REAL-WORLD OBSERVATIONAL STUDY OF ZAVICEFTA (REGISTERED) (CEFTAZIDIME-AVIBACTAM) TO CHARACTERIZE USE PATTERNS, EFFECTIVENESS AND SAFETY - EZTEAM STUDY
Conditions: Infection
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study Information
Title
Real-World Observational Study of Zavicefta® (ceftazidime-avibactam) to 
Characterize Use Patterns, Effectiveness and Safety – EZTEAM Study
Protocol number
C3591031
Protocol version identifier
4.0, amendment 3
Date of last version of protocol
29 April 2020
Active substance
ceftazidime-avibactam, ACT: J01DD52
Medicinal product
Zavicefta® (ceftazidime-avibactam)
Research question and 
objectives
The main objective of this non-interventional medical chart review study is 
to describe general treatment patterns, effectiveness, and safety of 
ceftazidime-avibactam in Europe including Russia and Latin America.
Authors
 MD
 
Pfizer, UK
Tel: 
, MSc, PhD
Pfizer, France
Tel: 
 MSc, PhD
IQVIA, France
Tel: 
This document contains confidential information belonging to Pfizer. Except as otherwise agreed to in 
writing, by accepting or reviewing this document, you agree to hold this information in confidence and not 
copy or disclose it to others (except where required by applicable law) or use it for unauthorized purposes. In 
the event of any actual or suspected breach of this obligation, Pfizer must be promptly notified.
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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................2
2. LIST OF ABBREVIATIONS................................................................................................4
3. RESPONSIBLE PARTIES....................................................................................................6
4. ABSTRACT...........................................................................................................................7
5. AMENDMENTS AND UPDATES.....................................................................................11
6. MILESTONES.....................................................................................................................15
7. RATIONALE AND BACKGROUND................................................................................16
8. RESEARCH QUESTION AND OBJECTIVES .................................................................18
9. RESEARCH METHODS ....................................................................................................19
9.1. Study Design ...........................................................................................................19
9.2. Setting......................................................................................................................21
9.2.1. Inclusion Criteria ........................................................................................22
9.2.2. Exclusion Criteria.......................................................................................22
9.3. Variables..................................................................................................................22
9.4. Data Sources............................................................................................................26
9.5. Study Size................................................................................................................27
9.5.1. Study Size in Europe ..................................................................................27
9.5.2. Study Size in Latin America.......................................................................28
9.6. Data Management ...................................................................................................29
9.7. Data Analysis ..........................................................................................................29
9.7.1. Exposure .....................................................................................................29
9.7.2. Outcomes ....................................................................................................30
9.7.3. Baseline Participant and Infection Characteristics .....................................31
9.7.4. Planned Analyses........................................................................................33
9.8. Quality Control........................................................................................................34
9.9. Limitations of the Research Methods......................................................................34
10. PROTECTION OF HUMAN SUBJECTS ........................................................................35
10.1. Patient Information................................................................................................35
10.2. Patient Consent......................................................................................................36
10.3. Patient Withdrawal................................................................................................36
10.4. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............36
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10.5. Ethical Conduct of the Study ................................................................................36
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................37
11.1. Single Reference Safety Document (SRSD).........................................................38
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........38
13. COMMUNICATION OF ISSUES ....................................................................................38
14. REFERENCES ..................................................................................................................39
15. LIST OF TABLES.............................................................................................................44
16. LIST OF FIGURES ...........................................................................................................44
ANNEX 1. DEFINITIONS OF DIFFERENT SUBCATEGORIES OF OUTCOME ............45
ANNEX 2. LIST OF STAND-ALONE DOCUMENTS.........................................................47
ANNEX 3: DEYO-CHARLSON COMORBIDITY INDEX..................................................48
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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
Adverse Event
AEM
Adverse Event Monitoring
APACHE
Acute Physiology and Chronic Health Evaluation 
Score
BSI
Bloodstream Infection 
CAI
Community-Acquired Infection
CI
Confidence Interval
cIAI
Complicated Intra-Abdominal Infection 
CLABSI
Central Line Associated Blood Stream Infection
CRE
Carbapenem-Resistant Enterobacteriaceae
CT
Computerized Tomography
cUTI
Complicated Urinary Tract Infection 
DCCI
Deyo-Charlson Comorbidity Index 
eCRF
Electronic Case Report Form 
EMA
European Medicines Agency 
FDA
Food and Drug Administration 
GEP
Good Epidemiological Practice
HAI
Hospital-Acquired Infection 
HAP
Hospital-Acquired Pneumonia
HAUTI
Healthcare-Associated Urinary Tract Infection 
HCAI
Healthcare-Associated Infection
HCAP
Healthcare-Associated Pneumonia
IAI
Intra-Abdominal Infection 
ICF
Informed Consent Form
ICU
Intensive Care Unit
IEC
Independent Ethics Committee 
IRB
Institutional Review Board 
LATAM
Latin America
LOS
Length of Stay
MDR
Multidrug-Resistant
MDRGN
Multidrug-Resistant Gram-Negative Organism
MRI
Magnetic Resonance Imaging
NI
Non-Interventional 
NIS
Non-Interventional Study 
NP
Nosocomial Pneumonia
SAE
Serious Adverse Event
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Abbreviation
Definition
SAP
Statistical Analysis Plan 
SAS
Statistical Analysis System
SRSD
Single Reference Safety Document
SSI
Surgical Site Infection 
UTI
Urinary Tract Infection 
VAP
Ventilator-Associated Pneumonia
WBDC
Web-Based Data Capture 
WHO
World Health Organization 
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3. RESPONSIBLE PARTIES
Principal Investigators of the Protocol
Name, degree(s)
Title
Affiliation
Address
 MD
 
Pfizer
Pfizer, UK
Tel: 
 
MSc, PhD
Pfizer
Pfizer, France
Tel: 
Pfizer
Pfizer, France
Tel: 
 MSPH
 
Pfizer
Pfizer, USA
Tel: 
 PhD
Pfizer
Pfizer, USA
Principal Investigator(s) of the Protocol
A full list of Principal Investigators and country coordinating investigators is available upon 
request.
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4. ABSTRACT
Title
Real-World Observational Study of Zavicefta® (ceftazidime-avibactam) to Characterize Use 
Patterns, Effectiveness and Safety
Rationale and Background
Antimicrobial resistance and healthcare-associated infections (HCAIs) are well known public 
health threats. Gram-negative bacteria cause common hospital-acquired infections (HAIs) 
and infection with multidrug-resistant gram-negative organisms (MDRGNs), and have been 
associated with increased morbidity, mortality, and healthcare costs. Zavicefta®
(ceftazidime-avibactam) is a unique combination of ceftazidime and avibactam developed to 
treat infections caused by gram-negative pathogens. In the European Union, Russia and 
several Latin American countries, ceftazidime-avibactam is an approved treatment of 
complicated intra-abdominal infection (cIAI), complicated urinary tract infections (cUTIs), 
hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and infection 
due to aerobic gram-negative organisms with limited treatment options.
Ceftazidime-avibactam has proven efficacious in non-inferiority Phase III trials but 
real-world evidence is needed about treatment characteristics, safety, and efficacy against 
Pseudomonas and multidrug-resistant (MDR) gram-negative bacteria, including 
carbapenem-resistant Enterobacteriaceae (CRE).
Research Question and Objectives
The main objective of this medical chart review study is to describe general treatment 
patterns, effectiveness, and safety of ceftazidime-avibactam in real-world settings in Europe 
(including Russia) and Latin America.
Study Design
This observational study will include approximately 700 hospitalized patients with a 
gram-negative infection, who have received at least one dose of ceftazidime-avibactam.
Patients will be recruited in approximately 62 sites across 12 countries in Europe (including 
Russia) and Latin America. Patients will be followed from ceftazidime-avibactam initiation 
until 60 days post hospital discharge, mortality, withdrawal from the study, or 
loss-to-follow-up, whichever occurs first. Data will be abstracted from medical records using 
an electronic case report form (eCRF). Baseline data include patient socio-demographics, 
medical history, and clinical and microbiological characteristics of the infection treated. 
Follow-up data will include details of treatment over time and clinical, microbiological, and 
healthcare resource utilization outcomes. Evaluation of clinical success will be performed in 
patients with at least ≥72 hours of exposure to ceftazidime-avibactam. Safety will be 
evaluated in all patients exposed to at least one dose of the product.
Population
Hospitalized patients with gram-negative infections treated with ceftazidime-avibactam. 
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Variables

Exposure: ceftazidime-avibactam.

Outcomes: clinical effectiveness, microbiological outcomes, adverse events (AEs), 
serious adverse events (SAEs), length of hospital stay, in-hospital healthcare resource 
utilization; mortality and hospital readmissions within 60 days of hospital discharge.

