Use Of Antifungal Therapy Research Articles

Effectiveness of Chitosan versus Natural Aloe Vera on Candida Adherence in Denture Soft Lining Material.

Soft denture lining materials act as a cushion between the denture base and tissues. Alongside having many advantages, its main problem is candida growth due to its rubbery and porous texture. Many interventions have been performed to halt the growth of candida within soft lining materials such as the use of antifungal therapy and strict oral and denture hygiene but there are consequences such as recurrence, drug resistance, and toxicity related to these interventions. Since natural agents such as aloe vera and chitosan have been proven to have antibacterial and antifungal properties with minimum adverse effects, this study aimed to study the effectiveness of chitosan and aloe vera powders incorporated within denture soft lining materials against candida adherence. Methodology. A total of 60 soft-lining material samples were prepared that were equally divided into three groups, viz., group 1 (chitosan incorporation), group 2 (aloe vera incorporation), and group 3 (control). Candida was obtained from the microbiology lab to form a candidal suspension, diluted in 0.9% NaCl to match the McFarland standard bacteriologic solution. Samples were incubated at 37°C for 24 hours in test tubes containing 100 mL of the candidal suspension and 9.9 mL of the previously prepared Sabouraud dextrose agar. Crystal violet stain was used to stain the adhering cells by fixing them with methanol 80%. For each sample, the adhering candida cells were counted on three standard fields by using an inverted light microscope, and the mean of those fields was recorded. The mean value for samples containing aloe vera was 41.15, while the mean values for samples containing chitosan and the control group were 16.05 and 79.1, respectively. Of all the three groups, aloe vera powder had a significant efficacy against candida growth as compared to the chitosan and control groups (P value = 0.001). Both herbal agents were effective against candida growth. In comparison, aloe vera was more effective against candida growth compared to chitosan.

Evaluation of photodynamic therapy efficacy vs. conventional antifungal therapy in patients with poor-fitting dentures suffering from denture stomatitis. A prospective clinical study

BackgroundThe long-term use of antifungal therapy in denture stomatitis (DS) treatment could be accompanied by antifungal-resistant strain onset, leading to compromised therapeutic procedure and disease reappearance. Photodynamic therapy (PDT) has shown the ability to eradicate oral infections and resistance strains. This prospective clinical study aimed to assess the PDT's effectiveness compared to the conventional treatment on clinical and microbiological parameters in patients with DS without denture wear during the treatment and follow-ups. MethodsForty-two patients diagnosed with DS were randomly assigned to one-session single PDT application (test group) or conventional antifungal therapy (control group). Clinical and microbiological parameters were assessed and analyzed before and at 3rd, 15th, and 30th day following the treatments. Microbiological samples were analyzed by a Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The data was statistically analyzed. ResultsPrior to the treatment, Candida species, including C. albicans (100%), C. glabrata (33%), C. tropicalis (31%), C. krusei (31%) were isolated in all patients. Both treatment procedures demonstrated a statistically significant reduction in C. albicans at all follow-up time intervals (p < 0.05). However, PDT displayed a statistically significant reduction in C. krusei compared to the conventional treatment at all follow-up periods (p < 0.05). Clinical parameters improved considerably in the test group compared to the control group at the 3rd and 15th day of follow-up. ConclusionOne-session single PDT application demonstrated significant improvement in both clinical and microbiological outcomes in a short-term period, resulting in complete Candida spp. eradication compared to conventional antifungal therapy.

Клиническое наблюдение криптококкового менингита у пациента с системной красной волчанкой

