Monitoring of Ceftolozane-Tazobactam Plasmatic Levels in Critical Patients

The aim of this study is to determine the Ceftolozane-Tazobactam Plasmatic Levels and and analyse the clinical impact that might have the dose regimens that have been used until now.

Study Overview

• Status: Unknown
• Conditions: Serious Infection
• Intervention / Treatment: Drug: Ceftolozane/tazobactam

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients older than 18 years old, hospitalised in the Virgen Macarena University Hospital for a serious infection that meet all the inclusion criteria and none of the exclusion criteria.

Description

Inclusion Criteria:

• Patients older than 18 years old.
• Hospitalised for a serious illness.
• Treated with Ceftolozane-Tazobactam
• Patients that signed the Informed Consent.

Exclusion Criteria:

• Allergic to any component of Ceftolozane-Tazobactam.
• Any surgical or medical evidence that according to the investigator could interfere with the pharmacodynamics of the medication: absorption, distribution, metabolism or excretion.
• Concomitant terminal illness.
• Unable to sign the Informed Consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Ceftolozane-Tazobactam cohort; Patients older than 18 years old that are hospitalised in the Virgen Macarena University Hospital that are being treated with Ceftolozane-Tazobactam in empiric or targeted treatment.

Drug: Ceftolozane/tazobactam; The dose will be 1g ceftolozane + 0,5 g tazobactam every 8 hours or 2 g ceftolozane + 1 g tazobactam, it´s recommended to use this last dose regimen in patients with pneumonia or septic shock of any focus. The patients will be followed as it´s done habitually. There will be done infection focus cultures and others according to usual clinical practice. It´ll be determined the clinical response and mortality in the days 14 and 30 after the beginning of the medicine, respectively. The Ceftolozane-Tazobactam levels determination will always be made in state of equilibrium (after the third dose). Four samples will be collected: Just before the antibiotic infusion.; One hour after the antibiotic infusion.; Three hours after the antibiotic infusion.; Six hours after the antibiotic infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Ceftolozane-Tazobactam seric concentrations and analyse the clinic impact that could have the dose regimens used until now.	Determination of the Ceftolozane-Tazobactam seric concentration by collecting 4 blood samples and measuring its antibiotic levels and if it´s achieved an adequate therapeutic efficacy assessed by the patient´s clinical and microbiological recovery. The dose regimens used until now are 1+0,5 g every 8 hours in case of intra-abdominal infection or complicated urinary infection and 2 +1 g every 8 hours in case of pneumonia or septic shock of any focus.	Up to 12 months after the antibiotic administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analyse if with both dose regimens are achieved the PK/PD parameters associated with the maximum therapeutic efficacy in patients with renal hyper clearance.	Determine if with both dose regimens are achieve the pharmacodynamic and pharmacokinetic parameters associated with the maximum therapeutic efficacy in patients that have creatinine clearance above 130 ml/min.	Up to 12 months after the antibiotic administration
Determine the Ceftolozane-Tazobactam seric concentrations and analyse if with both dose regimens are achieved the PK/PD parameters associated with the maximum therapeutic efficacy in patients with morbid obesity.	Determination of the Ceftolozane-Tazobactam seric concentration by collecting 4 blood samples and measuring its antibiotic levels and if with both dose regimens are achieve the pharmacodynamic and pharmacokinetic parameters associated with the maximum therapeutic efficacy in patients that have BMI (body mass index) above 40	Up to 12 months after the antibiotic administration
Determine the Ceftolozane-Tazobactam seric concentrations and analyse if with both dose regimens are achieved the PK/PD parameters associated with the maximum therapeutic efficacy in patients with continuous renal replacement technique.	Determination of the Ceftolozane-Tazobactam seric concentration by collecting 4 blood samples and measuring its antibiotic levels and if with both dose regimens are achieve the pharmacodynamic and pharmacokinetic parameters associated with the maximum therapeutic efficacy in patients that have their blood purified extracorporeally, replacing the renal function continuously 24 hours of the day.	Up to 12 months after the antibiotic administration
Determine if in patients with Gram-negative bacillary bacteremia are achieved concentrations that are 100 % of the time 4 times above the minimum inhibitory concentration (MIC).	Determination of if in patients with Gram-negative bacillary bacteremia (patients with their bloodstream invaded by Gram-negative bacillary which is diagnosed by blood culture) are achieved concentrations that are 100 % of the time 4 times above the MIC by strips of isolated pathogen gradient .	Up to 12 months after the antibiotic administration
Determine by a Monte Carlo simulation model the dose regimen that should be used.	Determination by a Monte Carlo simulation model of the dose regimen that should be used based on the pharmacokinetic parameters and according to the defined efficacy pharmacodynamic parameters.	Up to 12 months after the antibiotic administration
Describe the frequency of resistance´s development during the Ceftolozane-Tazobactam treatment and, if it´s possible to evaluate if there´s a correlation with the seric levels.	Description of the rate of resistance´s development during the Ceftolozane-Tazobactam and if there´s a correlation with the Ceftolozane-Tazobactam seric levels.	Up to 12 months after the antibiotic administration
Describe the Ceftolozane-Tazobactam treatment´s clinical result as well as existence of adverse effects.	Description of the Ceftolozane-Tazobactam clinical results as well as the rate and seriousness of adverse effects.	Up to 12 months after the antibiotic administration

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: José Garnacho Montero, Hospital Universitario Virgen Macarena

Study record dates

Study Major Dates

• Study Start (Anticipated): February 15, 2020
• Primary Completion (Anticipated): March 15, 2021
• Study Completion (Anticipated): June 15, 2022

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): February 6, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Ceftolozane-Tazobactam; Plasmatic Levels; Serious Infection; Dose adjustment
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Tazobactam; Ceftolozane; Ceftolozane, tazobactam drug combination
• Other Study ID Numbers: FIS-CEF-2019-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No