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Background During August 2021–September 2021, a Connecticut college experienced a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant outbreak despite high (99%) vaccination coverage, indoor masking policies, and twice-weekly testing. The Connecticut Department of Public Health investigated characteristics associated with infection and phylogenetic relationships among cases. Methods A case was a SARS-CoV-2 infection diagnosed by a viral test during August 2021–September 2021 in a student. College staff provided enrollment and case information. An anonymous online student survey collected demographics, SARS-CoV-2 case and vaccination history, and activities preceding the outbreak. Multivariate logistic regression identified characteristics associated with infection. Phylogenetic analyses compared 115 student viral genome sequences with contemporaneous community genomes. Results Overall, 199 of 1788 students (11%) had laboratory-confirmed SARS-CoV-2 infection; most were fully vaccinated (194 of 199, 97%). Attack rates were highest among sophomores (72 of 414, 17%) and unvaccinated students (5 of 18, 28%). Attending in-person classes with an infectious student was not associated with infection (adjusted odds ratio [aOR], 1.0; 95% confidence interval [CI],.5–2.2). Compared with uninfected students, infected students were more likely to be sophomores (aOR, 3.3; 95% CI, 1.1–10.7), attend social gatherings before the outbreak (aOR, 2.8; 95% CI, 1.3–6.4), and complete a vaccine series ≥180 days prior (aOR, 5.5; 95% CI, 1.8–16.2). Phylogenetic analyses suggested a common viral source for most cases. Conclusions SARS-CoV-2 infection in this highly vaccinated college population was associated with unmasked off-campus social gatherings, not in-person classes. Students should stay up to date on vaccination to reduce infection. [ABSTRACT FROM AUTHOR]

Background While there are ongoing regulatory convergence efforts, differences remain in primary end points recommended for community-acquired bacterial pneumonia (CABP) trials. The US Food and Drug Administration (FDA) recommends assessing CABP symptom resolution at an early time point (3–5 days after randomization). Other regulatory agencies recommend assessing overall clinical response at a later time point (5–10 days after therapy ends). Methods We analyzed participant-level data from 6 recent CABP trials submitted to the FDA (n = 4645 participants) to evaluate concordance between early and late end-point outcomes. We used multivariate logistic regression to identify factors associated with discordance. Results Early and late end-point outcomes were concordant for 85.6% of participants. The proportions of early end-point responders that ultimately failed and early end-point nonresponders that ultimately succeeded were similar (6.0% vs 8.4%, respectively). Early end-point response was highly predictive of late end-point success (positive predictive value, 92.9%). Multivariate logistic regression identified early end-point responders/late end-point failures as less likely to be obese and more likely to be infected with Chlamydophila pneumoniae or Staphylococcus aureus , have received antibacterial drug therapy prior to randomization, and have severe chest pain at baseline. The most common investigator-provided reasons for failure among early end-point responders/late end-point failures were receipt of nonstudy antibacterial drug therapy and loss to follow-up. Conclusions Early and late end-point outcomes were highly concordant. These data may be useful in the continuing efforts to reach international regulatory convergence on CABP clinical trial design recommendations. [ABSTRACT FROM AUTHOR]

During July–August 2021, a coronavirus disease 2019 (COVID-19) outbreak involving 21 residents (all fully vaccinated) and 10 staff (9 fully vaccinated) occurred in a Connecticut nursing home. The outbreak was likely initiated by a fully vaccinated staff member and propagated by fully vaccinated persons. Prior COVID-19 was protective among vaccinated residents. [ABSTRACT FROM AUTHOR]

