Efficacy and safety of caspofungin for the treatment of invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

OBJECTIVES: We assessed the efficacy of a 3-week primary or salvage caspofungin regimen in patients with chronic obstructive pulmonary disease (COPD) and concomitant proven or suspected invasive pulmonary aspergillosis (IPA). METHODS: Forty-four patients were treated with an initial loading caspofungin dose of 70 mg, followed by a daily dose of 50 mg for 20 days. The main efficacy endpoint was clinical effectiveness. Secondary endpoints included the clinical efficacy of caspofungin after 1 week, therapeutic efficacy based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, the sensitivity of different Aspergillus strains to caspofungin in vitro, and the safety of caspofungin. RESULTS: An assessment of 42 patients in the intention-to-treat group revealed efficacy rates of 33.33% within 1 week and 38.10% within 3 weeks. According to the EORTC/MSG criteria, the treatment success rate was 38.10%. The success rate of first-line treatment was 54.76%, whereas salvage treatment had a success rate of 45.24%. No adverse events were reported among the participants. CONCLUSIONS: Caspofungin is effective and safe as an initial or salvage treatment for patients with IPA and COPD.

Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer.

BACKGROUND: Empiric antifungal therapy is considered the standard of care for high-risk neutropenic patients with persistent fever. The impact of a preemptive, diagnostic-driven approach based on galactomannan screening and chest computed tomography scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. METHODS: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (arm A) or preemptively (arm B), while receiving fluconazole 400 mg daily prophylactically. The primary end point of this noninferiority study was overall survival (OS) 42 days after randomization. RESULTS: Of 556 patients recruited, 549 were eligible: 275 in arm A and 274 in arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy, and 93% of them were in the first induction phase. At day 42, the OS was not inferior in arm B (96.7%; 95% confidence interval [CI], 93.8%-98.3%) when compared with arm A (93.1%; 95% CI, 89.3%-95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95% CI, 4.5%-10.8%) in arm B vs 6.6% (95% CI, 3.6%-9.5%) in arm A. The rate of patients who received caspofungin was significantly lower in arm B (27%) than in arm A (63%; P < .001). CONCLUSIONS: The preemptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs. Clinical Trials Registration. NCT01288378; EudraCT 2010-020814-27.

Infecciones fúngicas invasivas en niños hospitalizados en un centro de referencia de Uruguay / Invasive fungal infections in children hospitalized at a pediatric reference hospital in Uruguay / Infecções fúngicas invasivas em crianças internadas em um centro hospitalar de referência no Uruguai

Introducción: las infecciones fúngicas invasivas (IFI) son un problema de salud en creciente aumento. Objetivo: describir las características epidemiológicas, microbiológicas y clínicas de los menores de 15 años con IFI hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre 2010- 2019. Metodología: estudio retrospectivo, mediante revisión de historias clínicas. Variables: edad, sexo, comorbilidades, factores de riesgo, clínica, patógenos, tratamiento y evolución. Resultados: se registraron 26 casos de IFI en 23 niños. La mediana de edad fue 8 años, de sexo femenino 17, con comorbilidades 17: infección por VIH 5, enfermedad hematooncológica 4. Todos presentaban factores de riesgo para IFI. Las manifestaciones clínicas de sospecha fueron: fiebre en 19, síntomas neurológicos 11, respiratorios 9, gastrointestinales 6, urinarios 2, sepsis/shock en 3. Los agentes identificados fueron: Candida spp en 14, Cryptococcus neoformans complex 8 y Aspergillus fumigatus complex 4. Tratamiento: se indicó fluconazol en 15, asociado a anfotericina B 11. Todas las infecciones por candida fueron sensibles a los azoles. Fallecieron 7 niños, la mediana de edad fue 1 año. En 4 se identificó Candida spp, Aspergillus fumigatus complex 2 y Cryptococcus neoformans complex 1. Conclusiones: las IFI son poco frecuentes, afectan en su mayoría a niños inmunocomprometidos asociando elevada mortalidad. El diagnóstico requiere alto índice de sospecha. Candida spp y Cryptococcus spp fueron los agentes más involucrados. El inicio precoz del tratamiento acorde a la susceptibilidad disponible se asocia a menor mortalidad.

