Complicated Intra-Abdominal Infection
Conditions
Keywords
Ceftazidime, Meropenem, Metronidazole, Anti-Bacterial Agents, Anti-Infective Agents, Antiprotozoal Agents, Antiparasitic Agents, cIAI, Complicated Intra-Abdominal Infection
Brief summary
The purpose of this study is to evaluate the effects of Ceftazidime Avibactam plus Metronidazole compared to Meropenem for treating hospitalized patients with complicated intra-abdominal infections.
Detailed description
A Phase III, Randomized, Multicenter, Double Blind, Double-Dummy, Parallel-Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections In Hospitalized Adults
Interventions
DRUGCAZ-AVI
Ceftazidime 2000 mg and 500 mg of avibactam
DRUGMetronidazole
500 mg of Metronidazole
DRUGMeropenem
1 gram of Meropenem
Sponsors
Forest Laboratories
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 90 years of age inclusive * Female patient is authorized to participate if at least one of the following criteria are met: 1. Surgical sterilization 2. Age ≥50 years and postmenopausal as defined by amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments 3. Age \<50 years and postmenopausal as defined by documented LH and FSH levels in the postmenopausal range PLUS amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments 4. Patient has a negative serum pregnancy test (serum ß-human chorionic gonadotropin \[ß-hCG\]) within 1 day prior to study entry, and agrees to use highly effective contraception methods during treatment and for at least 7 days after last dose of IV study therapy * Intraoperative/postoperative enrollment with confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis * Confirmation of infection by surgical intervention within 24 hours of entry: evidence of systemic inflammatory response; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdominal infections
Exclusion criteria
* Patient is diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which primary etiology is not likely to be infectious * Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation * Patient has suspected intra-abdominal infections due to fungus, parasites, virus or tuberculosis * Patient is considered unlikely to survive the 6 to 8 week study period or has a rapidly progressive or terminal illness, including septic shock that is associated with a high risk of mortality
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | TOC: 28 to 35 days after start of study drug | The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention is necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, death where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA. |
| Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | TOC: 28 to 35 days after start of study drug | The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. |
| Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]). | TOC: 28 to 35 days after start of study drug | The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU 42 to 49 days after start of study drug | Microbiological responses as per the protocoled criteria: responses other than indeterminate were classified as favorable or unfavorable. Favorable microbiological response assessments included eradication and presumed eradication. Unfavorable microbiological response assessments included persistence, persistence with increasing minimum inhibitory concentration (MIC), and presumed persistence. Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to a surgical review panel (SRP) assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence). |
| Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | TOC: 28 to 35 days after start of study drug. | The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure. |
| Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Test of Cure: 28 to 35 days after start of study drug | Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. |
| Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set | TOC: 28 to 35 days after start of study drug | The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. |
| Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Test of Cure: 28 to 35 days after start of study drug | Microbiological responses other than indeterminate were classified as favorable or unfavorable. Favorable microbiological response assessments included eradication and presumed eradication. Unfavorable microbiological response assessments included persistence, persistence with increasing minimum inhibitory concentration (MIC), and presumed persistence. Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence). |
| Number of Patients Afebrile at Last Observation in the Clinically Evaluable Analysis Set for Patients Who Have Fever at Study Entry | Test of Cure: 1 to 14 days after start of study drug | Time to first defervescence was calculated for patients with a fever (\>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day. |
| Plasma Concentrations for Ceftazidime and Avibactam | Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug | Blood samples were taken from all patients on Day 3 for the pharmacokinetic evaluation of ceftazidime and avibactam plasma concentrations |
| Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | TOC: 28 to 35 days after start of study drug | The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure. |
| Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set | TOC: 28 to 35 days after start of study drug | The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. |
| Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU: 42 to 49 days after start of study drug | Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. |
Countries
Argentina, Bulgaria, Croatia, Czechia, Hungary, India, Israel, Latvia, Malaysia, Mexico, Netherlands, Peru, Romania, Russia, South Africa, Spain, Taiwan, Thailand, Ukraine, United States
Participant flow
Recruitment details
Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA. First patient enrolled 22 March 2012 and last patient's last visit was 07 April 2014. Patients were adults hospitalised with complicated intra-abdominal infection (cIAI) that required surgery and IV antibiotics.
