Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens

1. Patients who have a history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)

2. Patients who need more than 3 systemic antibiotics as part of best available therapy (BAT) for the treatment of the Gram-negative infection (patients with mixed Gram-positive or anaerobic infections may receive appropriate concomitant narrow spectrum antibiotics \[eg, vancomycin, linezolid, metronidazole, clindamycin\])

3. Patients with coinfection caused by invasive aspergillosis, mucormycosis or other highly lethal mold

4. Patients who have central nervous system (CNS) infection (eg, meningitis, brain abscess, shunt infection)

5. Patients with infection requiring \> 3 weeks of antibiotic treatment (eg, bone and joint infection, endocarditis)

6. Patients with cystic fibrosis or moderate to severe bronchiectasis

7. Patients in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at the time of Randomization

8. Patients with severe neutropenia, ie, polymorphonuclear neutrophils (PMNs) \< 100 cells/μL

9. Female patients who have a positive pregnancy test at Screening or who are lactating

10. Patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score \> 30

11. Patients who have received a potentially effective antibiotic regimen for the carbapenem-resistant Gram-negative infection for a continuous duration of more than 24 hours in cUTI, or 36 hours in HAP/VAP/HCAP or BSI/sepsis during the 72 hours leading to Randomization

12. Patients with any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the study data

13. Patients who have received another investigational drug or device within 30 days prior to study entry

14. Patients who have previously been randomized in this study or received S-649266

15. Patients receiving peritoneal dialysis

What this study is about