The risk of serious infectious diseases is significantly increased in individuals with systemic lupus erythematosus (SLE). The article describes a clinical case of meningoencephalitis caused by Cryptococcus neoformans, in a 33-year-old female patient with SLE. The diagnosis was based on the results of cerebrospinal fluid analysis, brain magnetic resonance imaging scans, and retrospective analysis of chest computed tomography features. The antifungal therapy comprising liposomal amphotericin B and fluconazole was used successfully. Distinctive features of this clinical case include a delayed diagnosis due to the slow development and the presence of non-specific neurological symptoms, as well as the onset of acute renal disorders amid the use of antifungal therapy. The authors discuss the issues of diagnosing infectious complications in patients with SLE, particularly fungal infections, and the up-to-date approaches to therapy of cryptococcal meningitis. The presented clinical report could help therapists and rheumatologists to improve timely recognition of cryptococcal infections in SLE patients. The authors emphasized that CSF examination plays the key role in diagnosing cryptococcal meningitis. KEYWORDS: cerebral cryptococcosis, opportunistic infection, meningoencephalitis in patients with systemic lupus erythematosus, clinical case, fungal infection, systemic lupus erythematosus. FOR CITATION: Kuzminykh D.A., Eliseev Yu.V., Matrosova M.S. et al. A clinical case of cryptococcal meningitis in patient with systemic lupus erythematosus. Russian Medical Inquiry. 2023;7(3):174–180 (in Russ.). DOI: 10.32364/2587-6821-2023-7-3-174-180.

Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials. Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis. The searches identified six trials; none of which met the inclusion criteria for the review. We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update. At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.

Characterizing the prognostic utility of isolating yeast in surgical site infections and subsequent use of antifungal therapies

Background: Whether the isolation of yeast from surgical site infections (SSIs) affects outcomes is unclear. We hypothesized that for SSI, yeasts are nonpathogenic and that neither the isolation of yeast nor the use of antifungal agents affects outcomes.Methods: Incisional SSIs from general surgery patients at a single institution between 1997 and 2017 with positive cultures were analyzed, categorized by the presence of yeast. Demographics and in-hospital mortality were compared by Student's t-test and Chi-square analysis. Independent predictors of isolation of yeast and in-hospital mortality were determined by multivariate logistic regression analysis (MV).Results: In total, 977 infections with positive cultures were identified: 190 (19.4%) with yeast and 787 (80.6%) without. By univariate analysis, cultures positive for yeast were associated with a higher severity of illness/APACHE II score (15.6 ± 0.5 versus 11.6 ± 0.2; P < 0.0001), diagnosis in the ICU (83/190, 43.6% versus 154/787, 19.5%; P < 0.0001), age (55.2 ± 1.1 versus 52.4 ± 0.5; P = 0.015), and female sex (105/190, 55.3% versus 362/787, 46.0%; P = 0.027). Independent predictors of isolation of yeast included sex, APACHE II Score, and diagnosis after discharge from index procedure, and for mortality, age, APACHE II, diagnosis after discharge, and receiving antifungal treatment. Isolation of yeast was not associated with mortality (P = 0.12). For fungal SSI, antifungal treatment was not associated with decreased mortality.Conclusion: Isolation of yeast from incisional SSI is not associated with mortality, and the use of antifungal agent is associated with higher mortality. Routine fungal cultures of SSI are not warranted.

Leukotrienes Are Dispensable for Vaginal Neutrophil Recruitment as Part of the Immunopathological Response During Experimental Vulvovaginal Candidiasis

Recruitment of polymorphonuclear neutrophils (PMNs) into the vaginal lumen is the hallmark of an acute immunopathologic inflammatory response during vulvovaginal candidiasis (VVC) caused by Candida albicans. Recurrent VVC (RVVC) remains a chronic health burden in affected women worldwide despite the use of antifungal therapy. Based on the role leukotrienes (LTs) play in promoting inflammation, leukotriene receptor antagonists (LTRAs) targeted for LTB4 (etalocib) or LTC4, LTD4, and LTE4 (zafirlukast or montelukast) have been shown to reduce inflammation of epithelial tissues. An open-label pilot study using long-term regimens of zafirlukast in women with RVVC indicated the potential for some relief from recurrent episodes. To investigate this clinical observation further, we evaluated the effects of LT antagonistic agents and LT deficiency on the immunopathogenic response in a mouse model of VVC. Results showed that mice given daily intraperitoneal injections of individual LTRAs, starting 2days prior to vaginal inoculation with C. albicans and continuing through 14days post-inoculation, had no measurable reduction in PMN migration. The LTRAs were also ineffective in reducing levels of the hallmark vaginal inflammatory markers (S100A8, IL-1β) and tissue damage (LDH) associated with the immunopathogenic response. Finally, LT-deficient 5-lipoxygenase knockout mice showed comparable levels of vaginal fungal burden and PMN infiltration to wild-type mice following inoculation with a vaginal (ATCC 96113) or laboratory (SC5314) C. albicans isolate. These results indicate that despite some clinical evidence suggestive of off-target efficacy of LTRAs in RVVC, LTs and associated signaling pathways appear to be dispensable in the immunopathogenesis of VVC.

