Imipenem/Cilastatin/Relebactam Pharmacokinetics, Safety, and Outcomes in Adults and Adolescents With Cystic Fibrosis

Exclusion Criteria

• •If female, currently pregnant or breast feeding;
• •History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam agent (a history of mild rash to a β-lactam followed by uneventful re-exposure is not a contraindication);
• •At the time of enrollment, known or suspected infection caused by methicillin-resistant Staphylococcus aureus, Non-tuberculosis mycobacteria (NTM), Burkholderia cepacia complex, Achromobacter species, Stenotrophomonas maltophilia, or moulds; if these pathogens are identified AFTER enrollment, participants may continue to complete the study for objectives 1 and 2; additional treatment will be at the discretion of the treating clinician and discussion with the principal investigator;
• •Receiving or intent to receive any other intravenous antibiotic therapy except concomitant aminoglycosides or fluoroquinolones (concomitant azithromycin administered as chronic suppression therapy to increase duration between exacerbations is permitted); combination therapy to treat CF APE is considered standard of care with aminoglycosides and fluoroquinolones typically prescribed as second antibiotic; the use of combination therapy will not influence objective 1 and will be considered in assessment of objective 2;
• •Receiving or intent to receive any inhaled antibiotics;
• •Unlikely to remain hospitalized for at least 4 days to ensure pharmacokinetic sampling;
• •Inability to perform pulmonary function tests (PFT) at baseline or 2 weeks after end of therapy;
• •For ADULT Participants (18 years or older): Renal dysfunction defined as a creatinine clearance \< 60 mL/min (calculated by the Cockcroft-Gault equation);
• •For ADOLESCENT Participants (12-17 years): Renal dysfunction defined as a creatinine clearance \<90 mL/min/1.73m2 (calculated by the Revised Bedside Schwartz Equation) (Note. Imipenem/cilastatin/relebactam has not been studied in adolescent patients with creatinine clearance (CrCL) \< 90 ml/min/1.73m2);
• •Has used or plans to use any of the following medications, which are organic anion transporter (OAT) 1 or OAT3 inhibitors, within 1 week prior to screening or at any point between screening and the last PK sample collection: cimetidine, probenecid, indomethacin, mefenamic acid, furosemide or other loop diuretics (eg, bumetanide, torsemide, ethacrynic acid), angiotensin receptor blockers (eg, valsartan), and ketorolac;
• •Has used or plans to use imipenem or valproic acid within 7 days before study drug infusion;
• •Acute liver injury, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 times the upper limit of normal, or AST or ALT \> 3 times the upper limit of normal with an associated total bilirubin \> 2 times upper limit of normal;
• •Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator);
• •Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data