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This was an open-label, multicenter study in children ≤ 12 years of age with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa (PA) infection in the lower airways using three 28-day courses of Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily, each followed by 28 days off AZLI. The total treatment duration was to be 6 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-label AZLI | Experimental | Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZLI | Drug | AZLI 75 mg was administered 3 times daily via the investigational nebulizer. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons | Participants who discontinued study drug due to safety or tolerability reasons were defined as those with "Adverse Event (AE)/Safety or Tolerability" on the Study Drug Completion electronic case report form as the reason for early discontinuation. The 95% confidence interval (CI) was calculated using the exact binomial method. | Baseline to Day 168 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years | The change in FEV1 % predicted was assessed at the end of each 28-day AZLI treatment course. FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex, race, and body composition. | Baseline to Day 28, 84, and 140 |
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Inclusion Criteria:
Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:
Documented positive lower respiratory tract culture for PA at the screening visit plus two documented positive lower respiratory tract cultures for PA within 12 months prior to study entry (must have been a minimum 3 months apart.)
Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would have required administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Bresnik, M.D. | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital - Denver | Aurora | Colorado | 80045 | United States | ||
| Nemours Children's Clinic - Jacksonville |
74 participants were screened; 61 participants were enrolled and treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Subjects were enrolled at a total of 25 study sites in the United States and Europe. The first participant was screened on 29 December 2011. The last participant observation was on 03 April 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZLI | Participants received three 28-day courses of Aztreonam for Inhalation Solution (AZLI), each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years | The change in CFQ-R RSS score was assessed at the end of each 28-day AZLI treatment course. The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms. | Baseline to Day 28, 84, and 140 |
| Change in Pseudomonas Aeruginosa (PA) Sputum Density | The change in PA sputum density (log10 colony-forming units per gram [cfu/g]) was assessed at the end of each 28-day AZLI treatment course. | Baseline to Day 28, 84, and 140 |
| Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics | The percentage of participants who used additional (non-study) antipseudomonal antibiotics (IV, inhaled, oral, IV/inhaled, IV/inhaled/oral) was summarized (number and percent) for all subjects. | Baseline to Day 168 |
| Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event | Baseline to Day 168 |
| Number of Days Participants Were Hospitalized Due to a Respiratory Event | The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported. | Baseline to Day 168 |
| Percentage of Participants With Pulmonary Exacerbations | Pulmonary exacerbations were defined as respiratory hospitalizations or discrete courses of non-study IV/inhaled antipseudomonal antibiotics. Use of oral antibiotics alone for respiratory signs or symptoms was considered to be representative of milder clinical events and, therefore, was not included in the definition of pulmonary exacerbations. | Baseline to Day 168 |
| Time to Pulmonary Exacerbation | The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics. | Baseline to Day 168 |
| Percentage of Participants With Study-drug Induced Bronchospasm | Study-drug induced bronchospasm (airway reactivity) was assessed at the baseline visit as the percent change in FEV1 from the pretreatment measurement to 30 minutes following treatment for subjects ≥ 6 years or as from the Investigator's assessment for subjects < 6 years. | Pretreatment at Baseline to 30 minutes following treatment |
| Adverse Event Rates Adjusted for Study Duration | Adverse events occurring in ≥ 5% of participants adjusted for study duration were summarized. The adjustment was made by using a standardized rate calculated as the sum of study duration across patients divided by 28 for the total number of patient months. Rate calculations presented are the number of adverse events (AEs) per patient month. | Baseline to Day 168 |
| Jacksonville |
| Florida |
| 32207 |
| United States |
| Children's Memorial Hospital | Chicago | Illinois | 60614 | United States |
| Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States |
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States |
| Children's Mercy Hospital & Clinics | Kansas City | Missouri | 64108 | United States |
| SUNY Upstate Medical University | Syracuse | New York | 13210 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| University of Utah | Salt Lake City | Utah | 84108 | United States |
| C.H.U de Bordeaux | Bordeaux | France |
