# Iron(III)–Tropolone Complex as a Topical Agent Against Drug-Resistant MRSA Skin Infections

## TL;DR

A new iron-based compound shows strong antimicrobial activity against drug-resistant MRSA skin infections without causing resistance or irritation.

## Contribution

Fe(tropo)3 is a novel non-antibiotic topical agent effective against drug-resistant Staphylococcus aureus strains.

## Key findings

- Fe(tropo)3 effectively kills drug-resistant MRSA strains with a minimum inhibitory concentration of 2 µg/mL.
- The compound induces bacterial cell death through iron accumulation and reactive oxygen species generation.
- Fe(tropo)3 formulated as a 1% ointment reduces SA load by 98% in a mouse wound model without irritation.

## Abstract

Background/Objectives: The widespread use of mupirocin and fusidic acid for the treatment and decolonization of Staphylococcus aureus (SA) skin infections has led to a rapid emergence of resistant strains, limiting the effectiveness of the few topical agents currently available for clinical use. Methods: In this study, we evaluate Fe(tropo)3, a neutral and lipophilic iron(III)–tropolone complex, as a non-antibiotic topical antimicrobial candidate for the management of drug-resistant SA skin and soft tissue infections. Results: Fe(tropo)3 exhibits potent in vitro activity against methicillin-susceptible SA, methicillin-resistant SA (MRSA), vancomycin-intermediate SA, and strains with high-level resistance to mupirocin and fusidate, with minimum inhibitory concentrations of 2 µg/mL across all tested isolates. The compound effectively penetrates bacterial cells, induces intracellular iron accumulation, and triggers dose-dependent reactive oxygen species generation, resulting in rapid bacterial killing and significant antibiofilm activity. Importantly, Fe(tropo)3 shows a slower development of resistance compared with ciprofloxacin and displays synergistic activity with oxacillin against MRSA. When formulated as a 1% topical ointment, Fe(tropo)3 significantly reduces bacterial burden in a murine excisional wound infection model, achieving a 98% ± 1% reduction in SA load without detectable hemolysis or skin irritation. Conclusions: These pilot study results support Fe(tropo)3 as a clinically relevant, mechanism-distinct topical antimicrobial with potential utility in settings where resistance to existing topical antibiotics compromises standard care.