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Ambisome¨) Vs EV0949 Retrospective audit comparing the clinical efficacy and safety of liposomal amphotericin B (AmBisome®) vs. caspofungin vs. micafungin for treatment Hani Habayeb Antimicrobial & Critical Care Pharmacist Guildford Road, Chertsey, Surrey, KT16 0PZ United Kingdom of Candidaemia and Invasive Fungal Disease (IFD) Tel: 01932872000 H. Habayeb, C. Grundy, M. Barker, A. Al-Dujaili [email protected] ABSTRACT INTRODUCTION RESULTS DISCUSSION OBJECTIVES: Several studies have noted Echinocandins (micafungin and caspofungin) and During the study period 126 patients were reviewed and 94 included. 28 patients had candidaemia and 66 had IFD. Only 2 patients developed nephrotoxicity in the There was no statistically significant difference between the groups in clinical that candidaemia and invasive fungal disease AmBisome® have broad-spectrum activity against AmBisome® group (1 with candidaemia, 1 with IFD) compared to none in the echinocandin groups, which was not statistically significant. efficacy. However; 8 cases of hepatotoxicity were observed in the micafungin (IFD) are associated with high mortality, longer Candida species. Following an update of our group 8/29 (28%) compared to 1 in the caspofungin group 1/30 (3%) and none hospital stay and higher costs. We aimed to guidelines in August 2012, we aimed to compare In patients developing candidaemia and receiving caspofungin, 4 patients grew C. glabrata and 4 patients grew C. albicans and 1 patient grew C.tropicalis + C.albicans. in the AmBisome group. This was statistically significant in favour of caspofungin compare the efficacy and safety of micafungin the efficacy and safety of micafungin vs. and AmBisome®. Only 2 patients developed nephrotoxicity in the AmBisome® In the micafungin group, 4 patients grew C. albicans, 2 grew C. glabrata, 1 grew C. glabrata + C. albicans , 1 grew C. glabrata + C. tropicalis and 1 grew C. dubliniensis. versus caspofungin vs. AmBisome® for caspofungin vs. AmBisome® for treatment of group (1 with candidaemia, 1 with IFD) while none in echinocandins groups treatment of confirmed candidaemia or confirmed Candidaemia or clinically diagnosed IFD. In the AmBisome® group; 3 patients grew C. albicans, 3 grew C. glabrata, 1 grew C. Krusei, 1 grew C.tropicalis, 1 grew C.albicans + C.glabrata and 1 grew C. dubliniensis + which was Not statistically significant. clinically diagnosed IFD. We usually use fluconazole as first line for empirical C.albicans. For each group, clinical outcome, mean duration of treatment, adverse events, average cost of treatment per patient, average Candida score, and development Most of our candidas grown in blood cultures were non-albicans species 18/33 METHODS: Data from patients with and confirmed Candida albicans, liposomal of acute respiratory distress syndrome (ARDS) can be seen in the table below. isolates (55% ). C.glabrata was the most common isolate in the non-albicans candidaemia or clinically diagnosed IFD amphotericin or Voriconazole for invasive group 12/18 (67%) which suggests that we should not use fluconazole (Persistent mycological positive cultures + Aspergillosis and an Echinocandin or liposomal amphotericin for empirical or confirmed Candida empirically for treatment of candidaemia in our centre. compatible clinical signs) and treated with Candidaemia IFD micafungin or caspofungin or AmBisome® for non-albicans. In the IFD groups there were more isolates of C.albicans (56%) compared to 3 days between January 2008 and June ≥ We also aimed to evaluate the hepatotoxicity and Micafungin Caspofungin AmBisome® P Micafungin Caspofungin AmBisome® P C.non-albicans (46%) which suggest that we may still use fluconazole as first line 2014 , were reviewed retrospectively. Only nephrotoxicity of all 3 agents. Hepatotoxicity was (n=9) (n=9) (n=10) value (n=20) (n=21) (n=25) value although its best to take into consideration previous azole exposure and severity patients having temperature 38°C or 36°C ≥ ≤ assessed based on the Child-Pugh score and of illness. MIC sensitivities present a challenge as only 6/9(67%) of patients and no previous exposure to an echinocandin Increase in Liver function tests (specifically Age (years) 71.7 74.4 69.7 NS 68.5 67.7 64.16 NS recovered when candida isolates were MIC sensitive. or AmBisome® were included. Patients who transaminases). received another systemic antifungal agent Average Candida score 4.2 4.6 4.4 NS 3.4 3.1 3.36 NS (except fluconazole) were excluded. CONCLUSION RESULTS: 126 patients were reviewed and 94 Clinical outcome (%) included. 