Systemic Antifungal Medications Research Articles

P172 An integrated safety analysis of treatment-emergent fungal infections in patients with psoriasis, psoriatic arthritis, or axial spondyloarthritis treated with ixekizumab from 26 clinical studies

Abstract Background/Aims Interleukin (IL)-17 plays a role in host defense against common extracellular pathogens, including fungi. Treatment with IL-17 inhibitors has been associated with fungal infections. Ixekizumab (IXE) is an anti-IL-17A monoclonal antibody approved for the treatment of psoriasis (PsO) in adults and children, psoriatic arthritis (PsA) in adults, and axial spondyloarthritis (axSpA) in adults. This integrated post-hoc analysis investigates treatment-emergent fungal infections in IXE-treated patients across the approved indications. Methods Safety data on fungal infections were pooled from the IXE paediatric and adult clinical trial programs, comprising 26 clinical studies. Here, we describe the types of fungal infections, number of infections, recurrence (defined by at least two separate events irrespective of location), severity (defined at the investigator’s discretion), events that lead to discontinuation, and anti-fungal medications. Data are presented as frequency or incidence rate per 100 person-years (IR). Results Fungal infections were reported in patients with PsO (IR = 4.0), PsA (IR = 4.1), and axSpA (IR = 2.7). Across indications, most fungal infections were not recurrent and were classified as mild or moderate in severity. There were few severe fungal infections in patients with PsO (IR = 0.1), PsA (IR = 0.0), and axSpA (IR = 0.0). Most fungal infections in patients with PsO, PsA, and axSpA were candidiasis (IR = 1.9, IR = 2.5, IR = 1.4, respectively) and superficial dermatophytosis (IR = 1.5, IR = 1.0, IR = 1.0, respectively). No cases of subcutaneous and systemic mycosis infections were reported. The proportions of patients with PsO, PsA, and axSpA who received a topical vs systemic anti-fungal medication were 53.6% vs 1.1%, 47.8% vs 0.0%, and 45.6% vs 3.5%, respectively (Table 1). Most fungal infections did not lead to discontinuation of IXE (Table 1). Conclusion Consistent with previously disclosed IXE data, the majority of treatment-emergent fungal infections observed in patients with PsO, PsA, or axSpA treated with IXE were: (i) not recurrent; (ii) mild or moderate in severity, (iii) associated with candidiasis and superficial dermatophytosis, (iv) managed with topical anti-fungal medications or no treatment reported, and (v) not leading to drug discontinuation. Disclosure S. Schwartzman: Corporate appointments; SS reports being a board member of the National Psoriasis Foundation. Consultancies; S. Schwartzman has served as a speaker and/or consultant for AbbVie, Janssen, Eli Lilly and Company, Pfizer, UCB, Myriad, Novartis, Regeneron, Sanofi, Stelexis, Jubilant, Teijin. L. Puig: Corporate appointments; Board member of the International Psoriasis Council. Consultancies; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sandoz, Sanofi, UCB. Honoraria; Boehringer Ingelheim, Janssen, Eli Lilly and Company, Novartis, UCB, travel support from Janssen, Eli Lilly and Company, Pfizer, UCB. Grants/research support; L. Puig reports receiving grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sanofi, UCB. A.D. Cohen: Honoraria; AbbVie, Amgen, Boehringer Ingelheim, Dexcel Pharma; Janssen, Eli Lilly and Company, Neopharm, Novartis, Perrigo, Pfizer, Rafa. Grants/research support; A. D. Cohen has served on advisory board for Samsung, and reports receiving grants from AbbVie, Janssen, Novartis, Pfizer, travel support from AbbVie. S. Khattri: Consultancies; S. Khattri reports being part of Eli Lilly and Company speaker’s bureau, receiving consulting fees and honoraria from Eli Lilly and Company, AbbVie, UCB, Janssen, BI, Regeneron, Leo Pharma. C. Jossart: Shareholder/stock ownership; C. Jossart is a stockholder of Eli Lilly and Company and was an employee of Eli Lilly and Company when this study was conducted. C. Diaz: Shareholder/stock ownership; C. Diaz is employee and stockholder of Eli Lilly and Company. A. Garrelts: Shareholder/stock ownership; A. Garrelts is employee and stockholder of Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; D. Zhu is employee and stockholder of Eli Lilly and Company. N. Eberhart: Shareholder/stock ownership; N. Eberhart is employee and stockholder of Eli Lilly and Company. A. Eleftheriadi: Shareholder/stock ownership; A. Eleftheriadi is employee and stockholder of Eli Lilly and Company. N. Tangsirisap: Shareholder/stock ownership; N. Tangsirisap is employee and stockholder of Eli Lilly and Company. C. Schuster: Shareholder/stock ownership; C. Schuster is an employee and stockholder of Eli Lilly and Company. A.B. Gottlieb: Consultancies; Xbiotech (stock options for an RA project). Honoraria; Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapuetics, Dermavant, Lilly, Janssen, Leo, Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma. Grants/research support; AnaptysBio, Moonlake Immunotherapeutics, Novartis, BMS, and UCB Pharma; all funds go to the Icahn School of Medicine at Mount Sinai. M. Sheesh: Shareholder/stock ownership; MS is a full-time employee and minor share holder of Eli-Lilly and Company.

