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OBJECTIVE: To describe the efficacy, safety, and clinical utility of pharmacologic agents in the treatment of systemic sclerosis-related interstitial lung disease (SSc-ILD). DATA SOURCES: A review of the literature was performed using the terms lung diseases, (interstitial/therapy) AND (scleroderma, systemic/therapy) OR (scleroderma, systemic) AND (lung diseases, interstitial/therapy) in PubMed, Ovid MEDLINE, CINAHL, and Web of Science. ClinicalTrials.gov was also searched to identify ongoing studies. The initial search was performed in October 2022, with follow-up searches performed in October 2023. STUDY SELECTION AND DATA ABSTRACTION: Articles reviewed were limited to those written in the English language, human studies, and adult populations. DATA SYNTHESIS: A variety of therapeutic agents, including mycophenolate, azathioprine, cyclophosphamide (CYC), rituximab (RTX), nintedanib, and tocilizumab (TCZ) have slowed the rate of decline in forced vital capacity (FVC) and disease progression. Only nintedanib and TCZ have a labeled indication for SSc-ILD. Two agents, belimumab and pirfenidone, have shown encouraging results in smaller phase II and phase III studies, but have yet to be approved by the Food and Drug Administration. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Patients with pulmonary manifestations of SSc-ILD have worse outcomes and lower survival rates compared with those without. It is imperative that disease management be individualized to achieve optimal patient-centered care. Pharmacists are uniquely suited to support this individualized management. CONCLUSION: Numerous pharmacologic agents have been studied and repurposed in the treatment of SSc-ILD, with nintedanib and TCZ gaining approval to slow the rate of decline in pulmonary function in SSc-ILD. Other agents, including belimumab and pirfenidone, are on the horizon as potential treatment options; but further studies are needed to compare their efficacy and safety with the current standard of care.
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The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant Enterobacterales (CRE) infections as an "urgent" health care threat requiring public attention and research. Certain patients with CRE infections may be at higher risk for poor clinical outcomes than others. Evidence on risk or protective factors for CRE infections are warranted in order to determine the most at-risk populations, especially with newer beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics available to treat CRE. We aimed to identify specific variables involved in CRE treatment that are associated with clinical failure (either 30-day mortality, 30-day microbiologic recurrence, or clinical worsening/failure to improve throughout antibiotic treatment). We conducted a retrospective, observational cohort study of hospitalized patients with CRE infection sampled from 2010 to 2020 at two medical systems in Detroit, Michigan. Patients were included if they were ≥18 years old and culture positive for an organism in the Enterobacterales order causing clinical infection with in vitro resistance by Clinical and Laboratory Standards Institute (CLSI) breakpoints to at least one carbapenem. Overall, there were 140 confirmed CRE infections of which 39% had clinical failure. The most common infection sources were respiratory (38%), urinary (20%), intra-abdominal (16%), and primary bacteremia (14%). A multivariable logistic regression model was developed to identify statistically significant associated predictors with clinical failure, and they included Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.06 to 1.32), chronic dialysis (aOR, 5.86; 95% CI, 1.51-22.7), and Klebsiella pneumoniae in index culture (aOR, 3.09; 95% CI, 1.28 to 7.47). Further research on CRE infections is needed to identify best practices to promote treatment success. IMPORTANCE This work compares carbapenem-resistant Enterobacterales (CRE) infections using patient, clinical, and treatment variables to understand which characteristics are associated with the highest risk of clinical failure. Knowing which risk factors are associated with CRE infection failure can provide clinicians better prognostic and targeted interventions. Research can also further investigate why certain risk factors cause more clinical failure and can help develop treatment strategies to mitigate associated risk factors.