In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study.

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis. Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida. Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated. Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis. Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida.

Invasive Fusariosis in Nonneutropenic Patients, Spain, 2000-2015.

Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.

In vitro susceptibility of microorganisms isolated from cold stored corneas: increased gentamicin-resistance in cornea banking.

Donor cornea contamination is one of the major risks for corneal transplants. The use of antibiotics in storage media remains as one of the most important security measurements to minimize the contamination risk in corneal preservation. Since antibiotic resistance among microorganisms have been rising gradually, it is important to gain knowledge about the antimicrobial susceptibility pattern for choosing the most suitable antimicrobial agents. Thus, we evaluated the in vitro susceptibility of microorganisms isolated in donor corneas processed at the Center for Blood Transfusion, Tissues and Cells (Córdoba, Spain) during 4 years in order to evaluate the efficiency, and to promote changes for further antibiotics use. Our results show the high rate of resistance to gentamicin, an antibiotic used in corneal preservation media such as Optisol GS and Eusol-C. Conversely, all the analyzed microorganisms were sensitive to vancomycin. This suggests the possibility of replacing gentamicin with another more effective antibacterial agent such as vancomycin.

Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study).

Antifungal resistance is increasing by the emergence of intrinsically resistant species and by the development of secondary resistance in susceptible species. A previous study performed in Spain revealed levels of azole resistance in molds of between 10 and 12.7%, but secondary resistance in Aspergillus fumigatus was not detected. We used itraconazole (ITZ)-supplemented medium to select resistant strains. A total of 500 plates supplemented with 2 mg/liter of ITZ were sent to 10 Spanish tertiary hospitals, and molecular identification and antifungal susceptibility testing were performed. In addition, the cyp51A gene in those A. fumigatus strains showing azole resistance was sequenced. A total of 493 isolates were included in the study. Sixteen strains were isolated from patients with an infection classified as proven, 104 were isolated from patients with an infection classified as probable, and 373 were isolated from patients with an infection classified as colonization. Aspergillus was the most frequent genus isolated, at 80.3%, followed by Scedosporium-Lomentospora (7.9%), Penicillium-Talaromyces (4.5%), Fusarium (2.6%), and the order Mucorales (1%). Antifungal resistance was detected in Scedosporium-Lomentospora species, Fusarium, Talaromyces, and Mucorales Three strains of A. fumigatus sensu stricto were resistant to azoles; two of them harbored the TR34+L98H mechanism of resistance, and the other one had no mutations in cyp51A The level of azole resistance in A. fumigatus remains low, but cryptic species represent over 10% of the isolates and have a broader but overall higher range of antifungal resistance.

[Mixed invasive fungal infection due to Rhizomucor pusillus and Aspergillus niger in an immunocompetent patient]. / Infección fúngica invasiva mixta por Rhizomucor pusillus y Aspergillus niger en un paciente inmunocompetente.

BACKGROUND: Mucormycosis infections are rare in immunocompetent patients, and very few cases of mucormycosis associated with aspergillosis in non-haematological patients have been reported. CASE REPORT: A 17-year-old male, immunocompetent and without any previously known risk factors, was admitted to hospital due to a seizure episode 11 days after a motorcycle accident. He had a complicated clinical course as he had a mixed invasive fungal infection with pulmonary involvement due to Aspergillus niger and disseminated mucormycosis due to Rhizomucor pusillus (histopathological and microbiological diagnosis in several non-contiguous sites). He was treated with liposomal amphotericin B for 7 weeks (total cumulative dose >10 g) and required several surgical operations. The patient survived and was discharged from ICU after 5 months and multiple complications. CONCLUSIONS: Treatment with liposomal amphotericin B and aggressive surgical management achieved the eradication of a mixed invasive fungal infection. However, we emphasise the need to maintain a higher level of clinical suspicion and to perform microbiological techniques for early diagnosis of invasive fungal infections in non-immunocompromised patients, in order to prevent spread of the disease and the poor prognosis associated with it.

[Disseminated mucormycosis in immunocompetent patients: A disease that also exists]. / Mucormicosis diseminadas en pacientes sin inmunodeficiencias: una enfermedad que también existe.

Mucormycosis is usually an acute angioinvasive infections, which leads to non-suppurative necrosis and significant tissue damage. It represents 1.6% of all the invasive fungal infections and predominates in immunosuppressed patients with risk factors. Incidence has been significantly increased even in immunocompetent patients. Due to finding a case of disseminated mucormycosis caused by Rhizomucor pusillus in a young immunocompetent patient, a systematic review was carried out of reported cases in PubMed of mucormycosis in immunocompetent adults according to the main anatomic locations, and especially in disseminated cases. A review of the main risk factors and pathogenicity, clinical manifestations, techniques of early diagnosis, current treatment options, and prognosis is presented. Taxonomy and classification of the genus Mucor has also been reviewed.

Subcutaneous phaeohyphomycosis due to Alternaria infectoria in a renal transplant patient: surgical treatment with no long-term relapse.

BACKGROUND: Phaeohyphomycosis can be caused by a number of different species, being the most common Alternaria alternata and Alternaria infectoria. The biggest risk factor for the development of the infection is immunosuppression. AIMS: We present the case of a 64-year-old male renal transplant patient who came to hospital for presenting a tumour in the Achilles region which had been gradually growing in size. METHODS: A skin biopsy was taken for histological study and culture of fungi and mycobacteria. Blood tests and imaging studies were performed. RESULTS: Histopathology study and cultures identified A. infectoria as the causal agent. Imaging studies ruled out internal foci of infection. The lesion was surgically removed with no signs of recurrence after 24 months of follow-up. CONCLUSIONS: There are no treatment guidelines at present for cutaneous and subcutaneous Alternaria spp. infections. Various systemic antifungals have been used, either in combination with surgical removal or alone, with varying results. Surgery alone could be useful in the treatment of solitary, localised lesions in transplant patients in whom there are difficulties in controlling immunosuppression.