Common Oral Conditions: A Review.

Dry mouth, oral candidiasis, and recurrent aphthous ulcers are 3 of the most common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. In a meta-analysis of 26 population-based cohort and cross-sectional studies, the global prevalence of dry mouth symptoms was 23% (95% CI, 18% to 28%), placing individuals at risk of oral candidiasis, dental caries, dysgeusia, masticatory/speech impairment, and oropharyngeal dysphagia. Dry mouth is associated with using more than 3 oral medications per day (odds ratio [OR], 2.9 [95% CI, 1.4 to 6.2]), head and neck radiation, and Sjögren disease. Symptoms may include difficulty swallowing and speaking, thirst, and halitosis. Dry mouth is associated with an 11.5% (95% CI, 3.6% to 27%) higher risk of oral candidiasis, based on a meta-analysis of 6 observational cohorts. Management of dry mouth includes mechanical salivary stimulants, oral moisturizers, and/or systemic sialagogues. Oral candidiasis is an opportunistic fungal infection caused by overgrowth of the Candida genus with C albicans, which accounts for 76.8% of infections. The prevalence of oral candidiasis is higher in patients who are immunosuppressed, for example, those with HIV (35% [95% CI, 28% to 42%]) and those with salivary gland hypofunction (OR, 3.02 [95% CI, 1.73 to 5.28]). Common risk factors associated with oral candidiasis include use of antibiotics (P = .04) and oral mucosal disorders such as lichen planus. Oral burning and dysgeusia are common symptoms of oral candidiasis. Treatment includes addressing risk factors and use of topical and/or systemic antifungal medications. Recurrent aphthous stomatitis is characterized by symptomatic round or oval oral ulcers, which are covered by a gray-white fibrin layer and encircled by an erythematous ring. A meta-analysis of 10 case-controlled studies revealed an increased risk of recurrent aphthous stomatitis associated with polymorphism of IL-1β (+3954C/T) (OR, 1.52 [95% CI, 1.07 to 2.17]) and IL-1β (-511C/T) (OR, 1.35 [95% CI, 1.09 to 1.67]). Another meta-analysis of 9 case-control studies reported that patients with recurrent aphthous stomatitis had a higher frequency of nutritional deficiencies, including vitamin B12 (OR, 3.75 [95% CI, 2.38 to 5.94]), folic acid (OR, 7.55 [95% CI, 3.91 to 14.60]), and ferritin (OR, 2.62 [95% CI, 1.69 to 4.06]). Recurrent aphthous stomatitis can be associated with systemic diseases. A meta-analysis of 21 case-control studies revealed that celiac disease is associated with a higher incidence of recurrent aphthous stomatitis (25% vs 11%; OR, 3.79 [95% CI, 2.67 to 5.39]; P <.001). Topical corticosteroids are first-line agents to manage recurrent aphthous stomatitis; however, systemic medications may be necessary in more severe cases. Dry mouth, oral candidiasis, and recurrent aphthous ulcers are common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. First-line treatment includes over-the-counter sialagogues for dry mouth, topical antifungals for oral candidiasis, and topical corticosteroids for aphthous ulcers. Oral conditions that do not improve with first-line treatment may require treatment with systemic medications.

