Necrotizing fasciitis caused by community-associated MRSA is an emerging clinical entity. In areas in which community-associated MRSA infection is endemic, empirical treatment of suspected necrotizing fasciitis should include antibiotics predictably active against this pathogen.
Emerging reports suggest that obese patients who are hospitalized with COVID-19 may have worse outcomes; whether this association extends to those who are not hospitalized is unclear. This study examines the association between obesity and death 21 days after diagnosis of COVID-19 among patients who receive care in an integrated health care system, accounting for obesity-related comorbidities and sociodemographic factors.
We developed a novel model of invasive aspergillosis (IA) that recapitulates human disease. Mice were immunosuppressed with cyclophosphamide and cortisone acetate and then infected in an aerosol chamber. This procedure reproducibly delivered 1 ؋ 10 3 to 3 ؋ 10 3 conidia to the lungs. Lethal pulmonary IA developed over 2 weeks and was prevented by amphotericin B.The last 2 decades have seen a rise in the incidence of invasive infections due to Aspergillus species, particularly A. fumigatus (4,8). Despite the development of new antifungal agents, mortality from invasive aspergillosis (IA) remains at least 50% (1, 2, 6). As a result, there is an urgent need for further study of this disease and the development of new clinical strategies to reduce mortality associated with IA. A simple, reproducible animal model that recapitulates the pathogenesis of human IA is a critical tool for developing new methods to prevent, diagnose, and treat this disease (7).IA is initiated by the inhalation of small numbers of A. fumigatus conidia which, by virtue of their small size, evade the mucociliary barrier of the bronchial airways and are deposited in the pulmonary alveoli (7). In the immunosuppressed host, conidia germinate to produce invasive hyphal forms, which propagate by extension and invade local pulmonary tissues. Angioinvasion is a prominent histopathological and clinical feature of IA and is likely the mechanism for dissemination of hyphal fragments to other organs in a subset of patients.We have developed a murine model of invasive pulmonary aspergillosis that recapitulates many of the key factors of human IA. By using an inhalation chamber, a relatively small number of conidia are delivered by small-particle aerosol to immunocompromised mice. This delivery system is reproducible both among mice within an experiment and between experiments. This route of inoculation results in a lethal infection in 60 to 75% of animals within 16 days. Additionally, we show that amphotericin B (AMB) is protective in this model.Strains and media. A. fumigatus strain AF293 (a generous gift from P. Magee) was used for all experiments in this study. To prepare the inoculum, A. fumigatus was grown on Sabouraud dextrose agar plates for 2 weeks at 37°C. Conidia were collected by flooding the plates with sterile phosphate-buffered saline containing 0.2% (vol/vol) Tween 80. The conidia were concentrated by centrifugation and counted using a hemacytometer.Inhalation apparatus. To infect animals via inhalation, we adapted the aerosol chamber described by Pal and Horwitz (10) for use with A. fumigatus conidia (Fig. 1). Mice were introduced via a hinged doorway to a Plexiglas exposure chamber (South Bay Plastics, Torrance, Calif.). The inoculum was introduced by aerosolizing a conidial suspension with a smallparticle nebulizer (Hudson Micro Mist; Hudson RCI, Temecula, Calif.) driven by compressed air at 100 lb/in 2 . The nebulizer was connected to a channel that ran along the top of the chamber and vented the aerosol from the middle of the chamber c...
Efforts to control spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are often based on eradication of colonization. However, the role of nasal and non-nasal colonization in the pathogenesis of these infections remains poorly understood. Patients with acute S. aureus skin and soft tissue infection (SSTI) were prospectively enrolled. Each subject's nasal, axillary, inguinal and rectal areas were swabbed for S. aureus and epidemiological risk factors were surveyed. Among the 117 patients enrolled, there were 99 patients who had an SSTI and for whom data could be analysed. Sixty-five patients had a CA-MRSA SSTI. Among these patients, MRSA colonization in the nares, axilla, inguinal area and rectum was 25, 6, 11 and 13%, respectively, and 37% overall were MRSA colonized. Most (96%) MRSA colonization was detected using nose and inguinal screening alone. Non-nasal colonization was 25% among CA-MRSA patients, but only 6% among patients with CA-methicillin-susceptible S. aureus (MSSA) or healthcare-associated MRSA or MSSA. These findings suggest that colonization patterns in CA-MRSA infection are distinct from those in non-CA-MRSA S. aureus infections. The relatively high prevalence of non-nasal colonization may play a key role in CA-MRSA transmission and acquisition of infection.
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