Bacterial and Fungal Biofilms in Chronic Sinusitis and Antibiotics Resistance.  Treatment and Prevention of Recurring Fungal Sinusitis and Mold-Related Illness.

Biofilm of antibiotic resistant bacteria. Rod-shaped and spherical bacteria. E-coli, Pseudomonas, Mold spores, Staphylococcus aureus, MRSA. 3D illustration

By Cesar Collado

Chronic rhinosinusitis (CRS) is a challenging disease for both allergists andotorhinolaryngologic physicians (“ENTs”), partly because of its poorly understood pathophysiology and partly because ofits limited treatment options, which remain to be mostly antibiotics. It affects approximately 35 million adults and 6 million children.

When experiencing chronic rhinosinusitis (“CRS”), it is difficult to understand why the infection reoccurs so often, even after antibiotic treatment and/or surgery.  One reason for this is the possible coinfection or colonization of fungus in CRS.  In 1999, The May Clinic published a study where Allergic fungal sinusitis was diagnosed in 94 (93%) of 101 consecutive surgical cases with CRS, based on histopathologic findings and culture results. 1.

A later publication by many of the same researchers in 2006 focused on the role of airborne fungi in CRS. This paper described the process where fungi trigger an immune reaction in sinus tissue causing inflammation and mucous production. The immune system reacts to the fungi by deploying eosinophils.2. The eosinophils are released at levels far exceeding those needed to remove the fungi. This increased inflammation results in damage the sinus epithelial lining and cilia in the sinus tissue lining. When a rupture occurs, damage to the smooth endothelial lining, creates cavities in the sinus, where bacteria (staphylococcus aureus, locally found on the skin, hair, and in the nose) binds to the mucosal pits caused by the lysis of eosinophils when they attach to fungi to destroy it. With continuous inhalation and over  time, additional Staphylococcus bacteria binds to form a protective matrix around bacteria, called biofilm.  This matrix attracts additional bacteria, including fungi and other pathogens.

 

A biofilm comprises any consortium of microorganisms (bacteria and fungi) in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix.  The sticky extracellular matrix protects the bacteria and fungi from the immune system and antibiotics.3.

According to National Institutes of Health (NIH) about 65% of all microbial infections, and 80% of all chronic infections are associated with the presence of biofilms. Biofilm formation is a multi-step process starting with fungal or bacterial attachment to a surface, and then to the formation of a micro-colony that leads to the formation of three-dimensional mature and ultimately diverse pathogens. During biofilm formation many species of bacteria are able to communicate with one another to form a communal barrier against challenges to their well-being.  Thus, bacteria in biofilm are less accessible to antibiotics and the human immune system and pose a bigger threat to public health as they are involved in an ever-growing variety of infectious diseases.

The best treatment for biofilm formation in the sinuses, first line, is nasal irrigation with saline solution to just move the stuff along.If all the people in the world that have chronic sinusitis used nasal saline irrigations 2x per day, you can speculate that a significant proportion would not have any symptoms anymore.  An analogous example to illustrate the concept of using nasal irrigation to prevent biofilm development in the sinus is brushing and flossing your teeth to prevent the formation of plaque.7.  The mouth hosts a variety of bacteria and plaque is actually a formation of a biofilm on the teeth.  Brushing your teeth and flossing 2 times per day are the preventative activities we perform to prevent dental disease and maintain mouth health. These activities, like nasal rinsing stop the health issues associated with the formation of biofilm BEFORE it occurs.

Biofilms Host Both Bacteria and Fungi in the Matrix

Distinct pathogens such as staphylococcus aureus and aspergillus can coexist in biofilms.4.  For these reasons, treatment for CRS using antibiotics may provide temporary relief, but will not fully penetrate and dissolve the remaining biofilm. As soon as the antibiotic course is completed, the bacterial and/or fungal infection that is still present will become recalcitrant or chronic.  The fungal presence in biofilms also allows for “in -vivo” mycotoxin production, meaning that mycotoxins are being actively produced within the biofilm and within the host’s body.  To support this, science has shown an increase of the mycotoxin, Gliotoxin, from Aspergillus fumigatus biofilm formation in the sinus.5.   Increased gliotoxin production makes biofilm-related sinus infections particularly difficult to treat. –

Because fungal sinusitis poses the risk of mycotoxin production in biofilm deep in the sinuses, adjacent to cerebral spinal fluid and the brain, cognitive dysfunction can likely continue as the biofilm matures and disburses particles into the sinuses and the brain. Brain fog, headaches, memory issues, motor function issues throughout the body, dizziness, etc. may not ever go away while biofilms remain in the sinuses.