Pre-assignment details
After obtaining written informed consent patients underwent a preliminary evaluation for eligibility within the 24-hour period prior to initiation of IV study therapy. eligible patients were randomized to 1 of 2 treatment groups in a 1:1 ratio according to the central randomization schedule.
Participants by arm
| Arm | Count |
|---|---|
| CAZ-AVI + Metronidazole CAZ (2000mg)/AVI (500mg): IV treatment | 520 |
| Meropenem 1000 mg: IV treatment | 523 |
| Total | 1,043 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 7 |
| Overall Study | Condition improved/subject recovered | 1 | 0 |
| Overall Study | Lack of Efficacy | 7 | 8 |
| Overall Study | Not specified in study report | 11 | 5 |
| Overall Study | Withdrawal by Subject | 22 | 15 |
Baseline characteristics
| Characteristic | CAZ-AVI + Metronidazole | Meropenem | Total |
|---|---|---|---|
| Age, Continuous | 49.8 Years STANDARD_DEVIATION 17.48 | 50.3 Years STANDARD_DEVIATION 18.29 | 50.0 Years STANDARD_DEVIATION 17.88 |
| Sex: Female, Male Female | 194 Participants | 191 Participants | 385 Participants |
| Sex: Female, Male Male | 326 Participants | 332 Participants | 658 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 184 / 529 | 152 / 529 |
| serious Total, serious adverse events | 17 / 529 | 15 / 529 |
Outcome results
Primary
Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA).
The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention is necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, death where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure. Results from two identical protocols D4280C00001 and D4280C00005 combined into a single database with agreement from FDA and EMA.
Time frame: TOC: 28 to 35 days after start of study drug
Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | Clinical cure | 337 Participants |
| CAZ-AVI + Metronidazole | Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | Clinical failure | 37 Participants |
| CAZ-AVI + Metronidazole | Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | Indeterminate | 39 Participants |
| Meropenem | Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | Clinical cure | 349 Participants |
| Meropenem | Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | Clinical failure | 30 Participants |
| Meropenem | Clinical Response at the Test of Cure (TOC) Visit in the Microbiologically Modified Intent-To-Treat (mMITT) Analysis Set (Primary Outcome for FDA). | Indeterminate | 31 Participants |
Comparison: The primary objective of this study (FDA agreed) was to determine the noninferiority in the clinical cure rate for CAZ-AVI compared to that for Meropenem at TOC in the mMITT in adult subjects with cIAI.95% CI: [-8.64, 1.58]
Primary
Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]).
The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time frame: TOC: 28 to 35 days after start of study drug
Population: The CE analysis set included all patients who met the disease definition of cIAI and met the stringent criteria for clinical evaluation described in the protocol regarding dosing, concomitant medication, evaluation, etc.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical cure | 376 Participants |
| CAZ-AVI + Metronidazole | Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical failure | 34 Participants |
| Meropenem | Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical cure | 385 Participants |
| Meropenem | Clinical Response at the TOC Visit in the Clinically Evaulable (CE) Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical failure | 31 Participants |
Comparison: The co-primary objective of this study (ROW agreed) was to determine the noninferiority in the clinical cure rate for CAZ-AVI compared to that for Meropenem at TOC in the CE in adult subjects with cIAI.95% CI: [-4.61, 2.89]
Primary
Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]).
The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure.