The Prediction and Prognosis of Fungal Infection in Lung Transplant Recipients-A Retrospective Cohort Study in South Korea.

(1) Background: Lung transplant recipients (LTRs) are at substantial risk of invasive fungal disease (IFD), although no consensus has been reached on the use of antifungal agents (AFAs) after lung transplantation (LTx). This study aimed to assess the risk factors and prognosis of fungal infection after LTx in a single tertiary center in South Korea. (2) Methods: The study population included all patients who underwent LTx between January 2012 and July 2019 at a tertiary hospital. It was a retrospective cohort study. Culture, bronchoscopy, and laboratory findings were reviewed during episodes of infection. (3) Results: Fungus-positive respiratory samples were predominant in the first 90 days and the overall cumulative incidence of Candida spp. was approximately three times higher than that of Aspergillus spp. In the setting of itraconazole administration for 6 months post-LTx, C. glabrata accounted for 36.5% of all Candida-positive respiratory samples. Underlying connective tissue disease-associated interstitial lung disease, use of AFAs before LTx, a longer length of hospital stay after LTx, and old age were associated with developing a fungal infection after LTx. IFD and fungal infection treatment failure significantly increased overall mortality. Host factors, antifungal drug resistance, and misdiagnosis of non-Aspergillus molds could attribute to the breakthrough fungal infections. (4) Conclusions: Careful bronchoscopy, prompt fungus culture, and appropriate use of antifungal therapies are recommended during the first year after LTx.

Fungal co-infection in COVID-19 patients: evidence from a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) has infected tens of millions of people worldwide within the last year. However, the incidence of fungal co-infection in COVID-19 patients remains unclear. To investigate the association between fungal co-infection and mortality due to COVID-19, we systematically searched Medline, Embase, MedRxiv and Cochrane Library for eligible studies published in the period from 1 January to 1 December 2020. We performed a meta-analysis of nine studies that met the inclusion criteria. In total, data from 2780 patients and 426 patients were included who were admitted to the ICU. In eight of the articles, 211 participants died due to COVID-19 infection, which means an overall mortality rate of 10.9%. The overall pooled proportion of fungal co-infection in COVID-19 patients was 0.12 (95% CI = 0.07-0.16, n = 2780, I2 = 96.8%). In terms of mortality in COVID-19 patients with fungal infection, the overall pooled proportion of mortality was 0.17 (95% CI = 0.10-0.24, n = 1944, I2 = 95.6%). These findings provide evidence suggesting a favorable use for empirical antibiotics in the majority of patients when COVID-19 infection is diagnosed. Our analysis is investigating the use of antifungal therapy to treat COVID-19 can serve as a comprehensive reference for COVID-19 treatment.

Antimicrobial efficacy of silver nanoparticles against Candida albicans: A systematic review protocol.

Denture-induced stomatitis is one form of candidiasis. It is characterised as inflammation and erythema of the oral mucosa underneath the denture-bearing areas and clinically classified into three types according to severity. Denture hygiene, appropriate mouth rinses and the use of antifungal therapy are commonly used to treat the condition, but new technologies are emerging that may assist in its treatment. The aim of this systematic review is to determine if silver nanoparticles inhibit the growth of Candida Albicans when included in acrylic dentures and in different denture liners. A protocol was developed and published on PROSPERO (Registration No: CRD42019145542) and with the institutional ethics committee (Registration No: BM20/4/1). The protocol includes all aspects of a systematic review namely: selection criteria, search strategy, selection methods using predetermined eligibility criteria, data collection, data extraction, critical appraisal of included studies, and the intended statistical analyses such as calculating risk ratios (RR) for dichotomous outcomes and presented at 95% confidence intervals, a meta-analysis, if possible or a narrative report as needed. With rigorous inclusion criteria set and databases identified for searching, appropriate clinical and laboratory studies may be obtained but the results and its interpretation and translation into clinical practice may be a challenge as these depend on the quality of the research.

