Name Changes for Fungi of Medical Importance, 2016-2017.

This article lists proposed new or revised species names and classification changes associated with fungi of medical importance that were published in the years 2016 and 2017. While many of the revised names listed have been widely adopted without further discussion, some may take longer to achieve more general usage.

Name Changes for Fungi of Medical Importance, 2012 to 2015.

This article lists proposed new or revised species names and classification changes associated with fungi of medical importance for the years 2012 through 2015. While many of the revised names listed have been widely adopted without further discussion, some may take longer to achieve more general usage.

Trends in the epidemiology of invasive fungal infections.

Invasive fungal infections have increased in importance, largely because of the increasing size of the population at risk. Candida species remain the fourth most important cause of hospital-acquired bloodstream infections. Infections with Candida species other than C. albicans appear to have become more common, but significant geographic variation has been reported. Invasive aspergillosis and other mould infections are a leading cause of infection-related death in hematopoietic stem cell transplant recipients. Although Aspergillus fumigatus remains the most frequent cause of infection, A. terreus has emerged as an important pathogen, at least among certain populations. Despite marked reductions in the rates of AIDS-associated fungal infections, such as cryptococcosis, in the United States and other developed countries, the burden of these diseases in developing countries is large and increasing. Enhanced surveillance and reporting will be critical to improve our understanding of the importance of invasive fungal infections, to enable prioritization of research and prevention efforts, and to evaluate prevention strategies.

Candidemia in neonatal intensive care units: Barcelona, Spain.

BACKGROUND: Candida spp. are increasingly important hospital-acquired pathogens in neonatal intensive care units (NICU) and cause considerable mortality in preterm infants. Most studies have been limited to a single institution. The aim of this study was to determine the epidemiology of candidemia in all Barcelona NICUs. METHODS: We conducted prospective population-based surveillance for candidemia in Barcelona, Spain, during 2002-2003. This report focuses on the results from 5 participating hospitals with NICUs. RESULTS: We detected 24 cases, resulting in an annual incidence of 32.6 cases per 100,000 live births and 1.1 cases per 100 NICU discharges. Median gestational age was 27.5 weeks (range, 24-40.5), and there were 21 cases among very low birth weight infants. Among the 20 (83%) cases evaluated for the presence of end organ infection, endophthalmitis occurred in 2 cases, and endocarditis, meningitis and peritonitis occurred in 1 case each. Candida parapsilosis was the most frequent species isolated (67%). All isolates were fluconazole-susceptible. Crude mortality was 21%. CONCLUSIONS: The preponderance of C. parapsilosis candidemias observed in Barcelona NICUs is similar to reports from the literature. Morbidity and mortality associated with neonatal candidemia remain high.

Antifungal drug susceptibility testing and resistance in Aspergillus.

Aspergillus species are the most common causes of invasive mold infections in immunocompromised patients. The introduction of new antifungal agents, and recent reports of resistance emerging during treatment of aspergillus infections, have highlighted the need for standardized methods of antifungal drug susceptibility testing for filamentous fungi. This review describes the methods that are now being developed for the in vitro testing of Aspergillus species, and the results of attempts to correlate in vitro findings with in vivo outcome. The mechanisms and clinical importance of resistance to the different agents used in the treatment of human aspergillosis are discussed. Copyright 1999 Harcourt Publishers Ltd.

Fungal infections among returning travelers.

Endemic mycoses, such as histoplasmosis, coccidioidomycosis, and penicilliosis, have emerged as important health threats among travelers to regions of the world where these infections are endemic. Travelers have developed fungal infections as a result of a wide range of recreational and work activities, many of which have involved well-recognized risk factors for these diseases. In some instances, infections have been acquired during short trips, whereas, in other instances, infection has been acquired during a longer period of residence in an area where the infection is endemic. Travelers need to be made aware of the risks of acquiring mycotic diseases when visiting such regions. Health care providers need to consider these infections in their differential diagnosis among returning travelers with respiratory illness and should be familiar with the treatment and prevention of these diseases.

Outbreak of invasive aspergillosis among renal transplant recipients.

Invasive aspergillosis (IA) is rare among renal transplant recipients (RTRs). We investigated a cluster of IA among RTRs at a California hospital from January to February 2001, when construction was ongoing. We conducted a cohort study among RTRs who were hospitalized between January 1 and February 5, 2001, to determine risk factors for IA. IA was defined using established guidelines. Four IA cases occurred among 40 RTRs hospitalized during the study period. Factors associated with an increased risk of IA included prolonged hemodialysis, lengthy corticosteroid treatment posttransplant, and use of sirolimus alone or with mycophenolate (P<0.05). After the study period, three additional RTRs developed IA; two Aspergillus isolates recovered from these patients had indistinguishable profiles by DNA fingerprinting, suggesting common-source exposure. This study suggests that immunosuppressed RTRs can be at an increased risk for IA. Measures to prevent IA in these patients should be taken during hospital construction.

