Comparison of immunogenicity of adjuvanted and high dose influenza vaccination in long-term care facility residents.

Background: The CDC recommends the more immunogenic adjuvanted and high-dose flu vaccines over standard-dose, non-adjuvanted vaccines for individuals above 65 years old. The current study compares adjuvanted trivalent inactivated flu vaccine (aTIV, FLUAD) versus high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met non-inferiority standards for older long-term care facility (LTCF) residents. Methods: We collected blood from long-term care facility residents participating in a randomized 1:1 active control trial comparing MF59C.1 adjuvanted trivalent inactivated flu vaccine, aTIV versus HD-IIV3 over the course of two flu seasons, 2018-2019 and 2019-2020 (Trial, NCT03694808 ). We assessed humoral immunity at set time points via hemagglutinin inhibition assays (HAI) and anti-neuraminidase (enzyme-linked lectin assays (ELLA)). The recombinant influenza vaccine (RIV, Flublok) was assessed similarly in year two for a small number of participants who were carried over from year 1 (n=32). Results: We enrolled 387 volunteers and administered either aTIV (n=194), HD-IIV3 (n=193) over the course of the 2018-2019 and 2019-2020 flu seasons. Among those enrolled and randomized in year one, a subset were administered RIV and studied in year two (n = 32). At 28 days post-vaccination, aTIV exhibited non-inferiority to HD-IIV3 for HAI for both H1N1 and H3N2 strains (GMT ratios (95% CI) for HD-IIV3/aTIV of 1.03(0.76, 1.4) and 1.04(0.73, 1.48), respectively; both 95% CI upper bounds < 1.5 to meet non-inferiority criteria) but not for Influenza B (GMT ratio (95% CI) = 1.21 (0.91, 1.61)). Non-inferiority criteria for HAI seroconversion were not met for any of the three strains. Applying the same non-inferiority criteria to neuraminidase inhibition (NI), both day 28 titer and seroconversion in aTIV were non-inferior to HD-IIV3 for H1N1 and H3N2 strains. Conclusions: Both aTIV and HD-IIV3 elicited similar immune responses with robust antibody responses. For the primary outcome, aTIV is non-inferior to HD-IIV3 for HAI titer of H1N1 and H3N2 but failed to meet non-inferiority criteria for Influenza B and seroconversion for all assessed strains. For the secondary outcome, aTIV was non-inferior to HD-IIV3 for both titer and seroconversion of anti-neuraminidase for both H1N1 and H3N2.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs) but emerging variants and waning immunity challenge vaccine effectiveness. This study assesses the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Participants were subset of a longitudinal study of consented NHRs and Healthcare workers (HCWs) who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine post-FDA approval in Fall 2023. NHRs were categorized by whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). After XBB.1.5 vaccination, a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers was observed:17.3 (95% confidence interval [CI] 9.3, 32.4) and NHRs with interval infection and 11.3 (95% CI 5, 25.4) in those without and 13.6 (95% CI 8.4,22) in HCWs. For JN.1-specific titers, GMFRs were 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) in NHRs with and without interval infection, and 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher titers across all analyzed strains analyzed. The XBB.1.5 vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs with more pronounced in those previously infected with SARS-CoV-2 since bivalent vaccination.

The use of dual ß-lactams to restore susceptibility of Mycobacterium avium complex.

Background: The Mycobacterium avium complex (MAC) are non-tuberculous mycobacteria responsible for chronic and debilitating conditions. Guideline-recommended therapy for MAC is a combination of clarithromycin/azithromycin, ethambutol and a rifamycin. However, culture conversion rates with this regimen are 67%. Alternative treatment options are needed. Recent findings of ß-lactam combinations in the treatment of other mycobacterial diseases have been promising. The proposed mechanism is an additive inhibition of multiple enzymes in the peptidoglycan synthesis pathway by the ß-lactam combinations. Given the similarity in cell wall structures of MAC and M. abscessus, we hypothesize that using dual ß-lactams will result in interruption of peptidoglycan synthesis in MAC and reduction of MIC. In this study, we sought to determine the MIC of meropenem in combination with ceftaroline, cefdinir and cefuroxime in MAC. Methods: A total of 31 clinical MAC isolates were used for susceptibility testing using broth microdilution method. MICs were tested for meropenem, ceftaroline, cefdinir and cefuroxime, alone, as well as combinations of meropenem plus ceftaroline, cefdinir, or cefuroxime. Results: In vitro MAC susceptibility to meropenem was significantly enhanced with the addition of ceftaroline, cefdinir, and cefuroxime. This effect was most significant with addition of ceftaroline and cefdinir, with a change of meropenem MIC50/MIC90 from 16/32 to 0.125/0.5 and 0.125/4 mg/L, respectively (P value ≤0.0001, Wilcoxon signed-rank test). Conclusions: This study demonstrates that the susceptibility of MAC to meropenem is restored with the addition of ceftaroline and cefdinir. These findings underscore the potential effectiveness of combining ß-lactams as an alternative therapeutic strategy for MAC infections.