Summary: Introduction: invasive fungal infections (IFI) are an increasing health problem. Objective: describe the epidemiological, microbiological and clinical characteristics of children under 15 years of age with IFI hospitalized at the Pereira Rossell Hospital Center between 2010-2019. Methodology: retrospective study, review of medical records. Variables: age, sex, comorbidities, risk factors, symptoms, pathogens, treatment and evolution. Results: 26 cases of IFI were recorded involving 23 children. Median age 8 years, female 17, comorbidities 17, HIV infection 5, hematological-oncological disease 4. All with risk factors. Suspicion symptoms: fever 19, neurological symptoms 11, respiratory 9, gastrointestinal 6, urinary 2, sepsis / shock 3. Identified agents: Candida spp 14, Cryptococcus neoformans complex 8 and Aspergillus fumigatus complex 4. Treatment: fluconazole 15, associated with amphotericin B 11. All candida infections were sensitive to azoles. 7 died, median age 1 year. In 4, Candida spp was isolated, Aspergillus fumigatus complex in 2 and Cryptococcus neoformans complex in 1. Conclusions: IFI are rare, mostly affecting immunocompromised children, associated with high mortality. The diagnosis requires a high index of suspicion. Candida spp and Cryptococcus spp were the most involved agents. Early treatment according to available susceptibility is associated with lower mortality.

Introdução: as infecções fúngicas invasivas (IFI) são um problema de saúde crescente. Objetivo: descrever as características epidemiológicas, microbiológicas e clínicas de crianças menores de 15 anos com IFI internadas no Centro Hospitalar Pereira Rossell entre 2010 e 2019. Metodologia: estudo retrospectivo, revisão de prontuários. Variáveis: idade, sexo, comorbidades, fatores de risco, sintomas, patógenos, tratamento e evolução. Resultados: foram registrados 26 casos de IFI em 23 crianças. Idade mediana 8 anos, sexo feminino 17, comorbidades 17, infecção por HIV 5, doença hemato-oncológica 4. Todos com fatores de risco. Suspeita clínica: febre 19, sintomas neurológicos 11, respiratórios 9, gastrointestinais 6, urinários 2, sepse/choque 3. Agentes identificados: Candida spp 14, Cryptococcus neoformans complexo 8 e Aspergillus fumigatus complexo 4. Tratamento: fluconazol 15, associado à anfotericina B 11. Todas as infecções por cândida foram sensíveis aos azóis. 7 morreram, idade média de 1 ano. Em 4 das crianças Cândida spp foi isolada, Aspergillus fumigatus complexo em 2 e Cryptococcus neoformans complexo em 1. Conclusões: IFIs são raras, afetando principalmente crianças imunocomprometidas, associadas a alta mortalidade. O diagnóstico requer alto índice de suspeita. Cândida spp e Cryptococcus spp são os agentes mais envolvidos. O tratamento precoce de acordo com a suscetibilidade disponível está associado a menor mortalidade.

Gut-derived fungemia due to Kodamaea ohmeri combined with invasive pulmonary aspergillosis: a case report.

BACKGROUND: Kodamaea ohmeri is a rare pathogen with high mortality and is found among blood samples in a considerable proportion; however, gastrointestinal infection of K. ohmeri is extremely rare. Invasive pulmonary aspergillosis is also an uncommon fungal; these two fungal infections reported concomitantly are unprecedented. CASE PRESENTATION: We described a case of a 37-year-old male who got infected with K. ohmeri and invasive pulmonary aspergillosis. We used the mass spectrometry and histopathology to identify these two fungal infections separately. For the treatment of K. ohmeri, we chose caspofungin. As for invasive pulmonary aspergillosis, we used voriconazole, amphotericin B, and then surgery. The patient was treated successfully through the collaboration of multiple disciplines. CONCLUSIONS: We speculate that the destruction of the intestinal mucosa barrier can make the intestine one of the ways for certain fungi to infect the human body.

