Prescribing patterns of echinocandins in adult patients in a private hospital in Gauteng, South Africa
Type of article: Clinical Research Summary
MedED Catalogue Reference: MPCS008
Category: Infectious Diseases | Antimicrobials
Category Tags: Infectious Diseases, echinocandins, candidemia; antifungals, antimicrobial resistance
Source: Southern African Journal of Infectious Diseases
Key Take Aways
1. Globally, the Candida species group (spp) is the fourth leading cause of hospital-acquired infections.
2. Candida albicans account for the majority of these infections. However, infection by the non-Candida organisms is on the rise.
4. There has been a significant increase in multi-drug resistance to traditional anti-fungal agents, such as fluconazole.
5. Echinocandins are an effective alternative to these drugs in instances where there is already drug resistance.
6. The researchers found that the majority of the prescribing doctors in their study correctly administered the loading dose and daily dosage in keeping with the international guidelines.
7. They found that blood culture results had no significant impact on the duration of treatment and the resulting outcome.
8. The appropriate administration of antifungals, including loading doses, per day dosage and the duration of treatment, are vital to stemming the tide of multi-drug resistance in these organisms.
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Overview | Objectives | Study Design,Method & Management | Findings | In Summary| Conclusion
This is a summary of an original research article, reproduced under Creative Commons Attribution-NonCommercial 4.0 International License. It in no way replaces the original work, which has been linked below.
Overview
The Candida species (ssp) group is responsible for a fourth of all hospital-acquired infections. While Candida albicans accounts for the majority of these infectious, the number of patients infected with non-albicans Candidas – such as Candida glabrata, Candida parapsilosis, Candida krusei and Candida tropicalis - is steadily growing.
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 in indwelling devices and catheters - making infection difficult to detect early, resulting in the higher mortality and morbidity rates associated with these infectious diseases.
Inappropriate use of antifungals, including sub-therapeutic dosing and inappropriate or ineffective treatment periods, and the changing pattern of Candida epidemiology have significantly increased drug resistance to the more commonly prescribed antifungals such as fluconazole. Consequently, this has led to increased use of echinocandins for these infections. In addition to their effectiveness against the Candida group, echinocandins have an attractive safety profile, minimal drug interactions and adverse effects at therapeutic doses compared to other antifungal drugs. That said, the researchers of this paper note that a recent study conducted in the Eastern Cape points to an increase in multi-drug resistance, particularly for C. albicans, C. glabrata and C. tropicalis, a consequence of inappropriate antifungal prescription patterns.
There are various guidelines regarding the administration of antifungals in cases of Candida infectious. These approaches are aimed at minimising the treatment duration and reducing hospitalisation stays. The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) recommends a patient be given oral antibiotics once the ten-day IV protocol is completed. The Infectious Diseases Society of America (IDSA) recommended in its 2016 guideline that clinically stable patients should be changed from an IV form to an oral agent (i.e. fluconazole) within 5–7 days of commencement of treatment.
Many guidelines also recommend removing all indwelling catheters and IVs once Candida has been diagnosed. While treatment-related challenges made it challenging to reach a consensus regarding the recommended length of treatment, research has established that a 14-day IV treatment should be implemented after the first negative blood culture. With the concerning rise in multi-drug resistance among the Candidas ssp, conforming to these guidelines has become even more important.
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Objectives
The researchers of this study, Grey et al., sought to determine whether South African doctors comply with the available guidelines.
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Study Design, Methods & Measurements
The researchers opted for a quantitative research design method, using observational and descriptive metrics.
The total sample group included all adult patients over 18 years of age, admitted to a private hospital in Gauteng, who received antifungal treatments from 01 January 2015 – 31 Dec 2015. Patients were excluded if they were pregnant, were on any acute or chronic antifungals, or had their treatment changed from echinocandin to another antifungal during their hospital stay.
A total of 146 patients were identified.
The variables reviewed in the study included: the type of antifungal, the dosage of antifungal treatment, the duration of treatment, the de-escalation of therapy, blood results and cultures and the average cost of antifungal treatment.
Related Content | Learn More
IDSA Guidelines:
Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 Update by the infectious diseases society of America. Clin Infect Dis. 2016;62(4):1–50. https://doi.org/10.1093/cid/civ933
ESCMID Guidelines
Cornely OA, Bassetti M, Calandra T, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: Non-neutropenic adult patients. Clin Microbial Infect. 2012;18(Suppl. 7):19–37. https://doi.org/10.1111/1469-0691.12039
Italian Guidelines
Italian Guidelines Scudeller L, Viscoli C, Merichetti F, et al. An Italian consensus for invasive candidiasis management (ITALIC). Infection. 2013;42(2):263–279.
https://doi.org/10.1007/s15010-013-0558-0 https://doi.org/10.1007/s15010-013-0558-0
Australian Guidelines for Yeast Management
Bryant PA, Chang CC, Chen SC, Paige EK, Slavin MA, Sorrel TC. Consensus guideline for the treatment of yeast infections in the haematology, oncology and intensive care setting. Intern Med J. 2014;44(12b):1315–1332. https://doi.org/10.1111/imj.12597
Findings
Of the 146 patients:
- 102 (69.86%) received caspofungin
- 22 (20.13%) received anidulafungin
The mean days of therapy were 9.7 days, regardless of whether blood cultures were performed.
1. Loading Doses (LD)
Of the 102 patients receiving caspofungin:
- 99 ( 97.05%) received a loading dose of 70mg
- 3 (2.90%) received no loading dose
Of the 44 patients receiving anidulafungin:
- 30% (68.18%) received a loading dose of 200 ml
- 14% (31.82%) received either an inappropriate LD or no LD at all
2. Per Day Dosage (PDD)
Of the 146 patients:
- 98 (98.1%) received the correct PDD
- 4 (3.92% received only 70 mg per day
Of the patients who received anidulafungin, where the correct dose is 100mg IV per day:
- Only 19 (43.2%) received the correct PDD dose of 100mg daily
- 1 (2.3%) patient received 400mg
- 23 (52.3%) received 200mg
- 1 (2.3%) received 50mg daily
In Summary
The findings of this study were compared to the International Guidelines and a local Quality Alert by the private hospital under review. The guidelines were as follows: IDSA, ESIMD Guidelines, Italian Consensus for invasive Candidas management, and the Australian Consensus Guidelines for yeast management.
Grey et al., broadly noted the following findings:
1. Loading Doses and Daily Dosage
- Overall, the antifungals were correctly prescribed, according to the LD and PDD of the above guidelines.
- While patients received the correct daily dose of caspofungin, the daily dose of anidulafungin was not adhered to.
2. Duration of treatment
- The consensus in the literature is that therapy should be ceased after 14 days of IV treatment, after patients' first negative blood cultures.
- The researchers note that only 129 patients in their study had positive blood cultures, while 17 patients had no blood culture taken.
- The mean duration of echinocandin therapy for the former 129 patients was 0.3% lower than in the 17 patients with no culture taken.
- Grey et al., therefore, concluded that there was no statistically significant difference between the average duration of treatment of patients with blood cultures and those without
Conclusion
The researchers conclude that the prescribing doctors in this study, by and large, complied with international dosage guidelines for echinocandins. The one exception to that finding was the recommendation that the duration of treatment be based on blood culture. In this regard, the researchers found that the duration of treatment did not appear to be significantly influenced in the absence of blood cultures.
It is important to consider certain study limitations when interpreting the results, which include: potential inaccuracies in patients' prescription charts, a lack of clinical data regarding catheter changes, and using a random sample based on specific inclusion and exclusion criteria.
Furthermore, it is noteworthy that the private hospital where the study took place had implemented a Quality Alert system three years before the emergence of echinocandin-resistant organisms like C. auris. With the increasing prevalence of such resistance, it has become crucial to pay particular attention to the duration, dosage, and utilisation of blood cultures to address and mitigate the implications of these resistant organisms.
The localized study results can be utilized to develop hospital-specific algorithms for patients infected with Candida. Additionally, the study emphasizes the importance of guidelines related to available antifungal medications and highlights how their implementation can lead to more favourable outcomes.
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