An Unexpected Inverse Relationship Between Biofilm Formation and Antibiotic Resistance in Stenotrophomonas maltophilia

<b>Background/Objectives</b>: <i>Stenotrophomonas maltophilia</i> is an opportunistic pathogen causing severe infections, particularly in patients with cystic fibrosis (CF). Its intrinsic multidrug resistance and biofilm-forming capacity complicate treatment. Although biofilms are generally associated with antimicrobial tolerance, the relationship between biofilm formation and planktonic antibiotic resistance in <i>S. maltophilia</i> remains poorly understood. This study investigated the association between antibiotic resistance profiles and biofilm production in clinical isolates from CF and non-CF patients. <b>Methods</b>: A total of 86 clinical isolates (40 from CF airways and 46 from non-CF patients) were analyzed. Susceptibility to seven antibiotics was assessed by disk diffusion, and multidrug resistance profiles were defined using standard criteria. Biofilm formation was quantified after 24 h using a crystal violet microtiter plate assay and categorized by using a semiquantitative scale. <b>Results</b>: High resistance rates were observed, particularly to meropenem (87.2%), ciprofloxacin (80.2%), and rifampicin (72.1%). CF isolates exhibited significantly higher resistance to piperacillin/tazobactam and a greater prevalence of multidrug resistance. Biofilm formation was detected in 94.2% of isolates, with strong or powerful producers predominating. However, CF isolates formed significantly less biofilm than non-CF isolates. Notably, resistance to piperacillin/tazobactam and meropenem was associated with reduced biofilm biomass and a lower proportion of high biofilm producers. Across all isolates, an inverse correlation was observed between the number of antibiotic resistances and biofilm biomass. These trends persisted after stratification by clinical origin, although some comparisons did not reach statistical significance. <b>Conclusions</b>: This study reveals an unexpected inverse relationship between planktonic antibiotic resistance and biofilm-forming capacity in <i>S. maltophilia</i>. Enhanced biofilm production may represent an alternative persistence strategy in more antibiotic-susceptible strains, with important implications for infection management and therapeutic failure.