Objectives mRNA 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 get infected and suffer 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 multicenter cohort study of 17 hospitals included Pfizer/BioNTech's BNT162b2 fully-vaccinated patients 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 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). Notable, the cohort was characterized by a high rate of comorbidities predisposing to severe COVID-19, including hypertension (108, 71%), diabetes (73, 48%), CHF (41, 27%), chronic kidney and lung diseases (37, 24% each), dementia (29, 19%), and cancer (36, 24%), and only 6 (%) had no comorbidities. Sixty (40%) of the patients were immunocompromised. Higher SARS-CoV-2 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 titers 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 comorbidities. Our patients had a higher rate of comorbidities and immunosuppression compared to previously reported non-vaccinated hospitalized COVID-19 patients. 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.
Although the risk factors for acquiring infection by extended-spectrum beta-lactamase (ESBL)-producing bacteria have been investigated in hospitalized patients, such risk factors have not been defined in the community setting. In this study, clinical data from a total of 311 nonhospitalized patients with community-acquired urinary tract infection (128 with ESBL-positive strains and 183 with ESBL-negative strains) were obtained. According to a multivariate analysis, the following were identified as independent risk factors: previous hospitalization in the past 3 months (OR=8.95, 95%CI, 3.77-21.25), antibiotic treatment in the past 3 months (OR=3.23, 95%CI, 1.76-5.91), age over 60 years (OR=2.65, 95%CI, 1.45-4.83), diabetes (OR=2.57, 95%CI, 1.20-5.51), male gender (OR=2.47, 95%CI, 1.22-5.01), Klebsiella pneumoniae infection (OR=2.31, 95%CI, 1.17-4.54), previous use of third-generation cephalosporins (P=0.014, OR=15.8, 95%CI, 1.7-143), previous use of second-generation cephalosporins (P<0.0001, OR=10.1, 95%CI, 4.2-24), previous use of quinolones (P=0.001, OR=4.1, 95%CI, 1.8-9.0), and previous use of penicillin (P=0.003, OR=4.0, 95%CI, 1.6-9.0).
Candida species have emerged as frequent causes of nosocomial bloodstream infection (BSI) in association with well-defined risk factors, including prolonged hospitalization, abdominal surgery, antibiotic treatment, neutropenia and central venous catheterization (14). Candidemia is associated with high rates of attributable mortality, prolongation of hospital stay, and excessive costs (28). In recent years, there has been a shift in the distribution of Candida species causing invasive infection, with non-albicans species now surpassing Candida albicans in many institutions (14,25). Of particular concern is the rising incidence of the azolenonsusceptible species C. glabrata and the inherently fluconazoleresistant species C. krusei (11,25,27).Fluconazole is often used as empirical treatment of candidemia. However, given the correlation between the survival rate and the timely initiation of appropriate treatment for candidemia (8), accurate assessment of the risk of fluconazole-resistant Candida (FRC) BSI is of prime importance. Patients who were recently treated with an azole drug are at increased risk of infection with FRC (9) and should be treated initially with an echinocandin agent according to current guidelines (18). However, experimental and clinical data support the notion that nonantifungal antimicrobial agents also affect the risk of colonization and infection with FRC (15,17,22). Since exposure to antibacterial drugs among at-risk patients far exceeds exposure to antifungal agents, even modest effects of individual antibacterials could translate into significant overall changes in the susceptibility patterns of Candida spp. Nevertheless, the collateral effects of antibacterial drugs on Candida spp. are poorly understood. To address this question, we analyzed prospectively collected data from a nationwide study of candidemia in Israel and examined the association between exposure to antifungal and antibacterial agents and the risk of infection with FRC. MATERIALS AND METHODS Study design.We performed a prospective nationwide study of candidemia in Israel from November 2005 through June 2007. Eighteen medical centers, which together account for 75% of the hospital beds in Israel, were included. All candidemia episodes that occurred in the participating centers during the study period were eligible for inclusion in this study. Clinical data were prospectively entered into standardized data forms by on-site investigators at each of the centers. The Candida sp. clinical isolates underwent preliminary identification and susceptibility testing in each center according to local practices. Subsequently, the isolates were transferred together with the corresponding data forms to the central study site, where species identification and susceptibility testing were performed as detailed below. The data forms were collected by the study coordinator, reviewed by the principal investigator, and entered into a computerized database. The study was approved by the ethics committee of each of the participating centers.Data...
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