Expert consensus on diagnosis and treatment of severe COVID-19 associated pulmonary aspergillosis and mucormycosis

The incidence and mortality of COVID-19 associated pulmonary aspergillosis (CAPA) are high in critically ill patients. Although COVID-19 associated mucormycosis (CAPM) is relatively rare, its severity and often a delayed diagnosis or misdiagnosis lead to its high mortality. The diagnosis and treatment of CAPA and CAPM in critically ill patients are challenging. Early diagnosis and a standardized therapy are the two most important factors for a good outcome. Therefore, a working group of experts from Chinese Thoracic Society and Chinese Association of Chest Physicians Critical Care Group was organized to develop this consensus based on the current medical evidence and clinical practice, in order to improve the ability of clinical treatment for critically ill patients with CAPA and CAPM. The working group drafted a preliminary text based on the literature and clinical practice experience. Following two rounds of discussion, 16 final recommendations were made, with the recommendation strength divided into recommend, suggest and not recommend.-Utilization of chest images and bronchoscopy1. Chest CT, rather than chest X-ray, is recommended for possible CAPA or CAPM patients to provide diagnostic evidence and localization for bronchoscopy to obtain microbiological specimens. A diagnosis of CAPA could not be made on the basis of positive signs on chest CT alone. Chest contrast CT or pulmonary artery CT (CTPA) is recommended in patients with probable CAPM.2. In the case of possible CAPA or CAPM, it is recommended that bronchoscopy and BALF collection for microbiological examinations be pereformed as soon as possible.-The selection strategies of microbiological examinations3. Microscopic examination, culture, GM testing and PCR for aspergillus Spp. of BALF are recommended in patients with probable CAPA. Fungal staining and culture of BALF are suggested for possible CAPM. Selected appropriate specimens for molecular biological detection are suggested in critically ill patients and possible CAPM.-Diagnostic critieria4. The revised ECMM/ISHAM consensus statement is recommended as the diagnostic criteria for CAPA and the Delphi consensus statement is recommended as the diagnostic criteria for CAPM.-Appropriate time for antifungal therapy5. Prophylactic therapy of CAPA with amphotericin B or its liposomes is suggested for patients with severe COVID-19, especially those with risk factors for CAPA.6. It is recommended to start the empirical anti-Aspergillus therapy as soon as possible for possible CAPA, and obtain the microbiological evidence for aspergillosis at the same time.7. Prophylactic therapy for CAPM is not recommended for severe COVID-19 patients.8. Early initiation of empirical therapy for possible CAPM is recommended, and microbiological evidence should be obtained at the same time.-Clinical applications for antifungal agents9.Voriconazole or isavuconazole are recommended as initial treatment for CAPA. Amphotericin B liposomes are suggested as the initial treatment for CAPM. Isavuconazole or posaconazole may be an option in patients with renal insufficiency or amphotericin B liposome intolerance/unavailability.10. In CAPA patients with tracheobronchitis, antifungal drug inhalation is recommended in addition to systemic antifungal medication.11. Combination therapy is not recommended as initial therapy for CAPA, but may be used as a salvage therapy strategy. Triazole or amphotericin B in combination with caspofungin or micafungin is recommended; whereas amphotericin B in combination with triazole is not recommended. For CAPM patients with extensive lesions, rapid progression or poor general condition, a combination of amphotericin B liposome with isavuconazole or posaconazole is suggested.-Response assessment and treatment duration12. It is recommended that treatment response be assessed comprehensively according to the clinical symptoms/signs, imaging and microbiological examination of patients. CAPA can be evaluated in combination with the dynamic change in serum GM.13. The recommended treatment duration of CAPA is at least 6-12 weeks. A total course of at least 3-6 months is suggested for CAPM, and the sequential treatment should be considered according to the response to 4-6 weeks of intravenous therapy.-How to adjust the anti-inflammatory therapy14. In patients with severe COVID-19 combined with possible or probable filamentous fungal infection, it is suggested that of anti-inflammatory therapy be stopped or reduced appropriately, taking into account of the severity of the infection and inflammation of the disease course. The combination of baritinib and/or tozzizumab based on glucocorticoids is not suggested in these patients.-How to treat the underlying diseases15. In patients with diabetes, strict glycaemic control is suggested. In patients with long-term use of glucocorticoids and/or immunosuppressants, it is suggested to reduce the intensity of immunosuppression. Granulocyte colony-stimulating factor is suggested to use to improve the circulating granulocyte levels in patients with granulocyte deficiency due to various causes.-When an operation should be considered16. In patients with CAPA, surgery is not recommended unless large blood vessels, pericardium, or chest wall are involved, or the patient has recurrent or massive hemoptysis. For CAPM patients, early surgical removal of lesions after diagnosis is recommended. Surgery is a high-risk procedure in patients with severe COVID-19, and a multidisciplinary team discuss is suggested.

