Epidemiology of Invasive Fungal Infections in the Mediterranean Area

Ulrike Binder and Cornelia Lass-Flörl

Division of Hygiene and Medical Microbiology, Medical University Innsbruck, Austria.

Correspondence to: Cornelia Lass-Flörl, Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Medical University Innsbruck, Fritz Pregl Str. 3/3, A-6020 Innsbruck, Tirol, Austria. Tel.: +43(0)512 9003 70700; fax: +43(0)512 9003 73700. E-mail:  cornelia-lass-floerl@i-med.ac.at

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction
Invasive fungal infections (IFIs) are an increasingly important clinical dilemma, engendering high rates of morbidity and mortality, particularly in immunocompromised populations. As a result of growing numbers of patients with a variety of risk factors (e.g. transplantation, chemotherapy, HIV infection, use of corticosteroids or new immunosuppressive agents), the incidence of IFIs has increased substantially in recent years.[1,2,3,4,5,6,7] For example, aggressive new therapies for transplant recipients and patients with hematologic malignancies have led to more profound immunosuppression of longer duration.[7]
In addition, advances in medical care are extending the survival of critically ill patients, rendering them more vulnerable to IFIs. [1,2,8,9] The incidence and severity of IFIs as well as the causative pathogens are dependent on various risk factors concerning the patient such as the underlying condition, the state of immunosuppression, but also the geographic location of the patient.[2,6,10]
A wide variety of pathogens can be associated with IFIs. Historically, Candida species have by far been the most common infective organisms among fungi. However, the epidemiology has changed dramatically in recent years: IFIs caused by moulds – predominantly Aspergillus species - have increased substantially and newly emerging and rare fungal pathogens such as Glomeromycota (e.g. Rhizopus and Mucor species), hyaline moulds (e.g. Fusarium species) and other opportunistic species (e.g. Scedosporium species) are increasingly being reported.[7,8,11,12] This article will predominantly review the most common causatives of IFIs, concentrating on the changing epidemiology of fungal infections and focusing on surveys carried out in the Mediterranean area.

Yeasts and Yeast-Like Pathogens
Candida species: Candida infections are the most frequent cause of IFIs worldwide, with a case rate of 72.8 per 1,000,000 per year [13] and can result in a wide range of clinical symptoms, from mucocutaneous overgrowth to blood stream infections and metastatic infections.[8,14,15] More than 100 Candida species have been found to be pathogenic with their frequency varying according to the geographic setting.[16,17,18,19]
The burden of invasive candidiasis remains substantial; after a decline in mortality throughout the early to mid 1990s, mortality rates have leveled off in recent years.[13] In the United States, Candida species are the fourth most common cause of nosocomial blood stream infection.[13] Candida (C.) albicans remains by far the most common species causing invasive candidiasis worldwide (62% in 2003) although the frequency of candidiasis caused by other species including C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei has been increasing steadily over the last 10 years.[13] Two studies in Italy and Spain show the distribution of Candida species in the Mediterranean area which was shown to be generally similar to reports from other European countries.[20,21,22,23]
An Italian study [21] revealed, that C. albicans (61 % of all isolates) was followed by C. parapsilosis, C. glabrata and C.tropicalis, which is similar to reports from other European countries, with the only difference that here C. glabrata was shown to be the 3rd most common species, while it is the 2nd most common in Switzerland,[24] the UK25 and the US.[26] Interestingly, in a Spanish study, carried out in Barcelona, C. glabrata was shown to be only the 4th most common species, with C. tropicalis being the 3rd and C. parapsilosis the 2nd most common following C. albicans. [27] The same Spanish study [27] revealed, that the overall incidence of bloodstream infections caused by Candida in Barcelona is lower (4.3 cases per 100 000 population) than in the US (6-10 per 100 000 population).[3,28,29] Nevertheless, the number of incidence in Spain correlated well with reports from Northern European countries.[30,31] Candida bloodstream infections are in general very high among neonates and infants.[20,27,32] With 38.8 cases per 100 000 population the number of incidence in Barcelona/Spain is within the range of numbers obtained from studies in the US.26 However, C. parapsilosis was the most common species isolated from neonates in Spain (67% of all cases)20, whereas in the US C. albicans was the most common species and the proportion of C. parapsilosis infections was significantly lower (27-45%) than in Spain.[20,28,29]
Since the 1990s, fluconazole has been widely used for both treatment and prophylaxis of immunosuppressed patients resulting in decreasing rates of Candida bloodstream infections worldwide. The downside of this application was that C. glabrata, being less susceptible to fluconazole,[3,33] as well as other non-albicans infections are emerging, such as C. krusei which is fluconazole resistant. [34] In a nationwide surveillance study in Spain the frequency of antifungal resistance was determined next to species distribution and incident rates. This study revealed that 7 % of all isolates exhibited decreased susceptibility to fluconazole with a linear correlation to voriconazole resistance. Furthermore, MICs for voriconazole where increased in patients that received fluconazole before, than in those without previous exposure to fluconazole.[35] Another Spanish study investigated the susceptibility to voriconazole of more than 4000 clinical Candida isolates according to EUCAST testing, and revealed that among C. albicans, C. parapsilosis and C. tropicalis resistance to voriconazole was uncommon (with a maximum of 11%), but higher MICs were obtained for C. glabrata and C. krusei.[36] The antifungal susceptibility of the C. parapsilosis, which recently was found to consist of three different species, namely C. parapsilosis sensu strict, C. metapsilosis and C. parapsilosis, was shown to be low for echinocandins.[37,38] A Portuguese study testing 175 clinical and environmental isolates of the C. parapsilosis group showed that the majority (91.4 %) of all isolates are C. parapsilosis sensu stricto, and of those most isolates were susceptible to fluconazole. All of the isolates C. metapsilosis and C. parapsilosis were susceptible to azoles and amphotericinB, while a high number was non-susceptible to echinocandins.[38] The 10 year ARTEMIS DISK global antifungal surveillance study, where 256 882 isolates of Candida sp. were collected from 142 sites in 42 countries and tested against fluconazole, showed that the frequency of azole resistance varied considerably by geographic region.[39] Higher rates of resistance to both fluconazole and voriconazole were found in isolates from North America. Not only for C. glabrata and C. krusei decreased susceptibility was shown, but also for C. guilliermondii, C. inconspicua, C. rugosa and others, demonstrating that 13 out of the 31 species found exhibited increased resistance to fluconazole. As described before, cross- resistance between fluconazole and voriconazole is evident and seems to be more pronounced in some species of Candida than in others.[39]

