The prescribing practices of echinocandins in adult patients in a private hospital

Abstract

Background: Antifungal stewardship, an entity that has been largely deserted, needs to be included in the initiative to fight antimicrobial resistance. Fundamentals that need to be addressed are such as the appropriate use and dose of antifungal agents, simple indicators to the most relevant risk factors associated with these infections and the effective and appropriate timing of the antifungal agent administration, as well as to monitor the appropriate use of these agents. For the last decade conventional amphotericin B and azole antifungals has been the mainstay of antifungal therapy in the South African setting. However, high frequency of infusion-related toxicity and nephrotoxicity associated with amphotericin B and the occurrence of fluconazole-resistant strains of the C. glabrata species (spp.) urged a search for alternatives. Alarmingly, resistance to amphotericin B (the antifungal with the broadest spectrum of activity) has been reported in all Candida spp., whilst resistance to the azole group of antifungals, such as fluconazole, has been reported to be as high as 50% in Candida spp., warranting antifungal stewardship implementation. Fortunately, echinocandins, a newer generation antifungal class has broad spectrum activity against a variety of Candida spp. and is indicated for the treatment of invasive candidiasis Objective: The purpose of this study was to review the available literature regarding the appropriate prescribing of echinocandins and to compare the literature to the prescribing patterns of echinocandins in a private hospital in South Africa (SA). Method: A retrospective quantitative research design was applied to collect data from patient files using a pre-developed data collection form. The inclusion criteria was adult patients (>18 years) who were on echinocandin treatment from 1 January 2015 — 1 January 2016. Patients were excluded if antifungal therapy formed part of their chronic medication, pregnant patients and patients who received more than one intravenous echinocandin. The data collection was conducted from 1 August 2016 — 31 October 2016. The data collection tool was used to collect the data and required the following information: demographic information, including age (inclusion criteria states only patients >18 years), and ward admitted in hospital (to comply with inclusion and exclusion criteria); the IV echinocandin that the patient was started with; Loading dose (LD); prescribed daily dose (PDD); start date and end date of echinocandin treatment; de-escalation of therapy; if yes, active ingredient of oral agent; presence of blood cultures; result of blood cultures; cost of antifungal treatment (i.e. the total amount that the hospital pharmacy charged the patient for the medication alone); and cost of blood tests and blood cultures performed. Results: One hundred and forty six patients complied with the study criteria after a random selection. Among them 102 (69.863%) received caspofungin and 99 (97.058%) also received the correct LD while 3 (2.941%) did not receive a LD. 44 (20.127%) patients received anidulafungin, only 30 (68.18%) received the correct LD and 14 (31.819%) did not receive a LD. For the maintenance dose of caspofungin 98 (98.078%) patients received 50mg intravenous daily (IV) and 4 (3.922%) patients received 70mg IV per day. For anidulafungin 1 (2.273%) patient received 400mg IV per day, 23 (52.273%) patients received 200mg IV per day, 19 (43.182%) patients received 100mg IV per day and 1 (2.273%) patient received only 50mg IV per day. To determine whether there is an association between de-escalation of therapy and the presence of blood cultures the p-value (0.83) is bigger than 0.05, indicating that there were no association between the two variables. Cramér"s V (0.018) is less than 0.5 indicating a small effect with no practical significance, meaning that there is no association between de-escalation of treatment and the availability of blood cultures. The p-value of 0.888 is greater than the p-value of significance (0.05) meaning that there are no statistical significant difference between the average duration of treatment between patients with blood cultures and patients without blood cultures. Cohen"s d value = 0.031 indicating that there is a small effect with no practical significance, which indicates that the duration of echinocandin therapy is not dependant on the presence of a positive blood culture. The average cost between patients with positive blood cultures those patients without blood cultures do not differ statistically significantly from one another. Cohen"s d value is less than 0.8 indicating that there is a small effect with no practical significance. The p-value (0.801), is greater than the significant level of p = 0.05 (5%), indicating that the presence of blood cultures do not differ statistically significantly from one another. Conclusions and recommendations: The researcher has attempted to investigate and compare the prescribing patterns of echinocandins in a private hospital. After studying the literature it was observed that the prescribing doctors at this study setting are mostly compliant to the available guidelines regarding the appropriate use of echinocandins. In SA the cost of blood cultures are being weighed up against the cost of treatment and it is within this aspect that the doctors might feel that this requirement of the guidelines is not reachable. It is debatable if the literature is very practical in an environment where cost plays such a big role. It is recommended that future research projects on this topic should include clinical data such as removal of catheters or indwelling devices as this aspect plays a big role in the duration of therapy and the source of the infection. A cost campaign regarding blood cultures versus treatment should be introduced to doctors and laboratories. More research is needed to establish if there is an effect such as a shorter duration of stay when blood cultures are performed more often.