Huskins, W. Charles

Background: Measles is a highly transmissible virus. A single case can result in significant exposures within a healthcare facility and prompt action is needed to prevent secondary cases. In October 2025, Infection Prevention and Control (IPAC) was notified of a patient being admitted to our facility with recent international travel and symptoms consistent with measles. The patient was unvaccinated and had five healthcare facility visits prior to measles being suspected and subsequently confirmed. Objective: To describe our facility’s effective identification, prioritization, and prophylaxis of individuals exposed to measles. Methods: IPAC leveraged the electronic medical record to identify potentially exposed patients. Patients were quickly assessed for age and immune status, then prioritized and assigned to primary care teams. These teams promptly contacted patients and coordinated PEP administration. Results: Across five encounters, the index patient exposed 539 other patients. Due to delayed notification, our teams had less than four days to administer PEP for those exposed and still within PEP window. PEP administration began within hours of the index case’s positive test and patients received PEP within three days (Table 1). No secondary measles cases occurred within our facility. Conclusion: Timely and coordinated multidisciplinary effort enabled us to rapidly respond to our first measles case and control secondary transmission. Although the index case resulted in a large exposure, patients that were exposed and eligible for PEP were quickly prioritized to prevent secondary transmission.

Background: Advanced planning and adaptable response strategies are essential for preventing measles transmission in healthcare facilities. Objective: To describe a measles management plan and subsequent modifications in response to a cluster of measles cases. Methods: Drawing on previously published work (doi:10.1017/ice.2025.49), the Infection Prevention and Control (IPAC) team initiated a multi-disciplinary team and developed a measles preparedness plan with the following domains: Guidance and education; early detection and testing; isolation and patient movement; contact tracing and exposure management (Table 1). In October 2025, a patient was admitted during their fifth healthcare encounter and was diagnosed with measles. Two family members were later hospitalized with measles. Delayed recognition of the first case prompted enhancements to our preparedness framework (Table 1). Results: The first case resulted in 539 exposed patients. The second resulted in 87 exposures, and the third resulted in no exposure. Despite the extensive exposure, zero secondary measles were reported. Conclusion: Proactive planning enabled rapid response to our first case and controlled secondary transmission. Despite extensive planning, delayed identification of the first case caused significant exposures. As the cluster unfolded, we refined our plan, resulting in zero exposures from the last patient and zero secondary cases, despite over 850 exposures. These efforts may guide other healthcare facilities in improving their measles preparedness and response.

Background: A measles case requires immediate action to identify and administer prophylaxis to exposed individuals in healthcare settings. Infection preventionists (IPs) often balance proactive contact tracing with waiting for a positive test result. Objective: To develop a tool that enables IPs to stratify suspect measles cases by risk level, thereby supporting the decision to prioritize or defer active intervention while awaiting test results. Methods: In spring 2025, we developed a preliminary matrix and used 19 additional suspect patients to further refine the scoring of the tool. In August 2025, we deployed a finalized tool. The two-dimensional risk matrix incorporated both epidemiological risk factors and clinical risk factors, each scored numerically based on yes or no questions. The sum of both categories was used to assign a final risk level that determined the recommendations for IPs (Figure 1). The study population included patients tested for measles during the implementation period. Descriptive statistics were used to summarize the distribution of risk categories and outcomes. Among the whole cohort, Firth’s logistic regression was used to evaluate the association between clinical or epidemiological risk score and measles diagnosis. Among the production cohort, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to evaluate the diagnostic performance. Results: Since implementation, the matrix was applied to 56 patients tested for measles. Of these, 10.7% (n=6) were categorized as high risk, 32.1% (n=18) as medium, and 57.1% (n=32) as low. Four of the 56 patients were positive for measles, 3 were categorized as high-risk and 1 as medium risk. Each one-unit increase in epidemiological risk was associated with a 2 folds increase in the odds of a positive measles diagnosis (odds ratio = 2.0; 95% CI, 1.3–3.6). The low-risk category had an NPV of 1, indicating that all low?risk patients tested negative, thus supporting safe workload reduction by deprioritizing these cases. Conclusion: The Measles Exposure Response Risk Matrix effectively stratified cases and supported IP prioritization efforts. Low-risk groups required no action, expedited testing was reasonable for medium-risk cases, and proactive actions were reserved for high-risk cases. Clinical and epidemiologic risk scores progressed from arbitrary assignment to validated metrics, confirmed by statistical analysis. The flexible design permits adaptation to other infectious diseases, including avian influenza and mpox. With rising measles incidence, tools like this matrix will be essential to support rapid, evidence-based actions by infection prevention teams.