Cryptococcus species
The genus Cryptococcus includes encapsulated yeasts that lack a mycelium.[40,41,42] Infection is usually initiated in the pulmonary tract with later possible dissemination, usually to the CNS, causing meningitis.[43,44] Involvement of parenchyma of the brain and meningitis occurs in between 40 and 86% of patients.[44] Cryptococcosis usually occurs in patients with impaired immunity.[44] The concern about Cryptococcus sp. has dramatically increased as it still remains one of the most common life threatening fungal infections in HIV- patients, where the risk of a Cryptococcus infection is between 2.9 – 13.3%. In non-HIV infected individuals, incidence rates of 0.2–0.9% have been reported in the United States.[44] Patients with AIDS have a much higher risk of infection (2.9–13.3%). In non – AIDS patients, but those with hematologic malignancies, administration of steroids and diabetes mellitus were the most frequent risk factors (6 and 4 out of 17 patients, respectively), as demonstrated in a retrospective study conducted in Italy between 1993 and 2002.[45]
In SOT recipients, an incidence of 2.8% has been reported.[44] Risk factors for mortality are pre-existing renal failure and liver failure in transplant recipients.[44]
In humans two Cryptococcus species can provoke disease: C. neoformans and C. gattii, which include 5 different serotypes altogether. Two varieties of C. neoformans (C. neoformans var. neoformans and C. neoformans var. grubii) representing serotypes D, A and AD (a hybrid from of both A and D), respectively, have been isolated.[42,46,47] C. gattii was previously listed as a further variety of C. neoformans, but is now known to be a distinct species. C. gattii includes serotypes B and C, both commonly seen as true pathogens provoking disease also in immunocompetent persons.[41,46,48]
C. neoformans has a worldwide distribution and has been isolated from a variety of environmental sources, mainly from bird excreta, where the microorganism can survive for a long time due to protection from sun and high temperatures. Its capsule even makes it resistant to natural drying of the vector matter. The distribution of C. gattii was thought to be  restricted to tropical and subtropical environments, often associated with Eucalyptus trees and the koala bear.[49] Yet, in recent years, an outbreak of C. gattii infections has been reported from Vancouver Island/Canada, where more than 66 human cases with at least 4 fatalities have been reported in otherwise healthy persons, all due to infections with serotype B.50 In recent years, some other species such as C. laurentii and C. albidus were isolated from cryptococcosis patients.[51,52]
High mortality rates of 30-40%41 are mainly due to the difficulty in killing the pathogen. Without treatment, the invasive infection is fatal, which makes rapid diagnosis and treatment inevitable. A combination of amphothericin B and flucytosin, followed by fluconazole maintenance therapy is the therapeutic option in most cases,[53] although C. gattii was found to show resistance to amphotericin B and fluconazole.[54] Furthermore, a trend of increasing fluconazole resistance of C. neoformans isolates from the Asia-Pacific, Africa/Middle East, and Latin America regions but not among isolates from Europe or Northern America has been described in a 10 year antifungal surveillance study.[55]

Trichosporon species
Systemic trichosporonosis is a relatively uncommon but frequently fatal opportunistic fungal infection in immunocompromised individuals.[56] The taxonomy of the yeasts that cause trichosporonosis has been extensively revised.[56,57] It is now widely accepted that the previously named Trichosporon (T). beigelii actually consists of six species: T. asahii, T. asteroides, T. cutaneum, T. inkin, T. mucoides, and T. ovoides. Geotrichum capitatum, originally considered a species of Trichosporon and now reclassified, is also a common cause of trichosporonosis.[56] While any immunocompromised patient can develop invasive trichosporonosis, the risk is highest for those with hematologic malignancies.[58,59] Incidence rates of 0.4 and 0.5%, respectively, for infections due to Trichosporon sp. and G. capitatum have been reported in patients with leukemia.[59] One of the largest multicenter retrospective studies on invasive trichosporonosis, carried out in Italy, [56] revealed that acute myeloid leukemia was the most frequent underlying hematologic disease for trichosporonosis. A total of 17 of the 52 patients with hematological malignancies were diagnosed with infections caused by Trichosporon sp., while the majority of infections (35 out of 52) was attributed to G. capitatum. Furthermore, the study showed that the frequency of Trichosporon sp. infections is similar on all continents, while G. capitatum is predominantly a European pathogen, with high rates especially countries of the Mediterranean area.[56] Several Trichosporon sp. were shown to be multidrug resistant.[56] Echinocandins have poor activity against Trichosporon sp. as demonstrated by high MICs[58 ]and breakthrough cases in immunocompromised patients treated with caspofungin [59,60,61] or micafungin [61] have been reported.

