Antimycotic Treatment Research Articles

Case report: Candida krusei spondylitis in an immunocompromised patient

BackgroundInvasive infections with Candida krusei are uncommon and rarely complicated by spondylitis. Previous described cases were solely treated with antimycotic therapy, despite guidelines recommending surgical interventions.Case presentationWe describe a case of C. krusei spondylitis in a patient treated with chemotherapy for acute myeloid leukemia. After induction chemotherapy, the patient developed a candidemia, which was treated with micafungin. One month after the candidemia, the patient was admitted with severe lumbar pain. Spondylitis of the L4 and L5 vertebra was diagnosed on MR-imaging, with signs suggesting an atypical infection. The patient was treated with anidulafungin combined with voriconazole. Despite maximal conservative management symptoms gradually worsened eventually requiring surgical intervention.ConclusionsIn contrast to previous case reports, antimycotic treatment alone could be insufficient in treating C. krusei spondylitis.

Cutibacterium acnes regulates the epidermal barrier properties of HPV-KER human immortalized keratinocyte cultures

Our skin provides a physical barrier to separate the internal part of our body from the environment. Maintenance of complex barrier functions is achieved through anatomical structures in the skin, the stratified squamous epithelium specialized junctional organelles, called tight junctions (TJs). Several members of our microbial communities are known to affect the differentiation state and function of the colonized organ. Whether and how interactions between skin cells and cutaneous microbes, including Cutibacterium acnes (C. acnes), modify the structure and/or function of our skin is currently only partly understood. Thus, in our studies, we investigated whether C. acnes may affect the epidermal barrier using in vitro model systems. Real-time cellular analysis showed that depending on the keratinocyte differentiation state, the applied C. acnes strains and their dose, the measured impedance values change, together with the expression of selected TJ proteins. These may reflect barrier alterations, which can be partially restored upon antibiotic–antimycotic treatment. Our findings suggest that C. acnes can actively modify the barrier properties of cultured keratinocytes, possibly through alteration of tight cell-to-cell contacts. Similar events may play important roles in our skin, in the maintenance of cutaneous homeostasis.

Dosing of Antimycotic Treatment in Sepsis–Induced Liver Dysfunction by Functional Liver Testing with LiMAx®

Background Sepsis-treatment is one of the major challenges in our time. Especially fungal infections play an important role in patient's morbidity and mortality. In patients with septic shock, liver function is often significantly impaired and therefore also hepatic drug metabolism is altered. Case Presentation We report about a 56-year-old man suffering from invasive fungal infection with multiorgan failure, after complicated medical history due to symptomatic infrarenal aortic aneurysm. On the first postoperative day, a CT scan was undertaken due to massive back pain showing renal infarction on both sides. As qualitative and quantitative renal function was impaired, hemodialysis was started immediately. Subsequently, the patient developed a compartment syndrome of the left leg and underwent fasciotomy. On admission day 7, the patient presented with hematochezia leading to colonoscopy. During this procedure, an ischemic colitis was observed. As conservative treatment failed, the patient underwent Hartmann's procedure due to progredient ischemia followed by a worsening of the clinical status due to sepsis. The patient suffered from an invasive fungal infection with Candida spp. and Aspergillus spp. Systemic antifungal treatment was initiated. Although azoles are considered first-line treatment in these cases we chose the echinocandin caspofungin for its presumed lower impact on liver function compared to azoles like voriconazole or Amphothericin B. However, caspofungin is also metabolised in the liver and can cause hepatotoxic effects. Therefore we measured metabolic liver function capacity using LiMAx®and adapted the patient's dose of caspofungin to the evaluated liver function capacity to achieve an effective and liver-protective level of the active drug. After complicated medical history with 15 weeks of hospital stay, the patient was discharged in general good condition. Conclusions To our knowledge, this is the first report that relates antimycotic drug dosing to a functional liver test. We provide a new approach for sepsis treatment considering liver function capacity to optimize dosage of hepatically metabolised drugs with potential hepatotoxic effects.

A retrospective analysis of 1,717 paranasal sinus fungus ball cases from 2008 to 2017.

