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Vaccination uptake among individuals receiving HIV pre-exposure prophylaxis: real- world data (2021–2025) HIV pre-exposure prophylaxis (PrEP) programme provides regular clinical follow-up and represents an opportunity to improve vaccination coverage against preventable infections. We evaluated vaccination uptake among PrEP users and described associated variables in a tertiary care center.MethodsWe conducted a retrospective study including individuals receiving PrEP at Tor Vergata University Hospital (Rome, Italy) from January 2021 to September 2025. Demographic and behavioral data were collected. Vaccination status for hepatitis B virus (HBV), hepatitis A virus (HAV), human papillomavirus (HPV), meningococcal B (MenB), and mpox was assessed at baseline and during follow-up. HAV, HBV, HPV and MenB vaccines are administered at the vaccination clinic inside the hospital.ResultsA total of 285 individuals were included (median age 35 years, IQR 31–43). Most participants were single (77.3%); 5% reported chemsex practices. At baseline, HBV vaccination coverage was 88.4% (243/275), including 45 booster doses; 2.7% showed serological evidence of resolved infection. HAV coverage was 27.8% (75/270); HPV coverage was 30% (81/280). After PrEP initiation, 37% (100/271) completed the MenB vaccination cycle and 13.7% received the first dose. After PrEP start, HPV vaccination cycle was started in 47.4% (128/270), resulting in an overall coverage of 77.3%. Mpox vaccination prevalence was 32% (88/271). Mpox vaccination was not administered at our center and was provided through external public health services. Overall, vaccination coverage was high for HBV and HPV, while HAV and MenB uptake remained suboptimal.ConclusionsPrEP services represent an important platform to enhance preventive care beyond HIV protection. Structured integration of vaccination strategies within PrEP clinics may improve coverage for recommended vaccines in high- risk populations. Table 1.Characteristics of the PrEP Population and Vaccination StatusVariableCategoryFrequencyPercentageMarital statusSingle20177.31%Married249.23%Cohabiting3212.31%Separated31.15%Education levelPrimary school10.38%Lower secondary school93.46%Upper secondary school10640.77%University degree14455.38%Alcohol abuse (last 6 months)No18269.73%Yes7930.27%ChemSexNo24995.00%Yes135.00%Previous STIsNo9635.96%Yes17164.04%HBV vaccinationNo3211.64%Yes24388.36%HAV vaccinationNo19271.11%Yes7527.78%Previous infection31.11%HPV vaccinationNo7126.30%Yes16561.11%Unknown3412.59%Mpox vaccinationNo18267.16%0 doses4123.00%MenB vaccination1 dose10056.20%2 doses3720.80%

PrEP users (n=285, median 35 yrs) had high HBV (88.4%) & HPV (77.3%) coverage; low HAV (27.8%), MenB (37%), mpox (32%) uptake. Chemsex: 5%. Vaccines ↑ with PrEP. 💉

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Unusual presentations of osteoarticular tuberculosis: experience from a tertiary center in Liguria Osteoarticular tuberculosis (TB) is a rare but serious manifestation of extrapulmonary TB. Despite improvements in imaging and microbiological diagnostics, bone TB remains challenging to identify because its clinical presentation is often nonspecific. While the spine and knee are the most frequently affected sites, involvement of less typical skeletal locations can occur, further complicating timely diagnosis.MethodsWe retrospectively reviewed all cases of bone TB diagnosed at the ‘Malattie Infettive e Ortopedia Settica’ Department—ATS Liguria, Savona area, from 2022 to 2025. Diagnostic confirmation relied on imaging, histopathology, culture, and polymerase chain reaction (PCR) testing for Mycobacterium tuberculosis.ResultsEight patients (6 males, 2 females; mean age 50 years) were identified. Three were Italian, and five were foreign-born. Two patients had vertebral TB: an 80-year-old Ukrainian woman and a 25-year-old Gambian man. Both developed paraparesis requiring surgical stabilization; intraoperative cultures confirmed the diagnosis. Two patients (aged 19 and 23) presented with chronic knee arthritis. Initial arthrocentesis cultures and PCR were negative. Diagnosis was achieved through surgical biopsy; in one case, culture remained negative, but histopathology revealed necrotizing granulomas with Langhans giant cells, and PCR on the histological piece identified M. tuberculosis.A 75-year-old Italian woman with diabetes developed a tuberculous prosthetic joint infection, confirmed by synovial fluid culture. An 86-year-old Italian man with squamous cell carcinoma had mandibular TB diagnosed by bone biopsy, along with concurrent pulmonary TB.A 74-year-old Italian man presented with wrist pain and a draining fistula; bone culture was positive for M. tuberculosis. A 14-year-old boy had ankle inflammation and cervical lymphadenopathy; bone biopsy confirmed TB.All patients tested positive on the QuantiFERON-TB Gold assay. Only one had pulmonary involvement, and one had lymph node disease. All isolates were susceptible to first-line drugs. Treatment typically lasted 12 months, although one patient discontinued therapy after eight months due to hepatotoxicity.ConclusionsBone TB should be considered in cases of chronic osteoarticular infection, even in non-endemic settings and when atypical anatomical sites are involved. Diagnostic accuracy improves when culture, histopathology, and molecular testing are combined. Early recognition and multidisciplinary management are essential to optimize outcomes.

8 bone TB cases (6M/2F, avg age 50) in Italy; spine/knee common; all +QuantiFERON; 12-month tx; combo diagnostics ↑ accuracy; 1 stopped tx (hepatotoxicity) 🦴🦠🔬

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Low yield of blood cultures after end-of-therapy of an episode of infective endocarditis: a twelve years’ experience from a referral centre. AbstractIntroductionInfective endocarditis (IE) carries a significant risk of recurrence. European clinical guidelines recommend performing follow-up blood cultures (BC), although evidence regarding their utility is limited. We aimed to assess the yield of follow-up BC in these patients.Material and methodsSingle-centre post-hoc analysis of a prospective cohort including IE survivors diagnosed between 2012 and 2023 with at least 12 months of follow-up.ResultsAmong 225 patients included, follow-up BCs were performed in 153 (68.0%). Recurrence was diagnosed in 19 patients (8.4%). Patients with recurrence had higher mortality during follow-up (15.8% vs 4.4%, p=0.025).Among patients with follow-up BCs, there was one contaminant (0.7%) and, two true positive results (1.3%), both of them representing IE reinfections due to different microorganism. One of them had fever at BC extraction. The one-year recurrence rate and IE-associated mortality (including complications or recurrences) were similar in patients with and without BCs (7.8% vs 9.7%, p=0.789; and 1.4% vs 0.7%, p=0.538, respectively).In the index IE episode, patients with recurrence more frequently presented with previous IE (21.1% vs 5.3%, p=0.035), fungal etiology (10.5% vs 1.5%, p=0.010), and mycotic aneurysms (15.8% vs 1.0%, p=0.004), while they had a lower frequency of native valve (31.6% vs 54.6%, p=0.059) and Staphylococcus aureus (5.3% vs 23.2%, p=0.012).ConclusionFollow-up BCs after an IE episode appears to have low utility, with similar rates of true positives and contaminants. Patients with follow-up BCs did not have more recurrences diagnosed or lower mortality during follow-up.

IE recurrence was 8.4% with higher mortality (15.8% vs 4.4%🔥). Follow-up BCs (68%) had 1.3% true positives, similar recurrence (7.8% vs 9.7%) and mortality rates.

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Generative artificial intelligence for surgical site infection surveillance View abstract Background:Surgical site infection (SSI) surveillance can be time consuming and resource intensive. This study investigates the potential of generative artificial intelligence (GenAI) to augment the detection and classification of SSIs.Methods:A case control study of patients with SSI following spine surgery at one US hospital. SSIs were classified into superficial, deep, and organ space. All SSIs were confirmed by infection prevention (IP) experts as they occurred from October, 2023 to September, 2025 and matched 1:1 by year to surgeries deemed non-SSI. A secure GenAI was used to determine if patients had an SSI based on standardized prompts and clinical data. IP nurses used GenAI output to review cases with the ability to ask GenAI questions within the data provided or independently open the medical record. We compared GenAI determinations to initial IP nurses’ determinations.Results:A total of 555 patients had spine surgeries. All 16 SSIs were matched by year to 16 non-SSI. All SSIs were correctly identified by GenAI (sensitivity 100%, 16/16) and only 1 non-SSI was incorrectly identified as SSI (specificity 93.7%, 15/16). Although GenAI accurately identified all SSI cases, it was discordant with original review at classifying the level of infection in 37.5% (6/16) of cases. Upon final IP physician review, GenAI was correct in 66.7% (4/6) of discordant cases (often determining “organ space infections” rather than “deep”). Median time to complete GenAI assisted SSI reviews was 9 minutes (IQR 7–21).Conclusion:GenAI is a promising tool to assist in SSI surveillance following spinal surgery that could improve efficiency.

GenAI detected 100% (16/16) SSIs post-spine surgery, with 93.7% specificity, misclassifying 37.5% infection levels, but corrected in 66.7% cases. Review time: 9 mins ⏱️.

11 hours ago 0 0 0 0
Can machine learning support infection control measures by predicting carbapenemase-producing Enterobacterales colonization at admission? View abstract Background:Early identification of patients with carbapenemase-producing Enterobacterales (CPE) colonization is crucial for infection control; however, microbiological testing may delay detection and be costly. Machine learning may enhance predictive analytics for timely identification of at-risk patients.Methods:Four machine learning models: Decision Tree, Random Forest, Gradient Boosting, and XGBoost, were used to predict CPE colonization within 48 hours of admission using microbiological and demographic data. Model performance was assessed through sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Uniform Manifold Approximation and Projection (UMAP) evaluated topological separability of CPE-positive cases and CPE-negative controls.Results:From January 1, 2015 to December 31, 2024, 453,372 fecal specimens were submitted for CPE screening, with 194,917 (43.0%) collected within 48 hours of admission, comprising 3,328 CPE-positive cases (1.7%) and 191,589 CPE-negative controls. The Gradient Boosting classifier showed the best performance, achieving an AUROC of 0.598, sensitivity of 54.4%, and specificity of 59.1%. Demographic factors (age ≥ 75 and male sex), history of hospitalization, and known CPE colonization in the past year, and admission specialty (general medicine and general surgery) were consistently included in all models as top predictors. UMAP revealed significant overlap between CPE-positive and CPE-negative patients, indicating challenges in differentiating the risk profiles.Conclusions:This study highlights the complexities of using machine learning to predict CPE colonization within 48 hours of admission. The low AUROC values suggest that the models may not effectively predict CPE colonization at the patient level, potentially due to inherent rarity of events and overlapping risk profiles.