Time frame: TOC: 28 to 35 days after start of study drug
Population: The MITT analysis set included all randomized patients who met the disease definition of cIAI and who received any amount of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical cure | 429 Participants |
| CAZ-AVI + Metronidazole | Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical failure | 47 Participants |
| CAZ-AVI + Metronidazole | Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Indeterminate | 44 Participants |
| Meropenem | Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical cure | 444 Participants |
| Meropenem | Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Clinical failure | 39 Participants |
| Meropenem | Clinical Response at the TOC Visit in the Modified Intent-To-Treat Analysis Set (Co-primary Outcome for Rest of World [ROW]). | Indeterminate | 40 Participants |
Comparison: The co-primary objective of this study (ROW agreed) was to determine the noninferiority in the clinical cure rate for CAZ-AVI compared to that for Meropenem at TOC in the MITT in adult subjects with cIAI.95% CI: [-6.9, 2.1]
Secondary
Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set
The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time frame: TOC: 28 to 35 days after start of study drug
Population: Extended ME analysis set defined as all patients included in the CE set with at least 1 Gram negative, aerobic, pathogen in the initial/prestudy culture, regardless of susceptibility.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set | Clinical cure | 248 Participants |
| CAZ-AVI + Metronidazole | Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set | Clinical failure | 22 Participants |
| Meropenem | Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set | Clinical cure | 278 Participants |
| Meropenem | Clinical Cure at TOC in the Extended Microbiologically Evaluable Analysis Set | Clinical failure | 16 Participants |
Secondary
Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set
The number of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time frame: TOC: 28 to 35 days after start of study drug
Population: ME analysis set defined as all patients included in the CE set with at least 1 Gram negative, aerobic, susceptible pathogen in the initial/prestudy culture.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set | Clinical cure | 244 Participants |
| CAZ-AVI + Metronidazole | Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set | Clinical failure | 21 Participants |
| Meropenem | Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set | Clinical cure | 272 Participants |
| Meropenem | Clinical Cure at TOC in the Microbiologically Evaluable Analysis Set | Clinical failure | 15 Participants |
Secondary
Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set
Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Time frame: Test of Cure: 28 to 35 days after start of study drug
Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Morganella morganii | 1 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter cloacae | 2 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Pseudomonas aeruginosa | 2 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Serratia marcescens | 1 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Comamonas testosteroni | 1 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Escherichia coli | 19 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter aerogenes | 0 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Citrobacter freundii complex | 1 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Proteus mirabilis | 2 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Klebsiella pneumoniae | 10 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | All | 39 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Alcaligenes faecalis | 1 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Citrobacter freundii complex | 2 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Morganella morganii | 1 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | All | 55 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Serratia marcescens | 0 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Proteus mirabilis | 3 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter aerogenes | 1 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Comamonas testosteroni | 0 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter cloacae | 7 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Pseudomonas aeruginosa | 4 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Escherichia coli | 31 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Alcaligenes faecalis | 2 Participants |
| Meropenem | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Klebsiella pneumoniae | 9 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Serratia marcescens | 1 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | All | 47 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Citrobacter freundii complex | 1 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter aerogenes | 0 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter cloacae | 3 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Escherichia coli | 24 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Klebsiella pneumoniae | 13 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Morganella morganii | 2 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Proteus mirabilis | 2 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Alcaligenes faecalis | 1 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Comamonas testosteroni | 1 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Pseudomonas aeruginosa | 2 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Klebsiella pneumoniae | 13 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Escherichia coli | 37 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | All | 64 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Alcaligenes faecalis | 2 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter cloacae | 7 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Enterobacter aerogenes | 1 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Pseudomonas aeruginosa | 4 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Comamonas testosteroni | 0 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Citrobacter freundii complex | 2 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Proteus mirabilis | 3 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Morganella morganii | 1 Participants |
| Meropenem (TOC) | Clinical Response by Pathogen at TOC for Patients Infected With Ceftazidime-resistant Pathogens in Microbiological Modified Intent to Treat Analysis Set | Serratia marcescens | 0 Participants |
Secondary
Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT)
Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary. Indeterminate response are where study data were not available for evaluation of efficacy for any reason, including patient lost to follow-up or assessment not undertaken such that a determination of clinical response could not be made, dDeath where cIAI was clearly noncontributory or circumstances that precluded classification as a cure or failure.
