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Introduction: Despite diagnostic and therapeutic advances, infective endocarditis (IE) is still associated with high mortality rates. Currently, there are no good prognostic tools for the risk assessment of patients with IE. The CHA2DS2-VASc score, used to estimate the risk of ischemic stroke in patients with non-valvular atrial fibrillation (AF), has been shown to be a powerful predictor of stroke and death in patients without known AF associated with other cardiovascular conditions. Objective: We aimed to evaluate the usefulness of the CHA2DS2-VASc score as a prognostic tool in a population of patients with IE. Methods: The Rabin Medical Center Endocarditis Team (RMCET) registry is a retrospective cohort of all patients evaluated at our center due to acute or sub-acute bacterial endocarditis. The CHA2DS2-VASc score was extracted for all patients. All-cause mortality was depicted for all patients. Results: The cohort included 330 patients with a mean age of 65.2 ± 14.7 years (70% men). During a median follow-up of 24 months [IQR 4.7-48.6], 121 (36.7%) patients died. The median CHA2DS2-VASc score was 3, and any score above 2 was associated with increased overall mortality (50.8% vs. 19.9%, p < 0.001). A multivariate model incorporating important confounders not included in the CHA2DS2-VASc model showed consistent results with a risk increase of 121% for the higher CHA2DS2-VASc score groups (HR 2.21 [CI 1.12-4.39], p = 0.023). Conclusions: IE currently has no good risk stratification models for clinical practice. The CHA2DS2-VASc score might serve as a simple and available tool to stratify risk among patients with IE.
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Background: Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus-induced neurologic disease (VZV-ND). Methods: This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid. Results: We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non-VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25-128) and 82 days (IQR, 36-132) for VZV-ND and non-VZV-ND, respectively, not reaching statistical significance (P = .056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P = .2). Conclusions: We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance.
Subject(s)
Antifungal Agents , Aspergillus fumigatus , Cytochrome P-450 Enzyme System , Drug Resistance, Fungal , Fungal Proteins , Mutation , Triazoles , Humans , Male , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Aspergillus fumigatus/genetics , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/isolation & purification , Cytochrome P-450 Enzyme System/genetics , Drug Resistance, Fungal/genetics , Fatal Outcome , Fungal Proteins/genetics , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/microbiology , Microbial Sensitivity Tests , Neuroaspergillosis/genetics , Neuroaspergillosis/microbiology , Neuroaspergillosis/drug therapy , Triazoles/pharmacology , Triazoles/therapeutic use , AdultABSTRACT
OBJECTIVES: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. METHODS: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant. RESULTS: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). CONCLUSIONS: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.
Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Hematologic Neoplasms , Humans , Rituximab/adverse effects , COVID-19 Testing , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/epidemiologyABSTRACT
BACKGROUND: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients. OBJECTIVES: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients. METHODS: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects. RESULTS: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented. CONCLUSIONS: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.
