Trial Outcomes & Findings for Ceftolozane/Tazobactam (MK-7625A) Plus Metronidazole Versus Meropenem for Participants With Complicated Intra-abdominal Infection (MK-7625A-015) (NCT NCT03830333)

Last Updated: 2023-01-17

Results Overview

Clinical response was classified as "cure" or "failure". Clinical cure (favorable) was defined as complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure is required for the index infection. Clinical failure (unfavorable) was defined as death related to IAI at any time point; persisting or recurrent infection within the abdomen requiring additional intervention to cure; need for treatment with additional antibiotics for ongoing IAI symptoms; or post-surgical wound infection that requires additional antimicrobial therapy and/or non-routing wound care. The percentage of participants with clinical response of clinical cure or clinical failure at TOC was summarized.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

268 participants

Primary outcome timeframe

Up to approximately Day 30

Results posted on

2023-01-17

Participant Flow

Adult participants with complicated intra-abdominal infection (cIAI) were recruited at 21 study sites in China. Participants with severe impairment of renal function (estimated creatinine clearance \[CrCL\] \<30 mL/min) were excluded.

Participant milestones

Participant milestones
Measure	Ceftolozane/Tazobactam + Metronidazole Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Overall Study STARTED	134	134
Overall Study Clinically Evaluable Population	105	116
Overall Study COMPLETED	126	130
Overall Study NOT COMPLETED	8	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftolozane/Tazobactam + Metronidazole Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Overall Study Death	0	1
Overall Study Withdrawal by Subject	5	1
Overall Study Discontinuations associated with failure to return for follow-up assessments due to COVID-19	3	2

Baseline Characteristics

Ceftolozane/Tazobactam (MK-7625A) Plus Metronidazole Versus Meropenem for Participants With Complicated Intra-abdominal Infection (MK-7625A-015)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftolozane/Tazobactam + Metronidazole n=134 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=134 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).	Total n=268 Participants Total of all reporting groups
Age, Continuous	47.5 Years STANDARD_DEVIATION 16.2 • n=5 Participants	51.1 Years STANDARD_DEVIATION 15.7 • n=7 Participants	49.3 Years STANDARD_DEVIATION 16.0 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	49 Participants n=7 Participants	104 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	85 Participants n=7 Participants	164 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	134 Participants n=5 Participants	134 Participants n=7 Participants	268 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	134 Participants n=5 Participants	134 Participants n=7 Participants	268 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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 Site of Infection Bowel (small or large)	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Primary Site of Infection Other site of infection	129 Participants n=5 Participants	126 Participants n=7 Participants	255 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately Day 30

Population: All participants of the CE population who met the protocol definition of cIAI, had no significant protocol deviations, received the minimum duration of randomized IV study therapy, and had an efficacy assessment of cure or failure at the TOC visit were analyzed.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=105 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=116 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants With Clinical Response (Clinical Cure or Clinical Failure) at Test of Cure (TOC) Visit: Clinically Evaluable (CE) Population Clinical Cure (favorable)	95.2 Percentage of Participants	93.1 Percentage of Participants
Percentage of Participants With Clinical Response (Clinical Cure or Clinical Failure) at Test of Cure (TOC) Visit: Clinically Evaluable (CE) Population Clinical Failure (unfavorable)	4.8 Percentage of Participants	6.9 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately Day 30

Population: The ITT population consisted of all randomized participants. Participants in the ITT population were analyzed based on the treatment they were randomized to, irrespective of what they actually received.

Clinical response was classified as "cure", "failure", or "indeterminate". Clinical cure (favorable) was defined as complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure is required for the index infection. Clinical failure (unfavorable) was defined as death related to IAI at any time point; persisting or recurrent infection within the abdomen requiring additional intervention to cure; need for treatment with additional antibiotics for ongoing IAI symptoms; or post-surgical wound infection that requires additional antimicrobial therapy and/or non-routing wound care. Indeterminate (unfavorable) was defined as participants for whom study data were not available for evaluation of efficacy for any reason. The percentage of participants with clinical response of clinical cure, clinical failure, or indeterminate at TOC was summarized.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=134 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=134 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at TOC Visit: Intent to Treat (ITT) Population Clinical Cure (favorable)	85.1 Percentage of Participants	89.6 Percentage of Participants
Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at TOC Visit: Intent to Treat (ITT) Population Clinical Failure (unfavorable)	14.2 Percentage of Participants	9.7 Percentage of Participants
Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at TOC Visit: Intent to Treat (ITT) Population Indeterminate (unfavorable)	0.7 Percentage of Participants	0.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately Day 15

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=105 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=116 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants With Clinical Response (Clinical Cure or Clinical Failure) at End of Therapy (EOT) Visit: CE Population Clinical Cure (favorable)	98.1 Percentage of Participants	96.6 Percentage of Participants
Percentage of Participants With Clinical Response (Clinical Cure or Clinical Failure) at End of Therapy (EOT) Visit: CE Population Clinical Failure (unfavorable)	1.9 Percentage of Participants	3.4 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately Day 15

Clinical response was classified as "cure", "failure", or "indeterminate". Clinical cure (favorable) was defined as complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure is required for the index infection. Clinical failure (unfavorable) was defined as death related to IAI at any time point; persisting or recurrent infection within the abdomen requiring additional intervention to cure; need for treatment with additional antibiotics for ongoing IAI symptoms; or post-surgical wound infection that requires additional antimicrobial therapy and/or non-routing wound care. Indeterminate (unfavorable) was defined as participants for whom study data are not available for evaluation of efficacy for any reason. The percentage of participants with clinical response of clinical cure, clinical failure, or indeterminate at EOT was summarized.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=134 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=134 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at EOT Visit: ITT Population Clinical Cure (favorable)	92.5 Percentage of Participants	94.0 Percentage of Participants
Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at EOT Visit: ITT Population Clinical Failure (unfavorable)	7.5 Percentage of Participants	4.5 Percentage of Participants
Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at EOT Visit: ITT Population Indeterminate (unfavorable)	0.0 Percentage of Participants	1.5 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately Day 30

Population: The EME population consisted of all randomized participants who had cIAI as evidenced by identification of at least 1 baseline intra-abdominal pathogen, regardless of susceptibility to study drug and met all CE population criteria.