Antifungal treatment administered in OPAT programs is a safe and effective option in selected patients

IntroductionOutpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment. Nevertheless, the most common antimicrobials used are antibiotics, and there is less information about the use of antifungal therapy (AT). The aim of this study is to analyse a cohort of patients treated with AT administered via OPAT and to compare them with patients from the rest of the cohort (RC) treated with antibiotics. MethodsProspective observational study with post hoc (or retrospective) analysis of a cohort of patients treated in the OPAT program. We selected the patients treated with antifungals between July 2012 and December 2018. We recorded demographic and clinical data to analyse the validity of the treatment and to compare the differences between the AT and the RC. ResultsOf the 1101 patients included in the OPAT program, 24 (2.18%) were treated with AT, 12 Liposomal Amphotericin B, 6 echinocandins and 6 fluconazole. This result is similar to other cohorts. There were differences between the AT vs RC in the number of patients with neoplasia (58.3% vs 28%; p=0.001), IC Charlson>2 (58.3% vs 38.8; p=0.053), duration of treatment (15 days vs 10.39 days; p=0.001) and patients with central catheters (54.2% vs 21.7%; p=0.0001). These differences are justified because there were more hematologic patients included in the AT group. Nevertheless, there were no differences in adverse reactions (25% vs 32.3%; p=0.45) or re-admissions (12.5% vs 10%; p=0.686) and OPAT with AT was successful in 21/24 patients (87.5%). ConclusionsAT can be successfully administered in OPAT programs in selected patients, that are clinically stable and monitored by an infectious disease physician.

Changing scenario of superficial fungal infection: Emerging resistance, recurrence and remedy in Bangladesh

Superficial fungal infections (dermatophytes) affecting skin, nail and hair are the most common infective dermatosis seen in dermatology outpatient clinics. There is a rising prevalence of dermatophytosis, especially in tropical countries like Bangladesh, with a concomitant increase in the number of difficult to treat cases. The reason for this phenomenon is not yet clear, but may be related to inadequate treatment regimen or discontinuation of medication, difficulties in eliminating predisposing factors and sources of re-infection. The pathogenesis and severity of fungal infection depend on various immunological and nonimmunological factors. The rampant use of antifungal therapy in immunocompromised individuals marked the onset of antifungal drug resistance. Fungal resistance can be microbiological or clinical. Genetic alterations in the fungi cause microbiological resistance. Clinical resistance is due to host or drug related factors. All these factors may cause fungal resistance individually or in tandem. Appropriate drug dosing along with antifungal drug susceptibility testing, especially for the dermatophytes isolated from chronic, recurrent cases or those with atypical presentation should be encouraged. Other ways to avoid resistance is the use of combination antifungal therapy. Combination therapy offers advantages in increased synergistic action with enhanced spectrum activity. Finally, newer insights into molecular mechanisms of drug resistance will help in the development of appropriate antifungal therapy. Till then experience based treatment of dermatophytosis is more effective than the standard guideline.&#x0D; Bangladesh Crit Care J September 2020; 8(2): 108-111

A National Strategy to Diagnose Coronavirus Disease 2019-Associated Invasive Fungal Disease in the Intensive Care Unit.

BackgroundFungal co-infection is a recognised complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in COVID-19 patients with severe respiratory distress are being reported, but comprehensive data is lacking. The aim of this study was to determine the incidence, risk factors and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress.MethodsAn evaluation of a national, multi-centre, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients.ResultsOne-hundred and thirty-five adults (median age: 57, M/F: 2·2/1) were screened. The incidence was 26.7% (14.1% aspergillosis, 12·6% yeast infections). The overall mortality rate was 38%; 53% and 31% in patients with and without fungal disease, respectively (P: 0.0387). The mortality rate was reduced by the use of antifungal therapy (Mortality: 38·5% in patients receiving therapy versus 90% in patients not receiving therapy (P: 0.008). The use of corticosteroids (P: 0.007) and history of chronic respiratory disease (P: 0.05) increased the likelihood of aspergillosis.ConclusionsFungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.