Key covariates: patient demographics, indication, infection source 
(hospital/healthcare/community), treatment history, clinical characteristics.
Data Sources
Data from European and Latin American study sites will be used for this study. Sites will be 
qualified and then selected, based on responses to a series of questions intended to determine 
their capability of conducting the study and ability to contribute to the target patient 
population. Data will be abstracted from patient medical charts after treatment completion, 
and up to 60 days post hospital discharge or a censoring event (death, withdrawal from the 
study, or loss-to-follow-up).
Study Size
Overall, 700 patients with a gram-negative infection who have received at least one dose of 
ceftazidime-avibactam will be enrolled in this study.
Sample size was based on the following assumptions, assuming 75% of patients enrolled 
with at least 72 hours exposure to ceftazidime-avibactam and 70% clinical success, enrolling 
300 patients in Europe would yield approximately 225 evaluable patients for clinical success 
and an expected 95% confidence interval (CI) of 70.0% (63.6% - 75.9%).
Assuming 10% of patients with at least 72 hours exposure to ceftazidime-avibactam have no 
pathogen identification, and 80% experience microbiological success, enrolling 300 patients 
in Europe would yield approximately 202 evaluable patients for microbiological success and 
a 95% CI of 80.0% (73.8% - 85.3%).
Based on the same assumptions for treatment outcomes as in Europe, 400 patients will be 
included in Latin America to obtain 300 evaluable patients for clinical success, and 
270 evaluable patients for microbiological success. Using a two-sided exact method, 
enrolling 400 patients would yield an expected 95% CI of 70.0% (64.5% - 75.1%) of patients 
experiencing clinical treatment success and 80.0% (76.7% - 83.1%) of patients experiencing 
microbiological treatment success.
Data Analysis
Baseline characteristics will be summarized for ceftazidime-avibactam patients. Descriptive 
statistics will be used to summarize the treatment patterns (eg, dosage, indications, infection 
source), effectiveness (eg, clinical and microbiological outcomes), and safety (eg, mortality, 
AEs) of ceftazidime-avibactam and healthcare resource utilization by patients prescribed 
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ceftazidime-avibactam. AEs and SAEs will be recorded and summarized as the proportion of 
patients with each safety event out of all treated patients. Hospital readmissions will be 
analyzed as the proportion of patients readmitted to the hospital for recurrent infection within 
60 days of hospital discharge out of all patients discharged from the initial hospitalization. 
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Milestones
Start of data collection: November 2018.
End of data collection: approximately December 2020 or later if the sample size is not 
reached.
Final study report: Q3 2021 for Europe and Q1 2022 for Latin America.
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5. AMENDMENTS AND UPDATES
Amendment#1: 04 October 2019
Sections modified and updates
Reason
Study information: Update authors and milestones
6. Milestones: Final study report: Q3 2021 for Europe Q1 2022 for 
LATAM
Administrative
Study information; 4. Abstract; 9. Research methods 
This observational study will include approximately 1030 hospitalized 
patients with a gram-negative infection, who have received at least one 
dose of ceftazidime-avibactam. Patients will be recruited in 
approximately 62 sites across 12 countries in Europe and Latin 
America.
Extension of the study to Latin 
American countries, after local 
approval and launch of 
ceftazidime-avibactam.
8. Research question and objectives
Describe the microbiological outcomes among patients treated with 
ceftazidime-avibactam during the 14 days after ceftazidime-avibactam 
initiation. 
Describe safety outcomes in patients receiving ceftazidime-avibactam 
between treatment initiation and hospital discharge.
Microbiology results are 
collected for 14 days after 
treatment initiation with 
ceftazidime-avibactam. 
Safety information is available 
only during the initial 
hospitalization. 
9.1. Study design
Patients treated with at least one dose of ceftazidime-avibactam in 
routine clinical practice can be enrolled from the date of 
ceftazidime-avibactam launch in the country, or January 2018, or a 
maximum of 6 months before study start in the participating site, 
whichever is latest, onwards.
Extension of the study to Latin 
America.
9.5 Study size

Europe: 630 enrolled patients.

Latin America: 400 enrolled patients.
Extension of the study to Latin 
America.
9.7.1. Exposure
Addition of definitions for new line of therapy: 

A line of treatment is considered finished when at least one 
antibiotic given in combination is modified. 

Escalation after 4 days of treatment (dose increase or addition of 
another antibiotic for gram-negative) will be considered as a 
failure.

Stream lining (stop an antibiotic) or conversion to oral therapy will 
be considered as a success.
According to the decision of the 
Steering Committee, 
14 May 2019.
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Sections modified and updates
Reason
9.7.4. Planned analyses

Europe and Latin America will be analyzed separately.

Outcomes of interest will be stratified by indication, by bacteria
(Escherichia coli, Klebsiella spp., Enterobacter spp., Pseudomonas 
spp., others), and by country.
According to the decision of the 
Steering Committee, 
14 May 2019
Amendment#2: 9 December 2019
Sections modified and updates
Reason

Inclusion criterion 2: Change time period of 
ceftazidime-avibactam intake among participating patients (Patient 
received ≥1 dose of ceftazidime-avibactam in routine practice at 
participating site since 01 January 2018 OR the date of launch in 
the country if after 2018).

Patient information and consent 
1.
Remote consent can be completed if approved by local 
legislation. 
2.
A Next of Kin informed consent will be sought for deceased 
patients. For out of reach patients a waiver may be used in 
countries where it is acceptable and approved by local 
regulations.

Change number of sites to 62.
Administrative
Amendment#3: 29 April 2020
Sections modified and updates
Reason
3. Responsible parties
Michael Begnino has been removed from the responsible parties
Administrative
Study information; 4. Abstract; 9. Research methods
This observational study will include approximately 700 hospitalized 
patients with a gram-negative infection, who have received at least one 
dose of ceftazidime-avibactam.
9.5 Study size

Europe: 300 enrolled patients.

Latin America: 400 enrolled patients.
Sample size reduction in Europe
due to difficulty to recruit 
patients in this region.
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Sections modified and updates
Reason
Table 1. Sample Size and Precision of the Estimate for Clinical 
Treatment Success and Table 2. Sample Size and Precision of the 
Estimate for Microbiological Treatment Success have been updated 
with a row for 200 subjects
9.5.2. Study size in Latin America
The part of the sentence below that is marked in bold has been added:
Based on the same assumptions for treatment outcomes as in Europe, 
to obtain a 95% CI for treatment success that is approximately 
10.0 percentage points for both clinical and microbiological 
treatment success, 400 patients will be included in Latin America to 
obtain 300 evaluable patients for clinical success, and 270 evaluable 
patients for microbiological success.
9.1 Study design
Section added: In France data abstraction should be retrospective only 
and in this case data abstraction should start after the 60 days follow-
up date. Patient information sheet that is specific to France should be 
sent to patients before data abstraction starts. No follow-up calls with 
patients should occur in France.
Regulatory
To describe the data abstraction 
according to French regulatory 
framework.
9.1 Study design
Patients treated (for the indication that is approved in the country as 
per country label) with at least one dose of ceftazidime-avibactam in 
routine clinical practice at a participating site since 01 January 2018, 
or the date of launch in the country if after 2018, can be enrolled.
As this is an observational study, patients will be treated as per local 
label based on the standard of care at the discretion of their physician.
9.7.3 Baseline participant and infection characteristics
Indication for ceftazidime-avibactam prescription (will vary depending 
on country local label).
Other infection with limited treatment options: This indication is not 
approved in all participating countries.
Zavicefta® indications vary 
across countries, and 
prescriptions should follow the 
local label.
9.4. Data sources
Data will be abstracted from patient medical charts after treatment
completion, and up to 60 days post hospital discharge or a censoring 
event (death, withdrawal from the study, or loss-to-follow-up).
Administrative.
Language alignment.
9.9. Limitations of the research methods
Some editorial changes have been done in this section:

Deletion of the following sentences: 

To address this issue, data will only be collected for a limited 
period prior to study start.

Characteristics of patients treated prior to and after study start 
will be compared to examine any bias from this source.