Moulds
Aspergillus species: Aspergillus species are opportunistic moulds that can cause both allergic and invasive syndromes.[62] More than 300 Aspergillus species are known today of which only a small number cause opportunistic infections.[62] The most common species causing aspergillosis is Aspergillus (A.) fumigatus, accounting for approximately 90% of Aspergillus infections.[63] Depending on regional distinctions A. flavus, A. nidulans and A. terreus are frequently reported as well, and there is evidence that these non-fumigatus pathogens are increasingly common etiologic agents.[63,64,65] There are differences in the clinical presentations produced by these different species.
For example, A. flavus produces a disproportionate number of infections in the paranasal sinus, while A. nidulans is a common culprit in chronic granulomatous disease.[63] Although A. terreus remains uncommon, infection caused by this pathogen is associated with high mortality rates because of its resistance to amphotericin B.[64] A study including three European countries, namely Austria, Denmark and Spain, revealed that A. terreus seems to be endemic for Tirol, Austria as it was exclusively found in hospital samples from Austria.[66] In Spain/Madrid A. niger was the most isolated non-fumigatus species. Furthermore, it was shown that azole resistance of Aspergilli is significantly increasing, especially in the UK (Manchester) and the Netherlands (Nijmegen). The Dutch study, involving almost 2000 A. fumigatus isolates collected over a 14-year period in the Netherlands, of which 32 isolates exhibited increased resistance to all azoles tested, showed that 30 of the 32 strains had the same “dominant resistance mechanism”. They all exhibited a single amino acid change in the cyp51A gene (encoding the target enzyme cytochrome P450 sterol 14-α-demethylase) and an alteration in the promoter region of this gene. Six isolates out of 317 from other European countries also exhibited resistance to itraconazole. In a study by Pfaller et al. 1789 Aspergillus isolates from centers all over the world between 2001 and 2009 were evaluated for their susceptibility to triazoles (voriconazole, posaconazole, itraconazole). For each of the three triazoles tested, decreased susceptibility was observed and varied according to the species. 49 isolates exhibited MICs higher than 4 µg/ml for itraconazole, of which some were shown to be cross resistant to posaconazole and voriconazole.[68] There exist clinical reports on primary invasive Aspergillus infections due to resistant isolates involving various manifestations, e.g. in the lung, the brain, in bones.[69,70,71,72,73] Furthermore, cases have been shown, where itraconazole treatment is lacking clinical efficacy in patients with aspergilloma.[71,74] In Austria the occurrence of azole resistance among clinical A. fumigatus is 0% while in Spain it is 2%. Reasons for this increase in resistance are not clear yet, nevertheless there exists some evidence that it is due to excessive use of azoles in agriculture.[75,76]
Invasive aspergillosis has remained the predominate cause of invasive mould infections over the last 10–15 years.[77] Reasons for this include a continued increase in high-risk populations such as solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, HIV-infected individuals, and those receiving intensified chemotherapy regimens.[2,63,78,79] Invasive aspergillosis is associated with a high rate of mortality, however, there is some evidence that survival rates have increased in recent years among those undergoing HSCT, primarily because of the use of non-myeloablative conditioning regimens, the use of peripheral blood stem cells, prompt diagnosis, and the use of effective antifungal therapy.[6]
An Italian study on invasive aspergillosis in AML-patients (SEIFEM-2008 registry study)80 showed that there is a clear downward trend in the aspergillosis-attributable mortality rate. In various consecutive multicenter studies Pagano et al. showed a decrease from 48% (1987-1998), to 38.5% (1999-2003) and 27% (2004-2007).[5,80,81,82] It is important to note, that according to the latest study,80 about two-thirds of the patients developed invasive aspergillosis despite standard antifungal prophylaxis based on fluconazole and itraconazole, which points out that the use of systemic prophylaxis needs to be further discussed. Independently from whatever prophylaxis was applied, A.fumigatus was the most causative species of aspergillosis in the Italian study.

Fusarium species
Fusarium sp. can be found in soil, plants and air. Clinical manifestations are diverse and depend largely on the immune status of the patient. Often, Fusarium sp. affects the skin (70-90%), lungs and sinuses (70-80%). Fusariosis is a life-threatening and increasingly important mycosis in immunocompromised hosts.[82,83,84] Risk factors for such infections are skin lesions, burns, use of corticosteroids, prolonged neutropenia and hematological malignancy.[12,84,85,86] Fusarium sp. are angiotropic and angioinvasive moulds that produce hemorrhagic infarction and low tissue perfusion, resulting in tissue necrosis.[83] More than 50 species of Fusarium have been identified but only a few are pathogenic in humans.83 These include F. solani (causes 50% of cases), F. oxysporum, F. moniliforme, F. verticillioides, F. dimerum, and F. proliferatum.[87]
In terms of global occurrence, fusariosis is most common in the United States (50–80% of all cases), followed by France, Italy, and Brazil.[83,87,88] In the SEIFEM-2004 survey, Fusarium species were responsible for 0.1% of infections, the majority in AML patients (0.3%).[81] In another Italian study, including 14 haematological centers, Fusarium infection was documented in 6 out of 351 patients (1.7%),88 with aplastic anaemia and AML as the underlying diseases (3 cases each). While the incidence in Italy remains stable, it increased in some US centers.[84] Because the clinical presentation of fusariosis may be non-specific, differentiating it from invasive aspergillosis can be challenging.[83] More than 90% of cases of fusariosis have been reported in neutropenic patients with hematologic malignancies.[88] Incidence rates of 0.06% (acute leukemia), 0.2% (autologous bone marrow transplant [BMT]), and 1.2% (allogeneic BMT) have been reported.82 In patients with hematologic malignancies, persistent neutropenia (hazard ratio [HR] = 5.43) and use of corticosteroids (HR = 2.18) were the most important predictors of mortality. Ideal treatment of fusariosis is still unclear. Azoles and polyenes seem to be most effective. Nevertheless, Fusarium sp. exhibit high resistance to antifungal drugs.[81,84,89]

Scedosporium species
Scedosporium sp. are ubiquitously distributed worldwide, commonly found in soil, sewage or polluted water. S. apiospermum (also known by its teleomorphic name Pseudoallescheria boydii) and S. prolificans have the greatest impact in human infections.[12,90] These two species differ in their epidemiological niches, morphology and antifungal sensitivity and can cause infections in both immunocompetent and immunosuppressed populations.[85,90] S. apiospermum has a worldwide distribution usually in association with water, and is therefore often reported as a cause of pneumonia and disseminated infection in near-drowning victims.[91] On the other hand, S. prolificans is found in soil, mainly in Spain and Australia.[92] In a Spanish survey, conducted between 1990 and 1999, S. prolificans was the most frequent filamentous fungi isolated from blood cultures,[93] comprising 5.2% of all of the filamentous fungi isolated in the respective hospital (San Sebastion/Spain).[93]
Mycetoma, a disfiguring, but non-life-threatening infection of the skin and subcutaneous tissue, is one type of disease caused by S. apiospermum, frequently developed through thorn punctures, wood splinters or preexisting trauma.[11,12,85] Pseudallescheriasis or scedosporiosis is mainly found in immunocompromised patients with hematological malignancies or in organ transplant recipients. For 11 % of cases in SOT recipients fungemia with Scedosporium sp. was reported.[11] Interestingly, neutropenia was not a variable in connection with Scedosporium infection in SOT patients. Also S. prolificans was found to cause deep invasive disseminated infections associated with high mortality rates. Dissemination throughout the body might be easier for this organism due to its ability to produce conidia in tissue.[12] Both pathogenic species of Scedosporium are highly resistant to amphotericin B and echinocandins, with S. prolificans being highly resistant to almost all of the currently available antifungal drugs. Voriconazole seems to have the strongest effect on both, S. apiospermum and S. prolificans, although most data exist from in vitro studies, where MICs for S. prolificans are at a level that would not be achieved in human compartiments and not be beneficial for the patient. As an approach, synergistic killing was investigated with a combination of voriconazole and terbinafine, which might be worthwhile to try.[12,85,94,95,96,97]  Hence, mortality rates have been reported to be as high as 65-75 % for S. apiospermum and even higher (85-100%) for S. prolificans.

Glomeromycota (formerly Zygomycetes)
Infections with species of the Glomeromycota (medically referred to as zygomycosis or mucormycosis) play an increasingly important role in immunocompromised patients. Two orders of the Glomeromycota are clinically relevant: Mucorales and Entomophthorales.[98,99,100] Members of the Mucorales are distributed worldwide while Entomophthorales are generally limited to the tropics and subtropics.[101,102] Species provoking human disease mostly belong to the group of Mucorales, which is characterized by a rapidly evolving course, tissue destruction, and invasion of blood vessels.[101,103] The most common species causing mucormycosis are Rhizopus (R.) arrhizus (R. oryzae), R. microsporus var. rhizopodiformis, and R. pusillus. Other causative species include Absidia corymbifera, Mucor species, and Cunninghamella bertholletiae.[101] Mycoses caused by Entomophthorales are more indolent and chronically progressive.[101,103]
Commonly infections affect the paranasal sinus (39%), the lungs (24%), and the skin (19%) with the primary site of infection depending on the patient population.[7,104] Disseminated disease is reported in approximately one-fourth of patients,[104] resulting in high mortality rates (96%).[7]A case-control observational study found that prolonged neutropenie rather than a low neutrophil count is more common in patients with zygomycosis.[104] Frequent underlying risk factors are diabetes mellitus, particularly enhanced by ketoacidosis, hematological malignances and bone marrow or solid organs transplantation.[85,101,104] Diabetes still remains the most common risk factor with 36% to 88% among mucormycosis-cases having diabetes as a predisposing condition.[101] However, the cases of mucormycosis in patients with hematological malignancies or those who have received hematopoetic stem cell or SOTs is dramatically increasing in the past two decades.[85] Invasive mucormycosis is now considered to be the 2nd most frequent mould infection in patients with hematological malignances, with reported cumulative incidence ranging from 0.1 – 2.5 % in different series.104 An Italian study reports that 45 (11.5%) out of 391 patients with hematological malignancies had infections with a representative of the Mucorales.[105] In France the incidence rate within this patient group increased of 24 % per year from 1997 to 2006.[106] The so far largest and geographically most diverse study on epidemiology of zygomycosis in Europe, including 15 countries and 230 cases in total, once more pointed out that the most frequent underlying condition for zygomycosis is hematological malignancy (44% of all cases), whereas diabetes is only present in 17 % of all cases.[99] This is controversial to a study by,[103] reporting that diabetes account in 36 % of all cases to glomeromycota-infection. One possible explanation for this contrast might be the high increase of immunocompromised hosts in the recent decade.[99] The presence of available free iron predisposes to zygomycosis.[103] The application of the iron chelator deferoxamine allows the fungus to utilize deferoxamine-bound iron by recognizing it as a siderophore and enable it to acquire the – for the fungus inevitable – iron via siderophore-specific mechanism/high affinity non-reductive mechanism (sufficient levels of iron increases the ability proliferation and tissue penetration for the fungus). Other chelators (i.e., deferasirox) do not allow iron utilization and may decrease the risk of infection.[107,108] Antifungal prophylaxis with voriconazole also appears to be associated with an increased risk of developing zygomycosis.[85] For successful eradication of these pathogens a multifactorial treatment strategy is needed. This includes reducing the predisposing factors of the patient, surgical debridement and application of antifungal therapy. Amphotericin B, especially new lipid formulations, is still the agent of choice, and data exist that suggest a combinational therapy with posaconazole as promising.[85,109,110,111,112,113]

---

Table 1. Risk factors and mortality rates of IFIs caused by new emerging pathogens.

---

Conclusion
With invasive mould infections becoming increasingly important, including those caused by rare, unusual pathogens, the epidemiology of IFIs is shifting in Europe. In some populations mould infections have already overtaken candidiasis, which was once the predominant type of IFIs. Reasons for this shift are multifactorial, but the augmented use of fluconazole as prophylaxis may account, at least in part, for this phenomenon, especially regarding infections with previously rare pathogens that occur as breakthrough infections. The management of IFIs is challenging – complicated by the difficulty in diagnosis and increasing resistance of the pathogens to available antifungal drugs.

