Recent urinary tract infection guideline updates from multiple international medical societies highlight evolving recommendations, including a major shift in classification, moving from anatomy- and r...

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This cohort study evaluates whether any presenting symptoms are associated with timely antibiotic prescription among adults with community-onset presumed bacterial sepsis in Michigan.

Cephalexin is increasingly used as initial and oral transition therapy for severe infections, but optimal dosing in this setting remains uncertain.MethodsFour cephalexin pharmacokinetic (PK) datasets spanning preterm neonates through young adults were pooled to develop a unified population PK model. Simulations estimated probability of target attainment (PTA) and cumulative fractional response (CFR, target attainment weighted across the pathogen MIC distribution) across fT>MIC targets (free drug time above the minimum inhibitory concentration), MIC distributions for methicillin-susceptible Staphylococcus aureus (MSSA) and Enterobacterales, and multiple dosing regimens.ResultsSeventy-one subjects (age 9 days-29 years) contributed 360 plasma samples, best described by a one-compartment model with first-order absorption and lag time. Apparent volume and clearance scaled with fat-free mass, and clearance increased with post-menstrual age. Absorption was slower in neonates. Cephalexin 25 mg/kg/dose, maximum 1,000 mg, every 8 hours achieved 1-log kill targets for MSSA (PTA ≥98% for 35% fT>MIC at MIC = 4 mg/L); every 6-hour dosing was needed at MIC = 8 mg/L. For Enterobacterales, a 60% fT>MIC target was achieved only in infants <2 months. However, higher-dose regimens (37.5-50 mg/kg, maximum 1,500 mg, every 6 hours) achieved CFRs >90% for 40-50% fT>MIC targets when cefazolin MICs were ≤2 mg/L.ConclusionsCephalexin PK varies with age but is well-captured by a unified size- and maturation-scaled model. These data support dosing within the FDA-approved range for systemic MSSA infections. Higher-dose regimens are necessary for adequate target attainment against Enterobacterales. Appropriately dosed cephalexin represents a viable option for selected severe infections, including oral transition therapy.

