Empiric treatment of invasive fungal infections

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I am... READY TO HELP YOU TAKE ON THE NEXT SUSPECTED INVASIVE FUNGAL INFECTION1

Empiric indication

AmBisome® is indicated for the empirical treatment of presumed fungal infections in febrile neutropenic patients, where the fever has failed to respond to broad-spectrum antibiotics and appropriate investigations have failed to define a bacterial or viral cause.1

There are a number of signs and symptoms that can be indicative of an invasive fungal infection (IFI)2,3

Fever Cough Dyspnoea Hypotension Vomiting Diarrhoea

The symptoms of an IFI can often be non-specific, leading to difficulty when diagnosing.2

Scroll down to see why early IFI suspicion is important to your patient's survival and be ready for when the next IFI strikes.

Suspect Early, Treat Promptly, Treat Broad4-10

In a re-analysis of a prospective study, initiating AmBisome®(3 mg/kg/day) at the point of suspicion of an IFI (invasive aspergillosis or another mould infection; based on a pulmonary scan) improved patients' chances of a favourable response (p=0.095), and significantly increased the 12-week survival rate (p=0.004) vs. treating a probable or proven IFI.*8

Favourable response at end of treatment with AmBisome® (3 mg/kg/day)8

Possible IFI 56.0%
(n=35/62)
Probable/Proven IFI 40.0%
(n=18/45)
Graph adapted from Cornely et al. 2011

Treating early significantly improves survival8

12-week survival after treatment with AmBisome® (3 mg/kg/day)8

Probability of survival graph
Graph adapted from Cornely et al. 2011

*Reanalysis of the data from the AmBiLoad study - a prospective, randomised, double-blind study in 331 immunocompromised adults and children with proven or probable invasive aspergillosis or other mould infections (EORTC/MSG criteria). Patients were randomised (1:1) to receive 1st-line therapy with AmBisome® 3 mg/kg/day (standard dose) or a high-loading dose of 10 mg/kg/day for the first 14 days, followed by the standard dose.8,11

Scroll down to discover more about why AmBisome® is an effective treatment choice for suspected fungal infections in febrile neutropenic patients.

Treatment Success

AmBisome® has proven efficacy in the empirical treatment of presumed fungal infection in febrile neutropenic patients with persistent fever and neutropenia, and is as effective as voriconazole, caspofungin and conventional amphotericin B.12‑14

Overall treatment success rates of AmBisome® vs. voriconazole, caspofungin and conventional amphotericin B12‑14

AmBisome® vs. voriconazole in adults and children (≥12 years) with neutropenia and persistent fever**12

In an open-label, prospective study (n=837), voriconazole did not meet the primary endpoint of non-inferiority vs. AmBisome® in respect to overall response to empirical antifungal therapy (difference [95% CI]: -4.5 [-10.6 to 1.6]).**12

Notably, voriconazole is not indicated for empirical treatment of IFIs.**15

Overall response to empirical therapy12

KEY
  • AmBisome®
  • Voriconazole
AmBisome® 30.6%
Overall success rate: 30.6% (n=422)
vs.
Voriconazole 26.0%
Overall success rate: 26.0% (n=415)

**Open-label, prospective, randomised, multi-centre, non-inferiority study comparing AmBisome® (3 mg/kg/day) and voriconazole (6 mg/kg IV twice-daily on Day 1, followed by 3 mg/kg IV twice daily or 200 mg orally twice-daily after ≥3 days IV therapy) in patients (≥12 years) with neutropenia (<500/mm3 for 4 days and <250/mm3 within 24 hours of randomisation) and fever of unknown origin (>38°C within 24 hours of randomisation) despite 4 days of systemic, broad-spectrum antifungal therapy. Treatment was considered successful if the patient did not have a breakthrough fungal infection, survived for seven days beyond the end of therapy, did not discontinue therapy prematurely, had resolution of fever during the period of neutropenia, and was successfully treated for any baseline infection. Non-inferiority was pre-defined as a difference in success rates between voriconazole and AmBisome® of ±10%.12

AmBisome® vs. caspofungin in adults with neutropenia and persistent fever†13

In a double-blind, prospective study (n=1095), after patients were stratified according to risk (high‡ or low) and prior use of systemic antifungal prophylaxis, the overall success rates of patients treated with AmBisome® and caspofungin were comparable (difference [95% CI]: 0.2 [-5.6 to 6.0]).†13

Overall favourable response to empirical therapy13

KEY
  • AmBisome®
  • Caspofungin
AmBisome® 33.7%
Overall success rate: 33.7% (n=539)
vs.
Caspofungin 33.9%
Overall success rate: 33.9% (n=556)

