Fadda GL, Allevi F, Rosso C, Martino F, Pipolo C, Cavallo G, Felisati G, Saibene AM.
Treatment of Paranasal Sinus Fungus Ball: A Systematic Review and Meta-Analysis.
Ann Otol Rhinol Laryngol. 2021 Nov;130(11):1302-1310. doi: 10.1177/00034894211002431. Epub 2021 Mar 18.
Abstract/Text
OBJECTIVES: Paranasal sinus fungus ball is a common non-invasive mycosis with excellent long-term surgical treatment results. The present systematic review and meta-analysis were undertaken to define current treatment concepts and success rates in paranasal sinus fungus ball treatment.
METHODS: Systematic searches were performed in multiple databases with criteria designed to include all studies published until May 2020 focusing on paranasal sinuses fungus ball treatment in humans. We selected studies including at least 10 patients, specifying treatment modalities, providing a minimum 6-month follow-up, and objectivating treatment success. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for treatment modalities and success rates. Success rates were pooled in a random effect meta-analysis and compared according to the use of intraoperative sinus lavages and postoperative antibiotics.
RESULTS: Among 740 unique citations, 14 studies were deemed eligible. Most (n = 11) were retrospective case series. All studies relied on endoscopic sinus surgery. Intraoperative lavages were proposed in 10 studies and postoperative antibiotics in 7 (for all patients in 5 studies and for selected patients in 2). No significant heterogeneity was observed between results (Cochran's Q P = .639, I2 test = 0). Treatment success rate was 98.4% (95% confidence interval 97.4%-99.3%). Intraoperative sinus toilette and postoperative antibiotics didn't significantly improve the success rate.
CONCLUSION: Endoscopic sinus surgery shows excellent results in fungus ball treatment. Further prospective studies might help further reducing antibiotics prescriptions in these patients and improve their management.
市村恵一：耳鼻咽喉科領域真菌症の変遷. 特集：耳鼻咽喉科の真菌症―診断と治療―. Monthly Book ENTONI 2003;21: 1-8.
吉川 衛: 副鼻腔真菌症の診断と治療. 日耳鼻 2015;118:629-635.
Ueno R, Nishimura S, Fujimoto G, Ainiwaer D.
The disease burden of mucormycosis in Japan: results from a systematic literature review and retrospective database study.
Curr Med Res Opin. 2021 Feb;37(2):253-260. doi: 10.1080/03007995.2020.1846510. Epub 2020 Nov 18.
Abstract/Text
OBJECTIVE: To evaluate outcomes, healthcare resource utilization, and costs associated with mucormycosis in inpatient settings in Japan.
METHODS: We performed a systematic literature review, followed by a retrospective database study using hospital health claims for patients in Japan hospitalized with a diagnosis of mucormycosis between January 2010 and January 2019. Outcomes assessed included duration of index hospitalization; index stay mortality; hospital readmission within 30, 60, and 90 days after index hospitalization discharge; drug/treatment utilization and patterns; number of patients examined for mucormycosis during the index hospitalization; and index stay inpatient costs.
RESULTS: From our systematic literature review of articles describing 133 patients with mucormycosis, mortality in the index hospitalization was 55.6%. From our database study of 126 patients hospitalized for mucormycosis, mortality during the index hospitalization was 35.7% and mean index stay duration was 94 days. Hematologic malignancies were the most common risk factor in the literature review and the most common comorbidity in the database study. During the index stay, 39 patients (31.0%) received liposomal amphotericin B (L-AMB) treatment and 74 patients (58.7%) received other antifungal treatments. Median total inpatient costs for the index hospitalization were equivalent to approximately US$60,945, including US$29,283 in drug costs.
CONCLUSIONS: This study investigated the healthcare resource utilization and cost of medical resources caused by mucormycosis in Japan. The drug costs for antifungal treatments comprised about half of total inpatient costs. Mucormycosis leads to high mortality, high healthcare resource utilization, and high costs.
