What is the clinical significance of ‘heteroresistance’ in nonfermenting Gram-negative strains?

PURPOSE OF REVIEW: The aim of this study was to discuss the potential clinical significance of heteroresistance in nonfermenting Gram-negative bacilli (GNB). RECENT FINDINGS: Recently, heteroresistance has been considered potentially responsible for clinical failure in Acinetobacter baumannii infections. This raised a scientific debate, still open, about the potential clinical significance of heteroresistance in nonfermenting GNB. SUMMARY: We reviewed the literature of last 20 years and found a limited number of studies evaluating the relationship between heteroresistance and clinical outcome in nonfermenting GNB. Unlike Gram-positive bacteria, heteroresistance is reported in a significant proportion of nonfermenting GNB with some studies describing it in all tested strains and for several antibiotics (including tigecycline, carbapenems, levofloxacin, cefiderocol, colistin). One important issue is the need for validated detection method since the population analysis profile test, that is considered the gold standard, requires high costs and time. Studies evaluating the correlation between heteroresistance and clinical outcome are contrasting and have several limitations. Although in-vitro detection of heteroresistance in nonfermenting GNB has not been associated with in-vivo treatment failure, its presence may suggest to prefer combination regimens instead monotherapy when treating infections by nonfermenters. Further studies are needed to clarify the clinical significance of heteroresistance.