ML models predicted CPE colonization (1.7% cases in 194,917 tested) within 48h; best AUROC 0.598, sensitivity 54.4%, specificity 59.1%. Risk factors: age≥75, male, prior hospitalization.📊🔍

12 hours ago 0 0 0 0
Development and implementation of a quality improvement framework for the prevention hospital-onset bacteremia and fungemia View abstract Objective:Develop and implement a framework for reviewing hospital-onset bacteremia and fungemia (HOB) events to identify quality improvement opportunities.Design:Prospective, observational study.Setting:Six hospitals (3 academic and 3 community) associated with two health systems.Participants:Clinical team members involved in the care of patients with eligible HOB events.Methods:The Joint Commission Patient Safety Event Taxonomy was adapted to develop a framework for HOB, eliciting potential contributing factors in four categories: general infection prevention, infection-site-specific, system, and human factors. From 9/2022 to 4/2024, HOB events identified from hospital blood culture databases were selected using convenience sampling to a target enrollment of 75 events, limiting inclusion of events associated with neutropenia or central line infections. Multidisciplinary case reviews were performed, and the framework was refined using feedback from the first 17 reviews. We summarized HOB sources, contributing factors, and improvement opportunities using descriptive analyses.Results:Seventy-four HOB case reviews were analyzed, evenly distributed between academic and community hospitals, and 42% occurred in an ICU setting. A median of 3 care team members (IQR 2–4) participated in each review. At least one infection-site-specific factor was identified in 48% of case reviews, representing 63% of HOB events with a known source of infection. 50% of cases identified a general infection prevention factor, 35% a system factor, and 34% a human factor. 57% of the cases had an actionable finding.Conclusions:HOB events have diverse causes and elements of preventability, and multidisciplinary review can generate actionable findings beyond the current guideline-defined measures.

Study of 74 hospital-onset bacteremia/fungemia cases: 42% in ICU, 48% had infection-site factors, 50% infection prevention issues, 57% had actionable findings.🦠🏥

12 hours ago 1 1 0 0
Electronic Clinical Quality Measures of Antibiotic Use in Hospitalized Adults with Uncomplicated Community-acquired Pneumonia Community-acquired pneumonia (CAP) is the top indication for inpatient antibiotic use and overuse. We describe the development of two electronic clinical quality measures (eCQMs) assessing the percentage of hospitalized patients with uncomplicated CAP who had unsupported a) antibiotic duration beyond 5 days and b) empiric antibiotics targeting methicillin-resistant Staphylococcus aureus and/or Pseudomonas aeruginosa.MethodsBoth eCQMs were developed based on clinical guidelines, literature, and expert feedback and then specified electronically. The eCQMs were then applied to patient data from two academic medical centers and 109 VA healthcare systems to evaluate importance, reliability, validity, and feasibility, as defined by Centers for Medicare and Medicaid Services.ResultsAcross all hospitals, the mean percentage of eligible patients with unsupported excess duration and inappropriate empiric antibiotic use ranged from 40%-55% and 17%-56%, respectively. Within the VA cohort, reliability (median [1st -10th decile, n]) for duration and empiric eCQMs was high: 93% (63%-97%, 28,238) and 91% (63%-96%, 47,034), respectively. When compared to chart review at one academic hospital, both eCQMs had high sensitivity (96%, both) and specificity (92% and 93%, for duration and empiric eCQMs, respectively). Feasibility was maximized by using only data elements in structured electronic health record fields. Some technically complex elements (e.g., clinical stability) were retained for face validity.ConclusionsTwo eCQMs identifying unsupported excess antibiotic duration and inappropriately broad empiric antibiotic use in uncomplicated CAP patients had high importance, reliability, validity, and feasibility. These eCQMs could be benchmarked to assist antibiotic stewardship programs in understanding and improving their antibiotic use.

eCQMs found 40%-55% had excess antibiotic duration; 17%-56% had inappropriate empiric use in CAP. Reliability ~91%-93%, sensitivity 96%, specificity ~92%-93%.📊🦠

13 hours ago 1 1 0 0
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Azole Resistance in Aspergillus fumigatus From Diverse Environments in Ohio, United States, Is Primarily Driven by TR34/L98H and TR46/Y121F/T289A Environmental Signatures AbstractAspergillus fumigatus is a leading global human fungal pathogen. Triazole antifungal drugs are used in clinical settings, while triazole demethylase inhibitor (DMI) fungicides are widely applied in the environment to combat plant fungal diseases. Environmental exposure to triazole fungicides may drive cross-resistance to clinical triazoles. To address limited data on environmental azole-resistant A fumigatus (ARAF) in the United States, we conducted surveillance across 75 sites in Ohio, including agricultural (57.3%), naturalized (25.3%), urban (16%), and commercial (1.3%) environments. Samples collected comprised air (n = 411), soil (n = 352), and compost (n = 42). Nested polymerase chain reaction of 397 airborne spore samples detected A fumigatus DNA in 62.7%, with 35.5% wild-type, 17.9% tandem repeat (TR), and 9.3% with mixed genotypes. TR genotype distribution did not differ by environment or DMI use. Aspergillus fumigatus was cultured from 18.1% of air samples, with 1.5% positive for ARAF. From soil and compost, A fumigatus was recovered from 41.4% of samples, of which 9.2% were positive for ARAF. Compost yielded higher A fumigatus (83.3%) and ARAF (21.4%) than soil (36.4% and 1.7%, respectively). ARAF prevalence was higher in urban (9.5%) than agricultural (2.8%) or naturalized (1.4%) environments. Generalized linear models suggested that compost and propiconazole exposure were significant predictors of ARAF occurrence. Among 72 ARAF isolates, 50% and 43% carried TR34/L98H and TR46/Y121F/T289A mutations, respectively, suggesting these mutations as key resistance signatures in Ohio environments. These findings identify compost and DMI exposure as a fertile milieu for ARAF development, highlight urban hotspots, and underscore the need for One Health approaches to resistance management.

🌍 Aspergillus fumigatus found in 62.7% air spores, 18.1% air cultures (1.5% resistant). Soil/compost: 41.4% fungi, 9.2% resistant; compost high at 83.3%/21.4%. Urban ARAF 9.5% > agri 2.8%. Compost & propiconazole predict ARAF; 50% TR34/L98H mutations.

23 hours ago 1 0 0 0
Proactive access strategies for novel cryptosporidiosis therapeutics AbstractCryptosporidiosis is a major cause of parasitic diarrhea in lower income countries disproportionately affecting young children, malnourished populations, and people with compromised immunity. While still underemphasized on the global health agenda, the disease is gradually gaining momentum for therapeutic development. However, the real-world impact of any new medicine will hinge on its effective use in regions that currently face significant access barriers. This Perspective asks what it will take to achieve access to new cryptosporidiosis treatments and outlines strategies to bridge scientific progress with real-world delivery.

Cryptosporidiosis mainly hits young kids, malnourished, immunocompromised in low-income areas. New treatments need better access to impact 🌍💊📉.

23 hours ago 0 0 0 0
[Articles] Diagnostic and prognostic accuracy of the Mycobacterium tuberculosis host response 3-gene cartridge among tuberculosis household contacts in Mozambique, Tanzania, and Zimbabwe: a prospective, longitudinal, diagnostic and prognostic accuracy cohort study MTB-HR did not meet the 2025 WHO target product profile criteria for screening or prognostic use; however, its positive predictive value for incident tuberculosis was higher than that of currently used tests. These findings support a potential role for MTB-HR in screening and prevention strategies.

MTB-HR ❌2025 WHO targets but has higher positive predictive value for TB vs current tests, suggesting use in screening & prevention. 🚫✅📈🔬🛡️

1 day ago 0 0 0 0
The impact of tele-stewardship on rural and suburban pediatric ambulatory antibiotic prescribing View abstract Objective:Developing, implementing, and evaluating the effectiveness of outpatient pediatric antimicrobial stewardship interventions via tele-stewardshipDesign:Baseline data collected between January and December 2022. Intervention data collected from February 2023 to December 2024. Interrupted time series with regression discontinuity analysis used to compare rates of antibiotic prescription between the periods.Setting:Three pediatric primary care clinics and three emergency departments associated with Vanderbilt University Medical Center that served rural and suburban communities.Participants:All encounters with patients less than 18 years of age at participating sites.Interventions:Intervention bundle included patient/caregiver educational materials, antibiotic use commitment posters, prescriber education through quarterly teaching sessions on common pediatric infections, communication skills training, app-based microlearning modules, access to local guidelines using the Firstline app, and quarterly audit and feedback with peer comparison on guideline-concordant antibiotic use.Results:Among a total of 147,357 encounters (43,157 baseline, 100,200 intervention), overall percent of encounters with one or more antibiotics prescribed decreased from 12.4% to 11.9% (P = .01). Percent change varied by site and patient demographics. Overall guideline-concordant prescribing increased significantly for acute otitis media (77.7% baseline vs 85.7% intervention, P < .001), streptococcal pharyngitis (73.8% baseline vs 81.7% intervention, P < .001), and urinary tract infections (41.9% baseline vs 57.1% intervention P < .001). Five-day antibiotic courses increased significantly (6.3% baseline vs 19.7% intervention, P < .001). There was a significant decrease in rapid streptococcal testing (10.9% baseline vs 7.6% intervention, P < .001).Conclusions and Relevance:Tele-stewardship interventions were effective in outpatient pediatric primary care and emergency department settings, but effectiveness varied by site.

