Ceftolozane/Tazobactam: A Novel Cephalosporin/β‐Lactamase Inhibitor Combination

Cho, Jonathan C.; Fiorenza, Mallory; Estrada, Sandy

doi:10.1002/phar.1609

Cited by 60 publications

(34 citation statements)

References 34 publications

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“…The PK/PD index of ceftolozane that best correlates with in vivo efficacy is the percentage of the time in which free plasma drug concentrations exceed the minimum inhibitory concentration of a given pathogen % T MIC ). (6) The time above a threshold concentration has been determined to be the parameter that best predicts the efficacy of tazobactam in in vitro nonclinical models (threshold = 0.25 μg/ml, for isolates with high-β-lactamase expression). (7)…”

Section: Tablementioning

confidence: 99%

Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation in a lung transplant recipient

Arena¹,

Marchetti

Angelis³

et al. 2018

Preprint

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22Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation (ECMO) 23 has not been previously studied. In this work we report on the ceftolozane and tazobactam 24 plasmatic levels in a lung transplant recipient during ECMO, treated with ceftolozane-tazobactam 25 (2g/1g, intravenously every 8 h, 1 h infusion) for a Pseudomonas aeruginosa pulmonary infection. 26Ceftolozane Cmax and Cmin, monitored during 96 hrs, remained above 60 and 20 µg/mL, 27 respectively, with optimal drug exposure (100% %T MIC ). Tazobactam levels were above 1.9 µg/mL. 28 29 30patient had a normal renal function with creatinine clearance, estimated using the Cockcroft-Gault 83 formula, above 90 mg/min (range 90-150 mg/min) ( Figure 1). 84Ceftolozane and tazobactam plasma concentrations were monitored for 96 h following the first 85 administration. Plasma samples were obtained ½ h after the end of each ceftolozane-tazobactam 86 infusion and immediately before the beginning of the following dose (Cmax and Cmin 87 respectively). The samples were centrifuged at 1,600 g for 10 min to yield at least 1 ml of plasma. 88 Plasma samples were stored at −80°C until the assay. Ceftolozane and tazobactam concentrations 89 were quantified using a validated HPLC method at the Chemotherapy Laboratory of the Department 90 of Health Sciences (University of Florence, Italy). (11) 91In the following days the patient clinical conditions improved and, on day 3 after the lung 92 transplant, the vaECMO was switched again to vvECMO. 93In the 96 h of drug monitoring, the ceftolozane levels remained constantly above the isolate MIC. In 94 the first 48 h, ceftolozane Cmax were persistently above 100 µg/mL. Later, from 48 to 96 h, there 95 was a decline in Cmax and Cmin, which, however, remained above 60 and 20 µg/mL, respectively 96 ( Figure 1). Tazobactam concentration were above 1.9 µg/mL for all the monitored period. 97ECMO was halted on day 8 after lung transplantation. The patient's conditions eventually improved 98 and, on day 15 after lung transplantation, the antimicrobial therapy was discontinued. No adverse 99 events were attributed to the ceftolozane-tazobactam administration. Four consecutive tracheal 100 aspirate cultural exams, performed in the last day of treatment and 3, 4, and 7 days after the 101 antibiotics discontinuation, did not grow P. aeruginosa or any other pathogen. 102Concluding, we documenting the success of ceftolozane-tazobactam treatment for a case of 103 carbapenem-resistant P. aeruginosa LRTI in a lung transplant recipient subjected to ECMO 104 support. TDM revealed that optimal drug exposure was achieved, with a ceftolozane concentration 105 at 100% %T MIC . Of note, in this case, optimal Cmax and Cmin were obtained using a 3 g 106 cefotolozane-tazobactam dose every 8 h, using a standard 1 h infusion time. During the TDM 107 period we assisted to a decrease of ceftolozane/tazobactam Cmin and Cmax that could be attributed 108 6 to the increase in the patient's creatinine clearance values. In fact, it was previo...