Subject(s)
Anticholesteremic Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Humans , Antibodies, Monoclonal/therapeutic use , Anticholesteremic Agents/adverse effects , Cholesterol, LDL , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Proprotein Convertase 9 , Retrospective Studies , Middle AgedABSTRACT
BACKGROUND: Prophylaxis with fluoroquinolones (FQ) is commonly used in patients with acute leukemia (AL) during neutropenia. This practice is supported by an older meta-analysis reporting reduced mortality using FQ prophylaxis. Later meta-analyses have failed to reproduce this finding, presumably due to higher background FQ resistance rates limiting their effectiveness. SUMMARY: This article reviews the pros and cons of FQ prophylaxis mainly in patients with AL. Most current guidelines do not support universal prophylaxis but rather recommend a selective approach, weighing the benefits against the risks. This recommendation is based on the lack of mortality benefit reported in more recent meta-analyses. FQ prophylaxis was demonstrated to reduce bacteremia and febrile neutropenia episodes, although mostly in trials performed in low-resistance settings (<20%), whereas current FQ resistance rates may reach 30-60%. Other disadvantages of FQ include potential adverse events, antibiotic resistance development, cost, increase in Gram-positive infections and resistant Gram-negative infections following prophylaxis, Clostridioides difficile infection, and an effect on gut microbiota. KEY MESSAGES: Taking the above into consideration, alternative approaches other than universal FQ prophylaxis should be considered. Centers with high FQ resistance rates may consider either withholding prophylaxis or providing selective prophylaxis for high-risk patients screened negative for FQ-resistant bacteria.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Neutropenia , Humans , Anti-Bacterial Agents/therapeutic use , Fluoroquinolones/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/drug therapy , Neutropenia/etiology , Meta-Analysis as TopicABSTRACT
Long-term risk for malignancy is higher among solid organ transplant (SOT) recipients compared to the general population. Four non-hepatitis viruses have been recognized as oncogenic in SOT recipients-EBV, cause of EBV-associated lymphoproliferative diseases; human herpes virus 8 (HHV8), cause of Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease; human papilloma virus, cause of squamous cell skin cancers, and Merkel cell polyomavirus, cause of Merkel cell carcinoma. Two of these viruses (EBV and HHV8) belong to the human herpes virus family. In this review, we will discuss key aspects regarding the clinical presentation, diagnosis, treatment, and prevention of diseases in SOT recipients associated with the two herpesviruses.
Subject(s)
Epstein-Barr Virus Infections , Gammaherpesvirinae , Herpesviridae Infections , Herpesvirus 8, Human , Lymphoproliferative Disorders , Organ Transplantation , Humans , Herpesvirus 4, Human , Herpesviridae Infections/complications , Herpesviridae Infections/diagnosis , Herpesviridae Infections/drug therapy , Lymphoproliferative Disorders/etiology , Organ Transplantation/adverse effects , Transplant RecipientsABSTRACT
BACKGROUND: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel. OBJECTIVES: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence. METHODS: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events. RESULTS: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time. CONCLUSIONS: Clinician training regarding discharge of VTE patients from the ED should continue.
Subject(s)
Venous Thromboembolism , Humans , Venous Thromboembolism/drug therapy , Enoxaparin/adverse effects , Warfarin/adverse effects , Retrospective Studies , Emergency Service, Hospital , Anticoagulants/adverse effectsSubject(s)
Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Herpesvirus 6, Human , Adult , Humans , Herpesvirus 6, Human/genetics , Seizures/genetics , Seizures/drug therapy , Anticonvulsants/therapeutic use , Epilepsy, Tonic-Clonic/drug therapy , Electroencephalography , Epilepsy, Generalized/drug therapyABSTRACT
BACKGROUND: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce. OBJECTIVES: To compare the outcomes of patients with both the Omicron variant and influenza during 2021-2022. METHODS: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality. RESULTS: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25-0.81). CONCLUSIONS: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.
Subject(s)
COVID-19 , Influenza, Human , Humans , Aged , Influenza, Human/epidemiology , COVID-19/epidemiology , COVID-19/therapy , Retrospective Studies , SARS-CoV-2 , SeasonsABSTRACT
BACKGROUND: Congestive heart failure (CHF) with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF) is a common diagnosis in patients hospitalized in the department of internal medicine. Recently, the therapeutic regimens were updated, as the sodium-glucose cotransporter-2 (SGLT2) inhibitors became an integral part of the therapeutic regimen for either HFrEF or HFpEF. OBJECTIVES: To define the demographic and clinical characteristics of CHF patients hospitalized in the department of medicine. METHODS: We conducted a retrospective cohort study that included all patients hospitalized in the departments of medicine at the Rabin Medical Center, Israel, between 2016 and 2019. Demographic and clinical background, in-hospital procedures, discharge regimens, and outcome parameters were evaluated according to HFrEF/HFpEF. RESULTS: The cohort included 4458 patients. The majority (97%) presented with a preexisting diagnosis, whereas HF was an active condition in only half of them. The rates of HFrEF/HFpEF were equal. In most cases, the trigger of the exacerbation could not be determined; however, infection was the most common cause. There were basic differences in the demography, clinical aspects, and therapeutic regimens at discharge between HFrEF and HFpEF. Both conditions were associated with high in hospital mortality (8%) and re-admissions rates (30 days [20%], 90 days [35%]) without any difference between them. CONCLUSIONS: HFrEF/HFpEF patients differed by demographics and co-morbidities. They were equally represented among patients admitted to medical wards and had similar prognosis. For both diagnoses, hospitalization should be considered for updating therapeutic regimens, especially with SGLT2 inhibitors.
