Presentation is loading. Please wait.

Presentation is loading. Please wait.

Invasive Aspergillosis in Critically Ill Patients A New 21th Century Problem? Koenraad Vandewoude, MD Intensive Care Dpt. – Solid Organ Transplant Centre.

Similar presentations


Presentation on theme: "Invasive Aspergillosis in Critically Ill Patients A New 21th Century Problem? Koenraad Vandewoude, MD Intensive Care Dpt. – Solid Organ Transplant Centre."— Presentation transcript:

1 Invasive Aspergillosis in Critically Ill Patients A New 21th Century Problem? Koenraad Vandewoude, MD Intensive Care Dpt. – Solid Organ Transplant Centre Ghent University Hospital Ghent, Belgium

2 Invasive Aspergillosis Extensive data available in distinct high-risk patient populations: –Hemato-oncological patients Allogeneic SCT, graft-vs.-host disease Persistant neutropenia –Solid organ transplant patients, >> lung –Immunosuppressive therapy –Chronic granulomatous disease –Severe combined immunodeficiency –HIV –…

3 Aspergillus spp. Underestimated Pathogen in the ICU? Epidemiological data on incidence and outcome of Invasive Aspergillosis in Critically Ill patients are scarce … –Low index of suspicion –Positive cultures often discarded as colonization or contamination –Absence of feasible diagnostic reference standard

4 Invasive Pulmonary Aspergillosis in Critically Ill patients Differentiate between –Pts referred to the ICU with IPA e.g. pt. from Bone Marrow Transplant Unit with proven/probable IPA and respiratory failure 100% mortality? 1 –Pts. with IPA diagnosed in the ICU community acquired nosocomial ICU acquired grim prognosis 2 1.Janssen JJ. Outcome of ICU treatment in Invasive Aspergillosis. Intens Care Med 1996; 22: 1291-93 2.Vallés J. A 7 year Study of Severe Hospital Acquired Pneumonia requiring ICU Admission. Intens Care Med 2003; 29: 1981-88

5 Pulmonary Aspergillosis A Spectrum of Clinical Entities Depending on patient immune status –With tissue invasion 1,2 Acute invasive aspergillosis Subacute invasive aspergillosis Chronic cavitary and fibrosing pleuropulmonary aspergillosis Acute Tracheobronchitis with tissue invasion –Without tissue invasion Tracheobronchial colonization Tracheobronchitis Pulmonary Aspergilloma Clinical entity may change due immune defence alteration 1 Denning DW. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis. Clin Infect Dis 2003 2 Paterson DL. New clinical presentations of invasive pulmonary aspergillosis in non-conventional hosts. Clin Microbiol Infect 2004

6 IPA diagnosis in ICU patients EORTC/MSG Case Definitions 1 –Difficult to apply outside high risk populations –Not useful to guide therapy 1 Ascioglu S. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants. Clin Infect Dis 2002

7 Consensus Definitions Proven IPA –Histopathology + culture Probable IPA –1 host + 1 microbiological +1 clinical Host: neutropenia, fever, immunosuppressive therapy, steroids, GVHD Microbiological: –positive culture sputum, BAL –Non-invasive test: galactomannan, -D-glucan CT: halo, air-crescent, cavity within area of consolidation Possible IPA –1 host + 1 microbiological OR 1 clinical More specific signs / symptoms –CT: halo, air-crescent, cavity –New infiltrate + specific pulmonary: pl eural rub; pleural pain; hemoptysis

8 Particular Issues in ICU patients –Interpretation of Host Factors: not always clearly detectable … (combination of) underlying disease and/or critical illness induced immunosuppression with low or intermediate probability of invasive disease 1, 2 –Impaired phagocytic function –Organ dysfunctions, metabolic derangements Corticosteroids 3, 4 : –difficult assessment of treshold dose/duration of exposure* 1 Hartemink KJ. Immunoparalysis as a cause for invasive aspergillosis? Intensive Care Med 2003 2 Engelich G. Acquired disorders of phagocyte function complicating medical and surgical illnesses. Clin Infect Dis 2001 3 Lionakis M. Glucocorticoids and Invasive Fungal Infections. Lancet 2003; 362: 1828-38 4 Palmer LB. Corticosteroid Treatment as a Risk Factor for Invasive Aspergillosis in Patients with Lung Disease. Thorax 1991; 46: 15-20

9 Particular Issues in ICU patients –Signs and symptoms difficult to appreciate cough, chest pain, pleural rub, hemoptysis, dyspnea –non specific –evaluation difficult or impossible fever? clinical examination hampered by mechanical ventilation

10 Particular Issues in ICU patients –Medical Imaging: Concurrent pulmonary injury hampers interpretation –residual infiltrates, atelectasis, ARDS, … –CT scan feasible in case of high-grade ventilatory and inotropic dependency? Typical lesions: Halo, Air-crescent … –low incidence in non-neutropenic patients Greene RA. Radiologic findings in acute invasive pulmonary aspergillosis: utility of the halo and air-crescent sign for diagnosis and treatment of invasive pulmonary aspergillosis in high-risk patients. 13th ECCMID, 2002, Glasgow

11 Microbiological sampling … –>> lower respiratory tract samples –BAL not always feasible –Direct microscopy is mandatory!* –Serology Aspergillus galactomannan? ** –validation in neutropenic pts –sensitive/significant in other patients ß- glucan: ? *** Biopsy procedures … –transbronchial biopsy not possible –thoracoscopic procedure preferred –caveats: ventilator and pressor dependency coagulation disorders … * Uffredi ML. Significance of aspergillus fumigatus isolation from respiratory specimens in non- granulocytopenic patients. Eur J Clin Microbiol Infect Dis 2003 * * Maertens J. Screening for circulating galactomannan as a non-invasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients. Blood 2001; 97: 1604-10 ** *Ostrosky-Zeichner L. Multicenter clinical evaluation of the (1-3) beta-D-glucan assay as an aid in diagnosis of fungal infections in humans. Clin Infect Dis 2005; 41: 654-9

12 Invasive Aspergillosis in ICU Patients Fact or Fiction? Isolation of Aspergillus spp. in immunocompetent host is often/always interpreted as colonization …. Assessment of clinical signifance most difficult in patient groups with intermediate risk of invasive disease Literature data –Variable diagnostic criteria

13 Perfect J. Impact of culture isolation of Aspergillus species: a hospital-based survey of Aspergillosis. Clin Infect Diseases 2001

14 AuthorYearType of studyPatient categoryN.IncidenceMortality Lewis1985Case seriesIPA complicating influenza pneumonia Case report and literature review 6-100% Karam1986Cases seriesNon-neutropenic patients - 10 structural lung disease 7 steroid treatment 32-100% Janssen JJWM1996Monocentric Retrospective Medical ICU pts with hematological malignancy, immunosuppression for mixed connective tissue disease, ARDS 25-92% Pittet1996COPD patients in MICU Acquisition of IPA during mechanical ventilation due to high grade airborne inoculation 2-100% Rello1998MonocentricSeries of COPD patients and literature review24-100% Valles2002Two centres Observational, prospective study Hospital acquired pneumonia requiring ICI admission Aspergillus spp. identified in 17% of pts Mainly COPD pts 77% Bulpa2001Monocentric Case series COPD patients admitted to ICU diagnosed with IPA23-100% Meersseman2004Monocentric Retrospective Medical ICU 70% cases without malignancy 5 pts with IA without known predisposing condition (of whom 3 Child C cirrhosis) 1075.8%91% Garnacho- Montero 2005Multicentric Prospective 73 ICUs in Spain patients with LOS > 7 days 201.1%80% Vandewoude2006RetrospectiveMixed ICU 40% haematological pts 833.3/100077%

15 Invasive pulmonary aspergillosis in non- immunocompromised, non-neutropenic hosts* –Review of 32 cases –Underlying diseases: lung fibrosis, COPD, Influenza A, diabetes mellitus, alcoholism, short course of steroids, … –… IPA should be considered when Aspergillus spp. is isolated in resp. secretions and presence of pneumonia …. * Karam G. Invasive pulmonary aspergillosis in non-immunocompromised, non- neutropenic hosts. Reviews of infectious diseases 1986; 8: 357-63

16 COPD patients with IPA: benefits of ICU? * –23 pts, 16 proven, 7 probable (repeated isolation) –recent steroid treatment, or intensification of steroid treatment –severe bronchospasm (12/23) –all required mechanical ventilation –Mortality 100% * Bulpa P. COPD patients with invasive pulmonary aspergillosis: benefits of intensive care? Intens Care Med 2001; 27: 59-67

17 Invasive pulmonary aspergillosis in COPD patients: an emerging fungal pathogen* –13 cases of IPA in COPD pts admitted to ICU –bronchospasm ++ –steroid treatment often continued in spite of isolation of Aspergillus spp. –Mortality 100% - proven IPA by autopsy * Ader F. Invasive pulmonary aspergillosis in COPD patients: an emerging fungal pathogen. Clin Microbiol Infec 2005: Jun;11:427-9.

18 Retrospective cohort study based on prospectively gathered microbiology and autopsy data – UZ KULeuven: 127/1850 ptn Meersseman W. Invasive Aspergillosis in Critically Ill patients without Malignancy Am J Respir Crit Care Med 2004

19

20 Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Critical Care 2006 –Retrospective study –1997-2003 –Sole entry criterion = positive lower respiratory tract specimen –Adapted criteria to discriminate colonization vs. clinical relevant infection (i.e. : relevant to start antifungal treatment) –Incidence 3.3/1000 admission

21 Adapted Diagnostic Criteria … Definite IPA –positive histology (+culture) of lung tissue –positive culture from normally sterile site Probable IPA 1.Lower resp tract sample pos for Aspergillus 2.Compatible signs and symptoms 3.Abnormal medical imaging of chest 4.Either A.host risk factors: neutropenia, hemato-oncologic malignancy treated with cytostatics, steroid treatment > 20 mg/day, immunodeficiency B.BAL: –semiquantitative positive culture +/++ and –cytologic exam positive (branching hyhae) Vandewoude K. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Critical Care 2006

22

23

24

25 Survival curves for ICU patients with IPA vs Aspergillus spp. colonization

26 Does Invasive Aspergillosis has an impact on ICU patient outcome? –i.e.: is there an attributable mortality? –Case-control study 1:2 matching Matching criteria –APACHE II (admission) –Diagnostic category –Age »Two cohorts of pts with same expected mortality Vandewoude K. Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of stay and ventilator dependence. J Hosp Infection 2004

27 Vandewoude K. Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of stay and ventilator dependence. J Hosp Infection 2004

28 Conclusion Invasive Aspergillosis in ICU patient is a Fact … Incidence … –0.33 – 5.8% –Depending on patient mix: MICU > SICU –Limited patient groups, precluding firm conclusions … –Underestimated? Delayed diagnosis –Diagnosis post mortem … Grim prognosis –Mortality exceeding 77% –Observed mortality >> predicted mortality –Attributable mortality … ?

29 Conclusion Do not discard an Aspergillus spp. positive respiratory tract specimen in critically ill patients – consider the clinical significance even in the absence of EORTC/MSG host risk factors

30 ? Epidemiology: prospective multicenter observational studies needed to estimate incidence –Biopsy if possible? –Protocol based autopsy policy Validation of clinical diagnostic algorithm, –Useful to guide (pre-emptive) therapy –Development of criteria for pre-emptive treatment –Consideration of additional host risk factors: COPD, steroid treatment, MOF, …. Explore and measure immunoparalytic state Evaluation of non-invasive serologic markers in ICU pts –galactomannan –Beta-D-glucan –PCR


Download ppt "Invasive Aspergillosis in Critically Ill Patients A New 21th Century Problem? Koenraad Vandewoude, MD Intensive Care Dpt. – Solid Organ Transplant Centre."

Similar presentations


Ads by Google