Plasma Pharmacokinetics (PK) & Lung Penetration of Ceftolozane/Tazobactam in Participants With Pneumonia (MK-7625A-007)
Condition: Critically Ill; Pneumonia
MeSH terms: Pneumonia; Critical Illness
Intervention: Ceftolozane/Tazobactam - Multiple Doses; Ceftolozane/Tazobactam - Single Dose
Intervention description: 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows:
Participants with CLCR > 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours
Participants with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours
Participants with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours; Single dose of ceftolozane/tazobactam, 3 g, as a 60-minute intravenous infusion
Intervention MeSH terms: Tazobactam; Ceftolozane; Cephalosporins; Ceftolozane, tazobactam drug combination; Penicillanic Acid
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the pharmacokinetics and lung penetration of
      intravenous Ceftolozane/tazobactam in critically ill participants.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide written informed consent prior to any study-related procedure not part of
             normal medical care.

          2. If female,must not be pregnant or nursing, and is either:

               1. Not of childbearing potential, defined as postmenopausal for at least 1 year or
                  surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or
                  hysterectomy; or

               2. Of childbearing potential and:

                    -  Is practicing an effective method of contraception (e.g., oral/parenteral
                       contraceptives or a barrier method) and for at least 1 month prior to
                       baseline assessments, or

                    -  Has a vasectomized partner, or

                    -  Is currently abstinent from sexual intercourse. Participants must be willing
                       to practice the chosen contraceptive method or remain abstinent during the
                       conduct of the study and for at least 30 days after last dose of study
                       medication.

          3. Non-vasectomized males are required to practice effective birth control methods (e.g.,
             abstinence, use of a condom or use of other barrier device) during the conduct of the
             study and for at least 30 days after last dose of study medication;

          4. Participants in Group 1 must meet the following criteria:

               1. Males or females age 18 years or older;

               2. Intubated and on mechanical ventilation for at least 24 hours prior to time of
                  enrollment (includes participants with tracheostomy who are mechanically
                  ventilated);

               3. Proven or suspected bacterial pneumonia, as confirmed by the presence of at least
                  one of the prescribed clinical signs and symptoms.

               4. Receiving antibiotic therapy for proven or suspected bacterial pneumonia at the
                  time of enrollment and expected to continue on antibiotic therapy while in the
                  study

          5. Participants in Group 2 must meet the following criteria:

               1. Males or females aged 18 - 54 years;

               2. Acute Physiology and Chronic Health Evaluation II (APACHE II) score between 12
                  and 35, inclusive;

               3. CLCR ≥180 mL/min (as calculated by the Cockcroft-Gault equation using actual body
                  weight) within 24 hours of dosing;

               4. Documented infection or presumed infection.

        Exclusion Criteria:

          1. Has a documented history of any moderate or severe hypersensitivity or allergic
             reaction to any β-lactam antibacterial (a history of a mild rash followed by
             uneventful re-exposure is not a contraindication to enrollment);

          2. Hemoglobin < 7 g/dL at baseline;

          3. Prior (within 24 hours of first dose of study drug) or concomitant receipt of
             piperacillin/tazobactam, probenecid or ceftolozane/tazobactam (non-study use);

          4. Any rapidly-progressing disease or immediately life-threatening illness (defined as
             imminent death within 48 hours in the opinion of the Investigator);

          5. Any condition or circumstance that, in the opinion of the Investigator, would
             compromise the safety of the participant or the quality of study data;

          6. Planned or prior participation in any interventional drug study within the last 30
             days;

          7. Participants in Group 1 must not meet any of the following criteria:

               1. Receipt of effective systemic antibiotic therapy for the treatment of proven or
                  suspected bacterial pneumonia for more than 72 hours prior to start of the first
                  dose of study drug

               2. Any of the following diagnoses or conditions that may interfere with the PK
                  assessment/interpretation:

                    -  Cystic fibrosis, acute exacerbation of chronic bronchitis or obstructive
                       airway disease, chronic severe respiratory disease , or active pulmonary
                       tuberculosis,

                    -  Full thickness burns (greater than 15% of total body surface area),

                    -  Lung transplant recipient or donor,

                    -  Any condition or situation where bronchoscopy is not advisable;

          8. End-stage renal disease defined as a CLCR < 15 mL/min (as calculated by the
             Cockcroft-Gault equation using actual body weight), OR requirement for continuous
             renal replacement therapy or hemodialysis.