Inhaled Colistin Use in Adults With HospitalAcquired and

Inhaled Colistin Use in Adults With Hospital-Acquired and Ventilator. Associated Pneumonia Samantha L Gauthier, Pharm. D. PGY-1 Pharmacy Resident Unity Health – White County Medical Center

Disclosure • I have nothing to disclose • Neither I, nor my spouse, have at present and/or have had within the past 12 months a relevant financial relationship with a commercial interest 2

Pharmacist Objectives • Differentiate between available formulations • Compare doses of inhaled colistimethate, considering formulations and patient prognosis/severity • Identify patients that qualify to receive inhaled colistimethate per the 2016 IDSA and ATS HAP/VAP guidelines • Summarize appropriate use of inhaled colistimethate per the 2016 IDSA and ATS HAP/VAP guidelines 3

Technician Objectives • Identify which patients should receive inhaled colistimethate per the 2016 IDSA and ATS HAP/VAP guidelines. • Compare the different formulations of colistimethate. • Discuss the dosing techniques for colistimethate based on the patient’s severity. 4

Abbreviations • HAP: hospital-acquired pneumonia • VAP: ventilator-associated pneumonia • CMS: colistimethate sodium • CBA: colistin base activity • GNB: gram-negative bacilli • AG: aminoglycosides • MDR: multi-drug resistant 5

Outline • Background • Dosing/Administration • Patient Qualifications • Recommendations per IDSA/ATS • Summary 6

Background • Class: polymyxin • MOA: disruption of outer cell membrane • Bactericidal • Spectrum of Activity: • Narrow • P. aeruginosa • A. baumannii • Resistance: uncommon • Formulations: • Colistin sulfate • Colistimethate sodium (CMS) • Colistin Base Activity (CBA) • 1 mg CBA = 2. 67 mg CMS • Colistimethate Sodium (CMS) • 1 mg CMS = 12500 units CMS • Half-life: • CMS: 124 minutes • CBA: 251 7

Dosing/Administration • HAP/VAP due to MDR GNB • Nebulized: 150 mg CMS every 8 hours delivered over 60 minutes for 14 days* • Bronchodilator within 15 minutes prior to administration 8

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Patient Qualifications • VAP due to GNB susceptible to AG or polymyxins • Not responding to IV antibiotics alone • HAP/VAP due to Acinetobacter sensitive only to polymyxins • HAP/VAP due to carbapenem-resistant pathogens 10

IDSA/ATS HAP/VAP Guidelines Recommendations • VAP due to GNB susceptible to AG or polymyxins • IV + Inhaled • Compared: tobramycin, gentamicin, colistin • Organisms: • MDR Klebsiella pneumoniae • Pseudomonas aeruginosa • Acinetobacter baumannii • Improved clinical cure rate • No additional harmful effects • Reduced duration of mechanical ventilation 11

IDSA/ATS HAP/VAP Guidelines Recommendations (continued) • HAP/VAP due to Acinetobacter sensitive only to polymyxins • IV Polymyxin + Inhaled (adjunctive) • Higher clinical response • No increase in harm 12

IDSA/ATS HAP/VAP Guidelines Recommendations (continued) • HAP/VAP due to carbapenem-resistant pathogens • • • IV Polymyxin + Inhaled (adjunctive) Potential pharmacokinetic advantage Improved clinical outcomes Improved mortality No increase in harm • Routine antimicrobial susceptibility testing 13

Summary • IV + Inhaled colistin • • VAP due to GNB susceptible to AG or polymyxins Not responding to IV antibiotics alone HAP/VAP due to Acinetobacter sensitive only to polymyxins HAP/VAP due to carbapenem-resistant pathogens • No differences in clinical response rates, mortality, or nephrotoxicity. • Exception: improved mortality in carbapenem-resistant pathogens • Reasonable component of empiric regimens in intensive care units with high rates of resistance to agents from other classes. • Over use of polymyxins may jeopardize its current role as the antibiotic of last resort for resistant gram-negative pathogens. 14

References [1] Management of Patients with Hospital-acquired and Ventilatorassociated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Disease Society of American and the American Thoracic Society [2] Colistin: An overview, Up. To. Date. Mac. Laren, Spelman. March 14, 2017 [3] Colistimethate, Lexi-Drugs 15

Questions? 16