Graf, Erin H.

ABSTRACT Vancomycin is broadly used to treat gram-positive infections in both inpatient and outpatient settings. Its use is primarily for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), which is a common cause of pneumonia, skin and soft tissue infections, and bloodstream infections. Vancomycin therapy requires close clinical monitoring to maintain therapeutic efficacy and, importantly, patient safety. Vancomycin use is associated with acute kidney injury in up to 20% of cases, a number that can be driven down by pharmacokinetic dosing protocols. However, the best mitigation against adverse outcomes associated with vancomycin is to ensure it is only used when needed and rapidly de-escalated when not. As such, many stewardship programs, who are tasked with the safe and effective use of antimicrobial agents, have focused on optimizing vancomycin use. There is a strong correlation with MRSA colonization and infection, and a negative MRSA nares screen has a good negative predictive value for MRSA pneumonia (although this association is less well documented for other infections). As such, detection of MRSA in nares swabs, by nucleic acid amplification tests (NAATs) or culture, is a logical tool for stewarding vancomycin. However, the application of MRSA screening tests as MRSA diagnostics is complex, as these tests are cleared by the U.S. Food and Drug Administration for the detection of MRSA colonization, and not for therapeutic decision making. In this issue of the Journal of Clinical Microbiology, the issue of MRSA nares tests is debated by a clinical pharmacy team and the laboratory. The authors review the clinical evidence and regulatory background in which an MRSA nares NAAT may be used to inform treatment decisions.

Abstract Background While most pulmonary infections with Coccidioides spp. are self-limited, a subset of patients is at higher risk for severe disease and extrapulmonary dissemination, including individuals with certain ethnic backgrounds. Disseminated disease can involve soft tissues, bones, and the central nervous system with high morbidity and mortality in the absence of antifungal treatment. Diagnosis of coccidioidomycosis can be challenged by the availability of specimens for culture or histopathology, confusion with, or lack of availability of various antibody tests and overall lack of consideration of Coccidioides spp. as the etiology of disease, especially in immunocompetent hosts. Methods We set out to characterize cases of disseminated coccidioidomycosis at our institution over a 7-year period, solely in immunocompetent hosts, to highlight diagnostic delays and determine which, if any, primary screening test might be the most useful. Results A total of 40 cases met our inclusion criteria, and 100% of these cases had positive immunoglobulin G antibodies on a US FDA-cleared Coccidioides spp. enzyme immunoassay. Nearly all of the cases (87%) had a delay in diagnosis and associated worsening of disease (71%). Locations of initial presentations that led to delayed recognition included primary care settings (56%), emergency departments (33%), and urgent care centers (11%), all in the region of Coccidioides spp. endemicity. Conclusions These findings highlight the need for interventions to increase awareness of the risk factors for, the symptoms of, and the appropriate testing options to diagnose disseminated coccidioidomycosis.

AbstractEnterocutaneous fistulas (ECFs) profoundly impact patients’ quality of life, contributing to high morbidity rates and increased mortality due to ineffective treatment options. To address this challenge, ECFGel, a multifunctional, tissue adhesive injectable hydrogel, designed to occlude, sterilize, and promote healing of ECF tracts, is developed. ECFGel is formulated using gelatin and oxidized dextran (O‐Dex) as base components, which form chemical crosslinks within the hydrogel and with surrounding biological tissues, ensuring tissue adhesiveness. A choline and geranate‐based ionic liquid (IL) is incorporated to provide dual functionality, potent antimicrobial activity, and mechanical enhancement. By optimizing IL concentration, ECFGel achieves rapid gelation, enhanced mechanical strength, and improved elastic recoverability. Additionally, iohexol (IOH) is added for radiopacity, enabling real‐time imaging and further strengthening the hydrogel's mechanical properties. ECFGel demonstrates antiswelling properties, biodegradability, and effective tract occlusion in porcine soft tissues. It shows strong antimicrobial activity against highly resistant, patient‐derived pathogens isolated from clinical ECF cases. In a porcine perianal fistula model, ECFGel enables rapid occlusion and complete healing, promoting tissue maturation, reducing bacterial load, and increasing markers of cell proliferation and vascularization compared to untreated controls. These promising results highlight ECFGel's potential as a new therapeutic option for treating infected ECFs.

ABSTRACT Background As Coccidioides spp. are endemic in the southwestern United States, awareness of the risk factors for severe disease and dissemination is important to avoid delays in diagnosis and treatment. In addition to immunocompetent patients, individuals of certain ethnic backgrounds, especially African and Filipino ancestry, are at higher risk for dissemination. Diagnostic testing may be complicated by the lack of available invasive specimens for histopathologic examination and culture. Case Summary A 29-year-old African American woman presented with a 6-year history of abdominal bloating and discomfort, which was previously diagnosed as endometriosis and possible irritable bowel syndrome. After multiple visits to primary care, urgent care, and emergency settings, she was referred for outpatient gynecology and gastrointestinal follow-up. Imaging revealed diffuse peritoneal nodules potentially concerning for malignancy, and biopsies revealed Coccidioides spp. spherules on the frozen section. Routine bacterial and fungal cultures from the biopsied nodules grew Coccidioides immitis/posadasii . The patient was placed on fluconazole with rapid symptom resolution and was maintained on fluconazole at a 2-year follow-up. Conclusion The case presented highlights a reasonably common occurrence in endemic regions—the delayed diagnosis of coccidioidomycosis due to the lack of consideration as the etiology of the patient’s symptoms. This patient was at risk for dissemination due to her ethnicity, and while the differential for her presenting symptoms was broad, coccidioidomycosis should have been considered. In immunocompetent patients, like the case presented, serologic testing should be pursued, as severe or disseminated cases typically have positive IgG responses.

Abstract Enterocutaneous fistulas (ECF) are challenging to treat contributing to high morbidity and high mortality rates, significantly impacting the quality of life of the patients. Its susceptibility to antibiotic‐resistant infections often leads to chronic inflammation, complicating treatment with conventional methods. Here, 18NC75‐10P‐1IL is reported, which is a multi‐functional shear‐thinning hydrogel comprised of gelatin and nanosilicates for injectability, an ionic liquid for bactericidal effects, and platelet rich fibrin fraction for pro‐healing properties; this biomaterial is engineered for the treatment of ECFs. Through rigorous testing, the mechanical properties of 18NC75‐10P‐1IL were tailored for catheter injection to achieve durable occlusion of fistulous tracts under external pressures simulating clinical scenarios. 18NC75‐10P‐1IL demonstrated pro‐healing effects and anti‐microbial activity against highly resistant patient‐derived bacteria known to be associated with ECF. Subcutaneous implantation and anorectal fistula models confirmed its biocompatibility, pro‐healing, anti‐inflammatory, and anti‐microbial properties compared to control materials, suggesting promising potential for clinical translation in the treatment of human ECFs.