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Aspergillosis

Aspergilloses

Aspergillosis is a general term referring to the variety of infectious diseases caused by the genus of fungi Aspergillus. Lungs are the primary target if this type of infection.


Presentation

Aspergillosis has 4 main forms which differ in their general clinical manifestations: Allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, chronic necrotizing pulmonary aspergillosis (CNPA), and invasive aspergillosis.

ABPA is especially frequent in those affected by asthma and cystic fibrosis, which after a certain period of time result in a hypersensitivity reaction to fungi colonization. Its typical signs include cough, mucous plugs, fever and pulmonary infiltrates, which appear to be unresponsive to antibacterial therapy. ABPA frequently occurs in conjunction with allergic fungal sinusitis, which shows symptoms like chronic sinusitis with the related purulent sinus drainage.

The major sign of aspergilloma is undoubtedly hemopotysis, experienced by 40-60% of the patients affected by this form of aspergillosis, which might sometime be large in size and life threatening. Less common, but nevertheless typical of aspergilloma, are also cough and fever.

CNPA, instead, usually manifests itself with a subacute pneumonia, which also proves to be unresponsive to antibiotic therapy. This, then, while slowly progressing over the following weeks, is soon followed by the other classical signs such as fever, cough, and sometime night sweats and weight loss. CNPA is generally accompanied by underlying diseases or conditions, the most frequent of which are steroid-dependent chronic obstructive pulmonary disease and alcoholism.

To conclude, invasive aspergillosis usually presents itself in patients who have undergone prolonged neutropenia or immunosuppression, and manifests itself with the classical signs of fever, cough and hemoptysis, together with pleuritic chest pain and dyspnea. This form of aspergillosis is very frequent in those subjects who have received a solid organ transplant, particularly lung transplant which more likely shows aspergillosis-related complications. Invasive aspergillosis is also frequent in patients affected by chronic obstructive pulmonary disease, as serious adverse side effect.

Fever
  • The most common symptoms in the CPA patients were cough (92.8%), hemoptysis (63.8%), chronic sputum (23.2%), and fever (17.4%).[ncbi.nlm.nih.gov]
  • […] can cause massive bleeding from the lung Mucus plugs in the airways Permanent airway blockage Respiratory failure Call your provider if you develop symptoms of aspergillosis or if you have a weakened immune system and develop a fever.[nlm.nih.gov]
  • Common symptoms include fever, cough and sputum production; positive serum antibody precipitins may also be detected. 2.[web.archive.org]
  • Common symptoms are cough, fever, malaise, coughing up blood or mucus plugs, chest pain and shortness of breath.[symptoma.com]
  • A 64-year-old man who presented with repeated bouts of pneumothorax was admitted to our hospital because of gradually progressive dyspnea and repeated episodes of a fever.[ncbi.nlm.nih.gov]
Chills
  • Health problems from the disease or treatment include: Amphotericin B can cause kidney damage and unpleasant side effects such as fever and chills Bronchiectasis (permanent scarring and enlargement of the small sacs in the lungs) Invasive lung disease[nlm.nih.gov]
  • Possible Complications Health problems from the disease or treatment include: Amphotericin B can cause kidney damage and unpleasant side effects such as fever and chills Bronchiectasis (permanent scarring and enlargement of the small sacs in the lungs[ufhealth.org]
Cough
  • Common symptoms are cough, fever, malaise, coughing up blood or mucus plugs, chest pain and shortness of breath.[symptoma.com]
  • She was started on itraconazole during the hospitalization in attempt to decrease her systemic steroid dose, but she had ongoing coughing and wheezing.[ncbi.nlm.nih.gov]
  • […] year-old man who had previously undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia was diagnosed with invasive laryngeal-tracheobronchial-pulmonary aspergillosis after presenting with a persistent dry cough[ncbi.nlm.nih.gov]
  • We report a 9-year- and 6-month-old girl who complained of chronic cough and recurrent wheeze for 2 months. Bronchialithiasis were found under bronchoscope. Pathologic examination revealed aspergillosis.[ncbi.nlm.nih.gov]
  • Symptoms of allergic pulmonary aspergillosis may include: Cough Coughing up blood or brownish mucus plugs Fever General ill feeling (malaise) Wheezing Weight loss Other symptoms depend on the part of the body affected, and may include: Bone pain Chest[nlm.nih.gov]
Hemoptysis
  • Chronic pulmonary aspergillosis is a major cause of life-threatening hemoptysis. In symptomatic patients with simple aspergillomas, surgery is the main therapeutic method for preventing or treating life-threatening hemoptysis.[ncbi.nlm.nih.gov]
  • The most common symptoms in the CPA patients were cough (92.8%), hemoptysis (63.8%), chronic sputum (23.2%), and fever (17.4%).[ncbi.nlm.nih.gov]
  • […] if pulmonary function is adequate Bronchial artery embolization may be used for life-threatening hemoptysis in patients unlikely to tolerate surgery or in patients with recurrent hemoptysis (eg, patients with CF in whom hemoptysis may be related to underlying[emedicine.medscape.com]
Dyspnea
  • A 64-year-old man who presented with repeated bouts of pneumothorax was admitted to our hospital because of gradually progressive dyspnea and repeated episodes of a fever.[ncbi.nlm.nih.gov]
  • We herein report a case of slowly progressing chronic multiple nodular pulmonary aspergillosis in a 59-year-old man with rheumatoid arthritis, dyspnea, and fatigue. One nodule was surgically resected.[ncbi.nlm.nih.gov]
  • A 67-year-old man with granulomatous polyangiitis (Wegener granulomatosis) complicated by end-stage renal disease requiring hemodialysis and mild pulmonary fibrosis, was hospitalized with a 2-week history of worsening dyspnea and dry cough.[jamanetwork.com]
  • Infusion-Related Reactions including hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur.[cresemba.com]
  • Invasive aspergillosis : IV voriconazole Coccidioidomycosis ( Valley fever ) Pathogen: Coccidioides immitis Risk factors: travel to Southwestern United States, California Yes Often asymptomatic Acute pneumonia : fever, chest pain, cough, arthralgia, dyspnea[amboss.com]
Productive Cough
  • Overall, 109 (52.4%) had documented TB, 140 (67.3%) had a productive cough and 50 had haemoptysis. CPA prevalence was 8.7%; 10 (6.5%) had HIV infection and 8 (14.5%) were HIV-negative (Fisher's exact P 0.092).[ncbi.nlm.nih.gov]
  • There is productive cough with large amounts of thick green sputum and it might produce thick yellow mucus plugs. Cough with mucous plugs Inhalation of aspergillus spores produces type 1 hypersensitivity reaction in the bronchial wall.[medicaljoyworks.com]
  • Characteristic symptoms of allergic bronchopulmonary aspergillosis, seen especially in patients with chronic pulmonary diseases, include a chronic productive cough and purulent sputum occasionally tinged with blood and flecks of white or brownish mycelium[britannica.com]
  • He was admitted for fever and productive cough, after receiving inhaled colistin for one month for multidrug-resistant Pseudomonas aeruginosa respiratory tract colonization. We decided to suspend chemotherapy and started a diagnostic study.[archbronconeumol.org]
  • Common symptoms are fatigue, weight loss breathlessness, productive cough and haemoptysis (coughing up blood). The disease is often mistaken for pulmonary tuberculosis and both diseases can co-exist.[life-worldwide.org]
Chronic Cough
  • We report a 9-year- and 6-month-old girl who complained of chronic cough and recurrent wheeze for 2 months. Bronchialithiasis were found under bronchoscope. Pathologic examination revealed aspergillosis.[ncbi.nlm.nih.gov]
  • Advanced mycosis is characterized by weight loss, a chronic cough, tiredness, and coughing up blood (in 50 to 80% of infected people). Treatment depends on the size of the lesions and the affected area.[pasteur.fr]
  • Weight loss, chronic cough, feeling rundown and tired are common symptoms later. Coughing of blood (haemoptysis) can occur in up to 50-80% of affected people.[aspergillus.org.uk]
  • They can experience unintended weight loss, a chronic cough that produces mucus, the coughing up of blood, fatigue, and shortness of breath. Less often, fever or night sweats can occur.[rarediseases.org]

Workup

The main diagnostic tool to diagnose aspergillosis is optical microscopy. When using silver staining, aspergillosis fungi appear as elongated hyphae with walls neatly marked in gray-black color [16]. The hyphae appear septate and have a diameter ranging from 2.5 to 4.5 µm. These structures are not always clear and apparent, and they can be frequently mistaken with the members of Zygomycota [16], another phylum of terrestrial fungi which mainly live as parasites of animals and plants and sometime in symbiotic relationships with them. The peculiar characteristic of these hyphae is their progressive branching patter, which tends to form acute angles of 45° [16].

Aspergillosis can also be diagnosed with chest X-ray and CT scan, with which the colonies of hyphae appear as halo signs that later progressive in air crescent signs [17].

Pulmonary Infiltrate
  • The authors report on 4 patients with acute leukemia and invasive aspergillosis whose radiographs demonstrated a distinctive feature of one or more air crescents within an area of pulmonary infiltrate.[ncbi.nlm.nih.gov]
  • Pulmonary infiltrates do not respond to conventional antibiotics.[patient.info]
Cavitary Lesion
  • lesions aspergilloma well-formed cavitary lesion, often mobile (changes as the patient changes position) Monad sign air surrounding soft tissue mass, indicating pre-existing cavity ABPA bronchiectasis Bronchoscopy indication to obtain sample for culture[medbullets.com]
  • (b) Photograph of an autopsy specimen from the left upper lobe shows an irregular cavitary lesion with regular margins and a dark brown appearance caused by necrotic material and Aspergillus infection. Figure 9b.[pubs.rsna.org]
  • Thus, ABPA must be distinguished from invasive aspergillosis, which occurs in immunocompromised patients; from aspergillomas, which are collections of Aspergillus in patients with established cavitary lesions or cystic airspaces; and from the rare Aspergillus[msdmanuals.com]
  • A movable fungus ball within a cavitary lesion is characteristic on both, although most lesions are focal and solid. Sometimes imaging detects a halo sign (a hazy shadow surrounding a nodule) or cavitation within a necrotic lesion.[msdmanuals.com]
  • Aspergillus in patients with established cavitary lesions or cystic airspaces; and from the rare Aspergillus pneumonia, which occurs in patients who take low doses of prednisone long term (eg, patients with COPD ).[physio-pedia.com]
Pleural Mass
  • CT scan of the chest demonstrated bilateral pulmonary infiltrates, pleural masses ( Figure 1a , arrows) and a lytic lesion of the left fourth rib ( Figure 1b , arrow).[nature.com]
  • Empyema or pleural masses are rare.(6) In a small observational cohort study conducted in Spain, investigators identified 19 of 1,605 HIV-infected individuals with invasive pulmonary aspergillosis, yielding an incidence rate of 1.12%.(16) Ninety-five[hivinsite.ucsf.edu]
X-Ray Abnormal
  • The diagnosis of ABPA requires the presence of a constellation of symptoms, x-ray abnormalities and investigation results that provide evidence of the presence of sensitisation to Aspergillus as well as a ‘response’ by the body to the fungus.[lungfoundation.com.au]
Mycobacterium Kansasii
  • The most common causative NTM species were Mycobacterium avium complex (MAC; 37 patients; 59.7%) and Mycobacterium kansasii (20 patients; 32.3%). Survival was 83% after 1 year and 61% after 5 years.[ncbi.nlm.nih.gov]

Treatment

For the most aggressive forms of aspergillosis the medical treatments currently deployed are based on the combined use of two important antifungal agents, voriconazole and liposomal amphotericin B. In the most severe cases these two agents might not be sufficient, and their use should be coupled with the removal of the affected tissue, so that the healing of the remaining healthy part of the organ can be improved [18].

For the less aggressive forms of aspergillosis, like allergic bronchopulmonary aspergillosis, the medical treatment is largely based on the use of oral steroids for a prolonged period of time, usually ranging from 6 to 9 months. The treatment can be integrated with itracozanole, another triazole antifungal agent frequently prescribed for its “steroid sparing” effect which makes steroids’ action much more effective [14].

Other drugs used against aspergillosis include caspofungin, flucytosine, or the already mentioned itracozanole, many of them belonging to the class of compounds called triazoles, for the presence in their molecular structure of the triazole ring, a pentameric aromatic structure with two atoms of carbons and three atoms of nitrogen. It should be remembered that there is a growing portion of infections which turn out to be resistant to triazoles [19], like the previously mentioned Aspergillus fumigatus, the most common infecting species, which appears to be resistant to fluconazole [20]. Therefore, the antibiotic choice must be pondered with care.

Prognosis

The prognosis of aspergillosis is generally good provided that treatment is strictly followed, and clinical symptoms should begin to improve quickly after a few days from therapy initiation. The successful outcome of the treatment heavily depends on early diagnosis, early and effective antifungal therapy initiation, and immunological restoration. The outlook has very much improved over the last few decades, thanks to the availability of advanced tools for early diagnosis (e.g., high-resolution CT scan or fungal biomarkers) and increasingly better antifungal drugs which prove to be more effective than amphotericin B [14].

Aspergillosis tends to remain quiescent or dormant until another factor or event restarts immunosuppression, for example when immunotherapy, for whatever reason, is reintroduced. Therefore, the risk of relapse is quite high and cannot be underestimated. For instance, in subjects with prior history of aspergillosis and undergoing myeloablative chemotherapy, the risk of relapse is around 20%, a figure which does not allow to dismiss the reoccurrence of aspergillosis. As a rule, as way of secondary prophylaxis specialists tend to use voriconazole [15], a triazole antifungal medication recently become the standard of care in antifungal treatment.

Etiology

The fungi of the genus Aspergillus are ubiquitous and very common molds of the soil, which usually grow in organic matter as mycelium and hyphal stalks [7]. These fungi are hydrophobic in nature, and this characteristic helps their aerosolization [7] [8] [9]. There are approximately 180 species of Aspergillus known to cause aspergillosis. Among these, the most common is undoubtedly Aspergillus fumigatus, accounting for 50% to 70% of the aspergillus diseases, especially aspergilloma that is almost exclusively caused by this species. Instead, one of the most dangerous fungi is Aspergillus terreus, which is resistant to amphotericin B and the patients affected by it always have a very poor prognosis [10].

In rare occasions, the Aspergillus fungi might infiltrate the human body via direct cutaneous inoculation, a situation which especially occurs after a trauma [11].

Epidemiology

Aspergillosis is found all over the world, regardless the geographic region concerned, where it especially affects individuals with compromised immune systems due to malignancies and organ transplants, as well as the occurrence of major illnesses like AIDS and pulmonary disease.

The incidence of aspergillosis at 12 months varies according to the underlying condition which has triggered it. At 12 months after stem cell transplantation, the incidence of aspergillosis is 0.05% in autologous recipients, 2.3% in allogeneic recipients with HLA-matched related donors, and 3.9% in patients with a related donors [12]. At 12 months after solid organ transplantation, instead, the incidence is 2.4% for lung transplants, 0.8% for heart transplants, 0.3% for liver transplants, and 0.1% for kidney transplants [12].

Mortality at 1 year after stem cell transplantation has gradually decreased in these last few decades, but it still remains very high, stable in the range going from 50% to 80%. Mortality is even higher when aspergillosis affects the brain and the infection begins to spread throughout the body [13]. According to the data coming from the US, mortality has increased by 357 % between 1980 and 1997 [14], even though this is attributed to social phenomena, like the increased number of individuals at risk due to advances of medicine or simply the wider portion of the aging population.

Sex distribution
Age distribution

Pathophysiology

Aspergillus causes a variety of diseases, like hypersensitivity reactions, chronic necrotizing infections, or progressive angioinvasion, many of which result in death. Aspergillus always occurs in subjects with compromised immune systems due to underlying conditions, like the occurrence of a lung disease, the implementation of an immunosuppressive drug therapy, or an immunodeficiency acquired from a disease such as AIDS.

Aspergillus fumigatus is the most frequent pathogen responsible for this infection in humans, which has the ability of this species to grow and thrive in the environmental conditions found within the human body. In any case, many species manage to overcome the immune system defenses by producing toxic metabolites that inhibit the action of macrophages and neutrophils. These immune cells are also largely neutralized in immunosuppressive conditions, like the already mentioned occurrence of HIV or under pharmacogenetic immunosuppression.

Prevention

The prevention of aspergillosis is largely based on the reduction to mold and spore exposure, which should be implemented by taking proper environmental preventive measures. In particular, special care has to be given to the hospital setting, which should be equipped with proper elements such as high-efficient particulate air filters and positive-pressure ventilation and air exchange systems [21] [22] [23]. Careful cleaning of showers and water systems is also paramount for the reduction of fungi exposure [24].

The subjects who have received solid organ transplants or allogeneic stem cell transplantations are recommended to take preventive antifungal drugs such as posaconazole [25], voriconazole and fluconazole [26], especially in the cases involving severely compromised immune systems.

Summary

Aspergillosis is a classical example of opportunistic infection, which takes advantage of the moment of weakness of the immune system due to the occurrence of other diseases and conditions. This is the reason why aspergillosis is particularly frequent in patients affected by AIDS, or in those undergoing hematopoietic stem cell transplantation or chemotherapy for leukemia. Aspergillosis is also frequent in patients with underlying diseases affecting the respiratory system, in particular tuberculosis [1] and chronic obstructive pulmonary disease (COPD), which can indirectly trigger fungal infection even if the immune system is healthy and fully operational [2]. This can be explained by remembering that the species of the Aspergillus genus are ubiquitous organisms, capable of living under the most stressful environmental conditions, and people inhale thousands of spores every day without no sign of infection. When the immune system fails, the fungal cells can enter the bloodstream via the lungs and disseminate throughout the body, infecting major organs such as heart and kidneys.

The most common forms of aspergillosis are chronic pulmonary aspergillosis (CPA), aspergilloma, and allergic bronchopulmonary aspergillosis (ABPA), which frequently occur in intertwined forms. Taking together in all their forms, chronic, invasive and allergic, they cause around 600.000 deaths every year all around the world [1] [3] [4] [5] [6].

Patient Information

Aspergillosis is a general term referring to the variety of infectious diseases caused by the genus of fungi Aspergillus, whose primary target is the lungs. Aspergillosis is a classical example of opportunistic infection, which takes advantage of a moment of weakness of the immune system due to the occurrence of other diseases and conditions. It is particularly frequent in patients affected by AIDS, or in those undergoing stem cell transplantation or chemotherapy for leukemia. Aspergillosis is also common in patients with underlying diseases affecting the respiratory system, in particular tuberculosis and chronic obstructive pulmonary disease.

Aspergillosis has 4 main forms which differ in their signs and symptoms: Allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, chronic necrotizing pulmonary aspergillosis (CNPA), and invasive aspergillosis. Common symptoms are cough, fever, malaise, coughing up blood or mucus plugs, chest pain and shortness of breath

For the most aggressive forms of aspergillosis, the medical treatments currently deployed are based on the combined use of two drugs, voriconazole and liposomal amphotericin B. In the most severe cases these two agents might not be enough, and their use should be coupled with the removal of the affected tissue, so that the healing of the remaining healthy part of the organ can be improved. For the less aggressive forms of aspergillosis, the medical treatment is largely based on the use of oral steroids for prolonged periods of time.

The prognosis of aspergillosis is generally good provided that treatment is strictly followed, and clinical symptoms should begin to improve quickly after a few days from therapy initiation. The successful outcome of the treatment heavily depends on early diagnosis, early and effective antifungal therapy initiation, and immunological restoration. The outlook has very much improved over the last few decades, thanks to the availability of advanced tools for early diagnosis and increasingly better antifungal drugs.

References

Article

  1. Denning DW, Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis complicating sarcoidosis. European Respiratory Journal 2013 41 (3): 621–6.
  2. Smith N, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. European Respiratory Journal 2011 37 (4): 865–872.
  3. Guinea J, Torres-Narbona M, Gijón P, Muñoz P, Pozo F, Peláez T, de Miguel J, Bouza E. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010 16 (7): 870–7.
  4. Chen J, Yang Q, Huang J, Li L. Risk factors for invasive pulmonary aspergillosis and hospital mortality in acute-on-chronic liver failure patients: A retrospective cohort study. Int J Med Sci 2013 10 (12): 1625–31.
  5. Garcia-Vidal C, Upton A, Kirby KA, Marr KA. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: Biological risk factors for infection according to time after transplantation. Clin Infect Dis 2008 47 (8): 1041–50.
  6. Nam HS, Jeon K, Um SW, Suh GY, Chung MP, Kim H, Kwon OJ, Koh WJ. Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: A review of 43 cases. Int J Infect Dis 2010 14 (6): 479–482.
  7. Patterson TF. Aspergillus species. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases, 6th ed. New York, NY: Elsevier/Churchill Livingstone; 2005:2958-2973.
  8. Barnes PD, Marr KA. Aspergillosis: spectrum of disease, diagnosis, and treatment. Infect Dis Clin North Am. 2006;20:545-561.
  9. Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis. 2005;5:609-622.
  10. Walsh TJ, Petraitis V, Petraitiene R, et al. Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J Infect Dis. 2003;188:305-319.
  11. Mays SR, Bogle MA, Bodey GP. Cutaneous fungal infections in the oncology patient: recognition and management. Am J Clin Dermatol. 2006;7:31-43.
  12. Morgan J, Wannemuehler KA, Marr KA, et al. Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med Mycol. 2005;43:S49-S58.
  13. McNeil MM, Nash SL, Hajjeh RA, et al. Trends in mortality due to invasive mycotic diseases in United States, 1980-1997. Clin Infect Dis. 2001;33:641-647.
  14. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327-360.
  15. Sipsas NV, Kontoyiannis DP. Clinical issues regarding relapsing aspergillosis and the efficacy of secondary antifungal prophylaxis in patients with hematological malignancies. Clin Infect Dis. 2006;42:1584-1591.
  16. Kradin RL, Mark EJ. The pathology of pulmonary disorders due to Aspergillus spp. Arch Pathol Lab Med 2008 132 (4): 606–14.
  17. Curtis A, Smith G, Ravin C. Air crescent sign of invasive aspergillosis. Radiology 1979 133 (1): 17–21.
  18. Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, Safdar A, Kantarjian H, Champlin R, Walsh TJ, Raad II. Zygomycosis in a Tertiary‐Care Cancer Center in the Era ofAspergillus‐Active Antifungal Therapy: A Case‐Control Observational Study of 27 Recent Cases. The Journal of Infectious Diseases 2005 191 (8): 1350–1360.
  19. Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Bowyer P, Perlin DS. High-frequency Triazole Resistance Found In Nonculturable Aspergillus fumigatus from Lungs of Patients with Chronic Fungal Disease. Clin Infect Dis 2011 52 (9): 1123–9.
  20. Perea S, Patterson TF. Antifungal resistance in pathogenic fungi. Clinical infectious diseases:an official publication of the Infectious Diseases Society of America 2002 35 (9): 1073–80.
  21. Dykewicz CA; National Center for Infectious Diseases, Centers for Disease Control and Prevention; Infectious Diseases Society of America; American Society for Blood and Marrow Transplantation. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: focus on community respiratory virus infections. Biol Blood Marrow Transplant. 2001;7:19S-22S.
  22. Tablan OC, Anderson LJ, Arden NH, et al. Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Infect Control Hosp Epidemiol. 1994;15:587-627.
  23. Partridge-Hinckley K, Liddell GM, Almyroudis NG, et al. Infection control measures to prevent invasive mould diseases in hematopoietic stem cell transplant recipients. Mycopathologia. 2009;168:329-337.
  24. Anaissie EJ, Costa SF. Nosocomial aspergillosis is waterborne. Clin Infect Dis. 2001;33:1546-1548.
  25. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D. Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia. New England Journal of Medicine 2007 356 (4): 348–359.
  26. Wingard JR, Carter SL, Walsh TJ, et al. Blood and Marrow Transplant Clinical Trials Network. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010;116:5111-5118.

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Last updated: 2019-07-11 22:11