Validation of diagnoses of liver disorders in users of systemic azole antifungal medication in Sweden

BackgroundLiver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment.MethodsData from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group.ResultsAmong the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4–73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4–74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3–99.9%).ConclusionAmong patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.

CHRONIC HYPERPLASTIC CANDIDIASIS AS A RARE ADVERSE EVENT OF SECUKINUMAB THERAPY

Secukinumab is an anti-IL-17A monoclonal antibody used for the treatment of psoriasis, a frequent chronic inflammatory skin disease. However, IL-17 is essential in immunity against oral opportunistic fungal pathogens; therefore, oral candidiasis can occur in patients treated with this drug, although adverse oral events are not widely described. A 72-year-old male patient with arthritis psoriasis managed with Secukinumab 300 mg once a month, for 90 days, presented a burning white plaque on the mid dorsal posterior tongue. Fungal culture was performed and a diagnosis of oral candidiasis was established. Systemic and topical antifungal medication led to regression of the lesion and burning sensation resolution. No symptoms or recurrence of the lesion were observed after six months of follow up. This case highlighted the importance of monitoring patients who are under treatment with IL-17 blockers due to the risk of opportunistic infections. Secukinumab is an anti-IL-17A monoclonal antibody used for the treatment of psoriasis, a frequent chronic inflammatory skin disease. However, IL-17 is essential in immunity against oral opportunistic fungal pathogens; therefore, oral candidiasis can occur in patients treated with this drug, although adverse oral events are not widely described. A 72-year-old male patient with arthritis psoriasis managed with Secukinumab 300 mg once a month, for 90 days, presented a burning white plaque on the mid dorsal posterior tongue. Fungal culture was performed and a diagnosis of oral candidiasis was established. Systemic and topical antifungal medication led to regression of the lesion and burning sensation resolution. No symptoms or recurrence of the lesion were observed after six months of follow up. This case highlighted the importance of monitoring patients who are under treatment with IL-17 blockers due to the risk of opportunistic infections.

Antifungal Stewardship Programs in Children: Challenges and Opportunities.

Antifungal Stewardship Programs in Children: Challenges and Opportunities.

Biofilm: The invisible culprit in catheter-induced candidemia.