Addition of the part of the sentence marked in bold below:
Finally, this study will only capture adverse events (AEs) related to 
ceftazidime-avibactam or other products marketed by the sponsor
- that are reported in the patient medical records and not all AEs that 
occur.
Administrative.
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Sections modified and updates
Reason
10. Protection of human subjects
10.1 Patient Information and 10.2. Patient consent: sections updated 
according to the current template.
10.4. Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC)
The following paragraph has been changed:
There must be prospective approval of the study protocol, protocol 
amendments, and other relevant documents (eg, ICFs if applicable) 
from the relevant IRBs/IECs.  All correspondence with the IRB/IEC 
must be retained.  Copies of IRB/IEC approvals must be forwarded to 
Pfizer. 
11. Management and reporting of adverse events/adverse reactions 
The following paragraphs have been changed:
Scenarios involving drug exposure, including exposure during 
pregnancy, exposure during breast feeding, medication error, overdose, 
misuse, extravasation, lack of efficacy and occupational exposure 
associated with the use of a Pfizer product must be reported, within 
24 hours of awareness, to Pfizer Safety using the NIS AEM Report 
Form.
For these AEs with an explicit attribution or scenarios involving 
exposure to a Pfizer product, the safety information identified in the 
unstructured data reviewed is captured in the Event Narrative 
section of the report form, and constitutes all clinical information 
known regarding these AEs.  
To update the protocol to 
current template
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6. MILESTONES
Study Milestones
Milestone
Planned date
Start of data collection
November 2018
End of data collection
December 2020 or later if the sample 
size is not reached 
Final study report
Q3 2021 for Europe, Q1 2022 for 
Latin America
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7. RATIONALE AND BACKGROUND
According to the World Health Organization (WHO), infections were among the top 
3 leading causes of death worldwide as of 2012.1 Antimicrobial resistance and 
healthcare-associated infections (HCAIs) are well known major public health threats.2
The annual number of patients with at least one HCAI in European acute care hospitals was 
estimated at 3.2 million (95% confidence interval [CI]: 1.9–5.2 million) in 2011-2012.3
HCAI can result in prolonged hospital stay, long-term disability, high costs for patients and 
their families, and death, increased resistance of microorganisms to antimicrobial agents and 
financial burden for the health system.4,5 In Europe, the 2008 WHO report on communicable 
diseases estimated that HCAIs cause an estimated 16 million days of hospitalization and 
37,000 deaths annually, and contribute to an additional 110,000 deaths.6 In Latin America, 
the prevalence of HCAIs is high and has been reported to be around 12.7,8
Gram-negative bacteria develop resistance to commonly prescribed antibiotics through 
mutation and gene acquisition.9 Multidrug-resistant gram-negative organisms (MDRGNs) 
have emerged as a major threat to hospitalized patients and have been associated with 
mortality rates between 30% and 70%.10-16 Infections caused by drug-resistant, 
gram-negative bacteria represent a considerable financial burden to healthcare systems due to 
the increased costs of managing the infection, especially resulting from extended hospital 
stays.17 In 2009, the European Centre for Disease Prevention and Control (ECDC) and the 
European Medicines Agency (EMA) estimated that the total healthcare cost incurred in 
Europe due to resistant infections totaled at least €1.5 billion each year, with more than half 
of this total accounted for by resistant gram-negative pathogens, €867 million. Costs include 
both healthcare treatment and societal costs such as lost productivity due to absence from 
work and.18
Gram-negative bacteria cause the 4 most frequent types of hospital-acquired infections 
(HAIs): hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia 
[VAP]), intra-abdominal infection (IAI), urinary tract infection (UTI), and bloodstream 
infection (BSI); and caused 43% of all HCAIs, 65% of catheter-associated UTIs, 65% of 
HAP, and 22% of central line associated bloodstream infections (CLABSI) from 2009 to 
2010 in the United States.9 The most important gram-negative pathogens in the hospital 
setting include Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, 
which account for 27% of all pathogens and 70% of all gram-negative pathogens causing 
HCAIs.9
Urinary tract infection (UTI) is among the most common bacterial conditions in adults; it 
has been reported to represent 19% of the HCAIs in acute care hospitals in Europe and 
remains an important clinical problem with costly financial implications to society.3,19,20
Complicated urinary tract infection (cUTI) occurs in both men and women, usually 
associated with some functional or structural abnormality: calculi or stones, indwelling 
catheters or other drainage devices, obstruction, immunosuppression, renal failure, renal 
transplantation and pregnancy.19-21 Inappropriate practice, such as failure to remove a 
urinary catheter no longer needed for patient care, are associated with cUTI.21 Most of the 
nosocomial UTIs are complicated infections.20 The bacterial spectrum of 
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healthcare-associated urinary tract infections (HAUTIs) is broad, and antibiotic resistance is 
common.22 One study reported that the most commonly isolated groups of microorganisms 
in UTI are gram-negative Enterobacteriaceae (63.8;2 and the most commonly isolated 
microorganism overall was Escherichia. coli (15.2% overall, and 37.1% in UTIs), followed 
by Staphylococcus aureus (12.1% overall and 21.5% in surgical site infections [SSIs]).2 The 
UTI antimicrobial resistance patterns restrict effective antibiotic therapy, evolve over time 
and show geographical variability.20
Intra-abdominal infections (IAI) can be divided into several groups based on the 
underlying process: peritonitis (primary or secondary), abscess (intraperitoneal, liver, 
pancreatic), perforation (complicating appendicitis, diverticulitis or gastric and duodenal 
ulcers), diverticula of intestine and other infectious process such as cholangitis or.23,24
Complicated IAI (cIAI) occurs when the infection process affects more than one organ, 
causing localized or diffuse peritonitis. It requires both surgical and antibiotic therapy 
beyond the 24-hour regimen of perioperative antibiotics typically used in uncomplicated IAI. 
It is primarily a clinical diagnosis.24 Patients with poor nutritional status, 
immunosuppression and high Acute Physiology and Chronic Health Evaluation (APACHE) 
score are at increased risk for cIAI and subsequent mortality. Most IAIs are polymicrobial,
with enteric gram-negative pathogens contributing heavily. In healthcare-associated IAIs, 
highly resistant gram-negative pathogens may predominate. A study that evaluated a total of 
3,160 clinical isolates of E. coli from IAIs from 13 European countries between 2008 and 
2009 showed that 11% were found to produce extended-spectrum beta-lactamases 
(ESBLs).25 Risk of mortality among patients with intra-abdominal sepsis have been 
estimated between 25% to 35% but can exceed 70% depending on risk.26-29
Hospital-acquired pneumonia (HAP) is a type of healthcare-associated pneumonia
(HCAP) that consists of a lower respiratory infection that was not incubating at the time of 
hospital admission and that presents clinically 2 or more days after hospitalization.30 The 
VAP is a type of HAP in persons who had a device to assist or control respiration 
continuously through a tracheostomy or by endotracheal intubation within the 48-hour period 
before the onset of infection. It is associated with intubation, invasive mechanical 
ventilation, sedation, curarization, coma, trauma, the presence of enteral nutrition, and 
surgery.31 A study reported that the most commonly isolated groups of microorganisms in 
pneumonia are gram-negative non-Enterobacteriaceae (36.5%).2 The HAP has been 
associated with relatively high rates of antimicrobial resistance, especially in patients in 
intensive care units (ICUs) or those requiring mechanical ventilation.32 Several 
epidemiologic studies have suggested that the empiric administration of inadequate antibiotic 
treatment for HAP is an important determinant of hospital,33-35 which appears to be especially 
concerning with organisms associated with high resistance rates, including Pseudomonas 
spp., Serratia spp., Enterobacter spp., and Acinetobacter spp.32 Estimates of the risk of 
death among patients with VAP have ranged from 7% to 30%.36
For cUTI, cIAI and HAP/VAP and other HCAI, antibiotics are usually prescribed 
empirically before physicians are able to identify the causative pathogen. Failure of initial 
empiric antibiotic therapy is associated with increased morbidity, mortality, and may be 
associated with additional healthcare resource utilization and costs.37
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The available evidence shows that the proportion of gram-negative organisms resistant to 
commonly used antibiotics is increasing.38,41 For the past 3 decades, carbapenems played a 
central role in treating severe infections caused by suspected drug-resistant bacteria. This has 
been compromised by the emergence of pathogens resistance to carbapenems, especially in 
Enterobacteriaceae.42 In response to this threat, the novel beta-lactamase inhibitor 
avibactam was developed and is able to inactivate many of the class C and class A 
beta-lactamases, including Klebsiella pneumoniae carbapenemases (KPCs).43
Zavicefta® (ceftazidime-avibactam) is a unique combination of ceftazidime and avibactam 
administered intravenously that has been approved in the European Union, Russia and Latin 
American countries for the treatment of cIAI, cUTI, HAP/VAP, and infection due to aerobic 
gram-negative organisms with limited treatment options,44 including carbapenem-resistant 
Enterobacteriaceae (CRE).42
Ceftazidime-avibactam efficacy and safety have been assessed in Phase II trials45,46 and in 
non-inferiority Phase III trials. Ceftazidime-avibactam plus metronidazole was compared to 
meropenem in patients with cIAI, results demonstrated that ceftazidime-avibactam was 
non-inferior for clinical cure rate for;47 ceftazidime-avibactam was compared to meropenem 
in patients with nosocomial pneumonia (NP) including VAP, results showed that 
ceftazidime-avibactam was non-inferior for clinical cure rate and 28-day mortality for NP 
patients;48 ceftazidime-avibactam was compared to doripenem in patients with cUTI/acute 
pyelonephritis, ceftazidime-avibactam was proved non-inferior for symptomatic resolution 
and microbiological cure rate in.49 Ceftazidime-avibactam in vitro activity against CRE has 
been shown.42 In 7 Phase II and Phase III clinical trials, 2024 adult patients were treated 
with ceftazidime-avibactam. The most common adverse reactions occurring in ≥5% of 
patients treated with ceftazidime-avibactam were positive Coombs direct tests, nausea, and 
diarrhea. Nausea and diarrhea were usually mild or moderate in intensity.44 Real-world data 
examining the treatment characteristics, safety, and efficacy of ceftazidime-avibactam 
against multidrug-resistant (MDR) pathogens including CRE is needed.
8. RESEARCH QUESTION AND OBJECTIVES
The main objective of this non-interventional (NI) medical chart review study is to describe 
the general treatment patterns, effectiveness, and safety of ceftazidime-avibactam in 
real-world settings. 
The primary objective of this study is to describe the patterns of use of ceftazidime-
avibactam in real-world practice.

Describe the indications and reasons for use of ceftazidime-avibactam; provide 
detailed information about its use for the treatment of infections due to aerobic 
gram-negative organisms with limited treatment options.

Describe the usage patterns of ceftazidime-avibactam, including treatment line, dose, 
frequency of dose, duration, and polytherapy regimens.

Describe the microbiological evidence available for patients treated with 
ceftazidime-avibactam.
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
Describe the source of infection for which ceftazidime-avibactam is prescribed 
including community-acquired infections (CAIs), HCAIs, and HAIs.
The secondary objective of this study is to determine the effectiveness and safety of 
ceftazidime-avibactam in real-world practice. 

Describe the clinical outcomes of patients treated with ceftazidime-avibactam 
(ie, treatment success, failure, or indeterminate) in-hospital, and up to 30 and 60-days
after hospital discharge.

Describe the microbiological outcomes among patients treated with 
ceftazidime-avibactam during the 14 days after ceftazidime-avibactam initiation.

Describe safety outcomes in patients treated with ceftazidime-avibactam between 
treatment initiation and hospital discharge. 

Describe the in-hospital length of stay (LOS), LOS in ICU and healthcare resource 
utilization in patients treated by ceftazidime-avibactam. 

Determine the prevalence of hospital readmissions for recurrence of the same 
infection within 30 and 60 days of hospital discharge among patients treated with 
ceftazidime-avibactam. 

