E. Forsblom, E. Ruotsalainen, T. Mölkänen, J. Ollgren, O. Lyytikäinen et al., Predisposing factors, disease progression and outcome in 430 prospectively followed patients of healthcare-and community-associated Staphylococcus aureus bacteraemia, J Hosp Infect, vol.78, issue.2, pp.102-109, 2011.

G. Pedersen, H. C. Schonheyder, and H. T. Sorensen, Source of infection and other factors associated with case fatality in community-acquired bacteremia--a Danish populationbased cohort study from 1992 to 1997, Clin Microbiol Infect, vol.9, issue.8, pp.793-802, 2003.

K. Tamura, Clinical characteristics of infective endocarditis with vertebral osteomyelitis, J Infect Chemother, vol.16, issue.4, pp.260-265, 2010.

H. Ringberg, A. Thoren, and B. Lilja, Metastatic complications of Staphylococcus aureus septicemia. To seek is to find, Infection, vol.28, issue.3, pp.132-138, 2000.

R. Farhad, P. M. Roger, C. Pélligri, C. Touati, and P. Dellamonica, Six weeks antibiotic therapy for all bone infections: results of a cohort study, Eur J Clin Microbiol Infect Dis, vol.29, issue.2, pp.217-239, 2010.

, Med Mal Infect, vol.39, issue.11, pp.815-63, 2009.

D. R. Osmon, E. F. Berbari, A. R. Berendt, D. Lew, W. Zimmerli et al., Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America, Clin Infect Dis, vol.56, issue.1, pp.1-25, 2013.

W. Zimmerli, A. Trampuz, and P. E. Ochsner, Prosthetic-joint infections, N Engl J Med, vol.351, issue.16, pp.1645-54, 2004.

D. P. Lew, F. A. Waldvogel, and . Osteomyelitis, Lancet, vol.364, issue.9431, pp.369-79, 2004.

J. S. Davis, E. Eichenberger, T. L. Holland, and F. Vg, Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management

, Clin Microbiol Rev, vol.28, issue.3, pp.603-61, 2015.

, European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe, 2015.

V. Zeller, Y. Kerroumi, V. Meyssonnier, B. Heym, M. A. Metten et al., Analysis of postoperative and hematogenous prosthetic joint-infection microbiological patterns in a large cohort, J Infect, vol.76, issue.4, pp.328-362, 2018.

I. Uçkay, L. Tovmirzaeva, J. Garbino, P. Rohner, P. Tahintzi et al., Short parenteral antibiotic treatment for adult septic arthritis after successful drainage, Int J Infect Dis, vol.17, issue.3, pp.199-205, 2013.

F. Valour, A. Bouaziz, J. Karsenty, F. Ader, S. Lustig et al., Determinants of methicillin-susceptible Staphylococcus aureus native bone and joint infection treatment failure: a retrospective cohort study, BMC Infect Dis, vol.14, p.443, 2014.

L. Bernard, A. Dinh, I. Ghout, D. Simo, V. Zeller et al., Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial, Lancet, vol.385, issue.9971, pp.875-82, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01115445

G. E. Thwaites, J. D. Edgeworth, E. Gkrania-klotsas, A. Kirby, R. Tilley et al., Clinical management of Staphylococcus aureus bacteraemia, Lancet Infect Dis, vol.11, pp.208-230, 2011.

P. G. Ambrose, S. M. Bhavnani, C. M. Rubino, A. Louie, T. Gumbo et al., Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it's not just for mice anymore, Clin Infect Dis, vol.44, issue.1, pp.79-86, 2007.

J. E. Bennett, R. Dolin, and M. J. Blaser, Penicillins and beta-lactam inhibitors, Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, vol.1, pp.309-322, 2009.

G. L. Drusano, Antimicrobial pharmacodynamics: critical interactions of 'bug and drug, Nat Rev Microbiol, vol.2, issue.4, pp.289-300, 2004.

R. O. Douglas, E. F. Berbari, A. R. Berendt, D. Lew, W. Zimmerli et al.,

, Diagnosis and management of prosthetic joint infection : clinical practice guidelines by the Infectious Diseases Society of America, Clin Infect Dis, vol.56, pp.1-25, 2013.

H. Autorité-de-santé, Prothèse de hanche ou de genou : diagnostic et prise en charge de l'infection dans le mois suivant l'implantation. Recommandation de bonne pratique, 2014.