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Section: Tablementioning

confidence: 99%

Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation in a lung transplant recipient

Arena¹,

Marchetti

Angelis³

et al. 2018

Preprint

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“…To overcome this problem, new antibiotics, such as ceftolozane-tazobactam (C-T), which can be an effective and safe alternative for the treatment of MDRPA infections (5,6), were recently developed. C-T is a new combination of an antipseudomonal cephalosporin and a beta-lactamase inhibitor.…”

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confidence: 99%

Salvage Therapy with Ceftolozane-Tazobactam for Multidrug-Resistant Pseudomonas aeruginosa Infections

Castón

Torre

Ruiz‐Camps

et al. 2017

Antimicrob Agents Chemother

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Infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) present a major problem for therapeutic management. We report here our experience with 12 patients with a severe MDRPA infection (6 of which were pneumonia) who received salvage therapy with ceftolozane-tazobactam after inappropriate empirical treatment and/or suboptimal targeted treatment. Although 10 of the 12 patients (83.3%) experienced septic shock, only 3 patients (25%) died during the follow-up period. Microbiological cure in 7 patients (58.3%) was observed.

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“…C/T is currently approved by the United States Food and Drug Administration (FDA) for treatment of complicated intra-abdominal infections (cIAI), in combination with metronidazole, as well as for complicated urinary tract infections (cUTI), including pyelonephritis [ 1 , 3 ]. Ongoing Phase 3 trials are currently in progress for the treatment of ventilator-associated and nosocomial pneumonia [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Successful Treatment of Multi-Drug Resistant Pseudomonas aeruginosa Bacteremia with the Recommended Renally Adjusted Ceftolozane/Tazobactam Regimen

2016

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IntroductionCeftolozane/tazobactam (C/T) is a novel antibiotic approved for complicated intra-abdominal and urinary tract infections caused by Gram-positive and Gram-negative organisms, including some MDR strains. Little is known about the use of this agent for treatment of bacteremia and even less so about the appropriateness of the renally defined regimens. We describe a case of a 66-year-old man with a history of chronic kidney disease (baseline Cr = 3–4 mg/dl) and recurrent nephrolithiasis with bilateral stents who had positive concurrent urine and blood cultures for MDR Pseudomonas aeruginosa (PSA), susceptible only to amikacin and colistin. Due to the MDR phenotype and his underlying kidney disease, the 375 mg (250 mg/125 mg) dose of C/T was given as monotherapy every 8 h for his bloodstream infection.MethodsOnce steady state was anticipated, blood was obtained at the end of infusion (1 h), and at 3, 5 and 8 h for drug concentration determination using a validated high-performance liquid chromatography method at the Center for Anti-Infective Research and Development, Hartford Hospital, Hartford.ResultsThe minimum inhibitory concentration (MIC) for the PSA was 2/4 for C/T, indicating susceptibility. Concentration of ceftolozane of 21.87 µg/ml at 8 h indicated that serum concentrations were maintained above the MIC throughout the dosing interval. The patient was given 25 days of C/T and experienced a successful clinical outcome. Blood cultures obtained at 1 and 3 weeks after completion of treatment remained sterile. No adverse events were attributed to C/T.ConclusionIn this patient, the renally adjusted dose of C/T was safe and provided sufficiently high drug concentrations that exceeded the MIC of the infecting organism over the course of therapy. More data are required to determine the clinical utility of C/T in the setting of MDR PSA bacteremia.

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Ceftolozane/Tazobactam: A Novel Cephalosporin/β‐Lactamase Inhibitor Combination

Cited by 60 publications

References 34 publications

Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation in a lung transplant recipient

Ceftolozane-tazobactam pharmacokinetics during extracorporeal membrane oxygenation in a lung transplant recipient

Salvage Therapy with Ceftolozane-Tazobactam for Multidrug-Resistant Pseudomonas aeruginosa Infections

Successful Treatment of Multi-Drug Resistant Pseudomonas aeruginosa Bacteremia with the Recommended Renally Adjusted Ceftolozane/Tazobactam Regimen

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