Synergistic bacterial inactivation by combining antibiotics with nanosecond electric pulses

Antibiotic resistance mechanisms render current antibiotics ineffective, requiring higher concentrations of existing drugs or the development of more powerful drugs for infection treatment. This study demonstrates the synergistic inactivation of a gram-positive (Staphylococcus aureus) and a gram-negative (Escherichia coli) bacteria by combining either tobramycin or rifampicin with 300-ns electric pulses (EPs). For EPs depositing the same total energy density into the sample with no drug, higher electric fields induced greater inactivation, indicating a threshold for irreversible electroporation at these fields and membrane recovery in between lower intensity EPs. Synergistic inactivation generally increased with increasing drug concentration up to 20 μg/mL compared to strictly EP treatment. Combining even 1/20 of the clinical dose of tobramycin with a train of EPs induced between 2.5 and 3.5 log inactivation after only 10 min of exposure compared to hours to induce inactivation with a clinical dose with no EPs. Similarly, combining a train of EPs with a clinically relevant dose of rifampicin induced 7 to 9 log inactivation over the same time of exposure. These results indicate the promise of combining EPs with antibiotics to rapidly inactivate antibiotic-resistant bacteria in localized treatment areas.