Candidemia is the most common form of invasive fungal infection associated with several risk factors, and one of them is the use of medical devices, to which microbial biofilms can attach. Candidemia related to the use of peripheral intravascular and central venous catheters (CVC) is referred to as Candida catheter-related bloodstream infection, with more than 90% being related to CVC usage. The infection is associated with a higher morbidity and mortality rate than nosocomial bacterial infections. Candida spp. can protect themselves from the host immune system and antifungal drugs because of the biofilm structure, which is potentiated by the extracellular matrix (ECM). Candida albicans and Candida parapsilosis are the most pathogenic species often found to form biofilms associated with catheter usage. Biofilm formation of C. albicans includes four mechanisms: attachment, morphogenesis, maturation and dispersion. The biofilms formed between C. albicans and non-albicans spp. differ in ECM structure and composition and are associated with the persistence of colonization to infection for various catheter materials and antifungal resistance. Efforts to combat Candida spp. biofilm formation on catheters are still challenging because not all patients, especially those who are critically ill, can be recommended for catheter removal; also to be considered are the characteristics of the biofilm itself, which readily colonizes the permanent medical devices used. The limited choice and increasing systemic antifungal resistance also make treating it more difficult. Hence, alternative strategies have been developed to manage Candida biofilm. Current options for prevention or therapy in combination with systemic antifungal medications include lock therapy, catheter coating, natural peptide products and photodynamic inactivation.

483. Use of Terbinafine in Combination with Other Systemic Anti-fungal Agents As Treatment for Invasive Mold Infections. Experience from A National Cancer Institute Designated Cancer Center.

Abstract Background The severely Immunocompromised are at an increased risk of fatal infection caused by invasive molds. Amphotericin B and triazole agents with anti-mold activity are commonly used in treating invasive mold infections. There is some data from in-vitro experiments to suggest an enhanced killing of some molds when terbinafine is used in combination with certain azoles or amphotericin B. At our center, terbinafine is occasionally used in combination with other systemic anti-fungal agents in treating severely immunocompromised patients with invasive mold infections. Methods The study was a retrospective review of electronic medical records. Sixty-four patients treated for culture confirmed infection with mold isolates at the Moffitt Cancer Center from 1/1/2015 to 6/1/2021 were included in this study. There were 2 treatment groups: Group A comprised of those treated with a terbinafine containing regimen and Group B comprised of patients that were not treated with a terbinafine containing regimen. Results Treatment group A: Comprised of 14 patients. Twenty-nine percent (4/14) had skin/soft tissue infections, 21% (3/14) had rhinosinusitis, 21% (3/14) had pulmonary infections and 4 patients (29%) had disseminated infection. Thirty-six percent (5/14) were discharged with treatment response, 57% (8/14) did not respond to treatment or died due to the invasive mold infection and 7% (1/14) died as a result of malignancy. Treatment group B: Had 50 patients. thirty-eight percent (19/50) had pulmonary infections, 28% (14/50) with skin/soft tissue infections, 16% (8/50) had rhinosinusitis, 2% (1/50) were diagnosed with central nervous system infection, 2% (1/50) had gastrointestinal infection, 14% (7/50) had an unclear source of infection. Forty-eight percent (24/50) were discharged with treatment response, 42% (21/50) had treatment failure or died due to the invasive mold infection and 10% (5/50) died as a result of malignancy. Table 1Figure 1 Conclusion There was no statistically significant improvement in outcome observed in this study when terbinafine was used in addition to other systemic anti-fungal medications as treatment of invasive mold infections. There is a need for larger studies to determine if terbinafine has a role in the treatment of invasive mold infections. Disclosures All Authors: No reported disclosures.

Prescribing patterns of systemic antifungal medications in Indian patients with invasive fungal infections: a multicenter retrospective study