Tele-stewardship cut abx Rx 🩺 from 12.4%➡️11.9% (P=.01); guideline Rx ↑: AOM 77.7%➡️85.7%, strep 73.8%➡️81.7%, UTI 41.9%➡️57.1% (all P<.001). 5-day courses ↑ 6.3%➡️19.7%.

1 day ago 0 0 0 0
Risk of Invasive Meningococcal Disease in Children Aged &lt;11 Years in the United States Invasive meningococcal disease (IMD) is associated with high case-fatality rates and severe long-term sequelae. In the United States (US), IMD incidence rate (IR) is highest among infants aged <1 year, with most cases occurring in infants aged <6 months. This study estimated IMD incidence in commercially and Medicaid-insured infants, toddlers, and children aged <11 years.MethodsThis retrospective claims analysis utilized real-world data (01 January 2005 to 31 December 2022) from the MarketScan® Commercial and Multi-State Medicaid Research Databases of infants (aged <1 year), toddlers (aged 1–4 years), and children (aged 5–10 years). IMD incidence, time at risk for IMD, IR, and IR ratio (IRR) were evaluated overall and by demographic/clinical characteristics.ResultsWithin the commercially and Medicaid-insured cohorts, 21 and 115 infants, 34 and 80 toddlers, and 36 and 37 children with IMD were identified, respectively. Overall IMD IRs in infants, toddlers, and children were 0.45, 0.17, and 0.11 per 100 000 person-years (PY; commercially insured) and 1.97, 0.45, and 0.18 per 100 000 PY (Medicaid-insured), respectively. Incidence rates were highest in infants aged <4 months (1.03 and 4.65 per 100 000 PY for infants aged 2 to <3 months [commercially insured] and 1 to <2 months [Medicaid-insured], respectively). Significantly elevated IRRs were observed among infants and children with specific demographic and clinical characteristics, including residence in rural counties, immunocompromised status, and complement component deficiency.ConclusionsIMD incidence is low in the United States, but varies by age, insurance type, and demographic/clinical characteristics. Timely preventative interventions, such as early vaccination, may reduce the incidence, risk, and associated burden of IMD.

IMD IRs: infants 0.45🔥(comm) vs 1.97🔥(Medicaid), toddlers 0.17🔥 vs 0.45🔥, kids 0.11🔥 vs 0.18🔥/100k PY. Highest <4mo: 1.03🔥 & 4.65🔥. Risks↑ in rural, immunocompromised.🦠

1 day ago 0 0 0 0
Fecal Microbiota Transplant and Multidrug-Resistant Organism Decolonization in Gastrointestinal Disease: A Randomized Clinical Trial Importance  Gut colonization by multidrug-resistant organisms (MDROs) is a risk factor for infection with these pathogens. There are no approved therapeutic interventions to combat it.Objective  To assess the efficacy of fecal microbiota transplant (FMT) in causing MDRO decolonization and decreasing antimicrobial resistance (AMR) genes and its impact on gut microbiome, virome, and mycobiome composition in patients with gastrointestinal (GI) diseases.Design, Setting, and Participants  This randomized, double-blind, sham-controlled clinical trial was conducted in a gastroenterology ward and intensive care unit at a tertiary care center in India. Participants were patients with GI diseases with persistent MDRO colonization. Patient recruitment occurred from July 2022 to June 2024, with follow-up completed in July 2024. Data were analyzed from October 1, 2024, to April 25, 2025.Intervention  FMT via colonoscopy or sham intervention (sigmoidoscopy with saline injection).Main Outcomes and Measures  Co–primary outcomes were MDRO decolonization rate and decrease in antimicrobial resistance genes (AMR) at 4 weeks after the intervention. Secondary outcomes included changes in stool microbiome (16S ribosomal RNA amplicon sequencing), virome (viruslike particles shotgun sequencing), and mycobiome (ITS2 sequencing); incidence of MDRO infections; and adverse events within 4 weeks.Results  Of 114 randomized patients (mean [SD] age, 40.6 [12.5] years; 80 [70.2%] male; 52 patients [45.6%] with pancreatitis; 43 patients [37.7%] with cirrhosis; 19 patients [16.7%] with other GI disorders), 58 received FMT and 56 received the sham intervention. Most patients were colonized with carbapenem-resistant Enterobacteriaceae or extended-spectrum β-lactamase–producing Enterobacteriaceae at baseline (55 patients [94.8%] in the FMT group and 56 patients [100%] in the sham group). Five patients (2 in the FMT group, 3 in the sham group) were lost to follow-up. Intention-to-treat analysis showed no significant differences in MDRO decolonization (18 patients [31.0%] in the FMT group vs 17 patients [30.4%] in the sham group; absolute difference, 0.6% [95% CI, −16.2% to 17.6%]; P = .94) or AMR genes (median [IQR], 2.5 [1.2 to 3.0] genes in the FMT group vs 2.0 [1.0 to 3.0] genes in the sham group; P = .68), with comparable adverse events. Among 71 patients who underwent 16S ribosomal RNA gene sequencing at 4 to 6 weeks after the intervention, enrichment of bacteria capable of producing short-chain fatty acids was observed in the FMT group. These microbial alterations were not observed in the sham group. However, viral diversity remained unchanged after FMT. Mycobiome analysis revealed that FMT induced only modest, transient alterations in the gut mycobiome.Conclusions and Relevance  This randomized clinical trial found that while a single session of FMT did not significantly enhance MDRO decolonization or decrease AMR genes in patients with GI diseases, it modulated gut microbiome diversity and composition.Trial Registration  Clinical Trials Registry–India Registration No. 2022/07/043847

RCT on 114 pts w/ GI dx: FMT→31% MDRO decolonization vs 30.4% sham, no AMR gene drop. FMT🦠 ↑SCFA-producers, minor mycobiome change; viral diversity unchanged.

1 day ago 0 0 0 0
Acute Respiratory Failure and Ventilatory Support in Hospitalized Adults With Viral Respiratory Infection: A Retrospective Cohort Study This retrospective cohort study compares the risk and severity of acute respiratory failure (ARF) among adults hospitalized with different respiratory viruses.MethodsWe included 4927 adults admitted to Akershus University Hospital, Norway, from 2012 to 2021 with polymerase chain reaction–confirmed viral infection with influenza A/B, respiratory syncytial virus (RSV), parainfluenza virus (PIV), human metapneumovirus, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ARF was defined as the use of high-flow oxygen, noninvasive ventilation, or mechanical ventilation during the hospital admission. Logistic regression models estimated adjusted probabilities of respiratory failure and ventilatory support, using influenza A/B as the reference, with adjustment for age, sex, National Early Warning Score 2 (NEWS2), weighted Charlson Comorbidity Index, and other covariates.ResultsOverall, 11.8% of patients (n = 583) met the criteria for ARF. Compared with influenza A/B, all other virus groups except human metapneumovirus were associated with a higher adjusted probability of ARF. SARS-CoV-2 showed the highest risk, followed by PIV and RSV (all P < .01). A similar pattern was seen for noninvasive or mechanical ventilation. Sensitivity analyses using alternative comorbidity adjustments or analyzing patients before and after the coronavirus disease 2019 pandemic separately produced consistent relative rankings across virus groups.ConclusionsSARS-CoV-2, PIV, and RSV were associated with increased risk of ARF in hospitalized adults compared with influenza A/B. SARS-CoV-2 strains circulating during the early pandemic showed the greatest risk, while RSV and PIV also conferred a substantial excess ARF risk. These findings underscore the need for clinical vigilance and preventive strategies in patients admitted with viral respiratory tract infections.

Study of 4927 adults showed 11.8% had acute respiratory failure (ARF). SARS-CoV-2 had highest ARF risk, then parainfluenza, RSV; all >flu A/B (P<.01).🦠⚠️

1 day ago 0 0 0 0
Inappropriate antibiotic prescribing for acute respiratory illnesses in outpatient settings in New York City, 2019–2022 View abstract Background:Inappropriate antibiotic prescribing contributes to antibiotic resistance threats. In outpatient settings, antibiotics are often incorrectly prescribed for acute respiratory illnesses (ARI). Characteristics associated with inappropriate antibiotic prescribing at New York City (NYC) outpatient ARI visits were assessed to identify opportunities for interventions.Methods:Using IQVIA’s commercial Medical Claims and Longitudinal Prescription datasets, medical diagnosis codes identified outpatient visits for ARI during 2019–2022, which were linked to antibiotics obtained at a pharmacy (as a proxy for prescribed antibiotics) within 3 days post-visit. Univariate analyses were conducted describing visit, patient, and provider characteristics. Modified Poisson regression with robust error variance was used to calculate unadjusted relative risks (RR) and 95% CI for visit-level characteristics associated with inappropriate prescribing.Results:Among 3,493,444 ARI outpatient visits, 5.1% linked to an inappropriate antibiotic prescription. Among all ARI, bronchitis/bronchiolitis had the highest percentage (25.5% of bronchitis/bronchiolitis visits) and highest risk of inappropriate prescribing relative to asthma/allergy (RR: 18.03; 95% CI: 17.70, 18.38). Adults aged 65–79 years were over twice as likely to be prescribed inappropriate antibiotics relative to children (RR: 2.21; 95% CI: 2.17, 2.25). Inappropriate prescribing was highest in urgent care (8.4%) (RR: 1.25; 95% CI: 1.23, 1.27) relative to offices and among internal medicine physicians (8.0%); relative to these physicians, risk of inappropriate prescribing among all other physician specialties was lower.Conclusions:Inappropriate antibiotic prescribing at ARI outpatient visits was uncommon. Tailoring interventions to providers such as internal medicine physicians or those in urgent care settings may improve prescribing practices.

5.1% of 3.49M NYC ARI visits had inappropriate antibiotics; highest in bronchitis (25.5% 🫁), adults 65-79 (2.2x risk 🧓), urgent care (8.4%) & internal medicine docs.

