Since the efficacy of
beta-lactams against pathogens such as
methicillin-susceptible Staphylococcus aureus (MSSA) is related to the time for which serum
drug concentrations exceed the MIC for the pathogen, administration of anti-staphylococcal
beta-lactams by continuous infusion may provide a more suitable means of
drug delivery than intermittent dosing. To assess the clinical efficacy of continuous-infusion
therapy, we reviewed the outcomes for 20 consecutive patients with proven serious MSSA
sepsis (three with
endocarditis, ten
osteomyelitis, one
endocarditis plus
osteomyelitis and six deep
abscess) treated with continuous-infusion
flucloxacillin (8-12 g/day). Patients initially receiving routine intermittent-dose
flucloxacillin therapy were changed to continuous-infusion
flucloxacillin (mean duration 29 days; range 4-60 days) for completion of their treatment course. In the majority of cases this was given at home. Serum
flucloxacillin concentrations during continuous-infusion
flucloxacillin 12 g/day were 11.5->40 mg/L (ten patients) and those during continuous-infusion
flucloxacillin 8 g/day were 8->40 mg/L (five patients), these concentrations being well above the expected MIC of
flucloxacillin for MSSA. Continuous-infusion
flucloxacillin was well tolerated by most patients, and 14/17 patients (82%) who completed their course of continuous-infusion
flucloxacillin were judged clinically and microbiologically cured at long-term follow-up (mean 67 weeks; range 4-152 weeks). These preliminary data suggest that, following initial intermittent-dose
flucloxacillin therapy, continuous-infusion
flucloxacillin is an effective treatment option for serious MSSA
sepsis, and forms a feasible and possibly preferable alternative to
glycopeptides when considering home-based parenteral
therapy for these
infections. Further studies are needed to identify whether continuous-infusion
flucloxacillin can entirely replace intermittent-dose
therapy for such
infections.