•Modified wording describing the primary objective, clarifying that the primary comparison is a composite outcome and not clinical or microbiological responses individually •Clarified subject population (including restriction/stratification of subjects with uncomplicated pyelonephritis, number of pathogens that could be present in urine), duration of treatment, dose adjustment (based on Cockcroft-Gault equation) •Clarified period during which women should not attempt to get pregnant after study drug administration and also allowed for country specific requirements, which might be longer •Clarified “the what and the why” for prohibited medications •Clarified components of clinical evaluation and microbiological response •Clarified statistical section, incorporated 15% noninferiority margin, defined populations, clarified sample size, and clarified stratification at randomization •Clarified function of the DSMB as performing a safety evaluation and not an interim analysis of efficacy •Clarified that treatment duration of 7 to 14 days in hospital may be shortened to 5 days if it became in the subject’s best interest •Clarified minimum versus recommended treatment duration •Adjusted dosing tables to include dosing instructions for subjects weighing <40kg •Clarified the need to record all concomitant antimicrobial therapies and time frame involved, and reinforced that the use of antimicrobial therapies with only Gram-positive activities were allowed if needed; clarified timing for withdrawal and restarting these therapies in relation to treatment; added details for use of rescue therapy and prophylactic antimicrobials •Added Subject Structured Interview and changed terminology to “Structured Patient Interview” for consistency •Clarified definition of AEs in the context of study, study treatment, and population •Clarified follow-up time for SAEs, reporting time for pregnancy, and reasons for discontinuation •Specified timing of ECG in relation to infusion

• Increased the number of subjects (from 300 to 400) so that this study would provide the majority of subjects for the safety evaluation of the drug for the submission to the FDA • Increased the number of subjects with acute uncomplicated pyelonephritis and the time required for enrollment and revised statistical evaluation description • Allowed for collection of available safety laboratory information that may have been available prior to the subject entering the study, ie, prior to any drug treatment for subjects with previous short term antibiotic treatment (< 24 hours) • Clarified what needed to be completed in the event that a super infection or a new infection was identified • Clarified the primary analysis and the method of arriving at the result

• Increased the number of subjects (from 400 to 450) so that this study would provide sufficient safety subjects for submission to the FDA (for a total of 300 subjects treated with cefiderocol) • Increased the number of subjects with acute uncomplicated pyelonephritis and the time required for enrollment and revised statistical evaluation description