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Farahani A, Ghiasvand F, Davoudi S, Ahmadinejad Z. Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality. World J Transplant 2023; 13:264-275. [PMID: 37746042 PMCID: PMC10514749 DOI: 10.5500/wjt.v13.i5.264] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/17/2023] [Accepted: 09/04/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND Infections, including invasive fungal infections (IFIs), are among the leading causes of mortality in liver transplant recipients during the first year post-transplantation. AIM To investigate the epidemiology, clinical manifestations, risk factors, treatment outcomes, and mortality rate of post-liver transplantation invasive aspergillosis (IA). METHODS In this case-control study, 22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran, Iran, between 2014 and 2019. The control group comprised 38 patients without IA infection matched for age and sex. The information obtained included the baseline characteristics of liver transplant patients, operative reports, post-transplantation characteristics of both groups and information about the fungal infection of the patient group. RESULTS The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%. The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant, renal replacement therapy, antithymocyte globulin induction therapy, post-transplant bile leakage, post-transplant hepatic artery thrombosis, repeated surgery within 30 d after the transplant, bacterial pneumonia before the aspergillosis diagnosis, receiving systemic antibiotics before the aspergillus infection, cytomegalovirus infection, and duration of post-transplant hospitalization in the intensive care unit. The most prevalent form of infection was invasive pulmonary aspergillosis, and the most common chest computed tomography scan findings were nodules, pleural effusion, and the halo sign. In the case group, prophylactic antifungal therapy was administered more frequently than in the control group. The antifungal therapy response rate at 12 wk was 63.7%. The 3- and 12- mo mortality rates of the patients with IA were 36.4% and 45.4%, respectively (compared with the mortality rate of the control group in 12 mo, which was zero). CONCLUSION In this study, the prevalence of IA among liver transplant recipients was relatively low. However, it was one of the leading causes of mortality following liver transplantation. Targeted antifungal therapy may be a factor in the low incidence of infections at our facility. Identifying the risk factors of IFIs, maintaining an elevated level of clinical suspicion, and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.
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Affiliation(s)
- Azam Farahani
- Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
| | - Fereshteh Ghiasvand
- Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
| | - Setareh Davoudi
- Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
| | - Zahra Ahmadinejad
- Liver Transplantation Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
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2
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Osman H, Shaik AN, Nguyen PL, Cantor Z, Kaafarani M, Soubani AO. The Clinical Significance of Aspergillus Detected in Lower-Respiratory-Tract Samples of Critically Ill COVID-19-Positive Patients. Adv Respir Med 2023; 91:337-349. [PMID: 37736973 PMCID: PMC10514834 DOI: 10.3390/arm91050027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 08/28/2023] [Accepted: 08/28/2023] [Indexed: 09/23/2023]
Abstract
Objective: Critically ill patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications, including invasive aspergillosis. Our study aimed to characterize the clinical significance and outcome of Aspergillus species isolated from lower-respiratory-tract samples of critically ill OVID-19 patients at a single center. Design: We conducted a retrospective cohort study to evaluate the characteristics of patients with COVID-19 and aspergillus isolated from the lower respiratory tract and to identify predictors of outcomes in this population. Setting: The setting was a single-center hospital system within the metropolitan Detroit region. Results: The prevalence of Aspergillus isolated in hospitalized COVID-19 patients was 1.18% (30/2461 patients), and it was 4.6% in critically ill ICU patients with COVID-19. Probable COVID-19-associated invasive pulmonary aspergillosis (CAPA) was found in 21 critically ill patients, and 9 cases were classified as colonization. The in-hospital mortality of critically ill patients with CAPA and those with aspergillus colonization were high but not significantly different (76% vs. 67%, p = 1.00). Furthermore, the in-hospital mortality for ICU patients with or without Aspergillus isolated was not significantly different 73.3% vs. 64.5%, respectively (OR 1.53, CI 0.64-4.06, p = 0.43). In patients in whom Aspergillus was isolated, antifungal therapy (p = 0.035, OR 12.3, CI 1.74-252); vasopressors (0.016, OR 10.6, CI 1.75-81.8); and a higher mSOFA score (p = 0.043, OR 1.29 CI 1.03-1.72) were associated with a worse outcome. In a multivariable model adjusting for other significant variables, FiO2 was the only variable associated with in-hospital mortality in patients in whom Aspergillus was isolated (OR 1.07, 95% CI 1.01-1.27). Conclusions: The isolation of Aspergillus from lower-respiratory-tract samples of critically ill patients with COVID-19 is associated with high mortality. It is important to have a low threshold for superimposed infections such as CAPA in critically ill patients with COVID-19.
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Affiliation(s)
- Heba Osman
- Department of Medicine and Pediatrics, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Asra N. Shaik
- Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Paul L. Nguyen
- Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Zachary Cantor
- Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Mirna Kaafarani
- Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine, 3990 John R-3 Hudson, Detroit, MI 48201, USA
| | - Ayman O. Soubani
- Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine, 3990 John R-3 Hudson, Detroit, MI 48201, USA
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3
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Shiari A, Nassar M, Soubani AO. Major pulmonary complications following Hematopoietic stem cell transplantation: What the pulmonologist needs to know. Respir Med 2021; 185:106493. [PMID: 34107323 DOI: 10.1016/j.rmed.2021.106493] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/28/2021] [Accepted: 05/29/2021] [Indexed: 12/16/2022]
Abstract
Hematopoietic stem cell transplantation (HSCT) is used for treatment of a myriad of both malignant and non-malignant disorders. However, despite many advances over the years which have resulted in improved patient mortality, this subset of patients remains at risk for a variety of post-transplant complications. Pulmonary complications of HSCT are categorized into infectious and non-infectious and occur in up to one-third of patients undergoing HSCT. Infectious etiologies include bacterial, viral and fungal infections, each of which can have significant mortality if not identified and treated early in the course of infection. Advances in the diagnosis and management of infectious complications highlight the importance of non-infectious pulmonary complications related to chemoradiation toxicities, immunosuppressive drugs toxicities, and graft-versus-host disease. This report aims to serve as a guide and clinical update of pulmonary complications following HSCT for the general pulmonologist who may be involved in the care of these patients.
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Affiliation(s)
- Aryan Shiari
- Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Mo'ath Nassar
- Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Ayman O Soubani
- Division of Pulmonary, Critical Care and Sleep Medicine, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
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4
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Pourbaix A, Lafont Rapnouil B, Guéry R, Lanternier F, Lortholary O, Cohen JF. Smoking as a Risk Factor of Invasive Fungal Disease: Systematic Review and Meta-Analysis. Clin Infect Dis 2021; 71:1106-1119. [PMID: 31900476 DOI: 10.1093/cid/ciaa001] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 01/01/2020] [Indexed: 01/23/2023] Open
Abstract
To investigate the association between smoking and invasive fungal disease (IFD), we searched MEDLINE and Web of Science for studies published until September 2018. Two authors independently performed study selection and data extraction. Relative risks (RRs) were pooled using random-effects meta-analysis. We included 25 studies (18 171 participants; 2527 IFD cases). The meta-analysis showed an increased risk of IFD in smokers (RR 1.41 [95% confidence interval 1.09-1.81]; P = .008). The risk of IFD was higher in retrospective than in prospective studies (RR 1.93 [1.28-2.92] vs. 1.02 [0.78-1.34]; P = .04), in studies with multivariate adjustment compared to studies with univariate analysis (RR 2.15 [1.27-3.64] vs. 1.15 [0.88-1.51]; P = .06), and in studies published after 2002 (RR 2.08 [1.37-3.15] vs. 0.95 [0.75-1.22]; P = .008); other subgroup characteristics did not significantly influence the association in metaregression. Smoking cessation strategies should be implemented, especially in patients who are already at risk for IFD.