竹野幸夫, 宮原伸之: 真菌症. 特集主題：耳鼻咽喉科外来 薬の選び方・使い方・投与期間. Monthly Book ENTONI 2009;100: 147-154.
Vaughan C, Bartolo A, Vallabh N, Leong SC.
A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years?
Clin Otolaryngol. 2018 Dec;43(6):1454-1464. doi: 10.1111/coa.13175. Epub 2018 Aug 8.
Abstract/Text
BACKGROUND: Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet potentially lethal fungal infection. Although most cases originate from developing countries, an ageing population and increased prevalence of chronic illness may mean some clinicians practicing in developed countries will encounter ROCM cases in their careers. Yohai et al published a systematic review of 145 case reports from 1970 to 1993 assessing prognostic factors for patients presenting with ROCM. We present an updated review of the literature and assess whether survival outcomes have changed in the two decades since that seminal paper.
SEARCH STRATEGY: An extensive Medline literature search was performed for case reports published between 1994 and 2015.
RESULTS: In total, 210 published cases were identified from the literature review, of which 175 patients from 140 papers were included in this review. Fifty-five were female, with an overall mean age of 43 years. Overall survival rate was 59.5%, which was not significantly better than the previous series reported (60%) reported by Yohai et al. Survival rates in patients with chronic renal disease had improved, from 19% to 52%, and in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia remained poor prognostic indicators (33% and 39% survival rates, respectively). Early commencement of medical treatment related to better survival outcomes (61% if commenced within first 12 days of presentation, compared to 33% if after 13 days). Timing of surgery had less of an effect on overall survival. However, in 28 cases that did not receive any surgical treatment, survival was only 21%.
CONCLUSIONS: Although overall survival rates have not improved, survival in patients with renal disease were better, potentially due to the introduction of liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM, reversal of predisposing co-morbidities and aggressive medical treatment remain the cornerstone of managing this highly aggressive disease.
© 2018 John Wiley & Sons Ltd.
Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF; Infectious Diseases Society of America.
Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America.
Clin Infect Dis. 2008 Feb 1;46(3):327-60. doi: 10.1086/525258.
Abstract/Text
Denning DW, Lee JY, Hostetler JS, Pappas P, Kauffman CA, Dewsnup DH, Galgiani JN, Graybill JR, Sugar AM, Catanzaro A.
NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis.
Am J Med. 1994 Aug;97(2):135-44. doi: 10.1016/0002-9343(94)90023-x.
Abstract/Text
BACKGROUND: Invasive aspergillosis is the most common invasive mould infection and a major cause of mortality in immunocompromised patients. Response to amphotericin B, the only antifungal agent licensed in the United States for the treatment of aspergillosis, is suboptimal.
METHODS: A multicenter open study with strict entry criteria for invasive aspergillosis evaluated oral itraconazole (600 mg/d for 4 days followed by 400 mg/d) in patients with various underlying conditions. Response was based on clinical and radiologic criteria plus microbiology, histopathology, and autopsy data. Responses were categorized as complete, partial, or stable. Failure was categorized as an itraconazole failure or overall failure.
RESULTS: Our study population consisted of 76 evaluable patients. Therapy duration varied from 0.3 to 97 weeks (median 46). At the end of treatment, 30 (39%) patients had a complete or partial response, and 3 (4%) had a stable response, and in 20 patients (26%), the protocol therapy was discontinued early (at 0.6 to 54.3 weeks) because of a worsening clinical course or death due to aspergillosis (itraconazole failure). Twenty-three (30%) patients withdrew for other reasons including possible toxicity (7%) and death due to another cause but without resolution of aspergillosis (20%). Itraconazole failure rates varied widely according to site of disease and underlying disease group: 14% for pulmonary and tracheobronchial disease, 50% for sinus disease, 63% for central nervous system disease, and 44% for other sites; 7% in solid organ transplant, 29% in allogeneic bone marrow transplant patients, and 14% in those with prolonged granulocytopenia (median 19 days), 44% in AIDS patients, and 32% in other host groups. The relapse rates among those who completed therapy and those who discontinued early for possible toxicity were 12% and 40%, respectively; all were still immunosuppressed.