Background: Objectives of the study was to describe the utilization pattern of systemic antifungal agents in Indian patients with invasive fungal infections (IFIs).Methods: This real-world, multicenter (127 centers), retrospective analysis included data of patients receiving systemic antifungal medications at various centers across India. The study data was collected between April 2021 and March 2022.Results: Data of a total of 323 patients was analyzed. The mean age of patients was 54±13.52 years. There was male preponderance seen in this study (72.4%). Diabetes was the most common comorbidity (36.8%) followed by concomitant diabetes and hypertension (31.9%), hypertension (9.6%) and hematological malignancies (9.6%). The most common indication occurring in &gt;10% of the patients and for whom systemic antifungals were used included pulmonary mucormycosis (33.1%) followed by invasive candidiasis (16.1%), sepsis (13.3%) and fungal pneumonia (11.8%). In total 323 patients, the most common antifungal drug prescribed was posaconazole (38.6%) followed by anidulafungin (32.8%), caspofungin (10.5%), fluconazole (9.3%) and micafungin (8.7%). Posaconazole was most commonly used for pulmonary mucormycosis (84.8%), fluconazole for sepsis (33.3%), caspofungin for fungal pneumonia (23.5%) and anidulafungin (33.1%), and micafungin (39.3%) for invasive candidiasis.Conclusions: This study provides real-world evidence on the demographics of Indian patients with IFIs and utilization pattern of systemic antifungals by health care physicians in clinical practice.

Recurrent, bilateral endogenous Candida endophthalmitis with multiple focal chorioretinal lesions: management with pars plana vitrectomy and focal endolaser

PurposeBilateral endogenous Candida endophthalmitis (ECE) treatment usually involves administering systemic and intravitreal antifungal medications. In advanced cases with vitreous seeding, pars plana vitrectomy (PPV) is considered. The use of focal endolaser treatment to chorioretinal lesions has not been reported. We present a case of bilateral recurrent ECE treated with PPV and endolaser to elevated focal lesions.CaseA 45-year-old diabetic male presented with decreased visual acuity in both eyes (20/50 right eye, 20/150 left eye) and was found to have bilateral ECE with moderate vitritis and chorioretinal lesions. The initial treatment consisted of multiple intravitreal voriconazole injections to both eyes as well as systemic antifungal therapy. Resolution of ECE occurred after three months, but one year later despite therapy recurred bilaterally. Patient underwent PPV with endolaser to the elevated chorioretinal lesions in both eyes. One year later, his vision improved to 20/40 in both eyes, focal lesions were flat and resolved along with the ECE.ConclusionAdvanced or recurrent ECE that is refractive to intravitreal antifungal therapy may be treated with PPV. Endolaser therapy to the chorioretinal lesions is an additional local option that can resolve the activity of ECE.

Studies on the Efficacy of Various Antimycotic Drugs on Emerging and Reemerging, Superficial, Cutaneous and Subcutaneous Mycotic Infections

Introduction: The efficacy of five systemic and topical antifungal medications, Voriconazole, clotrimazol, beclometasone, Itraconazole, and Fluconazole, on dermatomycosis, which affects the superficial layers of the skin, nails, foot, and hair, was tested with 180 patients.&#x0D; Methods: Included were specimen collection, processing, microscopy, and culture, as well as antifungal susceptibility testing using the E-test method. The Candida species were confirmed and their susceptibility to Voriconazole and Fluconazole was tested using the automated Vitek 2.&#x0D; Results: The final strain identification indicated 41 dermatophytes (69.49%), 11 non-dermatophytic molds (NDM) (18.64%), and 7 yeasts (11.87%). (candida). Candida was the most prevalent nondermatophyte species found. Trichophyton rubrum was the most prevalent species isolated in Tinea corporis, T. cruris, T. capitis, and T. faciei. When tested with the E strips, all dermatophyte strains showed the greatest vulnerability to beclometasone and clotrimazole (MIC range of 0.04–0.64), but homogeneous resistance to Fluconazole (i.e. MIC 32 g/ml).&#x0D; Conclusion: Variation in species distribution was shown to be statistically significant (p = 0.001) in terms of clinical presentation.