Antifungal treatment administered in OPAT programs is a safe and effective option in selected patients

IntroductionOutpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment. Nevertheless, the most common antimicrobials used are antibiotics, and there is less information about the use of antifungal therapy (AT). The aim of this study is to analyse a cohort of patients treated with AT administered via OPAT and to compare them with patients from the rest of the cohort (RC) treated with antibiotics. MethodsProspective observational study with post hoc (or retrospective) analysis of a cohort of patients treated in the OPAT program. We selected the patients treated with antifungals between July 2012 and December 2018. We recorded demographic and clinical data to analyse the validity of the treatment and to compare the differences between the AT and the RC. ResultsOf the 1101 patients included in the OPAT program, 24 (2.18%) were treated with AT, 12 Liposomal Amphotericin B, 6 echinocandins and 6 fluconazole. This result is similar to other cohorts. There were differences between the AT vs RC in the number of patients with neoplasia (58.3% vs 28%; p=0.001), IC Charlson>2 (58.3% vs 38.8; p=0.053), duration of treatment (15 days vs 10.39 days; p=0.001) and patients with central catheters (54.2% vs 21.7%; p=0.0001). These differences are justified because there were more hematologic patients included in the AT group. Nevertheless, there were no differences in adverse reactions (25% vs 32.3%; p=0.45) or re-admissions (12.5% vs 10%; p=0.686) and OPAT with AT was successful in 21/24 patients (87.5%). ConclusionsAT can be successfully administered in OPAT programs in selected patients, that are clinically stable and monitored by an infectious disease physician.

Case Report: Treating Cryptococcal Meningoencephalitis with Chinese Herbal Medicine Based on Macro Natural Law of Traditional Chinese Medicine

Background: Over the past few decades, Expansion, Cryptococcus infection. Has become a worldwide Common fungal infections. Cryptococcus prevention has many difficulties in clinical application. Survivors Neurological sequelae are also common Cryptococcal Meningoencephal, CM. In China, Traditional Chinese Medicine tends to been used for poor fungal treatment or sequelae. Case presentation: We present a 47-year-old patient with cryptococcal encephalitis who’s clinical manifestations are atypical, and it is easy to misdiagnose. The first symptom was headache after tooth extraction, followed by fever. The diagnosis was confirmed 6 months after the onset of the disease. After antifungal treatment for 18 days, Headache and fever not reduced and multiple adverse effects such as impaired internal organs. The use of antifungal therapy has serious adverse reactions and poor treatment effects. When the disease is in critical condition, the modern medical antifungal treatment is ineffective and resistant to help. Using traditional Chinese medicine theory, it acknowledges the harmonious unity between man and nature, instead of looking for better resistance Fungal drugs, but by changing the internal environmental stability of the body, after 5 days of initial treatment, the patient no longer had fever, headache, snore, appetite restored and normal bowel movements, the nervous system function gradually recovers. No fever or headache occurred within 5 months, neurological function gradually recovered, head MRI improved, and cerebrospinal fluid culture was negative. After 7 months, the patient still had no fever, headache, snore, he can take care of himself, normal language expression can be done, farm work at home, one person can do food shopping and cooking, etc., limb muscle strength is normal, muscle tension is not high, No positive neurological examination. Conclusion: Traditional Chinese medicine modalities may be considered for treatment When western medicine treatment of cryptococcal encephalitis is not effective, based on appropriate syndrome pattern assessment.