A large histoplasmosis outbreak among high school students in Indiana, 2001.

BACKGROUND: A histoplasmosis outbreak occurred in an Indiana high school in November-December 2001. METHODS: To describe the risk factors for this outbreak, we conducted a cohort study of all available students and staff (N = 682) and an environmental investigation. RESULTS: Of the 523 (77%) persons who displayed serologic evidence of recent Histoplasma capsulatum infection, 355 (68%) developed symptoms consistent with acute pulmonary histoplasmosis. Rototilling of soil in a school courtyard known to be a bird roosting site had been performed during school hours on November 12, 2001, 14 days before both the peak of the onset of illness and a rise in student absenteeism. Being a student (odds ratio, 3.3; 95% confidence interval, 2.2-5.0) and being a student in a classroom near the courtyard during the rototilling (odds ratio, 3.1; 95% confidence interval, 1.8-5.2) were independently associated with infection and symptomatic illness. H. capsulatum was isolated from environmental samples, including soil from the courtyard and dust collected from a filter of a heating, ventilating and air-conditioning system. CONCLUSIONS: Soil-disrupting activities within a school courtyard caused the largest outbreak to date of histoplasmosis among adolescents. Improved efforts are needed to educate the community in endemic areas about histoplasmosis to prevent the occurrence of such outbreaks in the future. In addition, increased awareness among health care providers of this disease would facilitate appropriate diagnosis and treatment.

Histoplasmosis associated with exploring a bat-inhabited cave in Costa Rica, 1998-1999.

Between October 1998 and April 1999, 51 persons belonging to two separate groups developed acute pulmonary histoplasmosis after visiting a cave in Costa Rica. The first group consisted of 61 children and 14 adults from San Jose, Costa Rica; 44 (72%) were diagnosed with acute histoplasmosis. The second group comprised 14 tourists from the United States and Canada; 9 (64%) were diagnosed with histoplasmosis. After a median incubation time of 14 days, the most common symptoms were headache, fever, cough, and myalgias. Risk factors for developing histoplasmosis included crawling (odds ratio [OR] = 17.5, 95% confidence interval [CI] = 2.3-802) and visiting one specific room (OR = 3.4, 95% CI = 1.0-12.3) in the cave. Washing hands (OR = 0.1, 95% CI = 0.01-0.6) after exiting the cave was associated with a decreased risk of developing histoplasmosis. Histoplasma capsulatum was isolated from bat guano collected from inside the cave. Persons who explore caves, whether for recreation or science, should be aware of the risk bat-inhabited caves pose for developing histoplasmosis, especially if they are immunocompromised in any way.

A large outbreak of histoplasmosis among American travelers associated with a hotel in Acapulco, Mexico, spring 2001.

During spring 2001, college students from Pennsylvania reported an acute febrile respiratory illness after returning from spring break vacation in Acapulco, Mexico. Acute pulmonary histoplasmosis was presumptively diagnosed and the cluster of illness was reported to the Centers of Disease Control and Prevention. A large investigation then ensued, which included finding student-travelers for interviews and requesting sera for histoplasmosis testing. We defined a clinical case by fever and at least one of the following: cough, shortness of breath, chest pain, or headache, in an Acapulco traveler during March-May 2001. A laboratory-confirmed case had positive serology. An initial study determined that the likely site of histoplasmosis exposure was Hotel H; we therefore performed a large cohort study among travelers who stayed at Hotel H. Of 757 contacted, 262 (36%) met the clinical case definition. Of 273 serum specimens tested, 148 (54%) were positive. Frequent use of Hotel H's stairwells, where construction was ongoing, was associated with increased risk of illness (relative risk = 10.5, 95% confidence interval = 3.7-30.5; P < 0.001). This is the first histoplasmosis outbreak associated with a hotel undergoing construction. Hotels in endemic areas should consider construction precaution measures to prevent histoplasmosis among their guests.

Evolving strategies in the management of aspergillosis.

Aspergillus spp. remain the most common causes of invasive mould infections among patients with hematologic malignancies and recipients of solid-organ and hematopoietic stem-cell transplants. Despite advances in prevention and treatment, invasive aspergillosis continues to be a deadly disease. This paper reviews current approaches to treatment of aspergillosis in adults, including surgical and immune-based strategies, and developments in prophylaxis for aspergillosis in high-risk patient populations.

Coccidioides species as potential agents of bioterrorism.