To analyze the epidemiological characteristics, clinical features, and the outcomes of histopathology and microbiology for fungus ball (FB) in the last 10 years in our department. Database review. In total, 1,717 cases of FB were reviewed from the case database of Beijing Tongren Hospital (between 2008 and 2017). Epidemiologic data, clinical manifestations, histopathology, and microbiology were analyzed. In the past 10 years, there has been a significant increase in patients with FB presenting at our department (P < .05). The mean age of patients with paranasal sinus FB was 54 years, and 67% of patients were female (1,156/1,717). The average age and female predominance were consistent with previous reports. In total, 1,626 cases (94.7%) were unilateral, and the most common location was the maxillary sinus (76.6%). Aspergillus spp. (72.8%) was the most abundant fungal species in our study. The direct smear positive rate was 68.6%, and the fungal culture rate was 22.6%. All cases were treated with functional endoscopic sinus surgery, with a very low rate of postoperative complications and reoperation (20/1,717). Histopathological and microbiological analyses are essential for the diagnosis of FB. Surgery is the most effective method of treatment. Direct smear after surgery is not necessary. Oral or topical antimycotic treatments are not recommended after surgery or during the perioperative period. 4 Laryngoscope, 130:75-79, 2020.

Fungal infections

Invasive aspergillosis, mucormycosis, and cryptococcosis are severe opportunistic infections in patients with long phases of neutropenia and also after allogeneic stem cell and organ transplantation. Due to the late appearance of clinical signs and the often poor outcome, these diseases require special attention and proactive interventions. Published guidelines and selected current literature were reviewed for this article. Invasive aspergillosis and mucormycosis are typically observed in the upper and lower airways of severely immunocompromized patients. When invasive fungal diseases are suspected, sectional imaging and, if possible, serological testing should be performed as soon as possible. If imaging or serological tests confirm the suspected diagnosis, pre-emptive antimycotic treatment should be started and further confirmation of the diagnosis sought via microbiological and/or histological investigations. Treatment depends on comedication, comorbidity and risk factors, primarily with voriconazole, isavuconazole and liposomal amphotericinB. With the advent of antiretroviral treatment, adecrease of cryptococcosis cases in people with human immunodeficiency virus was observed; however, increasing cases have been reported in patients with new forms of immunosuppression. Cryptococcus spp. predominantly cause central nervous system infections but also pneumonia and bloodstream infections. Diagnostics include blood and cerebrospinal fluid cultures and antigen tests. First line treatment consists of acombination therapy with amphotericinB and flucytosine. An interdisciplinary approach with microbiologists, infectious diseases specialists and radiologists is needed for diagnostics and treatment of invasive fungal diseases.

Use of three-dimensional printing for reconstruction of a cranial surgical defect for mucormycosis with a preformed titanium cranial mesh implant

Background: Introduction It is important to reconstruct the skull for the recovery of a patient's quality of life. There are different methods and materials available for cranioplasty. Points to be considered are the resistance to stress of the material, good adaptation to the contour of the cranial defect, surgical operating time, risk of infection and aesthetic results. Clinical case A fifty three year old male patient presented with a severe cranial defect after right fronto orbito temporal and orbito zygomatic partial resection for mucormycosis. He had undergone three surgical procedures of resection. He had also received specific antimycotic treatment with good response but showed severe craniofacial sequelae.

Candida Antigen Titer Elevation and Mortality in Burn Patients

BACKGROUNDMortality in burn patients has several contributing factors as sex, age, degree of burns, or inhalation injuries. Usefulness of Candida antigen (CAG) titer is still being under debate to predict mortality. This study assessed correlation between CAG titer and mortality in burn patients.METHODSFrom 1988 to 2011, 877 burn intensive care patients were evaluated for age, sex, total burn surface area (TBSA), multi organ failure (MOF), burn depth, escharotomy, fasciotomy, antibiotic use, co-morbidities, CAG titer and intubation. RESULTSFrom 870 admitted patients, 190 patients were not enrolled. Increasing age was correlated with a higher mortality. The abbreviated burn severity index (ABSI) score of the deceased was 4 points and the TBSA was 20% higher than the survivors. The correlation for age, intubation, TBSA, inhalation injury, MOF, CAG titer, antibiotic use and escharotomy was significant. An increasing mortality was noted with antibiotic use and a CAG titer of 1:8 and higher. CAG titer of 1:8 and higher had a sensitivity of 51.1% and specificity of 86.3% for mortality. Multivariate analysis confirmed high influence of older age, MOF, comorbidities, antibiotic use and CAG titer of 1:8 and higher on mortality. There was a significant correlation for sex, younger age and CAG titer.CONCLUSIONCAG titers of 1:8 and higher might warrant beginning of antimycotic treatment in elderly patients with high TBSA to avoid increase in mortality.