1 day ago 0 0 0 0
Impact of intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine, dihydroartemisinin-piperaquine, and their combination on infant outcomes: A randomized controlled trial Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) is more effective than sulfadoxine-pyrimethamine (IPTp-SP) at reducing the burden of malaria in pregnancy in settings with high SP resistance. Paradoxically, IPTp-DP has been associated with lower birth weights compared with IPTp-SP. Whether the impacts of IPTp-DP extend after birth is unknown.MethodsWe conducted a double-blind randomized controlled trial to compare malaria burden and growth among infants born to mothers who were randomized to monthly IPTp-SP, IPTp-DP, or IPTp-DP+SP. Infants were followed to 12 months of age by passive and active surveillance. The primary outcome was clinical malaria incidence; secondary outcomes included parasite prevalence by microscopy or quantitative PCR, and infant growth outcomes.ResultsAmong 871 infants enrolled, there were 667 episodes of clinical malaria. Compared to infants whose mothers received IPTp-SP, malaria incidence was similar in infants whose mothers received IPTp-DP (incidence rate ratio [IRR] 1.04, 95% confidence interval (CI) 0.78-1.38) or IPTp-DP+SP (IRR=0.93, 95% CI 0.68-1.26). Overall parasite prevalence at monthly visits was 21.8%. Parasite prevalence was also similar between groups. The prevalence of wasting at birth was higher in infants whose mothers received IPTp-DP+SP (PR= 2.30, 95% CI 1.07, 4.97) or IPTp-DP (RR= 2.25, 95% CI 1.03, 4.94) than those that received IPTp-SP, but differences between groups resolved by 3-6 months of age.ConclusionThere were no significant differences in infant outcomes between the three IPTp arms apart from a transiently increased risk of wasting among infants born to mothers who received DP-containing IPTp regimens.

871 infants: 667 malaria episodes. Malaria incidence similar across IPTp-SP, IPTp-DP, IPTp-DP+SP (IRR ~1). Wasting ↑2.3x at birth with DP regimens, resolved by 3-6 months. 🦟👶📉

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Evaluation of serum antibodies as correlates of protection against norovirus infection and disease Norovirus is a major cause of acute gastroenteritis. Several vaccines are in development. Identifying a reliable immunological correlate of protection (CoP) would aid vaccine development and evaluation; however, no strong CoP has been established to date.MethodsWe evaluated the relationships between pre-challenge GI.1 and GII.4 norovirus antibodies and clinical outcomes in two human vaccine-challenge studies. One study evaluated a monovalent intranasal GI.1 vaccine, and the other evaluated a bivalent intramuscular GI.1/GII.4 vaccine. We analyzed genotype-specific histo-blood group antigen (HBGA) blocking titers, serum IgA and IgG, and total antibody ELISA (Pan-Ig). We used Bayesian logistic regression models to assess relationships between antibody levels and protection against: PCR-confirmed infection (InfProt), vomiting or diarrhea any day post-challenge (VorDProt), and protocol-defined illness (PDIProt). We used Bayesian gamma-poisson models to assess relationships between antibody levels and a modified Vesikari scoring (MVS) scale for disease severity.ResultsAssociations between antibody titers and protection were generally weak, and varied by genotype and vaccination status. GI.1 antibodies showed the strongest relationships, particularly among vaccinated participants, whereas naturally acquired GI.1 antibodies in unvaccinated individuals were weakly or not associated with protection. In contrast, GII.4 antibodies exhibited weak and inconsistent relationships among vaccinated participants, while unvaccinated participants showed only modest and more stable positive associations.ConclusionsCurrently measured serum antibodies do not provide reliable and robust estimates of protection against norovirus clinical outcomes in all settings. Immune markers beyond serum antibody titers should be evaluated to identify more robust correlates of protection for norovirus.

Norovirus vaccines show weak ⬇️ links between antibodies & protection. GI.1 antibodies better predict protection in vaccinated; GII.4 less clear. New immune markers needed.🦠💉

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Multicenter Evaluation of Ceftazidime/Avibactam in Pediatric Patients Across the United States: Real-World Insights into the Management of Drug-Resistant Gram-Negative Infections Antimicrobial resistance among gram-negative pathogens is a global threat, with children particularly vulnerable due to limited treatment options and age-specific clinical outcomes data. Ceftazidime/avibactam (CZA) is effective against resistant gram-negative bacteria and demonstrates high success rates in adults; however, pediatric data remain limited. This study examined CZA use in children across United States medical centers.MethodsThis multicenter, retrospective, observational cohort study included pediatric patients (<18 years) who received ≥48 hours of CZA for suspected or confirmed gram-negative infections between February 2015 and October 2023. The primary outcome was clinical success, defined as occurrence of all 3 components: (1) absence of all-cause mortality within 30 days of CZA initiation, (2) absence of microbiologic and clinical recurrence within 30 days of CZA discontinuation, and (3) resolution or improvement of infection-related signs and symptoms during CZA therapy without modification of therapy due to clinical failure. Secondary outcomes included adverse events attributable to CZA and resistance development to CZA.ResultsOne-hundred patients were included, with most receiving CZA for targeted therapy (67%). The median (IQR) age and weight were 9.8 (1.9–15.9) years and 24.2 (12.2–49.9) kg, respectively. Nearly all patients (88%) had comorbidities, 42% of patients were immunocompromised, and more than half were admitted to the intensive care unit at the time of index infection. Most infections originated from the respiratory tract (50%), followed by primary bloodstream infections (23%). Carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales were identified in 37% and 31% of patients, respectively. The most frequently administered CZA dosage regimen was 50 mg ceftazidime/kg/dose q8 hours, utilized in 44% of cases, with a median (IQR) treatment duration of 10.1 (6.7–15.7) days. Clinical success was achieved in 76% of patients, while no CZA-attributable adverse events were observed. CZA resistance emerged subsequently in 5% of cases.ConclusionsCZA demonstrated favorable outcomes and safety in a diverse pediatric cohort with drug-resistant infections, supporting its role as a viable therapeutic option in high-risk pediatric populations.

CZA used in 100 kids (median age 9.8y) with resistant infections; 76% clinical success, 0% adverse events, 5% resistance; mainly respiratory infections (50%) & ICU cases. 🦠💊✅

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What are patients’ and healthcare professionals’ views on managing penicillin allergy? A qualitative evidence synthesis AbstractObjectivesTo review the existing literature on patients’ and healthcare professionals’ views on managing penicillin allergy and provide an interpretation of the evidence that will inform the development of strategies to increase penicillin allergy evaluation and testing.MethodsWe systematically searched six databases for qualitative or mixed-methods studies reporting patients’ and healthcare professionals’ views on managing penicillin allergy. We followed three stages of thematic synthesis, including line-by-line coding, development of descriptive themes, and development of analytical themes, to analyse and interpret the findings of eligible studies.ResultsWe included 21 papers in the review and using thematic synthesis developed five analytical themes: (i) investigation of penicillin allergy was not a priority; (ii) healthcare systems did not support penicillin allergy assessment; (iii) penicillin allergy assessment required specific training; (iv) uncertainty over responsibility in managing penicillin allergy; and (v) management of penicillin allergy was associated with perception of risk and diagnostic uncertainty.ConclusionsTo increase penicillin allergy assessment and testing, the lack of prioritization of penicillin allergy assessment in clinical practice should be addressed. Education of patients and healthcare professionals should emphasize the benefits of penicillin allergy assessment and explain the risks associated with allergy testing and subsequent use of penicillin. Healthcare systems–related barriers hindering penicillin allergy assessment could be reduced through the redesign of electronic medical records and the revision of antibiotic guidelines. Future research should explore novel models for penicillin allergy assessment services involving different healthcare settings.

Review of 21 studies found penicillin allergy assessment is low priority, lacks training, faces unclear roles, and system barriers. Suggests education📚 & system redesign🖥️ to improve testing.

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Effective Treatment using Bumped Kinase Inhibitor 1708 in a Calf Clinical Model of Cryptosporidiosis AbstractCryptosporidium parvum, an apicomplexan parasite and the causative agent of cryptosporidiosis, contributes to a high burden in mortality and morbidity for humans and livestock. Currently, there are no reliably successful parasite-specific treatments for the debilitating diarrhea associated with the infection. Bumped kinase inhibitors (BKIs), which selectively target parasite calcium-dependent protein kinases (CDPKs), have been shown to decrease infections caused by several medical and veterinary-relevant parasites, including Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum. In the present study, various dosing regimens of BKI-1708 were evaluated for safety and clinical efficacy in the calf model for cryptosporidiosis, specifically with the aim of finding a minimum effective dose. The majority of the different BKI dosages produced notable improvements across nearly all clinical and parasitological measures, including diarrhea severity, oocyst shedding, and overall health status. These results provide strong evidence for advancing BKI-1708 as a preclinical candidate for treatment of cryptosporidiosis.

Cryptosporidium parvum causes severe diarrhea; no specific treatments exist. BKI-1708 reduced symptoms and oocyst shedding in calves, showing promise as a treatment.🦠🐄💊

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Correlation between antimicrobial susceptibility data and clinical efficacy for Helicobacter cinaedi bacteraemia Helicobacter cinaedi is the most common species of enterohepatic Helicobacter reported to cause bloodstream infections in humans. The establishment of effective treatment strategies for H. cinaedi bacteraemia is required, since the association between in vitro susceptibility and clinical response has yet to be demonstrated.MethodsThe medical records of all patients diagnosed with H. cinaedi bacteraemia at two Japanese hospitals between March 2009 and December 2016 were retrospectively reviewed. We investigated the antimicrobial susceptibility of H. cinaedi using the broth microdilution method and assessed the clinical efficacy of treatment regimens for H. cinaedi bacteraemia.ResultsWe evaluated the data of 131 patients with first-episode H. cinaedi bacteraemia for which MIC data were available for the causative strains. Carbapenems (imipenem and meropenem), aminoglycosides (gentamicin and kanamycin), tetracycline and chloramphenicol exhibited lower MIC values. Fluoroquinolones, especially ciprofloxacin and levofloxacin, demonstrated higher MIC values. Penicillins and cephalosporins showed a wide range of MIC values, from low to high. The MIC50 and MIC90 of amoxicillin were 4 mg/L and 8 mg/L, respectively. Treatment was successful in 42 of 45 patients (93.3%) who received intravenous β-lactam followed by oral amoxicillin switching therapy or amoxicillin monotherapy. Treatment failed in four of eight patients (50%) in the fluoroquinolone monotherapy group.ConclusionsBased on our MIC and clinical data, intravenous β-lactam-to-oral amoxicillin switching therapy or amoxicillin monotherapy may be a recommended option, whereas levofloxacin therapy is suboptimal and should be avoided.

