Invasive Fungal Sinusitis

Invasive fungal sinusitis can have a serious affect on you if you are an immunocompromised individual; however, immunocompetent patients are still susceptible to this condition. There two different forms of invasive fungal sinusitis varying in severity: acute invasive fungal sinusitis, and chronic invasive sinusitis. While acute invasive fungal sinusitis is the most serious and severe condition, it is important to discuss the both forms as all their associated problems still manifest themselves in harmful ways.

It is important to discuss the definition of immunodeficiency, as it is a condition that fosters invasive Fungal Sinusitis. A person who exhibits immunodeficiency is said to be immunocompromised. Being immunocompromised means your immune system is damaged and/or inhibited making it extremely difficult for your body to fight off infections and disease. This is especially concerning for patients infected with pathogenic fungus, like in invasive fungal sinusitis, as it is hard to rid the body of the infection.

Primarily exhibiting itself in immunocompromised patients, acute invasive fungal sinusitis is the most aggressive form of invasive fungal sinusitis with high mortality rates. The most common fungus found with invasive fungal sinusitis is Aspergillus. According to Dr. Bruno Di Muzio et al of Hospital Santa Paula in São Paulo, people with diabetes mellitus and patients with nervous system conditions like haematologic malignancies are prone to this form of invasive fungal sinusitis.1 Additionally, patients with advanced AIDS are susceptible to invasive fungal sinusitis. Infection begins in the nasal cavity and spreads to the paranasal sinuses. Symptoms can include a thickening of mucous consistency, bone destruction, and fat stranding outside the sinuses.2 Currently, the most effective treatment of acute invasive fungal sinusitis is early detection and diagnosis and subsequent surgical and medical treatment repair or bolster a compromised immune system. However, once the fungus infection establishes itself in the sinus, it is very hard to remove the fungus and cure the disease. Unfortunately, mortality rates in acute invasive fungal sinusitis are high.

Chronic invasive fugal sinusitis is a less severe form of invasive sinusitis and typically has a longer course of action. This variant of invasive sinusitis is found present in mostly immunocompetent individuals or individuals that are only mildly immunocompromised. This condition typically takes more than 12 weeks to manifest itself in a patient’s body. Its symptoms are similar but less severe than acute invasive fungal sinusitis.

Invasive fungal sinusitis is a serious problem for immunocompromised patients and is very damaging to the nervous system and the patient’s health. Its mortality rates are high and current treatment methods are vague and generally ineffective. This condition should be researched and understood, and solutions be explored and implemented.

1Muzio, Bruno, Dr., and Frank Gaillard, A.Prof. “Chronic Invasive Fungal Sinusitis | Radiology Reference Article | Radiopaedia.org.” Radiopaedia Blog RSS. Accessed June 13, 2016. http://radiopaedia.org/articles/chronic-invasive-fungal-sinusitis.

2 Deshazo, Richard D. “Syndromes of Invasive Fungal Sinusitis.” Medical Mycology 47, no. 1 (May 19, 2008). Accessed June 13, 2016. http://mmy.oxfordjournals.org/content/47/Supplement_1/S309.full.

Photodisinfection Technology

“Photodisinfection”, or Antimicrobial Photodynamic Therapy (aPDT), is a non-antibiotic broad spectrum topical treatment that utilizes a light-activated (photosensitizer) compound to target and destroy bacterial biofilms, virulence factors and inflammatory proteins.[i]  The primary mechanism of action of Photodisinfection is the production of large quantities of reactive oxygen species (ROS) such as singlet oxygen, superoxide anion and hydroxyl radical in close proximity to the target cell, resulting in rapid lysis of the cell and destruction/crosslinking of membrane-associated proteins and lipopolysaccharides.  Photodisinfection has been demonstrated to reduce CRS antibiotic resistant polymicrobial biofilms by >99.9% after a single treatment.[ii]  The Photodisinfection induced effect is target-specific to only those organisms that have absorbed the photosensitizer and are exposed to a specific wavelength of light.[iii]  Because the photosensitizer is cationically charged, the process has little to no effect on electrostatically neutral human tissues.[iv]

In addition to antibiotic resistant strains, Photodisinfection is equally effective against normal strains of bacteria.  Furthermore, there is no evidence of bacterial resistance occurring after repeated Photodisinfection treatment cycles.[v]  The Photodisinfection mechanism of lethality is completely different from that of oral and systemic antimicrobial agents.  There is no primary metabolic or thermal action involved with this minimally invasive therapy. Sinuwave™ Photodisinfection therapy is targeted for those patients unresponsive to, or ineligible for medicinal or surgical interventions.

 



[i] Wainwright M., Photodynamic antimicrobial chemotherapy (PACT). Journal of Antimicrobial Chemotherapy (1998) 42, 13-28

[ii] Biel, M.A.. Pedigo L., Gibbs A., Loebel N., Photodynamic therapy of antibiotic-resistant biofilms in a maxillary sinus model. Int Forum Allergy Rhol. 2014 Jan 10.

[iii] Kharkwal G.B. et al, Photodynamic Therapy for Infections: Clinical Applications. Lasers in Surgery and Medicine 43:755-767 (2011)

[iv] Demidova T.N. et al, Photodynamic Therapy Targeted to Pathogens. Int J Immunopathol Pharmaco. 2004;17(3): 245-254

[v] Dai, T. et al, Photodynamic therapy for localized infections – state of the art. Photodiagnosis Photodyn Ther. 2009; 6(3-4): 170-188.

Invasive Fungal Rhinosinusitis (IFS)

In immunocompetent patients, IFS typically presents with nasal congestion and periorbital discomfort.  In immunocompromised patients however, IFS often presents with masses, proptosis and bony erosion, typically with rapid progression.

Acute invasive fungal rhinosinusitis (AIFR) is a rare but frequently fatal infection that occurs primarily in immunocompromised individuals and diabetics.i It is characterized by fungal invasion into the mucosa and submucosal structures of the paranasal sinuses with frequent extension into adjacent structures, including the paranasal soft tissues, orbit and cranial vault.  Short term mortality has been reported to range from 20-68% across studies.[i]i

Surgery is the primary approach to IFS. Photodisinfection is a potent anti-fungal therapy that can help to address the IFS patient population with its minimally invasive advantages. 



[i] http://www.medscape.com/viewarticle/408751_2

ii Monroe Marcus M. et al, Invasive Fungal Rhinosinusitis: A 15 Year Experience with 29 Patients. The Laryngoscope 2013 Feb.

 

Sinuwaveis only available in Canada 

Bacterial Biofilms Implicated in Chronic Rhinosinusitis

Blockages can occur in the sinuses due to a number of factors causing trapped mucus to accumulate inside the sinuses and encouraging the growth of microorganisms in sessile layers known as biofilms.   One recent study found that biofilms were present on the mucosa of 75% of patients undergoing surgery for CRS.[i]

Different biofilm species are associated with different disease phenotypes.  H. influenzae biofilms are found in patients with mild disease, whereas S. Aureus is associated with a more severe, surgically recalcitrant pattern.[ii] [iii] Recent studieshave demonstrated that biofilm infections, involving known super-antigen producing bacteria such as S. aureus and P. aeruginosa, are implicated in CRS and reduce the effectiveness of antibiotics.[iv]

Eradication of these biofilm infections and associated virulence factors is important in effectively and successfully dealing with the disease.  Repeated antibiotic exposure and increasing antibiotic resistance is a treatment challenge faced by this patient population.

Photodisinfection has been proven to effectively target and destroy biofilms and associated virulence factors, offering a clear advantage over other therapies.[v]

 



[i] Ragab A. et al., Evaluation of bacterial adherence and biofilm arrangements as new targets in treatment of chronic rhinosinusitis. Eur Arch Otorhinolaryngol. 2012 Feb; 269(2): 537-44.

[ii] Foreman A., et al. Different biofilms, different disease? A clinical outcomes study. Laryngoscope. 2010 Aug; 120(8): 1701-6.

[iii] Foreman A. et al. Do biofilms contribute to the initiation and recalcitrance of chronic rhinosinusitis? Laryngoscope. 2011 May; 121(5): 1085-91.

[iv] Leid Jeff G. et al., The Importance of Biofilms in Chronic Rhinosinusitis. Biofilm Infections. Chapter 8

[v] Darveau Richard,  DNA and Cell Biology, Volume 28, Number 8, 2009, Pg 1-7.

Chronic Rhinosinusitis (CRS)

Chronic Rhinosinusitis or “CRS” is defined as sinus inflammation involving the nasal mucosa and paranasal sinuses with 2 or more symptoms persisting for 12 weeksor longer with incomplete resolution of symptoms.[i]

Refractory chronic rhinosinusitis (“RCRS”) is a term used to describe CRS that is unresponsive or refractory to medical and surgical therapy.[ii]

Fungal rhinosinusitis encompasses a wide variety of fungal infections that range from merely irritating to rapidly fatal.  Invasive fungal Rhinosinusitis (“IFS”) is classified as either acute or chronic, is difficult to treat and is a significant cause of morbidity and mortality in immunocompromised patients.

 

Figure 1: Outline of the complex cycle in the development of CRS.
 Factors that may contribute to the development of CRS include exposure to allergens and irritants, defects in mucociliary function, immunodeficiency and infections with bacteria, viruses and fungi.  The common endpoint is local inflammation and swelling of the sinonasal mucosa and impairment of normal sinus drainage.  The recognition that CRS represents a multifactorial inflammatory disorder, rather than simply a persistent bacterial infection, has led to the re-examination of the role of antimicrobials in CRS.

The medical management of CRS is now focused upon controlling the inflammation that predisposes patients to obstruction, thus minimizing the incidence of infections.  Despite this, all forms of CRS are associated with poor sinus drainage and secondary bacterial infections.  Most patients require antibiotics to clear infections at the outset of therapy and intermittently thereafter to treat acute exacerbations of CRS.  However, the role of these agents beyond these two indications remains an area of investigation.[i]


[i]  Rosenfeld Richard M et al; Clinical practice guideline: Adult sinusitis Otolaryngology-Head and Neck Surgery (2007) 137, S1-S31

[ii]  Desrosiers M., Refractory chronic rhinosinusitis: pathophysiology and management of chronic rhinosinusitis persisting after endoscopic sinus surgery. Cur Allergy Asthma Rep. 2004 May; 4(3):200-7

Immediate Harm

We’re beginning to understand the harm caused by our antibiotic 'bombs'.

According to a leading medical journal, viral infection is the cause of up to 98% of sinusitis and, in the USA, the disorder affects about 14% of the adult population every year, i.e. some 30 million Americans. Despite the likely viral cause, antibiotics are prescribed “more often than not;” indeed, sinusitis is the fifth leading reason for prescription of antibiotics by US primary care physicians.

What drives this massive over-prescription problem is a mindset among physicians that “antibiotics won’t do any harm and may help,” says highly-regarded infectious disease specialist Brad Spellberg, MD. He frames the issue this way:

“Perhaps if providers had a better grasp of the risk for immediate harm caused to the patient by the antibiotic prescription — as opposed to the vague and intangible notion of a small harm to society at large that may occur over time — they might be better armed to make a more appropriate risk/benefit decision about whether to prescribe the antibiotic … Resistance is not merely for the public at large. Resistance will occur in the individual patient as a consequence of their new prescription.” (My emphasis.)

The concern is not simply that antibiotics cause unwanted side effects like diarrhea, rashes, nausea, and stomach pain, and even life-threatening allergic reactions, kidney toxicity, and severe skin reactions, as the US Centers for Disease Control warns us. The story runs deeper than that. We think antibiotics are like laser-guided missiles that attack only the bugs that make us sick. But they’re not. They’re actually too powerful – like nuclear weapons that destroy everything, good bacteria included, said Margaret Riley, PhD, in her address to the Institute of Medicine this year.

We need our good bacteria – which is most of our bacteria – to keep us healthy. They help us digest food, build nutrients, and crucially, they’re part of our immune response. So if you knock them out with an antibiotic you are left more vulnerable to infection, immediately and in the long run.

The leading edge of antibiotic research is telling us things we couldn’t have imagined even a few years ago: for example, that the antibiotic-driven destruction of our microbiome – our internal collection of microbes, bacteria especially – is contributing to the rise of our “modern plagues:” obesity (antibiotics are The Fat Drug), asthma, allergies, diabetes, and certain forms of cancer.