Candida Antigen Titer Elevation and Mortality in Burn Patients

Mortality in burn patients has several contributing factors as sex, age, degree of burns, or inhalation injuries. Usefulness of Candida antigen (CAG) titer is still being under debate to predict mortality. This study assessed correlation between CAG titer and mortality in burn patients.From 1988 to 2011, 877 burn intensive care patients were evaluated for age, sex, total burn surface area (TBSA), multi organ failure (MOF), burn depth, escharotomy, fasciotomy, antibiotic use, co-morbidities, CAG titer and intubation.From 870 admitted patients, 190 patients were not enrolled. Increasing age was correlated with a higher mortality. The abbreviated burn severity index (ABSI) score of the deceased was 4 points and the TBSA was 20% higher than the survivors. The correlation for age, intubation, TBSA, inhalation injury, MOF, CAG titer, antibiotic use and escharotomy was significant. An increasing mortality was noted with antibiotic use and a CAG titer of 1:8 and higher. CAG titer of 1:8 and higher had a sensitivity of 51.1% and specificity of 86.3% for mortality. Multivariate analysis confirmed high influence of older age, MOF, comorbidities, antibiotic use and CAG titer of 1:8 and higher on mortality. There was a significant correlation for sex, younger age and CAG titer.CAG titers of 1:8 and higher might warrant beginning of antimycotic treatment in elderly patients with high TBSA to avoid increase in mortality.

The oral microbiome in oral lichen planus during a 1-year randomized clinical trial.

Several recent studies have investigated the oral bacteriome in oral lichen planus (OLP), but longitudinal changes in microbiome have not been investigated. To study the bacteriome and mycobiome in OLP over a 1-year period and the impact of topical treatment. Samples from 22 symptomatic OLP patients from a double-blinded, randomized intervention study were collected over a 1-year course at five visits. Bacterial and fungal abundances were investigated through lesional cytobrush (CB) and full mouthwash (MW). Initially, all patients received conventional (antimycotic or steroid) and probiotic or placebo treatment. The microbial composition differed between the MW and CB samples. During the study period, the microbial composition was individual, with pronounced variability between visits. Patients grouped according to initial conventional treatment. During the study period, unidirectional change in the bacteriome was seen in the antimycotic group, whereas the mycobiome was stable. Malassezia restricta was the most abundant fungus. The microbial composition of MW and CB differs in OLP. CB composition is less influenced by conventional and probiotic intervention. Initial antimycotic treatment influenced the bacteriome during the 1-year period. How the oral microbiome in health and disease is influenced by individual variability of fungi and bacteria, and Malassezia needs further investigation.

Recurrence of fungal keratitis in corneal transplant

В статье представлен клинический случай грибкового кератита в роговичном трансплантате. У пациента через 4 мес после сквозной кератопластики по поводу прогрессирующей язвы роговицы грибковой этиологии был диагностирован рецидив кератита. Была выполнена повторная сквозная кератопластика с последующим противовоспалительным лечением, но через 3 мес в центре трансплантата появился инфильтрат белого цвета с чёткими границами, который был иссечён. Лабораторное исследование иссечённого фрагмента выявило мицелий грибов рода Fusarium, проведена антимикотическая терапия амфотерицином В 0,2% местно и итраконазолом внутрь в течение 3 нед. Через 1 мес после проведённого лечения зрительные функции оставались на уровне правильной светопроекции, трансплантат был мутным на всей площади, отёк купирован, достигнута эпителизация роговицы. При осмотре в динамике через 2-3 мес болевой синдром отсутствовал, поверхность роговицы была гладкой без эпителиальных дефектов с помутнением трансплантата. Лабораторная диагностика является обязательной при подозрении на грибковую инфекцию. При проведении сквозной кератопластики при грибковом поражении роговицы необходимо иссечение инфильтрата в пределах здоровой ткани. Рецидивы грибковой инфекции в трансплантате роговицы происходят на границе «донор-реципиент».

