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Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited. This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%. We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, -2.6% [95% confidence interval, -10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm. In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. NCT01737320.

PurposeWe aimed to develop a machine-learning (ML) algorithm that can predict intensive care unit (ICU)-acquired bloodstream infections (BSI) among patients suspected of infection in the ICU.MethodsThe study was based on patients’ electronic health records at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts, USA, and at Rambam Health Care Campus (RHCC), Haifa, Israel. We included adults from whom blood cultures were collected for suspected BSI at least 48 h after admission. Clinical data, including time-series variables and their interactions, were analyzed by an ML algorithm at each site. Prediction ability for ICU-acquired BSI was assessed by the area under the receiver operating characteristics (AUROC) of ten-fold cross-validation and validation sets with 95% confidence intervals.ResultsThe datasets comprised 2351 patients from BIDMC (151 with BSI) and 1021 from RHCC (162 with BSI). The median (inter-quartile range) age was 62 (51–75) and 56 (38–69) years, respectively; the median Acute Physiology and Chronic Health Evaluation II scores were 26 (21–32) and 24 (20–29), respectively. The means of the cross-validation AUROCs were 0.87 ± 0.02 for BIDMC and 0.93 ± 0.03 for RHCC. AUROCs of 0.89 ± 0.01 and 0.92 ± 0.02 were maintained in both centers with internal validation, while external validation deteriorated. Valuable predictors were mainly the trends of time-series variables such as laboratory results and vital signs.ConclusionAn ML approach that uses temporal and site-specific data achieved high performance in recognizing BC samples with a high probability for ICU-acquired BSI.

Over the past decade, changes in the diagnosis and management of Legionella pneumonia occurred and risk factors for severe infection and increased mortality were identified. Previous reports found that nosocomial infection is associated with higher mortality while others showed no differences. We aimed to evaluate the differences in the clinical course and mortality rates between hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) caused by Legionella pneumophila. A retrospective cohort study of patients admitted due to Legionella pneumonia between January 2012 through November 2019 was conducted in a tertiary referral center (Rambam Health Care Campus, Haifa, Israel). The primary outcome was 30-day Legionella pneumonia–related mortality. A multivariable logistic regression was performed to determine whether a nosocomial infection is an independent predictor of mortality. One hundred nine patients were included. Seventy (64.2%) had CAP and 39 (35.8%) had HAP. The groups were comparable regarding age, gender, and comorbidities. Time to diagnosis was longer and the number of patients receiving initial empiric anti-Legionella spp. treatment was smaller in the HAP group (8 days [IQR 5.5–12.5] vs. 5 days [IQR 3–8], p < 0.001 and 65.5% vs. 78.6%, p = 0.003, respectively). Patients with HAP had higher 30-day mortality, 41% vs. 18.6%, p = 0.02. In a multivariable logistic regression model, only pneumonia severity index and nosocomial source were independently associated with increased mortality. HAP caused by Legionella spp. is independently associated with increased mortality when compared to CAP caused by the same pathogen. The possible reasons for this increased mortality include late diagnosis and delayed initiation of appropriate treatment.

Background: Venous access is a vital component of medical care for hospitalized patients, especially patients who present with difficult intravenous access and require long-term hospitalization. A promising solution for these challenges is the use of long peripheral catheters. This report highlights our experience with an innovative, easily inserted, over-the-needle-long peripheral catheter. Methods: A retrospective, observational study included patients admitted to internal medicine departments and underwent a new long peripheral catheter insertion. We provide data on patient characteristics, indications for long peripheral catheter insertion, insertion success rates, dwell times, and complications rates. Results: The study included 109 patients with a total of 128 long peripheral catheters. The leading indications for long peripheral catheter insertion were IV administration of antibiotics and vasopressors. A first-time user inserted 65% of long peripheral catheters on the first attempt, with an average insertion time of 131 ± 11 s. Success rates increased in parallel with experience gained (p < 0.05). The average dwell time was 8.8 ± 0.63 days. The long peripheral catheter was removed as the therapy was completed in 33.5% of the patients. The complication rate was 13/1000 catheter days, including dislodgement, occlusion, phlebitis and infiltration. In addition, 23 individuals were successfully discharged with the long peripheral catheter to complete therapy at home. The long peripheral catheters was used to draw blood in 28 patients and for vasopressor administration in 22 patients. Conclusions: The new long peripheral catheter provides a safe, rapid, and effective means of venous access. Its straightforward insertion technique, convenience, and suitability for “point of care” use make it a valuable option for patients requiring continuous intravenous therapy.

Covid-19 disease is implicated in increased mortality among immunocompromised patients. The JAK inhibitor, baricitinib (bar), or the IL-6 inhibitor, tocilizumab (toc), demonstrated a survival benefit in patients with severe disease.However, evidence supporting their use in immunocompromised patients with severe Covid-19 is scarce.We aimed to assess clinical outcomes of bar/toc treatment in immunocompromised patients. A multi-center registry of consecutive immunocompromised patients hospitalized due to severe Covid-19 during the Omicron variant dominance period. After excluding patients who did not require high oxygen supply, patients treated with bar/toc were compared to patients treated by standard of care (SOC). Primary outcome was in hospital mortality. Secondary outcomes were 30 and 60 day mortality, super-infection and thromboembolic events. Among an overall 228 immunocompromised patients hospitalized in six Israeli hospitals with severe Covid-19, 112 patients required high oxygen support, of whom 48 (43%) were treated with bar/toc. In-hospital mortality rates were exceptionally high and did not significantly differ between bar/toc and SOC treated patients (62.5% vs. 64.1%, p = 1.0). A logistic regression analysis revealed that advanced age and incomplete vaccination were predictors of in-hospital mortality. Patients treated with bar/toc had no excess of suspected super-infection (62.8% vs. 60.7%, p = 0.84) or thromboembolic events (8.3% vs 3.1%, p = 0.39). In immunocompromised patients with severe Covid-19 and a high oxygen demand, bar/toc therapy was not associated with reduced mortality or with a higher rate of associated complications, compared to SOC. Larger prospective studies should better address efficacy and safety.