| Centre Hospitalier Robert Bissons | Lisieux | France |
| Hopital Necker Enfants Malades | Paris | France |
| Charite Campus Virchow Klinikum | Berlin | Germany |
| Universitatsklinik St. Josef-Hospital | Bochum | Germany |
| Kinder und Jugendklinik, Abteilung Lungen Bronchialheikunde | Erlandgen | Germany |
| Universitatsklinikum Essen | Essen | Germany |
| J.W. Goethe University Hopsital | Frankfurt | Germany |
| Azienda Ospedaliero Universitaria - Policlinico di Catania | Catania | Italy |
| A. Meyer Children Hospital Florence | Florence | Italy |
| Azienda Ospedaliera Instituti Ospitalieri di Verona | Verona | Italy |
| Specjalistyczny Zespot Opieki Zdrowotnej nad Matka i Dzieckiem | Gdansk | Poland |
| Instytut Gruzlicy I Chorob Pluc | Rabka-Zdrój | Poland |
| Instytut Matki i Dziecka | Warsaw | Poland |
| Pediatric Pneunmonology and Cystic Fibrosis Clinic | Barcelona | Spain |
| Hospital Infantil La Paz | Madrid | Spain |
| Hospital Infantil Universitario Nino Jesus | Madrid | Spain |
| Hospital Ramon y Cajal | Madrid | Spain |
| Hosp. Mat-Inf. Carlos Haya | Málaga | Spain |
| COMPLETED |
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| NOT COMPLETED |
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The safety analysis set included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | AZLI | Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Age, Customized | Number | participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
| |||||||||||||||||||||||
| Region of Enrollment | Number | participants |
| |||||||||||||||||||||||
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
| ||||||||||||||||||||||
| Forced expiratory volume in 1 second (FEV1) % predicted | FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex, race, and body composition. Participants ≥ 6 years of age were analyzed at baseline for FEV1 % predicted (n = 52). | Mean | Standard Deviation | percentage of FEV1 % predicted |
| |||||||||||||||||||||
| FEV1 | FEV1 is defined as the maximal volume of air that can be exhaled in 1 second. Participants ≥ 6 years of age were analyzed at baseline for FEV1 (n = 52). | Mean | Standard Deviation | liters |
| |||||||||||||||||||||
| Forced vital capacity (FVC) | FVC is defined as the volume of air that can forcibly be blown out after taking a full breath. Participants ≥ 6 years of age were analyzed at baseline for FVC (n = 52). | Mean | Standard Deviation | liters |
| |||||||||||||||||||||
| FEV25-75 | FEF25-75 is defined as the forced expiratory flow from 25% to 75% of the FVC. Participants ≥ 6 years of age were analyzed at baseline for FEV25-75 (n = 52). | Mean | Standard Deviation | liters/sec |
| |||||||||||||||||||||
| CFQ-R RSS Score | Respiratory symptoms (eg, coughing, congestion, wheezing) were assessed with the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS). The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms. Participants ≥ 6 years of age were analyzed at baseline for CFQ-R RSS (n = 51; data was missing for one participant). | Mean | Standard Deviation | units on a scale |
| |||||||||||||||||||||
| Presence of Pseudomonas aeruginosa (PA) | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Who Discontinued Study Drug Due to Safety or Tolerability Reasons | Participants who discontinued study drug due to safety or tolerability reasons were defined as those with "Adverse Event (AE)/Safety or Tolerability" on the Study Drug Completion electronic case report form as the reason for early discontinuation. The 95% confidence interval (CI) was calculated using the exact binomial method. | Participants in the Full Analysis Set (enrolled and received at least 1 dose of study medication) who completed the study or discontinued study drug due to safety or tolerability reasons were analyzed. Two participants voluntarily withdrew from the study prior to completion (not due to AEs/safety or tolerability reasons). | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline to Day 168 |
|
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| Secondary | Change From Baseline in FEV1 % Predicted in Subjects Aged ≥ 6 Years | The change in FEV1 % predicted was assessed at the end of each 28-day AZLI treatment course. FEV1 % predicted is defined as FEV1 of the patient divided by the average FEV1 in the population for any person of similar age, sex, race, and body composition. | Participants in the Full Analysis Set ≥ 6 years of age were analyzed. | Posted | Mean | Standard Deviation | percentage of FEV1 % predicted | Baseline to Day 28, 84, and 140 |
|
| ||||||||||||||||||||||||||
| Secondary | Change From Baseline in CFQ-R Respiratory Symptoms Scale (RSS) Score in Subjects Aged ≥ 6 Years | The change in CFQ-R RSS score was assessed at the end of each 28-day AZLI treatment course. The range of scores (units) was 0 to 100 with higher scores indicating fewer symptoms. | Participants in the Full Analysis Set ≥ 6 years of age were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Baseline to Day 28, 84, and 140 |
|
| ||||||||||||||||||||||||||
| Secondary | Change in Pseudomonas Aeruginosa (PA) Sputum Density | The change in PA sputum density (log10 colony-forming units per gram [cfu/g]) was assessed at the end of each 28-day AZLI treatment course. | Participants in the Full Analysis Set ≥ 6 years of age were analyzed. | Posted | Mean | Standard Deviation | log10 CFU/g | Baseline to Day 28, 84, and 140 |
