Antifungal resistance poses a critical global health threat, particularly in immuno-compromised patients. Beyond the traditional resistance mechanisms rooted in heritable and stable mutations, a distinct phenomenon known as heteroresistance has been identified, wherein a minority of resistant fungal cells coexist within a predominantly susceptible population. Heteroresistance may be induced by pharmacological factors or non-pharmacological agents. The reversible nature of it presents significant clinical challenges, as it can lead to undetected resistance during standard susceptibility testing. As heteroresistance allows fungal pathogens to survive antifungal treatment, this adaptive strategy often leads to treatment failure and recurring infection. Though extensively studied in bacteria, limited research has explored its occurrence in fungi. This review summarizes the current findings on antifungal heteroresistance mechanisms, highlighting the clinical implications of fungal heteroresistance and the pressing need for deeper mechanism insights. We aim to bring together the latest research advances in the field of antifungal heteroresistance, summarizing in detail its known characteristics, inducing factors, molecular mechanisms, and clinical significance, and describing the similarities and differences between heteroresistance, tolerance and persistence. Further research is needed to understand this phenomenon and develop more effective antifungal therapies to combat fungal infections.

Eravacycline, a novel fluorocycline antimicrobial, was approved by China’s National Medical Products Administration (NMPA) in March 2023; however, clinical breakpoints and real-world data on its use in China remain limited. We conducted a retrospective, questionnaire-based analysis of eravacycline use across 21 provinces in China during the first year after NMPA approval (September 2023–September 2024). Data from 3369 patients who received eravacycline were collected. We analyzed the distribution of pathogens and specimens, reported in vitro susceptibility to eravacycline, imipenem, meropenem, tigecycline, and polymyxins and evaluated microbiological outcomes. Acinetobacter baumannii (52.0%, 1259/2419) and Klebsiella pneumoniae (26.1%, 631/2419) were the most commonly reported pathogens. High levels of carbapenem resistance were observed: 704 of 771 (91.3%) for A. baumannii and 323 of 392 (82.4%) for K. pneumoniae. In contrast, susceptibility to eravacycline was 95.5% (737/772) and 92.5% (297/321), respectively. Microbiological outcomes suggested potential activity against these resistant isolates, though post-treatment culture data were limited. This study demonstrates that eravacycline exhibited potent in vitro activity against prevalent carbapenem-resistant Gram-negative pathogens in real-world Chinese clinical practice during its first-year post-approval. Continuous monitoring of eravacycline resistance trends, together with prospective studies that correlate microbiological and clinical outcomes in specific infection types, will be crucial for defining its long-term therapeutic utility and the risk of resistance emergence.

Antifungal resistance poses a critical global health threat, particularly in immuno-compromised patients. Beyond the traditional resistance mechanisms rooted in heritable and stable mutations, a distinct phenomenon known as heteroresistance has been concerned, wherein a minority of resistant fungal cells coexist within a predominantly susceptible population. It may be induced by pharmacological factors or non-pharmacological agents. The reversible nature of it presents significant clinical challenges, as it can lead to undetected resistance during standard susceptibility testing. As heteroresistance allows fungal pathogens to survive antifungal treatment, this adaptive strategy often leads to treatment failure and infection recurrence. Though extensively studied in bacteria, limited research has explored its occurrence in fungi. This review synthesizes the current findings on antifungal heteroresistance mechanisms, highlighting the clinical implications of fungal heteroresistance and the pressing need for deeper mechanism insights. We aim to combine the latest research advances in the field of antifungal heteroresistance, summarizing in detail the characteristics, inducing factors, molecular mechanisms, and clinical significance of it, and describing the similarities and differences between heteroresistance, tolerance and persistence. Further research is essential to elucidate this phenomenon and develop more effective antifungal therapies to combat fungal infections.