Clinical and Safety Evaluation of Continuously Infused Ceftolozane/Tazobactam in the Outpatient Setting

Abstract

Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor currently dosed by 8-hour intervals to treat complicated and multidrug-resistant Pseudomonas aeruginosa infections in inpatients. This dosing strategy limits the ability to transition patients to outpatient antimicrobial therapy. There are limited data in the literature to support continuous infusion (CI) dosing. Methods This study is a retrospective chart review of patients who received CI C/T at an infusion center part of a community health system. Patients were evaluated from August 2016 through January 2018. Patients were included in the study if they were ≥18 years old and received their entire course of C/T as a CI in the outpatient setting. Patients were excluded if they received any part of their therapy as an inpatient. Results The primary outcome evaluated was symptom resolution. Secondary outcomes evaluated were microbiologic resolution as well as patient satisfaction. Seven patients received either 4.5 or 9 grams of continuous infusion C/T every 24 hours in the outpatient setting over the study period. For the primary outcome, 6 of 7 patients had symptom resolution. For the secondary outcomes, 3 of 3 patients had microbiologic resolution, and patient satisfaction scores were overall positive among respondents. Conclusions Ceftolozane/tazobactam delivered as a continuous infusion may be a safe, effective, and convenient way to treat infections caused by P aeruginosa. This novel treatment regimen can be an option for patients to avoid hospital admission or discharge to complete therapy as an outpatient.

Real-world use of ceftolozane/tazobactam: a systematic literature review

“…Including studies that recruited patients from multiple countries, the most common study locations were the US (N = 50), [ 21 , 22 , 24 , 27 – 29 , 33 , 34 , 39 – 41 , 43 – 45 , 50 , 51 , 54 , 56 , 57 , 59 , 61 , 62 , 68 – 71 , 73 – 77 , 79 – 85 , 87 – 92 , 94 , 95 , 97 – 100 ] Spain (N = 15) [ 26 , 28 , 30 – 32 , 35 – 37 , 42 , 47 , 49 , 58 , 66 , 79 , 96 ], and Italy (N = 13) [ 18 , 20 , 23 , 25 , 48 , 52 , 53 , 55 , 64 , 67 , 72 , 79 , 86 ]. A variety of study designs were captured: 27 were non-comparative retrospective studies [ 18 , 19 , 22 , 24 , 25 , 28 , 32 , 33 , 40 , 41 ,…”

“…(range): 14 (7–35) days 95 (18/19) 74 (14/19) 21 (4/19) Buonomo et al 2020 [ 20 ] Retrospective, single center case series Italy 4 PsA (50% MDR; 50% XDR) cSSTI in patients with chronic kidney disease - Dose C/T: creatine clearance adjusted (100.0%)—0.75 g q8h (75%), 0.375 g q8h (25%) Empiric C/T: 0.0% Confirmed C/T: 100.0% Duration: med. (range): 14 (14) days 100.0 (4/4) - 0 Jones et al 2020 [ 21 ] Retrospective single center, case series US 7 PsA (57.1% non-MDR; 42.9% MDR) infections (one patient also had an E. coli infection), including pneumonia (42.9%), cUTI (28.6%), and bacteremia (14.3%) – Dose C/T: 4.5 g qd (CI; 85.7%), 9 g qd (CI; 14.3%) Duration: med. (range): 14 (6–42) days 85.7 (6/7) 100.0 (3/3) 0 a Jorgensen et al 2020 [ 22 ] Retrospective, multicenter US 259 MDR gram-negative infections (91.1% PsA; 23.2% Enterobacterales) including, RTIs (62.9%), SSTIs (10.8%), and UTIs (10.0%).…”

Outpatient Parenteral Antimicrobial Therapy With Ceftolozane/Tazobactam via Continuous Infusion for Multidrug-Resistant Pseudomonas aeruginosa Osteomyelitis

“…Ceftolozane-tazobactam can be administered in continuous infusion, and it is stable for up to 24 hours at room temperature, allowing for potential administration as a continuous infusion by elastomeric pumps. In a study published recently, 7 patients were treated with ceftolozane-tazobactam in continuous infusion in the outpatient setting, and 6 of 7 patients had symptom resolution [ 1 ].…”

“…Outpatient parenteral antimicrobial treatment (OPAT) is an alternative for these infections but generally requires several injections per day, and elastomeric pumps are a good alternative. In reference to an article published in your journal recently by Jones, Huelfer, and Bland [ 1 ], we present a case of Pseudomonas aeruginosa osteomyelitis treated with surgery and antibiotic therapy with ceftolozane-tazobactam in continuous infusion at home using an elastomeric pump.…”

Clinical syndromes and treatment location predict utility of carbapenem sparing therapies in ceftriaxone-non-susceptible Escherichia coli bloodstream infection

“…Cefiderocol is only stable for four hours at room temperature and is not currently stable for use in OPAT [ 27 ]. A small case series has used infusions of ceftolozane-tazobactam over 24 hours in OPAT with good outcomes [ 28 ]. However, stability studies have shown ceftolozane-tazobactam to be stable for only 12 hours at 32 °C [ 29 ].…”