131 H. cinaedi cases studied; β-lactam + oral amoxicillin had 93.3% success✅; fluoroquinolone failed 50%❌. Recommend β-lactam/amoxicillin; avoid levofloxacin.

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Qualitative assessment of antibiotic stewardship teams’ efforts to perform prospective audit-and-feedback at hospital discharge View abstract Objective:How antibiotic stewardship programs can effectively reduce antibiotic overuse at hospital discharge is unclear. In this study, we assessed barriers and facilitators to performing prospective audit-and-feedback at this transition of care.Design:A qualitative study using semi-structured interviews.Setting:Ten acute-care hospitals participating in a stepped-wedge cluster-randomized trial, including three Veteran’s Health Administration hospitals, two academic medical centers and five community hospitalsParticipants:Fourteen antimicrobial stewards in participating hospitals across the United States.Methods (or Interventions):A semi-structured interview guide was created applying the RE-AIM framework to focus on perceptions of implementing the intervention. All interviews were audio recorded, transcribed, and coded in a three-person team. Using thematic analysis, codes were developed and collapsed into themes.Results:Half of the intervention sites struggled to identify patients at discharge, limiting the stewardship teams’ ability to conduct prospective audit-and-feedback at discharge. In contrast, strong provider–stewardship relationships and existing hospital initiatives, such as handshake stewardship and discharge planning meetings, facilitated implementation. Stewardship teams at four sites also reported not needing to guide antibiotic use for patients with Infectious Disease (ID) consults, as they agreed with the documented recommendations from the ID specialists.Conclusions:Our findings underscore the importance of accounting for the hospital and organizational context when implementing discharge-focused audit-and-feedback interventions, paying particular attention to existing policies, procedures, and the dynamics between antibiotic stewardship teams and front-line prescribers.

Study: 14 stewards at 10 US hospitals. 50% struggled to ID discharge pts for audit-feedback. Strong provider ties & existing initiatives aided success. ID consults eased guidance. 🏥🔍💊

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The changing epidemiology and long-term outcomes of patients with CRE infections View abstract Background:The impact of organism species and underlying comorbidities on long-term clinical outcomes for patients with carbapenem-resistant Enterobacterales (CRE) infections is unknown.Methods:Patients with CRE-positive cultures from 2011 to 2019 were monitored for 1-year. Patients without signs of infection were categorized as colonization. Recurrent cases were defined as isolation of the same CRE species >90 days after the index case.Results:720 patients met inclusion criteria and accounted for 749 index cases, which decreased over time. The median (range) age was 61 (20–97) years, 53% (397/749) were male, 20% (151/749) received solid organ transplant (SOT), and 44% resided in the ICU at the time of CRE isolation. The colonization rate was 34% (257/749). Pneumonia and bacteremia represented the most common infection types accounting for 25% (185/749) and 13% (95/749) of all cases, respectively. Klebsiella pneumoniae was most common pathogen (58%), followed by Enterobacter cloacae complex (23%), and Escherichia coli (10%). Of the 554 sequenced isolates, 35% (195/554) were KPC-2, 32% (175/554) KPC-3, and 32% (177/554) non-KPC-producing. This changed over time where KPC-2-producing CRE were most prevalent in 2011, KPC-3 most prevalent between 2015–2017, and non-KPC from 2018–2019. Among 90-day survivors, the CRE recurrence rate was 21% (108/513). Charlson comorbidity index (OR: 1.11; 95% CI: 1.05–1.18; P < .001), isolation of a prior CR pathogen (OR: 2.49; 95% CI 1.32–4.72; P = .005), and ICU admission (OR: 3.35; 95% CI 2.14–5.24; P < .001) were independently associated with 90-day mortality, while SOT was associated with lower 90-day mortality (OR: 0.55; 95% CI 0.32–0.94; P = .029). Overall, 90-day mortality rates were lower among patients with CRE-positive cultures between years 2016 – 2019 (24% [63/262]) compared to years 2011 – 2015 (35.5% [173/487]; P = .001).Conclusion:CRE are increasingly diverse and associated with significant morbidity and healthcare utilization across varying patient groups. Long-term survival of patients infected with CRE has improved over time while overall incidence of CRE has decreased.

720 pts w/749 CRE cases (34% colonization). K. pneumoniae 58%, pneumonia 25%. 90-day death 24% (2016-19) ↓ from 35.5% (2011-15). CRE recurrence 21%. ICU ↑death (OR3.35).📉

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Cryptosporidium parvum outbreak among volunteers of a licensed wildlife rehabilitation center housing raccoons—2024 AbstractZoonotic transmission of Cryptosporidium parvum (C. parvum) is often associated with ruminants. We report an investigation of cryptosporidiosis among persons who had contact with raccoons. In July 2024, two states identified 18 human cryptosporidiosis cases who volunteered at the same animal facility. One human specimen and two raccoon specimens tested positive for C. parvum. Molecular subtyping of the C. parvum (subtype IIaA15G2R1) suggested zoonotic transmission between raccoons, humans, or their shared environments. These findings can inform public health actions, developed in collaboration with specific populations (e.g., wildlife rehabilitation facilities) and include interventions tailored to such settings to mitigate future outbreaks.

🦠18 cryptosporidiosis cases in 2 states linked to raccoon contact. C. parvum subtype IIaA15G2R1 found in 1 human & 2 raccoons, suggesting zoonotic spread.

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Maternal cytomegalovirus serology results by geographic region in a large multicenter United States study AbstractCongenital cytomegalovirus (CMV) infection, due to both nonprimary and primary maternal infection, affects nearly 1% of neonates. In conducting a randomized trial of hyperimmune globulin for prevention of congenital CMV infection, we screened over 200,000 pregnancies across the United States for evidence of prior or primary CMV infection and evaluated their geographic variation. Although the majority were seropositive, seroprevalence and primary infection risk varied significantly by geographic region, with seroprevalence the highest (88%) and primary infection (0.2%) the lowest in the Southwest. This variation in seroprevalence by geography may inform planning of public health measures to decrease congenital CMV.

CMV👶 affects ~1% neonates. Screening 200k+ US pregnancies found 88% seropositive in Southwest, with lowest 0.2% primary infection. Geography impacts CMV risk.🌍

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Bacterial dysbiosis, cervicovaginal human papillomaviruses and inflammation persist in women living with HIV-1 after a year of antiretroviral treatment The cervicovaginal microbiome may affect HIV-1 susceptibility and can in turn influence the prevalence and clinical course of HIV-1 and other sexually transmitted diseases. As the determinants, immunological correlates and clinical effects of the dysbiosis observed in women living with HIV-1 (WWH) remain elusive, we evaluated the vaginal immunologic milieu, cervicovaginal microbiome and prevalence of human papillomaviruses (HPV) in antiretroviral-naïve WWH over their first year of antiretroviral therapy (ART).Methods83 ART-naïve Ugandan WWH were enrolled in a longitudinal observational trial. Clinical evaluation and sampling of cervicovaginal secretions and plasma were performed at 0, 8, 24 and 52 weeks post-ART initiation. Amplification of the 16S-rRNA gene V3–V4 region was used to determine the cervicovaginal microbiome. A multiplex bead-array assay was used to quantify the concentration of biomarkers while a PCR-based hybridization assay was utilized for HPV detection and genotyping.ResultsGardnerella was the most abundant genus with a median relative abundance of 35% before ART maintaining a high prevalence throughout the study. Vaginal bacterial diversity did not change after ART, although the relative abundance of some genera, including the bacterial-vaginosis-associated bacteria Peptostreptococcus and Prevotella, decreased compared to baseline. Inflammatory biomarkers remained elevated in the cervicovaginal compartment despite prompt decreases in plasma.The prevalence of high and low-risk HPV types remained stable despite ART.ConclusionsSuppression of HIV-1 replication is not sufficient to revert dysbiotic changes, proinflammatory immunological milieu and persistent HPV infections. Exploration of targeted strategies to restore cervicovaginal mucosal immunological functions in WWH is warranted.

ART in 83 Ugandan WWH didn't reduce Gardnerella (35%) or vaginal diversity. Inflammation stayed high; HPV types stable. HIV suppression ≠ microbiome or HPV restoration.🦠🔥 #HIV

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Renal and Cardiovascular Complications Following Type 2 Diabetes Mellitus in People With and Without HIV: Data from Cohort Study on Morbidity and HIV in Sweden (COSMOHS) between 2010-2024 Type 2 diabetes mellitus (T2DM) is common among people with HIV (PWH), although studies comparing T2DM-related complications in people with and without HIV (PWoH) remain limited. This was assessed using data from the Cohort Study on Morbidity and HIV in Sweden (COSMOHS).MethodNationwide study including Swedish residents born 1930–2006, diagnosed with T2DM between 2010 and 2019, followed until 2024-12-31, utilizing seven national registers including national HIV and diabetes registers. Follow-up began at T2DM diagnosis. Outcomes included renal events, cardiovascular events, and all-cause mortality. Cox proportional regression estimated hazard ratios (adjHR) by HIV status, stratified by propensity score quintiles of age, sex, migrant status, comorbidities, and socioeconomics.Results350 PWH and 311 668 PWoH were included, with similar median follow-up time (PWH: 7.8y, PWoH: 8.8y). PWH had higher renal risk compared to PWoH (major adverse kidney event: adjHR 2.04 95% CI 1.57-2.65) but no significantly increased risk of cardiovascular events (major adverse cardiovascular event: adjHR 1.18, 95% CI 0.87-1.60) or all-cause mortality. Findings were consistent across sensitivity analyses, including competing-risk models for death and excluding PWH receiving tenofovir disoproxil fumarate at baseline. Accounting for the benign P/S-creatinine increase associated with bictegravir, cobicistat, dolutegravir, and rilpivirine, the increased renal risk remained although not statistically significant. The renal risk was most prominent in PWH with BMI ≥30 kg/m2.ConclusionIn this nationwide cohort, PWH with T2DM exhibited higher risk of renal complications than PWoH, indicating enhanced renal monitoring may be warranted. Further research should investigate underlying mechanisms, including antiretroviral therapy, to guide clinical management.