CONCLUSION: Oral itraconazole is a useful alternative therapy for invasive aspergillosis with response rates apparently comparable to amphotericin B. Relapse in immunocompromised patients may be a problem. Controlled trials are necessary to fully assess the role of itraconazole in the treatment of invasive aspergillosis.
成尾一彦、阪上剛、山下哲範、蓮川昭仁、北原糺：良好な経過を辿った浸潤型副鼻腔真菌症例。日鼻誌 58(2): 209-219, 2019.
Nyunt TPK, Mullol J, Snidvongs K.
Predictive factors for invasive fungal rhinosinusitis in diabetic patients: Systematic review and data re-analysis.
Asian Pac J Allergy Immunol. 2021 Mar;39(1):1-8. doi: 10.12932/AP-250720-0929.
Abstract/Text
This systematic review aims to identify prognostic factors for the overall survival of invasive fungal rhinosinusitis (IFRS) in patients with diabetes using original data from the existing published articles. Systematic searches of Medline, EMBASE, and Cochrane Library databases were performed to include articles from 1988 to 2019 using the terms: "fung*" AND "rhinosinusitis" AND "invasive" AND "diabetes OR ketoacidosis". Data from 258 diabetic patients with IFRS (mean age 55.9 years, 55.6% male, 124 studies) were extracted for data analysis. The mortality rate was 31.8%. Seven variables: plasma glucose level, HbA1C, ketoacidosis, leukopenia, serum creatinine level, duration of diabetes, and the cavernous sinus extension were assessed. Univariate analysis was done for each variable and revealed that the cavernous sinus extension was a significant risk factor. Multivariable logistic regression analysis confirmed that the cavernous sinus extension independently predicted mortality in patients with diabetes (hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.2 to 5.4, p = 0.01). Kaplan Meier curve and Log-rank test were used for analyzing survival outcomes. The twelve-month overall survival rate of the patients with the cavernous sinus extension was 43.9% compared to 73.9% for the patients without the cavernous sinus extension (p = 0.01). Appropriate treatment of this condition could enhance the survival outcomes.
Dufour X, Kauffmann-Lacroix C, Ferrie JC, Goujon JM, Rodier MH, Karkas A, Klossek JM.
Paranasal sinus fungus ball and surgery: a review of 175 cases.
Rhinology. 2005 Mar;43(1):34-9.
Abstract/Text
OBJECTIVE: To analyze the surgical results after Functional Endoscopic Sinus Surgery (FESS) in patients with paranasal sinus fungus ball.
MATERIAL AND METHODS: Retrospective analysis of the results of FESS performed in 175 patients suffering from paranasal sinus fungus balls.
RESULTS: All maxillary (n = 150), sphenoidal (n = 20), and ethmoidal (n = 4) locations have been treated exclusively by FESS to obtain a wide opening of the affected sinuses, allowing a careful extraction of all fungal material without removal of the inflamed mucous membrane. No major complication occurred. Postoperative care was reduced to nasal lavage with topical steroids for 3 to 6 weeks. Only 1 case of local failure have been observed (maxillary sinus, n = 1), and 6 cases of persisting of fungus ball (maxillary sinus, n = 4; frontal sinus, n = 2) with a mean follow-up of 5 years. No medical treatment (antibiotic, antifungal) was required.
CONCLUSION: Surgical treatment of a fungus ball consists in opening the infected sinus cavity at the level of its ostium and removing fungal concretions while sparing the normal mucosa. No antifungal therapy is required. Finally, through this 175 patients study, FESS appears a reliable and safe surgical treatment with a low morbidity.
深在性真菌症のガイドライン作成委員会: 深在性真菌症の診断・治療ガイドライン 2014. 協和企画 , 東京 ; 2014: p.88-90.