Time frame: EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU: 42 to 49 days after start of study drug
Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical failure | 30 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical cure | 361 Participants |
| CAZ-AVI + Metronidazole | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Indeterminate | 22 Participants |
| Meropenem | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical failure | 19 Participants |
| Meropenem | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical cure | 379 Participants |
| Meropenem | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Indeterminate | 12 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical failure | 37 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical cure | 337 Participants |
| CAZ-AVI + Metronidazole (TOC) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Indeterminate | 39 Participants |
| Meropenem (TOC) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical failure | 30 Participants |
| Meropenem (TOC) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical cure | 349 Participants |
| Meropenem (TOC) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Indeterminate | 31 Participants |
| CAZ-AVI + Metronidazole (LFU) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical failure | 38 Participants |
| CAZ-AVI + Metronidazole (LFU) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical cure | 340 Participants |
| CAZ-AVI + Metronidazole (LFU) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Indeterminate | 35 Participants |
| Meropenem (LFU) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical cure | 347 Participants |
| Meropenem (LFU) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Indeterminate | 32 Participants |
| Meropenem (LFU) | Clinical Response by Visit in the Primary Population: Microbiologically Modified Intent-to-Treat (mMITT) | Clinical failure | 31 Participants |
Secondary
Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set
The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time frame: TOC: 28 to 35 days after start of study drug
Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Citrobacter freundii complex | 1 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Escherichia coli | 19 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Serratia marcescens | 1 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter aerogenes | 0 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Proteus mirabilis | 2 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Klebsiella pneumoniae | 10 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter cloacae | 2 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Pseudomonas aeruginosa | 2 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Comamonas testosteroni | 1 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Morganella morganii | 1 Participants |
| CAZ-AVI + Metronidazole | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Alcaligenes faecalis | 1 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Morganella morganii | 1 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Alcaligenes faecalis | 2 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Proteus mirabilis | 3 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Serratia marcescens | 0 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter cloacae | 7 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Pseudomonas aeruginosa | 4 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Escherichia coli | 31 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Comamonas testosteroni | 0 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Klebsiella pneumoniae | 9 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter aerogenes | 1 Participants |
| Meropenem | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Citrobacter freundii complex | 2 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Comamonas testosteroni | 1 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Citrobacter freundii complex | 2 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter aerogenes | 0 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter cloacae | 3 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Escherichia coli | 24 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Klebsiella pneumoniae | 13 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Morganella morganii | 2 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Proteus mirabilis | 2 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Serratia marcescens | 1 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Alcaligenes faecalis | 1 Participants |
| CAZ-AVI + Metronidazole (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Pseudomonas aeruginosa | 2 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Morganella morganii | 1 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Pseudomonas aeruginosa | 4 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Alcaligenes faecalis | 2 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Klebsiella pneumoniae | 13 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Escherichia coli | 37 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter cloacae | 7 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Comamonas testosteroni | 0 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Enterobacter aerogenes | 1 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Citrobacter freundii complex | 2 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Serratia marcescens | 0 Participants |
| Meropenem (TOC) | Favorable Per-pathogen Microbiological Response for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Proteus mirabilis | 3 Participants |
Secondary
Number of Patients Afebrile at Last Observation in the Clinically Evaluable Analysis Set for Patients Who Have Fever at Study Entry
Time to first defervescence was calculated for patients with a fever (\>38ºC) at baseline. Defervescence (≤37.8ºC) was defined as the absence of fever based on the highest temperature recorded on each study day.
Time frame: Test of Cure: 1 to 14 days after start of study drug
Population: Clinically evaluable (CE) with fever, defined as \>38ºC at study entry.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CAZ-AVI + Metronidazole | Number of Patients Afebrile at Last Observation in the Clinically Evaluable Analysis Set for Patients Who Have Fever at Study Entry | 84 Participants |
| Meropenem | Number of Patients Afebrile at Last Observation in the Clinically Evaluable Analysis Set for Patients Who Have Fever at Study Entry | 72 Participants |
Secondary
Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set.