But here’s the thing. These negative consequences happen even when you should use an antibiotic. Understandably, you have to risk it when dealing with a serious bacterial-driven infection which can be limb and life-threatening. But to prescribe antibiotics “more often than not,” when only 2% of sinusitis cases are bacterial is something our best clinician-researchers are telling us we need to stop – now.

 

 

 

Antibiotics: Cure or Curse?

Antibiotics: just say no!

First some background. Sinusitis is a huge problem that typically goes unnoticed. Over 30 million Americans are affected by sinusitis annually. In addition to the daily pain and suffering of those afflicted, additional  costs to society include 73 million days of restricted activity or lost work per year, and an estimated yearly financial burden of $5.8 billion.

Moreover, the vast majority of doctors themselves tell us they are dissatisfied with their ability to treat the disease. In a 2007 study published in The Journal of Allergy and Clinical Immunology, 202 doctors were surveyed from the US, UK, France, and Germany and  86% of them said they were generally unhappy with current treatment methods.

So here’s our issue – recent research gives us new insight into a major reason for our inability to treat sinusitis: the ill-advised use of antibiotics to treat a disease that’s typically viral-based.

Bacteria causes sinusitis in only 2% to 10% of cases, yet a national survey showed that 81% of adults presenting with acute sinusitis were prescribed antibiotics.

That’s like using a fishing rod to hunt deer, as bacteria and viruses are entirely different “animals.”

In fact antibiotics are so over-prescribed that sinusitis is now the fifth leading indication for antimicrobial prescriptions by primary care physicians.

The reason for wrongly prescribing antibiotics is that distinguishing between  bacterial and viral-bases sinusitis is difficult to do. Normally, the difference can’t be differentiated in the first 10 days of the onset of the illness.

So in 2012 the Infectious Disease Society of America issued guidelines to help doctors and their patients distinguish between the two.  Generally speaking the longer the symptoms last and the more severe they are the more likely it is that the problem is bacterial-based. IDSA defines severe symptoms as those that last for ≥10 days without improvement, high fever, i.e. ≥ 39°C  or  102°F, or a pussy nasal discharge or facial pain lasting for at least 3 to 4 consecutive days. 

Here’s one more thing to consider. What happens when you take an antibiotic when you shouldn’t? To begin with it won’t help you with your illness – you might as well have taken a sugar pill. But something else happens too: it kills off your “good” bacteria and what’s left over is the “bad” bacteria – those that are resistant to antibiotics (that’s why they’re still there). The resistant bacteria then go on to “multiply” taking over the space formerly occupied by the “good” bacteria.

So here’s the rub: say you eventually contract a bacterial-based ailment like pneumonia for which you require antibiotics – what happens when you take them? Nothing, the pneumonia will continue unchecked. And that’s because your bacteria are now resistant to antibiotics – remember, that’s what’s left after taking that first ill-advised batch of antibiotics. And that can put you in a very difficult spot when  you can’t treat something serious like a pneumonia – it can eventually heal on its own – or not.

The lesson? Before you ask for antibiotics or before your doctor decides prescribes them for you – for sinusitis or otherwise – be sure to ask this question: Doctor, how do you know my illness is caused by bacteria and not by a virus or some other pathogen?

The answer can be the difference between restored health and continued suffering – or between life and death.

 

 

 

 

 

 

 

 

 

 

Sinuwave Photodisinfection: Making a Difference for Refractory Chronic Sinusitis Patients

Carolyn Cross (CEO) with Sinuwave patient

Christina is from Winnipeg, Manitoba. She has been suffering for about ten years from recurring Chronic Rhinosinusitis (CRS). Over time, Christina found that she has become unresponsive to the medical and surgical treatments currently available. She is dealing with tenacious biofilms in her sinuses that have become resistant to antibiotics. She has had 5 or 6 surgeries and countless trips to an array of specialists. Christina lives with debilitating pain from recurring sinus infections and the ongoing concern about her future. Affecting her head and her breathing, this painful condition is hugely disruptive to everyday living. She is frustrated also, that by affecting her, CRS also impacts her entire family.

Otherwise a very healthy person, Christina worries that one day her medical options will run out. New technologies, like Sinuwave™ Photodisinfection, are important to people like Christina as they offer hope for a better quality of life. Christina is one of about 50,000 Canadians suffering from recurring refractory Chronic Rhinosinusitis. In the US, the refractory CRS population exceeds 500,000 and is growing by about 10% (50,000) each year.

