjusting for demographic, racial, and clinical variables, the USA300 variant of spa-CC008 was independently associated with metastatic complications (odds ratio 1.42; 95% confidence interval 1.02-1.99)., Conclusions: Systematic approaches for monitoring complications of SAB and genotyping the corresponding bloodstream isolates will help identify the emergence of hypervirulent clones and likely improve clinical management of this syndrome., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Antimicrobial resistance in gram-positive bacteria remains a challenge in infectious diseases. The mission of the Gram-Positive Committee of the Antibacterial Resistance Leadership Group (ARLG) is to advance knowledge in the prevention, management, and treatment of these challenging infections to improve patient outcomes. Our committee has prioritized projects involving methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) due to the scope of the medical threat posed by these pathogens. Approved ARLG projects involving gram-positive pathogens include (1) a pharmacokinetics/pharmacodynamics study to evaluate the impact of vancomycin dosing on patient outcome in MRSA bloodstream infection (BSI); (2) defining, testing, and validating innovative assessments of patient outcomes for clinical trials of MRSA-BSI; (3) testing new strategies for "step-down" antibiotic therapy for MRSA-BSI; (4) management of staphylococcal BSIs in neonatal intensive care units; and (5) defining the impact of VRE bacteremia and daptomycin susceptibility on patient outcomes. This article outlines accomplishments, priorities, and challenges for research of infections caused by gram-positive organisms., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Antimicrobial resistance in pathogenic gram-negative bacteria is one of the most pressing challenges in the field of infectious diseases and is one of 4 key areas of unmet medical need identified by the Antibacterial Resistance Leadership Group (ARLG). The mission of the Gram-Negative Committee is to advance our knowledge of these challenging infections and implement studies to improve patient outcomes. Studies have fallen primarily into 2 broad categories: prospective cohort studies and interventional trials. Among the observational studies, CRACKLE (Consortium on Resistance Against Carbapenems in Klebsiella pneumoniae and Other Enterobacteriaceae) has contributed seminal multicenter data describing risk factors and clinical outcomes of carbapenem-resistant Enterobacteriaceae (CRE) in sentinel US hospitals. Building on this success, CRACKLE II will expand the network to hospitals across the United States and Colombia. Similar protocols have been proposed to include Acinetobacter baumannii and Pseudomonas aeruginosa (SNAP and POP studies). In addition, the CREST study (Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplant Patients) has provided pivotal data on extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and CRE carriage among solid organ transplant recipients to inform management of this vulnerable patient population. Two clinical trials to define novel ways of using an existing antibiotic, fosfomycin, to treat ESBL-producing Enterobacteriaceae (one that has completed enrollment and the other in late protocol development) will determine the clinical efficacy of fosfomycin as step-down oral therapy to treat complicated urinary tract infections. Additional clinical studies and trials using immunotherapeutic or newly approved agents are also in the planning stage, with the main goals of generating actionable data that will inform clinical decision making and facilitate development of new treatment options for highly resistant gram-negative bacterial infections., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)