Study: 350 PWH vs 311,668 PWoH w/ T2DM. PWH had 2.04x⬆️ renal risk, no⬆️CV events/mortality. Risk highest if BMI≥30. Suggests more renal monitoring for PWH.🩺

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Long-Term Neurocognitive Outcomes After Severe Malaria Infection: No Peace of MIND In 1948, Salil Ghosh wrote of the near-miraculous recovery of several children with severe “malignant malaria” who had been treated with quinine.1 One illustrative patient, a “girl aged 9 years,” was admitted with 2 days of “unconsciousness with delirium” and found to have “rings plenty,” the classic finding of blood-stage Plasmodium falciparum infection seen on peripheral blood smear. Following administration of intramuscular, and then oral, quinine, the patient “went home in perfect health.” Today, malaria remains a leading cause of global morbidity and mortality, with an estimated 282 million cases and more than 600 000 deaths in 2024.2 The burden is concentrated in the World Health Organization’s Africa Region, which accounted for 94% of all malaria cases and 95% of malaria deaths in 2024. Malaria disproportionally affects children younger than 5 years, who account for more than three-fourths of all global deaths. During the past few decades, the widespread availability of artemisinin-based antimalarial drugs has significantly improved outcomes in acute malaria infection. For severe malaria, intravenous artesunate reduces the risk of mortality by about 24% compared with quinine, the previous standard of care.3 These medicines, along with malaria vaccines and insecticide-treated nets, are estimated to have averted more than 14 million deaths between 2000 and 2024.2 For decades, the dramatic recoveries following quinine (and later artemisinin-based therapies) observed by Ghosh and others reinforced a “common dogma”: that those surviving severe malaria infections made a full and uneventful recovery.4,5 However, it is now recognized that the consequences of malaria extend well beyond hospital discharge. Children with severe malaria are at higher risk of repeat hospitalization and mortality in the months after initial hospitalization.6,7 Acute kidney injury during infection can progress to chronic kidney disease.8 Two forms of severe malaria—cerebral malaria and severe malarial anemia—have also been associated with neurocognitive impairment in young children 1 to 2 years after infection.9 In this issue of JAMA, Bangirana and colleagues10 report results from the Malarial Impact on Neurobehavioral Development (MIND) study, which assessed long-term neurocognitive and academic outcomes among children with prior episodes of severe malaria. This study, conducted at 2 clinical sites in Uganda, included participants enrolled in 2 prior prospective studies of severe malaria conducted between 2008 and 2018. The first of these 2 cohorts enrolled children aged 18 months to 12 years at initial enrollment with cerebral malaria or severe malaria anemia, and the second cohort included children aged 6 months to 4 years at initial enrollment with 1 of 5 common forms of severe malaria (cerebral malaria, severe malaria anemia, respiratory distress, complicated seizures, or prostration). For both cohorts, community children without malaria were included as controls. For the MIND study, the primary outcomes were long-term effects on overall cognition, attention, reading, and math skills, all measured using validated assessment tools. In total, 939 participants were successfully identified and enrolled in the MIND study, representing 75% of participants from the 2 parent studies. This, in itself, is an incredible feat, given that some participants had originally been enrolled 15 years prior. For the entire MIND study population, participants were tested an average of 8.4 years (range, 4-15 years) after the initial enrollment episode of severe malaria. In the current study, the authors found that children with cerebral malaria or severe malaria anemia had lower overall cognitive ability scores and math achievement scores compared with community controls at long-term follow-up. No differences were observed in attention or reading scores between children with cerebral malaria and severe malaria anemia. These findings align with those from prior studies that showed cognitive impairment 1 to 2 years after infection. However, this new evidence suggests that this impairment may unfortunately persist for many years after an episode of severe malaria. Severe malaria infection is defined by the presence of 1 or more clinical features or laboratory findings, including impaired consciousness (in cerebral malaria), severe anemia (in severe malaria anemia), hyperparasitemia, acute kidney injury, respiratory distress, multiple convulsions, prostration, acidosis, shock, or bleeding. The presence of any of these findings indicates more severe disease and a higher risk of mortality. Using the second MIND cohort, the authors examined if other common forms of severe malaria—respiratory distress, complicated seizures, or prostration—were associated with long-term neurocognitive impairment. They observed no long-term differences between cognitive or academic outcomes for children with these severe malaria phenotypes when compared with community controls. Together, these findings suggest that the long-term cognitive impairment associated with cerebral malaria or severe malaria anemia is not simply related to severe illness or prolonged hospitalization. Rather, there appears to be something distinct about the pathophysiology of cerebral malaria and severe malaria anemia that contributes to longer-term cognitive decline. In P falciparum malaria, the parasite modifies the plasma membrane of its host cell with sticky, parasite-produced proteins that mediate adherence to vascular endothelium. Adherence of infected erythrocytes to the cerebral microvasculature is a key feature of cerebral malaria, causing an inflammatory cascade that results in blood-brain barrier dysfunction, cerebral edema, and ultimately, herniation (in fatal cases).11,12 Severe malaria anemia is complex and multifactorial. Erythrocyte turnover increases—in both infected and uninfected cells—even as production drops; however, vascular adherence and sequestration remain common features in severe malaria anemia, as they are in cerebral malaria.13 Substantial heterogeneity exists in the presentation and outcomes of individuals with cerebral malaria and severe malaria anemia. The authors also examined whether specific risk factors or biomarkers might predict long-term cognitive impairment. The presence of acute kidney injury, hyperuricemia, or elevated levels of angiopoietin-2 at the time of initial infection were associated with lower overall cognitive ability at the time of follow-up. Because angiopoietin-2 is a marker and potential driver of both endovascular injury and decreased blood-brain barrier integrity, this finding hints at a possible mechanism for how cerebral malaria and severe malaria anemia might compromise long-term cognition.14 For cerebral malaria, elevated levels of plasma tau, a marker of acute brain injury, at the time of initial infection was associated with long-term cognitive impairment, as was the presence of continued neurologic deficits, such as abnormal gait, aphasia, paresis, or impaired hearing or vision, 6 to 12 months after discharge. Cognitive scores at 12 months were associated with long-term cognitive impairment, both for patients with cerebral malaria and for those with severe malaria anemia, suggesting that early assessments could help predict future outcomes. The study by Bangirana and colleagues10 does have limitations. The study was conducted in a single country, and additional studies in other locations are necessary to determine how factors such as malaria transmission intensity or seasonality might affect generalizability. While many children (75%) from the initial studies were identified and reenrolled, loss to follow-up may have influenced the observed results. Last, given the prospective, descriptive study design, it is not possible to infer a causal relationship between severe malaria infection and future cognitive performance. Despite limitations, the demonstrated association of long-term cognitive impairment with cerebral malaria and severe malaria anemia highlights the urgent need to identify therapies to prevent or ameliorate these effects. Postdischarge malaria chemoprevention has been shown to decrease rates of readmission and death.15 It will be important to examine if these measures also improve cognitive outcomes. Importantly, studies have also shown that cognitive rehabilitation training can improve short-term cognitive outcomes in patients with severe malaria.16 Additional studies are necessary to determine if the benefits of cognitive rehabilitation persist over time and if specific modalities yield better long-term outcomes. Examining the underlying pathophysiology of long-term cognitive impairment in cerebral malaria and severe malaria anemia may help identify additional adjunctive therapies. Additional studies will help clarify whether hyperuricemia or elevations in angiopoietin-2 levels are drivers of cognitive impairment or simply markers of more severe malaria disease. Manipulation of endothelial angiopoietin signaling has become an attractive therapeutic target for cancer and other conditions, with multiple monoclonal antibodies and small molecule inhibitors in development.17 If elevations of angiopoietin-2 levels reflect a pathogenic role in severe malaria, adjunctive therapies at the time of acute infection might prove to be of benefit. Cognitive impairment has also been observed in pediatric and neonatal sepsis, and future studies should examine whether these effects occur through a common mechanism.18,19 Studies such as these will be critical in providing more comprehensive care for patients with severe malaria, with a focus on both decreasing mortality as well as improving long-term quality of life. Over the last 2 decades, substantial progress has been made in preventing infections and death due to malaria. Today, these gains are threatened by cuts to global aid and global health research. The findings of the MIND study are a poignant reminder that the burden of malaria extends far beyond the acute infection and reinforce the importance of continued investment in malaria elimination. Back to top Article Information Corresponding Author: Audrey R. Odom John, MD, PhD, Department of Pediatrics, Division of Infectious Diseases, Children’s Hospital of Philadelphia, 3501 Civic Center Blvd, 10006 CTRB, Philadelphia, PA 19104 (johna3@chop.edu).Published Online: April 18, 2026. doi:10.1001/jama.2026.4290Conflict of Interest Disclosures: Dr Sundararaman reported receiving grants from the National Institutes of Health, Thrasher Research Foundation, Pediatric Infectious Diseases Society, and St Jude Children’s Research Hospital outside the submitted work. Dr Odom John reported holding a patent (issued, no license) for malaria biomarkers. References 1.Ghosh  S.  A few interesting cases of malignant malaria.   Indian J Pediatr. 1948;15(1):17-21. doi:10.1007/BF02823129Google ScholarCrossref2.World Health Organization. World Malaria Report 2025. Published 2025. Accessed February 24, 2026. https://www.who.int/publications/i/item/97892400648983.Nyaaba  N, Andoh  NE, Amoh  G,  et al.  Comparative efficacy and safety of the artemisinin derivatives compared to quinine for treating severe malaria in children and adults: a systematic update of literature and network meta-analysis.   PLoS One. 2022;17(7):e0269391. doi:10.1371/journal.pone.0269391PubMedGoogle ScholarCrossref4.Phillips  RE, Solomon  T.  Cerebral malaria in children.   Lancet. 1990;336(8727):1355-1360. doi:10.1016/0140-6736(90)92903-UPubMedGoogle ScholarCrossref5.Programme  WHOMA; World Health Organization Malaria Action Programme.  Severe and complicated malaria.   Trans R Soc Trop Med Hyg. 1986;80(suppl):3-50. doi:10.1016/0035-9203(86)90407-4PubMedGoogle ScholarCrossref6.Opoka  RO, Namazzi  R, Datta  D,  et al.  Severe falciparum malaria in young children is associated with an increased risk of post-discharge hospitalization: a prospective cohort study.   Malar J. 2024;23(1):367. doi:10.1186/s12936-024-05196-3PubMedGoogle ScholarCrossref7.Phiri  KS, Calis  JCJ, Faragher  B,  et al.  Long term outcome of severe anaemia in Malawian children.   PLoS One. 2008;3(8):e2903. doi:10.1371/journal.pone.0002903PubMedGoogle ScholarCrossref8.Conroy  AL, Opoka  RO, Bangirana  P,  et al.  Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria.   BMC Med. 2019;17(1):98. doi:10.1186/s12916-019-1332-7PubMedGoogle ScholarCrossref9.Bangirana  P, Bond  C, Namazzi  R,  et al.  Cerebral malaria and severe malarial anemia, but not other forms of severe malaria, are associated with long-term cognitive impairment.   Clin Infect Dis. Published online February 3, 2026. doi:10.1093/cid/ciaf712PubMedGoogle ScholarCrossref10.Bangirana  P, Mellencamp  KA, Ren  J,  et al.  Long-term cognitive ability and academic achievement after childhood severe malaria.   JAMA. Published online April 18, 2026. doi:10.1001/jama.2026.0704ArticleGoogle Scholar11.Idro  R, Marsh  K, John  CC, Newton  CR.  Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome.   Pediatr Res. 2010;68(4):267-274. doi:10.1203/PDR.0b013e3181eee738PubMedGoogle ScholarCrossref12.Seydel  KB, Kampondeni  SD, Valim  C,  et al.  Brain swelling and death in children with cerebral malaria.   N Engl J Med. 2015;372(12):1126-1137. doi:10.1056/NEJMoa1400116PubMedGoogle ScholarCrossref13.Dalimot  JJ, Klei  TRL, Beuger  BM,  et al.  Malaria-associated adhesion molecule activation facilitates the destruction of uninfected red blood cells.   Blood Adv. 2022;6(21):5798-5810. doi:10.1182/bloodadvances.2021006171PubMedGoogle ScholarCrossref14.Lee  E, Kim  S, Zhu  CL,  et al.  Angiopoietin-2 aggravates Alzheimer’s disease by promoting blood-brain barrier dysfunction and neuroinflammation.   Cell Rep. 2026;45(1):116621. doi:10.1016/j.celrep.2025.116621PubMedGoogle ScholarCrossref15.Phiri  K, Esan  M, van Hensbroek  MB, Khairallah  C, Faragher  B, ter Kuile  FO.  Intermittent preventive therapy for malaria with monthly artemether-lumefantrine for the post-discharge management of severe anaemia in children aged 4-59 months in southern Malawi: a multicentre, randomised, placebo-controlled trial.   Lancet Infect Dis. 2012;12(3):191-200. doi:10.1016/S1473-3099(11)70320-6PubMedGoogle ScholarCrossref16.Boivin  MJ, Nakasujja  N, Sikorskii  A,  et al.  Neuropsychological benefits of computerized cognitive rehabilitation training in Ugandan children surviving severe malaria: a randomized controlled trial.   Brain Res Bull. 2019;145:117-128. doi:10.1016/j.brainresbull.2018.03.002PubMedGoogle ScholarCrossref17.Saharinen  P, Eklund  L, Alitalo  K.  Therapeutic targeting of the angiopoietin-TIE pathway.   Nat Rev Drug Discov. 2017;16(9):635-661. doi:10.1038/nrd.2016.278PubMedGoogle ScholarCrossref18.Ong  WJ, Seng  JJB, Yap  B,  et al.  Impact of neonatal sepsis on neurocognitive outcomes: a systematic review and meta-analysis.   BMC Pediatr. 2024;24(1):505. doi:10.1186/s12887-024-04977-8PubMedGoogle ScholarCrossref19.Als  LC, Nadel  S, Cooper  M, Pierce  CM, Sahakian  BJ, Garralda  ME.  Neuropsychologic function three to six months following admission to the PICU with meningoencephalitis, sepsis, and other disorders: a prospective study of school-aged children.   Crit Care Med. 2013;41(4):1094-1103. doi:10.1097/CCM.0b013e318275d032PubMedGoogle ScholarCrossref

