Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections and Reinfections Among Fully Vaccinated and Unvaccinated University Athletes-15 States, January-November 2021.

BACKGROUND: Limited data currently exist on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among fully vaccinated persons or reinfections in college-aged populations. Centers for Disease Control and Prevention (CDC) partnered with National Collegiate Athletic Association (NCAA) institutions to analyze retrospective data and present characteristics of positive coronavirus disease 2019 (COVID-19) cases among student athletes 18 years of age and older. METHODS: De-identified, individual-level data contributed by 21 universities on 1378 student athletes who tested positive for SARS-CoV-2 from January through November 2021 (pre-Omicron) were examined to determine percentages of infection among unvaccinated, partially vaccinated, and fully vaccinated individuals (breakthrough infections) as well as reinfections. Comparisons by demographic characteristics and regions were also made to further characterize these infections. RESULTS: Among the 1378 student athletes positive for SARS-CoV-2, 1070 (77.6%) were infected when unvaccinated and 22.4% (n = 308) were infected after full vaccination. There was a significant difference between Black (14.7%, n = 40) and White (23.9%, n = 168) student athletes who experienced a SARS-CoV-2 infection after being fully vaccinated (P < .01). Proportions of infections among fully vaccinated individuals did not differ statistically by sex (p = 0.06). CONCLUSIONS: This article adds to the knowledge of SARS-CoV-2 infections among fully vaccinated individuals in college-aged populations. The level of infections among fully vaccinated student athletes indicates the need for maintaining precautions to prevent infection. Further study of COVID-19 vaccination, infection, and reinfection among the well-resourced and diverse population of student athletes might contribute further understanding of factors that play a role in health equity among young adults.

Assessment of a cellular host response test to risk-stratify suspected COVID-19 patients in the Emergency Department setting.

OBJECTIVE: Assess the IntelliSep Index (ISI) for risk stratification of patients presenting to the Emergency Department (ED) with respiratory symptoms suspected of COVID-19 during the pandemic. METHODS: An observational single-center study of prospective cohort of patients presenting to the ED during the early COVID-19 pandemic with respiratory symptoms and a CBC drawn within 4.5 hours of initial vital signs. A sample of this blood was aliquoted for performance of the ISI, and patients were followed for clinical outcomes. The study required no patient-centered activity beyond standard of care and treating clinicians were unaware of study enrollment and ISI test results. MAIN FINDINGS: 282 patients were included. The ISI ranges 0.1 to 10.0, with three interpretation bands indicating risk of adverse outcome: low (green), 0.1-4.9; intermediate (yellow), 5.0-6.2; and high (red), 6.3-10.0. Of 193 (68.4%) tested for SARS-CoV-2, 96 (49.7%) were positive. The ISI resulted in 182 (64.5%) green, 54 (18.1%) yellow, and 46 (15.6%) red band patients. Green band patients had a 1.1% (n = 2) 3-day mortality, while yellow and red band had 3.7% (n = 2, p > .05) and 10.9% (n = 5, p < .05) 3-day mortalities, respectively. Fewer green band patients required admission (96 [52.7%]) vs yellow (44 [81.5%]) and red (43 [93.5%]). Green band patients had more hospital free days (median 23 (Q1-Q3 20-25) than yellow (median 22 [Q1-Q3 0-23], p < 0.05) and red (median 21 [Q1-Q3 0-24], p < 0.01). SOFA increased with interpretation band: green (2, [Q1-Q3 0-4]) vs yellow (4, [Q1-Q3 2-5], p < 0.001) and red (5, [Q1-Q3 3-6]) p < 0.001). CONCLUSIONS: The ISI rapidly risk-stratifies patients presenting to the ED during the early COVID-19 pandemic with signs or suspicion of respiratory infection.

Retrospective identification of infection in the emergency department: A significant challenge in sepsis clinical trials.

BACKGROUND: This study examined three methods for retrospectively identifying infection in emergency department (ED) patients: modified objective definitions of infection (MODI) from the CDC/NHSN, physician adjudication determination of infection, and ED treating physician behavior. METHODS: This study used a subset of data from a prospective sepsis trial. We used Fleiss's Kappa to compare agreement between two physicians retrospectively adjudicating infection based on the patient's medical record, modified infection definition from the CDC/NHSN, and ED treating physician behavior. RESULTS: Overall, there was similar agreement between physician adjudication of infection and MODI criteria (Kappa=0.59) compared to having two physicians independently identify infection through retrospective chart review (Kappa=0.58). ED treating physician behavior was a poorer proxy for infection when compared to the MODI criteria (0.41) and physician adjudication (Kappa = 0.50). CONCLUSIONS: Retrospective identification of infection poses a significant challenge in sepsis clinical trials. Using modified definitions of infection provides a standardized, less time consuming, and equally effective means of identifying infection compared to having multiple physicians adjudicate a patient's chart.

