New Jersey Department of Health

Congenital cytomegalovirus (cCMV) is the most common infectious cause of birth defects and non-genetic hearing loss in U.S. children. Variations in cCMV screening practices and the absence of national cCMV surveillance in the U.S. hinders assessment of disparities in disease burden, clinical care, and intervention. We describe clinical characteristics of neonates with cCMV identified through a novel surveillance program.Table 1.Clinical signs, neuroimaging, and treatment among neonates with congenital cytomegalovirus disease or confirmed infection status — Surveillance for Emerging Threats to Pregnant People and Infants Network 2014–2023 (N=387 neonates)1 Some neonates classified as having cCMV infection at birth may go on to develop signs and symptoms later (e.g., sensorineural hearing loss, cerebral palsy) which would move them to a cCMV disease classification. Follow up is ongoing, and these results are preliminary. Additionally, 60% of infection cases came from Minnesota where a universal screening program is in place.2Reported in the medical record or a reported head circumference <3 standard deviations below the mean for age and sex using INTEGROWTH-21st standards, ICD-10-CM code of Q02 or mention of microcephaly in the medical record.3Malformation of cortical development includes cortical dysplasia, lissencephaly, pachygyria, polymicrogyria, or schizencephaly.4Intraventricular hemorrhage and findings reported as directly related to intraventricular hemorrhage were not included.Figure 1.Council for State and Territorial Epidemiologist Standardized Case Definition for Congenital Cytomegalovirus (cCMV) Six states (Illinois, Iowa, Minnesota, New Jersey, New York state [excluding New York City], and Utah) ascertained neonates with cCMV through jurisdiction-specific screening practices (universal [n=1], hearing-targeted [n=3], high-risk [n=1], diagnostic codes [n=1], and clinical report [n=2]), including births from 2023 (5 states) or 2014 to 2023 (1 state). Case classification followed the 2023 Council of State and Territorial Epidemiologists surveillance case definition (Figure 1). Data were collected through vital statistics, laboratory reports, and birth hospitalization medical records. Among 387 neonates with completed medical record abstraction, 73% were classified as confirmed cCMV infection, 28% confirmed cCMV disease, and 2% probable cCMV disease (Table 1). The most commonly reported signs among neonates with cCMV disease were microcephaly (62%) and petechia/purpura (29%), and the most common brain abnormalities among those with imaging (n=104) were intracranial calcifications (26%) and leukomalacia (21%). Of infants with cCMV infection, 25% had other signs reported not within the disease case criteria (e.g., small-for-gestational-age, brain cysts). Overall, 22% (87/387) were reported to have started treatment with antivirals within the first 14 days of life, including 26 with cCMV infection. These preliminary surveillance data demonstrate the feasibility of conducting cCMV surveillance. These findings should be interpreted with caution given the likelihood of under-ascertaining those with infection or with cCMV-associated signs not in the screening criteria. Preliminary findings are informing ongoing state efforts to improve surveillance and inform outreach to providers and caregivers. Continued surveillance and longitudinal data collection will provide more information on disease burden. Sarah B. Mulkey, MD, PhD, Pfizer: Advisor/Consultant

Abstract Tuberculosis screening is not mandatory for prospective tissue donors. In 2021 and 2023, two different bone allograft products caused nationwide tuberculosis outbreaks. We assessed the morbidity and mortality of the second outbreak and reviewed donor and tissue screening to identify deficiencies. Thirty-six people residing in nine states received the product during spinal and dental procedures. Twenty-seven recipients had tuberculosis infection, 11 had microbiologic or imaging evidence of tuberculosis disease, and two died from tuberculosis within 12 months of outbreak detection. Another recipient died from tuberculosis nearly 3 years after product implantation. The bone donor died of pneumonia and septic shock. Polymerase chain reaction testing of the product before and after distribution did not detect Mycobacterium tuberculosis . Mycobacterial culture was not performed until after outbreak detection, when M. tuberculosis was isolated from 2 of 6 unused product units. This outbreak demonstrates persistent gaps in tissue transplant safety. Appropriate selection of donors and mycobacterial culture of donated tissues could reduce but not eliminate the risk of M. tuberculosis transmission. Therefore, it is important that clinicians monitor tissue recipients and promptly report adverse events to tissue establishments and health authorities.

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, CDC issued a national call for cases, defined as SAEs involving death or CPR within six hours of ceftriaxone injection, not otherwise explained and occurring in non-ICU settings during September 2024-August 2025. Epidemiologic and clinical data were collected by health departments and reported to CDC. Laboratory testing of ceftriaxone and lidocaine diluent was performed at FDA. 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 CPR, 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 (IQR: 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 FDA MedWatch.