Coccidioides species are soil fungi endemic to the southwestern USA, and parts of Central and South America. Natural infection occurs as a result of inhalation of airborne arthroconidia. There is a wide spectrum of clinical illness and, although most human cases are self-limiting and inconsequential, infection can result in severe effects and sometimes death. Both Coccidioides immitis and Coccidioides posadasii are potential bioterrorism agents. As such, in the USA and elsewhere, these organisms fall under stringent regulations that govern their possession, use and transfer. However, the public health consequences of their deliberate release among a susceptible civilian population are uncertain and most probably limited.

Fungal diseases: an evolving public health challenge.

The emergence of new fungal pathogens and the resurgence of mycotic diseases that had previously been uncommon is a serious and growing public health problem. This review examines the factors involved in the emergence or re-emergence of several mycotic diseases, including coccidioidomycosis and cryptococcosis, over the past two decades. New approaches to prevention and control are also discussed.

Comparison of multilocus sequence typing and Ca3 fingerprinting for molecular subtyping epidemiologically-related clinical isolates of Candida albicans.

Southern hybridization with the complex probe Ca3 is a well established tool for molecular subtyping of Candida albicans. Multilocus sequence typing (MLST) is a DNA sequence-based subtyping method recently applied to C. albicans and shown to have a high degree of intraspecies discriminatory power. However, its utility for studying the molecular epidemiology of sequential isolates from recurrent disease has not been established. We compared Ca3 Southern hybridization and MLST using seven housekeeping genes (CaAAT1a, CaACC1, CaADP1, CaPMI, CaSYA1, CaVPS13, CaZWF1b) for their ability to discriminate among 37 C. albicans isolates from recurrent cases of oropharyngeal candidiasis (OPC) in ten HIV-positive patients from India and the US. Among the 37 isolates, MLST identified 23 distinct genotypes (index of diversity = 97%); Ca3 Southern hybridization identified 21 distinct genotypes (index of diversity = 95%). Both methods clustered isolates into seven genetically-related groups and, with one exception, isolates that were indistinguishable by MLST were indistinguishable or highly related by Ca3 Southern hybridization. These results demonstrate that MLST performs equally well or better compared to Ca3 Southern hybridization for defining genetic-relatedness of sequential C. albicans isolates from recurrent cases of OPC in HIV-positive patients.

Evaluation of amphotericin B interpretive breakpoints for Candida bloodstream isolates by correlation with therapeutic outcome.

One hundred seven Candida bloodstream isolates (51 C. albicans, 24 C. glabrata, 13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C. lusitaniae strains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of >or=5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 microg/ml); the corresponding MFC values ranged from 0.5 to 4 microg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 microg/ml and 0.06 to 2 microg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 microg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.

Rapid acquisition of stable azole resistance by Candida glabrata isolates obtained before the clinical introduction of fluconazole.

Five azole-susceptible Candida glabrata isolates obtained before 1975 became resistant to fluconazole, itraconazole, and voriconazole within 4 days of in vitro fluconazole exposure. This cross-resistance was stable for at least 4 months after removal of fluconazole and was associated with increased CgCDR1 and CgCDR2 expression.

Assessment of ribosomal large-subunit D1-D2, internal transcribed spacer 1, and internal transcribed spacer 2 regions as targets for molecular identification of medically important Aspergillus species.

Molecular approaches are now being developed to provide a more rapid and objective identification of fungi compared to traditional phenotypic methods. Ribosomal targets, especially the large-subunit RNA gene (D1-D2 region) and internal transcribed spacers 1 and 2 (ITS1 and ITS2 regions), have shown particular promise for the molecular identification of some fungi. We therefore conducted an assessment of these regions for the identification of 13 medically important Aspergillus species: Aspergillus candidus, Aspergillus (Eurotium) chevalieri, Aspergillus (Fennellia) flavipes, Aspergillus flavus, Aspergillus fumigatus, Aspergillus granulosus, Aspergillus (Emericella) nidulans, Aspergillus niger, Aspergillus restrictus, Aspergillus sydowii, Aspergillus terreus, Aspergillus ustus, and Aspergillus versicolor. The length of ribosomal regions could not be reliably used to differentiate among all Aspergillus species examined. DNA alignment and pairwise nucleotide comparisons demonstrated 91.9 to 99.6% interspecies sequence identities in the D1-D2 region, 57.4 to 98.1% in the ITS1 region, and 75.6 to 98.3% in the ITS2 region. Comparative analysis using GenBank reference data showed that 10 of the 13 species examined exhibited a < or = 1-nucleotide divergence in the D1-D2 region from closely related but different species. In contrast, only 5 of the species examined exhibited a < or = 1-nucleotide divergence from sibling species in their ITS1 or ITS2 sequences. Although the GenBank database currently lacks ITS sequence entries for some species, and major improvement in the quality and accuracy of GenBank entries is needed, current identification of medically important Aspergillus species using GenBank reference data seems more reliable using ITS query sequences than D1-D2 sequences, especially for the identification of closely related species.