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Affiliation(s)
- Annabelle Pourbaix
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants malades Hospital, APHP, Paris University, Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Baptiste Lafont Rapnouil
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants malades Hospital, APHP, Paris University, Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Romain Guéry
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants malades Hospital, APHP, Paris University, Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Fanny Lanternier
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants malades Hospital, APHP, Paris University, Sorbonne Paris Cité, Imagine Institute, Paris, France.,Institut Pasteur, Molecular Mycology Unit, National Reference Center for Invasive Mycoses and Antifungals, UMR, CNRS, Paris, France
| | - Olivier Lortholary
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants malades Hospital, APHP, Paris University, Sorbonne Paris Cité, Imagine Institute, Paris, France.,Institut Pasteur, Molecular Mycology Unit, National Reference Center for Invasive Mycoses and Antifungals, UMR, CNRS, Paris, France
| | - Jérémie F Cohen
- Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants malades Hospital, APHP, Paris University, Sorbonne Paris Cité, Imagine Institute, Paris, France.,Inserm U1153, Centre of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris University, Paris, France
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5
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Bulpa P, Duplaquet F, Dimopoulos G, Vogelaers D, Blot S. Invasive Pulmonary Aspergillosis in Chronic Obstructive Pulmonary Disease Exacerbations. Semin Respir Crit Care Med 2020; 41:851-861. [PMID: 32599634 DOI: 10.1055/s-0040-1702210] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Nowadays, reports in the literature support that patients with severe chronic obstructive pulmonary disease (COPD) are at higher risk to develop invasive pulmonary aspergillosis (IPA). However, the interpretation of Aspergillus-positive cultures from the airways in critically ill COPD is still a challenge. Indeed, as the patient could be merely colonized, tissue samples are required to ascertain IPA diagnosis but they are rarely obtained before death. Consequently, diagnosis is often only suspected on the basis of a combination of three elements: clinical characteristics, radiological images (mostly thoracic CT scan), and microbiological, and occasionally serological, results. To facilitate the analysis of these data, several algorithms have been developed, and the best effectiveness has been demonstrated by the Clinical algorithm. This is of importance as IPA prognosis in these patients remains presently very poor and using such an algorithm could promote prompter diagnosis, early initiation of treatment, and subsequently improved outcome.While the most classical presentation of IPA in critically ill COPD patients features a combination of obstructive respiratory failure, antibiotic-resistant pneumonia, recent or chronic corticosteroid therapy, and positive Aspergillus cultures from the lower respiratory tract, the present article will also address less typical presentations and discuss the most appropriate treatments which could alter prognosis.
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Affiliation(s)
- Pierre Bulpa
- Department of Intensive Care Unit, Mont-Godinne University Hospital, CHU UCL Namur, Namur, Belgium
| | - Fabrice Duplaquet
- Department of Pneumology, Mont-Godinne University Hospital, CHU UCL Namur, Namur, Belgium
| | - George Dimopoulos
- Department of Critical Care Medicine, Attikon University Hospital, Haidari, Greece
| | - Dirk Vogelaers
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Stijn Blot
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
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6
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Khan SN, Manur R, Brooks JS, Husson MA, Leahy K, Grant M. Invasive pseudomembranous upper airway and tracheal Aspergillosis refractory to systemic antifungal therapy and serial surgical debridement in an Immunocompetent patient. BMC Infect Dis 2020; 20:13. [PMID: 31906888 PMCID: PMC6945574 DOI: 10.1186/s12879-019-4744-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 12/27/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The development of respiratory infections secondary to Aspergillus spp. spores found ubiquitously in the ambient environment is uncommon in immunocompetent patients. Previous reports of invasive upper airway aspergillosis in immunocompetent patients have generally demonstrated the efficacy of treatment regimens utilizing antifungal agents in combination with periodic endoscopic debridement, with symptoms typically resolving within months of initiating therapy. CASE PRESENTATION A 43-year-old previously healthy female presented with worsening respiratory symptoms after failing to respond to long-term antibiotic treatment of bacterial sinusitis. Biopsy of her nasopharynx and trachea revealed extensive fungal infiltration and Aspergillus fumigatus was isolated on tissue culture. Several months of oral voriconazole monotherapy failed to resolve her symptoms and she underwent mechanical debridement for symptom control. Following transient improvement, her symptoms subsequently returned and failed to fully resolve in spite of increased voriconazole dosing and multiple additional tissue debridements over the course of many years. CONCLUSIONS Invasive upper airway aspergillosis is exceedingly uncommon in immunocompetent patients. In the rare instances that such infections do occur, combinatorial voriconazole and endoscopic debridement is typically an efficacious treatment approach. However, some patients may continue to experience refractory symptoms. In such cases, continued aggressive treatment may potentially slow disease progression even if complete disease resolution cannot be achieved.
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Affiliation(s)
- Shihan N Khan
- Department of Internal Medicine, Yale Infectious Diseases, Yale School of Medicine, PO Box 208022, New Haven, CT, 06520, USA
| | - Rashmi Manur
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA, 19107, USA
| | - John S Brooks
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA, 19107, USA
| | - Michael A Husson
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, Philadelphia, PA, 19107, USA
| | - Kevin Leahy
- Department of Otorhinolaryngology: Head and Neck Surgery, Perelman School of Medicine, Philadelphia, PA, 19107, USA
| | - Matthew Grant
- Department of Internal Medicine, Yale Infectious Diseases, Yale School of Medicine, PO Box 208022, New Haven, CT, 06520, USA.
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7
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Shah AS, O'Horo JC, Tang S, Bryson AL, Wengenack NL, Sampathkumar P. Fungal Diagnostic Stewardship in Bronchoscopy Specimens for Immunocompetent Patients in the Intensive Care Unit. Mayo Clin Proc 2019; 94:1781-1785. [PMID: 31400906 DOI: 10.1016/j.mayocp.2019.02.020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 01/18/2019] [Accepted: 02/01/2019] [Indexed: 01/30/2023]
Abstract
OBJECTIVE To evaluate the diagnostic yield of fungal smears and cultures from bronchial lavage and wash specimens obtained from immunocompetent patients in the intensive care unit (ICU) because respiratory tract samples from patients in the ICU often undergo extensive microbiological testing. PATIENTS AND METHODS In total, we enrolled 112 immunocompetent adult patients treated in the medical and surgical ICU between July 1, 2016, and June 30, 2017. We evaluated whether the results of fungal smears and cultures of specimens obtained from bronchoscopy and bronchoalveolar lavage changed patient care. RESULTS In total, 131 bronchoscopic specimens and 31 bronchoalveolar lavage specimens were tested for fungi. Cultures were held for an estimated 4680 culture-days. Two results changed patient therapy. In both cases, other routine tests provided the same information as fungal culture before these results were returned. CONCLUSION In immunocompetent, critically ill patients, fungal culture of respiratory tract specimens does not add diagnostic value. Routine fungal culture of respiratory tract specimens should be discouraged in this population.