The number of patients with a favorable per-pathogen microbiological response: favourable microbiological response includes: Eradication Absence of causative pathogen from specimens at the site of infection. Presumed eradication where, repeat cultures were not performed/clinically indicated in a patient who had a clinical response of cure.
Time frame: TOC: 28 to 35 days after start of study drug.
Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Citrobacter freundii complex | 14 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parvimonas micra | 7 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides stercoris | 9 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Pseudomonas aeruginosa | 30 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides ovatus | 17 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter cloacae | 11 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Clostridium perfringens | 7 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus avium | 8 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus mitis group | 10 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella oxytoca | 14 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus bovis group | 2 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecalis | 22 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parabacteroides distasonis | 13 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter aerogenes | 4 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides vulgatus | 6 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecium | 13 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella pneumoniae | 40 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides fragilis | 45 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides thetaiotaomicron | 18 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Staphylococcus aureus | 17 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Eggerthella lenta | 5 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Escherichia coli | 218 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides uniformis | 4 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus anginosus group | 59 Participants |
| CAZ-AVI + Metronidazole | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Proteus mirabilis | 5 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus anginosus group | 50 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides thetaiotaomicron | 21 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus bovis group | 6 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus mitis group | 9 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides stercoris | 1 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides fragilis | 38 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides ovatus | 17 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella oxytoca | 12 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter aerogenes | 5 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Eggerthella lenta | 7 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella pneumoniae | 37 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Citrobacter freundii complex | 9 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Proteus mirabilis | 7 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Clostridium perfringens | 4 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Pseudomonas aeruginosa | 34 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus avium | 10 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter cloacae | 16 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides vulgatus | 6 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecalis | 23 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parvimonas micra | 8 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecium | 18 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parabacteroides distasonis | 12 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides uniformis | 6 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Staphylococcus aureus | 14 Participants |
| Meropenem | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Escherichia coli | 249 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides fragilis | 52 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Citrobacter freundii complex | 18 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter aerogenes | 5 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter cloacae | 13 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Escherichia coli | 271 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella oxytoca | 18 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella pneumoniae | 51 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Proteus mirabilis | 8 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Pseudomonas aeruginosa | 35 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus avium | 8 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecalis | 31 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecium | 16 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Staphylococcus aureus | 18 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus anginosus group | 72 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus bovis group | 3 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus mitis group | 15 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides ovatus | 22 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides stercoris | 10 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides thetaiotaomicron | 22 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides uniformis | 7 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides vulgatus | 8 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Clostridium perfringens | 10 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Eggerthella lenta | 5 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parabacteroides distasonis | 16 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parvimonas micra | 7 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides thetaiotaomicron | 25 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Staphylococcus aureus | 14 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecium | 22 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parvimonas micra | 10 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides uniformis | 7 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus faecalis | 28 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterococcus avium | 15 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Parabacteroides distasonis | 13 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides vulgatus | 9 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Pseudomonas aeruginosa | 36 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Proteus mirabilis | 9 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter aerogenes | 5 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Clostridium perfringens | 4 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella pneumoniae | 49 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Klebsiella oxytoca | 15 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Citrobacter freundii complex | 12 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Eggerthella lenta | 8 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides ovatus | 20 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides fragilis | 47 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus mitis group | 11 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Escherichia coli | 285 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Bacteroides stercoris | 1 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus bovis group | 7 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Streptococcus anginosus group | 61 Participants |
| Meropenem (TOC) | Per-pathogen Microbiological Response at TOC in the Microbiologically Modified Intent-To-Treat Analysis Set. | Enterobacter cloacae | 19 Participants |
Secondary
Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set
Microbiological responses other than indeterminate were classified as favorable or unfavorable. Favorable microbiological response assessments included eradication and presumed eradication. Unfavorable microbiological response assessments included persistence, persistence with increasing minimum inhibitory concentration (MIC), and presumed persistence. Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to an SRP assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time frame: Test of Cure: 28 to 35 days after start of study drug
Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Favourable | 39 Participants |
| CAZ-AVI + Metronidazole | Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Unfavourable | 7 Participants |
| CAZ-AVI + Metronidazole | Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | indeterminate | 2 Participants |
| Meropenem | Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Favourable | 55 Participants |
| Meropenem | Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | Unfavourable | 1 Participants |
| Meropenem | Per-patient Microbiological Response at TOC for Patients Infected With Ceftazidime-resistant Pathogens in mMITT Analysis Set | indeterminate | 8 Participants |
Secondary
Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set
Microbiological responses as per the protocoled criteria: responses other than indeterminate were classified as favorable or unfavorable. Favorable microbiological response assessments included eradication and presumed eradication. Unfavorable microbiological response assessments included persistence, persistence with increasing minimum inhibitory concentration (MIC), and presumed persistence. Indeterminate microbiologic response assessments included cases where the clinical response was changed to indeterminate due to a surgical review panel (SRP) assessment of inadequate source control (ie, circumstances that preclude classification as eradication, presumed eradication, persistence, persistence with increasing MIC, and presumed persistence).
