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