Abstract
Streptococcus pneumoniae (S. pneumoniae) and Nontypeable Hemophiles influenzae (NTHi) are two of the most common pathogens causing otitis media (OM), which is the primary reason for pediatric antibiotic prescriptions. They have been shown to coexist and, in some cases, form biofilms that are resistant to antibiotics, causing recurrent or chronic OM. The current treatment regimen requires a rigorous course of multidose antibiotics over 5-10 days, which is nevertheless found insufficient to eradicate the polymicrobial biofilms. To tackle this challenge, we utilized a nanozyme, i.e., vanadium pentoxide nanowires (V(2)O(5) NWs), to convert a metabolic product (H(2)O(2)) of S. pneumoniae into a potent antiseptic (HOBr), thus eradicating polymicrobial biofilms comprising S. pneumoniae and NTHi. Interestingly, when V(2)O(5) NWs were combined with conventional antibiotics (i.e., ciprofloxacin and moxifloxacin), they exhibited synergistic effects against monocultured pathogens, as demonstrated using isobologram analysis. Against S. pneumoniae, regardless of mono- or coculture, additive effects were observed, with the exception of the levofloxacin-ciprofloxacin pair, which resulted in antagonistic effects in cocultured conditions. The strategies developed in this study, therefore, have the potential to tackle polymicrobial OM, biofilm-induced infections and associated antimicrobial resistance while reducing the overall antibiotic exposure incurred by OM.