Time frame: EOT: within 24 hours after last dose of study drug. TOC: 28 to 35 days after start of study drug. LFU 42 to 49 days after start of study drug
Population: The mMITT analysis set included all randomized patients who met the disease definition of cIAI and had at least 1 etiologic pathogen identified at study entry (regardless of isolate susceptibilities). Patients with a bacterial species typically not expected to respond to both study drugs were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAZ-AVI + Metronidazole | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Unfavourable response | 30 Participants |
| CAZ-AVI + Metronidazole | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Favourable response | 362 Participants |
| CAZ-AVI + Metronidazole | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Indeterminate | 21 Participants |
| Meropenem | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Unfavourable response | 19 Participants |
| Meropenem | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Favourable response | 379 Participants |
| Meropenem | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Indeterminate | 12 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Unfavourable response | 37 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Favourable response | 337 Participants |
| CAZ-AVI + Metronidazole (TOC) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Indeterminate | 39 Participants |
| Meropenem (TOC) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Unfavourable response | 31 Participants |
| Meropenem (TOC) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Favourable response | 349 Participants |
| Meropenem (TOC) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Indeterminate | 30 Participants |
| CAZ-AVI + Metronidazole (LFU) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Unfavourable response | 38 Participants |
| CAZ-AVI + Metronidazole (LFU) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Favourable response | 340 Participants |
| CAZ-AVI + Metronidazole (LFU) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Indeterminate | 35 Participants |
| Meropenem (LFU) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Favourable response | 347 Participants |
| Meropenem (LFU) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Indeterminate | 31 Participants |
| Meropenem (LFU) | Per-patient Microbiological Response in the Microbiologically Modified Intent- To-Treat Analysis Set | Unfavourable response | 32 Participants |
Secondary
Plasma Concentrations for Ceftazidime and Avibactam
Blood samples were taken from all patients on Day 3 for the pharmacokinetic evaluation of ceftazidime and avibactam plasma concentrations
Time frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug
Population: PK analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CAZ-AVI + Metronidazole | Plasma Concentrations for Ceftazidime and Avibactam | 50823.0 (NG/ML) |
| Meropenem | Plasma Concentrations for Ceftazidime and Avibactam | 9229.4 (NG/ML) |
| CAZ-AVI + Metronidazole (TOC) | Plasma Concentrations for Ceftazidime and Avibactam | 40053.1 (NG/ML) |
| Meropenem (TOC) | Plasma Concentrations for Ceftazidime and Avibactam | 7163.9 (NG/ML) |
| CAZ-AVI + Metronidazole (LFU) | Plasma Concentrations for Ceftazidime and Avibactam | 10967.6 (NG/ML) |
| Meropenem (LFU) | Plasma Concentrations for Ceftazidime and Avibactam | 1690.7 (NG/ML) |