Subject(s)
Heart Failure , Humans , Heart Failure/diagnosis , Heart Failure/drug therapy , Heart Failure/epidemiology , Retrospective Studies , Stroke Volume , Internal Medicine , Hospital MortalityABSTRACT
BACKGROUND: Clostridioides difficile infection (CDI) can be divided according to its acquisition site, health care (HC) or community (CA) associated CDI. Studies showed severe disease, higher recurrence, and mortality among HC-CDI patients, while others reported the opposite. We aimed to compare the outcomes according to the CDI acquisition site. METHODS: The study analyzed medical records and laboratory computerized system data to identify patients (≥18 years old) who were hospitalized with the first CDI from January 2013 to March 2021. Patients were divided into HC-CDI and CA-CDI groups. The primary outcome was 30-day mortality. Other outcomes: CDI severity, colectomy, intensive care unit (ICU) admission, length of hospitalization, 30 and 90-day recurrence, and 90 days all-cause mortality. RESULTS: Of 867 patients, 375 were defined as CA-CDI and 492 as HC-CDI. CA-CDI patients had more underlying malignancy (26% vs 21% P = .04) and inflammatory bowel disease (7% vs 1%, P < .001). The 30 days mortality was similar (10% CA-CDI and 12% HC-CDI, P = .5), and the acquisition site was not found to be a risk factor. There was no difference in severity nor in complications, but the recurrence rate was higher among those with CA-CDI (4% vs 2%, P = .055). CONCLUSIONS: There were no differences between the CA-CDI and HC-CDI groups regarding rates, in-hospital complications, short-term mortality, and 90-day recurrence rates. However, the CA-CDI patients had a higher recurrence rate at 30 days.
Subject(s)
Clostridioides difficile , Clostridium Infections , Cross Infection , Humans , Adolescent , Cross Infection/epidemiology , Hospitalization , Risk Factors , Clostridium Infections/epidemiology , Delivery of Health Care , Retrospective StudiesABSTRACT
We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.
Subject(s)
COVID-19 , Candidiasis, Invasive , Humans , Candida/genetics , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida auris , Israel/epidemiology , COVID-19/epidemiology , Candidiasis, Invasive/drug therapy , Disease Outbreaks , Hospitalization , Microbial Sensitivity TestsABSTRACT
Patients with inflammatory bowel disease (IBD) have a higher incidence of Clostridioides difficile infection (CDI). Previous studies have demonstrated negative clinical outcomes in IBD patients with CDI compared to patients without CDI. The clinical presentation of CDI is indistinguishable from IBD exacerbation, thus posing a frequent clinical dilemma on the role of Clostridioides infection in the testing, diagnosis, and treatment of these patients. To compare clinical outcomes of CDI in patients with IBD to those without IBD. Retrospective cohort of adult patients admitted to Rabin Medical Center Israel between the years 2014 and 2020 with a concurrent diagnosis of IBD and CDI. Matching 1:2 was performed between the IBD patients and the non-IBD population with respect to age and sex. Sixty-seven patients with IBD and 134 patients without IBD were included in the study. The groups' median age was 40.6 (interquartile range [IQR] of 29.8-68.9), with 45.8% male and 54.2% female. The non-IBD group had a higher Charlson score with 2 (IQR 0; 5) versus 0 (IQR 0; 4) in the IBD group (P value <.01). Patients with IBD had more exposure to systemic antibiotics, 71.1% versus 26.3% (P value <.01). In a multivariable analysis we found no difference in 90-day mortality and rate of relapse between the 2 study groups with an odds ratio of 1.709 (95% confidence interval 0.321-9.905) and odds ratio of 0.209 (95% confidence interval 0.055-1.513) respectively. In our cohort patients with IBD who present with diarrhea and concomitant CDI have similar rates of relapse and mortality compared with patients without IBD.