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Affiliation(s)
- Aditya S Shah
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN.
| | - John C O'Horo
- Division of Infectious Diseases, Mayo Clinic, Rochester, MN; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | - Schirin Tang
- Department of Anesthesiology, Division of Anesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, Richmond
| | - Alexandra L Bryson
- Department of Laboratory Medicine and Pathology, Division of Clinical Microbiology, Virginia Commonwealth University, Richmond
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8
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Collateral Development of Invasive Pulmonary Aspergillosis (IPA) in Chronic Obstructive Pulmonary Disease (COPD) Patients. Fungal Biol 2019. [DOI: 10.1007/978-3-030-18586-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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9
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Emergence of Invasive Fungal Infection: Diagnosis and Treatment in Humans. Fungal Biol 2019. [DOI: 10.1007/978-3-030-18586-2_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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10
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Magira EE, Jiang Y, Economides M, Tarrand J, Kontoyiannis DP. Mixed mold pulmonary infections in haematological cancer patients in a tertiary care cancer centre. Mycoses 2018; 61:861-867. [PMID: 30015364 DOI: 10.1111/myc.12830] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 07/10/2018] [Accepted: 07/12/2018] [Indexed: 11/29/2022]
Abstract
There is a paucity of data regarding mixed mold pulmonary infections (MMPIs) in patients with haematological malignancies with or without haematopoietic stem cell transplantation (HSCT). We retrospectively studied 27 such patients (2005-2015) and compared them to patients with invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus. Factors associated with the diagnosis of MMPIs were significant corticosteroid use [20 (74%) vs 6 (22%), P < 0.001], sputum as the source specimen [13 (48%) vs 3 (11%), P = 0.003], younger age (median age: 58 vs 66 years, P = 0.006), and male sex [22 (81%) vs 13 (48%), P = 0.01]. Haematological cancers other than acute myeloid leukaemia (AML)/myelodysplastic syndromes (MDS) were less common in MMPIs than in IPA patients [AML/MDS: 6 (22%) vs 14 (52%), P = 0.04]. Only significant corticosteroid use [95% CI (2.7-42.7), P < 0.001], and sputum as the source specimen [95% (1.6-41.6), P = 0.012] were statistically significant as independently associated with increased risk of MMPIs diagnosis in multivariate analysis. Total mortality rate at day 42 postdiagnosis was comparable in both groups.
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Affiliation(s)
- Eleni E Magira
- Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas.,First Department of Critical Care Medicine, Evangelismos Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Ying Jiang
- Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Minas Economides
- Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeffrey Tarrand
- Department of Microbiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Dimitrios P Kontoyiannis
- Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
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11
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Abstract
Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.
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Affiliation(s)
- Shun-Ichi Kimura
- Division of Hematology, Saitama Medical Center, Jichi Medical University
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12
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Shpilberg O, Douer D, Goldschmied-Reouven A, Block C, Ben-Bassat I, Ramot B. Invasive Aspergillosis in Neutropenic Patients with Hematological Disorders. Leuk Lymphoma 2016; 4:257-62. [PMID: 27463045 DOI: 10.3109/10428199109068074] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Between 1983-1988, 72 patients with acute leukemia and 4 with aplastic anemia were treated in the Hematology Unit of The Chaim Sheba Medical Center. Ten patients with acute leukemia developed invasive pulmonary aspergillosis and 2 with aplastic anemia developed invasive aspergillosis of the nose and paranasal sinuses. These infections were diagnosed during a period of profound neutropenia while these patients were receiving broad spectrum antibiotics. The diagnosis of pulmonary aspergillosis was based on positive sputum cultures in 4 cases and on the appearance of typical clinical and radiologic features in six. In 2 culture-positive and in one culture-negative patient, the diagnosis was confirmed at autopsy. Thus, the diagnosis was definitive in 5 patients and probable in the remaining five patients. The 5 patients who achieved remission responded to antifungal treatment and recovered, while of the 5 who eventually died from the fungal infection, 4 did not achieve remission, and one died while in complete remission. In the 2 patients with aplastic anemia, aspergillosis was detected in cultures from necrotic nasal tissue. Both patients remained neutropenic, failed to respond to antifungal treatment and died within a short time after diagnosis. From this experience it appears that invasive aspergillosis in neutropenic patients is potentially curable if treated early by amphotericin B, provided that the neutrophil count recovers.
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Affiliation(s)
- O Shpilberg
- a Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer, and The Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - D Douer
- a Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer, and The Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - A Goldschmied-Reouven
- b Microbiology Laboratory, The Chaim Sheba Medical Center, Tel Hashomer, and The Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - C Block
- b Microbiology Laboratory, The Chaim Sheba Medical Center, Tel Hashomer, and The Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - I Ben-Bassat
- a Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer, and The Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - B Ramot
- a Institute of Hematology, The Chaim Sheba Medical Center, Tel Hashomer, and The Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel
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13
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Rhame FS. Nosocomial Aspergillosis: How Much Protection for Which Patients? Infect Control Hosp Epidemiol 2016. [DOI: 10.2307/30146470] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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14
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Shahi M, Ayatollahi Mousavi SA, Nabili M, Aliyali M, Khodavaisy S, Badali H. Aspergillus colonization in patients with chronic obstructive pulmonary disease. Curr Med Mycol 2015; 1:45-51. [PMID: 28680996 PMCID: PMC5490329 DOI: 10.18869/acadpub.cmm.1.3.45] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background and Purpose: Chronic obstructive pulmonary disease (COPD) has been recognized as a risk factor for invasive aspergillosis. Airway colonization by Aspergillus species is a common feature of chronic pulmonary diseases. Nowadays, the incidence of COPD has increased in critically ill patients. The aim of the present study was to isolate and identify Aspergillus colonies in the respiratory tract of COPD patients. Materials and Methods: This study was performed on 50 COPD patients, who were aged above 18 years, and were in intensive care units of three hospitals in Sari, Iran, for at least six days. All the samples obtained from sputum, bronchoalveolar lavage, and tracheal aspirates were cultured for fungi each week. According to the conventional techniques, Aspergillus isolates were initially based on growth and standard morphological characteristics. To confirm the identification of grown Aspergillus, the partial beta-tubulin gene was sequenced using specific primers. Results: A total of 50 patients, who met our inclusion criteria, were enrolled in the study during 2012-14. The results showed that 27 (54%) and 23 (46%) of the participants were male and female, respectively. The majority of the patients developed dyspnea followed by hemoptysis, chest pain, and high fever. Corticosteroids and broad-spectrum antibacterial agents were administered to 75% and 80% of the patients, respectively. Based on the conventional and molecular approaches, A. fumigatus (seven cases; 43.7%), A. flavus (five cases; 31.2%), A. niger (one case; 6.2%), A. terreus (one case; 6.2%), A. orezea (one case; 6.2%), and A. tubingensis (one case; 6.2%) were recovered. Conclusion: Recovery of Aspergillus species from the respiratory tract of COPD patients with pneumonia indicates two possibilities: either colonization or invasive aspergillosis.