Results from a Test-to-Release from Isolation Strategy Among Fully Vaccinated National Football League Players and Staff Members with COVID-19 - United States, December 14-19, 2021.

During December 2021, the United States experienced a surge in COVID-19 cases, coinciding with predominance of the SARS-CoV-2 B.1.1.529 (Omicron) variant (1). During this surge, the National Football League (NFL) and NFL Players Association (NFLPA) adjusted their protocols for test-to-release from COVID-19 isolation on December 16, 2021, based on analytic assessments of their 2021 test-to-release data. Fully vaccinated* persons with COVID-19 were permitted to return to work once they were asymptomatic or fever-free and experiencing improving symptoms for ≥24 hours, and after two negative or high cycle-threshold (Ct) results (Ct≥35) from either of two reverse transcription-polymerase chain reaction (RT-PCR) tests† (2). This report describes data from NFL's SARS-CoV-2 testing program (3) and time to first negative or Ct≥35 result based on serial COVID-19 patient testing during isolation. Among this occupational cohort of 173 fully vaccinated adults with confirmed COVID-19 during December 14-19, 2021, a period of Omicron variant predominance, 46% received negative test results or had a subsequent RT-PCR test result with a Ct≥35 by day 6 postdiagnosis (i.e., concluding 5 days of isolation) and 84% before day 10. The proportion of persons with positive test results decreased with time, with approximately one half receiving positive RT-PCR test results after postdiagnosis day 5. Although this test result does not necessarily mean these persons are infectious (RT-PCR tests might continue to return positive results long after an initial positive result) (4), these findings indicate that persons with COVID-19 should continue taking precautions, including correct and consistent mask use, for a full 10 days after symptom onset or initial positive test result if they are asymptomatic.

Assessment of a Cellular Host Response Test as a Sepsis Diagnostic for Those With Suspected Infection in the Emergency Department.

OBJECTIVES: Sepsis is a common cause of morbidity and mortality. A reliable, rapid, and early indicator can help improve efficiency of care and outcomes. To assess the IntelliSep test, a novel in vitro diagnostic that quantifies the state of immune activation by measuring the biophysical properties of leukocytes, as a rapid diagnostic for sepsis and a measure of severity of illness, as defined by Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation-II scores and the need for hospitalization. DESIGN SETTING SUBJECTS: Adult patients presenting to two emergency departments in Baton Rouge, LA, with signs of infection (two of four systemic inflammatory response syndrome criteria, with at least one being aberration of temperature or WBC count) or suspicion of infection (a clinician order for culture of a body fluid), were prospectively enrolled. Sepsis status, per Sepsis-3 criteria, was determined through a 3-tiered retrospective and blinded adjudication process consisting of objective review, site-level clinician review, and final determination by independent physician adjudicators. MEASUREMENTS AND MAIN RESULTS: Of 266 patients in the final analysis, those with sepsis had higher IntelliSep Index (median = 6.9; interquartile range, 6.1-7.6) than those adjudicated as not septic (median = 4.7; interquartile range, 3.7-5.9; p < 0.001), with an area under the receiver operating characteristic curve of 0.89 and 0.83 when compared with unanimous and forced adjudication standards, respectively. Patients with higher IntelliSep Index had higher Sequential Organ Failure Assessment (3 [interquartile range, 1-5] vs 1 [interquartile range, 0-2]; p < 0.001) and Acute Physiology and Chronic Health Evaluation-II (7 [interquartile range, 3.5-11.5] vs 5 [interquartile range, 2-9]; p < 0.05) and were more likely to be admitted to the hospital (83.6% vs 48.3%; p < 0.001) compared with those with lower IntelliSep Index. CONCLUSIONS: In patients presenting to the emergency department with signs or suspicion of infection, the IntelliSep Index is a promising tool for the rapid diagnosis and risk stratification for sepsis.

Time from Start of Quarantine to SARS-CoV-2 Positive Test Among Quarantined College and University Athletes - 17 States, June-October 2020.