An overall microbiological response was determined by the Sponsor for each participant based on individual microbiological responses for each baseline bacterial pathogen. A favorable individual microbiological response was eradication (absence of the baseline bacterial pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a participant who is assessed as a clinical cure). In order for the participant to have a favorable overall microbiological response, each individual baseline bacterial pathogen must have had a favorable microbiological outcome. The percentage of participants with a favorable per-participant microbiological response of eradication or presumed eradication was reported for the TOC visit.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=54 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=73 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants With Favorable Per-Participant Microbiological Response of Eradication or Presumed Eradication at TOC Visit: Expanded Microbiologically Evaluable (EME) Population	94.4 Percentage of Participants	93.2 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately Day 30

Population: The EME population consisted of all randomized participants with data available who had cIAI as evidenced by identification of at least 1 baseline intra-abdominal pathogen, regardless of susceptibility to study drug and met all CE population criteria.

A microbiological response was determined for each bacterial pathogen isolated at baseline by the Sponsor. Favorable microbiological responses included eradication (absence of the baseline bacterial pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a participant who is assessed as a clinical cure). The percentage of participants with a favorable microbiological response of eradication or presumed eradication was reported per pathogen for the TOC visit.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=54 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=73 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Gram-negative aerobes	94.0 Percentage of Participants	95.0 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population All Enterobacteriaceae	93.8 Percentage of Participants	95.0 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Citrobacter freundii complex	100.0 Percentage of Participants	—
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Citrobacter koseri	100.0 Percentage of Participants	—
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Enterobacter aerogenes	100.0 Percentage of Participants	—
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Enterobacter cloacae complex	100.0 Percentage of Participants	—
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Other Enterobacter spp.	—	100.0 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Escherichia coli	93.8 Percentage of Participants	95.7 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Klebsiella oxytoca	—	100.0 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Klebsiella pneumoniae	100.0 Percentage of Participants	90.9 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Morganella morganii	—	100.0 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Proteus mirabilis	50.0 Percentage of Participants	—
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Aeromonas hydrophila	100.0 Percentage of Participants	—
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Pseudomonas aeruginosa	75.0 Percentage of Participants	100.0 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Gram-positive aerobes	80.0 Percentage of Participants	88.2 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Gram-negative anaerobes	—	100.0 Percentage of Participants
Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population Gram-positive anaerobes	100.0 Percentage of Participants	100.0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to approximately Day 30

Population: The All Participants as Treated (APaT) population was used for the analysis of safety data in this study. The APaT population consisted of all randomized participants who received at least one dose of study treatment.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment. An AE could therefore have been 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. The percentage of participants who experienced 1 or more AEs were summarized.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=134 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=134 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants Who Experienced 1 or More Adverse Events (AEs)	50.0 Percentage of Participants	50.7 Percentage of Participants

SECONDARY outcome

Timeframe: Up to Day 14

Population: The APaT population was used for the analysis of safety data in this study. The APaT population consisted of all randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=134 Participants Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=134 Participants Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Percentage of Participants That Discontinued Study Treatment Due to an AE	2.2 Percentage of Participants	2.2 Percentage of Participants

Adverse Events

Ceftolozane/Tazobactam + Metronidazole

Serious events: 7 serious events

Other events: 28 other events

Deaths: 0 deaths

Meropenem + Placebo

Serious events: 7 serious events

Other events: 33 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Ceftolozane/Tazobactam + Metronidazole n=134 participants at risk Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=134 participants at risk Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Cardiac disorders Atrial fibrillation	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Small intestinal obstruction	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
General disorders Death	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholecystitis	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholelithiasis	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Abdominal infection	1.5% 2/134 • Number of events 2 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	1.5% 2/134 • Number of events 2 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Peritonitis	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Pulmonary mycosis	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/134 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.

Other adverse events

Other adverse events
Measure	Ceftolozane/Tazobactam + Metronidazole n=134 participants at risk Participants received ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam could be adjusted to 500 mg/250 mg if CrCL was 30 to ≤50 mL/min).	Meropenem + Placebo n=134 participants at risk Participants received meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem could be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
Gastrointestinal disorders Constipation	0.75% 1/134 • Number of events 1 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	6.0% 8/134 • Number of events 9 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Diarrhoea	6.0% 8/134 • Number of events 8 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	8.2% 11/134 • Number of events 12 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
General disorders Pyrexia	6.7% 9/134 • Number of events 11 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	10.4% 14/134 • Number of events 15 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypokalaemia	5.2% 7/134 • Number of events 7 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	1.5% 2/134 • Number of events 2 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	5.2% 7/134 • Number of events 7 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.	6.7% 9/134 • Number of events 9 • Up to approximately Day 30 The analysis population consisted of all randomized participants who received at least one dose of study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Publication restrictions are in place

Restriction type: OTHER