Subject(s)
Clostridioides difficile , Clostridium Infections , Inflammatory Bowel Diseases , Adult , Humans , Male , Female , Retrospective Studies , Clostridioides , Risk Factors , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/drug therapy , Clostridium Infections/complications , Clostridium Infections/drug therapy , Clostridium Infections/epidemiology , Diarrhea/epidemiology , Diarrhea/complications , RecurrenceABSTRACT
BACKGROUND: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings. OBJECTIVES: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine. METHODS: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models. RESULTS: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038). CONCLUSIONS: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.
Subject(s)
COVID-19 , Exercise Test , Humans , Post-Acute COVID-19 Syndrome , Cross-Sectional Studies , Exercise Tolerance , MyalgiaABSTRACT
BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.
Subject(s)
Bacteremia , Pseudomonas Infections , Male , Aged, 80 and over , Humans , Aged , Female , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Pseudomonas aeruginosa , Cohort Studies , Nonagenarians , Octogenarians , Pseudomonas Infections/drug therapy , Bacteremia/drug therapy , Bacteremia/epidemiology , Bacteremia/complications , Risk FactorsABSTRACT
BACKGROUND: There is an increasing use of anti-protein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs); however, real-world data is lacking. OBJECTIVES: To define the demographic and clinical characteristics of patients treated with anti-PCSK9 mAbs. To evaluate efficacy, tolerability, and differences between the approved agents. METHODS: A retrospective cohort study was conducted of patients treated at the lipid clinic at Rabin Medical Center (Beilinson Campus), Israel, from January 2016 to December 2019. Data from electronic records were evaluated for demographic and clinical characteristics, indication for use, response of lowering low-density lipoprotein cholesterol (LDL-C)/non-high-density lipoprotein cholesterol (non-HDL-C) levels and reaching target levels, side effects, tolerability, differences between the agents, and doses. RESULTS: The study cohort included 115 patients. Two-thirds (n=75) were at high cardiovascular risk, the rest at very high risk (n=40). The major indication for treatment was statin intolerance (n=97, 84%). Most patients (n=102, 88%) were treated by anti-PCSK9 mAbs agents only. LDL-C and non-HDL-C levels were decreased by 47% and 39%, respectively (156 + 49 to 81 + 39 and 192 + 53 to 116 + 42 mg/dl), within 6 months and remained stable. Two-thirds (n=76) of the patients reached their lipid target levels. No clinically significant differences were observed between the agents in efficacy or tolerability. CONCLUSIONS: In a real-world setting, anti-PCSK9 mAbs are used primarily as a single agent in high-risk and very high-risk cardiovascular populations with statin intolerance. They are well tolerated and effective in reduction of LDL-C levels. Further studies are needed to clarify comparisons between agents and doses.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Cholesterol, LDL , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Subtilisin , Proprotein Convertase 9 , Retrospective Studies , IsraelABSTRACT
BACKGROUND: We aimed to review the current state, challenges, and needs of antimicrobial stewardship programs (ASPs) in adult solid organ transplantation (SOT) centers in Israel. METHODS: We conducted a survey using electronic questionnaires sent during February 2022 to infectious disease (ID) consultants of SOT centers, encompassing general and organ-specific ASP issues. RESULTS: All six centers performing adult SOTs in Israel participated. The institutional ASPs in all centers included SOT recipients, and five centers had specific stewardship activities targeting SOT recipients. ASP activities were performed by ID consultants in all centers, with clinical pharmacists in most. ASP protocols and activity scope were highly variable. Formulary restriction with pre-authorization was used in all centers. Antibiotic allergy was addressed in ASP guidelines in half of the centers. Peri-transplantation antibiotic, antifungal, and antiviral prophylactic regimens varied based on center, transplanted organ, and patient risk group. Approaches to surveillance cultures, diagnosis and treatment of various graft infections were also variable. ASP outcome measurement was not performed in all centers. The main challenges and barriers to successful ASP implementation were difficulty in defining appropriate durations of therapy for certain infections, high rates of antimicrobial resistance (AMR), and lack of dedicated ASP teams. CONCLUSION: Antimicrobial stewardship in SOT centers in Israel is performed by ID consultants and practices vary. Challenges are related to high AMR rates, insufficient evidence to support practices, lack of dedicated ASP teams, and lack of outcome measurement. There is an urgent need to establish a national collaborative program including all SOT centers.
