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We describe our approach to addressing a nation-wide supply issue for blood culture bottles. Aerobic blood culture bottles received from our distributor July 1-15, 2024 was <1% of typical usage. Through education and ordering restrictions blood culture designed to minimize risk, orders were reduced by 49% over a one-week period., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The advancement of infectious disease diagnostics, along with studies devoted to infections caused by gram-negative and gram-positive bacteria, is a top scientific priority of the Antibacterial Resistance Leadership Group (ARLG). Diagnostic tests for infectious diseases are rapidly evolving and improving. However, the availability of rapid tests designed to determine antibacterial resistance or susceptibility directly in clinical specimens remains limited, especially for gram-negative organisms. Additionally, the clinical impact of many new tests, including an understanding of how best to use them to inform optimal antibiotic prescribing, remains to be defined. This review summarizes the recent work of the ARLG toward addressing these unmet needs in the diagnostics field and describes future directions for clinical research aimed at curbing the threat of antibiotic-resistant bacterial infections., Competing Interests: Potential conflicts of interest. All authors report funding support from the ARLG of the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID; UM1AI104681). K. E. H. reports holding leadership roles with ARLG as the Diagnostics Committee Chair and Study Principal Investigator (PI), the Clinical and Laboratory Standards Institute (CLSI) as an advisor, Journal of Clinical Microbiology (JCM) as a Mycology Section Editor, and Clinical Infectious Diseases as a Deputy Editor. S. B. D. reports grants or contracts from Gilead, Pfizer, F2G, Regeneron, Chan Zuckerberg Biohub, and NIAID/NIH; consulting fees from Genentech and Janssen/J+J; support from the Infectious Diseases Society of America (IDSA) for travel to speak at IDWeek; patent US20100143379A1 for Mif agonists and antagonist and therapeutic uses thereof; leadership on the IDSA Antibacterial Resistance Committee, Healthcare-Associated Infection Advisory Committee for the California Department of Public Health, Antibacterial Resistance Leadership Group (ARLG) Innovations Group, ARLG Laboratory Center, ARLG Mentorship Committee, ARLG Gram-positive Committee, and ARLG Immunosuppressed Host Group; and payment to her institution from Shinogi, Basilea, and the Duke Clinical Research Institute for clinical events committee/adjudication committee participation. S. R. E. reports grants from the NIAID/NIH, National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), Centers for Disease Control and Prevention (CDC), and Degruter (Editor-in-Chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, Johnson & Johnson, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, and SVB Leerink; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); meeting support from the US Food and Drug Administration, Deming Conference on Applied Statistics, Clinical Trial Transformation Initiative, Council for International Organizations of Medical Sciences, International Chinese Statistical Association Applied Statistics Symposium, and Antimicrobial Resistance and Stewardship Conference; and board member participation for the NIH, Breast International Group, University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, Abbvie, GSK, Eli Lilly, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, Novartis, American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. M. J. S. reports grants and contracts from Merck, Biomerieux, SNIPRBiome, and Selux Diagnostics; consulting fees from Shionogi; and participation on a Data and Safety Monitoring Board or Advisory Board for AbbVie. P. J. S. reports grants or contracts from BD Diagnostics, T2 Diagnostics, OpGen, Inc, Affinity Biosensors, and Qiagen Sciences, Inc; consulting fees from OpGen, Inc, Entasis, BD Diagnostics, Merck, Qiagen Sciences, Inc, and Shionogi; payment or honoraria from GenMark Dx, OpGen, Inc, and BD Diagnostics; leadership on the ARLG Diagnostics Committee, Clinical and Laboratory Standards Institute Antimicrobial Susceptibility Testing Subcommittee, and College of American Pathologists Microbiology Committee; and stock in GeneCapture. R. P. reports grants or contracts from ContraFect, TenNor Therapeutics Limited, BIOFIRE, and Adaptive Phage Therapeutics; a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics through the Mayo Clinic; consulting fees from PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, HealthTrackRx, Netflix, Abbott Laboratories, Trellis Bioscience, Inc, Oxford Nanopore Technologies, and CARB-X; honoraria from the National Board of Medical Examiners (NBME), Up-to-Date, and the Infectious Diseases Board Review Course; a patent on Bordetella pertussis/parapertussis polymerase chain reaction (PCR) issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued; and a financial relationship with Pathogenomix through the Mayo Clinic. 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) 2023. 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.)

