Amendment 1 was country specific applying only to study sites in Korea. The medical monitor was updated to Sue Cammarata, M.D. from Eugene Sun, M.D. It was added that for patients in the vancomycin treatment arm, vancomycin dose adjustments for impaired renal function will be allowed, and it was also added that patients with a CrCl of 15 - 29 mL/min at Screening may receive 1 gram of aztreonam every 12 hours. Patients receiving initial combination therapy with aztreonam with CrCl greater than 29 mL/min at Screening will receive 2 grams every 12 hours.

Changes to the protocol amendment included a statement that vancomycin dosing and monitoring as described in the protocol were a recommendation, not required, and that sites could elect to dose patients in accordance with local standard of care. In addition, PK sample time points on Day 5 were removed and blood sample collections on Day 3 were updated to 1.5 and 3 hours only. Monitoring of glucose on select days and pharmacoeconomic endpoints were removed. Pain assessments were to be made by paper patient reported instead of electronically, and anaerobic blood cultures were optional for sites that were unable to process. A modification was made that abscesses, and no other infection type, were to be stratified by treatment group. Finally, a clarification was made that CrCl was to be calculated with each blood chemistry panel, and concomitant medications were to be recorded starting at the time of first study drug dose instead of from the time of informed consent.

Changes to the protocol included removing a secondary objective for the FDA of clinical response of reduction of erythema of >=30% at 48 - 72 hours. For patients that withdrew and did not complete study treatment and receive other antibiotics, procedures were updated to not collect follow-up efficacy data. The update was made that digital photography and manual measurements made on Day 3 were to be collected within 2 hours before each dose and did not have to be 12 hours apart. A targeted physical examination was added to End of Treatment patients discontinuing prematurely from study treatment. A +3-day window was added to the Telephone Call Follow-up, and if a patient was positive for Hepatitis B or C at screening, it should be added to the medical history section of the eCRF as a pre-existing condition. An update to the delafloxacin dosing regimen was made that dose would not be modified based on CrCl levels as screening. The percentage of patients with a BMI of >=30 was increased to 40% of the total population and no more than 30% of enrolled patients would have wound infections. Secondary efficacy endpoints were updated and were to be tested using a fixed sequential procedure, and end of treatment was added to database for visits with the clinical response. Finally, administration of nonstudy antibacterials for treatment-related AE was included in clinical response definition of failure, and once a patient was considered failure at a particular visit, the patient was considered a failure at all later timepoints.

This protocol amendment included changes to the dosing of delafloxacin based on CrCl levels, and specified that patients with a BMI of >=30 were to make up no more than 50% of the enrolled population. Treatment differences reported for the primary and secondary endpoints from updated from vancomyin - delafloxacin to delafloxacin - vancomycin. Lastly, it was added that the sensitivity analyses of the primary endpoints were to be stratified by BMI (<30 and >=30).