🦟Malaria caused 282M cases & 600K+ deaths in 2024, 94% in Africa; kids <5y = 75% deaths. Cerebral malaria & severe anemia linked to ↓ cognition 📉 math scores, lasting 8.4y avg. vs controls.

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Pharmacokinetics of Dalbavancin in Complicated Staphylococcus aureus Bacteremia: A Secondary Analysis of the DOTS Randomized Clinical Trial Importance  Dalbavancin is an alternative to prolonged intravenous therapy for complicated Staphylococcus aureus bacteremia, yet its pharmacokinetics (PK) in patients with this condition are uncertain.Objective  To characterize dalbavancin PK and evaluate associations of total and unbound exposures of dalbavancin with clinical success in patients with complicated S aureus bacteremia.Design, Setting, and Participants  This study was an exploratory prespecified secondary analysis of PK and exposure response within Dalbavancin as an Option for Treatment of S aureus Bacteremia (DOTS), a multicenter, randomized, open-label, assessor-blinded clinical trial conducted from April 2021 to December 2023. Data analysis was conducted from January 2024 to December 2025. Adults with complicated S aureus bacteremia who achieved bloodstream clearance were randomized to dalbavancin or standard therapy; PK analyses included dalbavancin recipients with at least 1 postdose concentration measurement.Intervention  Dalbavancin 1500 mg intravenously on days 1 and 8 (1125 mg for patients with severe kidney impairment not receiving dialysis).Main Outcomes and Measures  Individual exposure metrics, including day 22 concentration and area under the concentration-time curve (AUC) from days 0 to 22, were derived using nonlinear mixed-effects population PK modeling. Exposure metrics were then assessed for association with clinical success at day 70 (exposure-response analysis).Results  A total of 97 patients (mean [SD] age, 54.5 [15.8] years; 69 male [71.1%]) contributing 640 PK samples were included. Clearance was estimated at 0.066 L/h (95% CI, 0.062 to 0.069 L/h), and the central volume of distribution was estimated at 5.67 L (95% CI, 5.37 to 5.99 L). Interindividual variability was 22.6% (95% CI, 18.9% to 25.6%) for clearance and 19.7% (95% CI, 13.8% to 25.0%) for the central volume of distribution. Clearance increased with creatinine clearance according to a power function (exponent, 0.21; 95% CI, 0.16 to 0.30). Distribution volumes increased with body weight following power relationships, including the central volume (exponent, 0.57; 95% CI, 0.37 to 0.86), second peripheral volume (0.82; 95% CI, 0.37 to 1.46), and third peripheral volume (0.56; 95% CI, 0.30 to 0.82). Albumin was inversely associated with the second peripheral volume (exponent, −0.81; 95% CI, −1.79 to −0.32) and unbound-fraction scaling factor (exponent, −0.78; 95% CI, −0.98 to −0.54), and age was positively associated with the third peripheral volume via a power relationship (exponent, 0.63; 95% CI, 0.44 to 0.83). Among 93 evaluable patients, 72 individuals (77.4%) achieved clinical success at day 70. Patients with a day 22 concentration greater than 32 μg/mL (30 patients [32.3% of evaluable patients receiving dalbavancin]) had higher clinical success compared with 63 patients with a day 22 concentration of 32 μg/mL or less (29 patients [96.7%] vs 43 patients [68.3%]; adjusted difference, 25.3 percentage points; 95% CI, 3.5-47.0 percentage points) and experienced similar rates of serious adverse events (8 patients [26.7%] vs 27 patients [42.9%]; unadjusted difference, −16.2 percentage points, 95% CI −36.2 to 3.8 percentage points).Conclusions and Relevance  In this study, dalbavancin pharmacokinetics were predictably influenced by kidney function, body weight, albumin levels, and age, and higher total day 22 concentrations were associated with greater clinical success without increased serious adverse events. These findings are exploratory and support further evaluation of exposure-guided dosing strategies.Trial Registration  Clinical Trials.gov Identifier: NCT04775953

Dalbavancin PK in 97 pts showed clearance 0.066 L/h; 77.4% clinical success at day 70. Day 22 conc >32 μg/mL linked to 96.7% success vs 68.3% 🩺💊