Curvularia dacryoadenitis and panophthalmitis: case report

Purpose: To examine the clinical course of dacryoadenitis and panophthalmitis from Curvularia infection. Methods: Retrospective case review. The authors reported a case of 36-year-old female who presented with dacryoadenitis and panophthalmitis. Clinical features, investigations and management were described. Results: A 36-year-old female with history of controlled bilateral pars planitis presented with dacryoadenitis and panophthalmitis in the right eye. Her medication at presentation was prednisolone 5 mg/d and mycophenolate mofetil 250 mg/d.&nbsp; She underwent tissue biopsy. The culture yielded Curvularia spp. Topical and systemic anti-fungal medications were given with a good response. Conclusion: Curvularia can be the cause of dacryoadenitis with panophthalmitis in immunocompromised hosts. Keywords: Curvularia, dacryoadenitis, panophthalmitis, fungus

257. Outcomes in Fungal Prosthetic Joint Infection

Abstract Background There is a paucity of data in the literature regarding the most effective treatment and related outcomes of fungal prosthetic joint infection. The majority of reported cases are treated using a two stage revision method in which the initial prosthesis is removed and the patient is treated with systemic antifungal medications and potentially irrigation of the joint cavity with antifungal and antibacterial agents. Alternately, others have suggested a one-stage revision in order to prevent a period of significant functional impairment and potentially improved functional outcomes and lower overall costs. Cases of radical removal of the prosthesis without replacement have been reported. To date, the largest studies of total hip arthroplasty and total knee arthroplasty have included 37 and 45 patients, respectively. Methods A retrospective record review of patients admitted within two health systems between January 1, 2007 and December 31, 2018 with prosthetic joints and a deep culture of the joint positive for fungal organisms was performed. Results Eighteen patients fit criteria. Nine patients had knee replacements and nine patients had hip replacements. The average age at time of infection was 61. Ten patients were female. Average BMI was 32.1. Twelve presented with a painful joint, eight presented with drainage, and one with dehiscence. Average WBC count was 9.3, average ESR was 47, and average CRP was 11.8. All patients were noted with Candida species. Eight patients were treated with two stage revisions, three received one stage revisions as destination therapy. One required amputation. All but one patient was associated with concurrent bacterial infection. Of the twelve patients that had known outcomes, six were noted with cure and six were noted with relapse. All patients that were cured received two stage exchange or girdlestone procedure. Conclusion In our study, fungal prosthetic joint infection was associated with poor outcomes. All of the patients in our study were noted with Candida species, which is in concordance with the known literature. Two stage exchange was associated with better outcomes. Disclosures All Authors: No reported disclosures

Fungal Endophthalmitis: A Comprehensive Review.

Endophthalmitis is a serious ophthalmologic condition involving purulent inflammation of the intraocular spaces. The underlying etiology of infectious endophthalmitis is typically bacterial or fungal. The mechanism of entry into the eye is either exogenous, involving seeding of an infectious source from outside the eye (e.g., trauma or surgical complications), or endogenous, involving transit of an infectious source to the eye via the bloodstream. The most common organism for fungal endophthalmitis is Candida albicans. The most common clinical manifestation of fungal endophthalmitis is vision loss, but other signs of inflammation and infection are frequently present. Fungal endophthalmitis is a clinical diagnosis, which can be supported by vitreous, aqueous, or blood cultures. Treatment involves systemic and intravitreal antifungal medications as well as possible pars plana vitrectomy. In this review, we examine these essential elements of understanding fungal endophthalmitis as a clinically relevant entity, which threatens patients’ vision.

EFFICACY OF HUMAN RECOMBINANT GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF, FILGRASTIM; NEUPOGEN®) IN NEUTROPENIC CETACEANS.

Neutrophils are one of the initial cell lines of protection against pathogens, and when their concentrations in the blood are low, animals are highly susceptible to infections. Neutropenia has been reported in cetaceans secondary to administration of systemic sulfa antibiotics or antifungal medications and severe, overwhelming infection. Filgrastim was administered to treat neutropenia over a 15-y period in 11 cetaceans comprising four species-beluga (Delphinapterus leucas, n = 1), bottlenose dolphin (Tursiops truncatus, n = 4), killer whale (Orcinus orca, n = 5), and short-finned pilot whale (Globicephala macrorhynchus, n = 1)] ranging in age from 1 wk to >24 y. Seven study animals received multiple doses (2-6). All animals responded to at least one dose (1-7 µg/kg) of parenteral filgrastim characterized by an increase in peripheral immature (band) neutrophils, segmented neutrophils, or both. In most cases (9/11), neutrophil counts increased within 48 h of a single dose. Duration of response varied but was at least 2 wk in eight of the 11 animals and 5-9 d in the remaining animals. No adverse reactions were observed in any cases.