Introduction Health care–associated infection (HAI) surveillance in US hospitals currently focuses on just 6 infections that constitute only a fraction of all serious HAIs.1 Hospital-onset sepsis surveillance using the US Centers for Disease Control and Prevention electronic Adult Sepsis Event criteria could expand the completeness and efficiency of HAI surveillance.2,3 Little is known, however, about the underlying causes and preventability of hospital-onset sepsis events, which are key considerations in assessing their potential use as hospital quality and safety metrics. We conducted detailed medical record reviews of hospital-onset sepsis events to address these knowledge gaps. Methods We performed a retrospective cohort study of adults age 18 years or older admitted between January 2021 and December 2023 to 9 Mass General Brigham acute care hospitals (2 academic and 7 community) in New England. We identified patients with hospital-onset sepsis using Centers for Disease Control and Prevention’s Adult Sepsis Event criteria (incorporating recently proposed updates),4 -6 which requires concurrent evidence of presumed serious infection and acute organ dysfunction starting on hospital day 4 or later (eTable 1 in Supplement 1). The study was approved by the Mass General Brigham institutional review board, which waived the need for direct patient consent, and was reported following the STROBE reporting guidelines. We randomly selected 250 cases for detailed record reviews by 2 physicians (F.M. and S.S.) to determine likelihood and source of infection (eTable 2 in Supplement 1). We then selected 100 infection-related cases for preventability assessments considering both patients’ intrinsic risks and extrinsic health care–related factors per the consensus of 3 physicians (F.M., M.K., and C.R.) using a 6-point Likert scale (eTable 3 in Supplement 1).7 Cases scored 1 to 3 were classified as potentially preventable, and those rated 4 to 6 as not likely preventable (eAppendix and eFigure in Supplement 1). Characteristics of potentially preventable and not likely preventable cases were compared using Fisher exact and Wilcoxon rank-sum tests. The 95% CIs for proportions were calculated using the Wilson method. Statistical significance was defined as P < .05 on 2-sided tests. Analyses were conducted using R statistical software version 2024.04.2+764 (R Project for Statistical Computing). Results Among 558 037 admissions, 5212 (0.9%) had hospital-onset sepsis. Of 250 events reviewed (133 male patients [53%]; median [IQR] age, 72 [61-80] years), 198 (79%; 95% CI, 74%-84%) were deemed attributable to infections and 52 (21%; 95% CI, 16%-26%) to noninfectious conditions (Table). Crude in-hospital mortality was 93 of 250 events (37%). Respiratory infections predominated (111 of 198 events [56%]), primarily nonventilator hospital-acquired pneumonia (NV-HAP; 88 of 198 events [44%]), followed by primary bloodstream (33 of 198; 17%]) and intra-abdominal infections (29 of 198 events [15%]). Only 25 of 198 events (13%) met surveillance criteria for currently reportable HAIs, and only 44 of 198 events (22%) had positive blood cultures with noncommensal organisms (hospital-onset bacteremia). Table.  Characteristics of Patients With Hospital-Onset Sepsis Events View LargeDownload (opens in new tab)Go to Figure in ArticleCharacteristicPatients, No. (%)Overall hospital-onset sepsis cohort (N = 250)aPreventability cohort (n = 100)Potentially preventable (n = 31)Not likely preventable (n = 69)Age, median (IQR), y72 (61-80)72 (64-80)72 (57-78)73 (64-81)Sex Male133 (53)46 (46)15 (48)31 (45) Female117 (47)54 (54)16 (52)38 (55)Hospital length of stay, median (IQR), d21 (13-36)21 (13-36)19 (14-29)22 (13-37)Location before admission Home207 (83)86 (86)27 (87)59 (86) Health care facility43 (17)14 (14)4 (13)10 (14)In-hospital death93 (37)37 (37)9 (29)28 (41)Discharge to hospice27 (11)12 (12)4 (13)8 (12)Inpatient time to hospital-onset sepsis, median (IQR), d8 (5-13)8 (6-14)10 (2– 14)8 (14-14)Agency for Healthcare Research and Quality Elixhauser Mortality Index, median (IQR)21 (10-35)23 (11-33)21 (5-33)24 (12-34)Infection likelihood Definite66 (26)28 (28)14 (45)14 (20) Probable36 (14)19 (19)6 (19)13 (19) Possible96 (38)53 (53)11 (35)42 (61) No infection52 (21)000Primary pathogen category Bacterial181 (91)92 (92)28 (90)64 (93) Viral10 (5)5 (5)2 (7)3 (4) Fungal6 (3)2 (2)02 (3) Parasitic1 (0)1 (1)1 (3)0Infection source Respiratory111 (56)56 (56)15 (47)41 (53) Abdominal or genitourinary42 (21)20 (20)10 (32)10 (14) Endovascular41 (21)18 (18)3 (9)15 (19) Head and neck or central nervous system3 (2)2 (2)02 (3) Musculoskeletal or skin soft tissue16 (8)7 (7)3 (9)4 (6) Other or unknown14 (7)7 (7)1 (3)6 (9)Reportable health care–associated infectionbClostridium difficile colitis2 (1)000 Central line–associated bloodstream infection10 (4)6 (6)2 (7)4 (6) Catheter-associated urinary tract infection6 (2)2 (2)2 (7)0 Methicillin-resistant Staphylococcus aureus bacteremia3 (1)3 (3)1 (3)2 (3) Colorectal surgical site infection4 (2)4 (4)04 (6) Hysterectomy site infection0000Sepsis organ dysfunctionc Cardiovascular164 (66)71 (71)23 (74)48 (70) Respiratory63 (25)25 (25)11 (35)14 (20) Lactic acidosis126 (50)51 (51)16 (52)35 (51) Kidney20 (8)10 (10)5 (16)5 (7) Hepatic19 (8)10 (10)2 (6)8 (12) Coagulation26 (10)14 (14)5 (16)9 (13) Among 100 infection-related cases evaluated for preventability, 31 (31%; 95% CI, 23%-41%) were judged potentially preventable (Likert scores: 1, n = 0; 2, n = 10; 3, n = 21; 4, n = 26; 5, n = 35; and 6, n = 8). The most common opportunities (n = 58) included suboptimal management of recognized infections before progression to sepsis (22 of 58 events [38%]), lack of NV-HAP prevention (22 of 58 events [38%]), and gaps in general medical care (6 of 58 events [10%]) (Figure). Lapses in traditional device-related infection prevention bundles were uncommon (5 of 58 events [9%]). Figure.  