[Clinical Characteristic, Diagnosis and Treatment of Acute Lymphoblastic Leukemia Combined with Pneumocystis Carinii Pneumonia in Children].

OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-ß-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION: PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.

Clinical impact of Candida respiratory tract colonization and acute lung infections in critically ill patients with COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19), which is attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been causing a worldwide health issue. Airways colonization by Candida spp. is prevalent among patients on automatic ventilation in intensive care units (ICUs). This research aimed to ascertain the risk factors and roles of Candida spp. respiratory tract colonization, and Candida lung infection during the progression of COVID-19 pneumonia in critically ill patients. In total, Candida spp. were recovered in 69 from 100 immunosuppressed patients with COVID-19. Bronchoscopy was used to collect the Bronchoalveolar lavage (BAL) specimens. For the identification of Candida spp. PCR sequencing was done using the ITS1 and ITS4 primers. The amplification of the HWP1 gene was conducted to identify the Candida albicans complex. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin against Candida spp. were evaluated using the Clinical and Laboratory Standards Institute M60. In 63.77% of the patients, Candida respiratory colonization at D0 and D14 had no impact on the severity of COVID-19. In comparison to C. albicans strains, Candida respiratory disorder with C. glabrata had influenced the severity of COVID-19 for critically ill patients following adjustment for the risk factors of COVID-19 (P < 0.05). Amphotericin B and caspofungin showed superior activity against all Candida spp. All antifungal agents showed 100% sensitivity against the two C. africana strains. Our observation on patients who used automatic ventilation, respiratory colonization by Candida spp. was not seen to influence the infection or death caused by COVID-19. Amphotericin B and caspofungin showed superior activity against all Candida spp. and were recommended for the treatment regime of pulmonary candidiasis associated with COVID-19 infection. Although "Candida pneumonia" is rarely being reported in critically ill patients, Candida airway colonization mainly by Candida albicans is common especially among patients with diabetes, malignancies, and kidney disorders.

Efficacy and Safety of Caspofungin Treatment in Febrile Neutropenic Patients with Hematological Disorders: A Multicenter Consecutive Case Series.

Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient. Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met. Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen. Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.

Mucormycosis in patients with COVID-19: A cross-sectional descriptive multicentre study from Iran.

PURPOSE: The aim of the study was to report clinical features, contributing factors and outcome of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). METHODS: A cross-sectional descriptive multicentre study was conducted on patients with biopsy-proven mucormycosis with RT-PCR-confirmed COVID-19 from April to September 2020. Demographics, the time interval between COVID-19 and mucormycosis, underlying systemic diseases, clinical features, course of disease and outcomes were collected and analysed. RESULTS: Fifteen patients with COVID-19 and rhino-orbital mucormycosis were observed. The median age of patients was 52 years (range 14-71), and 66% were male. The median interval time between COVID-19 disease and diagnosis of mucormycosis was seven (range: 1-37) days. Among all, 13 patients (86%) had diabetes mellitus, while 7 (46.6%) previously received intravenous corticosteroid therapy. Five patients (33%) underwent orbital exenteration, while seven (47%) patients died from mucormycosis. Six patients (40%) received combined antifungal therapy and none that received combined antifungal therapy died. CONCLUSION: Clinicians should be aware that mucormycosis may be complication of COVID-19 in high-risk patients. Poor control of diabetes mellitus is an important predisposing factor for CAM. Systematic surveillance for control of diabetes mellitus and educating physician about the early diagnosis of CAM are suggested.

Severe polymicrobial and fungal periprosthetic osteomyelitis persisting after hip disarticulations treated with caspofungin in risk patients: a case series.