An epidemic of coccidioidomycosis in Arizona associated with climatic changes, 1998-2001.

BACKGROUND: Reports of coccidioidomycosis cases in Arizona have increased substantially. We investigated factors associated with the increase. METHODS: We analyzed the National Electronic Telecommunications System for Surveillance (NETSS) data from 1998 to 2001 and used Geographic Information Systems (GIS) to map high-incidence areas in Maricopa County. Poisson regression analysis was performed to assess the effect of climatic and environmental factors on the number of monthly cases; a model was developed and tested to predict outbreaks. RESULTS: The overall incidence in 2001 was 43 cases/100,000 population, a significant (P<.01, test for trend) increase from 1998 (33 cases/100,000 population); the highest age-specific rate was in persons > or =65 years old (79 cases/100,000 population in 2001). Analysis of NETSS data by season indicated high-incidence periods during the winter (November-February). GIS analysis showed that the highest-incidence areas were in the periphery of Phoenix. Multivariable Poisson regression modeling revealed that a combination of certain climatic and environmental factors were highly correlated with seasonal outbreaks (R2=0.75). CONCLUSIONS: Coccidioidomycosis in Arizona has increased. Its incidence is driven by seasonal outbreaks associated with environmental and climatic changes. Our study may allow public-health officials to predict seasonal outbreaks in Arizona and to alert the public and physicians early, so that appropriate preventive measures can be implemented.

In vitro susceptibilities of bloodstream isolates of Candida species to six antifungal agents: results from a population-based active surveillance programme, Barcelona, Spain, 2002-2003.

OBJECTIVES: The antifungal drug susceptibilities of 351 isolates of Candida species, obtained through active laboratory-based surveillance in the period January 2002-December 2003, were determined (Candida albicans 51%, Candida parapsilosis 23%, Candida tropicalis 10%, Candida glabrata 9%, Candida krusei 4%). METHODS: The MICs of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and caspofungin were established by means of the broth microdilution reference procedure of the European Committee on Antibiotic Susceptibility Testing. RESULTS AND CONCLUSIONS: Amphotericin B and flucytosine were active in vitro against all strains. A total of 24 isolates (6.8%) showed decreased susceptibility to fluconazole (MIC > or = 16 mg/L) and 43 (12.3%) showed decreased susceptibility to itraconazole (MIC > or = 0.25 mg/L). Voriconazole and caspofungin were active in vitro against the majority of isolates, even those that were resistant to fluconazole.

Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, barcelona, Spain, from 2002 to 2003.

We conducted population-based surveillance for Candida bloodstream infections in Spain to determine its incidence, the extent of antifungal resistance, and risk factors for mortality. A case was defined as the first positive blood culture for any Candida spp. in a resident of Barcelona, from 1 January 2002 to 31 December 2003. We defined early mortality as occurring between days 3 to 7 after candidemia and late mortality as occurring between days 8 to 30. We detected 345 cases of candidemia, for an average annual incidence of 4.3 cases/100,000 population, 0.53 cases/1,000 hospital discharges, and 0.73 cases/10,000 patient-days. Outpatients comprised 11% of the cases, and 89% had a central venous catheter (CVC) at diagnosis. Overall mortality was 44%. Candida albicans was the most frequent species (51% of cases), followed by Candida parapsilosis (23%), Candida tropicalis (10%), Candida glabrata (8%), Candida krusei (4%), and other species (3%). Twenty-four isolates (7%) had decreased susceptibility to fluconazole (MIC > or = 16 microg/ml). On multivariable analysis, early death was independently associated with hematological malignancy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.1 to 10.4). Treatment with antifungals (OR, 0.05; 95% CI, 0.01 to 0.2) and removal of CVCs (OR, 0.3; 95% CI, 0.1 to 0.9) were protective factors for early death. Receiving adequate treatment, defined as having CVCs removed and administration of an antifungal medication (OR, 0.2; 95% CI, 0.08 to 0.8), was associated with lower odds of late mortality; intubation (OR, 7.5; 95% CI, 2.6 to 21.1) was associated with higher odds. The incidence of candidemia and prevalence of fluconazole resistance are similar to other European countries, indicating that routine antifungal susceptibility testing is not warranted. Antifungal medication and catheter removal are critical in preventing mortality.