Effect of Ceftaroline, Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam on Establishment of Colonization by Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice.

Background: The potential for promotion of intestinal colonization with healthcare-associated pathogens by new antibiotics used to treat infections due to multidrug-resistant Gram-negative bacilli is unclear. Methods: Mice treated for 3 days with daily subcutaneous phosphate-buffered saline (control), ceftazidime/avibactam, ceftolozane/tazobactam, ceftaroline, and meropenem/vaborbactam were challenged with 10,000 colony-forming units (CFU) of vancomycin-resistant Enterococcus (VRE) resistant to each of the antibioics or carbapenemase-producing Klebsiella pneumoniae 1 day after the final treatment dose. The concentrations of VRE or K. pneumoniae in stool were measured on days 1, 3, 6, and 15 after challenge. Results: Control mice had transient low levels of VRE or K. pneumoniae (<3 log10 CFU/g) detected in stool with negative cultures on days 6 and 15 after challenge. In comparison to control mice, each of the antibiotics promoted establishment of high-density colonization with VRE (mean concentration, >8 log10 CFU/g of stool on day 1 after challenge) that persisted at >4 log10 CFU/g of stool through day 15 (P<0.01). In comparison to control mice, meropenem/vaborbactam and ceftaroline promoted high-density colonization with K. pneumoniae (peak concentration, >8 log10 CFU/g of stool) (P<0.01), ceftolozane/tazobactam promoted colonization to a lesser degree (peak concentration, >5 log10 CFU/g of stool), and ceftazidime/avibactam did not promote colonization (P>0.05). Conclusions: Our results suggest that several beta-lactam antibiotics recently developed for treatment of infections with resistant Gram-negative bacilli have the potential to promote colonization by healthcare-associated pathogens. Additional studies are needed to examine the impact of these agents in patients.

Incubation period of Clostridioides difficile infection in hospitalized patients and long-term care facility residents: a prospective cohort study.

Background: The incubation period for Clostridioides difficile infection (CDI) is generally considered to be less than 1 week, but some recent studies suggest that prolonged carriage prior to disease onset may be common. Objective: To estimate the incubation period for patients developing CDI after initial negative cultures. Methods: In 3 tertiary care medical centers, we conducted a cohort study to identify hospitalized patients and long-term care facility residents with negative initial cultures for C. difficile followed by a diagnosis of CDI with or without prior detection of carriage. Cases were classified as healthcare facility-onset, community-onset, healthcare facility-associated, or community-associated and were further classified as probable, possible, or unlikely CDI. A parametric accelerated failure time model was used to estimate the distribution of the incubation period. Results: Of 4,179 patients with negative enrollment cultures and no prior CDI diagnosis within 56 days, 107 (2.6%) were diagnosed as having CDI, including 19 (17.8%) with and 88 (82.2%) without prior detection of carriage. When the data were censored to only include participants with negative cultures collected within 14 days, the estimated median incubation period was 6 days with 25% and 75% of estimated incubation periods occurring within 3 and 12 days, respectively. The observed estimated incubation period did not differ significantly for patients classified as probable, possible, or unlikely CDI. Conclusion: Our findings are consistent with the previous studies that suggested the incubation period for CDI is typically less than 1 week and is less than 2 weeks in most cases.

Acutely blocking excessive mitochondrial fission prevents chronic neurodegeneration after traumatic brain injury.

Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI. Pharmacologically preventing Fis1 from binding its mitochondrial partner, dynamin-related protein 1 (Drp1), for 2 weeks after TBI normalizes the balance of mitochondrial fission/fusion and prevents chronically impaired mitochondrial bioenergetics, oxidative damage, microglial activation and lipid droplet formation, blood-brain barrier deterioration, neurodegeneration, and cognitive impairment. Delaying treatment until 8 months after TBI offers no protection. Thus, time-sensitive inhibition of acutely elevated mitochondrial fission may represent a strategy to protect human TBI patients from chronic neurodegeneration.