Bar Graphs of Opportunities for Improvement Among Potentially Preventable Hospital-Onset Sepsis Events View LargeDownload (opens in new tab)Go to Figure in ArticleGraphs show lapses in clinical care identified among patients with potentially preventable sepsis cases. Specific missed opportunities in early infection management included delays in subspecialty consultation (7 of 58 events [12%]), source control (6 of 58 events [10%]), and microbiologic investigation (3 of 58 events [5%]). NV-HAP prevention gaps included delays in dysphagia evaluation (5 of 58 events [9%]), missed oral care (5 of 58 events [9%]), lack of aspiration precautions (4 of 58 events [7%]), oversedation (3 of 58 events [5%]), inadequate ileus and emesis management (2 of 58 events [3%]), and nosocomial respiratory virus transmission (2 of 58 events [3%]). General medical care gaps included inadequate treatment of constipation leading to urinary retention or stercoral colitis catalyzing sepsis (3 of 58 events [5%]) and suboptimal management of hypervolemia leading to progressive respiratory failure (1 of 58 events [2%]). Among the 52 noninfectious hospital-onset sepsis events, common precipitants included bleeding (7 of 52 events [14%]), cardiac ischemia or arrhythmia (7 of 52 events [14%]), and hypovolemia (6 of 52 events [12%]). All these events were treated with antibiotics, most for 4 or more days, despite no infection. Discussion In this cohort study, we evaluated 250 hospital-onset sepsis events across 9 hospitals and found that most were attributable to respiratory, bloodstream, and intra-abdominal infections; only 13% met current US criteria for reportable HAIs. Among the 100 infection-related sepsis events reviewed for preventability, approximately one-third were deemed potentially preventable. Principal opportunities included optimizing management of recognized infections to prevent progression to sepsis, instituting measures to prevent NV-HAP, and more aggressive control of emesis, constipation, urinary retention, and volume status. Our estimate that only one-third of hospital-onset sepsis events were potentially preventable is on the lower end of preventability estimates for HAIs, possibly reflecting the heterogeneous pathways leading to hospital-onset sepsis and the complexity of affected patients.7,8 Notably, one-fifth of hospital-onset sepsis events were attributable to noninfectious conditions, highlighting that hospital-onset sepsis surveillance can potentially inform antimicrobial stewardship and inpatient quality improvement programs beyond sepsis alone.9 Limitations of our study include small sample size owing to the resource-intensive preventability adjudication process, subjectivity in retrospective preventability assessment, and risk of cognitive bias despite structured consensus adjudication.10 Hospital-onset sepsis events identify serious complications of hospitalization that are largely missed by current HAI surveillance programs yet are highly morbid and often preventable. Hospital-onset sepsis surveillance could provide a more comprehensive framework for identifying preventable harms and expanding opportunities for quality improvement. Back to top Article Information Accepted for Publication: July 23, 2026.Published: September 17, 2026. doi:10.1001/jamanetworkopen.2026.34324Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License, which does not permit alteration or commercial use, including those for text and data mining, AI training, and similar technologies. © 2026 Manzoor F et al. JAMA Network Open.Corresponding Author: Fizza Manzoor, MD, Department of Population Medicine, Harvard Pilgrim Health Care Institute, 401 Park Dr, Ste 401, Boston, MA 02215 (fmanzoor@mgh.harvard.edu).Author Contributions: Dr Manzoor had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Concept and design: Manzoor, Klompas, Rhee.Acquisition, analysis, or interpretation of data: All authors.Drafting of the manuscript: Manzoor, Klompas, Rhee.Critical review of the manuscript for important intellectual content: All authors.Statistical analysis: Manzoor, Chan.Obtained funding: Klompas, Rhee.Administrative, technical, or material support: Seetharaman.Supervision: Klompas, Rhee.Conflict of Interest Disclosures: Dr Klompas reported receiving grants from Centers for Disease Control and Prevention (CDC) and personal fees from UpToDate outside the submitted work. Dr Rhee reported receiving grants from CDC and personal fees from UpToDate and DynaMed outside the submitted work. No other disclosures were reported.Funding/Support: This work was supported by the Agency for Healthcare Research and Quality (1R01HS0269660-01) and the Thomas O. Pyle Fellowship in the Department of Population Medicine at Harvard Pilgrim Health Care Institute.Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.Data Sharing Statement: See Supplement 2. References 1.National Healthcare Safety Network. CDC/NHSN surveillance definitions for specific types of infections. January 2026. Accessed August 4, 2026. https://www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef_current.pdf2.Ginestra  JC, Coz Yataco  AO, Dugar  SP, Dettmer  MR.  Hospital-onset sepsis warrants expanded investigation and consideration as a unique clinical entity.   Chest. 2024;165(6):1421-1430. doi:10.1016/j.chest.2024.01.028PubMedGoogle ScholarCrossref3.Manzoor  F, Rhee  C, Klompas  M.  Advancing surveillance of health care-associated infections: targeting hospital-onset sepsis.   N Engl J Med. 2025;393(15):1452-1454. doi:10.1056/NEJMp2507138PubMedGoogle ScholarCrossref4.Millham  L, Gupta  S, Klompas  M, Chan  CA, Dantes  RB, Rhee  C.  Evaluating potential modifications to the Centers for Disease Control and Prevention’s adult sepsis event definition: impact on sepsis incidence, outcomes, and clinical validity.   Infect Control Hosp Epidemiol. 2025;46(9):880-887. doi:10.1017/ice.2025.10218PubMedGoogle ScholarCrossref5.Rhee  C, Zhang  Z, Kadri  SS,  et al.  Sepsis surveillance using Adult Sepsis Events Simplified eSOFA criteria versus Sepsis-3 Sequential Organ Failure Assessment criteria.   Crit Care Med. 2019;47(3):307-314. doi:10.1097/CCM.0000000000003521PubMedGoogle ScholarCrossref6.Centers for Disease Control and Prevention. Hospital toolkit for adult sepsis surveillance. May 2018. Accessed January 19, 2026. https://www.cdc.gov/sepsis/media/pdfs/Sepsis-Surveillance-Toolkit-Aug-2018-508.pdf7.Dantes  RB, Rock  C, Milstone  AM,  et al.  Preventability of hospital onset bacteremia and fungemia: a pilot study of a potential healthcare-associated infection outcome measure.   Infect Control Hosp Epidemiol. 2019;40(3):358-361. doi:10.1017/ice.2018.339PubMedGoogle ScholarCrossref8.Leekha  S, Robinson  GL, Jacob  JT,  et al; CDC Prevention Epicenters Program.  Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.   BMJ Qual Saf. 2024;33(8):487-498. doi:10.1136/bmjqs-2023-016831PubMedGoogle ScholarCrossref9.US Centers for Disease Control and Prevention. Hospital sepsis management and practices: findings from the 2024 NHSN annual survey. US Department of Health and Human Services. 2025. Accessed February 24, 2026. https://www.cdc.gov/sepsis/media/pdfs/hospital-2024-annual-survey-508.pdf10.Hayward  RA, Hofer  TP.  Estimating hospital deaths due to medical errors: preventability is in the eye of the reviewer.   JAMA. 2001;286(4):415-420. doi:10.1001/jama.286.4.415ArticlePubMedGoogle ScholarCrossref

