Cefiderocol Concentrations in the Lungs of Hospitalized Patients With Bacterial Pneumonia
Condition: Bacterial Pneumonia
MeSH terms: Pneumonia; Pneumonia, Bacterial
Intervention: Cefiderocol; Standard of Care Antibiotic
Intervention description: Administered intravenously, at a dosage determined based on renal function.; Standard of care antibiotic treatment for pneumonia
Intervention MeSH terms: Anti-Bacterial Agents
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary purpose of the study is to determine the degree of penetration of cefiderocol
      into infected lung tissue in hospitalized adults with bacterial pneumonia who are being
      mechanically ventilated.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject is 18 years or older at the time written informed consent is obtained

          2. Subject has provided written informed consent or informed consent has been provided by
             subject's legally authorized representative

          3. Subject has a diagnosis or suspicion of bacterial pneumonia (even if later known that
             the subject does not have bacterial pneumonia, discontinuation of the study is not
             necessary)

          4. Subject is hospitalized and receiving standard of care antibiotic treatment for
             pneumonia

          5. Subject is mechanically ventilated or expected to be mechanically ventilated at least
             48 hours (or 72 hours for subjects with severe renal impairment) after the first dose
             of cefiderocol

          6. Subject has a life expectancy of at least 3 weeks from the Screening visit

          7. Subject is male (no contraception required) or female and meets 1 of the following
             criteria:

               1. Surgically sterile (has had a hysterectomy and/or bilateral oophorectomy, or a
                  bilateral salpingectomy or tubal ligation for the purpose of contraception for at
                  least 6 weeks with appropriate documentation of such surgery)

               2. Postmenopausal (defined as older than 45 years of age with cessation of regular
                  menstrual periods for at least 6 months and a follicle-stimulating hormone level
                  of > 40 mIU/mL, or amenorrhea for at least 12 months)

               3. Of childbearing potential and using combined (estrogen and progestogen) or
                  progestogen-only hormonal contraception associated with inhibition of ovulation
                  (including oral, intravaginal, injectable, implantable, and transdermal
                  contraceptives), or an intrauterine device (IUD), or intrauterine
                  hormone-releasing system for the entire duration of the study

               4. Of childbearing potential and practicing abstinence as a preferred and usual life
                  style and/or agrees to continue practicing abstinence from Screening for the
                  entire duration of the study

               5. Of childbearing potential and whose sole heterosexual partner has been
                  successfully vasectomized and agrees to not have other heterosexual partners for
                  the entire duration of the study

        Exclusion Criteria:

        Subjects who meet any of the following criteria will be excluded from the study:

          1. Subject has a chemical pneumonia that does not require antibiotic treatment (including
             aspiration of gastric acid, inhalation injury). The term chemical pneumonia refers to
             the aspiration of substances that are toxic to the lower airways causing chemical burn
             and injuries in the airway.

          2. Subject has 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)

          3. Subject has extensive cystic lesion(s) or severe structural abnormality (eg, cystic
             fibrosis, emphysema, cystic lesions of sarcoidosis or tuberculosis, postobstructive
             pneumonia due to lung cancer, etc) of the lung that hinders recovery of
             bronchoalveolar lavage fluid (BALF)

          4. Subject is receiving peritoneal dialysis

          5. Subject has severe renal impairment requiring hemodialysis (HD) or end-stage renal
             disease requiring HD

          6. Subject is in refractory septic shock defined as persistent hypotension despite
             adequate fluid resuscitation or despite vasopressive therapy at Screening

          7. Subject is a female who has a positive pregnancy test at Screening or who is lactating

          8. Subject has received another investigational drug within 30 days prior to Screening

          9. Subject has previously participated in this clinical study and has received at least 1
             dose of cefiderocol within 7 days

         10. Subject has any condition or circumstance that, in the opinion of the investigator,
             would compromise the safety of the subject or the quality of the study data