Epidemiology, species distribution and in vitro antifungal susceptibility of fungaemia in a Spanish multicentre prospective survey.

OBJECTIVES: To update the knowledge of the epidemiology of fungaemia episodes in Spain, the species implicated and their in vitro antifungal susceptibilities. METHODS: Episodes were identified prospectively over 13 months at 44 hospitals. Molecular methods were used to determine the cryptic species inside the Candida parapsilosis and Candida glabrata complexes. Susceptibility to amphotericin B, anidulafungin, caspofungin, fluconazole, flucytosine, itraconazole, micafungin, posaconazole and voriconazole was determined by a microdilution colorimetric method. New species-specific clinical breakpoints (SSCBPs) for echinocandins, fluconazole and voriconazole were applied. RESULTS: The incidence of the 1357 fungaemia episodes evaluated was 0.92 per 1000 admissions. The incidence of Candida albicans fungaemia was the highest (0.41 episodes/1000 admissions), followed by Candida parapsilosis sensu stricto (0.22). Candida orthopsilosis was the fifth cause of fungaemia (0.02), outnumbered by Candida glabrata and Candida tropicalis. Interestingly, the incidence of fungaemia by C. parapsilosis was 11 and 74 times higher than that by C. orthopsilosis and Candida metapsilosis, respectively. Neither Candida nivariensis nor Candida bracarensis was isolated. Fungaemia was more common in non-intensive care unit settings (65.2%) and among elderly patients (46.4%), mixed fungaemia being incidental (1.5%). Overall susceptibility rates were 77.6% for itraconazole, 91.9% for fluconazole and 96.5%-99.8% for the other agents. Important resistance rates were only observed in C. glabrata for itraconazole (24.1%) and posaconazole (14.5%), and in Candida krusei for itraconazole (81.5%). CONCLUSIONS: Fungaemia is more common in non-critical patients. C. albicans is the most common species, followed by C. parapsilosis and C. glabrata. Nearly 90% of yeasts are susceptible to all antifungal agents tested. Resistance rates change moderately when applying the new SSCBPs.

Epidemiology and antifungal susceptibility of bloodstream fungal isolates in pediatric patients: a Spanish multicenter prospective survey.

Data on fungemia epidemiology and antifungal susceptibility of isolates from children are scarce, leading frequently to pediatric empirical treatment based on available adult data. The present study was designed to update the epidemiological, mycological, and in vitro susceptibility data on fungal isolates from children with fungemia in Spain. All fungemia episodes were identified prospectively by blood culture over 13 months at 30 hospitals. Tests of susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, and micafungin were performed at participant institutions by a microdilution colorimetric method. New species-specific clinical breakpoints for fluconazole, voriconazole, and echinocandins were also applied. A total of 203 episodes of fungemia in 200 children were identified. A higher proportion of fungal isolates was from general wards than intensive care units (ICU). Candida parapsilosis (46.8%), Candida albicans (36.5%), Candida tropicalis (5.9%), Candida glabrata (3.9%), and Candida guilliermondii (2.5%) were the leading species. C. parapsilosis was the predominant species except in neonates. C. albicans was the most frequent in neonatal ICU settings (51.9%). Intravascular catheter (79.3%), surgery (35%), prematurity (30%), and neutropenia (11%) were the most frequent predisposing factors. Most Candida isolates (95.1%) were susceptible to all antifungals. When the new species-specific clinical breakpoints were applied, all C. parapsilosis isolates were susceptible to echinocandins except one, which was micafungin resistant. This is the largest published series of fungemia episodes in the pediatric setting. C. parapsilosis is the most prevalent species in Spain, followed by C. albicans and C. tropicalis. Resistance to azole and echinocandin agents is extremely rare among Candida species. The fluconazole resistance rate in Spain has decreased in the last 10 years.

Scedosporium apiospermum keratitis.

A case of Scedosporium apiospermum keratitis is reported in a 65-year-old farmer referred for treatment of an extensive corneal ulcer in the left eye. Direct examination of scrapes revealed abundant filamentous septate hyphae; all cultures were consistently positive for the same fungus, identified later as Scedosporium apiospermum. The patient successfully responded to treatment with amphotericin B.

[Salmonella spp. serotypes isolated at the Hospital Universitario Reina Sofía in Córdoba during an 8-year period, 1993-2000]. / Salmonella spp. Serotipos aislados en el Hospital Universitario Reina Sofía de Córdoba durante un período de 8 años (1993-2000).

BACKGROUND: As a producer of gastro-enteritis and other symptoms, Salmonella spp. Remains an important problem for world public health. Epidemiological knowledge at both general and local level by means of serotypification is considered one of the fundamental aspects for its control. MATERIAL AND METHOD: We studied 15.181 stool samples, and the others specimens. Isolation using the usual routine media, agar MacConkey, Salmonella-Shigella, selenito F. Identification using the automated Microscan and wider I method, serotypification with multi-purpose and monospecific serums (Difco), and confirmation of Salmonella and Shigella by the National Reference Laboratory, from the LNRSSE. RESULTS: Although 96.6% of Salmonella spp. Is detected in cultures of faeces and blood, it is also noted in LCR, sputum, rectal biopsy and vaginal secretions among other sites. In total of 1290 patients, 37 different serotypes were isolated, the most frequent of which were Enteritidis and Typhimurium. The presence of Virchow, isolated in both faeces and LCR, was notable in the years 94-99, as was as the presence of less typical serotypes, such as Blockley, London, Give and Mikawasima, among others.