We studied the performance of an algorithm combining multiplex polymerase chain reaction with phenotypic detection of extended-spectrum β-lactamases and carbapenemases directly from positive blood culture bottles in patients with gram-negative bacteremia and found good concordance with routine cultures. Such an algorithm may be a tool to improve time to optimal therapy in patients with gram-negative bacteremia., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Reductions in the use of broad-spectrum antibiotics is a cornerstone of antimicrobial stewardship. We aim to demonstrate use of the Desirability of Outcome Ranking Approach for the Management of Antimicrobial Therapy (DOOR MAT) to evaluate the treatment of Escherichia coli and Klebsiella pneumoniae bloodstream infections in patients from the Veterans Health Administration (VHA) across a decade., Methods: Using electronic records, we determined empiric and definitive antibiotic treatments, clinical characteristics, and 30-day mortality of patients with monomicrobial E. coli and K. pneumoniae bloodstream infections hospitalized in VHA medical centers from 2009 to 2018. Focusing on patients treated with parenteral β-lactams and with available antibiotic susceptibility testing results, we applied a range of DOOR MAT scores that reflect the desirability of antibiotic choices according to spectrum and activity against individual isolates. We report trends in resistance and desirability of empiric and definitive antibiotic treatments., Results: During the 10-year period analyzed, resistance to expanded-spectrum cephalosporins and fluoroquinolones increased in E. coli but not in K. pneumoniae, while resistance to carbapenems and piperacillin-tazobactam remained unchanged. In 6451 cases analyzed, we observed improvements in DOOR MAT scores consistent with deescalation. Improvement in desirability of definitive treatment compared with empiric treatment occurred in 26% of cases, increasing from 16% in 2009 to 34% in 2018. Reductions in overtreatment were sustained and without negative impact on survival., Conclusions: DOOR MAT provides a framework to assess antibiotic treatment of E. coli and K. pneumoniae bloodstream infections and can be a useful metric in antimicrobial stewardship., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000 pd) varies widely among children's hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (O:E) ratios were calculated by indirect standardization and compared with DOT/1000 pd. Outliers were defined by O:E z-scores. Antibacterial DOT/1000 pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552-679), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93-1.05). O:E ratios were moderately correlated with DOT/1000 pd (correlation estimate 0.44; 95% confidence interval, 0.19-0.64; P = .0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses, and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic. How best to use newer molecular tests for RTI in combination with clinical judgment and traditional methods can be bewildering given the plethora of available assays and rapidly evolving technologies. Here, we summarize the current state of the art with respect to the diagnosis of viral and bacterial RTIs, provide a practical framework for diagnostic decision making using selected patient-centered vignettes, and make recommendations for future studies to advance the field., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics., (© 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.)

Antibacterial resistance is increasing globally and has been recognized as a major public health threat. Antibacterial stewardship is the coordinated effort to improve the appropriate use of antibiotics with the aim to decrease selective pressure for multidrug-resistant organisms in order to preserve the utility of antibacterial agents. This article describes the activities of the Antibacterial Resistance Leadership Group (ARLG) in the area of antibacterial stewardship. To date, the ARLG has focused intensely on development of rapid diagnostic tests, which (when coupled with educational and institutional initiatives) will enable the robust stewardship that is needed to address the current crisis of antibacterial resistance. In addition to exploring the effectiveness of stewardship techniques in community hospitals, the ARLG has also developed strategy trials to assess the feasibility of reducing antibacterial usage while preserving patient outcome., (© 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.)

Many strategies and technologies are available to improve blood culture (BC)-based diagnostics. The ideal approach to BCs varies between healthcare institutions. Institutions need to examine clinical needs and practices in order to optimize BC-based diagnostics for their site. Before laboratories consider offering rapid matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) or expensive rapid panel-based molecular BC diagnostics, they should optimize preanalytical, analytical, and postanalytical processes and procedures surrounding BC systems. Several factors need to be considered, including local resistance rates, antibiotic prescribing patterns, patient- and provider-types, laboratory staffing, and personnel available to liaise with clinicians to optimize antibiotic use. While there is much excitement surrounding new high-technology diagnostics, cost-neutral benefits can be realized by optimizing existing strategies and using available tools in creative ways. Rapid BC diagnostics should be implemented in a manner that optimizes impact. Strategies to optimize these BC diagnostics in individual laboratories are presented here., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs., Methods: A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost., Results: Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost., Conclusions: rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation., Clinical Trials Registration: NCT01898208., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Reasons for the successful global dissemination of multidrug-resistant Escherichia coli sequence type 131 (ST131) are undefined, but may include enhanced transmissibility or ability to colonize the intestine compared with other strains., Methods: We identified a household in which 2 young children had urinary tract infection (UTI) caused by an extended-spectrum β-lactamase (ESBL)-producing, multidrug-resistant ST131 E. coli strain. We assessed the prevalence of ST131 intestinal colonization among the 7 household members (6 humans, 1 dog). Fecal samples, collected 3 times over a 19-week period, were cultured selectively for E. coli. Isolates were characterized using clone-specific polymerase chain reaction to detect ST131 and its ESBL-associated H30Rx subclone, pulsed-field gel electrophoresis, extended virulence genotyping, and antimicrobial susceptibility testing., Results: In total, 8 different E. coli pulsotypes (strains) were identified. The index patient's urine isolate represented ST131-H30Rx strain 903. This was the most widely shared and persistent strain in the household, colonizing 5 individuals at each sampling. In contrast, the 7 non-ST131 strains were each found in only 1 or 2 household members at a time, with variable persistence. The ST131 strain was the only strain with both extensive virulence and antimicrobial resistance profiles., Conclusions: An ESBL-producing ST131-H30Rx strain caused UTI in 2 siblings, plus asymptomatic intestinal colonization in multiple other household members, and was the household's most extensively detected and persistent fecal E. coli strain. Efficient transmission and intestinal colonization may contribute to the epidemiologic success of the H30Rx subclone of E. coli ST131., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Extensively drug-resistant (XDR) tuberculosis (TB) is a global public health emergency. We investigated the characteristics and extent of XDR TB in California to inform public health interventions., Methods: XDR TB was defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre-XDR TB was defined as TB with resistance to isoniazid and rifampin and either a fluoroquinolone or second-line injectable agent but not both. We analyzed TB case reports submitted to the state TB registry for the period 1993-2006. Local health departments and the state TB laboratory were queried to ensure complete drug susceptibility reporting., Results: Among 424 multidrug-resistant (MDR) TB cases with complete drug susceptibility reporting, 18 (4.2%) were extensively drug resistant, and 77 (18%) were pre-extensively drug resistant. The proportion of pre-XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 (P = .02)). Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were diagnosed in patients within 6 months after arrival in the United States. Mexico was the most common country of origin. Five cases (29%) of XDR TB were acquired during therapy in California. All patients with XDR TB had pulmonary disease, and most had prolonged infectious periods; the median time for conversion of sputum culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%) completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to receive treatment., Conclusions: XDR TB and pre-XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting.