Airborne fungi isolated from Fortaleza city, State of Ceará, Brazil

Airbone fungi are considered important causes of allergic rhinitis and allergic asthma. The knowledge of these fungi in a city or region is important for the ecological diagnosis and specific treatment of allergic manifestations induced by inhalation of fungal allergens. The airborne fungi of Fortaleza, State of Ceará, Brazil, were studied during a one year period. Five hundred and twenty Petri dishes with Sabouraud dextrose agar medium were exposed at ten different locations in the city. The dishes exposed yielded one thousand and five hundred and twenty one colonies of twenty four genera. The most predominants were: Aspergillus (44.7%), Penicillium (13.3%), Curvularia (9.8%), Cladosporium (6.8%), Mycelia sterilia (6.0%), Fusarium (3.5%), Rhizopus (3.1%), Drechslera (2.6%), Alternaria (2.4%) and Absidia (2.2%). The results shown that Aspergillus, Penicillium, Mycelia sterilia, Fusarium and Alternaria were found during all months in the year. Absidia was more frequent during the dry season. Anemophilous fungi and the high concentration of spores in the air are important because may result in an increased number of people with allergic respiratory disease.     

肺部真菌感染152例病原谱再评价

目的了解肺部真菌感染的病原谱和预后。方法根据欧洲癌症研究和治疗侵袭性真菌感染协作组（EORTC）、美国变态反应和感染性疾病协会真菌病研究组（MSG）2002年制定的定义以及血液病／恶性肿瘤患者侵袭性真菌感染的诊断标准,将北京协和医院2002年1月至2006年6月诊断的152例肺部真菌感染患者按照统一的定义进行重新分组：确诊组38例,临床诊断组24例,拟诊组35例,定植组55例,重新分析病原谱。结果38例确诊肺部真菌感染的患者中,肺曲霉菌感染占首位（15／38）,其次为肺隐球菌感染（13／38）,第三为毛霉菌和其他类型丝状真菌,而真正念珠菌肺炎少见,只有2例。临床诊断组曲霉菌和曲霉菌＋念珠菌占第1位,而拟诊组以及定植组以单纯念珠菌占首位。临床诊断组病死率为58．3％,高于拟诊组（25．7％）和定植组（16．4％）。拟诊组和定植组“念珠菌肺炎”分别为28例和50例,对这78例“念珠菌肺炎”患者的预后危险因素进行分析后发现,只有急性生理和慢性病评分（APACHEⅡ）与患者的预后有关,而是否抗真菌治疗及使用何种抗真菌药物与预后无关。结论肺部真菌感染以曲霉菌占第1位,其次为隐球菌和毛霉菌,念珠菌肺炎少见。痰标本念珠菌属培养阳性作为“念珠菌肺炎”的诊断标准值得商榷。     

Current data about fungi prevalence in various ontocenoses in women during procreation period

The aim of study was to analyse fungi prevalence in three ontocenoses (vagina, oral cavity and anus) in women during procreation period, which should be helpful in developing prophylactic programmes for pregnant womem, newborns and infants infected with fungi. In 716 examined women (age 20-45 years), 1411 samples of appropriate biological materials were taken and inoculated in the fluid Sabouraud medium and then axenic fungi strains were isolated in Sabouraud agar. High fungi prevalence in three ontocenoses of examined women was noted. Mean percentage for ontocenosis was: 39% +/- 1.8% for vagina, 42.18% +/- 1.8% for oral cavity and 25.03 +/- 1.6% for anus. These data indicate the necessity for further examinations of multifocal fungal infection in women during procreation period.     

Seasonal biodiversity of pathogenic fungi in farming air area. Case study

Poultry production proved to be a significant source of bioaerosols. The exposure to high concentration of microorganisms in the air can cause primarily irritations, infections, allergies, and toxic effects. The aim of the present study was to investigate the seasonal biodiversity of airborne fungi in the poultry house, in the surrounding area, as well as to estimate health risk. Seasonal investigations were conducted in the spring, summer, autumn and winter 2010 in the poultry house located near Wroc?aw in Lower Silesia (Poland). The air samples were collected with the use of a Merck MAS-100 onto nutrient Sabouraud agar and were incubated for 5 days at 26 degrees C. Subsequently the colony-forming units (CFU) were determined. The identification of the isolated fungi was made in accordance with the standard procedures. In the summer and autumn when the weather conditions are most friendly for the spread and the development of numerous microorganisms, fungi were more abundant in the surrounding area than in early spring and winter, when both humidity and temperature were lower. The total of 26 species were analysed (10 in the poultry house and 17 in the surrounding areas). Among 12 fungal genera: Aspergillus, Penicilium, Alternaria, Exophiala, Mycelia sterilla, Fusarium, Cladosporium, Scopulariopsis, Chaetomium, Acremonium, Candida and Rhodotorula nearly everything occurred to be the potential respiratory allergens.     

Particle counting and microbiological air sampling: Results of the simultaneous use of both procedures in different types of hospital rooms

Introduction

In order to assess the relationship between the concentrations of airborne fungi and particles, particle counting was combined with fungal air sampling in several rooms of a hospital.

Methods

Concentrations of ≥0.5 μm particles (P05) and ≥1 μm particles (P1) were measured using a particle counter; fungal air sampling was performed with volumetric air samplers, which impacted air on Rodac plates with Sabouraud chloramphenicol agar. Particle counts were categorised according to ISO 14644-1 standard cut-off points; their association with fungal detection was assessed with Fisher's exact test.

Results

Forty-two simultaneous samplings were carried out: 24 in operating rooms, 13 in rooms for burns or haematology patients, 3 in pharmacy clean rooms, and two in other procedure rooms. Filamentous fungi were recovered in 5 samples, which also had higher particle counts. No fungi were detected in 12 samplings with both P05 and P1 concentrations below the maximum for class 6 clean rooms; 4 of 7 samplings with both concentrations within the range for class 8 clean rooms were positive for fungi. The association between fungal detection and higher particle counts was statistically significant, both for P05 (p = .004) and P1 (p = .003). There was a partial overlap between the concentrations of particles of samplings which were positive or negative for fungi.

Conclusions

There is a relationship between the concentrations of P05 and P1 and airborne fungi in hospital rooms. When both P05 and P1 concentrations are below the maximum for class 6 clean rooms, a negative fungal detection can be predicted.     

In Vitro Susceptibility Testing in Fungi: What is its Role in Clinical Practice?

An increasing number of patients are undergoing transplantation procedures or receiving aggressive immunosuppression and chemotherapy. The growing population of immunocompromised hosts has led to a rise in the prevalence of invasive fungal infections due to yeasts and molds. The introduction of new antifungal agents and recent reports of resistance emerging during treatment of fungal infections have highlighted the need for in vitro susceptibility testing. Various testing procedures have been proposed, including macrodilution and microdilution, agar diffusion, disk diffusion, and Etest (AB Biodisk, Solna, Sweden). Establishing clinical correlation with antifungal susceptibility testing, however, is a huge challenge because susceptibility techniques do not take into account the dynamic and complex biology of fungi exposed to an antifungal in vivo. This paper reviews the available methods for antifungal susceptibility testing of yeasts and filamentous fungi and the data regarding the clinical implications of in vitro testing.     

Fungal infections after haematology unit renovation: evidence of clinical, environmental and economical impact

Objective and methods: The Haemato‐Oncology Unit, Hospital S. Joao, suffered extensive refurbishing intervention in order to adapt for autotransplant patients. Eight new individual rooms with central HEPA filtration system were built. All patients admitted in the department during 14 months prior to and 14 months after renovation works were enrolled. A total of 403 admissions were considered and a detailed analysis of all patients with fungal infections, air quality and antifungal consumption were evaluated in order to study clinical, environmental and economical impact after unit renovation. Results: Patients with acute myeloid leukaemia submitted to induction treatment were the most susceptible to acquisition of fungal infections. Fungal infections were reduced after installation of HEPA filters in individual rooms, particularly proven and probable fungal infections. No patients were diagnosed with proven or probable mould infection in the period after the unit renovation and no deaths were registered among patients with the diagnosis of possible fungal infection. Considering the group of patients diagnosed with fungal infection, the average of hospitalization was reduced 3 d in the latter period. The new high‐protected rooms showed a reduction of 50% and 95% of airborne fungi, respectively in the first week and after the second week. The consumption of voriconazole and caspofungin was reduced, respectively, 66% and 59% and the final cost with antifungal therapy was reduced by 17.4%. Conclusions: Autotransplant patients may be under higher risk of infection, however, the installation of high‐protective measures may efficiently prevent fungal infections in these patients. Renovation of haematology unit resulted in major clinical, environmental and economical improvements. The definition of reference values for airborne agents in hospital facilities remains urgent.     

Efficacy and safety of micafungin for treating febrile neutropenia in hematological malignancies

Less toxic antifungal drugs are required for empirical antifungal therapy. Micafungin is an echinocandin drug that is effective against both Candida and Aspergillus, and preliminary clinical studies have shown good antifungal activity. We prospectively examined the effect and safety of micafungin against febrile neutropenia with suspected fungal infection in 53 patients (median age, 56 years) who had undergone chemotherapy. The administered dose of micafungin was 150 mg/day, and its effect was evaluated as fever resolution as well as the results of chest imaging and serum fungal tests. Micafungin levels were measured on day 4 after the first administration using high-performance liquid chromatography. We also measured trough levels of micafungin. Underlying diseases comprised acute lymphoblastic leukemia (n = 4), acute myeloid leukemia (n = 20), multiple myeloma (n = 3), and non-Hodgkin's lymphoma (n = 26). The overall efficacy of micafungin was 70%. Breakthrough fungal infections were documented in two (3.8%) patients, both of whom died of invasive mycosis. None of the patients were switched to other antifungal drugs due to events unrelated to adverse effects. Plasma levels of micafungin and the degree of hepatic or renal dysfunction did not correlate. Micafungin is safe and effective for the empirical antifungal therapy of febrile neutropenia in patients with hematological malignancies.     

Emerging and less common fungal pathogens

Less common and emerging fungal pathogens are often resistant to conventional antifungal therapy and may cause severe morbidity and mortality in immunocompromised hosts. Some Scedosporium species may be completely resistant to antifungal therapy. Hyaline septated filamentous fungi, such as Fusarium species, Acremonium species, Paecilomyces species, and Trichoderma species, are increasingly reported as causing invasive mycoses refractory to amphotericin B therapy. Dematiaceous septated filamentous fungi, such as Bipolaris species may cause pneumonia, sinusitis, and CNS infections that are unresponsive to current medical interventions. Trichosporon spp are resistant to the fungicidal effects of amphotericin B. An increasing number of different members of the class Zygomycetes are reported as causing lethal infections, despite aggressive medical and surgical interventions. Infections due to these and other less common and emergent fungal pathogens will likely continue to develop in the settings of selective anti-fungal pressure, permissive environmental conditions, and an expanding population of immunocompromised hosts.     

Clinical features of human infection with Scedosporium inflatum.

We report on 17 Australian cases of human infection or colonization with Scedosporium inflatum. The spectrum of clinical manifestations was similar to that in infection caused by Scedosporium apiospermum. The patients were classified into three groups. Four immunocompetent patients who presented with localized infections of a joint, nail bed, eye, or sphenoidal sinus made up the first group. Our first case, in a boy with posttraumatic septic arthritis, responded to surgical drainage with amphotericin B followed by treatment with itraconazole. The other three cases were cured by surgery alone. The second group consisted of five immunocompromised patients who presented with disseminated infections in a variety of sites. Four of these patients did not respond to antifungal therapy and died. The fifth apparently responded to antifungal drugs after correction of his neutropenia. The third group included eight patients with asymptomatic colonization in the external ear (five cases) or respiratory secretions (three cases). The nine isolates of S. inflatum tested by both disk and agar dilution methods were resistant to antifungal drugs. In our first case, which responded clinically to itraconazole, the MIC of this drug for the fungal isolate was 25 micrograms/mL. Thus S. inflatum can cause a broad spectrum of human infections whose severity and prognosis depend largely on the host's immune status.     

Airborne fungi in indoor and outdoor of asthmatic patients' home, living in the city of sari

The aim of this study was identification of fungi in indoor and outdoor of asthmatic patients home environment. Opened plates (containing of Malt extract agar media) were used for isolation of fungi in the air of indoor (n=360) and outdoor (n=180) of 90 asthmatic patients home living in the city of Sari at the level of breathing height. Plates were incubated in room temperature for 7-14 days. Then grown fungi were identified by standard mycological techniques.A total of 1876 colonies with 31 and 1692 colonies with 27 genera of fungi were identified from indoor and outdoor of asthmatic patients' home respectively. The most common fungi isolated were Cladosporium, Aspergillus and Penicillium. Stachibotyris, Oedocephalum, and Stemphillium showed the least frequencies among the isolated fungi.Cladosporium, Aspergillus, Penicillium, and Alternaria as the most common allergenic moulds had the most frequencies in indoor air of the houses of asthmatic patients.     

Isolation rate and antifungal drug susceptibility of yeast like fungi isolated from blood or vascular catheter

Increased resistance of strains to antifungal drugs has gained increasing attention. We studied the status of fungal isolation from blood and vascular catheters at Juntendo University Hospital from 1994 to 2002. The major fungi isolated were Candida albicans, Candida parapsilosis, Candida glabrata and Candida trophicalis, or 86% yeast-like fungi. Isolation of these fungi from vascular catheters is increasing. The effectiveness of 6 anti-fungal agents against 116 yeast-like fungi was measured by microdilution. In antifungal activity of micafungin (MCFG), MIC90, was < or = 0.03 g/mL for C. albicans, C. glabrata and C. tropicalis. MCFG showed the strongest antifungal activity among the drugs tested for above Candida spp.. Five of 37 strains of C. albicans were resistant to fluconazole (FLCZ) showing MIC > or =64 g/mL. These strains were also resistant to itraconazole (ITCZ) but MICs of MGFG, flurocytosine (5-FC) and amphotericin B (AMPH-B). Two of 38 strains of C. parapsilosis are resistant to flurocytosine (5-FC) showing MIC > or =64 g/mL. There is no resistant strain of fungi (yeast-like organisms) tested against AMPH-B. Six patients from whom resistant fungi were isolated from blood and vascular catheters have severe diseases and/or are have just undergone a major surgical operation. These results indicate that it is vital for deep mycosis to start early treatment with appropriate drugs selected based on rapid detection and identification of organisms and the drug susceptibility of organisms.     

高病死率真菌肺炎的预防与管理

深部真菌感染是院内感染的重要病原。在传染病院里,真菌肺炎是重症肝炎病人高病死率的重要诱因。但又缺乏早期特异性诊断方法。为此,我们对影响真菌肺炎的高危因素进行早期预测,以求能及时采取预防措施。     

Pulmonary fungal infection: emphasis on microbiological spectra, patient outcome, and prognostic factors.

STUDY OBJECTIVES: To investigate the microbiological spectra, patient outcome, and prognostic factors of pulmonary fungal infection. DESIGN: The medical and microbiological records of patients with pulmonary fungal infection were retrospectively analyzed. SETTING: A university-affiliated tertiary medical center. Patients and methods: From January 1988 to December 1997, all cases of pulmonary fungal infection were reviewed. The criteria for inclusion were obvious lung lesion shown on chest radiographs and one of the following: (1) the presence of fungi in or isolation of fungi from the biopsy specimen of open thoracotomy, thoracoscopy, transbronchial lung biopsy, or ultrasound-guided percutaneous needle aspiration/biopsy; or (2) isolation of fungi from pleural effusion or blood, with no evidence of extrapulmonary infection. RESULTS: A total of 140 patients were included. Ninety-four cases of pulmonary fungal infection (67%) were community acquired. The most frequently encountered fungi were Aspergillus species (57%), followed by Cryptococcus species (21%) and Candida species (14%). There were 72 patients with acute invasive fungal infection, with a mortality rate of 67%. Multivariate logistic regression analysis showed that nosocomial infection (p = 0.014) and respiratory failure (p = 0.001) were significantly and independently associated with death of acute invasive fungal infection. CONCLUSIONS: Pulmonary fungal infection of community-acquired origins is becoming a serious problem. It should be taken into consideration for differential diagnosis of community-acquired pneumonia. Furthermore, acute invasive fungal infection is associated with a much higher mortality rate for patients with nosocomial infection or complicating respiratory failure. Early diagnosis with prompt antifungal therapy, or even with surgical intervention, might be warranted to save patients' lives.     

