The current state of Clinical Mycology in Eastern and South-Eastern Europe.

The ability of medical centers in Eastern and South-Eastern Europe to diagnose and treat fungal infections remains unknown. In order to investigate that, here we conducted a cross-sectional online survey, released at both The International Society for Human & Animal Mycology (ISHAM) and European Confederation of Medical Mycology (ECMM) websites. A total of 31 institutions responded to the questionnaire. Most centers (87.1%, n = 27) had access to Aspergillus spp. ELISA galactomannan testing as well as to Cryptococcus spp. antigen testing (83.9%, n = 26). Serological tests were mostly available for Aspergillus species (80.6%, n = 25); and most institutions reported access to mold-active antifungal drugs (83.9%; n = 26), but 5-flucytosine was available to only 29% (n = 9) of the participant centers. In conclusion, this study represents the first attempt to document the strengths and limitations of the Eastern and South-Eastern European region for diagnosing and treating fungal diseases. LAY SUMMARY: Our article is about the availability of diagnostic and treatments tools related to fungal infections in the countries of Eastern and South-Eastern region. Surveys like these are important to understand the gaps and point towards the fungal infections as a global health issue.

Comparison of Cryptococcus gattii/neoformans Species Complex to Related Genera (Papiliotrema and Naganishia) Reveal Variances in Virulence Associated Factors and Antifungal Susceptibility.

Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota. The genus Cryptococcus includes several species distributed around the world. The C. gattii/neoformans species complex is largely responsible for most cases of cryptococcosis. However, clinical series have been published of infections caused by Papiliotrema (Cryptococcus) laurentii and Naganishia albida (Cryptococcus albidus), among other related genera. Here, we examined the pathogenic potential and antifungal susceptibility of C. gattii/neoformans species complex (clades I and II) and related genera (Papiliotrema and Naganishia) isolated from environmental and clinical samples. P. laurentii (clade III), N. liquefasciens/N. albidosimilis (clade IV); and N. adeliensis/N. albida (clade V) strains produced higher levels of phospholipase and hemolysins, whereas the C. gattii/neoformans species complex strains (clades I and II) had markedly thicker capsules, produced more biofilm biomass and melanin, which are known virulence attributes. Interestingly, 40% of C. neoformans strains (clade II) had MICs above the ECV established for this species to amphotericin B. Several non-C. gattii/neoformans species complex (clades III to V) had MICs equal to or above the ECVs established for C. deuterogattii and C. neoformans for all the three antifungal drugs tested. Finally, all the non-C. gattii/neoformans clinical isolates (clades III to V) produced more melanin than the environmental isolates might reflect their particularly enhanced need for melanin during in vivo protection. It is very clear that C. gattii/neoformans species complex (clades I and II) strains, in general, show more similar virulence phenotypes between each other when compared to non-C. gattii/neoformans species complex (clades III to V) isolates. These observations together with the fact that P. laurentii and Naganishia spp. (clades III to V) strains were collected from the outside of a University Hospital, identify features of these yeasts important for environmental and patient colonization and furthermore, define mechanisms for infections with these uncommon pathogens.

Genotypic diversity and clinical outcome of cryptococcosis in renal transplant recipients in Brazil.

Genotypic diversity and fluconazole susceptibility of 82 Cryptococcus neoformans and Cryptococcus gattii isolates from 60 renal transplant recipients in Brazil were characterized. Clinical characteristics of the patients and prognostic factors were analysed. Seventy-two (87.8%) isolates were C. neoformans and 10 (12.2%) were C. gattii. VNI was the most common molecular type (40 cases; 66.7%), followed by VNII (9 cases; 15%), VGII (6 cases; 10%), VNB (4 cases; 6.7%) and VNI/II (1 case; 1.7%). The isolates showed a high genetic diversity in the haplotype network and six new sequence types were described, most of them for VNB. There was a bias towards skin involvement in the non-VNI population (P = .012). VGII isolates exhibited higher fluconazole minimum inhibitory concentrations compared to C. neoformans isolates (P = 0.008). The 30-day mortality rate was 38.3%, and it was significantly associated with fungemia and absence of headache. Patients infected with VGII had a high mortality rate at 90 days (66.7%). A variety of molecular types produce disease in renal transplant recipients in Brazil and highlighted by VGII and VNB. We report the clinical appearance and impact of the molecular type, fluconazole susceptibility of the isolates, and clinical characteristics on patient outcome in this population.

Outcomes of cryptococcosis in renal transplant recipients in a less-resourced health care system.

BACKGROUND: Cryptococcosis is the second most common cause of invasive fungal infections in renal transplant recipients in many countries, and data on graft outcome after treatment for this infection is lacking in less-resourced health care settings. METHODS: Data from 47 renal transplant recipients were retrospectively collected at a single institution during a period of 13 years. Graft dysfunction, graft loss, and mortality rates were evaluated. Predictors of mortality and graft loss were estimated. RESULTS: A total of 38 (97.4%) patients treated with amphotericin B deoxycholate (AMBd) showed graft dysfunction after antifungal initiation and 8 (18.2%) had kidney graft loss. Graft loss within 30 days after cryptococcosis onset was significantly associated with disseminated infection, greater baseline creatinine levels, and graft dysfunction concomitant to AMBd therapy and an additional nephrotoxic condition. The 30-day mortality rate was 19.2% and it was significantly associated with disseminated and pulmonary infections, somnolence at admission, high CSF opening pressure, positive CSF India ink, creatinine levels greater than 2.0 mg/dL at admission, graft dysfunction in patients treated with AMBd and an additional nephrotoxic condition and graft loss within 30 days. CONCLUSION: Graft dysfunction was common in renal transplant recipients with cryptococcosis treated with AMBd. The rate of graft loss rate was high, most frequently in patients with concomitant nephrotoxic conditions. Therefore, the clinical focus should be on the use of less nephrotoxic lipid formulations of amphotericin B in this specific population requiring a polyene induction regimen for treatment of severe cryptococcosis in all health care systems caring for transplantation recipients.