Determine the in-hospital mortality and mortality up to 30 and 60 days after hospital 
discharge in patients treated by ceftazidime-avibactam.
9. RESEARCH METHODS
9.1. Study Design
This is a NI medical chart review study aiming to examine the treatment patterns, 
effectiveness, and safety of ceftazidime-avibactam in approximately 12 countries and 62 sites 
in Europe (including Russia) and Latin America.
Patients treated with at least one dose of ceftazidime-avibactam (for the indication that is 
approved as per country label) in routine clinical practice at a participating site since 
01 January 2018 or the date of launch in the country if after 2018 can be enrolled.
As this is an observational study, patients will be treated as per local label based on the 
standard of care at the discretion of their physician. No drugs will be supplied for this study 
and patients will receive treatment through standard local practice. Patients treated as part of 
a compassionate program of ceftazidime-avibactam are not eligible to participate in the 
study. 
Written informed consent will be provided by the patients prior to enrolling in the study in 
accordance with local regulations. In most cases, hospitalized patients or their legal delegate 
(when applicable) will provide written informed consent in person. For discharged patients 
or patients for whom the legal delegate is not available in person, remote consenting will be 
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performed via telephone calls if approved by local regulation. After study information is 
provided remotely, an informed consent form (ICF) will be mailed to the patient or legal 
representative. The patient or legal representative will be required to sign and return the ICF 
to the Principal Investigator (PI) prior to enrollment.
All data will be collected through the abstraction of hospital medical records. Collected 
study data will include but will not be limited to patient characteristics, clinical and 
microbiological characteristics of the infection, and treatment patterns, effectiveness, and 
safety of ceftazidime-avibactam. The study data collection and assessment schedule are 
described in Figure 1.
Patients who were exposed to ceftazidime-avibactam for ≥72 hours will be eligible for 
effectiveness analyses, including evaluation of treatment success. To avoid a selection bias 
that could result from restricting to patients with extended exposure, a small set of data 
elements will be collected and analyzed among patients with <72 hours of exposure. These 
data include details about exposure, indication and safety. Safety data will be analyzed for 
all patients enrolled. 
Patients who meet all the inclusion and exclusion criteria will be followed through their 
medical records up to 60 days after hospital discharge, death, withdrawal from the study, or 
loss-to-follow-up, whichever occurs first.
Information about hospital readmissions or death after hospital discharge not available via 
medical chart abstraction will be ascertained by contacting the patient or their legal 
representative by phone >60 days after hospital discharge. 
In France data abstraction should be retrospective only and in this case data abstraction 
should start after the 60 days follow-up date. Patient information sheet that is specific to 
France should be sent to patients before data abstraction starts. No follow-up calls with 
patients should occur in France.
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Figure 1. Study Design
9.2. Setting
Patients will be enrolled from approximately 62 sites in 12 countries in Europe and in Latin 
America. Sites will be qualified and then selected based on responses to a series of questions 
intended to determine capability of conducting the study and ability to contribute to the target 
patient population.
Participating study sites will aim to enroll consecutive eligible patients who initiated 
ceftazidime-avibactam based on physician prescribing. If an eligible patient was approached 
and does not agree to participate in the study, the reason for non-participation will be 
documented in the enrollment log.
Besides routine treatment, no clinic visits are required as part of participation in this study. 
All data are intended to be collected by referencing the medical records. For patients missing 
any of the requested information, data will be reported as missing. Eligibility in the study 
has been summarized below in Section 9.2.1 and Section 9.2.2. Patients participating in 
clinical trials are excluded from this study because protocol driven activities may be outside 
of normal practice and could confound safety assessments.
Note: Data collection will begin 01 January 2018 or since the date of launch if after 01 January 2018.
̊Patients followed from ceftazidime-avibactam initiation until 60 days after hospital discharge or another censoring event.
* Indicates outcome that will be examined for patients exposed to ceftazidime-avibactam for ≥72 hours
Note: See Table 3 for an extended list of collected variables.
ICU=Intensive care unit; LOS=length of stay
Exposure: 
• ≥1 dose of 
ceftazidime-
avibactam
• Concomitant 
antibiotic 
treatment
• Ceftazidime-
avibactam 
dosage details 
Follow-up: 
Hospital discharge 
+ 30 days &
+ 60 days̊
Patients treated with ceftazidime-avibactam 
from January 01, 2018 to June 30, 2019
Outcomes:
• Clinical treatment success*
• Microbiologic treatment success*
• Hospital readmissions*
• Hospital and ICU LOS*
• Resource utilization*
• Safety
• In-hospital, 30* & 60*-day mortality
Covariates:
• Demographics
• Indication
• Comorbidities
• Prior antibiotic therapy
• Disease severity
• Microbiology
• Prior hospitalization
• Prior healthcare 
procedures
• Additional risk factors 
including travel (See 
Table 3)
Covariates 
Assessment: 
≤90 days before 
exposure
Real-World Observational Study of Zavicefta® (ceftazidime-avibactam) 
to Characterize Use Patterns, Effectiveness and Safety.
Patients treated with ceftazidime-avibactam 
from 01 January 2018 onwards
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9.2.1. Inclusion Criteria
Patients must meet all the following inclusion criteria to be eligible:
1. Hospitalized patient ≥18 years old or considered an adult in accordance with the age 
of majority in the participant’s country of residence at the time of treatment with 
ceftazidime-avibactam.
2. Patient received ≥1 dose of ceftazidime-avibactam in routine practice at participating 
site since 01 January 2018 or the date of launch in the country if after 2018.
3. Patient underwent microbiological sampling ≤5 days before the initiation of 
ceftazidime-avibactam (irrespective of results and actual bacteriological 
identification).
4. Patient has all required essential data elements which include:
a.
Start and stop dates of ceftazidime-avibactam;
b. Start and stop dates of prior antibiotic therapy used for the index infection;
c.
Type of combined antibiotic therapy (if applicable) and start and stop dates of any
antibiotic combined with ceftazidime-avibactam.
5. Evidence of a personally signed and dated informed consent document indicating that 
the patient (or a legally acceptable representative) has been informed of all pertinent 
aspects of the study where required by local regulations.
9.2.2. Exclusion Criteria
Patients must not meet any of the following exclusion criteria to be eligible:
1. The patient is enrolled in any clinical trial of an investigational product. Patients who 
are enrolled in non-interventional studies (NISs) (eg, registries) are eligible for 
inclusion.
2. The patient has received ceftazidime-avibactam in a compassionate care program 
setting.
3. The patient was exposed to ceftazidime-avibactam before use for the index infection.
9.3. Variables
Table 1 shows the list of exposures, outcomes, and other variables to be collected from the 
patient medical records including risk factors, comorbidities, and concomitant medications. 
All variables will be collected for patients exposed to ceftazidime-avibactam for ≥72 hours. 
For patients exposed to ceftazidime-avibactam for a duration of <72 hours, a limited set of 
variables will be collected, identified in Table 2.
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Table 1: List of Variables and Definitions for Patients Exposed to Ceftazidime-
avibactam for ≥72 hours (non-exhaustive)
Variable
Role
Operational definition
Informed consent
Required for 
participation
Signed ICF submitted to study personnel. 
Year of birth
Baseline characteristic
As reported by physician (if allowed by local 
regulations).
Sex
Baseline characteristic
As reported by physician.
Employment
Baseline characteristic
As reported by physician.
Height, weight
Baseline characteristic
Height and weight as reported by physician.
Recent hospitalization
Baseline characteristic
Within 90 days prior to date of admission for the 
current hospitalization, date of admission and 
discharge, reason for hospitalization.
History of antibiotic 
exposure
Baseline characteristic
Antibiotic(s) used within 90 days prior to date of 
admission for the current hospitalization, dates 
of administration, route, dose, and frequency.
Recent healthcare 
procedure(s)
Baseline characteristic
Within the 30 days before ceftazidime-
avibactam initiation: Date(s) and type(s) of 
healthcare procedure.
Pre-treatment disease 
severity (APACHE II or 
other prognostic 
assessment)
Baseline characteristic
Concurrent with index infection diagnosis (as 
close to diagnosis as possible, a maximum of 
7 days prior to treatment); measured in patients 
directly admitted to the ICU; Date of 
assessment.
Additional risk factors
Baseline characteristic
Travel to foreign country within the past 
3 months; country and date(s) of travel;
comorbidities (Deyo-Charlson Comorbidity 
Index, see Annex 3 for detailed description); 
pregnancy (weeks of gestation since last 
menstrual period); alcohol use (drinks per 
week); tobacco use (current smoker and 
cigarettes per week).
Source of infection
Baseline 
characteristic/sub-group 
identifier
As reported by physician (HAI, HCAI, CAI). See 
Section 9.7 Data Analysis for extended 
definitions.
Indication for ceftazidime-
avibactam
Baseline 
characteristic/sub-group 
identifier
As reported by physician (cIAI, cUTI, 
HAP/VAP, explain other; initial site of infection 
(organ)); See Section 9.7 Data Analysis for 
extended definitions. Date of diagnosis.
Indication for ceftazidime-
avibactam: Other (1)
Baseline 
characteristic/sub-group 
identifier
Type of infection (eg, SSI, CLABSI, primary 
BSI, meningitis, other; initial site of infection 
[organ]). See Section 9.7 Data Analysis for 
details.
Pre-treatment microbiology 
sample
Baseline characteristic
Microbiological culture(s) of current infection 
during the 5 days of ceftazidime-avibactam 
initiation (sample date(s), sample source(s)).
Pre-treatment microbiology 
results
Baseline 
characteristic/sub-group 
identifier
Results from microbiological culture (method of 
testing, identified pathogen(s), susceptibility, 
MDR). See Section 9.7 Data Analysis for 
details.
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Variable
Role
Operational definition
Antibiotic therapy: Prior 
lines of treatment
Baseline characteristic
Antibiotic(s) used for current infection before 
ceftazidime-avibactam initiation. Dates of 
administration, dose(s), frequency, duration, 
route of administration, reason for initiating 
(microbiology, progression on previous 
antibiotic), reason for discontinuation (AE, 
perceived clinical failure, isolation of a resistant 
pathogen, preference for empiric coverage, 
secondary infection requiring regimen change, 
switch to oral therapy, de-escalation).
Ceftazidime-avibactam
Exposure
Use of ≥1 dose as reported in records.
Ceftazidime-avibactam 
dosage
Exposure
Dates of administration, dose(s), frequency, 
duration, reason for initiating and reason for 
discontinuation (if applicable) (eg, AE, 
perceived clinical failure, isolation of a resistant 
pathogen, preference for empiric coverage, 
secondary infection requiring regimen change, 
switch to oral therapy, de-escalation, cure, 
death).
Concomitant antibiotic 
therapy
Exposure/sub-group 
identifier
Name(s) of antibiotic(s) used concurrently with 
ceftazidime-avibactam, dates of administration, 
dose(s), frequency, duration, route of 
administration, reason for initiating and reason 
for discontinuation (eg, AE, perceived clinical 
failure, isolation of a resistant pathogen, 
preference for empiric coverage, secondary 
infection requiring regimen change, switch to 
oral therapy, de-escalation, cure, death) (if 
applicable).
Clinical symptom 
improvement
Outcome
Symptom improvement or worsening as reported 
by the physician using clinical judgement within 
48 and 72 hours of ceftazidime-avibactam 
initiation.
Post-treatment initiation 
microbiology sample
Outcome
Microbiological culture(s) during the 14 days 
after ceftazidime-avibactam initiation (sample 
date, sample site). See Section 9.7 Data 
Analysis for definitions.
Post-treatment initiation 
microbiology results
Outcome
Results from microbiological culture after 
treatment initiation (method of testing, identified 
pathogen(s), susceptibility, MDR). See 
Section 9.7 Data Analysis for definitions.
Clinical treatment outcome
Outcome
Success, failure, and indeterminate. See 
Annex 1 for definitions.
Microbiological treatment 
outcome
Outcome
Success, failure, emergent infections and 
unevaluable. See Annex 1 for definitions.
Lines of antibiotic therapy
Outcome
Number of lines, reason for change in line 
(eg, AE, perceived clinical failure, isolation of a 
resistant pathogen, preference for empiric 
coverage, secondary infection requiring regimen 
change, switch to oral therapy, de-escalation, 
cure, death). See Section 9.7 Data Analysis for 
definitions.
In-hospital mortality
Outcome
Death occurring after treatment initiation but 
before hospital discharge (date, cause of death).
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Variable
Role
Operational definition
30-day mortality
Outcome
Death occurring within the 30 days after hospital 
discharge (date, cause of death).
60-day mortality
Outcome
Death occurring within the 60 days after hospital 
discharge (date, cause of death).
Safety
Outcome
All serious and non-serious AEs with explicit 
attribution to ceftazidime-avibactam that appear 
in the reviewed information and scenarios 
involving drug exposure to 
ceftazidime-avibactam, including exposure 
during pregnancy, exposure during breast 
feeding, medication error, overdose, misuse, 
extravasation, lack of efficacy and occupational 
exposure associated with the use of 
ceftazidime-avibactam.
Length of hospital stay
Outcome
Date(s) of hospital admission, date(s) of hospital 
discharge. See Section 9.7 Data Analysis for 
extended definition.
ICU length of stay
Outcome
Date(s) of ICU admission, date(s) of ICU 
discharge, diagnosis at admission. See 
Section 9.7 Data Analysis for an extended 
definition.
Hospital readmission
Outcome
Hospital readmission during the 30 and 60 days 
after initial discharge, reason for readmission. 
See Section 9.7 Data Analysis for an extended 
definition.
Healthcare utilization 
Outcome
Detailed list of healthcare utilization (diagnosis 
at admission, departments admitted/discharged, 
discharge diagnosis, mechanical ventilation, 
dialysis, CT/MRI imaging, tracheostomy, 
surgical intervention, percutaneous procedures, 
other) and dates of service. See Section 9.7 Data 
Analysis for an extended definition.
Hospital ward
Outcome
All wards attended, ward of admission, ward of 
diagnosis (surgical, medical, onco-hematology, 
infectious disease, ICU, other).
Physician specialty
Site characteristic
Medical specialty of the treating physician 
(eg, infectious disease, surgical).
Hospital information
Site characteristic
Care level, type number of beds, number of ICU 
beds.
Local gram-negative 
resistance patterns
Site characteristic
Most recent assessment of the proportion of 
gram-negative isolates exhibiting resistance to 
3rd generation cephalosporins or carbapenem 
antibiotics, and dates of assessment.
AE=adverse event; APACHE=Acute Physiology and Chronic Health Evaluation; BSI=bloodstream infection; 
CAI=community-acquired infection; CT: computerized tomography scan; cIAI=complicated intra-abdominal 
infection; CLABSI=central line associated blood stream infection; cUTI=complicated urinary tract infection; 
HAI=hospital-acquired infection; HAP=hospital-acquired pneumonia; HCAI= healthcare-associated infection; 
ICF=informed consent form; ICU=intensive care unit; MDR=multidrug-resistant; MRI: magnetic resonance 
imaging; SSI=surgical site infection; VAP=ventilator-associated pneumonia. (1) Other indications (infections 
due to aerobic gram-negative organisms with limited treatment options, see Section 7) are not included in the 
label for all participating countries.
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Table 2. List of Variables and Definitions for Patients Exposed to Ceftazidime-
avibactam for <72 hours (non-exhaustive)
Variable
Role
Operational definition
Year of birth
Baseline characteristic
As reported by physician (if allowed by local
regulations).
Sex
Baseline characteristic
As reported by physician.
Source of infection
Baseline 
characteristic/sub-group 
identifier
As reported by physician (HAI, HCAI, CAI). See 
Section 9.7 Data Analysis for extended 
definitions.
Indication for ceftazidime-
avibactam
Baseline 
characteristic/sub-group 
identifier
As reported by physician (cIAI, cUTI, 
HAP/VAP, explain other; initial site of infection 
(organ)); See Section 9.7 Data Analysis for 
extended definitions.
Indication for ceftazidime-
avibactam: Other (1)
Baseline 
characteristic/sub-group 
identifier
Type of infection (eg, SSI, CLABSI, primary 
BSI, meningitis, other; initial site of infection 
(organ)). See Section 9.7 Data Analysis for 
details.
Ceftazidime-avibactam
Exposure
Use of ≥1 dose as reported in records.
Ceftazidime-avibactam 
dosage
Exposure
Dates of administration, dose(s), frequency, 
duration, reason for initiating and reason for 
discontinuation (if applicable) (eg, AE, perceived 
clinical failure, isolation of a resistant pathogen, 
preference for empiric coverage, secondary 
infection requiring regimen change, switch to 
oral therapy, de-escalation, cure, death).
In-hospital mortality
Outcome
Death occurring after treatment initiation but 
before hospital discharge (date, cause of death).
Safety
Outcome
All serious and non-serious AEs with explicit 
attribution to ceftazidime-avibactam that appear 
in the reviewed information and scenarios 
involving drug exposure to 
ceftazidime-avibactam, including exposure 
during pregnancy, exposure during breast 
feeding, medication error, overdose, misuse, 
extravasation, lack of efficacy and occupational 
exposure associated with the use of 
ceftazidime-avibactam.
AE=adverse event; BSI=bloodstream infection; CAI=community-acquired infection; cIAI=complicated 
intra-abdominal infection; CLABSI=central line associated blood stream infection; cUTI=complicated urinary 
tract infection; HAI=hospital-acquired infection; HAP=hospital-acquired pneumonia; HCAI= healthcare-
associated infection; SSI=surgical site infection; VAP=ventilator-associated pneumonia. (1) Other indications
(infections due to aerobic gram-negative organisms with limited treatment options, see Section 7 are not 
included in the label for all participating countries.
9.4. Data Sources
The data source for this study will be patient medical records. Data will be abstracted from 
patient medical charts after treatment completion, and up to 60 days post hospital discharge 
or a censoring event (death, withdrawal from the study, or lost-to-follow-up). Patients should 
be carefully tracked to identify censoring events. 
AEs will be collected as part of standard practice. More information regarding the reporting 
of AEs is described in Section 11.
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9.5. Study Size
9.5.1. Study Size in Europe
Sample size for this study was calculated with the goal of maximizing precision when 
estimating clinical and microbiological treatment success.
Clinical Treatment Success Assumptions:47-49