BACKGROUND: Periprosthetic fungal infections are considered rare and opportunistic infections. Treatment is difficult, and established standards do not yet exist. The choice of the appropriate antifungal drug might affect the patient outcome. CASES: All the three cases presented showed polybacterial recurrent infection of the revision hip arthroplasty. All patients were of younger age, had multiple revisions of the endoprosthesis, each had a large partial femoral replacement greater than 40% of the femoral length, gentamycin-loaded cement, and a long anchoring distance of the used intramedullary stem. Due to the severe life-threatening infection with deep osteomyelitis, an amputation had to be performed. However, despite surgical intervention, the fungal dominated infection persisted. Finally, only the use of caspofungin allowed permanent infection control. CONCLUSION: The polybacterial infection is driven by the symbiosis between fungi and bacteria. Therefore, eradication of the fungus is required to achieve elimination of the bacteria. Antimycotics of the echinocandin-class, such as caspofungin, may be considered as initial treatment.

Caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in patients with human immunodeficiency virus infection.

OBJECTIVES: The effectiveness of trimethoprim/sulfamethoxazole (TMP/SMZ) for pneumocystis pneumonia (PCP) is limited with adverse events. Caspofungin, by inhibiting the cyst form of Pneumocystis jirovecii, may be an alternative therapy for PCP. However, the availability of clinical data about caspofungin combined with TMP/SMZ in the treatment of PCP in HIV-infected patients is limited. Thus, we aimed to examine the clinical effectiveness and safety of caspofungin combined with TMP/SMZ as a first-line therapy for moderate-to-severe PCP in HIV-infected patients. METHODS: From January 2017 to December 2019, data of HIV-infected patients with moderate-to-severe PCP who received either TMP/SMZ alone or caspofungin combined with TMP/SMZ as first-line therapy were retrospectively reviewed to assess the effectiveness and safety of each regimen. The Kaplan-Meier curve and log-rank test were used for survival analysis. RESULTS: A total of 278 patients met the criteria. The overall positive response rate of PCP treatment was 48.92%, and the overall all-cause in-hospital mortality rate was 33.09%. Patients who received combination therapy consisting of caspofungin and TMP/SMZ had a better positive response rate (59.44% vs. 37.78%, P < 0.001) and lower all-cause in-hospital mortality rate (24.48% vs. 42.22%, P = 0.003). Also, patients who received combination therapy had higher survival rate during a hospital stay (75.52% vs. 57.78%, P = 0.004), and those who received longer combination therapy were more likely to have higher survival rate (P = 0.042). We found that age (P = 0.019), CD4 cell count (P = 0.001) and therapeutic regimen (P = 0.002) were significant risk factors for all-cause in-hospital mortality rate in univariate analysis. In multivariate analysis, only CD4 cell count and therapeutic regimen were statistically significant factors associated with all-cause in-hospital mortality rate. Patients with a CD4 count of > 30 cells/µL and patients who received combination therapy consisting of caspofungin and TMP/SMZ were more likely to survive from PCP (P = 0.011 and P = 0.002, respectively). There were no additional severe adverse events caused by adding caspofungin. CONCLUSIONS: For HIV-infected patients with moderate-to-severe PCP, combination therapy with caspofungin and TMP/SMZ is an effective and promising first-line therapy with no greater number of adverse events compared with TMP/SMZ monotherapy. Patients who received caspofungin had better positive response rates and lower all-cause in-hospital mortality rates. Also, we recommend early initiation of caspofungin.

Fungal endocarditis with heart valve replacement and atrial fibrillation posing a treatment challenge: A case report.

