pharmacological comparison of continuous and intermittent infusions of cloxacillin

Conditions: Infection; Methicillin Susceptible Staphylococcus Aureus Infection; Cloxacillin Treatment

Summary: 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.

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.

Eligibility criteria:
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