Ibrutinib in the Treatment of Relapsed Chronic Lymphocytic Leukemia

Aim. To estimate ibrutinib efficacy in the treatment of early CLL relapses and in patients with &gt; 2 lines of preceding therapy. Analysis of treatment results in patients with del(17p) and monitoring of minimal residual disease (MRD) and ibrutinib safety profile. Materials &amp; Methods. The analysis included the results of ibrutinib treatment in 31 patients with CLL. Twenty eight patients were treated by bendamustine and fludarabine containing regimens. The median prior treatment lines were 2 (range 1-10). The indications for the treatment initiation were the first early relapse in 51 % of cases (n = 16) and a relapse after 2 and more lines of therapy in 49 % of cases (n = 15). Ibrutinib was administered in mono- (n = 15) and combined therapy (n = 14) as well as in the R-BAC scheme (n = 2). Using FISH analysis del(17p) was found in 9 patients (34 %). Results. Within the median follow up of 18 months (range 7-42+) the overall survival (OS) rate was reported to be 87 %, and the progression-free survival (PFS) rate was 77 %. The maximum MRD after a year of ibrutinib treatment was observed in case of combination with immunochemother-apy (e.g., R-BAC). Within the period of 18 months OS rate was 100 %, in the patient group with early relapses and 66 % in the group with a relapse after 2 and more therapy lines (p = 0.02). Within the same examination period PFS was significantly higher (94 %) in the patient group with early relapses compared to the previously treated patients (60 %) (p = 0.034). The most common adverse events were grade 1-2 purpura (30 %), grade 1-2 diarrhea (10 %), atrial fibrillation paroxysms (10 %) and arterial hypertension (10 %). Severe infectious complications registered in 6 % (n = 3) patients were successfully solved in the course of combined antibacterial and antimycotic treatment. Conclusion. Ibrutinib was shown to be effective drug for treatment of relapsed CLL. The OS and PFS values were more favourable in patients with early relapses compared to the patients with relapses after &gt; 2 lines of therapy prior to ibrutinib treatment. The maximum elimination of the tumor clone was observed after combined ibrutinib/immunochemotherapy treatment. The tolerance of ibrutinib was reported to be satisfactory with acceptable toxicity profile. No mortality due to infection complications was observed.

Fungus Ball of the Paranasal Sinuses: Analysis of Our Serie of Patients

Introduction and objectivesThe fungus ball is the most frequent type of fungal rhino-sinusitis. The objective of this study is to analyse the clinical and surgical features of our patients. MethodsRetrospective analysis of 35 patients with fungus ball treated in our centre between 2006 and 2014. ResultsMean age was 55 years old. 49% were men and 51% women. 75% involved the maxillary sinus, whereas 25% involved the sphenoid. 69% of our patients showed microcalcifications in the CT study. All the patients were surgically treated, with no cases of recurrence. ConclusionsClinical manifestations of fungus ball are non-specific, therefore endoscopy and image study are mandatory. The definitive diagnosis is made by histopathological study of the lesion. Endoscopic sinus surgery is the treatment of choice, with opening of the diseased sinus and complete removal of the fungus ball. The frequency of complications is very low. No oral or topical antimycotic treatments are necessary.

Vulvovaginal candidosis: contemporary challenges and the future of prophylactic and therapeutic approaches.