RATIONALE: Fungal endocarditis (FE) is a rare disease, in which antifungal treatment is necessary. When FE is complicated with prosthetic heart valve and/or atrial fibrillation, the coadministration of antifungal agents and warfarin is inevitable. We report a case of rheumatic heart disease with atrial fibrillation who developed FE following prosthetic heart valve replacement. The international normalized ratio (INR) increased significantly during the antifungal treatment with fluconazole. A discussion of the antifungal strategy in FE patients with prosthetic heart valves and/or atrial fibrillation and the interaction between antifungal agents and warfarin was performed. PATIENT CONCERNS: A 54-year-old Chinese woman experienced intermittent fevers, aphemia, and weakness in her right extremities. Her temperature was 38.7°C, and there was atrial fibrillation with heart rate 110 times/min. Neurological examination revealed that she had drowsiness, Broca aphasia, right central facial paralysis, and hemiplegia (Medical Research Council scale, upper limb grade 0, lower limb grade II). DIAGNOSES: Multiple infarction on magnetic resonance imaging and the occlusion of left middle cerebral artery suggested the occurrence of cerebral embolism. The presence of Candida parapsilosis in the results of 4 blood cultures and the existence of valve vegetation in the reexamination of echocardiogram supported the diagnosis of FE. INTERVENTIONS: The patient was given antifungal therapy with fluconazol. The INR increased dramatically on the 9th day of antifungal treatment, and subcutaneous bruising occurred at the intravenous infusion site. The antagonist of vitamin K1 was used and warfarin was reduced to a smaller dosage. The antifungal agent was replaced with caspofungin. OUTCOMES: Her speech improved significantly, and the muscle strength of her paralyzed side reached the Medical Research Council scale of grade IV. She continued to receive caspofungin for antifungal treatment with relatively stable INR and waited for heart valve surgery. LESSONS: The choice of antifungal agents is often a big challenge for FE patients, especially when they need warfarin for anticoagulation. It is better to administer a low dose of warfarin while carefully monitoring the INR or choose the antifungal drugs with little or no effect on warfarin.

Impact of biofilm production by Candida species and antifungal therapy on mortality of patients with candidemia.

BACKGROUND AND OBJECTIVES: Few studies have investigated the clinical outcomes of patients with candidemia caused by Candida species with different levels of biofilm formation. We aimed to investigate the impact of antifungal therapy on the outcome of candidemia caused by Candida species that were categorised as low biofilm formers (LBFs), moderate biofilm formers (MBFs), and high biofilm formers (HBFs). METHODS: Adults with candidemia caused by LBF and HBF/MBF Candida species that were susceptible to fluconazole and caspofungin were included to investigate the impact of treatment with fluconazole vs an echinocandin on 30-day crude mortality. RESULTS: In total, 215 patients with candidemia received fluconazole and 116 patients received an echinocandin. In multivariate analysis, Pittsburgh bacteremia score ≥ 4 (adjusted odds ratio [AOR] =2.42; 95% confidence interval [CI], 1.32-4.41), malignancy (AOR = 3.45; 95% CI, 1.83-6.51), not removing the central venous catheter within 48 hours of a positive blood culture (AOR = 4.69; 95% CI, 2.61-8.45), and treatment with fluconazole for candidemia due to HBF/MBF Candida spp. (AOR = 2.23; 95% CI, 1.22-4.06) were independent factors associated with 30-day mortality. Of the 165 patients infected by HBF/MBF Candida isolates, those who received azole therapy had a significantly higher sepsis-related mortality rate than those who received echinocandin therapy (44.9% [49/109] vs 26.8% [15/56], P = .03). CONCLUSIONS: There was a trend of an independent association between fluconazole treatment and poor outcomes in the patients infected by HBF/MBF Candida strains.

Quantification of 1,3-ß-d-glucan by Wako ß-glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study.

OBJECTIVES: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available ß-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. METHODS: BDG results by Wako ß-glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. RESULTS: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1-3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut-offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively). CONCLUSIONS: The classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

Rhodotorula dairenensis fungemia in a patient with cancer.

BACKGROUND: Rhodotorula species were traditionally considered non-virulent environmental microorganisms, but are nowadays considered important human pathogens, especially in immunocompromised individuals. CASE REPORT: We present the case of a 73 year-old man with diarrhea, anorexia and fever. In the blood analyses, both aerobic blood culture bottles yielded the growth of Rhodotorula dairenensis. The MALDI-TOF MS score was inadequate to provide an identification, which was achieved by means of molecular techniques. Treatment with an echinocandin was started, but the patient died. CONCLUSIONS: Basidiomycetous yeast genera such as Rhodotorula can cause invasive and severe infections, e.g., fungemia, especially in patients with central venous catheter or another indwelling device.

