Antifungals Used To Treat Fungal Sinusitis

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Introduction

The headaches, nasal congestion, and pain, many of us are well acquainted with those all too familiar signs that we may be suffering from a sinus infection (sinusitis).1

These uncomfortable symptoms that we all dread are due to the sinuses (air-filled cavities in our skulls) becoming inflamed, blocked and eventually infected.2

Viruses and sometimes bacteria are the usual culprits we think of when we decide to reach for the decongestant. However, most people do not consider that it may be a fungal infection which is the source of all their woes.1, 2

So let's take a closer look at what fungal sinusitis is and the antifungal medicines we use to treat it.

Quick facts about fungal sinusitis:

  • There is more nuance to fungal sinusitis than you might think. Broadly speaking fungal sinusitis can be divided into two groups: The non-invasive kind that tends to ‘stay put’ and the invasive aggressive kind that can invade other tissues and become life-threatening.3
  • The non-invasive types can be further subdivided into Allergic fungal sinusitis, fungus ball (Mycetoma), and saprophytic fungal sinusitis.2, 3
  • There are also two main invasive types and these are chronic and acute fungal sinusitis.2, 3
  • If you suffer from diabetes or have a compromised immune system the chance of you contracting fungal sinusitis may be higher than if you are healthy. However, either way you should remain vigilant and see your GP if your sinus infection doesn't clear up.3
  • If you have fungal sinusitis, these are some of the more common fungi/yeasts you may be dealing with: Aspergillus, Mucorales, Candida, Dermatiaceous fungi and Cryptococcus.3, 4, 5, 6

Diagnosis 

If you are having the symptoms of fungal sinusitis, then you must seek medical attention ASAP. This will allow you to get treatment like antifungals more quickly and prevent the infection from becoming more serious. When being diagnosed your doctor may perform the following tests and assessments:2

  • Clinical evaluation 
  • Imaging studies (CT, MRI) - to identify fungal masses
  • Nasal endoscopy - so the doctor can see the infection
  • Biopsy - to confirm the type of fungus
  • Laboratory tests

Introducing antifungal medications:

Azoles

Overview:

How long will my treatment last?

You may have treatment for a few weeks to a few months, though it depends on the type of fungi found in your sinuses and how serious your infection is.7, 8 

How does this medicine help to get rid of my infection?

Azoles prevent fungi from making a special substance called ergosterol which the fungi need to survive, without it the fungi die.9

What side effects may I experience when taking these medicines? 

  • Nausea  
  • Vomiting 
  • Headache
  • Skin rash
  • Visual disturbance (most commonly seen when taking voriconazole)
  • Always tell your doctor what medicines you are taking, these drugs may interact with other drugs.10

Types may include:

  • Itraconazole - effective against Candida species and Aspergillus.11
  • Voriconazole - mainly used to treat Aspergillus and Fusarium species.12

Polyenes (Amphotericin B)

What are polyenes used for? 

If you are taking a polyene for fungal sinusitis then you will most likely be prescribed the Polyene Amphotericin B. If your sinuses are infected by Mucor fungi then this is often the first choice. On the other hand, if you are infected with another fungus, an Azole or Echinocandin like Caspofungin may be better for you. This is because Amphotericin B’s side effects can be more unpleasant than other antifungals so it is more likely to be used in an emergency, with Mucor, or if other antifungals aren’t cutting it.3, 13

How is amphotericin B taken?

Amphotericin B exists in two forms: the conventional form and the lipid form which has less side effects. The dose you are given will be related to the type of formulation you receive.13

What side effects might I experience when taking Amphotericin B13

What types of fungi and yeast does Amphotericin B treat?13

  • Effective against most Candida: Candida parapsilosis, Candida albicans, Candida tropicalis and Candida krusei.
  • Cryptococcus
  • Mucor
  • Fusarium species
  • Sporothrix schenckii
  • Aspergillus 

How does amphotericin B treat my fungal sinusitis? 

Amphotericin B works against the same lipid (ergosterol) as the Azoles. However, it attaches itself to this lipid. Doing this sets off a chain of events which results in holes being punched into the fungal cell killing it.14

Echinocandins 

What is caspofungin?