†Double-blind, randomised, multi-centre study comparing AmBisome® (3 mg/kg/day) and caspofungin (70 mg on Day 1, followed by 50 mg once-daily) in patients (≥16 years) who had received chemotherapy for cancer or had undergone HSCT, were neutropenic (<500/mm3 for ≥4 days), and had fever of unknown origin (>38°C) despite four days of systemic, broad-spectrum antifungal therapy. The primary efficacy endpoint was favourable overall response. Treatment was considered successful if all five of the following criteria were met: successful treatment of any baseline infection, absence of any breakthrough fungal infection during therapy or within seven days after the completion of therapy, survival for seven days after completion of therapy, no premature discontinuation of study therapy because of drug-related toxicity or lack of efficacy, and resolution of fever (defined as a temperature below 38°C for at least 48 hours) during neutropenia.13

‡High-risk patients were those who had undergone allogenic stem cell transplantation or who had relapsed acute leukaemia.13

AmBisome® vs conventional amphotericin B in patients (2-80 years) with neutropenia and persistent fever§14

In a double-blind, prospective study (n=687), AmBisome® and conventional amphotericin B were comparable in terms of the overall success rate, survival (7 days after initiation of study drug), resolution of fever during the neutropenic period, and discontinuation of the study drug due to toxic effects or lack of efficacy.14

Notably, there were significantly fewer breakthrough fungal infections among patients treated with AmBisome® compared with conventional amphotericin B (p=0.009).§14

Overall success rate of empirical antifungal therapy14

KEY
  • AmBisome®
  • Conventional amphotericin B
AmBisome® 50.1%
Overall success rate: 50.1% (n=343)
vs.
Conventional amphotericin B 49.4%
Overall success rate: 49.4% (n=344)

§Double-blind, prospective, randomised, multi-centre study comparing AmBisome® (initial dose of 3 mg/kg/day) and conventional amphotericin B (cAMB; 0.6 mg/kg/day) as empiric antifungal therapy in adults and children (2-80 years) who were receiving chemotherapy for leukaemia, lymphoma or other cancer, or had undergone bone marrow or peripheral-blood stem cell transplantation, with persistent neutropenia (<500/mm3) and fever despite >5 days' empirical antibacterial therapy. Of all the patients in the study (n=687), almost half (n=333) had acute leukaemia. Treatment success (primary efficacy endpoint) was defined as a composite of five criteria: survival for seven days after initiation of the study drug, resolution of fever during the period of neutropenia, successful treatment of any baseline fungal infection (if present), the absence of breakthrough fungal infections during administration of the study drug or within seven days after the completion of treatment, and the absence of premature discontinuation of the study drug because of toxicity or lack of efficacy.14

When you suspect an IFI in your neutropenic patients, stay one step ahead with AmBisome®1

Dive into more data with our interactive gallery

View the gallery

AML: Acute myeloid leukaemia; CI: confidence interval; CNS: Central nervous system; EORTC/MSG: European Organization for Research and Treatment of Cancer/Mycoses study group; HSCT: Hematopoietic stem cell transplantation; IDSA: Infectious Diseases Society of America; IFI: Invasive fungal infection; IV: Intravenous.

References:

  1. AmBisome® Summary of Product Characteristics (UK). Available at: https://www.medicines.org.uk/emc/product/1022/smpc#gref. [Last accessed: June 2022].
  2. Zhang H et al. Infect Drug Resist. 2020;13 607–615.
  3. Armstrong-James D et al. BMJ Case Rep. 2020;13:e233072.
  4. Morrell M et al. Antimicrob Agents Chemother. 2005;49(9):3640–3645.
  5. Pappas PG et al. Nat Rev Dis Primers. 2018;4:18026.
  6. Nett JE and Andes DR. Infect Dis Clin North Am. 2016;30:51–83.
  7. Chandrasekar P. J Antimicrob Chemother. 2011;66(3):457–465.
  8. Cornely OA et al. Mycoses. 2011;54(5):e449–e455
  9. Lass-Flörl C et al. Antimicrob Agents Chemother. 2008;52(10):3637–3641.
  10. Almyroudis NG et al. Antimicrob Agents Chemother. 2007;51(7):2587–2590.
  11. Cornely OA et al. Clin Infect Dis. 2007;44:1289–1297.
  12. Walsh TJ et al. N Engl J Med. 2002;346(4):225–234.
  13. Walsh TJ et al. N Engl J Med. 2004;351(14):1391–1402.
  14. Walsh TJ et al. N Engl J Med. 1999;340(10):764–771.
  15. European Medicines Agency (EMA). Vfend. (voriconazole) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/vfend-epar-productinformation_en.pdf. [Last accessed: June 2022].

Job code: IHQ-AMB-0532
Date of Preparation: June 2022