Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin (CLOXA Continue)

Pharmacological Comparison of Continuous and Intermittent Infusions of Cloxacillin During Bone and Joint Infections: a Prospective, Randomized, Open-label, Monocentric Crossover Study.

Our objective is to establish pharmacological equivalence of intermittent and continuous infusion of cloxacillin during methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI). Twelve patients suffering MSSA BJI will receive both administration modalities and serum concentrations of cloxacillin will be determined after 3 days of II and 3 days of continuous infusion in a prospective, randomized, open-label, monocentric crossover study design.

Study Overview

• Status: Completed
• Conditions: Infection; Methicillin Susceptible Staphylococcus Aureus Infection; Cloxacillin Treatment
• Intervention / Treatment: Drug: Modification for administration mode of cloxacillin antibiotic

Detailed Description

Introduction Staphylococcus aureus is the main causative agent of bone and joint infections (BJI). More than 80% of the strains isolated in France are methicillin-susceptible (MSSA). During the early phase of MSSA BJI management national and international guidelines recommend the use of intra-venous type M penicillin with a dosage ranging from 100 to 200 mg/kg/day. Pharmacological properties of this class of penicillin require 4 to 6 infusions by day. Continuous infusion of beta-lactams is increasingly used especially in intensive care units. It allows an improvement of pharmacokinetic/pharmacodynamics (PK/PD) parameters and a reduction in time dedicated to infusion preparations by the nurses. However pharmacological data regarding such administration is required for type M penicillin.

Design A 6-day, prospective, randomized, open-label, monocentric crossover study

Participants Twelve adult patients with MSSA BJI

Intervention Patients will be randomized in two groups: the first group will receive 3 days of cloxacillin (150 mg/kg/day) through 4 intermittent infusions/day followed by 3 days of cloxacillin (150 mg/kg/day) through continuous infusion (2 infusions during 12 hours). In the second group the infusion modalities will be inverted and continuous infusion will be preceded by a loading dose. Serum concentrations of cloxacillin will be determined at Day 3 and Days 6 The area under the curve / minimal inhibitory concentration ratio will be use to establish the equivalence between both administration modalities.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France
    • CHU de Nice

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Staphylococcus aureus sensitive to methicillin and to be treated with cloxacillin by injectable antibiotic monotherapy For patients with Osteo-articular infection on material

  • Presence of a fistula in contact with the prosthesis or implant.
  • Pus in the joint or in contact with the prosthesis or implant
  • Presence of at least 1 positive sample (1 sampling by articular puncture or 1 peroperative sampling or by blood culture)
  • A histological analysis of the peri-prosthetic osteo-articular tissue which is the object of acute inflammation is a strong argument in favor of an Osteo-articular infection on material

For spondylodiscitis

• Culture of a disco-vertebral biopsy puncture to isolate a methicillin sensitive S. aureus
• Positive haemocultures for S. aureus sensitive to methicillin with imaging examination (CT or MRI of the spine) showing images of spondylodiscitis

For primitive arthritis :

• Culture of a positive methicillin-sensitive S. aureus articular fluid puncture
• Cultivation of a methicillin-sensitive S. aureus-positive surgical joint lavage fluid

For osteitis the diagnosis is based on the following criterion:

*Culture of surgical specimens from a focal zone of methicillin-sensitive S. aureus-positive osteitis

Exclusion Criteria:

• Allergy to betalactamines
• Taking penicillin M within 36 hours before inclusion Renal function impaired with a glomerular filtration rate measured by MDRD formula of less than 30 ml / min
• Patient with renal function expected to change within 6 days of inclusion

• Hepatocellular insufficiency, whatever the degree

  -*Methotrexate intake

• Polytransfused (more than 2 CGR) in the previous week
• Patients requiring resuscitation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intermittent administration of cloxacillin	Drug: Modification for administration mode of cloxacillin antibiotic; For intermittent administration, patients will benefit from cloxacillin treatment in conventional hospitalization, in accordance with national guidelines, at a dose of 150 mg / kg per day in 4 infusions, not exceeding the maximum daily dose of 12 g / day according to. For continuous administration the same quantity of cloxacillin 150 mg / kg per day, without exceeding the maximum daily dose of 12 g / day, will be delivered by a self-propelled syringe in twice 12 hours. Patients randomly assigned to receive continuous administration will receive a dose of cloxacillin equivalent to the dose administered 4 times daily during iterative administration using a self-pulsating syringe. For the first day of the study, this loading dose will be subtracted from the 150 mg / kg dose to be administered continuously over the remaining 23 hours of the first day of the study and never exceed 12g / day. Pharmacological dosages will be performed on the third and sixth day in both arms
Experimental: continuous administration of cloxacillin	Drug: Modification for administration mode of cloxacillin antibiotic; For intermittent administration, patients will benefit from cloxacillin treatment in conventional hospitalization, in accordance with national guidelines, at a dose of 150 mg / kg per day in 4 infusions, not exceeding the maximum daily dose of 12 g / day according to. For continuous administration the same quantity of cloxacillin 150 mg / kg per day, without exceeding the maximum daily dose of 12 g / day, will be delivered by a self-propelled syringe in twice 12 hours. Patients randomly assigned to receive continuous administration will receive a dose of cloxacillin equivalent to the dose administered 4 times daily during iterative administration using a self-pulsating syringe. For the first day of the study, this loading dose will be subtracted from the 150 mg / kg dose to be administered continuously over the remaining 23 hours of the first day of the study and never exceed 12g / day. Pharmacological dosages will be performed on the third and sixth day in both arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: T> minimal inhibitory concentration	Six days
The equivalence of the Pharmacokinetic-Pharmacodynamic indicators commonly used for the study of betalactamines: the area under the curve (AUC) / minimal inhibitory concentration	Six days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Johan Johan, MD, Centre Hospitalier Universitaire de Nice

Publications and helpful links

General Publications

• Courjon J, Garzaro M, Roger PM, Ruimy R, Lavrut T, Chelli M, Raynier JL, Chirio D, Demonchy E, Cabane L, Jehl F, Trojani C, Grillon A, Goutelle S. A Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin during Staphylococcus aureus Bone and Joint Infections. Antimicrob Agents Chemother. 2020 Nov 17;64(12):e01562-20. doi: 10.1128/AAC.01562-20. Print 2020 Nov 17.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2017
• Primary Completion (Actual): November 23, 2017
• Study Completion (Actual): September 18, 2018

Study Registration Dates

• First Submitted: July 28, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (Actual): August 11, 2017

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Anti-Infective Agents; Anti-Bacterial Agents; Cloxacillin
• Other Study ID Numbers: 16-PP-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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