This Phase IIb study aims to evaluate the safety and efficacy of BV100 in combination with low dose polymyxin B plus ceftazidime/avibactam or cefiderocol in patients with suspected or confirmed CRABC infections. The study is divided into two parts (Part A and Part B), recruiting in parallel. Approximately 10 subjects will be recruited in Part B, with enrollment ending once Part A enrollment is complete (at least 30 patients randomized to all of the three groups). Eligible patients, who have given informed consent, will be enrolled, and pre-treatment microbiology samples submitted to a local laboratory.

Part A will be the randomized, active-controlled portion of the study, evaluating patients with suspected or confirmed CRABC nosocomial pneumonia (VABP and HABP) and BSI of non-urinary tract origin. This is an open-label study, and therefore, no blinding will be done.

In Part A, patients will be randomized 1:1:1, to one of the three treatment groups until the CRABC m-MITT population includes 30 evaluable subjects per group:

• Group 1: 300 mg BV100 in combination with 500,000 IU (50 mg) polymyxin B infused over 2 hours every 12 hours (q12h), plus 2 g/0.5 g ceftazidime/avibactam*,# infused over 2 hours every 8 hours (q8h).

• Group 2: 300 mg BV100 in combination with 500,000 IU (50 mg) polymyxin B infused over 2 hours every 12 hours (q12h), plus 2 g cefiderocol infused over 3 hours every 8 hours (q8h).

• Group 3: Best Available Therapy (BAT), which is determined by the site for each individual patient according to local epidemiology and the patient's antibiotic history.

  • In case of non-Acinetobacter metallo-beta-lactamase (MBL)-producing infections confirmed by culture or identified by RDT, including polymicrobial infections,, aztreonam (2 g infused over 2 hours, q8h) should be infused simultaneously with ceftazidime-avibactam via a Y-site administration used per manufacturer's instructions, subject to Medical Monitor approval.

    • If rapid diagnostic test (RDT) on positive blood culture broths show Acinetobacter only, concomitant ceftazidime-avibactam can be omitted.

In Part A, no more than 30 patients with HABP will be enrolled across all treatment groups.

Part B is a prospective multicenter, open label, non-randomized, additional single cohort to evaluate the PK, safety, and efficacy BV100 in combination with both low dose polymyxin B and cefiderocol in patients with CRABC ventriculitis or meningitis. Optional intrathecal or intraventricular administration of polymyxin B or colistin, as well as dexamethasone therapy per local treatment standards, is permitted. After 14 days of treatment with BV100 and low dose polymyxin B, the BV100 therapy must be stopped, but patients may continue therapy with cefiderocol and best available additional therapy at the discretion of the investigator and as needed. Functioning external ventricular drains (EVDs) are required for safe and timely CSF sampling.

Approximately 10 patients are expected to be enrolled in part B, with enrollment concluding once the last patient in Part A is recruited.

Inclusion Criteria:

1. Provide written informed consent prior to any study-related procedures not part of normal medical care. Surrogate consent/use of a legally authorized representative may be provided if permitted by local country and institution-specific guidelines

2. Male subjects or female subjects ≥ 18 and ≤ 82 years of age at the time of signing informed consent.

3. A known or highly suspected infection caused by CRABC (VABP, HABP, or BSI of non-urinary tract origin) as either a single pathogen or member of a polymicrobial infection

4. Diagnosed with HABP, VABP or BSI

5. Acute Physiology and Chronic Health Evaluation (APACHE II) score ≤ 30, within 24 hours prior to randomization.

   Part B specific inclusion criteria

6. Confirmed CRABC ventriculitis or meningitis based on evidence from CSF culture collected within 72 hours prior to enrollment (as per standard of care).

7. Functioning EVD that can be used for safe and timely CSF sampling.

8. No contraindications to CSF sampling via EVD in the volumes required by the protocol

Main Exclusion Criteria:

1. Urinary tract infection as source of A. baumannii BSI2. Known or suspected community acquired bacterial pneumonia or viral (including SARS-CoV-2), pneumonia within the last 7 days 3. Known or suspected viral pneumonia within the last 7 days before screening e.g. positive for SARS-CoV-2 or influenza.

4. Known fungal or parasitic pneumonia. 5. Patients classified under futility of care, as determined by the medical team, indicating a lack of potential for benefit from intervention or patients who are permanent residents of long-term care facilities and have been assessed as receiving palliative or comfort-focused care.

6. Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure ≥ 65 mmHg (calculate mean arterial pressure = diastolic pressure plus 1/3 (systolic pressure minus diastolic pressure)) with patients requiring escalating vasopressor support to maintain adequate arterial pressure in conjunction with rising lactate.7. Known or suspected allergies to polymyxins, rifabutin, ceftazidime/avibactam, cefiderocol, or their excipients.

8. Inability to insert a central catheter or a peripherally inserted central catheter (PICC).11. Acute graft versus host disease Grade ≥ 3.

12. Expected survival < 72 hours or a Do Not Resuscitate Order. 13. Burns > 40% of total body surface area. 14. Presence of neutropenia (absolute neutrophil count < 1500/mm3) obtained from a local laboratory at Screening, or anticipated neutropenia with absolute neutrophil count < 1500 cells/mm3.

15. Severe renal disease defined as an estimated glomerular filtration rate (eGFR) as per Modification of Diet in Renal Disease (MDRD) formula (MDRD eGFR) < 30 mL/min/1.73 m2, or requirement for peritoneal dialysis, hemodialysis, hemofiltration, or a urine output < 20 mL/hour over a 24 hour period.