Spivak, Emily S

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) recommends a blood culture contamination (BCC) threshold of <3%, with ≤1% considered optimal. However, there is not a standardized definition of BCC, and the effect of multiple definitions on BCC rates or what definitions laboratories use remain unknown. We surveyed 52 hospitals and analyzed 362,078 blood cultures (BCx) collected 1 September 2019 to 31 August 2021 from 62 intensive care units (ICUs) and 231 wards from 48 of these hospitals. We calculated and compared BCC rates using the College of American Pathologists (CAP) or CLSI criteria (both utilize a limited number of skin commensals to define BCC) and the comprehensive National Healthcare Safety Network (NHSN) commensal list. We characterized factors associated with BCC and related outcomes (central-line associated bloodstream infection [CLABSI] and vancomycin use). BCC, BCx positivity, and single BCx rates were monitored by 100%, 39%, and 21% of hospitals, respectively. Hospitals used CAP (65%), CLSI (17%), and NHSN (17%) criteria to define BCC. Mean BCC rate by CAP (CAP-BCC) was 1.38% for ICUs and 0.96% for wards. BCC rates remained similar by CLSI criteria but increased when using NHSN list. Sharing BCC data outside of the laboratory, measuring additional BCx quality indicators, and limiting central catheter-drawn BCx were associated with lower BCC rates. BCC was associated with higher CLABSI rates in ICUs. This study demonstrated variability in laboratory practices and opportunities to optimize BCx stewardship. IMPORTANCE Blood culture contamination (BCC) is associated with patient harm and unnecessary use of healthcare resources. BCC thresholds have been established; however, multiple BCC definitions exist. There is limited data on how BCC rates differ depending on the BCC definition used, what definitions laboratories most commonly use, or their approach to other blood cultures (BCx) quality indicators such as single rates or BCx positivity. A cross-sectional multicenter survey and analysis of BCx data from intensive care unit and wards revealed that most laboratories did not track single BCx or BCx positivity rates and that there was variability in how BCC was defined. Additionally, BCC rates were influenced by the definition used. BCC was associated with increased central-line associated bloodstream infection rates.

ImportanceBlood culture (BC) use benchmarks in US hospitals have not been defined.ObjectiveTo characterize BC use in adult intensive care units (ICUs) and wards in US hospitals.Design, Setting, and ParticipantsA retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted. Critical access hospitals, less than 6 months of BC data, and non-US hospitals were excluded. The study included BC use data from September 1, 2019, to August 31, 2021. Data were analyzed from February 23 to July 14, 2024.Main Outcomes and MeasuresThe primary outcome was BC use per 1000 patient-days. Adjusted means with 95% CIs were calculated using mixed-effects negative binomial regression models adjusted for unit type, hospital bed size, geographic region, seasonality, and state COVID-19 case load, with random intercepts accounting for clustering at unit and hospital levels. Secondary outcomes included blood culture positivity, single BCs, BC contamination, and minimum threshold for BC use where blood culture positivity would be optimized.ResultsA total of 362 327 blood cultures were analyzed from 27 medical ICUs, 35 medical-surgical ICUs, 121 medical wards, and 109 medical-surgical wards from 48 hospitals in 19 states and the District of Columbia. The adjusted mean BC use per 1000 patient-days was 273.1 (95% CI, 270.2-275.9) for medical ICUs, 146.0 (95% CI, 144.5-147.5) for medical-surgical ICUs, 80.3 (95% CI, 79.8-80.7) for medical wards, and 65.1 for medical-surgical wards. Blood culture use was significantly higher across all 4 unit types in hospitals with more than 500 beds compared with 500 or less beds and in the West-Midwest compared with other regions. Single blood culture and positive blood culture rates were below 10% across all 4 unit types. Of the 292 units, 97% had a mean BC contamination rate within 3% of the recommended threshold, and 51% were within 1%. The minimum BC use thresholds (ie, BC use below this number may represent undertesting) were 120 BCs per 1000 patient-days for medical ICUs, 80 BCs per 1000 patient-days for medical-surgical ICUs, and 30 BCs per 1000 patient-days for medical-surgical wards.Conclusions and RelevanceThe findings of this study suggest that blood culture positivity may help determine appropriate BC use for individual unit types.

BACKGROUND COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS SARS-CoV-2 anti–S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors’ antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use. TRIAL REGISTRATION ClinicalTrials.gov NCT04373460. FUNDING Department of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

AbstractBackgroundCOVID‐19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS‐CoV‐2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.Study Design and MethodsWe analyzed data pertaining to transfusion‐related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders.ResultsThe combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic‐type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID‐19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43–1.31). Risk of urticaria and/or pruritus increased with a pre‐existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16–4.67). We did not observe any CCP‐attributed antibody disease enhancement in participants with COVID‐19 or increased risk of infection. There were no life‐threatening severe transfusion reactions and no patients required hospitalization related to transfusion‐associated complications.DiscussionOutpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID‐19.

Abstract Background Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. Methods We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. Results Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). Conclusions In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. Clinical Trials Registration NCT04373460.