Leder K, Turnidge J D, Korman T M, Grayson M L
Infectious Disease and Clinical Epidemiology Department, Monash Medical Centre, Clayton, VIC, Australia.
J Antimicrob Chemother. 1999 Jan;43(1):113-8. doi: 10.1093/jac/43.1.113.
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.
由于β-内酰胺类药物对诸如甲氧西林敏感金黄色葡萄球菌（MSSA）等病原体的疗效与血清药物浓度超过病原体最低抑菌浓度（MIC）的时间相关，因此通过持续输注给予抗葡萄球菌β-内酰胺类药物可能比间歇给药提供更合适的给药方式。为了评估持续输注疗法的临床疗效，我们回顾了20例经证实患有严重MSSA败血症的连续患者（3例患有心内膜炎，10例患有骨髓炎，1例患有心内膜炎加骨髓炎，6例患有深部脓肿）接受持续输注氟氯西林（8 - 12克/天）治疗的结果。最初接受常规间歇剂量氟氯西林治疗的患者改为持续输注氟氯西林（平均持续时间29天；范围4 - 60天）以完成其治疗疗程。在大多数情况下，这是在家中进行的。持续输注12克/天氟氯西林期间血清氟氯西林浓度为11.5->40毫克/升（10例患者），持续输注8克/天氟氯西林期间血清氟氯西林浓度为8->40毫克/升（5例患者），这些浓度远高于氟氯西林对MSSA的预期MIC。大多数患者对持续输注氟氯西林耐受性良好，在长期随访（平均67周；范围4 - 152周）中，完成持续输注氟氯西林疗程的17例患者中有14例（82%）在临床和微生物学上被判定治愈。这些初步数据表明，在最初的间歇剂量氟氯西林治疗后，持续输注氟氯西林是严重MSSA败血症的有效治疗选择，并且在考虑对这些感染进行家庭肠外治疗时，是糖肽类药物可行且可能更优的替代方案。需要进一步研究以确定持续输注氟氯西林是否能完全替代此类感染的间歇剂量疗法。
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