Caspofungin is a type of Echinocandin antifungal which may be great for treating your fungal sinusitis if you can’t tolerate other antifungals, or when the antifungal you are using isn’t clearing your infection.3

How much caspofungin do I have to take?

If you are taking Caspofungin you may take it in two different doses. A loading dose, which is a large dose designed to pack and punch and kill of your fungal infection, and a maintenance dose, which is a smaller dose that helps keep that fungus at bay.15

What are the possible side effects?15 

  • Fever
  • Phlebitis at injection site.
  • gastrointestinal symptoms.

How does caspofungin work?

Caspofungin works a little differently to the Azoles and Polyenes, it prevents fungi from making an essential substance called glucan. Without it, the protective cell walls are weakening, when these break down the fungi can’t survive.15

What fungi and yeasts do caspofungin treat?

If your infection is caused by Candida species, Caspofungin is a powerful ally. In fact, in the treatment of C. glabrata or C. krusei Caspofungin tends to be better than the Azoles. This drug is also an excellent choice for treating Aspergillus if you can’t tolerate Voriconazole or your Aspergillus infection is particularly recalcitrant.15

Allergic fungal sinusitis 

Of all the types of fungal sinusitis, Allergic fungal sinusitis is the most common type. If you have this illness, your body has an allergic reaction to inhaled fungus, which causes nasal polyps to form. You may be more likely to have this if you suffer from hay fever or asthma.2

Surgery may be offered to you as this is the main treatment for allergic fungal sinusitis. One study demonstrated that the use of 4 weeks of intravenous itraconazole before the operation led to improvement of allergic fungal sinusitis. 15 of the patients had complete resolution of disease.16

Another study used doses of 200mg of oral itraconazole for 2 days, followed by 100mg for 26 days. This was done both before and after surgery, it was found that this was more effective at preventing disease recurrence than taking itraconazole only before the operation.16

Fungus balls

When a fungus ball(s) occurs, fungi accumulate in the sinus and clump together as balls which can grow quite large and block the sinuses; these have to be removed surgically.2

In most cases, antifungals will not be used as they are not systemic, topical or invasive. So Fungus balls are usually treated by functional endoscopic surgery.3

Acute invasive fungal sinusitis 

Acute invasive fungal sinusitis occurs when a person has a compromised immune system. Because of this, the fungi causing the infection are able to become invasive and attack the blood vessels. This prevents blood from reaching some areas and the tissue in those areas dies. If left unchecked the fungus may spread to the eyes and brain causing blindness and death.2

Often a combined approach of surgery and early antifungal therapy is required. Cultures of the fungus will be sent to the lab, and while the patient is waiting on results Amphotericin B is often the first-line antifungal of choice. This is because it is capable of killing both Aspergillus and Mucorales fungus, one downside is that it does come with a lot of side effects. However, the invention of liposomal Amphotericin B has helped to ameliorate these somewhat. However, once your cultures have been identified, you may then be switched to Voriconazole if it is found that your fungus is Aspergillus, which has fewer and less severe side effects.3

Additionally, Caspofungin may occasionally be given if you have Aspergillus fungus and are either not tolerant of, or are not responding to Voriconazole.17

Chronic invasive sinusitis

If you have diabetes you may have an increased likelihood of experiencing chronic invasive sinusitis. With Chronic invasive sinusitis, you will have signs and symptoms that are similar to the acute form, however, the spread of infection will be less rapid.2

If you have diabetes you may have an increased likelihood of experiencing chronic invasive sinusitis. With Chronic invasive sinusitis, you will have signs and symptoms that are similar to the acute form, however, the spread of infection will be less rapid. 

The way your chronic invasive sinusitis is managed will be pretty much the same as you would be with an acute case in terms of the types of antifungals you take to fight off the fungi you have. The antifungals used, as with the acute form, will be chosen on the basis of the type of fungi causing your infection.3

Summary

  • Fungal sinusitis describes a condition where your sinuses become infected with a fungal agent.
  • Fungal sinusitis can be divided into non-invasive and invasive forms.
  • There are three groups of antifungals that you might use to treat your fungal sinusitis. These are the Azoles, Polyenes and Echinocandins and the ones which you take will be tailored to the specific fungi, type of infection and tolerance you have.
  • If you have forms such as allergic, acute and chronic types you may require both surgery and antifungals.
  • Conversely, if you have the fungus ball type surgery alone is more likely to be recommended.
  • For the allergic type, you are most likely to be prescribed an azole like itraconazole.
  • On the other hand if you suffer from the acute or chronic type Amphotericin B or Voriconazole may be better.

