For years, we’ve operated under a simple clinical assumption: if a diabetic foot ulcer (DFU) is infected, we reach for the antibiotics—often broad-spectrum heavy hitters like levofloxacin. But new molecular evidence suggests that while we are busy fighting bacteria, we may be unintentionally collateral-damaging the wound’s own healing machinery.
A recent study published in Scientific Reports has uncovered a “redox paradox” where common antibiotics appear to trigger oxidative stress, potentially locking chronic wounds in a state of non-healing.
The Hidden Cost of Bactericidal Therapy
We know that DFUs are already high-oxidizing environments. Chronic hyperglycemia and tissue hypoxia create a baseline of oxidative stress that stalls the healing process. However, the research by Hassan et al. reveals that levofloxacin might be pouring gasoline on this fire.
Key findings from the study indicate:
- Mitochondrial Interference: Bactericidal antibiotics don’t just target bacteria; they can disrupt mitochondrial function in human cells, leading to a surge in Reactive Oxygen Species (ROS).
- Gene Expression Shifts: Patients treated with levofloxacin showed a significant increase in the expression of genes associated with oxidative stress, including NFE2L2 (Nrf2) and HMOX-1.
- Healing Pathways Stalled: The study observed an upregulation of TGFB-1 and MMP-9 in antibiotic users. While these are necessary for healing, their excessive or persistent activation—triggered by antibiotic-induced stress—can lead to chronic inflammation and inefficient extracellular matrix formation.
Why “Nrf2” is a Double-Edged Sword
One of the most intriguing parts of this research is the role of NFE2L2 (Nrf2). Typically, Nrf2 is the “good guy”—a transcription factor that manages our antioxidant response.
However, in the context of levofloxacin treatment, the excessive and persistent activation of this pathway actually points to a wound site struggling to compensate for a massive spike in oxidative stress. This persistent activation can contribute to the “inflammatory stall” that prevents a DFU from moving into the proliferative phase of healing.
Clinical Implications: Time for a “Redox Rescue”?
This research doesn’t mean we should stop using antibiotics for severe infections. It does, however, suggest that we need to be more strategic.
- Avoid Over-Prescription: Using antibiotics “just in case” or for prolonged periods without evidence of infection may be actively delaying closure.
- The “Antioxidant Adjuvant” Strategy: The study suggests that combining antioxidants with antibiotic therapy might help neutralize the unintended oxidative damage to mammalian cells.
- Shorter Courses, Smarter Care: If antibiotics are causing biological changes at the wound site, the goal should be the shortest effective course to minimize redox disruption.
The Bottom Line: We need to stop viewing antibiotics as a “free pass” for wound healing. In our quest to eliminate pathogens, we must ensure we aren’t simultaneously handicapping the patient’s own ability to close the wound.
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