Plasma Pharmacokinetics (PK) & Lung Penetration of Ceftolozane/Tazobactam in Participants With Pneumonia (MK-7625A-007)

This is a Phase 1, prospective, multicenter, non-comparative, open-label study to
characterize the plasma pharmacokinetics and intrapulmonary penetration of
ceftolozane/tazobactam in two groups of participants.

Group 1: approximately 25 ventilated participants with suspected or proven pneumonia
receiving concurrent standard antibiotic therapy. Within Group 1, efforts will be made to
enroll approximately 5 participants with a CLCR ≥ 150 mL/min (as calculated by the
Cockcroft-Gault equation).

Group 2: 8-10 critically ill participants with CLCR ≥180 mL/min (as calculated by the
Cockcroft-Gault equation).

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.