American Journal of Health-System Pharmacy最新文献

Purpose: The purpose of this review is to discuss the role of toxin inhibition in select infections and to provide recommendations for appropriate antimicrobial selection when toxin inhibition is indicated.

Summary: For select organisms, specifically Clostridioides difficile, Staphylococcus aureus, and Streptococcus pyogenes, toxin production plays an integral role in overall disease pathogenesis and progression. Some expert recommendations include utilization of an antimicrobial with toxin inhibition properties as primary or adjunctive therapy for certain infections due to these organisms, but evolving data have made the choice of antitoxin agent less clear. Clindamycin has been the long-standing standard of care agent for toxin inhibition in necrotizing S. aureus and S. pyogenes infections, but linezolid shows promise as an alternative either in the setting of drug shortages or simply when clindamycin is not optimal, while tetracyclines require further study for this indication. The role for adjunctive toxin inhibition in C. difficile infection (CDI) is less defined, as current first-line therapies already have antitoxin properties.

Conclusion: Toxin inhibition plays a key role in successful management of patients with infections due to toxin-producing organisms. Adjunctive therapy with a tetracycline could be considered in severe, fulminant CDI, but the associated benefit is variable. The benefit of antitoxin treatment for necrotizing S. aureus and S. pyogenes has been more consistently documented. Recent studies support linezolid as an alternative to clindamycin as an adjunctive S. aureus treatment or as monotherapy when appropriate.

Purpose: This review explores the management of persistent methicillin-susceptible Staphylococcus aureus bacteremia (SAB), emphasizing the importance of timely intervention due to SAB's association with metastatic dissemination, relapse, and mortality.

Summary: The literature analysis first delves into risk factors for persistent SAB, highlighting the need for effective treatment strategies. The subsequent focus is on combination strategies for persistent SAB. Daptomycin, ertapenem, ceftaroline, fosfomycin, rifampin, and gentamicin are explored as adjuncts to cefazolin or antistaphylococcal penicillins. Daptomycin combination therapy is assessed through in vivo and clinical studies, indicating potential benefits, especially with higher-risk sources of infection. Ertapenem combination therapy has been demonstrated to have a synergistic effect with cefazolin, presenting a viable salvage option. Rifampin's ability to penetrate biofilm is examined, with discussion of inconclusive evidence on mortality benefits. The review also considers stewardship implications, discussing concerns such as resistance emergence, adverse events, and increased costs associated with combination therapy. Mathematical models suggest combination therapy as an effective approach to prevent resistance. Adverse events vary with each combination, and duration of therapy remains diverse across studies in the absence of well-established dosing guidelines.

Conclusion: The review provides a thorough exploration of the literature on treatment of persistent SAB, underscoring the need for evidence-based guidelines, further studies, and clinical judgment in tailoring treatment strategies. The multifaceted analysis contributes valuable insights for clinicians managing this challenging condition.

Purpose: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice.

Summary: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies.

Conclusion: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.