Vulvovaginal candidosis (VVC) is a common gynaecological disorder that is delineated by the inflammation of vaginal wall and it is caused by the opportunistic fungal pathogen Candida species. In fact, three out of every four women will experience at least one occasion of VVC during some point in their lives. Although uncomplicated VVC is relatively harmless, the complicated VVC such as recurrent attack often creates restlessness and depression in the patients, thus greatly affects their quality of life. Managements of VVC are usually associated with the use of antimycotic suppositories, topical cream or oral agents. These antimycotic agents are either available over-the-counter or prescribed by the clinicians. In recent decades, the rise of clinical challenges such as the increased prevalence of resistant Candida strains, recurrent VVC infection and adverse effects of multidrug interactions have necessitated the development of novel therapeutic or prophylactic options to combat the complicated VVC in the future. In this review, we discuss the current antimycotic treatments available for Candida vaginitis and the problems that exist in these seemingly effective treatments. Besides, we attempt to contemplate some of the future and prospective strategies surrounding the development of alternative therapeutic and prophylactic options in treating and preventing complicated VVC respectively.

Factors influencing healing of fungal keratitis under treatment: A clinical study

Purpose: To study the local and general factors influencing healing of fungal keratitis. To evaluate the effects of various antimycotic treatment regimens of fungal keratitis. Method: The patients were taken up from those attending the out-patient department of ophthalmology of Nehru hospital attached to B.R.D Medical College Gorakhpur from June 2006 to October 2007. All cases of corneal ulcer with clinical features of fungal keratitis and cases of corneal ulcer with positive 10% potassium hydroxide mount1,2 were selected, detailed history taken and examination done under (a) general examination, (b) systemic examination and detailed ocular examination along with blood investigations and 10% potassium hydroxide mount1,2 preparation. Treatment evaluation and follow up was done regularly for the period of one month, progression and treatment response noted and parameters were recorded .the ulcer was taken: Healed: If the epithelial defect had healed with negative fluorescein staining and there was no progressive stromal infiltration. Delayed healing: If the size of ulcer decreased but not fully healed and still require further active treatment and Failed: If the size of ulcer remained same or increased or ulcer got perforated requiring active surgical intervention. Result: 47 pts were included in study, 5 patients did not turn up. 18 patients (42.86%) leave the study with successful healing of corneal ulcer, 9 patients (21.43%) required further treatment due to delayed healing response and treatment failure occurred in 15 patients(35.71%) requiring active surgical treatment in form of conjunctival hooding, Amniotic membrane graft, evisceration etc. Conclusion: From the observation of this study it can be concluded that fungal keratitis is a suppurative, ulcerative disease of cornea, with a poor visual outcome even with the best efforts due to inability of highly sensitive and specific tools. Disease is more common in patients with reduced immunity, trauma with vege

Bola fúngica sinusal: análisis de nuestra casuística

Introduction and objectivesThe fungus ball is the most frequent type of fungal rhino-sinusitis. The objective of this study is to analyze the clinical and surgical features of our patients. MethodsRetrospective analysis of 35 patients with fungus ball treated in our centre between 2006 and 2014. ResultsMean age was 55 years old. 49% were men and 51% women. 75% involved the maxillary sinus, whereas 25% involved the sphenoid. 69% of our patients showed microcalcifications in the CT study. All the patients were surgically treated, with no cases of recurrence. ConclusionsClinical manifestations of fungus ball are non-specific, therefore endoscopy and image study are mandatory. The definitive diagnosis is made by histopathological study of the lesion. Endoscopic sinus surgery is the treatment of choice, with opening of the diseased sinus and complete removal of the fungus ball. The frequency of complications is very low. No oral or topical antimycotic treatments are necessary.

Modified Evisceration in a Blue-Fronted Amazon (Amazona aestiva) as AN Ocular Treatment Option in Parrots