References    

1. Holzheimer RG, Dralle H (2002) Management of mycoses in surgical patients -- review of the literature. Eur J Med Res 7: 200-226. PMid:12069912
2. Mahfouz T, Anaissie E (2003) Prevention of fungal infections in the immunocompromised host. Curr Opin Investig Drugs 4: 974-990. PMid:14508882
3. Marr KA, Seidel K, White TC, Bowden RA (2000) Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis 181: 309-316. doi:10.1086/315193 PMid:10608780
4. Muhlemann K, Wenger C, Zenhausern R, Tauber MG (2005) Risk factors for invasive aspergillosis in neutropenic patients with hematologic malignancies. Leukemia 19: 545-550. PMid:15729382
5. Pagano L, Girmenia C, Mele L, Ricci P, Tosti ME, et al. (2001) Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program. Haematologica 86: 862-870.PMid:11522544
6. Perkhofer S, Lass-Florl C, Hell M, Russ G, Krause R, et al. (2010) The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients. Int J Antimicrob Agents 36: 531-536. doi:10.1016/j.ijantimicag.2010.08.010 PMid:20947312
7. Richardson M, Lass-Florl C (2008) Changing epidemiology of systemic fungal infections. Clin Microbiol Infect 14 Suppl 4: 5-24. doi:10.1111/j.1469-0691.2008.01978.x PMid:18430126
8. Lass-Florl C (2009) The changing face of epidemiology of invasive fungal disease in Europe. Mycoses 52: 197-205.doi:10.1111/j.1439-0507.2009.01691.x
9. Peres-Bota D, Rodriguez-Villalobos H, Dimopoulos G, Melot C, Vincent JL (2004) Potential risk factors for infection with Candida spp. in critically ill patients. Clin Microbiol Infect 10: 550-555.  doi:10.1111/j.1469-0691.2004.00873.x  PMid:15191384
10. Galgiani JN (1999) Coccidioidomycosis: a regional disease of national importance. Rethinking approaches for control. Ann Intern Med 130: 293-300. PMid:10068388
11. Kubak BM, Huprikar SS (2009) Emerging & rare fungal infections in solid organ transplant recipients. Am J Transplant 9 Suppl 4: S208-226. doi:10.1111/j.1600-6143.2009.02913.x PMid:20070683
12. Varkey JB, Perfect JR (2008) Rare and emerging fungal pulmonary infections. Semin Respir Crit Care Med 29: 121-131.doi:10.1055/s-2008-1063851 PMid:18365994
13. Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20: 133-163. doi:10.1128/CMR.00029-06 PMid:17223626     PMCid:1797637
14. Eggimann P, Garbino J, Pittet D (2003) Management of Candida species infections in critically ill patients. Lancet Infect Dis 3: 772-785. doi:10.1016/S1473-3099(03)00831-4
15. Eggimann P, Garbino J, Pittet D (2003) Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 3: 685-702. doi:10.1016/S1473-3099(03)00801-6
16. Bodey G, Bueltmann B, Duguid W, Gibbs D, Hanak H, et al. (1992) Fungal infections in cancer patients: an international autopsy survey. Eur J Clin Microbiol Infect Dis 11: 99-109.doi:10.1007/BF01967060 PMid:6756909
17. Lass-Florl C, Resch G, Nachbaur D, Mayr A, Gastl G, et al. (2007) The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis 45: e101-104.doi:10.1086/521245 PMid:17806041
18. Post MJ, Lass-Floerl C, Gastl G, Nachbaur D (2007) Invasive fungal infections in allogeneic and autologous stem cell transplant recipients: a single-center study of 166 transplanted patients. Transpl Infect Dis 9: 189-195.doi:10.1111/j.1399-3062.2007.00219.x PMid:17511828
19. Singh N (2001) Trends in the epidemiology of opportunistic fungal infections: predisposing factors and the impact of antimicrobial use practices. Clin Infect Dis 33: 1692-1696.doi:10.1086/323895 PMid:11641825
20. Almirante B, Rodriguez D, Park BJ, Cuenca-Estrella M, Planes AM, et al. (2005) Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, barcelona, Spain, from 2002 to 2003. J Clin Microbiol 43: 1829-1835. doi:10.1128/JCM.43.4.1829-1835.2005 PMid:15815004    PMCid:1081396
21. Bassetti M, Trecarichi EM, Righi E, Sanguinetti M, Bisio F, et al. (2007) Incidence, risk factors, and predictors of outcome of candidemia. Survey in 2 Italian university hospitals. Diagn Microbiol Infect Dis 58: 325-331. doi:10.1016/j.diagmicrobio.2007.01.005 PMid:17350205
22. Pfaller MA, Hazen KC, Messer SA, Boyken L, Tendolkar S, et al. (2004) Comparison of results of fluconazole disk diffusion testing for Candida species with results from a central reference laboratory in the ARTEMIS global antifungal surveillance program. J Clin Microbiol 42: 3607-3612.doi:10.1128/JCM.42.8.3607-3612.2004 PMid:15297505   PMCid:497595
23. Tortorano AM, Biraghi E, Astolfi A, Ossi C, Tejada M, et al. (2002) European Confederation of Medical Mycology (ECMM) prospective survey of candidaemia: report from one Italian region. J Hosp Infect 51: 297-304. doi:10.1053/jhin.2002.1261 PMid:12183145
24. Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, et al. (2004) Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991-2000. Clin Infect Dis 38: 311-320. doi:10.1086/380637 PMid:14727199
25. Kibbler CC, Seaton S, Barnes RA, Gransden WR, Holliman RE, et al. (2003) Management and outcome of bloodstream infections due to Candida species in England and Wales. J Hosp Infect 54: 18-24. doi:10.1016/S0195-6701(03)00085-9
26. Diekema DJ, Messer SA, Brueggemann AB, Coffman SL, Doern GV, et al. (2002) Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organisms study. J Clin Microbiol 40: 1298-1302. doi:10.1128/JCM.40.4.1298-1302.2002 PMid:11923348   PMCid:140380
27. Almirante B, Rodriguez D, Cuenca-Estrella M, Almela M, Sanchez F, et al. (2006) Epidemiology, risk factors, and prognosis of Candida parapsilosis bloodstream infections: case-control population-based surveillance study of patients in Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 44: 1681-1685. doi:10.1128/JCM.44.5.1681-1685.2006 PMid:16672393    PMCid:1479182
28. Hajjeh RA, Sofair AN, Harrison LH, Lyon GM, Arthington-Skaggs BA, et al. (2004) Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol 42: 1519-1527.doi:10.1128/JCM.42.4.1519-1527.2004 PMid:15070998    PMCid:387610
29. Kao AS, Brandt ME, Pruitt WR, Conn LA, Perkins BA, et al. (1999) The epidemiology of candidemia in two United States cities: results of a population-based active surveillance. Clin Infect Dis 29: 1164-1170. doi:10.1086/313450 PMid:10524958
30. Asmundsdottir LR, Erlendsdottir H, Gottfredsson M (2002) Increasing incidence of candidemia: results from a 20-year nationwide study in Iceland. J Clin Microbiol 40: 3489-3492.doi:10.1128/JCM.40.9.3489-3492.2002 PMid:12202600    PMCid:130691
31. Poikonen E, Lyytikainen O, Anttila VJ, Ruutu P (2003) Candidemia in Finland, 1995-1999. Emerg Infect Dis 9: 985-990. PMid:12967498    PMCid:3020607
32. Lockhart SR, Messer SA, Pfaller MA, Diekema DJ (2008) Geographic distribution and antifungal susceptibility of the newly described species Candida orthopsilosis and Candida metapsilosis in comparison to the closely related species Candida parapsilosis. J Clin Microbiol 46: 2659-2664. doi:10.1128/JCM.00803-08 PMid:18562582    PMCid:2519489
33. Martino R, Subira M (2002) Invasive fungal infections in hematology: new trends. Ann Hematol 81: 233-243.doi:10.1007/s00277-002-0466-3 PMid:12029531
34. Laverdiere M, Rotstein C, Bow EJ, Roberts RS, Ioannou S, et al. (2000) Impact of fluconazole prophylaxis on fungal colonization and infection rates in neutropenic patients. The Canadian Fluconazole Study. J Antimicrob Chemother 46: 1001-1008.doi:10.1093/jac/46.6.1001 PMid:11102422
35. Cisterna R, Ezpeleta G, Telleria O, Guinea J, Regueiro B, et al. (2010) Nationwide sentinel surveillance of bloodstream Candida infections in 40 tertiary care hospitals in Spain. J Clin Microbiol 48: 4200-4206. doi:10.1128/JCM.00920-10 PMid:20826636    PMCid:3020865
36. Cuenca-Estrella M, Gomez-Lopez A, Cuesta I, Zaragoza O, Mellado E, et al. (2011) Frequency of Resistance In Vitro to Voriconazole among Spanish Clinical Isolates of Candida spp. According to Breakpoints by the Antifungal Subcommittee of the European Committee on Antimicrobial Susceptibility Testing. Antimicrob Agents Chemother.
37. Canton E, Espinel-Ingroff A, Peman J, del Castillo L (2010) In vitro fungicidal activities of echinocandins against Candida metapsilosis, C. orthopsilosis, and C. parapsilosis evaluated by time-kill studies. Antimicrob Agents Chemother 54: 2194-2197.doi:10.1128/AAC.01538-09 PMid:20145083    PMCid:2863676
38. Silva AP, Miranda IM, Lisboa C, Pina-Vaz C, Rodrigues AG (2009) Prevalence, distribution, and antifungal susceptibility profiles of Candida parapsilosis, C. orthopsilosis, and C. metapsilosis in a tertiary care hospital. J Clin Microbiol 47: 2392-2397. doi:10.1128/JCM.02379-08 PMid:19494078    PMCid:2725652
39. Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Ellis D, et al. (2010) Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida Species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J Clin Microbiol 48: 1366-1377. doi:10.1128/JCM.02117-09 PMid:20164282    PMCid:2849609
40. Halliday CL, Bui T, Krockenberger M, Malik R, Ellis DH, et al. (1999) Presence of alpha and a mating types in environmental and clinical collections of Cryptococcus neoformans var. gattii strains from Australia. J Clin Microbiol 37: 2920-2926.PMid:10449476    PMCid:85414
41. Iatta R, Napoli C, Borghi E, Montagna MT (2009) Rare mycoses of the oral cavity: a literature epidemiologic review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 108: 647-655.doi:10.1016/j.tripleo.2009.07.010 PMid:19836721
42. Perfect JR, Casadevall A (2002) Cryptococcosis. Infect Dis Clin North Am 16: 837-874, v-vi. doi:10.1016/S0891-5520(02)00036-3
43. Husain S, Wagener MM, Singh N (2001) Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome. Emerg Infect Dis 7: 375-381. PMid:11384512    PMCid:2631789
44. Wu G, Vilchez RA, Eidelman B, Fung J, Kormos R, et al. (2002) Cryptococcal meningitis: an analysis among 5,521 consecutive organ transplant recipients. Transpl Infect Dis 4: 183-188.doi:10.1034/j.1399-3062.2002.t01-1-02005.x PMid:12535260
45. Pagano L, Fianchi L, Caramatti C, D'Antonio D, Melillo L, et al. (2004) Cryptococcosis in patients with hematologic malignancies. A report from GIMEMA-infection. Haematologica 89: 852-856. PMid:15257938
46. Kwon-Chung KJ, Varma A (2006) Do major species concepts support one, two or more species within Cryptococcus neoformans? FEMS Yeast Res 6: 574-587.doi:10.1111/j.1567-1364.2006.00088.x PMid:16696653
47. Lucas S, da Luz Martins M, Flores O, Meyer W, Spencer-Martins I, et al. (2010) Differentiation of Cryptococcus neoformans varieties and Cryptococcus gattii using CAP59-based loop-mediated isothermal DNA amplification. Clin Microbiol Infect 16: 711-714. doi:10.1111/j.1469-0691.2009.02919.x PMid:19694768
48. Franzot SP, Salkin IF, Casadevall A (1999) Cryptococcus neoformans var. grubii: separate varietal status for Cryptococcus neoformans serotype A isolates. J Clin Microbiol 37: 838-840.PMid:9986871    PMCid:84578
49. Vilcins I, Krockenberger M, Agus H, Carter D (2002) Environmental sampling for Cryptococcus neoformans var. gattii from the Blue Mountains National Park, Sydney, Australia. Med Mycol 40: 53-60. PMid:11860013
50. Fraser JA, Subaran RL, Nichols CB, Heitman J (2003) Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii: implications for an outbreak on Vancouver Island, Canada. Eukaryot Cell 2: 1036-1045. doi:10.1128/EC.2.5.1036-1045.2003 PMid:14555486    PMCid:219376
51. Dorneanu O, Filip O, Miftode E, Radu I, Nicolau C, et al. (2008) [Cryptococcus meningitis, five years of experience and literature review]. Rev Med Chir Soc Med Nat Iasi 112: 100-103.PMid:18677910
52. Vlchkova-Lashkoska M, Kamberova S, Starova A, Goleva-Mishevska L, Tsatsa-Biljanovska N, et al. (2004) Cutaneous cryptococcus Laurentii infection in a human immunodeficiency virus-negative subject. J Eur Acad Dermatol Venereol 18: 99-100. doi:10.1111/j.1468-3083.2004.00434.x PMid:14678544
53. Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, et al. (2000) Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis 30: 710-718. doi:10.1086/313757 PMid:10770733
54. Khyriem AB, Sujatha S, Parija SC (2004) Chronic meningitis in an immunocompetent adult caused by Cryptococcus neoformans var gatti. Indian J Med Microbiol 22: 275.PMid:17642758
55. Pfaller MA, Diekema DJ, Gibbs DL, Newell VA, Bijie H, et al. (2009) Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J Clin Microbiol 47: 117-123. doi:10.1128/JCM.01747-08 PMid:19005141    PMCid:2620874
56. Girmenia C, Pagano L, Martino B, D'Antonio D, Fanci R, et al. (2005) Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature. J Clin Microbiol 43: 1818-1828.doi:10.1128/JCM.43.4.1818-1828.2005 PMid:15815003    PMCid:1081342
57. Gueho E, de Hoog GS, Smith MT (1992) Neotypification of the genus Trichosporon. Antonie Van Leeuwenhoek 61: 285-288.PMid:1497333
58. Espinel-Ingroff A (2003) In vitro antifungal activities of anidulafungin and micafungin, licensed agents and the investigational triazole posaconazole as determined by NCCLS methods for 12,052 fungal isolates: review of the literature. Rev Iberoam Micol 20: 121-136. PMid:15456349
59. Goodman D, Pamer E, Jakubowski A, Morris C, Sepkowitz K (2002) Breakthrough trichosporonosis in a bone marrow transplant recipient receiving caspofungin acetate. Clin Infect Dis 35: E35-36. doi:10.1086/341305 PMid:12115115
60. Akagi T, Yamaguti K, Kawamura T, Nakumura T, Kubo K, et al. (2006) Breakthrough trichosporonosis in patients with acute myeloid leukemia receiving micafungin. Leuk Lymphoma 47: 1182-1183. doi:10.1080/10428190500272499 PMid:16840220
61. Matsue K, Uryu H, Koseki M, Asada N, Takeuchi M (2006) Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin. Clin Infect Dis 42: 753-757.doi:10.1086/500323 PMid:16477548
62. Denning DW (1998) Invasive aspergillosis. Clin Infect Dis 26: 781-803; quiz 804-785.
63. Marr KA, Patterson T, Denning D (2002) Aspergillosis. Pathogenesis, clinical manifestations, and therapy. Infect Dis Clin North Am 16: 875-894, vi. doi:10.1016/S0891-5520(02)00035-1
64. Lass-Florl C, Griff K, Mayr A, Petzer A, Gastl G, et al. (2005) Epidemiology and outcome of infections due to Aspergillus terreus: 10-year single centre experience. Br J Haematol 131: 201-207. doi:10.1111/j.1365-2141.2005.05763.x PMid:16197450
65. Marr KA, Carter RA, Boeckh M, Martin P, Corey L (2002) Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100: 4358-4366. doi:10.1182/blood-2002-05-1496 PMid:12393425
66. Mortensen KL, Mellado E, Lass-Florl C, Rodriguez-Tudela JL, Johansen HK, et al. (2010) Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli in Austria, Denmark, and Spain. Antimicrob Agents Chemother 54: 4545-4549. doi:10.1128/AAC.00692-10 PMid:20805399
67. Snelders E, van der Lee HA, Kuijpers J, Rijs AJ, Varga J, et al. (2008) Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med 5: e219.doi:10.1371/journal.pmed.0050219 PMid:18998768    PMCid:2581623
68. Pfaller M, Boyken L, Hollis R, Kroeger J, Messer S, et al. (2011) Use of epidemiological cutoff values to examine 9-year trends in susceptibility of Aspergillus species to the triazoles. J Clin Microbiol 49: 586-590. doi:10.1128/JCM.02136-10 PMid:21123534
69. Hodiamont CJ, Dolman KM, Ten Berge IJ, Melchers WJ, Verweij PE, et al. (2009) Multiple-azole-resistant Aspergillus fumigatus osteomyelitis in a patient with chronic granulomatous disease successfully treated with long-term oral posaconazole and surgery. Med Mycol 47: 217-220. doi:10.1080/13693780802545600 PMid:19101840
70. Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, et al. (2009) Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 15: 1068-1076. doi:10.3201/eid1507.090043 PMid:19624922    PMCid:2744247
71. Howard SJ, Pasqualotto AC, Denning DW (2010) Azole resistance in allergic bronchopulmonary aspergillosis and Aspergillus bronchitis. Clin Microbiol Infect 16: 683-688.doi:10.1111/j.1469-0691.2009.02911.x PMid:19673966
72. van der Linden JW, Jansen RR, Bresters D, Visser CE, Geerlings SE, et al. (2009) Azole-resistant central nervous system aspergillosis. Clin Infect Dis 48: 1111-1113.doi:10.1086/597465 PMid:19272019
73. Verweij PE, Mellado E, Melchers WJ (2007) Multiple-triazole-resistant aspergillosis. N Engl J Med 356: 1481-1483.doi:10.1056/NEJMc061720 PMid:17409336
74. Chen J, Li H, Li R, Bu D, Wan Z (2005) Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma. J Antimicrob Chemother 55: 31-37. doi:10.1093/jac/dkh507 PMid:15563516
75. Snelders E, Huis In 't Veld RA, Rijs AJ, Kema GH, Melchers WJ, et al. (2009) Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles. Appl Environ Microbiol 75: 4053-4057. doi:10.1128/AEM.00231-09 PMid:19376899    PMCid:2698372
76. Verweij PE, Howard SJ, Melchers WJ, Denning DW (2009) Azole-resistance in Aspergillus: proposed nomenclature and breakpoints. Drug Resist Updat 12: 141-147.doi:10.1016/j.drup.2009.09.002 PMid:19879181
77. Alangaden GJ (2011) Nosocomial fungal infections: epidemiology, infection control, and prevention. Infect Dis Clin North Am 25: 201-225. doi:10.1016/j.idc.2010.11.003 PMid:21316001
78. Singh N, Paterson DL (2005) Aspergillus infections in transplant recipients. Clin Microbiol Rev 18: 44-69.doi:10.1128/CMR.18.1.44-69.2005 PMid:15653818    PMCid:544171
79. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA (2007) Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis 44: 531-540.doi:10.1086/510592 PMid:17243056
80. Pagano L, Caira M, Candoni A, Offidani M, Martino B, et al. (2010) Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica 95: 644-650. doi:10.3324/haematol.2009.012054 PMid:19850903    PMCid:2857195
81. Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, et al. (2006) The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 91: 1068-1075. PMid:16885047
82. Pagano L, Caira M, Nosari A, Van Lint MT, Candoni A, et al. (2007) Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis 45: 1161-1170. doi:10.1086/522189 PMid:17918077
83. Lionakis MS, Kontoyiannis DP (2004) Fusarium infections in critically ill patients. Semin Respir Crit Care Med 25: 159-169.PMid:16088459
84. Nucci M, Anaissie EJ, Queiroz-Telles F, Martins CA, Trabasso P, et al. (2003) Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer 98: 315-319. doi:10.1002/cncr.11510 PMid:12872351
85. Malani AN, Kauffman CA (2007) Changing epidemiology of rare mould infections: implications for therapy. Drugs 67: 1803-1812. doi:10.2165/00003495-200767130-00001 PMid:17722951
