This is an open-label, multi-center study in pediatric patients age 3 months to less than 18 years with cystic fibrosis (CF) and newly detected Pseudomonas aeruginosa (PA) pulmonary colonization/infection. All eligible participants will be treated with a 28-day course of Aztreonam for Inhalation Solution (AZLI) 75 mg 3 times daily. After completion of study drug, subjects will be followed up through Day 196 for safety and recurrence of PA.

The primary objective is to evaluate the proportion of participants with PA-negative cultures at all time points during a 6-month monitoring period (through Day 196) after cessation of AZLI treatment. Microbiological cultures will be obtained at Baseline, Day 28 (end of AZLI treatment), Day 56 (1 month after completing AZLI treatment), Day 112 (3 months after completing AZLI treatment), and Day 196 (6 months after completing AZLI treatment).

Inclusion Criteria:

• Males or females age 3 months to less than 18 years
• Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria:
• Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test OR
• Abnormal nasal transepithelial potential difference test OR
• Two well-characterized, disease-causing genetic mutations in the CF transmembrane conductance regulator (CFTR) gene AND
• One or more clinical features consistent with CF
• Documented new onset of positive lower respiratory tract culture (e.g., throat swab, sputum, or BAL) for PA within 30 days of study entry (prior to screening visit) defined as either first lifetime documented PA-positive culture OR PA recovered after at least a 2 year history of PA-negative respiratory cultures (at least 2 cultures per year)
• Forced expiratory volume in 1 second (FEV1) ≥ 80% predicted at screening visit (subjects ≥ 6 years of age)
• 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.
• All sexually active females who were of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study. Females utilizing hormonal contraceptives as a birth control method must have used the same method for at least 3 months prior to study drug dosing.
• Males must agree to use barrier contraception (condom with spermicide) during heterosexual intercourse from screening through to study completion and for 90 days from the last dose of study investigational medicinal product
• Participants and/or parent/guardian must be able to give written informed consent prior to any study related procedure

Exclusion Criteria:

• Use of IV or inhaled antipseudomonal antibiotics within 2 years of study entry (screening visit)
• Use of oral antipseudomonal antibiotics within 30 days of study entry (screening visit)
• History of sputum or throat swab culture yielding Burkholderia spp. within 2 years prior to screening visit
• History of local or systemic hypersensitivity to monobactam antibiotics
• History of intolerance to inhaled short acting beta 2 agonists
• History of lung transplantation
• History of AZLI (or Cayston®) administration
• Administration of any investigational drug or device within 28 days prior to screening visit or within 6 half-lives of the investigational drug (whichever is longer)
• Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone per day or 20 mg prednisone every other day
• Current requirement for daily continuous oxygen supplementation or requirement of more than 2 L/minute at night
• Hospitalization for pulmonary-related illness within 28 days prior to screening visit
• Changes in or initiation of chronic azithromycin treatment within 28 days prior to screening visit
• Changes in antimicrobial, bronchodilator (BD), corticosteroid, dornase alfa, or hypertonic saline medications within 7 days prior to screening visit; for participants on a stable regimen of hypertonic saline (28 days on/28 days off), beginning or ending a cycle of hypertonic saline is allowed
• Changes in physiotherapy technique or schedule within 7 days prior to screening visit
• Abnormal renal or hepatic function results at most recent test within the previous 12 months, defined as:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit of normal (ULN), or
• Serum creatinine > 2 times ULN for age
• Pregnant or lactating females; a negative urine pregnancy test is required for all females of childbearing potential (unless surgically sterile), and confirmatory serum pregnancy test in the event of an initial positive urine test result
• Any serious or active medical or psychiatric illness (including drug or alcohol abuse), which in the opinion of the investigator, would interfere with treatment, assessment, or compliance with the protocol
• Presence of a condition or abnormality that would compromise the patient's safety or the quality of study data, in the opinion of the investigator