An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab.

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.

An emergency department intervention to improve earlier detection of community-onset bloodstream infection among hospitalized patients.

BACKGROUND: Blood cultures (BCs) are essential microbiologic tests, but blood culturing diagnostic stewardship is frequently poor. We aimed to study the process-related failures and to evaluate the effect of an emergency department (ED) intervention on BCs collection practices and yield. METHODS: We implemented an ED-quality improvement intervention including educational sessions, phlebotomists addition, promoting single-site strategy for BC-collection and preanalytical data feedback. BC-bottles collected, positive BCs, blood volumes and documentation of collection times were measured, before (December 2021-August 2022) and after (September 2022-July 2023) intervention. Results were corrected to hospitalizations admissions or days. We used interrupted-time series analyses for comparisons. RESULTS: A total of 64,295 BC bottles were evaluated, 26,261 before and 38,034 postintervention. The median ED-BCs collected per week increased from 88 to 105 BCs (P < .0001), resulting from increased early sampling (P = .0001). Solitary BCs decreased (95%-28%), documented times increased (2.8%-25%), and average blood volume increased (3 mL to 4.5 mL) postintervention. Community-onset Bloodstream infections (BSIs) increased (39.6-52 bottles/1,000 admissions, P = .0001), while Health care-associated BSIs decreased (39-27 bottles/10,000 days, P = .0042). Contamination rates did not change. CONCLUSIONS: An ED-focused intervention based on the education sessions and single-site strategy improved culturing stewardship and facilitated the early identification of BSI without an increase in contamination.

BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel.

OBJECTIVES: The mRNA coronavirus disease 2019 (COVID-19) vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease and death. Nevertheless, a minority of vaccinated individuals might become infected and experience significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination. METHODS: A retrospective multicentre cohort study of 17 hospitals included patients fully vaccinated with Pfizer/BioNTech's BNT162b2 vaccine who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed. RESULTS: A total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notably, the cohort was characterized by a high rate of co-morbidities predisposing to severe COVID-19, including hypertension (108; 71%), diabetes (73; 48%), congestive heart failure (41; 27%), chronic kidney and lung diseases (37; 24% each), dementia (29; 19%) and cancer (36; 24%), and only six (4%) had no co-morbidities. Sixty (40%) of the patients were immunocompromised. Higher viral load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titres of anti-Spike IgG, but these differences did not reach statistical significance. CONCLUSIONS: We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social distancing, or by additional active or passive vaccinations.

Prevalence, impact, and management strategies for asymptomatic bacteriuria in the acute care elderly patient: a review of the current literature.

Introduction: It is unclear how to prevent the negative impact of inappropriate urine cultures in older acute care patients who have a high rate of asymptomatic bacteriuria.Areas covered: A nonsystematic literature review of the definition, impact, and management of elderly acute care patients with asymptomatic bacteriuria (ASB).Expert opinion: In the elderly, patients with ASB include those with extra-urinary tract diseases (e.g. pneumonia) and those with symptoms/signs that resolve without antibiotic therapy, but the diagnosis of ASB is unclear in febrile patients responding to antibiotics. We consider four management strategies that could decrease the negative impact of culturing the urine including unnecessary antibiotic therapy in those with ASB: (1) Prevent urine testing in patients with extra-urinary tract reasons for their acute care (2) Cancel urine cultures if the urine dipstick is negative. (3) Avoid catheterization in stable patients who cannot provide a urine specimen on demand and (4) Withhold antibiotics in stable non-febrile elderly patients who do not have new local urinary tract symptoms or decompensation on follow-up, and pursue further investigations for another etiology/diagnosis.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Ibrutinib-associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: An observational study.

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. OBJECTIVES: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. METHODS: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. RESULT: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. CONCLUSIONS: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.

Disseminated "Haemophilus quentini" infection in a patient with multiple myeloma - a case report and review of the literature.

We describe a case report of a 56-year-old male with undiagnosed multiple myeloma who had severe sepsis associated with pneumonia, meningitis, polyarthritis, and osteomyelitis related to invasive "Haemophilus quentini" infection. The genus was misidentified as H. influenzae by the common bacterial identification systems including newly introduced syndromic PCR-based methods. We review the epidemiological, clinical, and laboratory aspects of this rare, cryptic species of Haemophilus.

Two Cases of Israeli Spotted Fever with Purpura Fulminans, Sharon District, Israel.