86. Nucci M (2003) Emerging moulds: Fusarium, Scedosporium and Zygomycetes in transplant recipients. Curr Opin Infect Dis 16: 607-612. doi:10.1097/00001432-200312000-00015 PMid:14624113
87. Torres HA, Raad, II, Kontoyiannis DP (2003) Infections caused by Fusarium species. J Chemother 15 Suppl 2: 28-35.PMid:14708964
88. Girmenia C, Pagano L, Corvatta L, Mele L, del Favero A, et al. (2000) The epidemiology of fusariosis in patients with haematological diseases. Gimema Infection Programme. Br J Haematol 111: 272-276. doi:10.1046/j.1365-2141.2000.02312.x PMid:11091211
89. Boutati EI, Anaissie EJ (1997) Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years' experience at a cancer center and implications for management. Blood 90: 999-1008. PMid:9242529
90. Meletiadis J, Meis JF, Mouton JW, Rodriquez-Tudela JL, Donnelly JP, et al. (2002) In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob Agents Chemother 46: 62-68.doi:10.1128/AAC.46.1.62-68.2002 PMid:11751112    PMCid:126988
91. Dworzack DL, Clark RB, Borkowski WJ, Jr., Smith DL, Dykstra M, et al. (1989) Pseudallescheria boydii brain abscess: association with near-drowning and efficacy of high-dose, prolonged miconazole therapy in patients with multiple abscesses. Medicine (Baltimore) 68: 218-224.
92. Berenguer J, Rodriguez-Tudela JL, Richard C, Alvarez M, Sanz MA, et al. (1997) Deep infections caused by Scedosporium prolificans. A report on 16 cases in Spain and a review of the literature. Scedosporium Prolificans Spanish Study Group. Medicine (Baltimore) 76: 256-265.doi:10.1097/00005792-199707000-00004 PMid:9279332
93. Idigoras P, Perez-Trallero E, Pineiro L, Larruskain J, Lopez-Lopategui MC, et al. (2001) Disseminated infection and colonization by Scedosporium prolificans: a review of 18 cases, 1990-1999. Clin Infect Dis 32: E158-165.doi:10.1086/320521 PMid:11340550
94. Gilgado F, Serena C, Cano J, Gene J, Guarro J (2006) Antifungal susceptibilities of the species of the Pseudallescheria boydii complex. Antimicrob Agents Chemother 50: 4211-4213.doi:10.1128/AAC.00981-06 PMid:17015631    PMCid:1694014
95. Meletiadis J, Mouton JW, Meis JF, Verweij PE (2003) In vitro drug interaction modeling of combinations of azoles with terbinafine against clinical Scedosporium prolificans isolates. Antimicrob Agents Chemother 47: 106-117.doi:10.1128/AAC.47.1.106-117.2003 PMid:12499177    PMCid:149034
96. Meletiadis J, te Dorsthorst DT, Verweij PE (2003) Use of turbidimetric growth curves for early determination of antifungal drug resistance of filamentous fungi. J Clin Microbiol 41: 4718-4725. doi:10.1128/JCM.41.10.4718-4725.2003 PMid:14532210    PMCid:254297
97. Howden BP, Slavin MA, Schwarer AP, Mijch AM (2003) Successful control of disseminated Scedosporium prolificans infection with a combination of voriconazole and terbinafine. Eur J Clin Microbiol Infect Dis 22: 111-113.PMid:12627286
98. Hibbett DS, Binder M, Bischoff JF, Blackwell M, Cannon PF, et al. (2007) A higher-level phylogenetic classification of the Fungi. Mycol Res 111: 509-547. doi:10.1016/j.mycres.2007.03.004 PMid:17572334
99. Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, et al. (2011) Zygomycosis in Europe: Analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect.
100. White MM, James TY, O'Donnell K, Cafaro MJ, Tanabe Y, et al. (2006) Phylogeny of the Zygomycota based on nuclear ribosomal sequence data. Mycologia 98: 872-884.doi:10.3852/mycologia.98.6.872 PMid:17486964
101. Chayakulkeeree M, Ghannoum MA, Perfect JR (2006) Zygomycosis: the re-emerging fungal infection. Eur J Clin Microbiol Infect Dis 25: 215-229. doi:10.1007/s10096-006-0107-1 PMid:6756909
102. Gonzalez CE, Rinaldi MG, Sugar AM (2002) Zygomycosis. Infect Dis Clin North Am 16: 895-914, vi.doi:10.1016/S0891-5520(02)00037-5
103. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, et al. (2005) Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 41: 634-653. doi:10.1086/432579 PMid:16080086
104. Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, et al. (2005) Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis 191: 1350-1360. doi:10.1086/428780 PMid:15776383
105. Pagano L, Offidani M, Fianchi L, Nosari A, Candoni A, et al. (2004) Mucormycosis in hematologic patients. Haematologica 89: 207-214. PMid:15003897
106. Bitar D, Van Cauteren D, Lanternier F, Dannaoui E, Che D, et al. (2009) Increasing incidence of zygomycosis (mucormycosis), France, 1997-2006. Emerg Infect Dis 15: 1395-1401. doi:10.3201/eid1509.090334 PMid:19788806    PMCid:2819884
107. Boelaert JR, van Roost GF, Vergauwe PL, Verbanck JJ, de Vroey C, et al. (1988) The role of desferrioxamine in dialysis-associated mucormycosis: report of three cases and review of the literature. Clin Nephrol 29: 261-266. PMid:3293856
108. Daly AL, Velazquez LA, Bradley SF, Kauffman CA (1989) Mucormycosis: association with deferoxamine therapy. Am J Med 87: 468-471. doi:10.1016/S0002-9343(89)80836-8
109. Herbrecht R, Auvrignon A, Andres E, Guillemain R, Suc A, et al. (2001) Efficacy of amphotericin B lipid complex in the treatment of invasive fungal infections in immunosuppressed paediatric patients. Eur J Clin Microbiol Infect Dis 20: 77-82. doi:10.1007/s100960000437
110. Herbrecht R, Letscher-Bru V, Bowden RA, Kusne S, Anaissie EJ, et al. (2001) Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion. Eur J Clin Microbiol Infect Dis 20: 460-466. doi:10.1007/s100960100528
111. Kofteridis DP, Karabekios S, Panagiotides JG, Bizakis J, Kyrmizakis D, et al. (2003) Successful treatment of rhinocerebral mucormycosis with liposomal amphotericin B and surgery in two diabetic patients with renal dysfunction. J Chemother 15: 282-286. PMid:12868556
112. Sun QN, Fothergill AW, McCarthy DI, Rinaldi MG, Graybill JR (2002) In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob Agents Chemother 46: 1581-1582. doi:10.1128/AAC.46.5.1581-1582.2002 PMid:11959605    PMCid:127128
113. Sun QN, Najvar LK, Bocanegra R, Loebenberg D, Graybill JR (2002) In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob Agents Chemother 46: 2310-2312. doi:10.1128/AAC.46.7.2310-2312.2002 PMid:12069997    PMCid:127310