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A Multinational Trial of Rapid Antimicrobial Susceptibility Testing: Is FASTer Better? Selecting the right antibiotic to treat an infection is the cornerstone of effective antibacterial therapy and lifesaving in severe infections.1 The growing epidemic of antimicrobial resistance is making decisions about empiric treatment increasingly difficult and elevating the importance of having pathogen susceptibility data.2 Unfortunately, the time to get this vital information remains agonizingly long. In most microbiology laboratories, organisms must be grown and then tested after isolation from blood culture samples, a process that usually takes more than 24 hours. While awaiting this crucial information, clinicians are faced with a difficult dilemma: choose potentially excessively broad-spectrum antibiotics and risk potentially preventable adverse events or risk ineffective therapy. In nearly all cases, clinicians will choose the former, helping fuel the downward spiral of antimicrobial resistance because broad-spectrum antibiotics increase the selective pressure for resistant organisms, which, in turn, require even broader-spectrum antibiotics. Faster results on antibiotic susceptibility could provide at least a partial off-ramp. Knowing the right antibiotic in hours, rather than days, would allow clinicians to optimize therapy earlier in the treatment course, perhaps in time to change outcomes for the better. Fortunately, the technology to make this possible is not science fiction. Rapid susceptibility testing systems are commercially available and have been associated with lower lengths of stay and even mortality reductions in some studies.3 However, that literature has been challenging to interpret. The evidence for shorter length of stay and mortality benefits has come mostly from observational studies. Prospective trials have shown benefits in decreased time to optimal therapy, but not mortality or length of stay, although all have been conducted in settings with low rates of antibiotic resistance. Against this backdrop, we now have the results of the Fast Antimicrobial Susceptibility Testing for Gram-Negative Bacteremia Trial (FAST) published in this issue of JAMA.3 In a multinational randomized clinical trial, Banerjee and colleagues evaluated whether rapid antimicrobial susceptibility testing (AST) performed directly from positive blood culture bottles improves clinical outcomes for gram-negative bacteremia compared with standard AST methods. The FAST trial included 850 hospitalized adults and children across 7 centers in Greece, India, Israel, and Spain. Cephalosporin or carbapenem resistance was detected in 44% of patients overall. Participants were randomized to undergo either rapid AST using the VITEK REVEAL system plus standard AST or standard AST alone. All patients were evaluated by local antimicrobial stewardship programs, which issued treatment recommendations based on initial Gram stain results, organism identification, and susceptibility findings. The trial’s primary end point—the desirability of outcome ranking (DOOR) at day 30—integrated mortality, clinical response, discharge outcomes, and deleterious events, such as kidney failure or acquisition of multidrug-resistant organisms. The DOOR methodology has been used in many of the trials run by the National Institutes of Health–funded Antibacterial Resistance Leadership Group, and its strengths and limitations have been described elsewhere.4 The authors also examined several secondary outcomes and explored outcomes in the subsets of patients with cephalosporin- and carbapenem-resistant infections. Rapid AST did not achieve superiority over standard AST. The probability that a patient in the rapid testing group would have a more desirable DOOR outcome than a patient in the standard group was 48.8% (95% CI, 45.3%-52.4%), narrowly failing to exceed the prespecified 50% threshold for superiority. However, rapid AST was associated with important benefits in duration of hospitalization. Although overall length of stay was similar between the rapid and standard AST groups, the percentage of patients who remained hospitalized at 30 days post enrollment was 4% lower in the rapid than standard AST group and this difference increased to 13% among patients with carbapenem-resistant infections. Likewise, the median number of days hospitalized after enrollment was 3 days shorter in patients with cephalosporin-resistant infections. There were also important process of care benefits in the group randomized to undergo rapid AST. Patients undergoing rapid AST had significantly shorter time to first antibiotic modification, with a median of 22 hours compared with 36 hours in the standard group. This advantage was magnified among patients with cephalosporin- or carbapenem-resistant infections, where antibiotic changes were made 23 and 29 hours faster, respectively. Additionally, and perhaps most important, in patients receiving undertreatment, rapid AST led to antibiotic escalation a full 24 hours earlier than standard AST. The FAST trial presents the same interpretation conundrum as some of the other trials of rapid AST: if patients were given proper therapy faster, why were there not clearer benefits related to mortality and length of stay? This could partly be a sample size challenge. One would expect to see a mortality benefit from rapid AST primarily in the subset of patients who had severe infections, such as sepsis, who were also receiving ineffective empiric therapy. Despite the size of the FAST trial, only approximately one-quarter of patients had septic shock. Additionally, despite the high rates of resistance, more than 60% of patients were already receiving effective antibiotics when they were enrolled. It is likely that the subset of patients with septic shock and receiving ineffective therapy enrolled in the FAST trial was too small to assess outcome differences between rapid and standard AST. Attempting to conduct a study that enrolled only patients with septic shock and receiving ineffective empiric therapy would require an enrollment size that is likely well beyond what could be realistically supported with current research resources. The authors also point out that in some cases, the optimal antibiotic was not available because of various access issues, such as a national shortage of aztreonam in Greece during the study. Rapid AST would obviously have had no benefit in cases where the agent identified by the test was not available to the patient. Issues with access to effective antibiotics, especially newer agents, remain an important challenge in resource-limited settings.5 Unlike previous rapid AST trials, the FAST study did show some important benefits in duration of hospitalization, especially among patients with resistant infections. It appears that the length of stay benefits occurred primarily in patients with long durations of hospitalization; for example, patients still hospitalized 30 days after enrollment. Considering this finding, it was interesting to see the major difference in antibiotic deescalation. Among patients receiving unnecessarily broad-spectrum antibiotics, the median time to deescalation was faster in the rapid testing group because less than 50% of patients in the standard group underwent any deescalation. Studies have shown important benefits to deescalation that can reduce the risk of prolonged hospitalization, including reduced risks of acute kidney injury6 and development of antibiotic resistance.7 Banerjee and colleagues should be commended for undertaking this challenging study, which was not only evaluating a rare outcome, but also posed substantial implementation challenges regarding workflow. It would have been interesting to see details on the cost differences between rapid and standard AST, but these might not have been available because the technology was implemented as part of a trial. In US hospitals, the added costs of adopting rapid AST could be at least partially offset by New Technology Add-On Payments from the Centers for Medicare & Medicaid Services, for which the system studied in the FAST trial does appear to qualify.8 Additionally, as with most new technologies, it is likely that the price will drop over time. The FAST trial should move hospitals firmly in the direction of implementing rapid AST. Certainly, the benefits are likely to be greater in patients with resistant-organism infections and septic shock. However, the former is never known at the time of presentation and the latter can easily develop after blood cultures are obtained and before results are known. Therefore, trying to focus rapid AST on a subset of patients where it might have clear mortality benefit seems impractical and unnecessary. Nearly every hospital in the US, and many globally (including all the hospitals in the FAST trial), have antibiotic stewardship programs focused on ensuring that patients receive optimal antibiotic therapy.9 If we have a tool that will help antibiotic stewardship programs support clinicians in optimizing therapy faster, an outcome that is consistent across all studies of rapid AST, should we not work toward making that tool available? The answer from a patient-centric perspective is clearly yes. Back to top Article Information Corresponding Author: Arjun Srinivasan, MD, Joint Commission, 1 Renaissance Blvd, Oakbrook Terrace, IL 60181 (asrinivasan@jointcommission.org).Published Online: April 18, 2026. doi:10.1001/jama.2026.5504Conflict of Interest Disclosures: None reported. References 1.Leung  LY, Huang  HL, Hung  KK,  et al.  Door-to-antibiotic time and mortality in patients with sepsis: systematic review and meta-analysis.   Eur J Intern Med. 2024;129:48-61. doi:10.1016/j.ejim.2024.06.015PubMedGoogle ScholarCrossref2.Kumar  NR, Balraj  TA, Kempegowda  SN, Prashant  A.  Multidrug-resistant sepsis: a critical healthcare challenge.   Antibiotics (Basel). 2024;13(1):46. doi:10.3390/antibiotics13010046PubMedGoogle ScholarCrossref3.Banerjee  R, Komarow  L, Li  Y,  et al; Antibacterial Resistance Leadership Group.  Fast antimicrobial susceptibility testing for gram-negative bacteremia: the FAST randomized clinical trial.   JAMA. Published online April 18, 2026. doi:10.1001/jama.2026.5487ArticleGoogle Scholar4.Ong  SWX, Petersiel  N, Loewenthal  MR, Daneman  N, Tong  SYC, Davis  JS.  Unlocking the DOOR—how to design, apply, analyse, and interpret desirability of outcome ranking endpoints in infectious diseases clinical trials.   Clin Microbiol Infect. 2023;29:1024-1030. doi:10.1016/j.cmi.2023.05.003PubMedGoogle ScholarCrossref5.Patel  TS, Sati  H, Lessa  FC,  et al.  Defining access without excess: expanding appropriate use of antibiotics targeting multidrug-resistant organisms.   Lancet Microbe. 2024;5(1):e93-e98. doi:10.1016/S2666-5247(23)00256-2PubMedGoogle ScholarCrossref6.Kam  KQ, Chen  T, Kadri  SS,  et al.  Epidemiology and outcomes of antibiotic de-escalation in patients with suspected sepsis in US hospitals.   Clin Infect Dis. 2025;80(1):108-117. doi:10.1093/cid/ciae591PubMedGoogle ScholarCrossref7.Teshome  BF, Park  T, Arackal  J, Hampton  N, Kollef  MH, Micek  ST.  Preventing new gram-negative resistance through beta-lactam de-escalation in hospitalized patients with sepsis: a retrospective cohort study.   Clin Infect Dis. 2024;79(4):826-833. doi:10.1093/cid/ciae253PubMedGoogle ScholarCrossref8.Department of Health and Human Services. Medicare program; hospital Inpatient Prospective Payment Systems for acute care hospitals (IPPS) and the Long-Term Care Hospital Prospective Payment System and policy changes and fiscal year (FY) 2026 rates; changes to the FY 2025 IPPS rates due to court decision; requirements for quality programs; and other policy changes; health data, technology, and interoperability: electronic prescribing, real-time prescription benefit and electronic prior authorization. August 4, 2025. Accessed March 23, 2026. https://public-inspection.federalregister.gov/2025-14681.pdf 9.Centers for Disease Control and Prevention. Hospital antibiotic stewardship. Accessed March 23, 2026. https://arpsp.cdc.gov/profile/stewardship

FAST trial with 850 pts found rapid AST ∅ ↑mortality but shortened hospital stay by 3 days in resistant infections & cut antibiotic changes time from 36h to 22h ⏳🦠 #AntibioticStewardship

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