We describe 2 cases of Plasmodium knowlesi malaria in persons from Israel who traveled to Thailand in 2023. One patient, likely infected in northwestern Thailand, might signal geographic expansion into areas not previously associated with human infection. The infection's rarity in travelers, diagnostic challenges, and potential severity underscore the importance of clinical awareness.

Acute non-variceal upper gastrointestinal bleeding (NV-UGIB) is associated with significant morbidity and mortality. Early and efficient risk stratification can facilitate management and improve outcomes. We aimed to determine whether the level of ionized calcium (Ca++), an essential co-factor in the coagulation cascade, is associated with the severity of bleeding and the need for advanced interventions among these patients. This was a retrospective single-center cohort study of all patients admitted due to NV-UGIB. The primary outcome was transfusion of ≥ 2 packed red blood cells, arterial embolization, or emergency surgery. Secondary outcomes included (1) transfusion of ≥ 2 packed red blood cells, (2) arterial embolization, or emergency surgery, and (3) all-cause in-hospital mortality. Multivariable logistic regression was performed to determine whether Ca++ was an independent predictor of these adverse outcomes. 1345 patients were included. Hypocalcemia was recorded in 604 (44.9%) patients. The rates of primary adverse outcome were significantly higher in the hypocalcemic group, 14.4% vs. 5.1%, p < 0.001. Secondary outcomes—multiple transfusions, need for angiography or surgery, and mortality were also increased (9.9% vs. 2.3%, p < 0.001, 5.3% vs. 2.8%, p = 0.03, and 33.3% vs. 24.7%, p < 0.001, respectively). Hypocalcemia was an independent predictor of primary and all the secondary outcomes, except mortality. Hypocalcemia in high-risk hospitalized patients with NV-UGIB is common and independently associated with adverse outcomes. Ca++ monitoring in this population may facilitate the rapid identification of high-risk patients. Trials are needed to assess whether correction of hypocalcemia will lead to improved outcomes.

Abstract Background In recent years, multiple outbreaks of measles associated with vaccine hesitancy occurred in high-income countries, where measles incidence had previously been low. Most safety data about the measles, mumps and rubella (MMR) vaccine are derived from studies conducted among children, whereas evidence regarding the safety profile of the vaccine in adults is scarce. Methods In 2017, during an outbreak of measles in Europe, Israeli travellers to high-risk locations who were incompletely vaccinated, were urged to complete the two MMR vaccination schedule before their travel. In this prospective cohort study, we analysed adverse events (AEs) of MMR and MMRV (measles, mumps, rubella and varicella) vaccines among these travellers. All participants were followed up using structured questionnaires 2–4 weeks after vaccination. Results Seven hundred and eighty-five adult travellers whose median age was 49.2 years were vaccinated and followed up. Any AEs were reported by 25.2% of all participants; 11.6% reported local AEs, and 18.6% reported systemic AEs, none of which were severe. In general, AEs were much more common among female travellers (19.4% of males vs 30.1% of females (P < 0.001)). Local AEs, overall systemic AEs, headache and arthralgia were much more common among females, whereas rates of general malaise and fever were not statistically different between genders. We did not observe any significant differences in the rates of total, local or systemic AEs between the MMR and MMRV vaccines. Higher rates of systemic AEs were observed among participants who were younger and probably immunized once with MMR compared to older vaccines immunized once to measles only and to those who were never immunized. Conclusions The current study demonstrated low rates of systemic AEs and no serious AEs following either MMR or MMRV administration. More AEs were reported among females, and rates of AEs were similar after either MMR or MMRV.

Typhoid fever (TF) continues to cause considerable morbidity and mortality in Nepal, but only limited epidemiologic data is available about TF outside Kathmandu. As part of an interventional trial, we performed a prospective cohort study of bacteremic TF patients in Dhulikhel Hospital between October 2012 and October 2014. Demographic, epidemiological, clinical, and microbiologic data were recorded. 116 bacteremic typhoid patients were included in the study. Most were young, healthy, adults (mean age 27.9±12 years), 41.4% of whom were female. More than 70% of patients were employed in non-manual services or were university students. Salmonella Typhi accounted for 64/115 (55.7%) of all isolates, while Salmonella Paratyphi accounted for 51/115 (44.3%), of which 42 were Paratyphi A and 9 Paratyphi B. A significant proportion of TF cases occurred also during the dry season (48/116, 41.6%). The clinical presentation of Salmonella Typhi and Paratyphi infections was similar, except for a greater proportion of arthralgia in patients with Salmonella Typhi. Most Salmonella Typhi and Paratyphi isolates were resistant to nalidixic acid and susceptible to older antibiotics. One Salmonella Paratyphi isolate was resistant to ceftriaxone. TF remains common in the Dhulikhel area, even among those with a high level of education. Public health measures aimed at reducing the incidence of TF in the Dhulikhel area are warranted. The relative burden of TF caused by Salmonella Paratyphi is rising; a vaccine with activity against Salmonella Paratyphi is needed. Since Salmonella Paratyphi B was more prevalent in this cohort than in large cohorts of patients from Kathmandu, it is likely that there are significant regional variations in the epidemiology of TF outside Kathmandu.

To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60-80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01-1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5-8.6), low Norton score (OR, 0.87; 95% CI 0.79-0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14-3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12-4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04-1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21-0.78). Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.