ABSTRACT Novel β-lactam/β-lactamase inhibitors (βL/βLIs) are important therapies for carbapenem-resistant Pseudomonas aeruginosa (CRPA). However, the global extent of resistance to these agents and the impact of resistance on patient outcomes are unclear. We therefore evaluated patients with CRPA isolates at 35 hospitals (nine countries) from December 2018 to November 2019. Antimicrobial susceptibility testing was performed at a central laboratory by agar dilution for ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) and by broth microdilution for imipenem-relebactam (I/R). Characteristics and outcomes, including desirability of outcome rankings (DOOR), were compared between patients infected with isolates not susceptible vs susceptible to each agent. Of 800 CRPA isolates, susceptibility to C/T, CZA, and I/R was 69%, 67%, and 33%, respectively. USA isolates ( n = 526) were more frequently susceptible to these agents than isolates from other countries ( n = 274; C/T: 83% vs 42%; CZA: 77% vs 47%; I/R: 37% vs 23%; P < 0.001 for each comparison) and isolates with carbapenemases ( n = 157) were less frequently susceptible than isolates without carbapenemases ( n = 643; C/T: 7% vs 84%; CZA: 24% vs 77%; I/R: 6% vs 39%; P < 0.001 for each comparison). Thirty-day mortality and DOOR were similar overall in patients infected with isolates not susceptible vs susceptible to each βL/βLI. However, the adjusted probability of a better DOOR outcome for a randomly selected patient with bacteremia due to a C/T-not susceptible vs -susceptible isolate was 38.2% (95% confidence interval, 25.6%–52.7%). Resistance to novel βL/βLIs, especially I/R, is common in CRPA, particularly outside the USA and in carbapenemase-producing isolates. Additional treatment options are needed for CRPA infections.

ABSTRACT The most common infectious disease responsible for paediatric developmental disability is congenital infection with human cytomegalovirus (cCMV). Many serious sequelae are caused by cCMV, including microcephaly, intracranial calcifications, neuronal migration defects, seizure disorders, developmental delay, and sensorineural hearing loss (SNHL). Although long‐term neurodevelopmental impairment is clearly more common in newborns with clinically apparent disease at birth, more knowledge is needed about management in the era of universal cCMV screening, since screening identifies infants that, in the past, would not have been discovered during routine newborn care—infants that we reference in this review as having clinically inapparent cCMV (CICMV) infections. For newborns identified with CICMV infections by universal cCMV screening, longitudinal audiologic assessment is needed, but other necessary laboratory and neuroimaging studies, as well as indications for antiviral therapy, are uncertain. This review summarises current concepts about the approach to cCMV infections identified by universal screening, with emphasis on the CICMV infant. We identify areas for future research that should inform and direct future evaluation and management of these infants.

Abstract Background Ceftriaxone-resistant Escherichia coli infections are increasingly common, partially because of the emergence of E. coli sequence type 131 (ST131), including its subclade C2/H30Rx, which produce extended-spectrum β-lactamases. Methods A prospective cohort including 14 US sites, which enrolled monomicrobial ceftriaxone-resistant and susceptible E. coli bloodstream infection (BSI) cases in a 1:1 ratio, was used to compare ST131 versus non-ST131 E. coli BSI, with specific attention to E. coli ST131 C2/H30Rx. Desirability of outcome ranking was determined at 30 days after infection onset. Results This analysis included 282 patients with E. coli BSI; 43% (121/282) were E. coli ST131 and 23% (66/282) belonged to the C2/H30Rx subclade. Resistance to ceftriaxone was present in 79% (96/121) ST131, 86% (57/66) E. coli ST131 C2/H30Rx, and 27% (43/161) E. coli non-ST131. Compared to patients with non-ST131 E. coli BSI, patients with ST131 BSI were older (median 70 years, [Q1 62, Q3 76] years vs 65 years, [51, 74]; P = .005) and more often admitted from long-term care facilities (21/121 [17%] vs 7/161 [4%], P &lt; .001). Overall and empiric carbapenem use was more frequent in the treatment of patients with ST131 BSI compared with non-ST131 BSI (overall 89/121 [74%] vs 50/161 [31%]; empiric: 58/121 [48%] vs 31/161 [19%], P &lt; .001). Desirability of outcome ranking outcomes were similar between groups. Conclusions Most ceftriaxone-resistant E. coli from US patients with E. coli BSI belong to ST131, particularly E. coli ST131 C2/H30Rx, serving as an important driver of carbapenem use.

