Fighting serious candida infections in critically ill patients

Candidaemia: A rising tide in critically ill patients^3-5

Severely ill or medically unstable patients who require close monitoring are often managed in the intensive care unit (ICU). Candidaemia is a serious healthcare-related infection associated with poor clinical outcomes in this setting.^3-5

In Australia, critical care units account for almost a quarter of candidaemia cases in hospital,⁶ with crude mortality rates of 56% reported in this population by Marriott et al.⁷ The study also showed an association between mortality and hostrelated factors such as increasing age, mechanical ventilation, non-multitrauma management and presence/non-removal of vascular access devices.

Dr Geoffrey Playford, co-author of an Australian study ‘Determinants of Mortality in Non-Neutropenic ICU Patients with Candidaemia’, and an infectious disease specialist at the Princess Alexandra Hospital, Queensland, acknowledged that “crude mortality rates for candidaemia in the ICU setting remain high. Our recent study demonstrated that median time to death after first positive blood culture is 7 days. More than 25% of deaths involved patients not treated with an anti-fungal agent, two-thirds of whom died less than 48 hours after candidaemia onset.”⁷ A Glockner study indicated that the outcome of candidaemia largely depends on the early initiation of effective anti-fungal therapy.⁸

Population-based surveillance data in Australia have revealed that candidaemia is more prevalent in the very young (?1 year) and the elderly (>65 years).⁶ Most Candida infections are caused by C. albicans, C. parapsilosis and C. glabrata.⁶

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“Given the time delay in obtaining species identification and anti-fungal susceptibility results, and the importance of prompt effective antifungal therapy, the potential for clinical features to predict whether candidaemia is caused by a potentially non-azole susceptible Candida species needs to be examined.”⁹

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Eraxis^®: Superior efficacy over fluconazole²

Eraxis^® (anidulafungin), available for intravenous (IV) use in Australia, is the only echinocandin to have demonstrated superior efficacy to fluconazole,² the gold standard in the treatment of candidaemia and other forms of candidiasis.^8,10

In a pivotal trial comparing Eraxis^® to fluconazole, Reboli et al – the only head-to-head comparison between fluconazole and an echinocandin to date – showed superior efficacy with Eraxis^® vs fluconazole (75.6% vs. 60.2%; 95% CI, 3.9-27.0; p=0.02).² The study demonstrated a higher global response to treatment of C. albicans infections (81% vs. 62%; p=0.02).²

The study was designed as a prospective, randomised, double-blind, multi-centre comparison of adult patients with invasive candidiasis, randomised to receive IV anidulafungin (200 mg on day 1, then 100mg daily; n=127) or IV fluconazole (800 mg on day 1, then 400 mg daily; n=118). IV treatment was given for at least the first 10 days before patients could be switched to oral fluconazole therapy.²

Among candidaemia-only patients (89% of all patients), a higher successful response was seen with Eraxis^® vs. fluconazole at the end of IV treatment (75.9% vs 61.2%; 95% CI, 2.5-26.9; p=0.02).² Sub-group analysis by APACHE II scores also showed a significant difference in global treatment response favouring Eraxis^® in patients with APACHE II score ?15 and those with severe sepsis and multiple organ dysfunction, supporting the use of Eraxis^® in these populations.^9,11

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“Recent North American and Australian guidelines have emphasised that in situations where C. glabrata or C. krusei is likely (such as with prior azole exposure), or for patients with haemodynamic instability, an echinocandin is favoured as first line therapy.”⁴

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ERAXIS^®: Well-tolerated; no dose change needed in hepatic or renal impairment^1,2

Eraxis^® has been shown to be as safe as fluconazole,² with fewer patients discontinuing treatment due to adverse events or worsening clinical status compared with fluconazole.²

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“Of importance to critically ill patients or patients with acute organ dysfunction, Eraxis^® dosage does not have to be altered in the presence of renal or hepatic impairment.”⁹

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No clinically relevant drug-drug interactions have been noted between Eraxis^® and other licensed anti-fungal agents and immunosuppressive therapies.¹

ERAXIS^® (anidulafungin 100 mg) Powder for Injection.

BEFORE PRESCRIBING REFER TO THE FULL PRODUCT INFORMATION

(Available at www.pfizer.com.au).

Use: Invasive candidiasis, including candidaemia.

Contraindications: Hypersensitivity to anidulafungin or any excipients or to other medicines of the echinocandin class.

Precautions: Infusion-related reactions: Must not be given by bolus injection. Infusion rate must not exceed 1.1 mg/minute; Hepatic effects; Children < 18 years; Pregnancy Category B3: ensure effective contraception; Lactation.

Interactions: No clinically relevant interactions. (See full PI).

Adverse Reactions: Common - thrombocytopenia, coagulopathy, hyperkalaemia, hypokalemia, hypomagnesaemia, convulsion, headache, flushing, diarrhoea, abnormal LFTs, rash, pruritis, increased blood bilirubin and creatinine, decreased platelet count, QT prolonged. Others - neutropenia, leukopenia, anaemia, paraesthesia, central pontine myelinolysis, Guillain- Barré syndrome, deafness, hypotension, hepatic necrosis, angioneurotic oedema, renal failure. (See full PI).

Dosage: 200 mg loading dose and 100 mg daily thereafter. Should not exceed 1 month. Reconstituted with WFI and diluted with 0.9% NaCl or 5% glucose. (See full PI). Pfizer Pty Ltd, ABN 50 008 422 348, 38-42 Wharf Road, West Ryde, NSW 2114. Based on TGA approved Product Information of 25 March 2009 and amended 24 June 2009. ERAXIS^® is a registered trademark.

References
1. Eraxis Approved Product Information, 24 June 2009
2. Reboli AC et al. N Engl J Med 2007; 356: 2472?2482
3. Eggimann P et al. Lancet Infect Dis 2003; 3: 685–702
4. Ostrosky-Zeichner L, Pappas P. Crit Care Med 2006; 34: 857–863
5. Blot S et al. Am J Med 2002; 113: 480–485
6. Chen S et al. Emerg Infect Dis 2006; 12: 1508-1516
7. Marriott D et al. Crit Care 2009; 13(4): R115
8. Glockner A et al. Mycoses 2009; 52: 476–486
9. Kett D et al. Int J Antimicrob Agents 2008; 32: S99-S102
10. Pappas P et al. Clin Infect Dis 2009; 48: 503–535
11. Kett D et al. International Symposium on Intensive Care and Emergency Medicine 2010, abstract number A75