Improving diagnostic stewardship of Streptococcus pneumoniae urine antigen testing among cancer patients - Volume 6 Issue 1

Infectious disease test results frequently finalize after hospital discharge, and many are clinically actionable. Standardized workflows for reviewing these results remain limited. Although pharmacist-led culture follow-up is well established in emergency departments, evidence evaluating inpatient transitions-of-care models is sparse. This study assessed the impact of a pharmacist-led service on outpatient antimicrobial appropriateness and clinical outcomes.MethodsWe conducted a single-center, retrospective pre–post study at a community hospital comparing patients discharged with pending infectious disease test results before and after service implementation. The intervention included thrice-weekly review of finalized results, clinical assessment, prescriber communication, outpatient prescription changes, and patient counseling. The primary outcome was appropriate outpatient antimicrobial therapy 7 days after discharge. Secondary outcomes included time to appropriate therapy among patients requiring prescription modification and 30-day infection-related outcomes. Multivariable logistic regression adjusted for urine culture source, discharge service, and inpatient infectious diseases consultation. Time-to-therapy analyses used Kaplan–Meier and Cox proportional hazards.ResultsAmong 191 patients (93 preintervention; 98 postintervention), appropriate antimicrobial therapy at 7 days increased from 69% to 92%. Adjusted analyses showed a 21.3% higher predicted probability of appropriate therapy (95% CI, 10.6–32.0). Among patients requiring prescription changes (n = 63), median time to appropriate therapy improved from 7 to 4 days, with a 5-fold higher rate of achieving appropriate therapy (hazard ratio, 5.09; 95% CI, 2.13–12.18). Thirty-day outcomes were similar between groups.ConclusionsA pharmacist-led service improved antimicrobial appropriateness and accelerated transitions to appropriate therapy, supporting pharmacist-driven follow-up as an effective stewardship strategy.

