Kelly M. Hatfield

Background: Carbapenem-resistant Enterobacterales (CRE) infections are an urgent public health threat in the United States. Despite infection prevention and control measures, hospital CRE rates have not declined in the past decade. Novel drug-based pathogen reduction approaches may decrease CRE incidence, and mathematical models can assess implementation strategies. Methods: We used agent-based modeling to evaluate a hypothetical drug with pathogen reduction properties for reducing CRE transmission in an example acute-care hospital. We compared a strategy that treated only clinically detected CRE-colonized patients—using three drug effectiveness (DE) levels (25%, 50%, 75%)—with strategies that treated patients identified through surveillance screening in addition to clinical cultures. Surveillance screenings (intensive care unit (ICU) or all-admission screenings) were implemented at 50% and 100% patient participation (PP). Model parameters were informed by administrative healthcare data and published literature. Results: The baseline mean CRE colonization incidence was 27.4 per 10,000 patient-days (interquartile range [IQR]: 11.7–39.9). Compared to baseline, at DE = 25% the reduction in mean colonization incidence was 1.2% (−0.8%–3.2%) for the treatment-only strategy. At DE = 50%, treatment + ICU screening reduced incidence by 9.0% (7.1%–11.0%) at PP = 50% and 13.2% (11.4%–15.1%) at PP = 100%. The reduction reached 38.5% (37.1%–40.0%) for treatment + all-admission screening at DE = 75% and PP = 100%. Conclusions: This study underscores the potential of novel drugs as pathogen reduction measures to reduce CRE incidence in US hospitals if deployed strategically. Findings highlight the value of developing pathogen reduction strategies for colonized patients to prevent CRE transmission and infections.

Background: Reports of ceftriaxone serious adverse events (SAEs), including deaths, from multiple jurisdictions during December 2024–January 2025 prompted a nationwide investigation to evaluate product safety, characterize SAEs, and assess for changes in baseline adverse event occurrence via national databases. Methods: In February 2025, the Centers for Disease Control and Prevention issued a national call for cases, defined as SAEs involving death or cardiopulmonary resuscitation within 6 hours of ceftriaxone injection, not otherwise explained and occurring in non–intensive care unit settings during September 2024–August 2025. Epidemiologic and clinical data were collected by health departments and reported to the Centers for Disease Control and Prevention. Laboratory testing of ceftriaxone and lidocaine diluent was performed at Food and Drug Administration. Temporal trends in adverse events (2016–2019 vs 2020–2024) were assessed via Medicare claims and National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance System analyses. Results: Among 31 cases identified from 27 healthcare facilities (65% outpatient) across 18 states during September 2024–August 2025, all involving death or cardiopulmonary resuscitation, 12 (39%) persons died, 23 (74%) had anaphylaxis-type presentations (65% without skin/mucosal involvement), 21 (68%) had previous ceftriaxone exposure, and 24 (77%) had cardiac comorbidities. Median age was 67 years (interquartile range: 60–81). Antihypertensive use was common (n = 19/28, 68%). Product testing revealed no evidence of tampering, adulteration, endotoxin, or purity/potency issues. National adverse event trends were stable across 2016–2019 and 2020–2024. Conclusions: SAEs, including deaths, can occur after ceftriaxone receipt. Product testing and trend analyses did not identify evidence of a new safety issue. This investigation highlights the need for ongoing vigilance for ceftriaxone SAEs and reporting to Food and Drug Administration MedWatch.

Objective: Inappropriate urine cultures (UCs) are common and lead to inappropriate antimicrobial use. Urinalyses (UAs) have been increasingly incorporated into diagnostic stewardship interventions, but the impact of these interventions nationally has not been assessed. We describe UA and UC utilization practices using a nationwide dataset of patients admitted to acute care hospitals. Methods: Design, Setting and Participants: We performed a retrospective cohort study of index UCs and their associated UAs performed for adult patients (age ≥ 18 years) admitted in U.S. acute care hospitals, participating in the PINC AI™ Healthcare Database (PHD) from January 1, 2017, through December 31, 2020. A positive UA was defined as >10 leukocytes per high power field, positive leukocyte esterase, or positive nitrite. Results: The overall rate of UCs in this study was 124.7 per 1000 discharges and annual UC rates decreased from 2017 (129.2) to 2020 (120.0). The proportion of UCs that had a positive UA increased from 60.5% in 2017 to 68.1% in 2020; UCs without a UA decreased from 19.3% to 10.5%, and UCs with a negative UA did not significantly change (20.2% to 21.5%). A multivariate multinomial logistic regression model identified male sex, age <65, and a diagnosis of cancer to be predictors of having a UC with a negative UA or no UA. Conclusions: UC utilization decreased over the study period. The proportion of UCs with a positive UA increased. This may suggest a positive impact of diagnostic stewardship practices at the national level although further progress is needed.