A coronavirus disease 2019 outbreak in a residential living facility with suboptimal ventilation in resident rooms.

We report a large outbreak of severe acute respiratory syndrome coronavirus 2 in a residential living facility. Measurements of carbon dioxide levels, aerosol particle clearance, and airflow were used to identify and remediate areas with suboptimal ventilation. A simple intervention involving continuous operation of bathroom fans was effective in significantly improving ventilation in resident rooms.

Nonendoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma in At-Risk Veterans.

INTRODUCTION: Although rates of esophageal adenocarcinoma (EAC) in the United States continue to rise, many patients at risk of disease are not screened. EsoCheck (EC), a nonendoscopic esophageal balloon sampling device coupled with EsoGuard (EG), a DNA-based screening assay, is an US Food and Drug Administration-approved minimally invasive alternative to the traditional screening method of upper endoscopy. The objective of this study was to prospectively determine the diagnostic accuracy, tolerance, and acceptability of the EC/EG test in a screening population. METHODS: We recruited veterans who met the American College of Gastroenterology Guideline criteria for endoscopic Barrett's esophagus (BE) and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center. All study participants completed unsedated EC-guided distal esophageal sampling followed by a sedated esophagogastroduodenoscopy (EGD). Diagnostic yield of the EG assay and EGD was recorded and used in calculation of sensitivity and specificity of EC/EG in prospective screening. The abbreviated Spielberger State-Trait Anxiety Inventory questionnaire was administered before and after completion of EC. Overall tolerance of EC sampling was evaluated on a 10-point Likert scale. RESULTS: Esophageal cancer screening was accepted by 130 of 782 eligible veterans (16.6%), and we analyzed results of those who completed both screening tests (N = 124). Prevalence of BE/EAC among studied veterans was 12.9% (16/124), based on EGD. Sensitivity and specificity of EC/EG for EGD-detected BE/EAC were 92.9% (95% confidence interval [CI] 66.1-99.8) and 72.2% (95% CI 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI 18.6-49.1) and 98.6% (95% CI 92.4-100), respectively. Baseline Spielberger State-Trait Anxiety Inventory-6 scores were reflective of notable levels of anxiety among veterans in the periprocedural setting. The mean postprocedure acceptability score for the EC test was 7.23 (SD 2.45). DISCUSSION: Our data suggest excellent sensitivity and negative predictive value of EC/EG in a screening population of veterans, making this modality a powerful screening tool for BE and EAC.

Impact of a Switch From Ciprofloxacin to Ceftriaxone Prophylaxis on Infectious Complications After Transrectal Ultrasound-Guided Biopsy of the Prostate.

In a 12-year single-center quasi-experimental study, a switch from ciprofloxacin to ceftriaxone prophylaxis for transrectal ultrasound-guided prostate biopsy procedures was associated with a significant reduction in 30-day postprocedure urinary tract infection, urinary tract infection-related hospitalizations, antibiotic prescriptions, and isolation of fluoroquinolone-resistant organisms from urine or blood cultures.

Identifying and Remediating Super-splasher Sinks to Reduce Dispersal of Pathogens From Sink Drains.

Testing for dispersal of fluorescent gel from sink drains was sensitive for detection of sinks that dispersed gram-negative bacilli outside the bowl. Reducing the flow rate of sinks with rapid water inflow and/or elimination of obstruction leading to slow outflow was effective in preventing dispersal of fluorescence and gram-negative bacilli.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination.

BACKGROUND: Bivalent SARS-CoV-2 vaccines were developed to counter increasing susceptibility to emerging SARS-CoV-2 variants. We evaluated the durability of immunity and protection following first bivalent vaccination among nursing home residents. METHODS: We evaluated anti-spike and neutralization titers from blood in 653 community nursing home residents before and after each monovalent booster, and a bivalent vaccine. Concurrent clinical outcomes were evaluated using electronic health record data from a separate cohort of 3783 residents of Veterans Affairs (VA) nursing homes who had received at least the primary series monovalent vaccination. Using target trial emulation, we compared VA residents who did and did not receive the bivalent vaccine to measure vaccine effectiveness against infection, hospitalization, and death. FINDINGS: In the community cohort, Omicron BA.5 neutralization activity rose after each monovalent and bivalent booster vaccination regardless of prior infection history. Titers declined over time but six months post-bivalent vaccination, BA.5 neutralization persisted at detectable levels in 75% of infection-naive and 98% of prior-infected individuals. In the VA nursing home cohort, bivalent vaccine added effectiveness to monovalent booster vaccination by 18.5% for infection (95% confidence interval (CI) -5.6, 34.0%), and 29.2% for hospitalization or death (95% CI -14.2, 56.2%) over five months. INTERPRETATION: The level of protection declined after bivalent vaccination over a 6 month period and may open a window of added vulnerability before the next updated vaccine becomes available, suggesting a subset of nursing home residents may benefit from an additional vaccination booster. FUNDING: CDC, NIH, VHA.

Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers.

Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8 months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.

Longitudinal Analysis of Nursing Home Residents' T-Cell Responses After SARS-CoV-2 mRNA Vaccinations Shows Influence of Biological Sex and Infection History.

BACKGROUND: Vaccines and vaccine boosting have blunted excess morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older nursing home residents (NHR). However, the impact of repeated vaccination on the T-cell response based on biological sex and prior infection of NHR remain understudied. METHODS: We examined T-cell responses to SARS-CoV-2 mRNA vaccines in a cohort of NHR and healthcare workers (HCW) over 2 years. We used interferon-γ ELIspot and flow cytometry to assess T-cell response before, 2 weeks, and 6 months after the initial series and each of 2 booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T-cell effector function. RESULTS: Prior SARS-CoV-2 infection and female sex contributed to higher T-cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T-cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations. CONCLUSIONS: These results suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T-cell response to mRNA vaccination.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

Background: SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs). However, emerging variants coupled with waning immunity, immunosenescence, and variability of vaccine efficacy undermine vaccine effectiveness. We therefore need to update our understanding of the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Methods: The current study focuses on a subset of participants from a longitudinal study of consented NHRs and HCWs who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine after FDA approval in Fall 2023. NHRs were classified based on whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. Results: The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). Following XBB.1.5 monovalent vaccination, there was a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers of 17.3 (95% confidence interval [CI] 9.3, 32.4) and 11.3 (95% CI 5, 25.4) in NHRs with and without interval infection, respectively. The GMFR in HCWs was 13.6 (95% CI 8.4,22). Similarly, we noted a robust GMFR in JN.1-specific neutralizing antibody titers of 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) among NHRs with and without interval infection, and a GMFR of 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher neutralizing antibody titers across all analyzed strains following XBB.1.5 monovalent vaccination, compared to NHRs without interval infection. Conclusion: The XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs. This response was more pronounced in individuals known to be infected with SARS-CoV-2 since bivalent vaccination. Impact Statement: All authors certify that this work entitled " Broad immunogenicity to prior strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents " is novel. It shows that the XBB.1.5 monovalent vaccine significantly elevates Omicron-specific neutralizing antibody titers in both nursing home residents and healthcare workers to XBB and BA.28.6/JN.1 strains. This work is important since JN.1 increased from less than 0.1% to 94% of COVID-19 cases from October 2023 to February 2024 in the US. This information is timely given the CDC's latest recommendation that adults age 65 and older receive a Spring 2024 XBB booster. Since the XBB.1.5 monovalent vaccine produces compelling immunogenicity to the most prevalent circulating JN.1 strain in nursing home residents, our findings add important support and rationale to encourage vaccine uptake. Key Points: Emerging SARS-CoV-2 variants together with waning immunity, immunosenescence, and variable vaccine efficacy reduce SARS-CoV-2 vaccine effectiveness in nursing home residents.XBB.1.5 monovalent vaccination elicited robust response in both XBB.1.5 and JN.1 neutralizing antibodies in nursing home residents and healthcare workers, although the absolute titers to JN.1 were less than titers to XBB.1.5Why does this paper matter? Among nursing home residents, the XBB.1.5 monovalent SARS-CoV-2 vaccine produces compelling immunogenicity to the JN.1 strain, which represents 94% of all COVID-19 cases in the U.S. as of February 2024.

14-Year Epidemiologic study of Pseudomonas aeruginosa bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009-2022.

Background: Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures. Objectives: We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population. Methods: We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort. Results: We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality. Conclusions: PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.

Change in Provider Specialty Was Associated With Less Fluoroquinolone Use at a Veterans Affairs Long-Term Care Setting.