OBJECTIVES:To report long-term oncological outcomes for men with clinically localised prostate cancer (PCa) treated with contemporary modalities in a population-based United States cohort. PATIENTS AND METHODS:The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study prospectively enrolled men with clinically localised PCa from 2011 to 2012. Patients were stratified into two groups: favourable prognosis (clinical T stage [cT]1-T2a/bN0M0, prostate-specific antigen [PSA] level ≤ 20 ng/mL, Grade Group 1-2) and unfavourable prognosis (cT2cN0M0, PSA level 20-50 ng/mL, or Grade Group 3-5). Main outcomes were PCa-specific mortality (PCSM), composite progression to advanced disease (metastasis, PCSM event, or systemic therapy), and overall survival (OS). Cox regression models adjusted for demographic and clinical covariates. RESULTS:Of the 2604 men included, 73% were White, 15% Black, and 7% Hispanic. All hazard ratios (HRs) were adjusted for demographic and clinical covariates using multivariable Cox and Fine-Gray models. In the favourable group, compared with surgery, external beam radiotherapy (EBRT; HR 1.5, 95% confidence interval [CI] 1.1-2.1, P < 0.01), brachytherapy (HR 2.1, 95% CI 1.3-3.3, P < 0.01), and active surveillance (HR 1.5, 95% CI 1.1-2.1, P = 0.02) were associated with higher all-cause mortality; the 10-year cumulative incidence of PCSM was ≤1.5% for all five strategies, and progression did not differ. In the unfavourable group, EBRT was associated with worse OS (HR 2.8, 95% CI 1.9-4.3, P < 0.01), with no adjusted differences in PCSM (10-year cumulative incidence 3.5% after surgery vs 8.8% after EBRT) or progression across treatments. CONCLUSION:In this population-based cohort treated with contemporary modalities, the 10-year risk of PCa death was low across all treatment strategies, including active surveillance. OS differences favouring surgery likely reflect residual confounding from baseline health and treatment selection. These findings underscore the importance of patient values and comorbidities in shared decision-making for localised PCa.

Wednesday, October 22, 2025: 11:30 AM Background: Serious adverse events (SAEs) related to ceftriaxone, a widely used cephalosporin antibiotic, are considered rare. After a 2024 SAE cluster in Alabama, the Centers for Disease Control and Prevention (CDC), with state/local partners and the US Food and Drug Administration (FDA), conducted a nationwide investigation of SAEs, including deaths, among patients who received ceftriaxone.Table.Clinical summary of serious adverse event cases (n=26), September 2024–June 2025Abbreviations: SAE: serious adverse event, ACH: acute care hospital, ED: emergency department, OP: outpatient clinic, F: female, M: male, Pt: patient (used when sex not reported); NR: not reported, NOS: not otherwise specified, EKG: electrocardiogram, PEA: pulseless electrical activity, IV: intravenous, IM: intramuscular, N/A: not applicable, PMH: past medical history, CA: cancer, CAD: coronary artery disease, CHF: congestive heart failure, CKD/ESRD: chronic kidney disease or end stage renal disease; COPD: chronic obstructive pulmonary disease, DM: diabetes mellitus, HTN: hypertension, HLD: hyperlipidemia, dx: disease CPR: cardiopulmonary resuscitation.Figure 1a-b.Epidemic curve: Frequency of reported serious adverse event cases following ceftriaxone administration from September 2024 to June 2025, by event month and US region (a) or ceftriaxone manufacturer (b), n=26Figure includes SAEs meeting CDC case definition: Adverse events following injectable ceftriaxone exposure, occurring after September 1, 2024, which: 1) occurred within 6 hours after receipt of injectable ceftriaxone in a non-ICU setting, 2) resulted in death or required cardiopulmonary resuscitation (CPR), and 3) were not attributed by the treating provider(s) to a cause other than ceftriaxone administration (such as known infection, other underlying medical condition, or exposure to a medication or medical product other than ceftriaxone). Figure 1a (left) displays epidemic curve by US Census Bureau region, reflecting case-patient state of residence. Southern region includes AL, AR, DC, DE, FL, GA, KY, LA, MD, MS, NC, OK, SC, TN, TX, VA, WV. Figure 1b (right) displays epidemic curve by the ceftriaxone product reported as administered to case-patient or present in the facility at the time of adverse event. Abbreviations: NR: not reported, US: United States. (R Core Team, 2024). Methods: CDC issued a national call for cases, defined as death or cardiopulmonary resuscitation within 6 hours of ceftriaxone receipt in non-intensive care settings without other apparent cause, occurring after Sep 1, 2024. Health departments collected clinical data for analysis at CDC. We further classified cases as anaphylaxis-type if determined by treating provider to be allergic or if involved two or more of: hypotension, respiratory compromise, cutaneous manifestations, and gastrointestinal symptoms. For SAEs reported Dec 2024-Jan 2025, FDA collected available ceftriaxone/diluent for testing and requested internal product investigations by manufacturers.Figure 2.Medications (other than ceftriaxone) prescribed proximal and prior to serious adverse event, by individual case-patient, n=23Abbreviations: ARB: angiotensin receptor blocker, ACE: angiotensin-converting enzyme, NSAID: non-steroidal anti-inflammatory drugs. Results: We report 26 cases (65% outpatient; 35% inpatient), including 12 deaths, from 22 healthcare facilities across 15 states from Sep 1, 2024 to Jun 30, 2025 (Figure 1a). Case-patients had a median age of 70 years (IQR: 60-81) and received 1g (n=15, 58%), 2g (n=9, 35%), or unspecified (n=2, 7%) ceftriaxone doses via intravenous (IV) push (n=15, 58%), IV infusion (n=9, 35%), or intramuscular injection (n=2, 7%). Presentations varied (Table); 69% (n=18) were anaphylaxis-type. Prior ceftriaxone exposure (n=16, 62%), cardiac comorbidities (n=20, 77%), and/or concurrent use of antihypertensives (n=17, 65%, Figure 2) were common. Product exposures included 22 lots from 6 ceftriaxone manufacturers (Figure 1b). FDA testing of ceftriaxone (5 lots, 4 manufacturers) and lidocaine diluent (3 lots, 2 manufacturers) found no evidence of tampering, adulteration, endotoxin, or purity/potency issues. Manufacturers (n=4) did not report product anomalies. Conclusion: SAEs, including deaths, can occur after ceftriaxone use. This investigation did not identify a common-source etiology, nor a link to a specific ceftriaxone product. Providers in all settings should monitor for SAEs, including anaphylaxis, and report to the FDA MedWatch Program. Disclosures: All Authors: No reported disclosures