Ellis Michael, Frampton Chris, Joseph Jose, Alizadeh Hussain, Kristensen Jorgen, Hauggaard Anders, Shammas Fuad
Pulmonary and Critical Care Division, UCSF Fresno School of Medicine, 445 S Cedar Ave., Fresno, CA 93702, USA.
J Med Microbiol. 2006 Oct;55(Pt 10):1357-1365. doi: 10.1099/jmm.0.46452-0.
In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2-45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients.
在临床非试验环境中,对73例血液系统恶性肿瘤患者的发热性中性粒细胞减少或侵袭性真菌感染,比较了卡泊芬净与两性霉素B脂质体的疗效和安全性。卡泊芬净的药物毒性发作次数少于两性霉素B脂质体(58.3%对83.7%,P=0.02)。用卡泊芬净或两性霉素B脂质体治疗的发热性中性粒细胞减少发作的良好反应率分别为37.5%和53.8%,相似,但在未接受抗真菌预防的这些患者中,卡泊芬净导致的突破性真菌感染比两性霉素B脂质体更多(33.3%对0%,P<0.05)。与两性霉素B脂质体治疗的4例中的3例相比,4例念珠菌血症或肝脾念珠菌病发作中无一例对卡泊芬净有反应。与两性霉素B脂质体治疗相比,卡泊芬净治疗的死亡率显著更高(6/24对2/49,P=0.01),主要是由于真菌感染过多(P=0.04)。在多因素逻辑回归模型中考虑脓毒症严重程度、长期中性粒细胞减少和抗真菌治疗时长时,卡泊芬净治疗是死亡率的显著独立预测因素[比值比=7.6(95%置信区间1.2 - 45.5)]。在临床实践中,有迹象表明卡泊芬净在预防发热性中性粒细胞减少患者的突破性侵袭性真菌感染或预防真菌相关死亡方面可能不如两性霉素B脂质体有效。由于这项观察性研究存在潜在偏倚,这些初步发现应谨慎解读,并通过更大规模的患者队列进行阐明。