OBJECTIVE: In July 2021, as part of a planned multiyear broad and long-term organizational realignment, the general medicine service assumed continuous care of residents at a Community Living Center (CLC), which are nursing homes within the Veterans Affairs (VA) health care system. We hypothesized that practitioners accustomed to caring for patients in acute care would be more likely to prescribe antibiotics to long-term care residents. DESIGN: Retrospective cohort study. SETTINGS AND PARTICIPANTS: Residents of a 105-bed CLC associated with a large VA medical center. METHODS: Our cohort included CLC residents between July 1, 2020, and June 30, 2022. We used administrative data to assess resident demographics and medical conditions in the 1 year before and after the change of practitioners. We also compared antibiotics agents prescribed and the following antibiotic use metrics in the year before and after the change: days of therapy (DOT) per 1000 bed days of care (BDOC), antibiotic starts/1000 BDOC, and mean length of therapy in days. RESULTS: Resident characteristics and overall antibiotic use metrics were similar before and after the change in staffing. The specific agents prescribed differed, with a decrease in fluoroquinolones (14.3 to 5.8 DOT/1000 BDOC; P < .01) and an increase doxycycline (7.4 vs 19.1 DOT/1000 BDOC; P < .01) after the staff change. Rates of Clostridioides difficile infection also decreased, from 6.23 to 3.41 cases/10,000 BDOC after the change in staffing. CONCLUSIONS AND IMPLICATIONS: The comparable antibiotic use metrics before and after the general medical service assumed care of the CLC residents may be explained by constancy in resident population and other facility-related factors. Differences in the types of agents used suggests that antibiotic stewardship efforts can be tailored not only to the setting and patient population but also to the practitioners' discipline.

Pulsed dosing and extended daily dosing of oral vancomycin do not facilitate clearance of Clostridioides difficile colonization in mice.

Vancomycin taper and pulse regimens are commonly used to treat recurrent Clostridioides difficile infections, but the mechanism by which these regimens might reduce recurrences is unclear. Here, we used a mouse model to test the hypothesis that pulse dosing of vancomycin after a 10-day treatment course enhances clearance of C. difficile from the intestinal tract. Mice with C. difficile colonization received 10 days of once-daily oral vancomycin followed by 20 days of treatment with saline (controls), daily vancomycin, or pulse dosing of vancomycin every 2 or 3 days. Stool samples were collected to measure the concentration of C. difficile during and after treatment, vancomycin concentrations, and growth of vegetative C. difficile during every 3 days dosing. Pulse dosing of vancomycin was not effective in maintaining suppression of C. difficile (P > 0.05 in comparison to saline controls); growth of vegetative C. difficile occurred between pulse doses when vancomycin decreased to undetectable levels. Daily dosing of vancomycin suppressed C. difficile during treatment, but recurrent colonization occurred after treatment in more than 75% of mice, and by post-treatment day 14, there was no significant difference among the control, pulse dosing, and daily dosing groups (P > 0.05). These findings demonstrate that pulse dosing of vancomycin every 2 or 3 days does not facilitate the clearance of C. difficile spores in mice. Studies are needed to examine the impact of vancomycin taper and pulsed regimens in patients.

Syndromic Antibiograms and Nursing Home Clinicians' Antibiotic Choices for Urinary Tract Infections.

Importance: Empirical antibiotic prescribing in nursing homes (NHs) is often suboptimal. The potential for antibiograms to improve empirical antibiotic decision-making in NHs remains poorly understood. Objective: To determine whether providing NH clinicians with a urinary antibiogram improves empirical antibiotic treatment of urinary tract infections (UTIs). Design, Setting, and Participants: This was a survey study using clinical vignettes. Participants were recruited via convenience sampling of professional organization listservs of NH clinicians practicing in the US from December 2021 through April 2022. Data were analyzed from July 2022 to June 2023. Interventions: Respondents were randomized to complete vignettes using a traditional antibiogram (TA), a weighted-incidence syndromic combination antibiogram (WISCA), or no tool. Participants randomized to antibiogram groups were asked to use the antibiogram to empirically prescribe an antibiotic. Participants randomized to the no tool group functioned as controls. Main Outcomes and Measures: Empirical antibiotic selections were characterized as microbiologically (1) active and (2) optimal according to route of administration and spectrum of activity. Results: Of 317 responses, 298 (95%) were included in the analysis. Duplicate responses (15 participants), location outside the US (2 participants), and uninterpretable responses (2 participants) were excluded. Most respondents were physicians (217 respondents [73%]) and had over 10 years of NH practice experience (155 respondents [52%]). A mixed-effects logistic model found that use of the TA (odds ratio [OR], 1.41; 95% CI, 1.19-1.68; P < .001) and WISCA (OR, 1.54; 95% CI, 1.30-1.84; P < .001) were statistically superior to no tool when choosing an active empirical antibiotic. A similarly constructed model found that use of the TA (OR, 1.94; 95% CI, 1.42-2.66; P < .001) and WISCA (OR, 1.7; 95% CI, 1.24-2.33; P = .003) were statistically superior to no tool when selecting an optimal empirical antibiotic. Although there were differences between tools within specific vignettes, when compared across all vignettes, the TA and WISCA performed similarly for active (OR, 1.09; 95% CI, 0.92-1.30; P = .59) and optimal (OR, 0.87; 95% CI, 0.64-1.20; P = .69) antibiotics. Conclusions and Relevance: Providing NH clinicians with a urinary antibiogram was associated with selection of active and optimal antibiotics when empirically treating UTIs under simulated conditions. Although the antibiogram format was not associated with decision-making in aggregate, context-specific effects may have been present, supporting further study of syndromic antibiograms in clinical practice.