A National Strategy to Diagnose COVID-19 Associated Invasive Fungal Disease in the ICU

Rationale: Fungal co-infection is a recognised complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in COVID-19 patients with severe respiratory distress are being reported, but comprehensive data is lacking. Objectives: To determine the incidence, risk factors and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress. Methods: An evaluation of a national, multi-centre, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients. Measurements and Main Results: One-hundred and thirty-five adults (median age: 57, M/F: 2·2/1) were screened. The incidence was 25·9% (13·3% aspergillosis, 12·6% yeast infections). The overall mortality rate was 38%; 51% and 31% in patients with and without fungal disease, respectively (P: 0·0398). The mortality rate was reduced by the use of antifungal therapy (Mortality: 38·5% in patients receiving therapy versus 89% in patients not receiving therapy (P: 0·0178). The use of corticosteroids (P: 0·002) and history of chronic respiratory disease (P: 0·043) increased the likelihood of aspergillosis. Conclusions: Fungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.

Histologic Characterization of Histoplasmomas

Abstract Introduction Histoplasmomas are often found incidentally in surgical specimens, but there are no clear reporting guidelines to describe the subtle differences in the stages of organization of the granuloma. This study establishes grading criteria to more clearly communicate the stage of organization and resolution of these lesions, with the hope that this information could inform clinical decisions. Methods For an 11-year period, all surgical pathology cases with histoplasmomas in the final diagnosis with slides available were included in the study. After confirmation that Histoplasma yeasts were present, the granulomas were graded as follows grade 1, active granulomas with or without necrosis with minimal to no fibrous rim formation; grade 2, minimal to moderate granulomatous inflammation remained associated with a well-developed fibrous rim; and grade 3, no granulomatous inflammation remained, and a well-developed fibrous rim was present. Calcification and necrosis were also noted. Histoplasma yeasts was semiquantified. One to five yeasts were characterized as rare, 6 to 10 as few, 11 to 50 as moderate, and &gt;50 yeasts as many. Results Forty-two cases were included in the study. The lesions were graded as follows 3 grade 1, 19 grade 2, and 20 grade 3 lesions. Calcifications increased with grade (grade 1: 0 [0%], grade 2: 10 [52.6%], grade 3: 18 [95%]). All histoplasmomas had necrosis. The number of yeasts detected, stratified by grade, was as follows grade 1, rare (1) and many (2); grade 2, rare (6), few (1), moderate (1), and many (11); and grade 3, rare (2), moderate (4), and many (14). None of the patients developed active histoplasmosis for the duration of their follow-up at our institution. Conclusion The proposed grading of histoplasmomas provides an indication to clinicians of the stage of activity or resolution of an excised histoplasmoma. These data do not support the use of antifungal therapy in patients with grade 2 or 3 histoplasmomas.

Mucormycosis in South America: A review of 143 reported cases

SummaryMucormycosis is a rare but important invasive fungal disease that most often affects immunocompromised hosts. The incidence of mucormycosis appears to be increasing worldwide, as risk factors such as the use of immunosuppressive therapies become more common. We report the results of a literature review of 143 mucormycosis cases reported in South America between 1960 and 2018. The number of reported cases has increased by decade, from 6 in the 1960s to 51 in the 2010s. The most common underlying conditions associated with mucormycosis in South America were diabetes mellitus (42.0%) and penetrating trauma/burns (20.0%). Underlying conditions involving immunosuppression, including treatment of haematologic malignancy, solid organ transplant, and corticosteroid use, also accounted for a large proportion of cases (45.5%). Between 1960 and 2018, cases of mucormycosis associated with conditions involving immunosuppression accounted for the highest mortality rate (58.5%), followed by diabetes mellitus (45.0%), and penetrating trauma/burns (37.9%). Overall mortality decreased from 100% to 39.4% during this period, mainly driven by the increasing availability and use of antifungal therapies and surgical intervention. However, these treatments are not yet universally utilised across the region in the treatment of mucormycosis; efforts to improve availability of effective treatments would be likely to improve outcomes.

