Antifungal StewardshipPrescribing Patterns of Echinocandins in Adult Patients in a Private Hospital in Gauteng, South Africa

Worldwide, the Candida species (spp.) group is the leading cause of invasive candidiasis and the fourth leading cause of hospital-acquired infection. While Candida albicans accounts for the majority of these infections, the number of patients infected with non-albicans Candida — Candida glabrata, Candida parapsilosis, Candida krusei and Candida tropicalis — is steadily growing.¹

Each Candida has its own distribution and treatment challenges. The problem is further exacerbated as these organisms are often found in deep-seated organs and can form biofilms, particularly on indwelling devices and catheters, making infection difficult to detect early and contributing to the higher mortality and morbidity associated with these infections.¹

Inappropriate use of antifungals — sub-therapeutic dosing, and inappropriate or ineffective treatment periods — together with the changing pattern of Candida epidemiology, has significantly increased drug resistance to the more commonly prescribed antifungals such as fluconazole. This has in turn led to increased use of echinocandins for these infections.¹

Beyond their effectiveness against the Candida group, echinocandins carry an attractive safety profile, with minimal drug interactions and few adverse effects at therapeutic doses compared with other antifungal classes. That said, the authors note that a study conducted in the Eastern Cape points to an increase in multidrug resistance, particularly for C. albicans, C. glabrata and C. tropicalis — a consequence of inappropriate antifungal prescription patterns.^1,2

Several guidelines address the administration of antifungals in Candida infection, all aimed at minimising treatment duration and reducing hospital stay. The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) recommends that a patient be moved to oral therapy once the ten-day intravenous protocol is completed.³ The Infectious Diseases Society of America (IDSA) recommended in its 2016 guideline that clinically stable patients be changed from an intravenous form to an oral agent, such as fluconazole, within five to seven days of commencing treatment.⁴

Many guidelines also recommend removing all indwelling catheters and intravenous lines once Candida has been diagnosed. While treatment-related challenges have made consensus on length of therapy difficult to reach, research has established that a 14-day intravenous course should follow the first negative blood culture. With the rise in multidrug resistance among Candida spp., conforming to these guidelines has become more important still.¹

The researchers opted for a quantitative research design, using observational and descriptive metrics. The target population comprised all adult patients over 18 years of age, admitted to a private hospital in Gauteng, who received antifungal treatment between 1 January and 31 December 2015.¹

Patients were excluded if they were pregnant, were on any acute or chronic antifungals, or had their treatment changed from an echinocandin to another antifungal during their hospital stay. A total of 146 patients met the criteria.¹

The variables reviewed were the type of antifungal, the dosage of antifungal treatment, the duration of treatment, de-escalation of therapy, blood results and cultures, and the average cost of antifungal treatment.¹

Of the 146 patients included, 102 (69.9%) received caspofungin and 44 (30.1%) were treated with anidulafungin. The mean duration of therapy was 9.7 days, regardless of whether blood cultures were performed.¹

Loading doses

Of the 102 patients receiving caspofungin, 99 (97.1%) received a loading dose of 70 mg, and 3 (2.9%) received no loading dose at all. Of the 44 patients receiving anidulafungin, 30 (68.2%) received a loading dose of 200 mg, while 14 (31.8%) received either an inappropriate loading dose or none.¹

Per-day dosage

Among the caspofungin patients, 98 (98.1%) received the correct daily dose of 50 mg, and 4 (3.9%) received 70 mg per day. Among those who received anidulafungin, where the correct dose is 100 mg intravenously per day, only 19 (43.2%) received that dose. Twenty-three patients (52.3%) received 200 mg, one (2.3%) received 400 mg, and one (2.3%) received 50 mg daily.¹

Blood cultures and duration of therapy

Of the 146 patients, 129 had blood cultures taken and 17 did not. Mean treatment duration was 9.7 days in the group with cultures and 10.0 days in the group without — a difference of 0.3 days that was not statistically significant (p = 0.888).¹

The findings were compared with the international guidelines and with a local Quality Alert issued by the private hospital group under review: the IDSA and ESCMID guidelines, the Italian consensus for invasive candidiasis management, and the Australian consensus guidelines for yeast management.^1,3,4,5,6

Loading doses and daily dosage

• Overall, the antifungals were correctly prescribed in terms of the loading dose and per-day dose set out in those guidelines.
• While patients received the correct daily dose of caspofungin, the daily dose of anidulafungin was not adhered to.

Duration of treatment

• The consensus in the literature is that therapy should cease after 14 days of intravenous treatment, counted from the patient's first negative blood culture.
• In this cohort, 129 patients had blood cultures taken, while 17 patients had no blood culture taken.
• Mean duration of echinocandin therapy was 0.3 days shorter in the 129 patients with cultures than in the 17 without.
• Grey and colleagues therefore concluded that there was no statistically significant difference between the average duration of treatment in patients with blood cultures and those without.

The researchers conclude that the prescribing doctors in this study, by and large, complied with international dosage guidelines for echinocandins. The one exception was the recommendation that duration of treatment be based on blood culture: here the authors found that duration did not appear to be significantly influenced by the absence of cultures.¹

Certain limitations should be considered when interpreting the results. These include potential inaccuracies in patients' prescription charts, a lack of clinical data regarding catheter changes, and the use of a sample drawn on specific inclusion and exclusion criteria.¹

1. Grey, A., Joubert, R., Steyn, S., & Julyan, M. (2023). Prescribing patterns of echinocandins in adult patients in a private hospital in Gauteng, South Africa. Southern African Journal of Infectious Diseases, 38(1), a470. https://doi.org/10.4102/sajid.v38i1.470
2. Mnge, P., Okeleye, B. I., Vasaikar, S. D., & Apalata, T. (2017). Species distribution and antifungal susceptibility patterns of Candida isolates from a public tertiary teaching hospital in the Eastern Cape Province, South Africa. Brazilian Journal of Medical and Biological Research, 50(6), 5797–5804. https://doi.org/10.1590/1414-431x20175797
3. Cornely, O. A., Bassetti, M., Calandra, T., et al. (2012). ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clinical Microbiology and Infection, 18(Suppl. 7), 19–37. https://doi.org/10.1111/1469-0691.12039
4. Pappas, P. G., Kauffman, C. A., Andes, D. R., et al. (2016). Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 62(4), 1–50. https://doi.org/10.1093/cid/civ933
5. Scudeller, L., Viscoli, C., Menichetti, F., et al. (2013). An Italian consensus for invasive candidiasis management (ITALIC). Infection, 42(2), 263–279. https://doi.org/10.1007/s15010-013-0558-0
6. Bryant, P. A., Chang, C. C., Chen, S. C., Paige, E. K., Slavin, M. A., & Sorrell, T. C. (2014). Consensus guideline for the treatment of yeast infections in the haematology, oncology and intensive care setting. Internal Medicine Journal, 44(12b), 1315–1332. https://doi.org/10.1111/imj.12597
7. Szymanski, M., Chmielewska, S., Czyzewska, U., Malinowska, M., & Tylicki, A. (2022). Echinocandins — structure, mechanism of action and use in antifungal therapy. Journal of Enzyme Inhibition and Medicinal Chemistry, 37(1), 876–894. https://doi.org/10.1080/14756366.2022.2050224