The war on cryptococcosis: A Review of the antifungal arsenal.

Cryptococcal meningitis is the most common central nervous system infection in the world today. It occurs primarily, but not exclusively, in immunocompromised individuals and despite substantial improvement in management of clinical events like AIDS, the numbers of cases of cryptococcosis remain very high. Unfortunately, despite several antifungal agents available for treatment, morbidity and mortality rates remain high with this fungal infection. In this Review, we will describe the treatments and strategies for success, identify the failures, and provide insights into the future developments / improvements for management. This sugar-coated yeast can play havoc within the human brain. Our goals must be to either prevent or diagnose disease early and treat aggressively with all our clinical tools when disease is detected.

The war on cryptococcosis: A Review of the antifungal arsenal

Cryptococcal meningitis is the most common central nervous system infection in the world today. It occurs primarily, but not exclusively, in immunocompromised individuals and despite substantial improvement in management of clinical events like AIDS, the numbers of cases of cryptococcosis remain very high. Unfortunately, despite several antifungal agents available for treatment, morbidity and mortality rates remain high with this fungal infection. In this Review, we will describe the treatments and strategies for success, identify the failures, and provide insights into the future developments / improvements for management. This sugar-coated yeast can play havoc within the human brain. Our goals must be to either prevent or diagnose disease early and treat aggressively with all our clinical tools when disease is detected.

When primary antifungal therapy fails.

The prognosis for persons with invasive fungal infections has improved over the past 2 decades because of the development of new diagnostic tools, a better understanding of the epidemiology and prognostic factors of these infections, and the availability of new antifungal agents. Nevertheless, antifungal therapy failure is still a substantial clinical problem. When this occurs, the clinician is tempted to attribute therapeutic failure to specific drug resistance and then to change therapy or add another antifungal drug to the regimen. However, other factors may play an even greater role in antifungal therapy failure, such as host factors, low concentration of the drug at the site of infection, drug toxicities, wrong diagnosis, and misdiagnosis of failure because of the occurrence of immune reconstitution inflammatory syndrome. In this review, we discuss the differential diagnosis and management of antifungal therapy failure in invasive mycoses, to help clinicians appreciate the meaning of primary antifungal therapy failure.

Phenotypic and genotypic evaluation of fluconazole resistance in vaginal Candida strains isolated from HIV-infected women from Brazil.

We conducted a study to determine the antifungal susceptibility of vaginal Candida isolates from HIV-infected Brazilian women. Among 127 women enrolled, positive cultures for yeast were obtained from 31 of 38 (81%) women with symptomatic vulvovaginitis, and from 41 of 89 (46%) asymptomatic women. Susceptibility testing demonstrated 11 of the 72 isolates had either resistance or dose-dependent susceptibility to azole drugs, including four Candida albicans strains. Expression of the MDR1, CDR1, CDR2 and ERG11 genes was evaluated in all of the C. albicans isolates, and all four of the strains with reduced susceptibility to fluconazole had increased expression of CDR1 as compared to the fluconazole-sensitive strains. No increased expression of the other genes was identified. This large survey of Candida isolates from HIV-infected women from Brazil demonstrates that reduced susceptibility to azoles occurs at a low frequency among vaginal yeast isolates, and when present in C. albicans, azole resistance is associated with increased expression of CDR1.

Comparison of caspofungin and amphotericin B for invasive candidiasis.

BACKGROUND: Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis. METHODS: We enrolled patients who had clinical evidence of infection and a positive culture for candida species from blood or another site. Patients were stratified according to the severity of disease, as indicated by the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the presence or absence of neutropenia and were randomly assigned to receive either caspofungin or amphotericin B. The study was designed to compare the efficacy of caspofungin with that of amphotericin B in patients with invasive candidiasis and in a subgroup with candidemia. RESULTS: Of the 239 patients enrolled, 224 were included in the modified intention-to-treat analysis. Base-line characteristics, including the percentage of patients with neutropenia and the mean APACHE II score, were similar in the two treatment groups. A modified intention-to-treat analysis showed that the efficacy of caspofungin was similar to that of amphotericin B, with successful outcomes in 73.4 percent of the patients treated with caspofungin and in 61.7 percent of those treated with amphotericin B (difference after adjustment for APACHE II score and neutropenic status, 12.7 percentage points; 95.6 percent confidence interval, -0.7 to 26.0). An analysis of patients who met prespecified criteria for evaluation showed that caspofungin was superior, with a favorable response in 80.7 percent of patients, as compared with 64.9 percent of those who received amphotericin B (difference, 15.4 percentage points; 95.6 percent confidence interval, 1.1 to 29.7). Caspofungin was as effective as amphotericin B in patients who had candidemia, with a favorable response in 71.7 percent and 62.8 percent of patients, respectively (difference, 10.0 percentage points; 95.0 percent confidence interval, -4.5 to 24.5). There were significantly fewer drug-related adverse events in the caspofungin group than in the amphotericin B group. CONCLUSIONS: Caspofungin is at least as effective as amphotericin B for the treatment of invasive candidiasis and, more specifically, candidemia.