Subject(s)
Antimicrobial Stewardship , Organ Transplantation , Humans , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Antiviral Agents/therapeutic use , IsraelABSTRACT
Highly variable estimates of COVID-19-associated fungal diseases (IFDs) have been reported. We aimed to determine the incidence of clinically important fungal diseases in hospitalized COVID-19 patients during the first year of the pandemic. We performed a multicenter survey of IFDs among patients hospitalized with COVID-19 in 13 hospitals in Israel between February 2020 and May 2021. COVID-19-associated pulmonary mold disease (PMD) and invasive candidiasis (IC) were defined using ECMM/ISHAM and EORTC/MSG criteria, respectively. Overall rates of IC and PMD among patients with critical COVID-19 were 10.86 and 10.20 per 1000 admissions, respectively, with significant variability among medical centers. PMD rates were significantly lower in centers where galactomannan was a send-out test versus centers with on-site testing (p = 0.035). The 30-day mortality rate was 67.5% for IC and 57.5% for PMD. Treatment with an echinocandin for IC or an extended-spectrum azole for PMD was associated with significantly lower mortality rates (adjusted hazard ratio [95% confidence interval], 0.26 [0.07-0.91] and 0.23 [0.093-0.57], respectively). In this multicenter national survey, variable rates of PMD were associated with on-site galactomannan testing, suggesting under-detection in sites lacking this capacity. COVID-19-related IFDs were associated with high mortality rates, which were reduced with appropriate antifungal therapy.
ABSTRACT
INTRODUCTION: Oesophageal candidiasis is a common infection among individuals with immunosuppression, associated with significant morbidity. Available guidelines recommend fluconazole as the preferred treatment; however, data regarding its effectiveness in an era of increased fluconazole resistance has not been systematically compiled. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) addressing systemic antifungal therapy for oesophageal candidiasis was undertaken. The primary outcome was clinical response. Subgroup analysis was planned based on immune status and Candida spp. RESULTS: Twelve RCTs were included, of which six compared fluconazole with other azoles, four compared fluconazole with echinocandins, and two compared amphotericin deoxycholate with echinocandins. Most RCTs mainly included human-immunodeficiency-virus-positive individuals. No significant differences were found between fluconazole and comparators for the outcomes of clinical response or combined clinical and endoscopic response [relative risk (RR) 1.02, 95% confidence interval (CI) 0.97-1.07 and RR 1.06, 95% CI 0.98-1.15, respectively]. No differences were found between fluconazole and other azoles for other outcomes; however, compared with echinocandins, fluconazole had significantly higher mycological response rates and lower early relapse rates (RR 1.09, 95% CI 1.02-1.17 and RR 0.42, 95% CI 0.26-0.68, respectively). No significant differences were demonstrated between fluconazole and comparators for overall or severe adverse events. Information required for the planned subgroup analyses was not available. CONCLUSIONS: No differences in efficacy or safety were found between fluconazole and other azoles for the treatment of candida oesophagitis. The use of echinocandins resulted in lower mycological cure rates and higher relapse rates. Additional RCTs should evaluate these interventions among broader patient populations and a wider spectrum of Candida spp.