overview sul rischio infettivo da ifi nel paziente critico f. cristini … · 2016. 5. 4. ·...
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Overview sul rischio infettivo da IFI nel paziente critico
F. Cristini (Bologna)
An Italian consensus for invasive candidiasis management (ITALIC).
Scudeller L, Viscoli C, Menichetti F, del Bono V, Cristini F, Tascini C, Bassetti M, Viale P; ITALIC Group. Infection. 2014
Apr;42(2):263-79.
Clinical practice guidelines for the management of invasive Candida infections in adults in the Middle East region: Expert panel
recommendations.
Alothman AF, Al-Musawi T, Al-Abdely HM, Salman JA, Almaslamani M, Yared N, Butt AA, Raghubir N, Morsi WE, Al Thaqafi AO.
J Infect Public Health. 2014 Feb;7(1):6-19
Recommendations for the management of candidemia in adults in Latin America. Latin America Invasive Mycosis Network.
Nucci M, Thompson-Moya L, Guzman-Blanco M, Tiraboschi IN, Cortes JA, Echevarría J, Sifuentes J, Zurita J, Santolaya ME,
Alvarado Matute T, de Queiroz Telles F, Colombo AL; Latin America Invasive Mycosis Network.
Rev Iberoam Micol. 2013 Jul-Sep;30(3):179-88
JSMM clinical practice guidelines for diagnosis and treatment of invasive candidiasis.
Japanese Society of Mycology. Med Mycol J. 2013;54(2):147-251
Diagnosis and therapy of Candida infections: joint recommendations of the German Speaking Mycological Society and the Paul-
Ehrlich-Society for Chemotherapy.
Ruhnke M, Rickerts V, Cornely OA, Buchheidt D, Glöckner A, Heinz W, Höhl R, Horré R, Karthaus M, Kujath P, Willinger B,
Presterl E, Rath P, Ritter J, Glasmacher A, Lass-Flörl C, Groll AH, German Speaking Mycological Society, Paul-Ehrlich-Society
for Chemotherapy.
Mycoses. 2011 Jul;54(4):279-310.
NO HAEMATO/ONCO, NO PEDIATRIC POPULATION
Guidelines for the treatment of Invasive Candidiasis and other yeasts. Spanish Society of Infectious Diseases and Clinical
Microbiology (SEIMC). 2010 Update.
Aguado JM, Ruiz-Camps I, Muñoz P, Mensa J, Almirante B, Vázquez L, Rovira M, Martín-Dávila P, Moreno A, Alvarez-Lerma F,
León C, Madero L, Ruiz-Contreras J, Fortún J, Cuenca-Estrella M; Grupo de Estudio de Micología Médica de la SEIMC
(GEMICOMED).
Enferm Infecc Microbiol Clin. 2011 May;29(5):345-61
NON NEUTROPENIC PATIENT
Canadian clinical practice guidelines for invasive candidiasis in adults.
Bow EJ, Evans G, Fuller J, Laverdière M, Rotstein C, Rennie R, Shafran SD, Sheppard D, Carle S, Phillips P, Vinh DC.
Can J Infect Dis Med Microbiol. 2010 Winter;21(4):e122-50.
NO HAEMATO/ONCO, NO PEDIATRIC POPULATION
ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients.
Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman W, Akova M, Arendrup MC, Arikan-
Akdagli S, Bille J, Castagnola E, Cuenca-Estrella M, Donnelly JP, Groll AH, Herbrecht R, Hope WW, Jensen HE, Lass-Flörl C,
Petrikkos G, Richardson MD, Roilides E, Verweij PE, Viscoli C, Ullmann AJ; ESCMID Fungal Infection Study Group.
Clin Microbiol Infect. 2012 Dec;18 Suppl 7:19-37
A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts.
Bassetti M, Marchetti M, Chakrabarti A, Colizza S, Garnacho-Montero J, Kett DH, Munoz P, Cristini F, Andoniadou A, Viale P,
Rocca GD, Roilides E, Sganga G, Walsh TJ, Tascini C, Tumbarello M, Menichetti F, Righi E, Eckmann C, Viscoli C, Shorr AF,
Leroy O, Petrikos G, De Rosa FG.
Intensive Care Med. 2013 Dec;39(12):2092-106
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.
Peter G. Pappas, Carol A. Kauffman, David R. Andes, Cornelius J. Clancy, Kieren A. Marr, Luis Ostrosky-Zeichner, Annette C.
Reboli, Mindy G. Schuster, Jose A. Vazquez, Thomas J. Walsh, Theoklis E. Zaoutis, and Jack D. Sobel
Clin Infect Dis. 2016 Feb 15;62(4):e1-e50. doi: 10.1093/cid/civ933. Epub 2015 Dec 16
NON NEUTROPENIC PATIENT
SOT
Italian guidelines for diagnosis, prevention, and treatment of invasive fungal infections in solid organ transplant recipients.
Grossi PA, Dalla Gasperina D, Barchiesi F, Biancofiore G, Carafiello G, De Gasperi A, Sganga G, Menichetti F, Montagna MT,
Pea F, Venditti M, Viale P, Viscoli C, Nanni Costa A.
Transplant Proc. 2011 Jul-Aug;43(6):2463-71.
NON NEUTROPENIC PATIENT
Invasive fungal infections in solid organ transplant recipients
J. Gavalda, Y. Meije, J. Fortun, E. Roilides, F. Saliba, O. Lortholary, P. Munoz, P. Grossi, M. Cuenca-Estrella
on behalf of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH)
Clin Microbiol Infect 2014; 20 (Suppl. 7): 27–48
Candida Infections in Solid Organ Transplantation
F. P. Silveira, S. Kusne and the AST Infectious Diseases Community of Practice
American Journal of Transplantation 2013; 13: 220–227
Aspergillosis in Solid Organ Transplantation
N. M. Singh, S. Husain and the AST Infectious Diseases Community of Practice
American Journal of Transplantation 2013; 13: 228–241
ASPERGILLOSIS
Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America.
Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens
DA, van Burik JA, Wingard JR, Patterson TF. Infectious Diseases Society of America
Clin Infect Dis. 2008 Feb 1;46(3):327-60. UPDATE IN PROGRESS
Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of
Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious
Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.
De Pauw B et al
Clin Infect Dis. 2008 Jun 15;46(12):1813-21. UPDATE IN PROGRESS
The biology of pulmonary aspergillus infections Warris A - Journal of Infection (2014) 69, S36eS41
Classification of pulmonary aspergillosis
IPA can be classified histopathologically in angio-invasive and airway-invasive disease
3 clinical syndromes
Saphrophytic Infections: colonization and aspergilloma
Allergic disease: Extrinsic allergic alveolitis, ABPA and allergic asthma
Invasive disease: - acute angio-invasive aspergillosis
- acute bronchopneumonia
- chronic necrotizing pulmonary aspergillosis
- tracheobronchitis
The clinical spectrum of pulmonary aspergillosis Kosmidis C, Denning DW - Thorax 2015;70:270–277
Tipically
Neutropenic pts
HSCT
SOT
Tipically
NON-neutropenic pts
Interaction of Aspergillus with host
The clinical spectrum of pulmonary aspergillosis Kosmidis C, Denning DW - Thorax 2015;70:270–277
Pathological features and characteristics of various forms of pulmonary aspergillosis
The clinical spectrum of pulmonary aspergillosis Kosmidis C, Denning DW - Thorax 2015;70:270–277
Simple aspergilloma Chronic cavitary pulmonary aspergillosis
Aspergillus bronchitis without significant immunocompromise Ales Chrdle et al - Ann. N.Y. Acad. Sci. 1272 (2012) 73–85
Septate branching hyphae typical
of Aspergillus superficially within
bronchial tissue
…… It is distinct from asymptomatic fungal colonization and other forms of aspergillosis
(allergic, chronic, or invasive aspergillosis)
Report of 38 cases of tracheobronchitis in non-immunocompromised patients
with dual isolation of Aspergillus in lower respiratory tract samples Barberán J et al - Rev Esp Quimioter 2014;27(2): 110-114
38 cases of tracheobronchitis (26 simple, 12 invasive) were identified, all considered
probable aspergillar tracheobronchitis (no histopathology performed).
Only patients with a bronchoscopy report of tracheobronchitis in clinical records were
considered for the present study.
Among the 245 patients with at least two valuable cultures of respiratory samples yielding
Aspergillus spp. identified from October 2002 to July 2010 in 29 Spanish hospitals:
Simple: mucosal inflammation and mucus secretions
Invasive: ulceration and pseudomembrane formation
Transplant recipients and patients presenting neutropenia (<1000 neutrophils/mm3),
diagnosis of aspergilloma or allergic bronchopulmonary aspergillosis were excluded
Report of 38 cases of tracheobronchitis in non-immunocompromised patients
with dual isolation of Aspergillus in lower respiratory tract samples Barberán J et al - Rev Esp Quimioter 2014;27(2): 110-114
• Local damage of the airway wall and non fungal infections may be predisposing factors for Aspergillus
infection.
• Clinical signs and rx findings are often clouded by concurrent viral or bacterial infection in COPD patients.
• A high index of suspicion is needed for early performance of bronchoscopy since clinical and radiographic
findings rarely point to aspergillar tracheobronchitis.
• In our study, although mortality was 15.4% among patients with simple tracheobronchitis, invasive
tracheobronchitis presented higher mortality rates (41.7%).
• Aspergillus tracheobronchitis should be considered in any COPD patient with worsening dyspnea
and/or cough who fails to improve with empiric antimicrobial therapy.
Predictors of mortality in non-neutropenic patients with invasive pulmonary
aspergillosis: does galactomannan have a role? Russo A et al - Diagnostic Microbiology and Infectious Disease 80 (2014) 83–86
Retrospective analysis in the University Hospital “Umberto I” in Rome
All infectious disease consultations for patients with the following features:
• “proven” or “probable” IPA (period January 2010 - November 2013)
• patient age ≥18 years
• absence of neutropenia at the time of diagnosis
• mycological criteria for defining IPA as “probable” including GM antigen in BAL fluid in all cases
and positive culture in addition, and no evidence of invasive fungal infections other than IPA.
Patients with risk conditions such as COPD and cirrhosis and presenting with persistent
fever and respiratory disease were also examined for GM antigen in BAL fluid.
Predictors of mortality in non-neutropenic patients with invasive pulmonary
aspergillosis: does galactomannan have a role? Russo A et al - Diagnostic Microbiology and Infectious Disease 80 (2014) 83–86
Univariate analysis of factors associated with death (6w) among patients with invasive pulmonary aspergillosis
A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill
Patients Blot SI ...and AspICU Study Investigators - Am J Respir Crit Care Med Vol 186, Iss. 1, pp 56–64, Jul 1, 2012
Proven invasive pulmonary aspergillosis
Idem EORTC/MSG criteria
Putative invasive pulmonary aspergillosis (all four criteria must be met)
1. Aspergillus-positive lower respiratory tract specimen culture (= entry criterion)
2. Compatible signs and symptoms (one of the following) •Fever refractory to at least 3 d of appropriate antibiotic therapy
•Recrudescent fever after a period of defervescence of at least 48 h while still on antibiotics and without other
apparent cause
•Pleuritic chest pain
•Pleuritic rub
•Dyspnea
•Hemoptysis
•Worsening respiratory insufficiency in spite of appropriate antibiotic therapy and ventilatory support
3. Abnormal medical imaging by portable chest X-ray or CT scan of the lungs
4. Either 4a or 4b
4a. Host risk factors (one of the following conditions) •Neutropenia (absolute neutrophil count <500/mm3) preceding or at the time of ICU admission
•Underlying hematological or oncological malignancy treated with cytotoxic agents
•Glucocorticoid treatment (prednisone equivalent, >20 mg/d)
•Congenital or acquired immunodeficiency
4b. Semiquantitative Aspergillus-positive culture of BAL fluid (+ or ++), without
bacterial growth together with a positive cytological smear showing branching hyphae
Aspergillus respiratory tract colonization
When ≥1 criterion necessary for a diagnosis of putative IPA is not met, the case is classified as
Aspergillus colonization.
ALTERNATIVE CLINICAL ALGORITHM (to EORTC/MSG criteria)
A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill
Patients Blot SI ...and AspICU Study Investigators - Am J Respir Crit Care Med Vol 186, Iss. 1, pp 56–64, Jul 1, 2012
A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill
Patients Blot SI ...and AspICU Study Investigators - Am J Respir Crit Care Med Vol 186, Iss. 1, pp 56–64, Jul 1, 2012
Epidemiology of invasive aspergillosis in critically ill patients: clinical
presentation, underlying conditions, and outcomes Taccone FS… on behalf of the AspICU Study Investigators - Critical Care (2015) 19:7
NO data on the incidence of positive Aspergillus culture.
Importantly, IA remains a rare disease. It was reported in 1% to 2% of ICU patients in a large
international database.
Epidemiology of invasive aspergillosis in critically ill patients: clinical
presentation, underlying conditions, and outcomes Taccone FS… on behalf of the AspICU Study Investigators - Critical Care (2015) 19:7
Epidemiology of invasive aspergillosis in critically ill patients: clinical
presentation, underlying conditions, and outcomes Taccone FS… on behalf of the AspICU Study Investigators - Critical Care (2015) 19:7
Epidemiology of invasive aspergillosis in critically ill patients: clinical
presentation, underlying conditions, and outcomes Taccone FS… on behalf of the AspICU Study Investigators - Critical Care (2015) 19:7
*
EORTC Definition:
•neutropenia (<500 neutrophils/mm3)
•receipt of an allogeneic stem cell transplant
•prolonged use of corticosteroids (0.3 mg/kg/day of prednisone equivalent for 13 weeks)
•treatment with other recognized T cell immunosuppressants
•severe inherited immunodeficiency
Multicenter evaluation of a lateral-flow device test for diagnosing invasive
pulmonary aspergillosis in ICU patients Eigl S et al - Critical Care (2015) 19:178
Rapid immunochromatography test for the
qualitative detection of Aspergillus
diagnostic antigen* in human serum and
bronchoalveolar lavage fluid.
* an extracellular mannoprotein antigen
that is secreted exclusively during active
growth of Aspergillus species.
Multicenter evaluation of a lateral-flow device test for diagnosing invasive
pulmonary aspergillosis in ICU patients Eigl S et al - Critical Care (2015) 19:178
149 BAL fluid samples obtained from 133 ICU patients with clinical suspicion of IPA who were
tested routinely for the presence of Aspergillus species between January 2010 and June 2014
(SOT patients excluded).
ADVANTAGES:
•Point-of-care test
•Rapid single-sample
•Simplicity
•Minimal staff training
•BAL fluid samples do not need pretreatment
•Available within 10 to 15 minutes of sample receipt
IFI in non-neutropenic/ICU hosts: Key messages ……
-The clinical suspicion is often delayed:
-IMI in non-neutropenic hosts do not have typical CT scan
-symptoms often masked by underlying conditions (e.g. COPD)
-The diagnosis is challenging:
-Difficult to differentiate Aspergillus colonization from infection
-Low diagnostic sensitivity of plasmatic GM antigen
-use of GM antigen in BAL fluid has become standard of care. PCR? LFD?
-The treatment is difficult:
-non-neutropenic hosts with IMI are commonly older than neutropenic hosts
AND have more co-morbidities
High risk of drug interactions and organ toxicity
- Multidisciplinary management is important in most cases
“NEW” ESTABLISHED CLINICAL CONDITIONS TO BE CONSIDERED AS RF:
Prolonged corticosteroid administration
Chronic obstructive pulmonary disease (COPD)
Advanced liver cirrhosis
Pulmonary/airways Aspergillus infections represent a wide and pleomorphic range of
diseases