Surgical and pathogenetic considerations of frontal sinus fungus ball.

Fungus ball (FB) is an non-invasive form of mycosis, that generally affects immunocompetent and non-atopic subjects. Involvement of the frontal sinus is extremely rare. We report two cases with frontal sinus fungus ball that underwent endoscopic endonasal frontal Draf type IIb or III sinusotomy with complete removal of the cheesy clay-like material. There were no intra-operative or postoperative complications, and no recurrence of disease was evident during the follow-up of 51 and 26 months, respectively. The Draf type IIb or type III frontal sinusotomy seems to be highly effective for the treatment of frontal sinus FB and can represent a valid alternative to the traditional external approaches.

Long-Term Safety of Topical Bacteriophage Application to the Frontal Sinus Region.

Background:Staphylococcus aureus biofilms contribute negatively to a number of chronic conditions, including chronic rhinosinusitis (CRS). With the inherent tolerance of biofilm-bound bacteria to antibiotics and the global problem of bacterial antibiotic resistance, the need to develop novel therapeutics is paramount. Phage therapy has previously shown promise in treating sinonasal S. aureus biofilms. Methods: This study investigates the long term (20 days) safety of topical sinonasal flushes with bacteriophage suspensions. The bacteriophage cocktail NOV012 against S. aureus selected for this work contains two highly characterized and different phages, P68 and K710. Host range was assessed against S. aureus strains isolated from CRS patients using agar spot tests. NOV012 was applied topically to the frontal sinus region of sheep, twice daily for 20 days. General sheep wellbeing, mucosal structural changes and inflammatory load were assessed to determine safety of NOV012 application. Results: NOV012 could lyse 52/61 (85%) of a panel of locally derived CRS clinical isolates. Application of NOV012 to the frontal sinuses of sheep for 20 days was found to be safe, with no observed inflammatory infiltration or tissue damage within the sinus mucosa. Conclusion: NOV012 cocktail appears safe to apply for extended periods to sheep sinuses and it could infect and lyse a wide range of S. aureus CRS clinical isolates. This indicates that phage therapy has strong potential as a treatment for chronic bacterial rhinosinusitis.

Safety and efficacy of topical bacteriophage and ethylenediaminetetraacetic acid treatment of Staphylococcus aureus infection in a sheep model of sinusitis.

BACKGROUND: Treatment of sinonasal bacterial biofilms continues to be a challenge in modern rhinology. This study's objective was to assess the safety and efficacy of topically applied Cocktail of S. aureus specific phage (CTSA) alone and in combination with ethylenediaminetetraacetic acid (EDTA) for treatment of Staphylococcus aureus biofilms in vivo. METHODS: Using a sheep model of sinusitis, frontal sinuses (n = 6 per treatment) were flushed once daily with a CTSA (2 × 10(6) plaque forming units [PFU]/mL), with or without EDTA (0.075 mg/mL), and compared to a control flush containing saline and heat-inactivated CTSA. Safety was assessed using histology and scanning electron microscopy (SEM) after treatment for 3 days. Efficacy was assessed by quantifying the generation of S. aureus biofilms in the frontal sinuses after 5 days of treatment. Biofilm mass was compared between treatment groups and controls using LIVE/DEAD BacLight staining and confocal scanning laser microscopy to visualize the tissue sections. COMSTAT2 software was used to compute the biofilm mass present on tissue sections. RESULTS: Tissue morphology was conserved, with no significant signs of inflammation, when comparing control and test treatments. Furthermore, SEM analysis indicated test treatments were not toxic or damaging to mucosal cilia. COMSTAT2 quantification of biofilm showed a significant reduction in biofilm levels when comparing the control with CTSA (p = 0.0043), EDTA (p = 0.0095), and CTSA-EDTA (p = 0.0022) treatments. CONCLUSION: Results indicate that CTSA and EDTA are safe and efficacious for short-term topical application against S. aureus infection in a sheep sinusitis model, and have the potential to be translated to a clinical setting.