Emergence of azole resistant-Aspergillus fumigatus infections during STAT3-deficiency.

Introduction. Signal transducer and activator of transcription 3 (STAT3) deficiency is a rare primary immunodeficiency associated with increased susceptibility to bacterial and fungal infections, notably pulmonary aspergillosis.Aim. We describe the emergence of azole-resistant Aspergillus fumigatus infections in STAT3-deficient patients.Methodology. During a retrospective study of 13 pulmonary aspergillosis cases in STAT3-deficient patients conducted in France, we identified patients infected with azole-resistant A. fumigatus isolates.Results. Two out of the 13 STAT3-deficient patients with aspergillosis had azole-resistant A. fumigatus infection, indicating an unexpectedly high prevalence of resistance. The first patient with STAT3 deficiency presented several flares of allergic bronchopulmonary aspergillosis-like episodes. He was chronically infected with two azole-resistant A. fumigatus isolates (TR34/L98). Despite prolonged antifungal treatment, including caspofungin and amphotericin B, the patient was not able to clear the azole-resistant A. fumigatus. The second patient had chronic cavitary pulmonary aspergillosis (CCPA). The A. fumigatus isolate was initially azole susceptible but harboured three F46Y, M172V and E427K point mutations. Despite prolonged antifungal therapies, lesions worsened and the isolate became resistant to all azoles. Surgery and caspofungin treatments were then required to cure CCPA. Resistance was probably acquired from the environment (TR34/L98) in the first case whereas resistance developed under antifungal treatments in the second case. These infections required long-term antifungal treatments and surgery.Conclusions. The emergence of azole-resistant A. fumigatus infections in STAT3-deficiency dramatically impacts both curative and prophylactic antifungal strategies. Physicians following patients with primary immune-deficiencies should be aware of this emerging problem as it complicates management of the patient.

Cost-Effectiveness of Antifungal Supplementation of Corneal Cold Storage Media.

PURPOSE: To evaluate the cost-effectiveness of supplementing hypothermic cold storage media (CSM) with antifungal therapy. DESIGN: Cost-effectiveness analysis (CEA). PARTICIPANT: Base case of a patient with Fuch's endothelial dystrophy undergoing a first eye keratoplasty. METHODS: Cost-effective analysis of the base case with corneal tissue stored in CSM or CSM supplemented with antifungal therapy over a 16-year time horizon. Multiple clinical scenarios were considered, including endothelial keratoplasty (EK) and penetrating keratoplasty (PK); amphotericin B, voriconazole, caspofungin, and combination therapy; and third-party payer and societal perspectives. The incidences were derived from PubMed literature searches and average wholesale prices of medications; all costs were discounted 3% per annum and adjusted for inflation to 2019 US dollars. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs). RESULTS: In the reference case, a corneal endothelial graft stored in amphotericin B-supplemented CSM was the most cost-effective approach from a third-party payer and societal perspective. Probability sensitivity analysis (PSA) of the societal model for the EK was robust, with 93.5% being below an arbitrary willingness-to-pay threshold (WTP) of $20 000 per fungal infection averted. Voriconazole, caspofungin, and combination antifungals were less cost-effective than amphotericin B. The main factors influencing the CEA were the incidences of postkeratoplasty fungal infections, potential increases in graft failures, and antifungal costs. For grafts intended for PKs, antifungal supplementation was less cost-effective than for EKs. CONCLUSIONS: Antifungal supplementation with amphotericin B for EK grafts was the most cost-effective approach of the studied antifungals; however, the CEA was sensitive to potential changes in graft failure rates, underlining the importance of long-term safety studies. For full-thickness corneal grafts, antifungal supplementation was less cost-effective.

Candida Parapsilosis Endocarditis Following Transcatheter Pulmonary Valve Implantation.

Fungal prosthetic valve endocarditis (PVE) is rare and carries a high mortality rate. While uncommon, fungal endocarditis in transcatheter aortic valves has been reported. We present a unique case of Candida parapsilosis fungal PVE in a patient with a transcatheter pulmonary valve replacement.