AbstractIntroductionExcept for their role in bacterial endocarditis, non-pneumococcal Streptococcus mitis group (SMG) bacteria have traditionally been regarded as commensals of the oropharynx. Widespread adoption of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has increased identification of these organisms and has led to increased concern about their clinical significance. We evaluated SMG bacteremia in a large multicenter cohort to characterize associated clinical syndromes and better define their clinical relevance.MethodsWe performed a retrospective review of all adult patients from 2017 to 2025 who had SMG bacteremia at three hospitals within the Texas Medical Center. SMG bacteremia was defined as isolation of S. mitis, S. mitis/oralis, or S. mitis group as determined by MALDI-TOF. Clinical syndromes were identified through chart review and assigned using consistent classification approaches informed by physician documentation, imaging, and microbiologic data.ResultsAmong 253 patients, neutropenia-associated bacteremia was most common (29.6%) followed by pneumonia (9.5%), infective endocarditis (8.7%), skin, soft tissue, or bone infections (7.9%), and other identified sources (12%). No clear source was identified in 9.5% of cases. Only 22.9% were classified as contaminants. High-grade bacteremia was common, with 47% of cases having ≥ 3 positive blood culture bottles. In contrast, patients in whom SMG was regarded as contaminant nearly always had only a single bottle positive.ConclusionSMG bacteremia was associated with a broad spectrum of clinical syndromes, with most isolates being regarded as representing clinically significant infection.

AbstractWe conducted a retrospective review to characterize adverse events (AEs) in patients receiving oral linezolid, trimethoprim-sulfamethoxazole, voriconazole, and itraconazole monitored under an outpatient parenteral antimicrobial therapy (OPAT) program. Among 118 patients, 61% incurred at least one AE during treatment, highlighting the need for evidence-based monitoring protocols for complex outpatient antimicrobial therapy (COpAT).

Across all patients in DOTS, mean medical costs associated with Staphylococcus aureus bacteremia were about $4600 to $5900 lower in the dalbavancin group v

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