We report a series of 5 case-patients who had Israeli spotted fever, of whom 2 had purpura fulminans and died. Four case-patients were given a diagnosis on the basis of PCR of skin biopsy specimens 3-4 days after treatment with doxycycline; 1 case-patient was given a diagnosis on the basis of seroconversion. Rickettsia spp. from the 2 case-patients who died were sequenced and identified as Rickettsia conorii subsp. israelensis. Purpura fulminans has been described in association with R. rickettsii and R. indica, but rarely with R. conorii subsp. israelensis.

Streptococcus anginosus endocarditis and multiple liver abscesses in a splenectomised patient.

An unusual case of infective endocarditis and concurrent multiple liver abscesses both caused by Streptococcus anginosus in a splenectomised patient is reported. The microorganism is a very rare cause of endocarditis and its presentation with multiple liver abscesses is highly unusual. It was initially misdiagnosed as Streptococcus sanguinis and issues relating to the different clinical presentations of S. anginosus including the rare cases of endocarditis, the role of the patient's splenectomy and problems that may contribute to its potential laboratory misidentifications are discussed.

Roles of NF-kappaB activation and peroxisome proliferator-activated receptor gamma inhibition in the effect of rifampin on inducible nitric oxide synthase transcription in human lung epithelial cells.

Rifampin (rifampicin), an important antibiotic agent and a major drug used for the treatment of tuberculosis, exerts immunomodulatory effects. Previous studies have found that rifampin increases inducible nitric oxide (NO) synthase (iNOS) expression and NO production. The present study investigated the potential mechanism(s) underlying these actions. The incubation of human lung epithelial A549 cells with a cytokine mix (interleukin-1beta, tumor necrosis factor alpha, and gamma interferon) induced the expression of iNOS mRNA. The addition of rifampin increased the iNOS level by 1.9 +/- 0.3-fold at a dose of 10 microg/ml (P < 0.01) and by 4.0 +/- 0.3-fold at a dose of 50 microg/ml (P < 0.001). Rifampin treatment also affected the transcription factors that regulate iNOS mRNA: there was an increased and prolonged degradation of the inhibitory subunit of NF-kappaB, a corresponding increase in the level of cytokine-induced DNA binding of NF-kappaB (2.1 +/- 0.2-fold), and a decrease in the level of expression of peroxisome proliferator-activated receptor gamma (PPARgamma). Specifically, the level of PPARgamma expression dropped by 15% in response to cytokine stimulation and by an additional 40% when rifampin was added (P < 0.001). Rifampin had no effect on the activation of mitogen-activated protein kinases or the signal transducer and transcription activator (STAT-1). In conclusion, rifampin augments NO production by upregulating iNOS mRNA. It also increases the level of NF-kappaB activation and decreases the level of PPARgamma expression. The increases in the levels of NF-kappaB activation and NO production probably contribute to the therapeutic effects of rifampin. However, given the role of NF-kappaB in upregulating many inflammatory genes and the roles of PPARgamma in downregulating inflammatory genes and in lipid and glucose metabolism, these findings have implications for potential adverse effects of rifampin in patients with chronic inflammatory diseases and glucose or lipid disorders.

Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis.

BACKGROUND: It has long been believed that breastfeeding provides protection against ulcerative colitis and Crohn disease. Studies designated to test this hypothesis were conducted without reaching conclusive results. OBJECTIVE: The aim of this meta-analysis was to examine the role of breastfeeding in preventing inflammatory bowel disease and to summarize the evidence gathered about this subject. DESIGN: A meta-analysis was performed on 17 relevant articles that were found by using MEDLINE, EMBASE, the Internet, and articles' references. The publications were fully reviewed and divided, on the basis of their quality, into 3 groups. RESULTS: Studies showed heterogeneous results. The pooled odds ratios of all the 17 reviewed studies, calculated according to the random-effects model, were 0.67 (95% CI: 0.52, 0.86) for Crohn disease and 0.77 (0.61, 0.96) for ulcerative colitis. However, only 4 studies for Crohn disease and 4 for ulcerative colitis were eventually included in the highest quality group. In this group, the pooled odds ratio was 0.45 (0.26, 0.79) for Crohn disease and 0.56 (0.38, 0.81) for ulcerative colitis. CONCLUSIONS: The results of this meta-analysis support the hypothesis that breastfeeding is associated with lower risks of Crohn disease and ulcerative colitis. However, because only a few studies were graded to be of high quality, we suggest that further research, conducted with good methodology and large sample sizes, should be carried out to strengthen the validity of these observations.