Background: A shortage of BD BACTECTM blood culture bottles occurred in 2024. We describe the clinical impact of that shortage. Methods: We conducted a National Healthcare Safety Network (NHSN) questionnaire and retrospective cohort study using inpatient hospitalization data from the Premier Healthcare Database. In the retrospective cohort, facilities were categorized into BD BACTEC™ (n = 11) and non-BD BACTEC™ (n = 28) hospitals; non-shortage and shortage periods were considered from May 2023 to June 2024 and July to November 2024. We used a generalized linear model for the rate of blood cultures with an offset for patient days and adjusted for facility characteristics and other factors. Similarly, we modeled the rate of unique adult hospitalizations with a pathogen-positive blood culture per hospitalization. Results: Of 3196 facilities responding, 1456 (45.6%) indicated a use of BD BACTECTM to the NHSN questionnaire; of those, 1103 (75.8%) reported a shortage impact. In the retrospective cohort study, there was a 27.4% decrease in cultures at BD BACTEC™ hospitals during the shortage period (95% CI: −31.2% to −23.4%). BD BACTEC™ facilities had a median change in culturing rate of −33.3% (IQR: −47.0% to 2.0%) between the non-shortage and shortage periods. There was a 15.3% decrease in the rate of patients positive for a pathogen at affected facilities during the shortage (95% CI: −22.4% to −7.5%). Conclusions: BD BACTEC™ facilities experienced substantial and non-uniform decreases in blood culture rates. Impacted facilities had a decrease in the rate of observed bloodstream infections, which has implications for patient safety and surveillance.

Background: Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. However, they lack specimen collection and diagnosis dates to assign location of onset. Algorithms to classify CDI onset location using claims data have been published, but the degree of misclassification is unknown. Methods: We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016–2021 to Medicare beneficiaries with fee-for-service Part A/B coverage. We calculated sensitivity of ICD-10-CM codes in claims within ±28 days of EIP specimen collection. CDI was categorized as hospital, long-term care facility, or community-onset using three different Medicare claims-based algorithms based on claim type, ICD-10-CM code position, duration of hospitalization, and ICD-10-CM diagnosis code presence-on-admission indicators. We assessed concordance of EIP case classifications, based on chart review and specimen collection date, with claims case classifications using Cohen’s kappa statistic. Results: Of 12,671 CDI cases eligible for linkage, 9,032 (71%) were linked to a single, unique Medicare beneficiary. Compared to EIP, sensitivity of CDI ICD-10-CM codes was 81%; codes were more likely to be present for hospitalized patients (93.0%) than those who were not (56.2%). Concordance between EIP and Medicare claims algorithms ranged from 68% to 75%, depending on the algorithm used (κ = 0.56–0.66). Conclusion: ICD-10-CM codes in Medicare claims data had high sensitivity compared to laboratory-confirmed CDI reported to EIP. Claims-based epidemiologic classification algorithms had moderate concordance with EIP classification of onset location. Misclassification of CDI onset location using Medicare algorithms may bias findings of claims-based CDI studies.

The COVID-19 pandemic has caused substantial disruption throughout the world since early 2020. Early in the pandemic, US hospitals adopted aggressive infection control measures and enhanced the use of personal protective equipment (eg, universal masking of staff and patients, testing of asymptomatic patients, and use of N95 respirators and eye protection) to prevent transmission of SARS-CoV-2, the virus that causes COVID-19.¹

Background: The 2014 US National Strategy for Combating Antibiotic-Resistant Bacteria aimed to reduce inappropriate inpatient antibiotic use by 20% for monitored conditions, such as community-acquired pneumonia (CAP), by 2020. Clinical guidelines recommend treating uncomplicated CAP with a minimum of 5 days of antibiotic therapy. Total length of therapy (LOT) >7 days or >3 days after clinical improvement is rarely necessary. In a previous study estimating LOT in uncomplicated CAP patients, 71% of patients ≥65 years exceeded recommended duration of antibiotics in 2012–2013 (Yi et al, 2018). We evaluated annual trends in LOT in adults ≥65 years hospitalized with uncomplicated CAP from 2013 to 2020. Methods: We conducted a retrospective cohort study among patients in the CMS database with a primary diagnosis of bacterial or unspecified pneumonia using International Classification of Diseases 9th and 10th Revision codes, length of stay (LOS) of 2–10 days, discharged home with self-care, and not rehospitalized in the 3 days following discharge. Discharge home was used as a surrogate for clinical improvement. Because inpatient LOT is not available in CMS data, we used linear regression to model inpatient LOT as a function of LOS using data on CAP patients ≥65 years from the PINC AI healthcare database. Postdischarge LOT was based on prescriptions filled following discharge. Total LOT was calculated by summing estimated inpatient LOT and actual postdischarge LOT (Fig. 1). Total LOT >7 days and postdischarge LOT >3 days were considered indicators of likely excessive LOT. We reported trends in the proportion of patients with likely excessive LOT during the study period. Results: From 2013 through 2020, there were 400,928 uncomplicated CAP hospitalizations among patients aged ≥65 years. Patients were more likely to be female (55%), and they had a median age of 76 years and a median LOS of 3 days. The median total LOT decreased from 9.5 days in 2013 to 7.7 days in 2020. The proportion of patients with total LOT >7 days decreased from 68% in 2013 to 50% in 2020 (% change, −27%); the proportion with postdischarge LOT >3 days decreased from 73% in 2013 to 62% in 2020 (% change, −16%) (Fig. 2). Conclusions: Likely excessive total LOT for adults ≥65 years hospitalized with uncomplicated CAP decreased by 27% in 2020, a considerable improvement from 2013. However, the high proportion of patients with likely excessive postdischarge LOT in 2020 (62%) demonstrates the need for antibiotic stewardship to optimize prescribing at hospital discharge. Disclosures: None