25% of the enrolled patients discontinue ceftazidime-avibactam before 72 hours of 
exposure (eg, due to AE, microbiological results);

75% of patients are exposed to ceftazidime-avibactam for ≥72 hours and are 
assessable for clinical effectiveness.70% of the assessable patients experience clinical 
treatment success, as defined in Annex 1.
Table 3. Sample Size and Precision of the Estimate for Clinical Treatment Success
Prevalence of Clinical Treatment Success
N
60%
65%
70%
75%
80%
200 (52.9% -
66.8%)
(58.0% - 71.6%)
(63.1% - 76.3%)
(68.4% - 80.8%)
(73.8% - 85.3%)
300 (54.2% -
65.6%)
(59.3% - 70.4%)
(64.5% - 75.1%)
(69.7% - 79.8%)
(75.0 % - 84.4%)
400 (55.0% -
64.8%)
(60.1% - 69.7%)
(65.2 % - 74.5%)
(70.5% - 79.2%)
(75.7% - 83.8%)
500 (55.6% -
64.3%)
(60.6% - 69.2%)
(65.8% - 74.0%)
(71.0% - 78.7%)
(76.2% - 83.4%)
600 (56.0% -
63.9%)
(61.0% - 68.8%)
(66.2% - 73.6%)
(71.3% - 78.4%)
(76.6% - 83.1%)
Note: Displayed range is the 95% confidence interval (CI) around the estimate of treatment success.
Microbiological Treatment Success Assumptions:47-49

