Research progress on clinical challenges and prevention strategies of drug-resistant Nocardia infections.

Drug-resistant Nocardia infections have become an increasingly intractable clinical challenge globally, with the incidence rising steadily among both immunocompromised and immunocompetent populations in recent decades. The clinical management of drug-resistant Nocardia infections is hindered by distinct regional variations in species distribution, complex molecular resistance mechanisms, and sophisticated species-specific immune escape strategies, all of which contribute to frequent treatment failure and poor patient outcomes. In this review, we synthesize the latest research progress on drug-resistant Nocardia from a clinical and translational perspective, focusing on its epidemiological characteristics (global epidemic trends, regional heterogeneity, and high-risk population stratification), pathological mechanisms (genomic features, drug resistance molecular basis, and species-specific immune escape pathways), and clinical diagnostic and therapeutic advances. We systematically compare the performance of conventional and novel diagnostic technologies for Nocardia identification and resistance detection, and summarize evidence-based antibiotic selection strategies, individualized treatment regimens for special populations (e.g., patients with hepatic/renal impairment, pregnant women, and pediatric patients), and rational combined antimicrobial therapies for different infection sites. Additionally, we critically analyze and characterize the interdependent relationships among the unresolved clinical bottlenecks-including regional resistance heterogeneity, diagnostic delays in resource-limited settings, and insufficient clinical evidence for special populations-and further translate these identified research gaps into prioritized and actionable research directions for the field. We further analyze how novel anti-Nocardia agents, innovative diagnostic/therapeutic technologies, and multidisciplinary collaboration can synergistically address these challenges, providing a forward-looking framework for advancing clinical management and translational research. This review aims to provide a comprehensive and up-to-date reference for clinical practitioners, microbiologists, and translational researchers, and to offer insights for optimizing the clinical diagnosis and treatment strategies of drug-resistant Nocardia infections.