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Affiliation(s)
- M Shahi
- Department of Medical Mycology and Parasitology, Faculty of Medicine, Tropical and Infectious Diseases Center, Kerman University of Medical Sciences, Kerman, Iran
| | - S A Ayatollahi Mousavi
- Department of Medical Mycology and Parasitology, Faculty of Medicine, Tropical and Infectious Diseases Center, Kerman University of Medical Sciences, Kerman, Iran
| | - M Nabili
- Students Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
| | - M Aliyali
- Pulmonary and Critical Care Division, Mazandaran University of Medical Sciences, Sari, Iran
| | - S Khodavaisy
- Department of Medical Parasitology and Mycology, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Medical Parasitology and Mycology, Tehran University of Medical Sciences, Tehran, Iran
| | - H Badali
- Invasive Fungi Research Center (IFRC), Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. THE LANCET. INFECTIOUS DISEASES 2015; 15:461-74. [PMID: 25771341 DOI: 10.1016/s1473-3099(15)70006-x] [Citation(s) in RCA: 135] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Invasive fungal diseases are an important cause of morbidity and mortality in a wide range of patients, and early diagnosis and management are a challenge. We therefore did a review of the scientific literature to generate a series of key recommendations for the appropriate use of microbiological, histological, and radiological diagnostic methods for diagnosis of invasive fungal diseases. The recommendations emphasise the role of microscopy in rapid diagnosis and identification of clinically significant isolates to species level, and the need for susceptibility testing of all Aspergillus spp, if treatment is to be given. In this Review, we provide information to improve understanding of the importance of antigen detection for cryptococcal disease and invasive aspergillosis, the use of molecular (PCR) diagnostics for aspergillosis, and the crucial role of antibody detection for chronic and allergic aspergillosis. Furthermore, we consider the importance of histopathology reporting with a panel of special stains, and emphasise the need for urgent (<48 hours) and optimised imaging for patients with suspected invasive fungal infection. All 43 recommendations are auditable and should be used to ensure best diagnostic practice and improved outcomes for patients.
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Naaraayan A, Kavian R, Lederman J, Basak P, Jesmajian S. Invasive pulmonary aspergillosis - case report and review of literature. J Community Hosp Intern Med Perspect 2015; 5:26322. [PMID: 25656673 PMCID: PMC4318821 DOI: 10.3402/jchimp.v5.26322] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 12/05/2014] [Accepted: 12/12/2014] [Indexed: 11/14/2022] Open
Abstract
Invasive pulmonary aspergillosis (IPA) is a severe fungal infection with a high mortality rate. The incidence of IPA is on the rise due to an increase in the number of patients undergoing transplants and receiving chemotherapy and immunosuppressive therapy. Diagnosis is challenging due to the non-specific nature of symptoms. Voriconazole is the mainstay of therapy. We present a case of an elderly woman presenting with acute bronchitis and asthma exacerbation, who succumbed to overwhelming IPA. It is uncommon for IPA to develop in patients on short-term steroid therapy for asthma exacerbation. The possibility of aspergillosis in immunocompetent patients should be considered in those on systemic steroids and deteriorating pulmonary functions.
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Affiliation(s)
- Ashutossh Naaraayan
- Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA;
| | - Ronak Kavian
- Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA
| | - Jeffrey Lederman
- Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA
| | - Prasanta Basak
- Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA
| | - Stephen Jesmajian
- Department of Internal Medicine, Montefiore New Rochelle Hospital, Albert Einstein College of Medicine, New Rochelle, NY, USA
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Hahn T, Cummings KM, Michalek AM, Lipman BJ, Segal BH, McCarthy PL. Efficacy of High-Efficiency Particulate Air Filtration in Preventing Aspergillosis in Immunocompromised Patients With Hematologic Malignancies. Infect Control Hosp Epidemiol 2015; 23:525-31. [PMID: 12269451 DOI: 10.1086/502101] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Objectives:To describe and investigate the cause of an outbreak of 10 cases of nosocomial invasive infection withAspergillus flavusin a hematologic oncology patient care unit.Design:A retrospective cohort study.Setting:The hematologic oncology unit of a comprehensive cancer center.Patients:Ninety-one patients admitted to the hematologic oncology service between January 1 and December 31,1992, for 4 or more consecutive days were included in the study.Results:Ten (18%) of 55 patients admitted from July to December 1992 were diagnosed as having invasive aspergillosis compared with 0 (0%) of 36 patients admitted from January to June 1992 to the same patient care units. Patient characteristics, mortality rate, autopsy rate, and admitting location did not change significantly during the course of the year to result in a sudden increase in the number of aspergillosis cases. The source of the outbreak was the high counts ofAspergillusconidia determined from air sampling in the non–bone marrow transplant wing during the outbreak. After high-efficiency particulate air (HEPA) filters were installed as an infection control measure, there were only two additional cases of nosocomial aspergillosis in the 2 years following the outbreak.Conclusions:This outbreak occurred among hematologic oncology patients with prolonged granulocytopenia housed in an environment with neither HEPA filters nor laminar air flow units. Our data demonstrate that in the setting of an outbreak of aspergillosis, HEPA filters are protective for highly immunocompromised patients with hematologic malignancies and are effective at controlling outbreaks due to air contamination withAspergillusconidia.
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Affiliation(s)
- Theresa Hahn
- Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
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Shashidhar N, Tripathy SK, Balasubramanian S, Dhanakodi N, Venkataramaiah S. Aspergillus spondylodiscitis in an immunocompetent patient following spinal anesthesia. Orthop Surg 2014; 6:72-77. [PMID: 24590999 PMCID: PMC6583265 DOI: 10.1111/os.12091] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2013] [Accepted: 11/05/2013] [Indexed: 02/05/2023] Open
Affiliation(s)
- Nandeesh Shashidhar
- Department of OrthopaedicsMeenakshi Mission Hospital and Research CenterMaduraiIndia
| | - Sujit Kumar Tripathy
- Department of OrthopaedicsMeenakshi Mission Hospital and Research CenterMaduraiIndia
| | | | - Naresh Dhanakodi
- Department of OrthopaedicsMeenakshi Mission Hospital and Research CenterMaduraiIndia
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21
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Wang S, Zhang WM, Reineks E. Breath Tests for Detection of Helicobacter pylori and Aspergillus fumigatus. ADVANCED TECHNIQUES IN DIAGNOSTIC MICROBIOLOGY 2013:13-30. [DOI: 10.1007/978-1-4614-3970-7_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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22
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Neofytos D, Lu K, Hatfield-Seung A, Blackford A, Marr KA, Treadway S, Ostrander D, Nussenblatt V, Karp J. Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy. Diagn Microbiol Infect Dis 2012; 75:144-9. [PMID: 23142166 DOI: 10.1016/j.diagmicrobio.2012.10.001] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Revised: 09/27/2012] [Accepted: 10/04/2012] [Indexed: 12/15/2022]
Abstract
This is a retrospective, single-center study of adult patients with newly diagnosed acute myelogenous leukemia (AML), who received intensive induction timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%) patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%) probable, and 103 (95.4%) were possible, using current definitions. Overall, 6-month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and without an IFI, respectively. Older age (≥50 years; hazard ratio [HR]: 2.5, P < 0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We report relatively low rates of IC despite lack of routine primary antifungal prophylaxis, albeit associated with poor long-term survival. High rates of IMI, the vast majority with a possible diagnosis, were observed. Host-related variables (demographics and baseline organ dysfunction) were identified as the most significant risk factors for IFI and mortality predictors in this series.
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Affiliation(s)
- Dionissios Neofytos
- Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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23
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Aigner M, Mutschlechner W, Lass-Flörl C. [Diagnosis of Aspergillus infections in hematology and oncology]. Mycoses 2012; 55 Suppl 2:3-9. [PMID: 22519626 DOI: 10.1111/j.1439-0507.2012.02177.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Maria Aigner
- Department für Hygiene, Mikrobiologie und Sozialmedizin, Medizinische Universität Innsbruck, Innsbruck, Österreich
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24
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Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev 2011; 20:156-174. [PMID: 21881144 PMCID: PMC9584108 DOI: 10.1183/09059180.00001011] [Citation(s) in RCA: 456] [Impact Index Per Article: 32.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2011] [Accepted: 03/10/2011] [Indexed: 11/05/2022] Open
Abstract
Aspergillus is a mould which may lead to a variety of infectious, allergic diseases depending on the host's immune status or pulmonary structure. Invasive pulmonary aspergillosis occurs primarily in patients with severe immunodeficiency. The significance of this infection has dramatically increased with growing numbers of patients with impaired immune state associated with the management of malignancy, organ transplantation, autoimmune and inflammatory conditions; critically ill patients and those with chronic obstructive pulmonary disease appear to be at an increased risk. The introduction of new noninvasive tests, combined with more effective and better-tolerated antifungal agents, has resulted in lower mortality rates associated with this infection. Chronic necrotising aspergillosis is a locally invasive disease described in patients with chronic lung disease or mild immunodeficiency. Aspergilloma is usually found in patients with previously formed cavities in the lung, whereas allergic bronchopulmonary aspergillosis, a hypersensitivity reaction to Aspergillus antigens, is generally seen in patients with atopy, asthma or cystic fibrosis. This review provides an update on the evolving epidemiology and risk factors of the major manifestations of Aspergillus lung disease and the clinical manifestations that should prompt the clinician to consider these conditions. Current approaches for the diagnosis and management of these syndromes are discussed.
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Affiliation(s)
- M Kousha
- Division of Pulmonary Critical Care and Sleep Medicine, Wayne State University School of Medicine, Harper University Hospital, 3990 John R, Detroit, MI 48201, USA.
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25
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Hsu JL, Ruoss SJ, Bower ND, Lin M, Holodniy M, Stevens DA. Diagnosing invasive fungal disease in critically ill patients. Crit Rev Microbiol 2011; 37:277-312. [PMID: 21749278 DOI: 10.3109/1040841x.2011.581223] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Fungal infections are increasing, with a changing landscape of pathogens and emergence of new groups at risk for invasive disease. We review current diagnostic techniques, focusing on studies in critically ill patients. Microbiological cultures, the current "gold standard", demonstrate poor sensitivity, thus diagnosis of invasive disease in the critically ill is difficult. This diagnostic dilemma results in under- or over-treatment of patients, potentially contributing to poor outcomes and antifungal resistance. While other current diagnostic tests perform moderately well, many lack timeliness, efficacy, and are negatively affected by treatments common to critically ill patients. New nucleic acid-based research is promising.
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Affiliation(s)
- Joe L Hsu
- Division of Pulmonary and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, USA
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26
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Luong ML, Clancy CJ, Vadnerkar A, Kwak EJ, Silveira FP, Wissel MC, Grantham KJ, Shields RK, Crespo M, Pilewski J, Toyoda Y, Kleiboeker SB, Pakstis D, Reddy SK, Walsh TJ, Nguyen MH. Comparison of an Aspergillus Real-time Polymerase Chain Reaction Assay With Galactomannan Testing of Bronchoalvelolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis in Lung Transplant Recipients. Clin Infect Dis 2011; 52:1218-26. [DOI: 10.1093/cid/cir185] [Citation(s) in RCA: 104] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Lee S, Yun NR, Kim KH, Jeon JH, Kim EC, Chung DH, Park WB, Oh MD. Discrepancy between histology and culture in filamentous fungal infections. Med Mycol 2010; 48:886-8. [DOI: 10.3109/13693780903512835] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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30
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Chambers ST, Syhre M, Murdoch DR, McCartin F, Epton MJ. Detection of 2-pentylfuran in the breath of patients with Aspergillus fumigatus. Med Mycol 2010; 47:468-76. [PMID: 19301177 DOI: 10.1080/13693780802475212] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Aspergillus fumigatus produces 2-pentylfuran (2-PF) when cultured on blood agar, nutrient agar and other media. As 2-PF is not known to be produced by mammalian metabolism we hypothesized that it is detectable in breath of patients colonized or infected with A. fumigatus. Breath was tested for 2-PF from normal subjects, those undergoing chemotherapy, and adults at risk of colonization or infection with A. fumigatus because of bronchiectasis, cystic fibrosis, or immune suppression. Breath samples were collected in five L tedlar bags and analyzed by Gas Chromatography/Mass Spectroscopy (GC/MS) in MS-MS mode. 2-PF was not detected in breath 14 healthy controls, in one of 10 neutropenic subjects and 16 of 32 patients with lung disease. The sensitivity and specificity of the 2-PF breath tests when compared with recurrent isolation of aspergillus from sputum or from bronchoalveolar lavage over two months was 77% and 78% respectively. As 2-PF is not normally found in human breath its presence may reflect the active metabolism of A. fumigatus in the airways and form the basis of a new diagnostic breath test for Aspergillus infection.
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Affiliation(s)
- Stephen T Chambers
- Department of Pathology, University of Otago Christchurch, Christchurch, New Zealand.
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31
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Kimura SI, Odawara J, Aoki T, Yamakura M, Takeuchi M, Matsue K. Detection of sputum Aspergillus galactomannan for diagnosis of invasive pulmonary aspergillosis in haematological patients. Int J Hematol 2009; 90:463-470. [PMID: 19838867 DOI: 10.1007/s12185-009-0429-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2009] [Revised: 09/09/2009] [Accepted: 09/10/2009] [Indexed: 10/20/2022]
Abstract
We investigated the diagnostic utility of Aspergillus galactomannan (GM) in sputum for diagnosis of invasive pulmonary aspergillosis (IPA) in haematologic patients and compared the results with those of bronchial lavage fluid (BLF) and serum. Patients were classified into 4 groups using modified European Organization for Research and Treatment of Cancer criteria: group A, proven IPA; group B, probable IPA; group C, possible IPA; group D, others. Groups A and B were considered the IPA group (n = 6); group D was considered non-IPA group (n = 37); group C (n = 13) was equivocal for IPA. As a true negative control, sputa from patients with community-acquired pneumonia (CAP) without risk factors (group E, n = 22) were used. From the receiver-operating characteristic curves, the cut-off levels were determined as 1.2 in sputum, 0.5-1.3 in BLF and 0.5 in serum. The sensitivity and specificity of sputum, BLF and serum GM were 100 and 62.2%, 66.7 and 100%, and 83.3 and 81.1%, respectively. Twenty-two patients with CAP (group E) showed median GM levels in the sputa of 0.1 (range 0.0-1.0). Sputum GM is a useful non-invasive test for screening of IPA in haematological patients, and may also be useful for assessment of the risk of developing IPA.
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Affiliation(s)
- Shun-Ichi Kimura
- Division of Hematology/Oncology, Department of Medicine, Kameda General Hospital, 929 Higashi-chou, Kamogawa, Chiba, 296-8602, Japan
| | - Jun Odawara
- Division of Hematology/Oncology, Department of Medicine, Kameda General Hospital, 929 Higashi-chou, Kamogawa, Chiba, 296-8602, Japan
| | - Takatoshi Aoki
- Division of Hematology/Oncology, Department of Medicine, Kameda General Hospital, 929 Higashi-chou, Kamogawa, Chiba, 296-8602, Japan
| | - Masayuki Yamakura
- Division of Hematology/Oncology, Department of Medicine, Kameda General Hospital, 929 Higashi-chou, Kamogawa, Chiba, 296-8602, Japan
| | - Masami Takeuchi
- Division of Hematology/Oncology, Department of Medicine, Kameda General Hospital, 929 Higashi-chou, Kamogawa, Chiba, 296-8602, Japan
| | - Kosei Matsue
- Division of Hematology/Oncology, Department of Medicine, Kameda General Hospital, 929 Higashi-chou, Kamogawa, Chiba, 296-8602, Japan.
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Ader F, Bienvenu AL, Rammaert B, Nseir S. Management of invasive aspergillosis in patients with COPD: rational use of voriconazole. Int J Chron Obstruct Pulmon Dis 2009; 4:279-87. [PMID: 19684861 PMCID: PMC2722867 DOI: 10.2147/copd.s4229] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Invasive pulmonary aspergillosis (IPA) is an important cause of mortality in patients with hematologic malignancies. The reported incidence of IPA in the context of chronic obstructive pulmonary disease (COPD) seems to increase. Approximately 1%-2% of overall fatal cases of IPA occur in COPD patients. The combination of factors such as lung immune imbalance, long-term corticosteroid use, increasing rate of bacterial exacerbations over time, and malnutrition are responsible for the emergence of IPA in these patients. The diagnosis of IPA is difficult to establish, which explains the delay in implementing accurate antifungal therapy and the high mortality rate. Persistent pneumonia nonresponsive to appropriate antibiotic treatment raises the concern of an invasive fungal infection. Definite diagnosis is obtained from tissue biopsy evidencing Aspergillus spp. on microscopic examination or in culture. Culture and microscopy of respiratory tract samples have a sensitivity and specificity of around 50%. Other diagnostic tools can be useful in documenting IPA: computed tomography (CT) scan, nonculture-based tests in serum and/or in bronchoalveolar lavage such as antibody/antigen tests for Aspergillus spp. More recent tools such as polymerase chain reaction or [1-->3]-beta-D-glucan have predictive values that need to be further investigated in COPD patients. Antifungal monotherapy using azole voriconazole is recommended as a first-line treatment of IPA. This review assesses the use of voriconazole in COPD patients.
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Affiliation(s)
- Florence Ader
- Service des Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, Hôpital de La Croix-Rousse, Lyon, France.
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Samarakoon P, Soubani AO. Invasive pulmonary aspergillosis in patients with COPD: a report of five cases and systematic review of the literature. Chron Respir Dis 2008; 5:19-27. [PMID: 18303098 DOI: 10.1177/1479972307085637] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND There are increasing reports describing invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD) without the classic risk factors for this severe infection. The available literature on this association is based on case reports or small case series. The aim of this review is to systematically review these cases and describe the clinical features, diagnostic studies and outcome. METHODS We identified all the cases of IPA and COPD reported in the literature and had enough clinical information. We also included five cases of IPA in patients with COPD identified by the authors. These cases were systematically reviewed for clinical features, diagnostic studies and outcome. RESULTS There were 60 cases of IPA in patients with COPD identified from the literature. The total number of cases reviewed was 65. The mean age was 65.1 years, the mean FEV1 was 39% of predicted (n = 17, range 19-56%). Forty-nine patients were documented to be on systemic corticosteroids. The mean dose was 24 mg/day (range 15-65 mg/day). Five patients were only on inhaled corticosteroids and in 11 patients there was no documentation of corticosteroid therapy. The clinical and radiological findings were nonspecific. Thirteen patients had documented evidence of disseminated IPA. Sputum examination was positive for Aspergillus in 76% and bronchoscopy with bronchoalveolar lavage that was positive in 70%. The diagnosis of IPA was definite in 43 patients and probable in 22 patients. Forty-six patients were treated with anti-fungal therapy. Fifty-nine patients (91%) died with IPA. CONCLUSION Invasive pulmonary aspergillosis is an emerging serious infection in patients with COPD. The majority of these patients have advanced COPD and/or on corticosteroid therapy. The clinical and radiological presentation is nonspecific. High index of suspicion is necessary for the timely treatment of these patients.
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Affiliation(s)
- P Samarakoon
- Division of Pulmonary, Allergy, Critical Care and Sleep, Wayne State University School of Medicine, Harper University Hospital, Detroit, MI 48201, USA
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Scott CJ, Lambert JS, Taylor CB, Poulton MB. Invasive Aspergillus fumigatus associated with liver and bone involvement in a patient with AIDS. Int J Infect Dis 2007; 11:550-3. [PMID: 17383211 DOI: 10.1016/j.ijid.2006.12.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2006] [Accepted: 12/12/2006] [Indexed: 11/30/2022] Open
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Diagnostic yield of bronchoscopy with bronchoalveolar lavage in febrile patients with hematologic malignancies and pulmonary infiltrates. Ann Hematol 2007; 87:291-7. [PMID: 17932672 DOI: 10.1007/s00277-007-0391-6] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2007] [Accepted: 09/13/2007] [Indexed: 10/22/2022]
Abstract
Infectious complications are a major cause of morbidity and mortality in immunosuppressed patients. Febrile patients with hematologic malignancies and pulmonary infiltrates have high mortality rates, especially if mechanical ventilation is required. The diagnostic value of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) in these patients is controversial. We retrospectively analyzed the microbiological results of BAL samples obtained during 249 FOB examinations from 199 febrile patients with hematologic malignancies and pulmonary infiltrates (underlying diseases: acute leukemia 103 patients, lymphoma 84 patients, other malignancies 12 patients). Two hundred forty-six examinations could be evaluated. Seventy-three out of 246 BAL samples were sterile; 55 samples showed microbiological findings classified as contamination or colonization. One hundred eighteen samples showed positive microbiological results of bacteria and/or fungi classified as causative pathogens. Thereof, in 70 samples, only bacterial pathogens were detectable (Gram-positive, 35; Gram-negative, 30; mixed Gram-positive and Gram-negative, 5). Thirteen samples showed both fungi and bacterial pathogens. In 33 samples, only fungi were detectable, thereof, in 15 samples Aspergillus species, in 16 samples Candida species, and in 2 both. In two samples, a viral pathogen could be detected. Three nonlethal complications (bleeding, arrhythmia) occurred that required early termination of FOB. In 94 (38.2%) patient episodes, antibiotic treatment was modified as a result of microbiological findings in BAL samples. Our results show that FOB with BAL is a valuable diagnostic tool with low complication rates in high-risk febrile patients with hematologic malignancies and pulmonary infiltrates, contributing crucial results for the individual case, and also improving epidemiologic knowledge.
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Abbes K, Khabir A, Chtourou I, Fakhfakh IS, Gouiaa N, Bahri I, Dhouib H, Ghorbel A, Boudawara TS. Lésion inhabituelle de la thyroïde. J Mycol Med 2007. [DOI: 10.1016/j.mycmed.2007.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Nguyen MH, Jaber R, Leather HL, Wingard JR, Staley B, Wheat LJ, Cline CL, Baz M, Rand KH, Clancy CJ. Use of bronchoalveolar lavage to detect galactomannan for diagnosis of pulmonary aspergillosis among nonimmunocompromised hosts. J Clin Microbiol 2007; 45:2787-92. [PMID: 17596367 PMCID: PMC2045248 DOI: 10.1128/jcm.00716-07] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Pulmonary aspergillosis in nonimmunocompromised hosts, although rare, is being increasingly recognized. The diagnosis of pulmonary aspergillosis is difficult, since the recovery of Aspergillus from respiratory samples cannot differentiate colonization from invasion. We assessed the role of bronchoalveolar lavage (BAL) in detecting galactomannan (GM) for diagnosing pulmonary aspergillosis in 73 nonimmunocompromised patients with pulmonary infiltrates for whom the test was ordered. Six patients had pulmonary aspergillosis, two each with acute invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and aspergilloma. All six patients had a BAL GM level of >/=1.18. The sensitivity, specificity, and negative predictive value (NPV) for a BAL GM level of >/=1.0 were 100%, 88.1%, and 100%, respectively. Notably, the positive predictive value (PPV) was only 42.9%, likely reflecting the low prevalence of pulmonary aspergillosis among nonimmunosuppressed patients. The combination of BAL microscopy and culture had a sensitivity and NPV similar to those of BAL GM detection but a higher specificity and PPV (92.5% and 54.6%, respectively). Moreover, a BAL GM test did not identify any cases that were not diagnosed by conventional methods like microscopy and culture. In conclusion, there was no conclusive benefit of determining BAL GM levels in the diagnosis of pulmonary aspergillosis among nonimmunocompromised hosts. Given the likelihood of false-positive results, a BAL GM test should not be ordered routinely in this population.
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Affiliation(s)
- M Hong Nguyen
- Department of Medicine, University of Florida College of Medicine, Gainesville, Florida 32610, USA
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Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol 2007; 45:321-46. [PMID: 17510856 DOI: 10.1080/13693780701218689] [Citation(s) in RCA: 505] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
Invasive fungal infections are increasingly common in the nosocomial setting. Furthermore, because risk factors for these infections continue to increase in frequency, it is likely that nosocomial fungal infections will continue to increase in frequency in the coming decades. The predominant nosocomial fungal pathogens include Candida spp., Aspergillus spp., Mucorales, Fusarium spp., and other molds, including Scedosporium spp. These infections are difficult to diagnose and cause high morbidity and mortality despite antifungal therapy. Early initiation of effective antifungal therapy and reversal of underlying host defects remain the cornerstones of treatment for nosocomial fungal infections. In recent years, new antifungal agents have become available, resulting in a change in standard of care for many of these infections. Nevertheless, the mortality of nosocomial fungal infections remains high, and new therapeutic and preventative strategies are needed.
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Affiliation(s)
- Joshua Perlroth
- Division of Infectious Diseases, Harbor-University of California Los Angeles (UCLA) Medical Center, California 90502, USA
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41
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Muñoz P, Guinea J, Bouza E. Update on invasive aspergillosis: clinical and diagnostic aspects. Clin Microbiol Infect 2006. [DOI: 10.1111/j.1469-0691.2006.01603.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Vandewoude KH, Blot SI, Depuydt P, Benoit D, Temmerman W, Colardyn F, Vogelaers D. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Crit Care 2006; 10:R31. [PMID: 16507158 PMCID: PMC1550813 DOI: 10.1186/cc4823] [Citation(s) in RCA: 189] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2005] [Revised: 12/31/2005] [Accepted: 01/20/2006] [Indexed: 11/17/2022] Open
Abstract
Introduction The diagnosis of invasive pulmonary aspergillosis, according to the criteria as defined by the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG), is difficult to establish in critically ill patients. The aim of this study is to address the clinical significance of isolation of Aspergillus spp. from lower respiratory tract samples in critically ill patients on the basis of medical and radiological files using an adapted diagnostic algorithm to discriminate proven and probable invasive pulmonary aspergillosis from Aspergillus colonisation. Methods Using a historical cohort (January 1997 to December 2003), all critically ill patients with respiratory tract samples positive for Aspergillus were studied. In comparison to the EORTC/MSG criteria, a different appreciation was given to radiological features and microbiological data, including semiquantitative cultures and direct microscopic examination of broncho-alveolar lavage samples. Results Over a 7 year period, 172 patients were identified with a positive culture. Of these, 83 patients were classified as invasive aspergillosis. In 50 of these patients (60%), no high risk predisposing conditions (neutropenia, hematologic cancer and stem cell or bone marrow transplantation) were found. Typical radiological imaging (halo and air-crescent sign) occurred in only 5% of patients. In 26 patients, histological examination either by ante-mortem lung biopsy (n = 10) or necropsy (n = 16) was performed, allowing a rough estimation of the predictive value of the diagnostic algorithm. In all patients with histology, all cases of clinical probable pulmonary aspergillosis were confirmed (n = 17). Conversely, all cases classified as colonisation had negative histology (n = 9). Conclusion A respiratory tract sample positive for Aspergillus spp. in the critically ill should always prompt further diagnostic assessment, even in the absence of the typical hematological and immunological host risk factors. In a minority of patients, the value of the clinical diagnostic algorithm was confirmed by histological findings, supporting its predictive value. The proposed diagnostic algorithm needs prospective validation.
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Affiliation(s)
- Koenraad H Vandewoude
- Department of Intensive Care, Ghent University Hospital, Ghent, Belgium
- Hogeschool Gent, Health Care Department "Vesalius", Ghent, Belgium
| | - Stijn I Blot
- Department of Intensive Care, Ghent University Hospital, Ghent, Belgium
- Hogeschool Gent, Health Care Department "Vesalius", Ghent, Belgium
| | - Pieter Depuydt
- Department of Intensive Care, Ghent University Hospital, Ghent, Belgium
| | - Dominique Benoit
- Department of Intensive Care, Ghent University Hospital, Ghent, Belgium
| | - Werner Temmerman
- Department of Intensive Care, Ghent University Hospital, Ghent, Belgium
| | - Francis Colardyn
- Department of Intensive Care, Ghent University Hospital, Ghent, Belgium
| | - Dirk Vogelaers
- Department for Infectious Diseases, Ghent University Hospital, Ghent Belgium
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Hofmeister CC, Czerlanis C, Forsythe S, Stiff PJ. Retrospective utility of bronchoscopy after hematopoietic stem cell transplant. Bone Marrow Transplant 2006; 38:693-8. [PMID: 16980989 DOI: 10.1038/sj.bmt.1705505] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is thought to be the procedure of choice to evaluate pulmonary infiltrates in hematopoietic stem cell transplant (HSCT) recipients. We retrospectively reviewed 91 bronchoscopies performed on 190 in-patient HSCT recipients admitted or treated for pneumonia from January 1994 to December 2004. These yielded a diagnosis 49% of the time with an overall survival of 35 days post-bronchoscopy. We were unable to detect any survival benefit from an addition to the treatment regimen after a positive result from analysis of the BAL fluid or transbronchial biopsy. The most common bacteria isolated was Pseudomonas that was often resistant to the patient's current antibiotics, suggesting that in lieu of this diagnostic procedure, changes to better cover resistant Gram-negative bacteria are reasonable. Although transbronchial biopsies provided an additional diagnosis in one out of 21 biopsies performed, six of the seven complications in our series were directly related to the transbronchial biopsy. With approximately a 50% yield from a bronchoscopy, additional treatment given after only 20% of all bronchoscopies, and no detectable survival benefit with a bronchoscopy that yielded a diagnosis, the utility of a bronchoscopy in this patient population is questioned by these data.
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Affiliation(s)
- C C Hofmeister
- Division of Hematology, Department of Medicine, The Ohio State University, Arthur G James Cancer Hospital, B321 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA.
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Alexander BD, Pfaller MA. Contemporary Tools for the Diagnosis and Management of Invasive Mycoses. Clin Infect Dis 2006. [DOI: 10.1086/504491] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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Segal BH, Walsh TJ. Current Approaches to Diagnosis and Treatment of Invasive Aspergillosis. Am J Respir Crit Care Med 2006; 173:707-17. [PMID: 16387806 DOI: 10.1164/rccm.200505-727so] [Citation(s) in RCA: 215] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Filamentous fungi (moulds) are ubiquitous soil inhabitants whose conidia are inhaled into the respiratory tract, where they may cause life-threatening infections. Among these infections is invasive aspergillosis, which is a major cause of morbidity and mortality in the severely immunocompromised. Risk factors for invasive aspergillosis include prolonged and severe neutropenia, hematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease. Invasive aspergillosis most commonly involves the sinopulmonary tract reflecting inhalation as the principal portal of entry. Chest computed tomography scans and new non-culture-based assays such as antigen detection and polymerase chain reaction may facilitate the early diagnosis of invasive aspergillosis, but have limitations. Reflecting an important unmet need, there has been a significant expansion in the antifungal armamentarium. The second-generation triazole, voriconazole, was superior to conventional amphotericin B as primary therapy for invasive aspergillosis, and is the new standard of care for this infection. There is significant interest in combination antifungal therapy pairing an echinocandin with either an azole or amphotericin B formulation as therapy for invasive aspergillosis. In addition, there has been an increased understanding of the immunology of Aspergillus infection, paving the way to novel immune augmentation strategies in animal models that merit evaluation in phase I clinic trials.
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Affiliation(s)
- Brahm H Segal
- Department of Medicine, SUNY at Buffalo, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
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Ribeiro P, Costa F, Monteiro A, Caldas J, Silva M, Ferreira G, Veiga J, Sousa MO, Viegas MP, Santos E, Gonçalves AJ, Sousa AB. Polymerase chain reaction screening for fungemia and/or invasive fungal infections in patients with hematologic malignancies. Support Care Cancer 2006; 14:469-74. [PMID: 16435098 DOI: 10.1007/s00520-005-0903-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2005] [Accepted: 10/20/2005] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Invasive fungal infections (IFIs) are a life-threatening complication in patients with hematologic malignancies, mainly in acute leukemia patients, following chemotherapy. IFI incidence is increasing, and associated mortality remains high due to unreliable diagnosis. Antifungal drugs are often limited by inadequate antimicrobial spectrum and side effects. Thus, the detection of circulating fungal DNA has been advocated as a rapid, more sensitive diagnostic tool. PATIENTS AND METHODS Between June 01 and January 03, weekly blood samples (1,311) were screened from 193 patients undergoing intensive myelosuppressive or immunosuppressive therapy. IFI cases were classified according to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Fungal DNA was extracted from whole blood and amplified using polymerase chain reaction (PCR) published primers that bind to the conserved regions of the fungal 18S rRNA gene sequence. In our study, two or more consecutive positive samples were always associated with fungal disease. RESULTS PCR screening predicted the development of IFI to be 17 days (median). This test had a specificity of 91.1% and a sensitivity of 75%. IFI incidence was 7.8%. DISCUSSION Therefore, our results confirm the potential usefulness of PCR serial screening and the clinical applicability in everyday routine. PCR screening offers a noninvasive repeatable aid to the diagnosis of IFI.
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Affiliation(s)
- Patrícia Ribeiro
- Department of Hematology, Hospital dos Capuchos, Lisbon, Portugal.
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Peikert T, Rana S, Edell ES. Safety, diagnostic yield, and therapeutic implications of flexible bronchoscopy in patients with febrile neutropenia and pulmonary infiltrates. Mayo Clin Proc 2005; 80:1414-1420. [PMID: 16295020 DOI: 10.4065/80.11.1414] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To evaluate the safety, diagnostic yield, and therapeutic implications of flexible bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy in patients with febrile neutropenia and pulmonary infiltrates. PATIENTS AND METHODS We retrospectively reviewed the medical records of all patients with neutropenic fever and pulmonary infiltrates evaluated by flexible bronchoscopy and BAL between January and December 2002 at the Mayo Clinic in Rochester, Minn. Appropriate demographic, clinical, microbiological, and histological data and procedure-related complications were summarized. Therapeutic decisions implemented based on Information obtained by bronchoscopy, and 28-day mortality were determined. RESULTS Thirty-five patients with febrile neutropenia and associated pulmonary infiltrates were identified. Flexible bronchoscopy, including 35 BALs and 9 transbronchial biopsies, was performed safely (3 complications). The diagnostic yield of BAL was 49%. Sputum analysis was underused (only 34%) but complementary to BAL. The combined diagnostic yield of BAL and sputum analysis was 63%. Transbronchial biopsy provided additional information to BAL and sputum analysis In only 1 patient and did not substantially increase the combined diagnostic yield. The most common diagnoses identified were fungal pneumonias (15/35 [43%]) and diffuse alveolar hemorrhage (5/35 [14%]). Bronchoscopic findings resulted in management changes in 51% of patients. The 28-day mortality rate was 26% and was highest in patients who required mechanical ventilatory assistance before bronchoscopy. CONCLUSION The favorable safety record, good diagnostic yield, and frequent therapeutic implications support the routine use of BAL for the evaluation of pulmonary inflitrates in neutropenic patients. Bronchoalveolar lavage should be combined with the analysis of several sputum specimens. Transbronchial biopsy did only change the management of 1 patient.
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Affiliation(s)
- Tobias Peikert
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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Hope WW, Walsh TJ, Denning DW. The invasive and saprophytic syndromes due to Aspergillus spp. Med Mycol 2005; 43 Suppl 1:S207-38. [PMID: 16110814 DOI: 10.1080/13693780400025179] [Citation(s) in RCA: 150] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
Aspergillus spp. produce a wide range of invasive and sapropytic syndromes which may involve any tissue. Within a given tissue or organ the pathology and pathogenesis varies enormously, ranging from angioinvasive disease to noninvasive saprophytic disease. The individual invasive and saprophytic syndromes in which a causative role can be attributed to Aspergillus spp. are detailed specifically with reference to the underlying pathology and pathogenesis, the clinical setting and features, and the manner in which a diagnosis can be established.
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Affiliation(s)
- W W Hope
- University of Manchester and Wythenshawe Hospital, Manchester UK
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Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. THE LANCET. INFECTIOUS DISEASES 2005; 5:609-22. [PMID: 16183515 DOI: 10.1016/s1473-3099(05)70238-3] [Citation(s) in RCA: 355] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Invasive aspergillosis occurs in a wide range of clinical scenarios, is protean in its manifestations, and is still associated with an unacceptably high mortality rate. Early diagnosis is critical to a favourable outcome, but is difficult to achieve with current methods. Deep tissue diagnostic specimens are often difficult to obtain from critically ill patients. Newer antifungal agents exhibit differential mould activity, thus increasing the importance of establishing a specific diagnosis of invasive aspergillosis. For these reasons, a range of alternate diagnostic strategies have been investigated. Most investigative efforts have focused on molecular and serological diagnostic techniques. The detection of metabolites produced by Aspergillus spp and a range of aspergillus-specific antibodies represent additional, but relatively underused, diagnostic avenues. The detection of galactomannan has been incorporated into diagnostic criteria for invasive aspergillosis, reflecting an increased understanding of the performance, utility, and limitations of this technique. Measurement of (1,3)-beta-D glucan in blood may be useful as a preliminary screening tool for invasive aspergillosis, despite the fact that this antigen can be detected in a number of other fungi. There have been extensive efforts directed toward the detection of Aspergillus spp DNA, but a lack of technical standardisation and relatively poor understanding of DNA release and kinetics continues to hamper the broad applicability of this technique. This review considers the application, utility, and limitations of the currently available and investigational diagnostic modalities for invasive aspergillosis.
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Affiliation(s)
- W W Hope
- School of Medicine, University of Manchester and Wythenshawe Hospital, Manchester, UK
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