To safely resume sports, college and university athletic programs and regional athletic conferences created plans to mitigate transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Mitigation measures included physical distancing, universal masking, and maximizing outdoor activity during training; routine testing; 10-day isolation of persons with COVID-19; and 14-day quarantine of athletes identified as close contacts* of persons with confirmed COVID-19. Regional athletic conferences created testing and quarantine policies based on National Collegiate Athletic Association (NCAA) guidance (1); testing policies varied by conference, school, and sport. To improve compliance with quarantine and reduce the personal and economic burden of quarantine adherence, the quarantine period has been reduced in several countries from 14 days to as few as 5 days with testing (2) or 10 days without testing (3). Data on quarantined athletes participating in NCAA sports were used to characterize COVID-19 exposures and assess the amount of time between quarantine start and first positive SARS-CoV-2 test result. Despite the potential risk for transmission from frequent, close contact associated with athletic activities (4), more athletes reported exposure to COVID-19 at social gatherings (40.7%) and from roommates (31.7%) than they did from exposures associated with athletic activities (12.7%). Among 1,830 quarantined athletes, 458 (25%) received positive reverse transcription-polymerase chain reaction (RT-PCR) test results during the 14-day quarantine, with a mean of 3.8 days from quarantine start (range = 0-14 days) until the positive test result. Among athletes who had not received a positive test result by quarantine day 5, the probability of having a positive test result decreased from 27% after day 5 to <5% after day 10. These findings support new guidance from CDC (5) in which different options are provided to shorten quarantine for persons such as collegiate athletes, especially if doing so will increase compliance, balancing the reduced duration of quarantine against a small but nonzero risk for postquarantine transmission. Improved adherence to mitigation measures (e.g., universal masking, physical distancing, and hand hygiene) at all times could further reduce exposures to SARS-CoV-2 and disruptions to athletic activities because of infections and quarantine (1,6).

Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis.

OBJECTIVES: This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC ß-lactamase. METHODS: Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum ß-lactam/ß-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. REGISTRATION: PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). RESULTS: Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. CONCLUSIONS: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.

Neutropenia Associated with Long-Term Ceftaroline Use.

Ceftaroline is a fifth-generation cephalosporin with potent antimicrobial activity against Gram-positive and Gram-negative pathogens. Neutropenia is a rare serious adverse event for the class of cephalosporins; however, we observed several cases of severe neutropenia in our outpatient infectious disease practice believed to be associated with ceftaroline use. The aim of this study was to determine the incidence of neutropenia among patients receiving ceftaroline therapy for more than 7 days. We conducted a retrospective cohort analysis of patients admitted to an 800-bed regional medical center between June 2012 and December 2014 who received ceftaroline for more than 7 days to assess the incidence of developing clinically significant neutropenia. Demographic and patient care data points as well as underlying admitting and chronic diagnoses were retrospectively collected from the medical record. Clinically significant neutropenia was defined as an absolute neutrophil count (ANC) less than 1,500 cells/mm(3). Analysis was performed to determine the incidence, severity, and outcome of neutropenia following ceftaroline administration. A total of 39 patients were included in the cohort. The median duration of therapy was 27 days. Seven patients (18%) developed neutropenia while on ceftaroline therapy. Four (10%) of the neutropenic patients had an ANC of <500 cells/mm(3). The median first neutropenic day was day 17, with the median ANC nadir of 432 cells/mm(3) on day 24. We determined that extended ceftaroline infusion is associated with the development of neutropenia. We recommend obtaining a complete blood count (CBC) with differential at the onset of therapy and weekly thereafter. Should the ANC fall below 2,500 cells/mm(3), then twice-weekly CBCs should be monitored for the duration of ceftaroline therapy, and therapy should be discontinued if the ANC falls to 1,500 cells/mm(3) or less.

Treatment outcomes in patients with third-generation cephalosporin-resistant Enterobacter bacteremia.

BACKGROUND: Infections with resistant Enterobacter spp. are increasingly described, yet data on outcomes associated with these infections are limited. METHODS: A retrospective cohort study was conducted to investigate outcomes of hospitalized patients with third-generation cephalosporin-resistant (CR) Enterobacter bacteremia. Cephalosporin resistance was detected using cefotaxime and cefpodoxime. Patients with Enterobacter spp. bacteremia from January 2006 through February 2008 defined the population. We defined cases as those with CR isolates; controls were patients with bacteremia due to non-CR isolates. Treatment failure was defined as persistence of the presenting signs of infection 72 h after initial culture collection. RESULTS: Of the 95 Enterobacter cases identified, 31 (33%) were CR. CR cases were significantly associated with treatment failure (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.14-6.94). This association was not seen after adjustment for age, simplified acute physiology score (SAPS II), and inappropriate empiric antibiotic therapy. Inappropriate empiric therapy (adjusted OR 3.86, 95% CI 1.32-11.31) and SAPS II score (adjusted OR 1.09, 95% CI 1.02-1.16) were significantly associated with treatment failure in the multivariate analysis. CONCLUSIONS: Third-generation cephalosporin-resistant Enterobacter bacteremia is associated with treatment failure due to receipt of inappropriate empiric antibiotic therapy and severity of illness.