28 patients had candidaemia and 66 Our audit confirms the high mortality rate in patients with candidaemia. No had IFD. Only 2 patients developed Success 55.6 66.7 60.0 NS 70.0 81.0 76.0 NS statistically significant difference in efficacy was observed between the three nephrotoxicity in the AmBisome® group (1 METHODS Failure 22.2 22.2 20.0 NS 15.0 0 12.0 NS groups however Micafungin was significantly more hepatotoxic compared to with candidaemia, 1 with IFD) compared to caspofungin or AmBisome®. none in the echinocandin groups, which was We reviewed retrospectively records of patients Relapse 0 0 10.0 NS 0 0 4.0 NS not statistically significant. who had caspofungin or micafungin or AmBisome® The trend for lower treatment cost in favour of AmBisome® (1mg/kg OD) in IFD Clinical outcome: No statistically significant 1mg/kg IV OD between January 2008 and June Indeterminate 22.2 11.1 10.0 NS 15.0 19.0 8.0 NS was statistically significant compared to caspofungin and micafungin. difference between the 3 groups. 2014. We included patients who had Candidaemia We should not use fluconazole empirically for treatment of candidaemia in our (confirmed presence of Candida species in the Duration of treatment (days) 13.6 12.7 13.9 NS 13.9 13.4 13.48 NS Hepatotoxicity: Post hoc analysis showed a centre as we had higher percentage of C.non-albican isolates so an blood) or Invasive fungal disease (defined as statistical difference between micafungin and Adverse events (%) echinocandin or AmBisome® should be considered first. caspofungin groups (P=0.0448) and between persistent mycological positive cultures or multifocal micafungin and AmBisome® groups candida colonization + compatible clinical signs) Worsening in liver functiona 22.2 0 0 NS 30.0b 4.8 0 <0.05 . (P=0.0048). and treated with micafungin or caspofungin or Cost per patient: Post hoc analysis showed a AmBisome® for ≥ 3 days. Systemic reactions 0 0 0 NS 0 0 0 NS REFERENCES statistical difference between AmBisome® and Only adult patients > 18 years old with temperature Average cost per patients (£) 3917.6 4438.8 3149.0 NS 4017.1 4692.0 2634.9c <.0001 caspofungin groups (P<0.0001) and between 1.O.A Comley et al. ESCMID guideline for the diagnosis and management of Candida disease 2012: non- ≥ 38°C or ≤ 36°C and no previous exposure to an neutropenic adult patients. Clin Microbial Infect 2012; 18(7):19-37 AmBisome® and micafungin groups echinocandin or AmBisome® were included. Development of ARDS (%) 33.3 44.4 30.0 NS 15.0 14.3 12.0 NS (P=0.0006). Hematology and invasive Aspergillosis patients 2. León C, Ruiz-Santana S, Saavedra P, et al. A bedside scoring system ("Candida score") for early CONCLUSIONS: No statistically significant Prior use of broad spectrum antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med. Mar were excluded as well as patients who received 100.0 100.0 100.0 NS 85.0 90.5 88.0 NS 2006;34(3):730-737 difference in efficacy was observed between another systemic antifungal agent (except antibiotic(s) (%) the three groups. Micafungin was more 3. Pappas PG et al. Micafungin versus caspofungin for treatment of candidaemia and other forms of invasive fluconazole) . candidiasis. CLIN Infect Dis: Oct 2007; 45(6): 1735-1745. hepatotoxic compared to caspofungin or Prior exposure to fluconazole (%) 11.1 22.2 20.0 NS 15.0 14.0 20.0 NS AmBisome®. The trend for lower treatment Candida scoring system was carried out based on: a Determined by changes in Child-Pugh Score from day 0, up to day 7 after treatment, if applicable 4. Alexander BD et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis, 2013,56(12): multifocal candida colonization (1 point ), surgery b Post hoc analysis showed a statistically significant difference between micafungin and caspofungin groups (P=0.0448) and between micafungin and AmBisome® groups (P=0.0048). cost in favour of AmBisome® in IFD was 1724-1732. statistically significant. (1), Receipt of Total Parenteral nutrition (1) and C Post hoc analysis showed a statistically significant difference between AmBisome® and caspofungin groups (P<0.0001) and between AmBisome® and micafungin groups (P=0.0006). clinical signs of severe sepsis (2). NS: Not statistically significant ; ARDS: Acute Respiratory Distress Syndrome I acknowledge and thank the contribution of Dr Sebastien Van de Velde for his help and support in doing the statistical analysis .
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