Early diagnosis and treatment of invasive aspergillosis as a main determinant of outcome – review of literature according to the presented case report
More details
Hide details
II Department of Anaesthesiology and Intensive Care, Medical University, Lublin, Poland
Department of Internal Medicine, Medical University of Lublin.
Corresponding author
Andrzej Prystupa   

Department of Internal Medicine, Medical University of Lublin.
Ann Agric Environ Med. 2017;24(1):100-103
Aspergillus spp infection is not the major cause of morbidity in Intensive Care Units (ICUs), mortality among patients treated for it is tremendous. Moreover, invasive aspergillosis (IA) is an independent risk factor of hospital costs and length of stay. The prevalence of this disease is inversely correlated with the immunocompetence of individuals; for instance, the incidence of IA among patients with leukemia is estimated as high as 12.7%. Although there is a significant improvement in the antifungal armamentarium, the appropriate treatment is still being given too late, mostly because of late diagnosis. As well as the diagnosis, the criteria for recognition of IA constitute a challenge.

The aim of this review, based on a case report, is to introduce the problem of poor diagnosis and treatment of IA, especially in the critical care settings. The presented scenario is an example which assists in showing the evidence-based medicine (EBM) approach to the treatment of fungal infections. Furthermore, to demonstrate the appropriate approach to diagnosis and treatment of invasive aspergillosis, the guidelines of The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) are presented.

According to presented literature, Galactomannan assay enables early diagnosis and remains a specific and sensitive tool to diagnose Asppergillosis, both in serum and BAL fluid. The guidelines recommend voriconazole as a first line treatment in IA. Failure to detect and implement proper antifungal treatment may lead to fatal consequences, as in the presented case.

Pfaller MA, Diekema DJ. Epidemiology of invasive Candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007; 20:133–63.
Neofytos D, Horn D, Anaissie E, et al. Epidemiology andoutcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of multicenter Prospective Antifungal Therapy (PATH) alliance registry, Clin Infect Dis. 2009; 48: 265–73.
Nicolle MC, Benet T, Thiebaut A et al. Invasive aspergillosis in patients with hematologic malignancies: incidence and description of 127 casesenrolled in a single institution prospective survey from 2004 to 2009, Haematologica. 2011; 96: 1685–91.
Baddley JW, Stephens JM, Ji X, Gao X, Schlamm HT, Tarallo M. Aspergillosis in Intensive Care Unit (ICU) patients: epidemiology and economic outcomes BMC Infect Dis. 2013; 13: 29.
Kim A, Nicolau DP, Kuti JL. Hospital costs and outcomes among intravenous antifungal therapies for patients with invasive aspergillosis in the United States, Mycoses. 2011; 54: 301–12.
Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004; 39: 309–17.
De Lucca AJ, Boué SM, Carter-Wientjes CH, Bland JM, Bhatnagar D, Cleveland TE. Volatile profiles of toxigenic and non-toxigenic Aspergillus flavus using SPME for solid phase extraction. Ann Agric Environ Med. 2010; 17: 301–8.
Hidron AI, Edwards JR, Patel J, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the national healthcare safety network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol. 2008; 29: 996–1011.
Chamilos G, Luna M, Lewis RE, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006; 91: 986–9.
Meersseman W, Lagrou K, Maertens J, et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients, Am J Resp Crit Care Med. 2008; 177: 27–34.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, et al. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008; 46: 1813–21.
Tsitsikas DA, Morin A, Araf S, Murtagh B, Johnson G, Vinnicombe S, et al. Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis. Med Mycol. 2012; 50: 538–42.
Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter clinical evaluation of the (1 → 3) β-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis. 2005; 41: 654–9.
Leslie CE, Flannigan B, Milne LJR. Morphological studies on clinical isolates of Aspergillus fumigatus. J Med Vet Mycol. 1988; 26: 335–41.
Horvath JA, Dummer S. The use of respiratory-tract cultures in the diagnosis of invasive pulmonary aspergillosis. Am J Med. 1996; 100: 171–8.
Levine SJ. An approach to the diagnosis of pulmonary infections in immunosuppressed patients. Semin Respir Infect. 1992; 7: 81–95.
Bergeron A, Belle A, Sulahian A, et al. Contribution of galactomannan antigen detection in BAL to the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies. Chest. 2010; 137: 410–15.
Maertens J, Maertens V, Theunissen K, et al. Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases. Clin Infect Dis. 2009, 49: 1688–93.
Torelli R, et al. 2011. Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay. J Clin Microbiol. 2011; 49: 4273–8.
Luong ML, Clancy CJ, Vadnerkar A, et al. Comparison of an aspergillus real-time polymerase chain reaction assay with galactomannan testing of bronchoalvelolar lavage fluidfor the diagnosis of invasive pulmonary aspergillosis in lung transplant recipients. Clin Infect Dis. 2011; 52: 1218–26.
Balajee SA, Gribskov JL, Hanley E, Nickle D, Marr A. Aspergillus lentulus sp. nov., a new sibling species of A. fumigatus. Eukaryotic Cell. 2005; 4:625–32.
Walsh TJ, Wissel MC, Grantham KJ, et al. Molecular detectionand species-specific identification of medically important Aspergillus species by real-time PCR in experimental invasive pulmonary aspergillosis. J Clin Microbiol. 2011; 49: 4150–7.
Riwes MM, Wingard JR. Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies. Expert Rev Hematol. 2012; 5: 661–9.
Denning DW, Kibbler CC, Barnes RA. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections. Lancet Infect Dis. 2003; 3: 230–40.
Paterson PJ, Seaton S, McHugh TD, et al. Validation and clinical application of molecular methods for the identification of molds in tissue. Clin Infect Dis. 2006; 42: 51–56.
Kang EM, Marciano BE, DeRavin SS, Zarember K, Holland SM, Malech HL. Chronic Granulomatous Disease: Overview and Hematopoietic Stem Cell Transplant. J Allergy Clin Immunol. 2011; 127: 1319–26.
Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003; 362: 1828–38.
O’Donnell MR, Schmidt GM, Tegtmeier BR, et al. Prediction of systemic fungal infection in allogeneic marrow recipients: impact of amphotericin prophylaxis in high-risk patients. J Clin Oncol. 1994; 12: 827–34.
Grow WB, Moreb JS, Roque D, et al. Late onset of invasive Aspergillus infection in bone marrow transplant patients at a university hospital. Bone Marrow Transplan. 2002; 29: 15–19.
Gustafson TL, Schaffner W, Lavely GB, et al. Invasive aspergillosis in renal transplant recipients: correlation with corticosteroid therapy. J Infect Dis. 1983; 148: 230–8.
Balloy V, Huerre M, Latge JP, Chignard M. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect Immun. 2005; 73: 494–503.
Greene RE, Schlamm HT, Oestmann JW, et al. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis. 2007; 44: 373–9.
Salonen J, Lehtonen OP, Teräsjärvi MR, Nikoskelainen J. Aspergillus antigen in serum, urine and bronchoalveolar lavage specimens of neutropenic patients in relation to clinical outcome, Scand J Infect Dis. 2000; 32: 485–90.
Obayashi T, Yoshida M, Mori T, et al. Plasma (1 → 3)-β-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes. The Lancet. 1995; 345: 17–20.
Miceli MH, Grazziutti ML, Woods G, et al. Strong correlation between serum Aspergillus galactomannan index and outcome of aspergillosis in patients with hematological cancer: clinical and research implications. Clin Infect Dis. 2008; 46: 1412–22.
Maertens J, Maertens V, Theunissen K, et al. Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases. Clin Infect Dis. 2009; 49: 1688–93.
Klont RR, Mennink-Kersten MASH, Verweij PE. Utility of Aspergillus antigen detection in specimens other than serum specimens. Clin Infect Dis. 2004; 39: 1467–74.
Swanink CMA, Meis JFGM, Rijs AJMM, Donnelly JP, Verweij JP. Specificity of a sandwich enzyme-linked immunosorbent assay for detecting Aspergillus galactomannan. J Clin Microbiol. 1997. 35: 257–60.
Sulahian A, Touratier S, Ribaud P. False positive test for aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam. N Engl J Med. 2003; 349: 2366–7.
Racil Z, Kocmanova I, Lengerova M, Winterova J, Mayer J. Intravenous PLASMA-LYTE as a major cause of false positive results of platelia Aspergillus test for galactomannan detection in serum. J Clin Microbiol. 2007; 45: 3141–2.
Sherif R, Segal BH. Pulmonary Aspergillosis: clinical presentation, diagnostic tests, management and complications. Curr Opin Pulm Med. 2010; 16: 242–50.
Delisle MS, Williamson DR, Albert M, Perreault MM, Jiang X, Day AG et al. Impact of Candida species on clinical outcomes in patients with suspected ventilator-associated pneumonia Can Respir J. 2011; 18: 131–6.
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: 327–60.
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002; 347: 408–15.
Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004; 39: 1563–71.
Journals System - logo
Scroll to top