|
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| Secondary | Percentage of Participants Who Used Additional (Non-study) Antipseudomonal Antibiotics | The percentage of participants who used additional (non-study) antipseudomonal antibiotics (IV, inhaled, oral, IV/inhaled, IV/inhaled/oral) was summarized (number and percent) for all subjects. | Full Analysis Set | Posted | Number | percentage of participants | Baseline to Day 168 |
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| Secondary | Percentage of Participants Hospitalized at Least Once Due to a Respiratory Event | Full Analysis Set | Posted | Number | percentage of participants | Baseline to Day 168 |
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| Secondary | Number of Days Participants Were Hospitalized Due to a Respiratory Event | The average number of days hospitalized due to a respiratory event, among the 11 participants who were hospitalized for respiratory event, was reported. | Full Analysis Set | Posted | Mean | Standard Deviation | days | Baseline to Day 168 |
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| ||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Pulmonary Exacerbations | Pulmonary exacerbations were defined as respiratory hospitalizations or discrete courses of non-study IV/inhaled antipseudomonal antibiotics. Use of oral antibiotics alone for respiratory signs or symptoms was considered to be representative of milder clinical events and, therefore, was not included in the definition of pulmonary exacerbations. | Full Analysis Set | Posted | Number | percentage of participants | Baseline to Day 168 |
|
| |||||||||||||||||||||||||||
| Secondary | Time to Pulmonary Exacerbation | The median days to first pulmonary exacerbation was summarized using Kaplan-Meier (KM) summary statistics. | Full Analysis Set | Posted | Median | 95% Confidence Interval | days | Baseline to Day 168 |
|
| ||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Study-drug Induced Bronchospasm | Study-drug induced bronchospasm (airway reactivity) was assessed at the baseline visit as the percent change in FEV1 from the pretreatment measurement to 30 minutes following treatment for subjects ≥ 6 years or as from the Investigator's assessment for subjects < 6 years. | Full Analysis Set | Posted | Number | percentage of participants | Pretreatment at Baseline to 30 minutes following treatment |
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| Secondary | Adverse Event Rates Adjusted for Study Duration | Adverse events occurring in ≥ 5% of participants adjusted for study duration were summarized. The adjustment was made by using a standardized rate calculated as the sum of study duration across patients divided by 28 for the total number of patient months. Rate calculations presented are the number of adverse events (AEs) per patient month. | Full Analysis Set | Posted | Number | AEs (per patient month) | Baseline to Day 168 |
|
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Baseline to Day 168
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZLI | Participants received three 28-day courses of AZLI, each followed by 28 days off-treatment. AZLI 75 mg was administered 3 times daily via the investigational nebulizer. | 13 | 61 | 50 | 61 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendiceal mucocoele | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Gastrointestinal infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Bronchopneumonia | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
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| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 16.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Pulmonary function test decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Forced expiratory volume decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Rhonchi | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
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After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met:
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosures | Gilead Sciences, Inc. | ClinicalTrialDisclosures@gilead.com |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| D011552 | Pseudomonas Infections |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D001398 | Aztreonam |
| ID | Term |
|---|---|
| D008997 | Monobactams |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| ≥ 6 years to ≤ 12 years |
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| Unknown or Not Reported |
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| Other |
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| Not Permitted |
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| Spain |
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| Poland |
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| Germany |
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| Italy |
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| Denominators |
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| Categories |
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| Never hospitalized |
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| Hospitalized at least once |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
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