A. C. Oliveira, P. C. Garcia, and L. S. Nogueira, Nursing workload and occurrence of adverse events in intensive care: a systematic review, Rev Esc Enferm USP, vol.50, issue.4, pp.683-694, 2016.

M. F. Waineo, T. C. Kuhn, and D. L. Brown, The pharmacokinetic/pharmacodynamic rationale for administering vancomycin via continuous infusion, J Clin Pharm Ther, vol.40, issue.3, pp.259-65, 2015.

J. Cousson, T. Floch, T. Guillard, V. Vernet, P. Raclot et al., Lung concentrations of ceftazidime administered by continuous versus intermittent infusion in patients with ventilator-associated pneumonia, Antimicrob Agents Chemother, vol.59, issue.4, pp.1905-1914, 2015.

J. A. Roberts, M. H. Abdul-aziz, J. S. Davis, J. M. Dulhunty, M. O. Cotta et al., Continuous versus Intermittent ?-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials, Am J Respir Crit Care Med, vol.194, issue.6, pp.681-91, 2016.

M. C. Verdier, O. Tribut, P. Tattevin, C. Michelet, and D. Bentué-ferrer, Assessment of interindividual variability of plasma concentrations after administrazion of high doses of intravenous amoxicillin or cloxacillin in critically ill patients, J Chemother, vol.23, issue.5, pp.277-81, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00875258

D. W. Hughes, C. R. Frei, P. R. Maxwell, K. Green, J. E. Patterson et al., Continuous versus intermittent infusion of oxacillin for treatment of infective endocarditis caused by methicillin-susceptible Staphylococcus aureus, Antimicrob Agents Chemother, vol.53, issue.5, pp.2014-2023, 2009.

, Assurance de la qualité des produits pharmaceutiques -Recueil de directives et autres documents, vol.1, 1998.

C. B. Landersdorfer, C. M. Kirkpatrick, M. Kinzig-schippers, J. B. Bulitta, U. Holzgrabe et al., Population pharmacokinetics at two dose levels and pharmacodynamic profiling of flucloxacillin, Antimicrob Agents Chemother, vol.51, issue.9, pp.3290-3297, 2007.

N. R. Florea, S. Kotapati, J. L. Kuti, E. C. Geissler, C. H. Nightingale et al., Cost analysis of continuous versus intermittent infusion of piperacillin-tazobactam: a timemotion study, Am J Health Syst Pharm, vol.60, issue.22, pp.2321-2328, 2003.

S. Kotapati, J. L. Kuti, E. C. Geissler, C. H. Nightingale, and D. P. Nicolau, The clinical and economic benefits of asministering piperacillin-tazobactam by continuous infusion, Intensive and Critical Care Nursing, vol.21, pp.87-93, 2005.

J. G. Hobbs, M. K. Ryan, B. Ritchie, J. K. Sluggett, A. J. Sluggett et al., Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study, BMJ Open, vol.7, issue.7, p.16763, 2017.

C. B. Landersdorfer, J. B. Bulitta, M. Kinzig, U. Holzgrabe, and F. Sörgel, Penetration of antibacterials into bone: pharmacokinetic, pharmacodynamic and bioanalytical considerations, Clin Pharmacokinet, vol.48, issue.2, pp.89-124, 2009.

A. Ferrero, M. M. Vree, T. B. Baars, A. M. Slooff, and T. J. , Plasma and bone concentrations of cefuroxime and flucloxacillin. Oral versus parenteral administration in 20 arthroplasties, Acta Orthop Scand, vol.64, issue.5, pp.525-534, 1993.

J. Sirot, R. Lopitaux, C. Dumont, J. J. Delisle, S. Rampon et al., Penetration of cloxacillin into human bone tissue after oral administration, Patho Biol, vol.30, issue.6, pp.332-337, 1982.

S. E. Walker, A. Dufour, and J. Iazzetta, Concentration and solution dependent stability of cloxacilllin intravenous solutions, The Canadian Journal of Hospital Pharmacy, vol.51, issue.1, pp.13-19, 1998.

W. A. Craig, Pharmacokinetic/pharmacodynamics parameters : rationale for antibacterial dosing of mice and men, Clin Infect Dis, vol.26, issue.1, pp.1-10, 1998.