25% of the enrolled patients discontinue ceftazidime-avibactam before 72 hours of 
exposure (eg, due to AE, microbiological results);

75% of patients are exposed to ceftazidime-avibactam for ≥72 hours;

10% of patients exposed ≥72 hours (across all indications) have no pathogen 
identification and are not assessable for microbiological success;

80% of the assessable patients experience microbiological treatment success as 
defined in Annex 1. 
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Table 4. Sample Size and Precision of the Estimate for Microbiological Treatment 
Success
Prevalence of Microbiological Treatment Success
N
70%
75%
80%
85%
90%
200 (63.1% -
76.3%)
(68.4% - 80.8%)
(73.8% - 85.3%)
(79.3% - 89.6%)
(85.0% - 93.8%)
300 (64.5% -
75.1%)
(69.7% - 79.8%)
(75.0% - 84.4%)
(80.4% - 88.8%)
(86.0% - 93.2%)
400 (65.2% -
74.5%)
(70.5% - 79.2%)
(75.7% - 83.8%)
(81.1% - 88.4%)
(86.6% - 92.8%)
500 (65.8% -
74.0%)
(71.0% - 78.7%)
(76.2% - 83.4%)
(81.6% - 88.0%)
(87.0% - 92.5%)
600 (66.2% -
73.6%)
(71.3% - 78.4%)
(76.6% - 83.1%)
(81.9% - 87.8%)
(87.3% - 92.3%)
Note: Displayed range is the 95% confidence interval (CI) around the estimate of treatment success.
Table 3 and Table 4 display estimates of clinical and microbiological treatment success, 
respectively, and the asymptotic precision of each estimate (95% CI), for sample sizes 
ranging from 300 to 600 evaluable patients.
To obtain a 95% CI for treatment success, that is approximately 12.3 percentage points or 
less for both clinical and microbiological treatment success, 225 evaluable patients are 
required. Given the assumptions above for both treatment outcomes, a minimum of 
300 patients should be enrolled to obtain 225 evaluable patients. Minor gains in precision 
can be achieved by enrolling a larger number of patients. 
Enrolling 300 patients would lead to 225 patients with ≥72 hours exposure to 
ceftazidime-avibactam evaluable for clinical success, and 202 patients evaluable for 
microbiological success. It would yield an expected 95% CI of 70.0% (63.6% - 75.9%) of 
patients experiencing clinical treatment success and 80.0% (73.8% - 85.3%) of patients 
experiencing microbiological treatment success using a two-sided exact method.
Note: The precision estimates were calculated using the Clopper Pearson (exact) CIs using 
statistical analysis system (SAS)® software version 9.2.50
9.5.2. Study Size in Latin America
Based on the same assumptions for treatment outcomes as in Europe, to obtain a 95% CI for 
treatment success that is approximately 10.0 percentage points for both clinical and 
microbiological treatment success, 400 patients will be included in Latin America to obtain 
300 evaluable patients for clinical success, and 270 evaluable patients for microbiological 
success. Using a two-sided exact method, enrolling 400 patients would yield an expected 
95% CI of 70.0% (64.5% - 75.1%) of patients experiencing clinical treatment success and 
80.0% (74.7% - 84.6%) of patients experiencing microbiological treatment success.
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9.6. Data Management
Data will be entered in the web-based data capture (WBDC) system at the investigator’s site. 
The investigator (or delegate) will be responsible for entering data into the WBDC system 
and according to the Investigator Instructions Manual. The Investigator Instructions Manual 
will also provide the site with data entry instructions.
Data entered in the WBDC system will be immediately saved to a central database and 
changes tracked to provide an audit trail. When data have been entered, reviewed and edited, 
the investigator will be notified to sign the electronic case report form (eCRF) electronically 
as per the agreed project process. A copy of the eCRF will be archived at the investigator’s 
site.
9.7. Data Analysis 
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a Statistical Analysis Plan (SAP), which will be dated, filed and 
maintained by the sponsor. The SAP may modify the plans outlined in the protocol; any 
major modifications of primary endpoint definitions or their analyses would be reflected in a 
protocol amendment. All analyses will be carried out using SAS® software version 9.4 or 
higher or another similar statistical software package.
Extended analytic definitions for primary variables can be found below, categorized by role. 
See Section 9.3 Variables for a full list of collected data.
9.7.1. Exposure
To qualify for participation, patients must have had ≥1 dose of ceftazidime-avibactam. 
All analyses will be performed among patients with ≥72 hours of ceftazidime-avibactam 
exposure. 
A limited number of analyses will be conducted among patients with <72 hours of 
ceftazidime-avibactam exposure. These sub-analyses will examine patient, infection, 
treatment characteristics, safety and mortality. 
Antibiotic regimens including ceftazidime-avibactam will be examined. An antibiotic 
regimen is a planned therapeutic intervention which may involve 1 or more drugs. Each 
regimen is a line of therapy. 
A new line of therapy is defined by:
1. Where a treatment regimen is discontinued, and a different regimen is started, the 
new regimen is considered a new line of therapy. 
2. A line of treatment is considered finished when at least one antibiotic given in 
combination is modified. 
3. Escalation, increasing the dosage, the dose or the unplanned addition or substitution
of ≥1 drug(s) in an existing regimen is considered a new line of therapy.
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
Escalation after 4 days of treatment (dose increase or addition of another 
antibiotic for gram-negative), will be considered as a failure.
4. De-escalation, or reducing the dosage or eliminating ≥1 drug(s) from an existing 
regimen, or switching to oral antibiotics, is not considered a new line of therapy.

Stream lining (stop an antibiotic) or conversion to oral therapy will be considered 
as a success.
9.7.2. Outcomes

Clinical treatment outcome: please refer to Annex 1 for details on clinical treatment 
outcomes. Each line of therapy that includes ceftazidime-avibactam will be evaluated 
for the clinical outcome. 

Microbiological treatment outcome: please refer to Annex 1 for details on 
microbiological treatment outcomes. Each line of therapy that includes ceftazidime-
avibactam will be evaluated for the microbiological outcome, providing that a 
pathogen was identified. Microbiological treatment outcome should be assessed at 
the end of each regimen containing ceftazidime-avibactam. 

Hospital LOS will be calculated as: 1) the total number of consecutive days the 
patient was treated in the hospital from admission to discharge during their initial 
hospitalization; 2) the total number of hospital days between diagnosis of infection 
and discharge; 3) the total number of days the patient was treated in the hospital after 
ceftazidime-avibactam initiation up to hospital discharge, including the first day of 
treatment.

ICU LOS will be calculated as: 1) the total number of consecutive or non-consecutive 
days the patient was treated in the ICU during their initial hospitalization; and 2) the 
total number of days the patient was treated in the ICU after ceftazidime-avibactam 
initiation, including the first day of treatment.

Healthcare resource utilization data (medical/surgical/percutaneous procedures, 
CT/magnetic resonance imaging (MRI) imaging, days of mechanical ventilation, days 
of dialysis) will be abstracted from the patient medical records. 

Reasons for initiating or discontinuing antibiotic therapy (any line) include but are not 
limited to AE, perceived clinical failure, isolation of a resistant pathogen, secondary 
infection requiring regimen change, switch to oral therapy, de-escalation, cure, death.

Prevalence of hospital readmissions; analyzed as the proportion of patients readmitted 
to the hospital for a recurrence of the index infection out of all patients discharged 
from the initial hospitalization.

Cumulative mortality, in-hospital, at 30- and 60-days post-discharge.
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9.7.3. Baseline Participant and Infection Characteristics

Indication for ceftazidime-avibactam prescription (will vary depending on country 
local label).

cUTI: a clinical diagnosis of UTI that occurs associated with calculi/stones, 
indwelling catheters or other drainage devices, obstruction, immunosuppression, 
renal failure, renal transplantation, pregnancy, functional or anatomical 
abnormalities of the urinary tract such as partial obstructive uropathy (acquired or 
congenital), elevated postvoiding residual volume (>100 mL residual), established 
diagnosis of neurogenic bladder or instrumentation of the urinary tract, including 
urogenital surgery in the 7 days prior to symptoms initiation, as registered in the 
medical chart or record, and the diagnosis of acute prostatitis is excluded by 
physical exam. Hospital-acquired (nosocomial) cUTI will be defined as cUTI that 
develops at least 48 hours after the hospital admission. Healthcare-associated 
cUTI will be defined as cUTI among patients with presence of chronic indwelling 
urinary catheters, residence in nursing home or long-term care facility, regular 
hemodialysis clinic visits, or evidence of urological procedures within 3 months 
prior to the inpatient admission or during the inpatient admission.51

cIAI: a clinical diagnosis of IAI (ie, peritonitis, intraperitoneal abscess, liver 
abscess, pancreatic abscess, appendicitis, diverticulitis, gastric or duodenal ulcers, 
cholangitis, cholecystitis) and evidence of involvement of more than one organ, 
causing peritonitis and requiring both surgical and antibiotic therapy (beyond 
24 hours regimen), as registered in the medical chart or record. Hospital-acquired 
cIAI will be defined as cIAI that develops at least 48 hours after the hospital 
admission. Healthcare-associated cIAI will be defined as cIAI that occurs while 
receiving treatment for other conditions in a healthcare facility (eg, nursing home, 
long-term care, hemodialysis clinic, hospital) within 3 months prior to the 
inpatient admission or during the inpatient admission.52

HAP/VAP: a clinical diagnosis of pneumonia and evidence of nosocomial origin 
(HAP/VAP) as registered in the medical chart or record. HAP is defined as 
pneumonia that occurs at least 48 hours after hospital admission; VAP is defined 
as pneumonia that occurs at least 48 hours after endotracheal intubation or 
tracheostomy.