A 39-year-old blue-fronted Amazon parrot (Amazona aestiva) was presented with a traumatic corneal perforation (2mm × 0.1mm) with gelatinous material protruding from the defect and a severely edematous moderately vascularized cornea. A surgical repair of the perforation was attempted but was unsuccessful. Following the surgical effort, an evisceration was performed. The evisceration technique used for the parrot was originally described in raptor species; however, modifications were required for the smaller-eyed patient. After executing a lateral canthotomy, a stab incision into the cornea was made at the limbus and a full-thickness 360° keratectomy was performed. This was followed by stepwise removal of uvea, lens, vitreous body, conjunctiva, nictitating membrane, and eyelids. Absorbable hemostatic gelatin sponge and cold fluids were used to reduce hemorrhage. Periorbital subcutaneous tissues and skin were closed with continuous and simple interrupted sutures, respectively. Antibiotic, antimycotic, and analgesic treatments were administered to the parrot for 2 weeks following the surgical procedure. Over a follow-up period of 12 months, the bird was in good general condition and achieved a satisfactory cosmetic result over the orbit from which the eye was removed. Alterations in normal behaviors such as flying, preening, feeding, and social interactions were not observed. Therefore, the authors conclude that this modified evisceration technique is a faster and less invasive surgical technique with reduced manipulation of the optic nerve and has a lower risk of orbital bone fracture and hemorrhage compared to previously reported enucleation procedures for parrot species. This modified ocular evisceration technique is a treatment option for inoperable ocular trauma in psittacine cases deemed appropriate.

Ligation of the ipsilateral common carotid artery and topical treatment for the prevention of epistaxis from guttural pouch mycosis in horses

The objective of the study was to evaluate the effect of ligation of the ipsilateral common carotid artery (CCA) combined with various antimycotic treatments for the prevention of epistaxis in...

Susceptibilty Testing of Candida spp. Strains to Ketoconazole Using Minimum Inhibitory Concentration Strip Test

Candida spp. infections in animals are becoming problematic and very frequent in the last decades. Antimycotic treatment is usually successful, but recently common cases of resistance are recorded. Minimum inhibitory concentration (MIC) test strips is a quantitative assay for determining the MIC of antimicrobial agents against microorganisms to indicate appropriate patient treatment and for identifying resistance patterns.The aim of this paper was the susceptibility testing of Candida strains isolated from animals in the area of Cluj-Napoca to ketoconazole, using MIC strip technique.Materials and methods: A total number of twenty-three Candida spp. strains isolated from both humans and animals were suspended in saline, and 1 ml of the resulted suspension (0.5 McFarland scale) was used to flood the Sabouraud Dextrose agar Petri dish. The suspension was then removed and the strip was placed in the middle of the plate. The incubation was performed at 28°C for 48 hours. When the strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is transferred into the agar matrix.The MIC is read directly from the scale in terms of I¼g/ml, at the point where the edge of the inhibition ellipse intersects with the MIC Test Strip. MIC for the 23 Candida spp. tested strains varied between 0.002 and 8 I¼g/ml, with an average of 3.6 I¼g/ml.Susceptibility testing of 23 Candida spp. isolates from Cluj-Napoca area to ketoconazole using the MIC strips is an accurate, simple, fast and accessible quantitative method, recommend for diagnostic in microbiological laboratories. Â

Pulmonary Aspergilloma: Indications for Surgery and Surgical Techniques

Aspergillus species may infect preexisting lung cavities and cause pulmonary aspergillomas, which may lead to life-threatening haemoptysis. The objective of this review article is to summarise current strategies for the management of pulmonary aspergillomas. Symptomatic aspergillomas should be treated surgically, with lobectomy being the treatment of choice. Minimally-invasive approaches may be appropriate in selected cases. The role of perioperative antifungal therapy in immunocompetent patients remains controversial. Antimycotic treatment and embolisation of bronchial arteries may be useful treatment options for inoperable patients.

Cluster analysis of Scedosporium boydii infections in a single hospital

Scedosporiosis is a rare, but often fatal mycotic infection occurring in immunosuppressed as well as in immunocompetent patients. Over a period of 14 months, Scedosporium boydii isolates were sent to our reference laboratory from six immunocompetent patients treated at a single hospital in Germany. In analogy to the EORTC/MSG criteria, four patients were classified as proven invasive scedosporiosis cases, and two patients as probable or possible cases. Of note, in five patients scedosporiosis was diagnosed between 1 and 14 months (median 5.0 months) after cardiac surgery. Despite antimycotic treatment two patients died, and three were lost for long-term follow-up. All clinical S. boydii isolates were characterized by molecular analysis using multilocus sequence typing (MLST). An identical MLST type was found in five patients who had been treated in the surgery unit, suggesting a link between these infections. The source of S. boydii has not been identified. Within an observation period of 2 years before and after this cluster of infections no further cases of scedosporiosis were reported from this hospital.