Recent advances in the epidemiology, prevention, diagnosis, and treatment of fungal pneumonia

Although pneumonia caused by fungi is not a common occurrence in the general population, disease in an enlarging immunocompromised population is encountered with increasing frequency. Fungal pneumonias are most frequently caused by Aspergillus spp., dimorphic fungi and Cryptococcus neoformans. Recent studies have identified risk factors of thrombocytopenia, environmental events (such as construction or renovation) and immunosuppressive drug therapies as being specific risk factors for invasive fungal disease in select patient populations. Diagnostic strategies to detect circulating antigens and polymerase chain reaction based detection systems have been explored to improve identification prior to the progressive advanced disease. Advances in prophylactic strategies include increased use of aerosolized formulations of amphotericin B, usually in conjunction with new and old systemic antifungal agents. Despite recent published guidelines for treatment of fungal pneumonia based on etiology, mortality remains high in some infections with advanced disease. Caspofungin, a new echinocandin antifungal, has recently been approved by the US Food and Drug Administration for the treatment of invasive Aspergillus infections in patients unresponsive to or unable to receive amphotericin B. A triazole antifungal, voriconazole, has shown promise in phase III clinical trials in patients with refractory fungal infections and is expected to be available in early 2002. Other echinocandin and triazole antifungals are under development in attempts to provide improved effective therapy for fungal pneumonia.     

脓毒症患者血浆血管生成素2与（1,3）-β-D葡聚糖水平变化及其相关性分析

目的 观察脓毒症患者血浆血管生成素2（Ang-2）和（1,3）-β-D-葡聚糖（BG）水平变化,并分析二者的关系.方法 选择66例脓毒症患者,其中深部真菌感染11例（A组）、二重感染（G-杆菌合并真菌感染）36例（B组）、G-杆菌感染19例（C组）,另选20例健康体检者为对照（D组）.24h内进行急性生理和慢性健康状况（APACHEⅡ）评分、序贯器官衰竭（SOFA）评分,检测血浆Ang-2、BG.结果 脓毒症各组血浆Ang-2均高于D组（P均≤0.05）,而脓毒症各组间血浆Ang-2差异无统计学意义（P均＞0.05）.脓毒症各组血浆BG均高于D组（P均≤0.05）;A、B组血浆BG均高于C组（P均≤0.05）,而A、B组间差异无统计学意义（P＞0.05）.脓毒症患者血浆Ang-2与APACHEⅡ、SOFA评分均呈正相关（r分别为0.599、0.723,P均≤0.05）,Ang-2与APACHEⅡ、SOFA评分均独立相关（β分别为0.468、0.626,P均≤0.05）.除C组外脓毒症患者血浆Ang-2与BG呈正相关（r=0.371,P≤0.05）;血浆BG与Ang-2独立相关（β=0.393,P≤0.05）.结论 脓毒症患者血浆Ang-2、BG水平升高,Ang-2是影响脓毒症患者病情严重程度的独立危险因素,BG是影响真菌感染脓毒症患者血浆Ang-2水平的独立危险因素.     

Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Caspofungin (CAS) is the first of a new class of antifungal agents, the echinocandins, that interfere with fungal cell wall synthesis by inhibition of glucan synthesis. Here, we report the results of 31 patients treated with CAS following allogeneic SCT. CAS was administered as a second-line agent to patients with invasive fungal infection (IFI) (n=15) or fever of unknown origin (n=16) who were recalcitrant to or intolerant of prior antifungal therapy. Unsuccessful first-line regimes included amphotericin B (n=17), liposomal amphotericin B (n=5), fluconazole (n=3), itraconazole (n=1), and voriconazole (n=2). All patients received concomitant immunosuppressive therapy for graft-versus-host disease. In 23 patients, cyclosporin A (CSA) and CAS were administered concurrently without any major side effects detected. Observed increases in GPT were not clinically significant. Normalization of serum creatinine and significant reductions in C-reactive protein were observed in response to CAS. Favorable outcome to CAS were documented in eight of 15 patients with IFI and in 15 of 16 patients with fever of unknown origin. CAS is a promising alternative in patients with IFI and fever of unknown origin in the setting of allogeneic SCT.     

Effect of an elastin growth substrate on cholesteryl ester synthesis and foam cell formation by cultured aortic smooth muscle cells

Exposure of smooth muscle cells cultured on plastic or glass to hyperlipidemic serum did not result in the formation of foam cells. Since elastin binds serum lipids, and vascular smooth muscle cells are normally closely associated with elastin, we investigated the effects of an elastin substrate on lipid metabolism and on the accumulation of lipid vacuoles by rabbit aortic smooth muscle cells in culture. When cells were grown in plastic petri dishes, cholesteryl ester synthesis, as measured by [14C]oleate incorporation into cholesteryl esters, was 3 times greater in rabbit hyperlipidemic serum (HLS) than in normolipemic serum (NLS) (P less than 0.001). For cells of the same subculture grown on the elastin substrate, the synthetic rate was 6-fold greater in HLS compared to NLS (P less than 0.005). The cells grown on the elastin membranes in the presence of HLS contained large numbers of Oil red O stainable lipid vacuoles and resembled foam cells, while those grown in petri dishes and exposed to HLS showed only an occasional cell containing a few vacuoles. Pre-incubation in lipoprotein-deficient serum markedly enhanced the stimulatory effect of HLS on cholesteryl ester synthesis for cells growing in plastic petric dishes but had much less stimulatory effect on the cells growing on elastin membranes. These studies indicate that close association with elastin modulates the response of smooth muscle cells to hyperlipidemia and suggest a role for elastin in the formation of foam cells of smooth muscle origin during atherogenesis.     

Antifungal hydrogels

Fungi are increasingly identified as major pathogens in bloodstream infections, often involving indwelling devices. Materials with antifungal properties may provide an important deterrent to these infections. Here we describe amphogel, a dextran-based hydrogel into which amphotericin B is adsorbed. Amphogel kills fungi within 2 h of contact and can be reused for at least 53 days without losing its effectiveness against Candida albicans. The antifungal material is biocompatible in vivo and does not cause hemolysis in human blood. Amphogel inoculated with C. albicans and implanted in mice prevents fungal infection. Amphogel also mitigates fungal biofilm formation. An antifungal matrix with these properties could be used to coat a variety of medical devices such as catheters as well as industrial surfaces.     

The use of itraconazole as prophylaxis against invasive fungal infection in blood and marrow transplant recipients

Invasive fungal infections play a key role in contributing to morbidity and mortality in patients undergoing treatment for haematological malignancies and related diseases. Risk factors for development of invasive fungal infections after blood or bone marrow transplantation include the use of broad‐spectrum antibiotics, steroids, mismatched or unrelated donor transplant, right atrial catheters, and prolonged or profound neutropenia. Previous attempts at use of oral itraconazole as antifungal prophylaxis in the setting of chemotherapy‐induced neutropenia were unsuccessful because of its poor absorption in capsule form. Itraconazole‐cyclodextrin is well absorbed even in the presence of chemotherapy‐induced neutropenia. Plasma levels of 250–500 ng/ml are required for prophylaxis. Studies to date show a favourable outcome in patients receiving itraconazole as prophylaxis against invasive fungal infections, although many studies looked at small numbers of patients and the incidence of invasive fungal infection in the control groups was low, prohibiting meaningful statistical evaluation. Fungi differ in their sensitivity to antifungal agents, and itraconazole is not the agent of choice in all patients. With the widespread use of antifungal prophylaxis, the possibility of resistance to antifungal agents and an increase in the number of invasive fungal infections caused by ubiquitous fungi previously considered nonpathogenic must be considered as potential problems.