Christina came to Vancouver from Winnipeg seeking help with her uncontrollable sinus infections. I had the privilege of spending time this week getting to know Christina and got a better understanding of the nature of the suffering that she gallantly endures. Seen here with me having her second Sinuwave treatment, I was thrilled to learn that her initial Sinuwave treatment the day before had already yielded some positive results for her.  It has taken us about 14 years to develop our innovative non-antibiotic antimicrobial technology to the point where it is now helping refractory CRS patients like Christina. I would like to take this time to thank each member of my very talented team for their personal efforts, sacrifices and dedication that contributed to an important new CRS treatment to help people like Christina.

— Carolyn Cross, CEO

How does Photodisinfection Work?

Photodisinfection is a topical, non-antibiotic antimicrobial therapy that destroys a broad spectrum of pathogens including fungi, bacteria and virus without damaging human tissue. Unlike antibiotics, Photodisinfection selectively kills virulence factors such as the endotoxins and exotoxins produced by pathogens, leading to a clinically observable anti-inflammatory effect. The treatment process takes only minutes, making it over 1,000 times more effective at biofilm killing than antibiotics.

Photodisinfection is a minimally invasive non-thermal therapy involving the light activation of a photosensitizer to eliminate topical infections in a highly targeted approach. Photodisinfection has been proven to be safe and effective in other applications such as for the dental, sinusitis and hospital acquired infection prevention markets. In dentistry, Photodisinfection has been proven to be highly effective for the treatment of caries, endodontics, restorative dentistry, periodontitis, peri-implantitis and halitosis. Many new applications of Photodisinfection are now under development.

The Photodisinfection Process: Instant Antimicrobial Therapy

Apply Photosensitizer to Infection Site & Illuminate with Appropriate Wavelength for Several Minutes

A photosensitizing solution is applied to the treatment site where the photosensitizer molecules preferentially bind to the targeted microbes.  The photosensitizer molecules are inactive at this stage.  A light of a specific wavelength and intensity illuminates the treatment site and a photocatalytic reaction occurs.  The wavelength is carefully chosen to maximize absorption of light energy by the photosensitizer.

This 2 step procedure results in the destruction of the targeted microbes and their virulence factors without damaging host cells.  This reaction involves the formation of short-lived, highly reactive free-radical oxygen species.  These radicals cause a physical disruption of the microbial cell membrane through oxidative reactions, resulting in immediate rupture and destruction of the cell.  This process occurs in seconds with total kills completed in minutes.

The Photodisinfection process has also been shown to eliminate a multitude of virulence factors, unlike antibiotics. When the light isremoved, the photocatalytic reaction ceases along with all antimicrobial action. Photodisinfection does not promote the development of resistance.

The Photodisinfection process is both pain-free and stress-free due to lack of side-effects or damage to human tissue.

Source: Eastman Dental Institute, UK

Sinuwave Introduced to ENT Community at the American Rhinologic Society Conference

Clinicians attending the 59th Annual Meeting of the American Rhinologic Society Conference held on September 28th, 2013 in Vancouver were introduced to the Sinuwave™ Photodisinfection System. Sinuwave is the first Photodisinfection based therapy for the sinusitis market.  An abstract, entitled “Sinuwave Photodisinfection for the treatment of refractory chronic rhinosinusitis: a case series”, was submitted by researchers from the University of Montreal (Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, Canada) and presented at the Conference.

Sinuwave Photodisinfection System is Health Canada approved and was developed by Ondine Biomedical Inc. of Vancouver, the global leader in Photodisinfection, also known as antimicrobial Photodynamic Therapy (aPDT). Photodisinfection is a topical, non-antibiotic antimicrobial therapy that destroys a broad range of pathogens and their virulence factors, leading to a clinically observable anti-inflammatory effect.  Photodisinfection is a minimally invasive non-thermal therapy involving the light activation of a photosensitizer to eliminate topical infections in a highly targeted approach. Photodisinfection has been proven to be safe and effective in other applications such as for the dental and hospital acquired infection prevention markets. For more information about Sinuwave Photodisinfection, please visit www.sinuwave.com

Related Posts Plugin for WordPress, Blogger...

Staypressed theme by Themocracy