Background New drug development for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) is critical. Challenges remain in the conduct of HABP/VABP trials, especially in the contexts of enrollment, endpoints, nonstudy antibacterial drug therapy, and antimicrobial resistance. Methods Four Phase 3 noninferiority trials (n = 2433 participants) submitted to the Food and Drug Administration after 2015 were analyzed for enrollment statistics, participant characteristics associated with 28-day all-cause mortality (ACM), microbiology, and receipt of nonstudy antibacterial drugs. All trials primarily enrolled patients with gram-negative bacterial infections. Results The mean trial length was 2.7 years and the mean recruitment rate was 0.17 participants/site/month. ACM at 28 days was 17.1% and was higher among participants diagnosed with ventilated HABP (31.9%) or VABP (19.0%) than nonventilated HABP (9.9%). VABP participants tended to be younger, less likely to have chronic obstructive pulmonary disease, and more likely to have previously sustained an injury. Age, South American residence, diagnosis of ventilated HABP or VABP, and Acinetobacter baumannii infection were all associated with 28-day ACM in a multivariate logistic regression model. Infection by A. baumannii was most common in Eastern European and Asia/Pacific participants, and Eastern European isolates exhibited the highest levels of meropenem resistance. Concomitant nonstudy antibacterial drug therapy most commonly included beta-lactams and was initiated earliest in Western Europe. Conclusion This analysis of recent trials may assist in trial considerations for HABP/VABP development programs and promote needed antibacterial drug development for patients with serious infections. [ABSTRACT FROM AUTHOR]

Background As drug development has globalized, trials have increasingly enrolled participants from all parts of the world rather than just the United States and Western Europe. For antibacterial drug trials, understanding enrollment trends and regional differences is important for generalizability considerations. Methods We retrospectively analyzed 42 phase 3 trials submitted to the US Food and Drug Administration after 2001 for complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), community-acquired bacterial pneumonia (CABP), and acute bacterial skin and skin structure infection (ABSSSI) (n = 29 282 participants). Enrollment numbers, demographics, clinical characteristics, and microbiological data were compared to identify temporal and geographic trends. Results For cUTI, cIAI, and CABP trials, Eastern European enrollment greatly increased over the study period. For ABSSSI trials, North American enrollment increased. Demographic characteristics and regional microbiology among regions were broadly similar with several exceptions. For cIAI trials, Eastern European participants had the lowest proportion of participants with prior antibacterial drug therapy. For ABSSSI trials, North American participants more commonly reported intravenous drug use. Microbiological differences relative to North America included a greater proportion of Klebsiella pneumoniae among Asian cIAI isolates (17.8% vs 9.0%, P  = .0057), a higher proportion of cephalosporin resistance in South American Enterobacteriaceae cUTI isolates (26.8% vs 15.7%, P  = .044), and a lower proportion of Staphylococcus aureus in Eastern European ABSSSI isolates (43.7% vs 61.9%, P  < .0001). Conclusions Geographic trends in recruitment for recent antibacterial clinical trials differ by indication. Regional similarities in demographic characteristics and microbiology across regions lessen concerns regarding generalizability due to shifting enrollment trends. [ABSTRACT FROM AUTHOR]

We assessed the relationship between municipality COVID-19 case rates and SARS-CoV-2 concentrations in the primary sludge of corresponding wastewater treatment facilities. Over 1700 daily primary sludge samples were collected from six wastewater treatment facilities with catchments serving 18 cities and towns in the State of Connecticut, USA. Samples were analyzed for SARS-CoV-2 RNA concentrations during a 10 month time period that overlapped with October 2020 and winter/spring 2021 COVID-19 outbreaks in each municipality. We fit lagged regression models to estimate reported case rates in the six municipalities from SARS-CoV-2 RNA concentrations collected daily from corresponding wastewater treatment facilities. Results demonstrate the ability of SARS-CoV-2 RNA concentrations in primary sludge to estimate COVID-19 reported case rates across treatment facilities and wastewater catchments, with coverage probabilities ranging from 0.94 to 0.96. Lags of 0 to 1 days resulted in the greatest predictive power for the model. Leave-one-out cross validation suggests that the model can be broadly applied to wastewater catchments that range in more than one order of magnitude in population served. The close relationship between case rates and SARS-CoV-2 concentrations demonstrates the utility of using primary sludge samples for monitoring COVID-19 outbreak dynamics. Estimating case rates from wastewater data can be useful in locations with limited testing availability, testing disparities, or delays in individual COVID-19 testing programs. [ABSTRACT FROM AUTHOR]