Background: Residents of nursing homes experience disproportionate morbidity and mortality related to coronavirus disease 2019 (COVID-19) and were prioritized for vaccine introduction. We evaluated COVID-19 vaccine effectiveness (VE) in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among nursing home residents. Methods: We used a retrospective cohort of 4315 nursing home residents during 14 December 2020–9 November 2021. A Cox proportional hazards model was used to estimate hazard ratios comparing residents with a completed vaccination series with unvaccinated among those with and without prior SARS-CoV-2 infection, by vaccine product, and by time period. Results: Overall adjusted VE was 58% (95% confidence interval [CI], 44% to 69%) among residents without a history of SARS-CoV-2 infection. During the pre-Delta period, the VE within 150 days of receipt of the second dose of Pfizer-BioNTech (67%; 95% CI, 40% to 82%) and Moderna (75%; 95% CI, 32% to 91%) was similar. During the Delta period, VE measured >150 days after the second dose was 33% (95% CI, −2% to 56%) for Pfizer-BioNTech and 77% (95% CI, 48% to 91%) for Moderna. Rates of infection were 78% lower (95% CI, 67% to 85%) among residents with prior SARS-CoV-2 infection and completed vaccination series compared with unvaccinated residents without a history of SARS-CoV-2 infection. Conclusions: COVID-19 vaccines were effective in preventing SARS-CoV-2 infections among nursing home residents, and history of prior SARS-CoV-2 infection provided additional protection. Maintaining high coverage of recommended doses of COVID-19 vaccines remains a critical tool for preventing infections in nursing homes.

Background. Understanding the viral load and potential infectivity of individuals in nursing homes (NH) with repeat positive SARS-CoV-2 tests ≥ 90 days after initial infection has important implications for safety related to transmission in this high-risk setting. Methods. We collected epidemiologic data by reviewing records of a convenience sample of NH residents and staff with respiratory specimens who had positive SARS-CoV-2 rRT-PCR test results from July 2020 through March 2021 and had a SARS-CoV-2 infection diagnosed ≥ 90 days prior. No fully vaccinated individuals were included. Each contributed one repeat positive specimen ≥ 90 days after initial, which was sent to CDC and retested using rRT-PCR. Specimens were assessed for replication-competent virus in cell culture if Cycle threshold (Ct) < 34 and sequenced if Ct < 30. Using Ct values as a proxy for viral RNA load, specimens were categorized as high (Ct < 30) or low (if Ct ≥ 30 or rRT-PCR negative at retesting). Continuous variables were compared using Wilcoxon signed-rank tests. Proportions were compared using Chi-squared or Fisher’s exact tests. Results. Of 64 unvaccinated individuals with specimens from 61 unique NHs, 14 (22%) were sent for culture and sequencing. Ten of 64 (16%) had a high viral RNA load, of which four (6%) were culture positive and none were known variants of interest or concern (Figure 1). Median days to repeat positive test result were 122 (Interquartile range (IQR): 103–229) and 201 (IQR: 139–254), respectively, for high versus low viral load specimens (p=0.13). More individuals with high viral loads (5/10, 50%) reported COVID-19 symptoms than with a low viral load (1/27, 4%, p=0.003). Most individuals (46/58, 79%) were tested following known or suspected exposures, with no significant differences between high and low viral load (p=0.18). In this study, nearly 1 in 6 NH residents and staff with repeat positive tests after 90 days demonstrated high viral RNA loads and viable virus, indicating possible infectivity. While individuals with high RNA viral load may be more likely to be symptomatic, distinguishing asymptomatic individuals who have high viral loads may be difficult with timing since initial infection, other test results, or exposure history alone. John A. Jernigan, MD, MS, Nothing to disclose.