Successful outcome of mucormycosis in a child with acute lymphoblastic leukemia

Invasive fungal infections may cause morbidity and mortality in pediatric patients with hematologic and oncologic malignancies treated with intensive protocols. We present a case of mucormycosis in an 8-year-old boy with acute lymphoblastic leukemia. In our patient, the suspicion for an oculoorbital and paranasal infection only due to mild pain in the orbital area without any abnormal pathologic findings in the ophthalmologic and otolaryngologic examination, led us to an early diagnosis. Despite the use of antifungal therapy, the lesion persisted and fever subsided after surgical drainage of the periorbital abscess. Antifungal treatment continued during chemotherapy. He has been in remission for four years. Mucormycosis should be in the differential diagnosis in infections in children with cancer, especially leukemia, according to clinical and radiologic findings. A high degree of suspicion and prompt systemic empirical antifungal therapy, as well as surgical debridement, are crucial for the survival of patients. Beside antifungals, early surgery plays an important role in patients with mucormycosis.

410. Impact of Pediatric Antifungal Adverse Drug Reactions on Prescribing Practices

BackgroundWhile antibiotics frequently cause adverse drug reactions (ADR), the rate of antifungal (AF) ADR is unknown. The mechanisms of AF ADR and cross-reactivity among a drug class (i.e., azoles) are poorly understood. Given the use of AF therapy is on the rise, it is important to better understand the prevalence of AF ADR and how these reactions influence prescribing.MethodsThirty-two hospitals participated in a quarterly pediatric point prevalence survey that documented details on all admitted patients 0–17 years receiving any systemic antimicrobials, including drug, dose, and documented history of an antimicrobial ADR between June 2016 and December 2017. Patients who were recorded as receiving at least one systemic AF were included. A comparison of AF prescribing practices between those with and without an AF ADR was performed.ResultsAmong 13,179 total patients, 2,213 AF were prescribed to 2,101 unique patients. The most common indications for AF included prophylaxis (64%), fever with neutropenia (4%), neonatal sepsis (3%), and catheter-related bloodstream infection (3%). The prevalence of patients with any documented AF ADR was 2.9%. Amphotericin was most commonly associated with an ADR. Fluconazole was the most commonly prescribed AF in those with no ADR (49%) when compared with those with an AF ADR (13%; P < .05). Patients with an amphotericin ADR were more likely to receive voriconazole (29%) when compared with those without (15%; P < .05). Interestingly, posaconazole use was highest in those with an azole ADR (22%) when compared with those with no azole ADR (4%; P < .05). Echinocandin ADR were infrequent, and those with a reported ADR still received an echinocandin 62% of the time.ConclusionSignificant differences in antifungal prescribing exists based on ADR status. More work is needed to be able to effectively classify AF ADR, determine safe prescribing practices in those with an AF ADR, and evaluate outcomes associated with AF ADR status. Disclosures All authors: No reported disclosures.

Vincristine-associated Neuropathy With Antifungal Usage: A Kaiser Northern California Experience.

The dose-limiting toxicity for vincristine is peripheral neuropathy which can be potentiated with concurrent usage of azole antifungals. The current retrospective study assessed the incidence of concurrent vincristine and azole antifungal usage to determine if it led to increased neurotoxicity for the Kaiser Northern California pediatric acute lymphoblastic leukemia (ALL) and Hodgkin lymphoma patient population. Data were obtained from the electronic medical record (2007 to 2014). In total, 130 subjects received at least one dose of vincristine for ALL or Hodgkin lymphoma (median age 9, 88% ALL, 58% male, 47% Caucasian). Thirty one percent of patients received concurrent antifungal usage (fluconazole, 78%; voriconazole, 10%; fluconazole/voriconazole, 12%); however, concurrent antifungal usage accounted for <15% of vincristine doses. Grade 2 or greater neuropathy occurred in 51% of patients; grade 3 neuropathy was present in 8% of patients. No difference in the incidence of grade 2 or greater neuropathy was observed with the concurrent use of antifungal therapy (P=0.35), sex (P=0.59), type of cancer (P=0.41), ethnicity (P=0.29), or age (P=0.39), but was higher with increasing amount of vincristine doses (P=0.004). These results suggest that concurrent azole antifungal usage with vincristine for patients with ALL and Hodgkin lymphoma was low in the Kaiser Northern California population and limited usage as needed may be reasonable and safe.