References

  1. Cleveland Clinic [Internet]. [cited 2024 Jan 19]. Sinus infection: common causes & how to treat it. Available from: https://my.clevelandclinic.org/health/diseases/17701-sinusitis
  2. Cleveland Clinic [Internet]. [cited 2024 Jan 19]. Fungal sinusitis: what is it, symptoms & treatment. Available from: https://my.clevelandclinic.org/health/diseases/17012-fungal-sinusitis-fungal-sinus-infection
  3. Deutsch PG, Whittaker J, Prasad S. Invasive and non-invasive fungal rhinosinusitis—a review and update of the evidence. Medicina (Kaunas) [Internet]. 2019 Jun 28 [cited 2024 Jan 19];55(7):319. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681352/
  4. Swarajyalakshmi M, Jyothilakshmi G. Candida kefyr in invasive paranasal sinusitis. Indian J Otolaryngol Head Neck Surg [Internet]. 2014 Jan [cited 2024 Jan 19];66(Suppl 1):371–4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918296/
  5. Zieske LA, Kopke RD, Hamill R. Dematiaceous fungal sinusitis. Otolaryngol Head Neck Surg [Internet]. 1991 Oct [cited 2024 Jan 19];105(4):567–77. Available from: https://pubmed.ncbi.nlm.nih.gov/1762793/
  6. Ferraro RA, Ivanidze J, Margolskee E, Tsang H, Sconomiglio T, Jhanwar YS. Invasive granulomatous cryptococcal sinusitis in an adult with multiple myeloma. Clin Imaging [Internet]. 2017 [cited 2024 Jan 19];41:65–8. Available from: https://pubmed.ncbi.nlm.nih.gov/27816878/
  7. Seiberling K, Wormald PJ. The role of itraconazole in recalcitrant fungal sinusitis. Am J Rhinol Allergy [Internet]. 2009 [cited 2024 Jan 19];23(3):303–6. Available from: https://pubmed.ncbi.nlm.nih.gov/19490806/
  8. Debbarma S, Gupta R, Patro SK, Gupta AK, Pandhi P, Shafiq N. Randomised comparison of safety profile and short term response of itraconazole, voriconazole and amphotericin b in the management of chronic invasive fungal rhinosinusitis. Indian J Otolaryngol Head Neck Surg [Internet]. 2019 Nov [cited 2024 Jan 19];71(Suppl 3):2165–75. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848640/
  9. Lakhani P, Patil A, Majumdar S. Challenges in the polyene- and azole-based pharmacotherapy of ocular fungal infections. J Ocul Pharmacol Ther [Internet]. 2019 Feb 1 [cited 2024 Jan 19];35(1):6–22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354613/
  10. Voriconazole (Oral route) side effects - mayo clinic [Internet]. [cited 2024 Jan 19]. Available from: https://www.mayoclinic.org/drugs-supplements/voriconazole-oral-route/side-effects/drg-20095248?p=1
  11. Kurn H, Wadhwa R. Itraconazole. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 19]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557874/
  12. Greer ND. Voriconazole: the newest triazole antifungal agent. Proc (Bayl Univ Med Cent) [Internet]. 2003 Apr [cited 2024 Jan 19];16(2):241–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1201014/
  13. Noor A, Preuss CV. Amphotericin b. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 19]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK482327/
  14. Stone NR, Bicanic T, Salim R, Hope W. Liposomal Amphotericin B (Ambisome®): A review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs [Internet]. 2016 Mar [cited 2024 Jan 19];76(4):485–500. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856207/
  15. Dongmo Fotsing LN, Bajaj T. Caspofungin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 19]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK545140/
  16. Medikeri G, Javer A. Optimal management of allergic fungal rhinosinusitis. J Asthma Allergy [Internet]. 2020 Sep 11 [cited 2024 Jan 19];13:323–32. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494399/
  17. Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis [Internet]. 2004 Dec [cited 2024 Jan 19] 1;39(11):1563–71. Available from: https://pubmed.ncbi.nlm.nih.gov/15578352/

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