Onychomycosis in older adults: The age and associated factors affecting the complete cure rate.

Limited studies exist on the factors associated with a complete cure of onychomycosis in older adults. To determine the age and factors associated with a complete cure among older adults diagnosed with toenail onychomycosis. A retrospective cohort study was conducted of 95 older adult patients (aged ≥ 60 years) diagnosed with toenail onychomycosis between January 2016 and December 2017. Demographic data, mycological findings, treatments and durations to a complete cure were reviewed. The complete cure rates of the patients aged < 70 years and ≥70 years were 67.4% and 44.9%, respectively (P = 0.027). Patients aged ≥ 70 years were significantly higher in male gender, had higher history of smoking, peripheral arterial disease, impaired renal function, antihypertensive drug and amorolfine nail lacquer usage, and polypharmacy. A multivariate analysis revealed that being aged ≥70 years and having a nail thickness >2 mm were associated with failure to achieve a complete cure. The median times to a complete cure for older adults aged <70 years and ≥70 years were 20 months and 47 months, respectively (P = 0.007). An age ≥ 70 years was related to a lower cure rate and delays in achieving a complete cure. A nail thickness > 2 mm was a poor prognostic factor for a complete cure. Moreover, very old adults were more likely to suffer side effects arising from the use of systemic antifungal medications.

27472 Onychomycosis: Patterns of systemic antifungal medication in practice

Background: Onychomycosis (OM) is the most common nail disorder. Though there are treatment guidelines, overall cure rate is not sufficient so that diverse regimens are applied in real-world.

Three-stage revision arthroplasty for the treatment of fungal periprosthetic joint infection: outcome analysis of a novel treatment algorithm : a prospective study.

AimsFungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI.MethodsFrom 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined.ResultsEradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures).ConclusionTherapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results.Cite this article: Bone Jt Open 2021;2(8):671–678.

American Academy of Ophthalmology Recommendations on Screening for Endogenous Candida Endophthalmitis

The American Academy of Ophthalmology evaluated the practice of routine screening for intraocular infection from Candida septicemia. In the United States, ophthalmologists are consulted in the hospital to screen for intraocular infection routinely for patients with Candida bloodstream infections. This practice was established in the era before the use of systemic antifungal medication and the establishment of definitions of ocular disease with candidemia. A recent systematic review found a rate of less than 1% of routinely screened patients with endophthalmitis from Candida septicemia. Other studies found higher rates of endophthalmitis but had limitations in terms of inaccuracies in ocular disease classification, lack of vitreous biopsies, selection biases, and lack of longer-term visual outcomes. Some studies attributed ocular findings to Candida infections, rather than other comorbidities. Studies also have not demonstrated differences in medical management that are modified for eye disease treatment; therefore, therapy should be dictated by the underlying Candida infection, rather than be tailored on the basis of ocular findings. In summary, the Academy does not recommend a routine ophthalmologic consultation after laboratory findings of systemic Candida septicemia, which appears to be a low-value practice. An ophthalmologic consultation is a reasonable practice for a patient with signs or symptoms suggestive of ocular infection regardless of Candida septicemia.

Subacute postoperative endophthalmitis secondary to sutureless self-sealing corneal wound infection at both main cornea and side port wounds: A case report

<br>Corneal wound infection following cataract surgery is rare. We describe a case of wound infection at both the main wound and the side port wound following uncomplicated phacoemulsification. <i>Candida albicans</i> was isolated, and the condition worsened with progression to endophthalmitis. Vitrectomy was done, and the infection was controlled after 3 months of topical and systemic antifungal medications.<br>