Association of COVID-19 coinfection with increased mortality among patients with Pseudomonas aeruginosa bloodstream infection in the Veterans Health Administration system.

Objective: Pseudomonas aeruginosa bloodstream infection (PA-BSI) and COVID-19 are independently associated with high mortality. We sought to demonstrate the impact of COVID-19 coinfection on patients with PA-BSI. Design: Retrospective cohort study. Setting: Veterans Health Administration. Patients: Hospitalized patients with PA-BSI in pre-COVID-19 (January 2009 to December 2019) and COVID-19 (January 2020 to June 2022) periods. Patients in the COVID-19 period were further stratified by the presence or absence of concomitant COVID-19 infection. Methods: We characterized trends in resistance, treatment, and mortality over the study period. Multivariable logistic regression and modified Poisson analyses were used to determine the association between COVID-19 and mortality among patients with PA-BSI. Additional predictors included demographics, comorbidities, disease severity, antimicrobial susceptibility, and treatment. Results: A total of 6,714 patients with PA-BSI were identified. Throughout the study period, PA resistance rates decreased. Mortality decreased during the pre-COVID-19 period and increased during the COVID-19 period. Mortality was not significantly different between pre-COVID-19 (24.5%, 95% confidence interval [CI] 23.3-28.6) and COVID-19 period/COVID-negative (26.0%, 95% CI 23.5-28.6) patients, but it was significantly higher in COVID-19 period/COVID-positive patients (47.2%, 35.3-59.3). In the modified Poisson analysis, COVID-19 coinfection was associated with higher mortality (relative risk 1.44, 95% CI 1.01-2.06). Higher Charlson Comorbidity Index, higher modified Acute Physiology and Chronic Health Evaluation score, and no targeted PA-BSI treatment within 48 h were also predictors of higher mortality. Conclusions: Higher mortality was observed in patients with COVID-19 coinfection among patients with PA-BSI. Future studies should explore this relationship in other settings and investigate potential SARS-CoV-2 and PA synergy.

Carbon Dioxide Monitoring Demonstrates Variations in the Quality of Ventilation on Public Transportation Buses and University Student Shuttle Vans and Identifies Effective Interventions.

Background: There is a risk for transmission of severe acute respiratory syndrome 2 (SARS-CoV-2) and other respiratory viruses in motor vehicles, particularly if ventilation is inadequate. Methods: We used carbon dioxide monitoring to examine the quality of ventilation in several public transportation buses and in university student shuttle vans in the Cleveland metro area during peak and non-peak travel times. Carbon dioxide levels above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation for the number of people present. In the shuttle vans, we evaluated the impact of an intervention to improve ventilation. Results: In large articulated buses with 2 ventilation systems, carbon dioxide concentrations never exceeded 800 ppm, whereas in standard buses with 1 ventilation system concentrations rose above 800 ppm during peak travel times and on some trips during non-peak travel times. In shuttle vans, the ventilation system was not turned on during routine operation, and carbon dioxide levels rose above 800 ppm on all trips during peak and non-peak travel times. In the shuttle vans, an intervention involving operation of the existing ventilation system resulted in a significant reduction in carbon dioxide levels (mean concentration, 1,042 no intervention versus 785 with intervention; P < 0.001). Conclusions: Our findings demonstrate substantial variability in the quality of ventilation in public transportation buses and university shuttle vans. There is a need for efforts to assess and optimize ventilation in motor vehicles used for public transportation to reduce the risk for aerosol-mediated transmission of respiratory viruses. Carbon dioxide monitoring may provide a useful tool to assess and improve ventilation.