Other infection with limited treatment options: any infection, based upon empiric 
or microbiological evidence, for which ceftazidime-avibactam is prescribed. 
Detailed information on the infection should be collected for analysis including 
type of infection (eg, primary BSI, SSI, CLABSI, meningitis), and original source 
of infection (ie, specific organ/locale). This indication is not approved in all 
participating countries.
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
Pathogen susceptibility: All susceptibility information will be collected for the 
isolated pathogens including tested antibiotic by classes (eg, aminoglycosides, 
amphenicol, beta-lactams, carbapenems, cephalosporins, glycopeptides, 
glycylcyclines, lipopeptides, macrolides, monobactams, nitroimidazoles, 
oxazolidinones, penicillins, penicillins and beta-lactamase inhibitors, quinolones,
streptogramins, tetracyclines, other) and within class, and sensitivity to each 
antibiotic susceptible, intermediate, resistant). 

Multidrug-resistance: The isolate is non-susceptible to at least 1 agent in 
≥3 antimicrobial categories, excluding antibiotic classes to which the pathogen is 
intrinsically resistant. Categories include but are not limited to aminoglycosides, 
carbapenems, cephalosporins, cephamycins, fluoroquinolones, folate pathway
inhibitors, glycylcyclines, penicillins, monobactams, phosphonic acids, polymyxins, 
tetracyclines.53

Source of infection (healthcare-associated, hospital-acquired, community-acquired).54

HCAI.

Infection present ≤48 hours after hospital admission in patients who met one 
or more of the following criteria: 

Received home healthcare (intravenous [IV], wound care, specialized 
nursing) during the past 30 days, excluding oxygen use;

Received healthcare in a clinical setting or received IV chemotherapy 
during the past 30 days;

Hospitalized in an acute care hospital for 2 or more days in 3 months 
before baseline enrollment;

Resided in a nursing home or other long-term care.55

HAI.

Infection that occurred ≥48 hours after hospital admission that were not 
incubating at the time of admission.

CAI.

Infection detected ≤48 hours after hospital admission that does not qualify as a 
HCAI.

Infection site: This refers to the origin of the infection (eg, appendix, bladder, kidney, 
large intestine, lungs, liver, gallbladder, pancreas, peritoneum small intestine, 
stomach, urethra, other). 
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
Treatment line number: A new line of therapy starts when the antibiotic therapy is 
modified because an antibiotic is discontinued, the dose increased, patient is switched 
to an oral antibiotic therapy/regimen or a new antibiotic is added. Up to 5 lines of 
therapy will be collected. Assessment of treatment line will be based on generic 
name (ie, active ingredient) of the drug (ie, change in trade name with same active 
ingredient, dose and strength will not be classified as a treatment line change).

APACHE II score56 will be collected from medical records for patients directly 
admitted to the ICU among sites that routinely calculate this measure. If the 
APACHE II score is not present in the medical records, it will not be calculated for 
the purpose of this study. Other common measures of disease severity (eg, Sequential
Organ Failure Assessment [SOFA], simplified acute physiologic score [SAPS], 
multiple organ dysfunction score [MODS], organ dysfunction and infection system 
[ODIN], APACHE III) will be collected, if reported in medical records.

The Deyo-Charlson Comorbidity Index (DCCI57 will be used to predict patients’ 
10-year probability of survival and will be used as a measure of overall health. The 
comorbidities evaluated in the DCCI will be collected at baseline from medical 
records to calculate the score. Details of this index are provided in Annex 3. 
9.7.4. Planned Analyses
All computations and generation of tables, listings and data for figures will be performed 
using SAS® software version 9.4 or higher or another similar statistical software package. 
The analysis plan will be fully described in a written and approved SAP. 
Baseline (where baseline is defined as study entry) characteristics will be summarized for 
ceftazidime-avibactam patients. Descriptive statistics will be used to summarize the 
treatment patterns (eg, dosage, indications, infection source), effectiveness (eg, clinical and 
microbiological outcomes), and safety (eg, mortality, AEs) of ceftazidime-avibactam and 
healthcare resource utilization by patients prescribed ceftazidime-avibactam. AEs will be 
recorded and summarized as the proportion of patients with each safety event out of all 
treated patients. Hospital readmissions will be analyzed as the proportion of patients 
readmitted to the hospital for recurrent infection out of all patients discharged from the initial 
hospitalization.
Descriptive analyses will be performed to gain an understanding of the qualitative and 
quantitative nature of the data collected and the characteristics of the sample studied. 
Continuous variables will be described by the mean with standard deviation and 95% CI, 
median, upper and lower quartiles and maximum and minimum values. Categorical variables 
will be reported as number and percentages with 95% CIs. 
Missing data will be described in all summaries.
A detailed flow diagram will be provided to describe the patient selection process. Patient
and treatment characteristics of the analytic cohort will be summarized using descriptive 
statistics as described above.
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The outcomes of interest will be derived as necessary from collected data and examined 
descriptively. Outcomes will be further examined after stratification by patient 
characteristics including baseline disease severity.
Outcomes of interest will be also stratified by indication, by bacteria (Escherichia coli, 
Klebsiella spp., Enterobacter spp., Pseudomonas spp., others) and by country.
Data from Europe and Latin America (LATAM) will be analyzed separately. 
9.8. Quality Control
Data will be collected and entered by site personnel for all data. The team will receive 
training that will include protocol/eCRF training and training on the electronic data capture 
(EDC) system that will be used for the study. All data will be entered directly into the 
database through web-based eCRFs. The eCRFs include programmable edit checks to 
provide feedback (automatic queries) on potential errors or missed fields. Data collection 
and validation procedures will be detailed in appropriate operational documents. All data 
collection will be performed in compliance with regulations.
Each study site will be responsible for ensuring that data entered into the study database are 
accurate and reflect the data found in the source documents (ie, medical records). Data 
monitoring may be performed, as applicable, considering data privacy requirements in each 
of the participating countries. 
Data entered into the database will be reviewed on a periodic basis to ensure plausibility; 
data queries may be issued to the participating sites as needed.
9.9. Limitations of the Research Methods
There are some limitations in this study. First, because data will be collected via medical 
chart abstraction, it is likely that some of the requested information will be missing, 
incomplete, or inaccurate. Safeguards against missing and inaccurate data will be employed 
throughout the research process. This includes choosing qualified sites, checking primary 
variables of interest are those that are routinely collected, using required fields and validation 
techniques in eCRFs, and employing analytic techniques including evaluating and describing 
patterns of missingness and using multiple imputations, when appropriate.
It is also possible that this study will have a selection bias. Some patients will be treated 
prior to the start of the study-related data collection. Obtaining informed consent from 
patients with good outcomes will be more difficult than among patients who died and as a 
result, would be eligible for waived informed consent. Further, remote consenting will 
increase the likelihood of capturing patients discharged from hospitalization prior to study 
start. 
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It is possible that patients treated at study sites, or patients selected for treatment with 
ceftazidime-avibactam, are not representative of the patient population that would be eligible 
for treatment. For example, patients at healthcare facilities capable of participating in 
research may be sicker, on average, than those who attend smaller tertiary care facilities. 
Results will be interpreted within this context.
Outcome misclassification may occur in this study. Patients will be followed for 60 days 
after hospital discharge for any indication of readmission for the same infection. It will be 
difficult to distinguish patients who were lost to follow-up from those who were readmitted 
at a different healthcare facility. This may result in an underestimate of some outcomes. To 
mitigate this risk, best effort will be made to identify outcome information by contacting 
patients or their legal representatives by telephone at the end of the follow-up period to 
ascertain information about hospital readmissions or mortality. 
Finally, this study will only capture AEs related to ceftazidime-avibactam or other products
marketed by the sponsor - that are reported in the patient medical records and not all AEs that 
occur. Reported AEs are likely only those deemed clinically significant or those that need to 
be captured in the medical records for other reasons (eg, hospital regulation). Evaluation of 
safety results will be interpreted within this context. 
10. PROTECTION OF HUMAN SUBJECTS
10.1. Patient Information
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of patient personal data.  Such 
measures will include omitting patient names or other directly identifiable data in any 
reports, publications, or other disclosures, except where required by applicable laws.
The personal data will be stored at the study site in encrypted electronic and/or paper form 
and will be password protected or secured in a locked room to ensure that only authorized 
study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer and other authorized 
parties, patient names will be removed and will be replaced by a single, specific, numerical 
code, based on a numbering system defined by Pfizer.  All other identifiable data transferred 
to Pfizer or other authorized parties will be identified by this single, patient-specific code.
The investigator site will maintain a confidential list of patients who participated in the study, 
linking each patient’s numerical code to his or her actual identity. In case of data transfer, 
Pfizer will maintain high standards of confidentiality and protection of patients’ personal data
consistent with the clinical study agreement and applicable privacy laws.
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10.2. Patient Consent
The ICF must be in compliance with local regulatory requirements and legal requirements.
The ICF used in this study, and any changes made during the course of the study, must be 
prospectively approved by both the Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC) and Pfizer before use.
The investigator must ensure that each study patient, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation. The investigator, or a person designated by the 
investigator, will obtain written informed consent from each patient or the patient’s legally 
acceptable representative before any study-specific activity is performed. When the 
informed consent cannot be completed in person, patients or their legal representative will be 
consented remotely via telephone and will be mailed an ICF to sign, date, and return by mail, 
if approved by local legislation. The investigator will retain the original of each patient's 
signed consent form. A Next of Kin informed consent will be sought for deceased patients. 
And for out of reach patients a waiver may be used in countries where it is acceptable and 
approved by local regulations.
10.3. Patient Withdrawal
Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, 
or administrative reasons. In any circumstance, every effort should be made to document 
patient outcome, if possible. The investigator should inquire about the reason for withdrawal 
and follow-up with the patient regarding any unresolved AEs.
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
10.4. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
There must be prospective approval of the study protocol, protocol amendments, and other 
relevant documents (eg, ICFs if applicable) from the relevant IRBs/IECs. All 
correspondence with the IRB/IEC must be retained. Copies of IRB/IEC approvals must be 
forwarded to Pfizer. 
10.5. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices 
described in: Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE); Good Epidemiological Practice 
(GEP) guidelines issued by the International Epidemiological Association (IEA); Good 
Practices for Outcomes Research issued by the International Society for Pharmacoeconomics 
and Outcomes Research (ISPOR); International Ethical Guidelines for Epidemiological 
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Research issued by the Council for International Organizations of Medical Sciences 
(CIOMS); EMA European Network of Centres for Pharmacoepidemiology and 
Pharmacovigilance (ENCePP) Guide on Methodological Standards in 
Pharmacoepidemiology; and Food and Drug Administration (FDA) Guidance for Industry: 
Good Pharmacovigilance and Pharmacoepidemiologic Assessment, FDA Guidance for 
Industry; and FDA Staff: Best Practices for Conducting and Reporting of 
Pharmacoepidemiologic Safety Studies Using Electronic Healthcare Data Sets; Guidance for 
Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to 
Support Labeling Claims and/or equivalent.
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS 
This study protocol requires human review of patient-level unstructured data; unstructured 
data refer to verbatim medical data, including text-based descriptions and visual depictions of 
medical information, such as medical records, images of physician notes, neurological scans, 
X-rays, or narrative fields in a database. The reviewer is obligated to report AEs with 
explicit attribution to any Pfizer drug that appear in the reviewed information (defined per the 
patient population and study period specified in the protocol). Explicit attribution is not 
inferred by a temporal relationship between drug administration and an AE but must be based 
on a definite statement of causality by a healthcare provider linking drug administration to 
the AE. 
The requirements for reporting safety events on the non-interventional studies (NIS) adverse 
event monitoring (AEM) Report Form to Pfizer Safety are as follows:

All serious and non-serious AEs with explicit attribution to any Pfizer drug that 
appear in the reviewed information must be recorded on the WBDC system at the 
investigator’s site and reported, within 24 hours of awareness, to Pfizer Safety using 
the NIS AEM Report Form.

Scenarios involving drug exposure, including exposure during pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation, lack of 
efficacy and occupational exposure associated with the use of a Pfizer product must 
be reported, within 24 hours of awareness, to Pfizer Safety using the NIS AEM 
Report Form.
For these AEs with an explicit attribution or scenarios involving exposure to a Pfizer product, 
the safety information identified in the unstructured data reviewed is captured in the Event 
Narrative section of the report form, and constitutes all clinical information known regarding 
these AEs.  No follow-up on related AEs will be conducted.
All research staff members will complete the Pfizer requirements regarding training on the 
following: “Your Reporting Responsibilities: Monitoring the Safety, Performance and 
Quality of Pfizer Products (Multiple Languages)” and any relevant Your Reporting 
Responsibilities supplemental training. 
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These trainings must be completed by research staff members prior to the start of data 
collection. All trainings include a “Confirmation of Training Certificate” (for signature by
the trainee) as a record of completion of the training, which must be kept in a retrievable 
format. Copies of all signed training certificates must be provided to Pfizer. Re-training 
must be completed on an annual basis using the most current Your Reporting 
Responsibilities training materials.
11.1. Single Reference Safety Document (SRSD)
The region-specific product label will serve as the SRSD during the study, which will be 
used by Pfizer Safety to assess any safety events reported to Pfizer Safety by the investigator 
during this study. 
The SRSD should be used by the investigator for prescribing purposes and guidance.
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
A final study report will be generated after all data collection is complete. The final report 
will encompass all planned analyses, including a description of the complete study 
population. Study details will be described in the SAP.
13. COMMUNICATION OF ISSUES
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable 
Competent Authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of a Pfizer 
product, Pfizer should be informed immediately.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this NIS protocol that the investigator becomes aware of.
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WHO. Annual epidemiological report on communicable disease in Europe 2008 2008 
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Geerdes HF, Ziegler D, Lode H, Hund M, Loehr A, Fangmann W, et al. Septicemia in 
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15. LIST OF TABLES 
Table 1: List of Variables and Definitions for Patients Exposed to Ceftazidime-
avibactam for ≥72 hours (non-exhaustive)...............................................23
Table 2. List of Variables and Definitions for Patients Exposed to Ceftazidime-
avibactam for <72 hours (non-exhaustive)...............................................26
Table 3. Sample Size and Precision of the Estimate for Clinical Treatment Success .............27
Table 4. Sample Size and Precision of the Estimate for Microbiological Treatment 
Success......................................................................................................28
16. LIST OF FIGURES
Figure 1. Study Design ............................................................................................................21
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ANNEX 1. DEFINITIONS OF DIFFERENT SUBCATEGORIES OF OUTCOME
Detail criteria for evaluation of clinical and microbiological outcome58
Clinical 
Evaluation
Clinical 
Success
Cure
Resolution of all signs and symptoms of 
infection with no need for escalation of 
antimicrobials.
De-escalation of antibiotic therapy is 
considered a treatment success unless 
ceftazidime-avibactam was used in a regimen 
with one or more other antibiotics and is the 
only antibiotic de-escalated.
Clinical 
Failure
Failure
Inadequate response to ceftazidime-avibactam 
therapy or resistant, worsening, or new 
recurrent signs and symptoms at the end of 
ceftazidime-avibactam therapy.
This may include antimicrobial escalation 
(ceftazidime-avibactam dose increase, or 
additional antibiotic) after 4 days of treatment, 
discontinuation of ceftazidime-avibactam 
without clinical cure (eg, AE, insufficient 
effect), or readmission to a hospital with same 
infection within 60 days of the initial hospital 
discharge date. This may also include cIAI 
patient who required an additional unplanned 
source control procedure after 
ceftazidime-avibactam initiation.
Clinical 
Indeterminate
Indeterminate
There is not enough information to conclude 
whether the antibiotic regimen containing 
ceftazidime-avibactam was a clinical failure or 
a success.
Microbiological 
Evaluation
Microbiological 
Success
Eradication
Absence of causative pathogen from 
appropriately obtained specimens at the site of 
infection.
Presumed 
Eradication
Repeat cultures were not performed/clinically 
indicated in a patient who had a clinical 
response of cure.
Colonization
Detection of new pathogen from the site of 
infection during therapy without signs of 
infection and need for antimicrobial treatment, 
or a superinfection with a microbiological 
agent outside the treatment spectrum of 
ceftazidime-avibactam (G+/fungi).
Microbiological 
Failure
Verified 
Persistence
The failure to eradicate the original pathogen 
from the site of isolation after completion of
therapy.
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Presumed 
Persistence
Absence of appropriate material for culture or
absence of results of control microbiological 
tests coupled with lack of clinical 
improvement after a pathogen was initially 
isolated.
Persistence with 
Increasing minimal 
inhibitory 
Continued presence of the causative organism 
in a culture during or upon completion of 
treatment with IV study therapy that displays a 
≥4-fold higher MIC to IV study therapy after 
treatment with IV study therapy.
Emergent 
Infections
Superinfection
Detection of a new pathogen from the site of 
infection during therapy with need for 
antimicrobial treatment.
New Infection
Detection of a new pathogen from the site of 
infection after therapy with need for 
antimicrobial treatment.
Microbiological 
Unevaluable
Unevaluable
Patients without cultures or evident pathogens 
from the presumed site of infection.
AE=adverse event; cIAI=complicated intra-abdominal infection; MIC=minimum inhibitory concentration; 
IV=intravenous.
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ANNEX 2. LIST OF STAND-ALONE DOCUMENTS
Documents in the list below are available upon request. Note that changes to this list do not 
require a protocol amendment.
Number
Document reference number
Date
Title
NA=Not applicable.
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ANNEX 3: DEYO-CHARLSON COMORBIDITY INDEX
This table outlines the Deyo-Charlson Comorbidity Index. To quantify comorbidity, the 
Deyo-Charlson Comorbidity score is computed by adding the weights that are assigned to the 
specific diagnoses. A score of 1 is attributed to myocardial infarction, congestive heart 
failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic obstructive 
pulmonary disease, rheumatologic disease, peptic ulcer disease, mild liver disease, 
depression, use of warfarin, hypertension and diabetes mild to moderate. The following 
diseases are scored as 2: hemiplegia or paraplegia, moderate or severe renal disease, skin 
ulcers/cellulitis, diabetes and complications and malignancy including leukemia and 
lymphoma. Moderate or severe liver disease is scored 3. Finally, a score of 6 is assigned to 
metastatic solid tumor and AIDS. 
Comorbidity
Deyo-Charlson Weight
Myocardial Infarction
1
Congestive Heart Failure
1
Peripheral Vascular Disease
1
Cerebrovascular Disease
1
Dementia
1
Chronic Obstructive Pulmonary Disease
1
Rheumatologic Disease
1
Peptic Ulcer Disease
1
Depression
1
Use of Warfarin
1
Hypertension
1
Mild Liver Disease
1
Diabetes Mild to Moderate
1
Hemiplegia or Paraplegia
2
Moderate or Severe Renal Disease
2
Diabetes with Complications
2
Skin Ulcers/Cellulitis
2
Malignancy (solid, non-metastatic)
2
Hematological malignancy (leukemia, lymphoma)
2
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Comorbidity
Deyo-Charlson Weight
Moderate to Severe Liver Disease
3
Metastatic Solid Tumor
6
AIDS
6
Any transplant (bone marrow, solid organ)
6
AIDS=acquired immunodeficiency syndrome.
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