781. Pharmacokinetic Assessment of Continuous Infusion Ceftolozane/Tazobactam for Drug-Resistant Pseudomonas aeruginosa Left Ventricular Assist Device Driveline Infection
Session: Poster Abstract Session: Treatment of Resistant Infections - Clinical Analyses
Thursday, October 5, 2017
Room: Poster Hall CD
Background: Pseudomonas aeruginosa is a common pathogen in left ventricular assist device (LVAD) infections. Ceftolozane/tazobactam (C/T) is a beta-lactam/beta-lactamase inhibitor with activity against P. aeruginosa, including multi-drug resistant (MDR) isolates. We describe the novel use of continuous infusion (CI) C/T with therapeutic drug monitoring in a 70-year-old man who developed a MDR P. aeruginosa LVAD driveline infection.

Methods: The patient received CI C/T 6g IV over 24 hours to facilitate long-term outpatient therapy after receipt of five days of intermittent infusion (3g IV every 8 hours over 1 hour). Blood samples were collected in heparinized tubes immediately prior to and at 6, 12, 18, 24, and 48 hours after initiating CI. The samples were centrifuged at 2,500 rpm for 10 min and stored at -80°C until assayed. Ceftolozane and tazobactam concentrations were quantified using previously validated high-performance liquid chromatography (HPLC) methods.

Results: Ceftolozane and tazobactam concentrations are shown in Table 1. The susceptibility profile (VITEK® 2) demonstrated the following minimum inhibitory concentrations (MICs): gentamicin ≤ 1 mcg/mL, cefepime = 32 mcg/mL, ciprofloxacin ≥ 4 mcg/mL, meropenem = 8 mcg/mL. Colistin, polymyxin B, and C/T MICs were confirmed via E-test (2 mcg/mL, 2 mcg/mL, and 1.5 mcg/mL, respectively). The patient clinically improved with resolution of signs and symptoms of infection after 6 weeks with CI C/T. Suppressive therapy was continued indefinitely in lieu of source control. A subjective increase in gout pain was reported, but no other major adverse events were noted during therapy.

Conclusion: Adequate systemic drug concentrations of C/T well above the MIC were achieved when administered as a CI of 6g over 24 hours. Based on serum ceftolozane concentrations, dose modification of CI may be possible with future evaluation. Continuous infusion represents a potentially well-tolerated delivery for C/T and warrants further study.

Table 1. Ceftolozane and tazobactam drug concentrations.

Collection Time

Ceftolozane Concentration (µg/ml)

Tazobactam Concentration (µg/ml)

Intermittent Infusion

Trough, steady state

97.83

25.62

Continuous Infusion

6 hour

55.12

16.91

12 hour

47.49

13.32

18 hour

39.36

9.31

24 hour

39.90

10.92

48 hour

40.64

19.64

Rachel Foster, PharmD, MBA1, Alyssa P. Gould, PharmD2, Julie Ann Justo, PharmD, MS, BCPS-AQ ID3, Stella Okoye, MD4, David P. Nicolau, PharmD, FCCP, FIDSA5 and P. Brandon Bookstaver, PharmD, FCCP, FIDSA, BCPS, AAHIVP3, (1)Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, Columbia, SC, (2)Palmetto Health Richland, Columbia, SC, (3)Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, SC, (4)University of South Carolina School of Medicine, Columbia, SC, (5)Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT

Disclosures:

R. Foster, None

A. P. Gould, None

J. A. Justo, None

S. Okoye, None

D. P. Nicolau, Merck: Investigator and Speaker's Bureau , Research support

P. B. Bookstaver, Rock Pointe: Content Developer , Consulting fee

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