Biofilm Treatment and Prevention

Antibiotics are dosed to treat planktonic (individual, free flowing) bacteria; however, biofilms harbor a 10–1000-fold higher resistance to antimicrobials due to the slimy matrix protection over the microbial filled cavities.5.Further, antibiotics do not kill mold or fungi.  Although ENT physicians will acknowledge and diagnose acute fungal sinusitis and will remove fungal balls surgically, traditional protocols to treating the infection have not evolved over the years to address fungus.  Standard treatment for infection usually includes antibiotics and possibly surgery.

Another observation is that most ENT physicians skip the diagnostic or culture identification process to determine species of the infection in the interest of time, cost, and practicality, since removing the infection physically and treatment with antibiotics is standard. But, the utilization of antifungal medications is not standard.

Taking any medication designed to kill organisms or cells carries risks to the patient demonstrated through side effects. For example, antibiotics impact the gut flora and cause GI distress and fungal overgrowth. Topical agents have the least danger of toxicity because they are not distributed systemically or metabolized by the liver and kidneys.  More toxic agents used to kill fungal or cancer cells, that are resilient, can have severe toxicities to the liver and/or kidneys when metabolized.  Oral antifungals have improved and provide limited toxicities as older agents are dosed to minimize danger to the patient but are limited in their efficacy.  Intravenous medications have severe organ and metabolic dangers.

Some ENT physicians have discovered the efficacy of using the more potent antifungals topically in the sinuses have had success in treating chronic fungal sinusitis. With current evidence pointing to the fungal etiology of CRS, there has been a trend towards treatment of CRS with topical antifungal medication, namely Amphotericin B.   With current evidence pointing to the fungal etiology ofCRS, there has been a trend towards treatment of CRS with topical antifungal medication, primarily Amphotericin B.

With evidence of fungal causes of CRS, there has been a trend by some ENTs to treating CRS with topical antifungal medication, typically Amphotericin B intranasally. The toxicity of amphotericin B intravenously has been characterized with significantly higher concentrations than are used topically in the sinuses. There is also clear evidence that amphotericin b is poorly absorbed in the gut when taken orally.  Therefore, there is little or no potential for systemic exposure when used topically and intranasally.8.

Endoscopic Surgery for Chronic Fungal Sinusitis

Doctor Dennis and other ENTs often perform endoscopic sinus surgery to remove the obstructions that cause mucous retention and prevent proper sinus drainage that then causes infection.  During this surgery,
diseased tissue and visible biofilms are physically removed using suction.  Following the physical alteration of the anatomy, new tools to essentially “pressure wash” the sinus lining removes residual biofilms, mold and mycotoxins.  The sinuses are then irrigated with amphotericin B to eliminate residual fungal hyphae. Read about the treatment of severe mycotoxicosis in chronic sinusitis published by Dr. Don Dennis and Dr. JackT hrasher with sinus surgery and maximum therapy HERE.

Biofilm Maintenance and Prevention

In addition to nasal rinsing with CitriDrops Dietary Supplement, Dr. Dennis also prescribes Amphotericin B in a mixture with saline to deliver via nebulizer. This is effective in distributing the antifungal deep into the sinuses with daily consistency.

Sinus Defense is also helpful as it targets the same fungi that tested positive in the study described in the May Clinic article in 1999. CellTropin then used to provide support for the pituitary gland which is usually impaired from the mycotoxin onslaught. This is an important piece of treatment, because the pituitary controls 8 hormonal systems.  Sinus infections, inflammation, and the presence of mycotoxins in the body can damage tissue and gland function.  The result is often chronic fatigue and adrenal dysfunction.

Tip to Finding an ENT That Will Listen to a Patient’s Concerns About Mold and Fungus

Many patients suggest to their ENT that mold might be their issue.  This suggestion often finds an unsympathetic ear and a dogmatic opinion as it may be interpreted as trying to tell them how to practice medicine.  This is frustrating.  One solution is that any patient can call a local “Compounding Pharmacy” and ask which local ENT physicians prescribe Amphotericin B in drops or nebulization. Compound Pharmacies provide physicians the ability to custom mix or dose a patient with existing medicines.

Doctors must have these critical sinus delivered prescriptions specially made in a compounding pharmacy, and there is no violation of any rules or laws for a pharmacist to provide a patient with this information, since no personal patient information is being solicited from or provided for such an inquiry.  Physicians having antifungals compounded for patients are more likely to already treat fungal sinusitis given the specific use of the product.  This also saves time and money.

If you would like to comment on this article share your story, please do so in comments.  You can also email me directly at cesarcollado@icloud.com.

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