Methods are taught for treating chronic wounds and skin and soft tissue infections with antibiotic tumescent injection. In such methods, the region of tumescent drug delivery is monitored and expanded by the infusate in order to be 2×-5× larger in area and volume in the region of the wound or infection, the drug in the infusate creates a tissue concentration greater than the MIC in the tumescent volume for selected period of time, and the high concentration has a residence lifetime in the tissue long enough to kill the bacteria. Typically, the methods are performed without the use of vasoconstrictors such as epinephrine and in a manner that avoids physical manipulation of the wound.
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