S. M. Bhavnani, J. A. Passarell, J. S. Loutit, S. B. Porter, and P. G. Ambrose, Pharmacokineticpharmacodynamic relationships describing the efficacy of oritavancin in patients with Staphylococcus aureus bacteremia, Antimicrob Agents Chemother, vol.50, pp.994-1000, 2006.

P. M. Roger, E. Cua, J. Courjon, L. Landraud, M. Carles et al., The impact of bacteremia on the outcome of bone infections, Med Mal Infect, vol.44, issue.8, pp.380-386, 2014.

L. Alou, L. Aguilar, D. Sevillano, M. J. Giménez, O. Echeverría et al., Is there a pharmacodynamic need for the use of continuous versus intermittent infusion with ceftazidime against P. aeruginosa ? An in vitro pharmacodynamics model, J Antimicrob Chemother, vol.55, issue.2, pp.209-222, 2005.

J. W. Mouton, D. Hollander, and J. G. , Killing of Pseudomonas aeruginosa during continuous and intermittent infusion of ceftazidime in an in vitro pharmacokinetic model

, Antimicrob Agents Chemother, vol.38, issue.5, pp.931-937, 1994.

J. A. Roberts, S. K. Paul, M. Akova, M. Bassetti, J. J. De-waele et al., DALI: defining antibiotic levels in intensive care unit patients: are current ?-lactam antibiotic doses sufficient for critically ill patients, Clin Infectious Disease, vol.58, issue.8, pp.1072-83, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01954093

S. Imani, H. Buscher, D. Marriott, S. Gentili, and I. Sandaradura, Too much of a good thing : a retrospective study of ?-lactam concentration-toxicity relationships, J Antimicrob Chemother, vol.72, issue.10, pp.2891-2897, 2017.

M. Neuville, N. El-helali, E. Magalhaes, A. Radjou, R. Smonig et al., Systematic overdosing of oxa-and cloxacillin in severe infections treated in ICU: risk factors and side effects, Ann Intensive Care, vol.7, p.34, 2017.

T. Nguyen and . Luitré, Letter to : pharmaciens hospitaliers, 2016.

M. Mignot, Located at : 26, quai Charles Pasqua -CS 90067, vol.1, 2017.

G. Spilf, Propositions d'alternative à l'oxacilline ou la cloxacilline par voie IV chez l'adulte et l'enfant en contexte de rupture de stock, 2016.

F. A. Manian, S. Aradhyula, S. Greisnauer, D. Senkel, J. Setzer et al., Is it Clostridium difficile infection or something else ? A case-control study of 352 hospitalized patients with new-onset diarrhea, South Med J, vol.100, pp.782-788, 2007.

C. D. Salgado, P. D. Mauldin, P. J. Fogle, and J. A. Bosso, Analysis of an outbreak of Clostridium difficile infection controlled with enhanced infection control measures, Am J Infect Control, vol.37, pp.458-64, 2009.

, ABSTRACT Introduction: The time-dependant antibiotic cloxacillin is the gold standard treatment for the early phase of methicillin-susceptible Staphylococcus aureus bone and joint infections (BJI)

, Continuous infusion of some ?-lactams is associated with pharmacokinetic/pharmacodynamic parameters improvement and more data are required to allow the extended use of cloxacilline through continuous infusion. We aimed to compare continuous and intermittent infusion of cloxacillin using in vivo

, Methods: We conducted a prospective open-label trial to compare plasma concentrations of cloxacillin in each patient with either two 12-hour perfusions of 75 mg/kg per day (continuous period) or with four one-hour perfusions of 37,5 mg/kg daily

, Pharmacologic assays were performed at H1, H2, H3, H4 and H6 during intermittent period and at H1, H6 and H11 during continuous period. Free drug concentration was considered for the analysis. We also assessed the patient's comfort and the nurses' preference for each period

, Among seven patients with all data available, 70% f T>MIC was achieved for 100% during continuous period and 86% during intermittent period (p>0,999). 100% f T>MIC was achieved for 100% during continuous period and 29% during intermittent period (p=0,021), p.20

, Conclusion: Continuous infusion provides higher plasmatic cloxacillin levels without specific side-effects. These results could allow its use in home-based care. Key words : Bone and joint infections ; methicillin-susceptible Staphylococcus aureus

, Continuous infusion