Bacteriology of normal frontal sinuses.

PURPOSE: The aim of this cross-sectional trial was to identify the bacterial flora and to quantify the level of bacterial presence in healthy adult frontal sinus cavities. MATERIALS AND METHODS: Ninety five consecutive patients undergoing craniotomy of the anterior cranial fossa were enrolled. All patients were evaluated preoperatively by a sino-nasal questionnaire, nasal endoscopy and CT scan. Exclusion criteria were patients with sinus tumours, presenting a cold in the past 8 weeks, having signs or symptoms suggestive of sinus disease, history suggestive of allergic rhinitis and/or asthma, having undergone hospitalization or an outpatient clinic visit within the past 12 months, patients with known systemic disease, having previous sinus or nose surgery, history of trauma of the sino-nasal region, or having used systemic antibiotics, steroids, or nasal spray in the past 8 weeks. Lavages were obtained from frontal sinuses before craniotomy through trephination of the anterior wall. The sinus was irrigated with sterile saline followed by aspiration. Specimens were inoculated for aerobic and anaerobic organisms. RESULTS: After applying the exclusion criteria, 42 patients (84 sinuses) were finally included in the study. Bacterial organisms were recovered in 12 of 84 (14.28%) sinuses. However, 85.72% of the sinuses were found to be sterile. Bacteria recovered included three different coagulase-negative staphylococci, one Citrobacter diversus and two Micrococcus spp. No anaerobic organism was isolated. CONCLUSIONS: This study demonstrated that the majority of frontal sinuses of asymptomatic adults with normal CT and endoscopic appearance are sterile.

Trephination of the frontal sinuses and instillation of clotrimazole cream: a computed tomographic study in canine cadavers.

OBJECTIVE: To use computed tomography (CT) to assess the distribution of surgically administered clotrimazole cream and associated filling of the frontal sinuses and caudal aspect of the nasal cavities in canine cadavers. STUDY DESIGN: Observational study. ANIMALS: Small (n = 1) and medium-large (n = 11) breed canine cadavers. METHODS: CT scans of 12 cadaveric canine heads were used to confirm absence of sinonasal disease. Then after creating an opening into the left and right frontal sinuses with a 3.2 mm Steinmann pin at standardized landmarks, clotrimazole cream (20 g) was instilled into each side. Postoperative CT scans of the heads was used to assess the distribution and degree of filling of the sinonasal cavities with clotrimazole cream, and to identify any damage to local structures. RESULTS: Filling was excellent in 22 sinuses, very poor in 2, and excellent in all caudal nasal cavities. Two cadavers had damage: unilateral penetration of the cranium (2) and unilateral penetration of the lateral sinus wall (1). CONCLUSION: Excellent filling of most of the frontal sinuses and caudal nasal cavity of cadavers with clotrimazole cream is achieved when administered by this technique. Damage to local structures may occur intraoperatively using this technique.

Isolated primary frontal sinus aspergillosis: role of endonasal endoscopic approach.

BACKGROUND: Frontal sinus involvement in aspergillosis associated with the nose and paranasal sinuses is a common occurrence, but the incidence of primary frontal sinus aspergillosis is rare, and there are few reports in the English literature. OBJECTIVE: This study aimed to evaluate the role of the endonasal endoscopic surgical approach for isolated primary frontal sinus aspergillosis. METHOD: This paper describes a retrospective study of 16 cases of primary frontal sinus aspergillosis. The patients had presented to the out-patient services of the Department of Otolaryngology and Head and Neck Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India, between January 1999 and July 2011. RESULTS: The overall success rate of the endonasal endoscopic approach was 82.25 per cent. The disease recurred in three patients and was subsequently managed using the modified Lothrop procedure. CONCLUSION: Minimally invasive endonasal endoscopic sinus surgery was found to be an effective and a safe approach for managing primary frontal sinus aspergilloma, even in cases with larger bony defects involving the posterior table of the frontal sinus.

[A new method for the treatment of acute frontitis in the adult patients].

The objective of the study is to estimate the efficacy of Bioparox (fusafungine) when used for the treatment of the adult patients presenting with acute frontitis. Twenty two of the 45 patients with this condition were given adjuvant therapy using this preparation. It resulted in a decrease of the concentration of Staphylococcus aureus and S. epidermidis to 10 CFU/ml and 500 CFU/ml respectively. S. haemoliticus was completely eradicated. The concentrations of these microorganisms in patients of the control group were higher. The level of interleukin 1-beta in the secretion within 5 days after the onset of therapy was twice lower than in the patients of control group. The concentration of IL 1-beta in the serum of the treated with Bioparox patients was 4 pg/ml compared with 8 pg/ml in the control group. The efficacy of therapy of acute frontitis with fusafungine was confirmed in the X-ray study. It is concluded that the use of Bioparox for the management of acute frontitis increases the efficacy of the treatment and result in the marked improvement of the patients' condition within 5 days after the onset of therapy.

Efficacy of NVC-422 against Staphylococcus aureus biofilms in a sheep biofilm model of sinusitis.

BACKGROUND: Bacterial biofilms are a major obstacle in management of recalcitrant chronic rhinosinusitis. NVC-422 is a potent, fast-acting, broad-spectrum, nonantibiotic, antimicrobial with a new mechanism of action effective against biofilm bacteria in in vitro conditions. The aim of this study was to investigate the safety and efficacy of NVC-422 as local antibiofilm treatment in a sheep model of rhinosinusitis. METHODS: After accessing and occluding frontal sinus ostia in 24 merino sheep via staged endoscopic procedures, S. aureus clinical isolate was instilled in frontal sinuses. Following biofilm formation, ostial obstruction was removed and sinuses irrigated with 0.1% and 0.5% NVC-422 in 5 mM acetate isotonic saline at pH 4.0. Sheep were monitored for adverse effects and euthanized 24 hours after treatment. Frontal sinuses were assessed for infection and changes in mucosa after the treatment. S. aureus biofilms were identified with Baclight-confocal scanning microscopy protocol and the biofilm biomass assayed by applying the COMSTAT2 program to recorded image stacks. RESULTS: After 2 irrigations with 0.1% NVC-422, S. aureus biofilm biomass was reduced when compared to control sinuses (p = 0.0001), though this effect was variable in samples. NVC-422 0.5% solution irrigations reduced biofilm even more significantly and consistently over all samples (p < 0.0001). NVC-422 0.5% was also more effective than 0.1% NVC-422, vehicle control, and normal saline sinus irrigations in reducing biofilm biomass (p < 0.05 for all subgroups). No adverse events were observed in sheep after sinus irrigations with 0.1% and 0.5% NVC-422 solutions. CONCLUSION: NVC-422 is an effective topical agent against S. aureus biofilms, with dose-dependent efficacy in this animal model of biofilm-associated sinusitis.

Quantitative analysis of in vivo mucosal bacterial biofilms.

BACKGROUND: Quantitative assays of mucosal biofilms on ex vivo samples are challenging using the currently applied specialized microscopic techniques to identify them. The COMSTAT2 computer program has been applied to in vitro biofilm models for quantifying biofilm structures seen on confocal scanning laser microscopy (CSLM). The aim of this study was to quantify Staphylococcus aureus (S. aureus) biofilms seen via CSLM on ex situ samples of sinonasal mucosa, using the COMSTAT2 program. METHODS: S. aureus biofilms were grown in frontal sinuses of 4 merino sheep as per a previously standardized sheep sinusitis model for biofilms. Two sinonasal mucosal samples, 10 mm × 10 mm in size, from each of the 2 sinuses of the 4 sheep were analyzed for biofilm presence with Baclight stain and CSLM. Two random image stacks of mucosa with S. aureus biofilm were recorded from each sample, and analyzed using COMSTAT2 software that translates image stacks into a simplified 3-dimensional matrix of biofilm mass by eliminating surrounding host tissue. Three independent observers analyzed images using COMSTAT2 and 3 repeated rounds of analyses were done to calculate biofilm biomass. RESULTS: The COMSTAT2 application uses an observer-dependent threshold setting to translate CSLM biofilm images into a simplified 3-dimensional output for quantitative analysis. Intraclass correlation coefficient (ICC) between thresholds set by the 3 observers for each image stacks was 0.59 (p = 0.0003). Threshold values set at different points of time by a single observer also showed significant correlation as seen by ICC of 0.80 (p < 0.001). CONCLUSION: COMSTAT2 can be applied to quantify and study the complex 3-dimensional biofilm structures that are recorded via CSLM on mucosal tissue like the sinonasal mucosa.

[Unilateral frontal sinus aspergillosis: the combined endoscopic and mini-trephination approach]. / Aspergillose unilatérale du sinus frontal: voie d'abord combinée endoscopique et par clou de Lemoyne.

OBJECTIVE: Aspergillosis is a common fungal infection of the paranasal sinuses. Localization in the frontal sinus is usually secondary to involvement of one of the other sinuses. Isolated frontal sinus aspergillosis is rare and only 5 cases are described in literature. CLINICAL CASE: We report a case of a patient with a frontal sinus aspergilloma associated with ipsilateral chronic ethmoidal and maxillary sinusitis, successfully treated with a combined endoscopic and mini-trephination approach "Lemoyne technique". DISCUSSION AND CONCLUSION: The endoscopic approach to the frontal sinus is considered the best way to deal with frontal sinus aspergilloma, but it is sometimes not sufficient to guarantee the complete removal of the fungus ball. In such cases a mini-trephination of the frontal sinus with associated irrigation provides a more accurate visualization and toilette of the sinus.

[Cranioencephalic complications of bacterial sinusitis in children and adolescents: eight cases in Libreville (Gabon)]. / Complications cranioencéphaliques des sinusites bactériennes chez l'enfant et l'adolescent: étude de huit cas vus à Libreville (Gabon).

OBJECTIVE: To review the pathologic, diagnostic and therapeutic aspects of the cranioencephalic complications of bacterial sinusitis. MATERIAL AND METHODS: This retrospective study included children who underwent diagnostic imaging at the Omar Bongo Ondimba military hospital between January 2006 and December 2010 and treatment of cranioencephalic complications of sinusitis. RESULTS: During the study period, 58 children were hospitalized with sinusitis, and eight (13.8%) had cranioencephalic complications for an annual incidence of 1.6% and a sex ratio of 5 boys to 3 girls. Their mean age was 13 years. Symptoms developed over a mean duration of 14 days (range: 3-45 days). The clinical picture was dominated by febrile headaches and neurologic signs. Palpation of the sinus pressure points was painful in all cases. Disorders of consciousness were found in five cases, with a mean Glasgow score of 9 (range: 7-13). Seven children had multifocal sinusitis and one frontal sinusitis. Five children had a subdural empyema, two associated with thrombophlebitis of the sagittal sinus, one with a brain abscess with thrombophlebitis of the sagittal sinus, and another with meningitis and thrombophlebitis of the sagittal sinus. Two children had osteomyelitis of the frontal sinus table, including a frontal lobe abscess for one. Another had multiple cerebral abscesses. Five children had sinus and neurosurgical drainage, two sinus drainage only, and one neurosurgical drainage only. Microbiology was positive for microbes in four cases: Streptococcus eqinus (one case), Staphylococcus aureus (one case), both S. pneumoniae and Haemophilus influenzae (one case), and Aerococcus viridans (one case). Outcome was favourable in seven cases, including four without sequelae. Two children had recurrences, and one died. CONCLUSION: Diagnosis of the cranioencephalic complications of sinusitis rely on medical imagery. Early multidisciplinary therapeutic management is essential.

A sheep model to investigate the role of fungal biofilms in sinusitis: fungal and bacterial synergy.

BACKGROUND: The role of fungi in the spectrum of chronic rhinosinusitis (CRS) is poorly understood. Fungal biofilms have recently been discovered in CRS patients. We have developed an animal model for the investigation of sinonasal fungal biofilms. The role of type I hypersensitivity and pathogenic bacteria is presented. METHODS: Thirty sheep were sensitized with fungal antigens-Aspergillus fumigatus and Alternaria alternata, or control. Endoscopic surgery was performed to expose both frontal sinus ostia-1 was occluded. Fungi with or without Staphylococcus aureus were inoculated into the sinus. Skin-prick tests assessed for fungal allergy. Fungal and S. aureus biofilms, histology, and culture rates were assessed. RESULTS: Forty-five percent of experimental sheep were sensitized to fungal antigen. Only 1 sinus inoculated with fungus developed minimal fungal biofilm. Eighty percent developed fungal biofilm when S. aureus was co-inoculated. The presence of hypersensitivity to fungus was not related to fungal biofilm development. CONCLUSION: Significant fungal biofilm only occurred when S. aureus was the co-inoculum. Hypersensitivity was not requisite. The relationship of S. aureus to fungal biofilms is of great clinical interest. Fungi may be opportunistic pathogens that simply require inflamed mucosa with weakened innate defenses; alternatively, a cross-kingdom synergy could be contributing to fungal proliferation.

Sinonasal tumor in 3 dogs after successful topical treatment for frontal sinus aspergillosis.

Three dogs diagnosed with aspergillosis developed sinonasal tumors several months after successful treatment with topical clotrimazole solution. Chronic rhinosinusitis was also detected in all cases prior to diagnosis of sinonasal tumors. The inflammatory response to Aspergillus, clotrimazole treatment, and chronic inflammation after treatment are discussed as possible neoplastic promoting factors.

Isolated frontal sinus aspergillosis treated by endoscopic modified Lothrop procedure.

Aspergillosis is a common fungal infection of the paranasal sinuses. Isolated frontal sinus aspergillosis is extremely rare, with only three cases reported in the literature. We report a case of isolated frontal sinus aspergillosis that was accompanied by a contralateral frontal sinus cyst enclosed osseously. The patient was treated successfully by an endoscopic modified Lothrop procedure that permitted complete removal of the fungus ball and wide opening of the frontal sinus. The patient is without evidence of disease 18 months after surgery.

Fine needle aspiration in aspergilloma of frontal sinus: a case report.

BACKGROUND: The increased incidence of fungal diseases in humans is most likely due to indiscriminate use of broad-spectrum antibiotics and increased numbers of immunocompromised patients. Although Aspergillus species are ubiquitous and normally nonpathogenic, they can be opportunistic pathogens in immunocompromised individuals. CASE: A 22-year-old immunocompetent man presented with a gradually increasing subcutaneous swelling near the root of his nose for previous 6 months. The mass was soft to firm, solid, nontender and immobile. There was no superficial skin ulceration and no local signs of inflammation. Proptosis of the left eye was present without any visual impairment. An osteolytic lesion that was contiguous with the subcutaneous mass, with the opacities of both the fontal sinuses was observed radiographically. Fine needle aspiration cytology (FNAC) demonstrated presence of branching hyphae in the cytoplasm of multinucleated giant cells along with mixed inflammatory cells. The species was identified by culture in Sabouraud's agar with chloramphenicol and wet mount with lactophenol cotton blue stain. CONCLUSION: Aspergillosis can remain dormant over a long period. Although uncommon, it can occur in immunocompetent patients. FNA is a very useful tool in establishing the diagnosis