Abstract Background Drug-resistant E. coli is a leading cause of antimicrobial resistance-associated deaths globally. Specifically, resistance to ceftriaxone (CRO-R) is increasing in E. coli. High-risk clonal group ST131 and its pandemic H30 subclone are of high concern yet studies characterizing these infections are limited. We evaluated baseline characteristics and clinical outcomes associated with H30 ST131, non-H30 ST131 and non-ST131 E. coli bloodstream infections (BSI). Methods Patients with monomicrobial carbapenem-susceptible E. coli BSI that were matched 1:1 by study site (CRO-R and CRO-susceptible community-acquired and hospital onset cases) were prospectively enrolled from 14 United States hospitals between November 12, 2020 to April 28, 2021 in the multicenter Study of Highly Resistant E. coli (SHREC). Isolates underwent whole genome sequencing. The primary outcome was a 30-day Desirability of Outcome Ranking (DOOR) after index culture including clinical response to treatment and all-cause mortality. Results There were 92 (33%) H30 ST131, 29 (10%) non-H30 ST131, and 161 (57%) non-ST131 isolates in 282 E. coli BSI (Table 1). Most ceftriaxone resistance was conferred by CTX-M-15 produced by H30 ST131 isolates (Figure 1, Table 1). H30 ST131 BSI patients were older (median age [IQR] 70.5 [63,76] vs. 67 [56,77] vs 65 [51,74] years, p = 0.017), had higher Charlson comorbidity indices (3 [2,5] vs. 2 [1,4] vs. 2 [1,4], p=0.009), and were more often admitted from long-term care facilities (18/92 [20%] vs. 3/29 [10%] vs. 7/161 [4%], p = 0.003) compared to non-H30 ST131 and non-ST131 BSI patients. Among H30 ST131 isolates, high rates of antibiotic resistance were observed to cephalosporins and fluoroquinolones, resulting in significantly more carbapenem use compared with non-H30 ST131 and non-ST131 isolates (75/92 [82%] vs. 14/29 [48%] vs. 50/161 [31%], p &lt; 0.001) (Figure 2). 30-day DOOR and hospital length of stay did not differ between groups (Table 2). Conclusion Compared with non-H30 ST131 and non-ST131 E. coli BSI, H30 ST131 E. coli BSI have a unique epidemiology with more healthcare exposures, comorbidities and antibiotic resistance and are more likely to be treated with carbapenems, though no significant difference in clinical outcomes was observed. Disclosures Yohei Doi, MD, PHD, AbbVie: Honoraria|Entasis: Grant/Research Support|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Meiji Seika: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Elie Saade, MD, MPH, FIDSA, Janssen Global Services: Advisor/Consultant|Janssen Global Services: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support Michael J. Satlin, MD, AbbVie: DSMB participant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Selux Diagnostics: Grant/Research Support|SNIPRBiome: Grant/Research Support W. Charles Huskins, MD, MSc, ADMA Biologics: Advisor/Consultant|Bristol Myers Squibb: Stocks/Bonds (Public Company)|Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds (Public Company)|Zimmer Biomet: Stocks/Bonds (Public Company) Carol Hill, PhD, Glaxo SmithKline: Retirement Health, Cash Balance Plan|Glaxo SmithKline: Stocks/Bonds (Public Company) Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

Importance Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. Objective To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. Design, Setting, and Participants This retrospective cohort study used data from 51 US children’s hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. Exposure The number of minutes from emergency department arrival to antibiotic administration. Main Outcomes and Measures The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. Results A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. Conclusions and Relevance In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Abstract Background Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). Objectives To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. Methods Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. Results The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients’ race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%–56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. Conclusions Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults.