Trial Outcomes & Findings for Plasma Pharmacokinetics (PK) & Lung Penetration of Ceftolozane/Tazobactam in Participants With Pneumonia (MK-7625A-007) (NCT NCT02387372)

Last Updated: 2019-08-28

Results Overview

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for creatinine clearance (CLCR), every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the Cmax, maximum plasma concentration, of ceftolozane or tazobactam. Pharmacokinetic (PK) data analysis was performed by non-compartmental analysis (NCA) method using Phoenix WinNonlin version 6.3 or later.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

37 participants

Primary outcome timeframe

Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Results posted on

2019-08-28

Participant Flow

Adult males or non-pregnant or non-nursing females that were mechanically ventilated or critically ill were enrolled in this study.

Participant milestones

Participant milestones
Measure	Mechanically Ventilated Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Critically Ill Critically ill participants with CLCR ≥180 mL/min (as calculated by the Cockcroft-Gault equation) will receive a single dose of ceftolozane/tazobactam, 3 g, as a 60-minute intravenous infusion.
Overall Study STARTED	27	10
Overall Study Treated	26	10
Overall Study COMPLETED	26	10
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Mechanically Ventilated Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Critically Ill Critically ill participants with CLCR ≥180 mL/min (as calculated by the Cockcroft-Gault equation) will receive a single dose of ceftolozane/tazobactam, 3 g, as a 60-minute intravenous infusion.
Overall Study Not Treated	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mechanically Ventilated n=26 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Critically Ill n=10 Participants Critically ill participants with CLCR ≥180 mL/min (as calculated by the Cockcroft-Gault equation) will receive a single dose of ceftolozane/tazobactam, 3 g, as a 60-minute intravenous infusion.	Total n=36 Participants Total of all reporting groups
Age, Continuous	63.5 Years STANDARD_DEVIATION 15.85 • n=5 Participants	36.2 Years STANDARD_DEVIATION 9.65 • n=7 Participants	55.9 Years STANDARD_DEVIATION 18.90 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	4 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	10 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	9 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Population: All mechanically ventilated participants who received at least 1 dose of study drug at the correctly assigned dose level, and whose plasma drug concentration was determined. Critically ill participants were not analyzed in this outcome measure.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Maximum Plasma Concentration (Cmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	73.0 ug/mL Interval 61.4 to 86.9	22.6 ug/mL Interval 18.9 to 27.1
Maximum Plasma Concentration (Cmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	100 ug/mL Interval 84.2 to 120.0	26.1 ug/mL Interval 21.8 to 31.3

PRIMARY outcome

Timeframe: Up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 h after the start of the last infusion.

Population: All mechanically ventilated participants who received at least 1 dose of study drug at the correctly assigned dose level, and whose plasma and ELF drug concentrations were both determined. Critically ill participants were not analyzed in this outcome measure.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples and epithelial lining fluid (ELF) were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the epithelial lining fluid, ELF to plasma ratio of ceftolozane and tazobactam.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=22 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=22 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Epithelial Lining Fluid (ELF) / Plasma Ratio (Intrapulmonary Penetration) of Ceftolozane and Tazobactam Concentrations in Mechanically Ventilated Participants. 6 Hr Post-dose	1.02 Ratio Standard Deviation 0.773	2.59 Ratio Standard Deviation 2.36
Epithelial Lining Fluid (ELF) / Plasma Ratio (Intrapulmonary Penetration) of Ceftolozane and Tazobactam Concentrations in Mechanically Ventilated Participants. 8 Hr Post-dose	0.786 Ratio Standard Deviation 0.248	1.06 Ratio Standard Deviation 0.543
Epithelial Lining Fluid (ELF) / Plasma Ratio (Intrapulmonary Penetration) of Ceftolozane and Tazobactam Concentrations in Mechanically Ventilated Participants. 1 Hr Post-dose	0.213 Ratio Standard Deviation 0.130	0.234 Ratio Standard Deviation 0.140
Epithelial Lining Fluid (ELF) / Plasma Ratio (Intrapulmonary Penetration) of Ceftolozane and Tazobactam Concentrations in Mechanically Ventilated Participants. 2 Hr Post-dose	0.360 Ratio Standard Deviation 0.212	0.471 Ratio Standard Deviation 0.241
Epithelial Lining Fluid (ELF) / Plasma Ratio (Intrapulmonary Penetration) of Ceftolozane and Tazobactam Concentrations in Mechanically Ventilated Participants. 4 Hr Post-dose	1.76 Ratio Standard Deviation 3.24	2.34 Ratio Standard Deviation 4.25

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the Tmax, time of maximum plasma concentration, of ceftolozane or tazobactam. PK data analysis was performed by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Time of Maximum Plasma Concentration (Tmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	1.00 Hours Interval 0.883 to 2.0	1.00 Hours Interval 0.883 to 1.12
Time of Maximum Plasma Concentration (Tmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	1.00 Hours Interval 0.917 to 2.17	1.00 Hours Interval 0.917 to 2.17

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the Clast, last quantifiable plasma concentration, of ceftolozane or tazobactam. PK data analysis was performed by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Last Quantifiable Plasma Concentration (Clast) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	14.0 ug/mL Interval 10.3 to 19.0	1.14 ug/mL Interval 0.721 to 1.81
Last Quantifiable Plasma Concentration (Clast) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	24.0 ug/mL Interval 17.7 to 32.5	1.52 ug/mL Interval 0.955 to 2.4

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the Tlast, time of last quantifiable plasma concentration, of ceftolozane or tazobactam. PK data analysis was determined by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Time of Last Quantifiable Plasma Concentration (Tlast)) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	7.95 Hours Interval 5.77 to 8.17	7.95 Hours Interval 5.77 to 8.17
Time of Last Quantifiable Plasma Concentration (Tlast)) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	7.98 Hours Interval 6.12 to 8.33	7.98 Hours Interval 6.0 to 8.33

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the AUC0-last, AUC from the first to time of the last dose, of ceftolozane or tazobactam. PK data analysis was determined by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Area Under the Concentration Time Curve (AUC) From the First to Time of the Last Dose (AUC0-last) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	242 h*ug/mL Interval 199.0 to 293.0	50.7 h*ug/mL Interval 40.8 to 63.0
Area Under the Concentration Time Curve (AUC) From the First to Time of the Last Dose (AUC0-last) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	390 h*ug/mL Interval 321.0 to 473.0	63.0 h*ug/mL Interval 50.6 to 78.4

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the AUC0-∞, AUC from the time of the dose to infinity, of ceftolozane or tazobactam. PK data analysis was determined by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
AUC From the Time of the Dose to Infinity (AUC0-∞) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	353 h*ug/mL Interval 269.0 to 464.0	58.1 h*ug/mL Interval 45.1 to 74.7
AUC From the Time of the Dose to Infinity (AUC0-∞) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	605 h*ug/mL Interval 461.0 to 795.0	69.8 h*ug/mL Interval 54.1 to 90.0

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the t1/2, terminal elimination half-life, of ceftolozane or tazobactam. PK data analysis was performed by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Terminal Elimination Half-life (t1/2) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	4.15 Hours Geometric Coefficient of Variation 56.1	2.15 Hours Geometric Coefficient of Variation 56.4
Terminal Elimination Half-life (t1/2) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	4.86 Hours Geometric Coefficient of Variation 61.5	2.33 Hours Geometric Coefficient of Variation 49.7

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the Vss, volume of distribution at steady state, of ceftolozane or tazobactam. PK data analysis was performed by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Volume of Distribution at Steady State (Vss) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	27.5 Liter Geometric Coefficient of Variation 29.9	39.9 Liter Geometric Coefficient of Variation 28.9
Volume of Distribution at Steady State (Vss) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	29.4 Liter Geometric Coefficient of Variation 45.5	40.4 Liter Geometric Coefficient of Variation 38.8

PRIMARY outcome

Timeframe: Day 1 up to Day 2 at 0 (pre-dose), 1, 2, 4, 6 and 8 hours (h) after the start of the first and last infusions.

Mechanically ventilated participants received a 60 minute infusion of ceftolozane/tazobactam, adjusted for CLCR, every 8 hours; then blood samples were collected at 1, 2, 4, 6, and 8 hours post start of the final infusion after the last dose of study drug in order to determine the CL, plasma clearance, of ceftolozane or tazobactam. PK data analysis was performed by NCA method using Phoenix WinNonlin version 6.3 or later.

Outcome measures

Outcome measures
Measure	Mechanically Ventilated- Ceftolozane n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours	Mechanically Ventilated -Tazobactam n=25 Participants Participants with proven or suspected pneumonia, undergoing mechanical ventilation will receive 4-6 doses of ceftolozane/tazobactam every 8 hours as a 60-minute intravenous infusion as follows: * Those with Creatinine clearance (CLCR) \> 50 mL/min will receive 4-6 doses of 3 g ceftolozane/tazobactam every 8 hours * Those with CLCR 30 - 50 mL/min will receive 4-6 doses of 1.5 g ceftolozane/tazobactam every 8 hours * Those with CLCR 15 - 29 mL/min will receive 6 doses of 750 mg ceftolozane/tazobactam every 8 hours
Plasma Clearance (CL) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. First Dose	4.90 L/h Geometric Coefficient of Variation 64.1	15.0 L/h Geometric Coefficient of Variation 68.5
Plasma Clearance (CL) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment. Last Dose	4.52 L/h Geometric Coefficient of Variation 67.7	14.1 L/h Geometric Coefficient of Variation 75.6

SECONDARY outcome

Timeframe: Up to 5 days

Population: All treated participants

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.