Department of Infectious Diseases, Austin and Repatriation Medical Centre, Studley Road, Heidelberg, Victoria 3084, Australia
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Abstract |
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Introduction |
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To assess the clinical efficacy, safety and feasibility of continuous infusion therapy, we reviewed the outcomes for a larger group of patients with cellulitis or serious MSSA infections who were treated with continuous infusion flucloxacillin at home after a period of intermittent flucloxacillin in hospital.
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Patients and methods |
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Patients with suspected, but unproven MSSA infection were excluded. Serious MSSA infection was defined as bacteraemia, deep tissue or prosthetic device infection, with isolation of MSSA from a sterile site. The end points for serious MSSA infections were cure, or for patients with prosthetic joint infection, adequate suppression of the infection. The end point for cellulitis patients was resolution of rash. Patients with bacteraemia, endocarditis and deep abscesses were considered cured if they had no clinical or microbiological evidence of relapse 6 weeks after the completion of antibiotic therapy. For patients with osteomyelitis, septic arthritis, or prosthetic joint or graft infection a minimum follow-up period of 3 months after the completion of antibiotic therapy was required. Patients with prosthetic joint infection were continued on long-term oral antibiotics if the prosthesis was not removed. Adequate suppression of infection in these patients was defined as no clinical or laboratory evidence of active infection 3 months after stopping iv therapy.
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Results |
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Twenty-four of 26 (92%) patients had resolution of cellulitis at the end of antibiotic therapy. One patient had persisting leg erythema and another with diabetes and leg ulcers failed to respond to flucloxacillin alone. Both patients were treated after 1997 when the infusion method had changed. In the serious MSSA infection group follow-up was available for a median of 20 weeks (mean 30.4 weeks, range 2111 weeks), and was incomplete in four cases. Three patients died from a serious pre-existing illness and one patient travelled overseas. None had evidence of relapsed MSSA infection at the time of last review. Twenty-seven of 28 (96%) patients who completed therapy and follow-up were cured, or had adequate suppression of prosthetic joint infection. One patient had a second episode of MSSA bacteraemia 5 weeks after completing therapy. The second episode was Hickman catheter related. This patient was also treated after 1997.
Four patients complained of nausea and two developed mild, transient neutropenia while receiving flucloxacillin 8 g/day. One patient developed Hickman-related Gram-negative bacteraemia after completing flucloxacillin therapy. Blockage of the PICC line occurred in three patients.
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Discussion |
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In this study, continuous infusion flucloxacillin was safe, convenient and effective for the home-based treatment of serious MSSA infections and cellulitis in patients who were clinically stable. The two failures in the cellulitis group were explained by reasons other than mode of administration. A diabetic patient who had cellulitis associated with chronic leg ulcers probably had polymicrobial infection. A second patient had persistent leg erythema that did not require further treatment, indicating that infection had been cured. A number of patients in the cellulitis group received a relatively long course of iv treatment. This may reflect the tendency for more severe cases to be referred for continued iv treatment at home. The one treatment failure in the serious MSSA infection group most likely suffered a new infection. None of the patients with incomplete follow-up had evidence of infection at the time of last review. The potential treatment failures were not related to the use of the 24 h infusions before the end of 1997.
The optimal dosing of flucloxacillin by continuous infusion is currently unknown. In all patients where serum flucloxacillin concentrations were measured, levels appeared adequate. Patients receiving flucloxacillin 8 g/day had levels many times above the MIC for MSSA, which is 0.5 mg/L.9 The serum concentration of 12.4 mg/L in the patient receiving flucloxacillin 4 g/day was also well above the expected MIC for S. aureus and Streptococcus pyogenes.9 These concentrations can be considered quite high, and support the possibility that lower total daily doses can be used during continuous infusion therapy. Although the free serum concentration of flucloxacillin was not measured directly, assuming a normal level of protein binding in this patient group (94%),9 the patients receiving continuous infusion flucloxacillin 8 g/day would have had a mean serum free flucloxacillin concentration of 3.0 mg/L (range 2.03.8), still well above the expected MIC for MSSA.
This study has a number of limitations. It is not comparative, and the in-patient and oral antibiotic therapy confuses the results. The high success rates with continuous infusion therapy make it unlikely that comparative studies with intermittent dosing or alternative agents will show better outcomes. Benefits are likely to lie with patient convenience, and less quantifiable benefits such as the reduced selective pressure for antimicrobial resistance with the use of narrow-spectrum agents. Flucloxacillin concentrations were measured in a small number of patients, but were consistently high. The period of follow-up for patients with prosthetic joint infection and osteomyelitis was relatively short as late relapses can occur; however, continuous infusion therapy did achieve adequate control of these infections.
Further studies are warranted to address the optimal dosing and duration of continuous infusion flucloxacillin, and the role of continuous infusion flucloxacillin in the initial acute management of serious MSSA infections in particular.
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Acknowledgments |
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Notes |
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Present address. Victorian Infectious Disease Service, Royal Melbourne Hospital, Grattan Street, Carlton, Victoria 3053, Australia
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References |
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Received 8 January 2001; returned 7 March 2001; revised 17 April 2001; accepted 21 May 2001