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I principali markers di sepsi e la loro importanza nella fase diagnostico-terapeutica Alessandro Russo Department of Public Health and Infectious Diseases Sapienza University of Rome a.russo@uniroma1.it
Effect of timing on survival Fraction of total patients Time from hypotension onset (hours) Crit Care Med 2006;34:1589-96
Emergency
Possible sources of 35 infection 30 25 20 15 10 5 0 Lung Intra- Genito- SSTI Bloodstream abdominal urinary Crit Care Med. 2006;34:1589-96.
Positivity of blood cultures in different clinical syndromes Endocarditis and bloodstream infections 85% - 95% Bacteremic pneumonia 5% - 30% Ascending Pyelonefritis 30% - 50% Ematogenous osteomyelitis 30% - 50% Bacterial Meningitis Intra-abdominal abscesses FUO Variable Variable Variable Crit Care Med. 2006;34:1589-96.
Surviving sepsis campaign 3
Uses of biomarkers Screening To identify patients at increased risk of adverse outcome to inform a prophylactic intervention or further diagnostic test Diagnosis To establish a diagnosis to inform a treatment decision and to do so more reliably, more rapidly, or more inexpensively than available methods Risk stratification To identify subgroups of patients within a particular diagnostic group who may experience greater benefit or harm with therapeutic intervention Monitoring To measure response to intervention to permit the titration of dose or duration of treatment Surrogate endpoint To provide a more sensitive measure of the consequences of treatment that can substitute for a direct measure of a patient-centered outcome 10
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12 Ann Emerg Med. 2005; 45:524-28.
Algoritmo paziente infetto
Sepsis: Diagnostic Methods and Protocols, Methods in Molecular Biology, vol. 1237
16 Sepsis: Diagnostic Methods and Protocols, Methods in Molecular Biology, vol. 1237
PCT levels accurately differentiate sepsis from noninfectious inflammation Simon L. et al. Clin Infect Dis. 2004; 39:206-217. 17
SIGNIFICATO CLINICO DELLA PROCALCITONINA POSSIBILE SEPSI ELEVATO RISCHIO DI PROGRESSIONE A SEPSI SEVERA E/O A SHOCK SETTICO BASSO RISCHIO DI PROGRESSIONE A SEPSI SEVERA E/O A SHOCK SETTICO
CINETICA DELLA PROCALCITONINA La cinetica della PCT mostra : 1.un aumento rispetto al valore basale dopo 3-6 ore dalla somministrazione di endotossina (o dell invasione batterica) 2.un incremento significativo dopo circa 6 ore 3.il valore di picco viene raggiunto tre le 12 e le 48 ore 4.Ha un'emivita di 24 ore. 5.Cinetica migliore per descrivere l evento infettivo rispetto alla PCR
I livelli di PCT sono progressivamente maggiori a seconda della severità della sepsi Zeni et al. Clin Intens Care 1994; 5: 2 I livelli di PCT correlano con il grado di insufficienza dorgano nei pazienti settici, valutato con il SOFA-score Luzzani et al. Crit Care Med 2001; Vol.31 No.6
EVIDENZE SULL UTILITA DELLA PCT NELLA GESTIONE DELL ANTIBIOTICOTERAPIA
Procalcitonin in septic shock Muller and Trampuz. Int J Antimicrob Agents 2007; 30 Suppl 1: S16-23
IL SETTING CLINICO INFLUISCE SUI VALORI NORMALI DELLA PCT
Expert Rev. Clin. Immunol. 10(9), 1255 1262 (2014) 26
Lancet Infect Dis 2016; 16:819-27
Conditions causing elevation of C- reactive protein Bacterial infections Hypersensitivity complications of infections Inflammatory diseases Transplantation Cancer Necrosis Trauma Burns Fractures 29
Situations where the PCT elevations may be due to a non-bacterial cause Newborns Massive stress (severe trauma, surgery, cardiac shock, burns) Pancreatitis Treatment with agents which stimulate cytokines (OKT3, antilymphocyte globulins, alemtuzumab, IL-2, granulocyte transfusion ) Malaria and fungal infections Prolonged, severe cardiogenic shock or organ perfusion abnormalities Some forms of vasculitis and acute graft vs. host disease Paraneoplastic syndromes due to medullary thyroid and small cell lung cancer Significantly compromised renal function, especially ESRD/hemodialysis 30
Serum procalcitonin measurement contribution to the early diagnosis of candidemia in critically ill patients Charles E et al Intensive Care Med (2006) 32:1577 1583
Early diagnosis of candidemia in ICU patients with sepsis: a prospective comparison of (1 3)-b-D-glucan assay, Candida score, and colonization index Posteraro B, Antonelli M, Tumbarello M,..& Sanguinetti M Crit Care Med, 2012
Beta 1 3 D glucan as a prognostic marker of treatment response in invasive candidiasis Jaijkul S et al Clin Infect Dis 55: 521, 2012
Un possibile approccio pre-emptive nel paziente critico BDG>250 pg/ul inizia echinocandina BDG <200 - >80 pg/ul Candida score >=3 inizia echinocandina
BioMed Research International Volume 2014, Article ID 985813, 10 pages
Platelet Activation Is Associated With Myocardial Infarction in Patients With Pneumonia Cangemi, R., et al., J Am Coll Cardiol. 2014; 64(18):1917 25. Potential Mechanisms for Platelet Activation During Severe Pneumonia
Expert Rev. Clin. Immunol. 10(9), 1255 1262 (2014) 37
PRESEPSIN AS A POTENTIAL USEFUL MARKER TO PREDICT A BACTERIAL INFECTION RELAPSE IN CRITICAL CARE UNIT PATIENTS. PRELIMINARY STUDY Sargentini V, Ceccarelli G, Morelli A, Venditti M & Bachettoni A et Clin Chem Lab Med. 2014 Clinical course of Presepsin and Procalcitonin in a septic patient 38
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42 Trends Mol Med. 2009 March ; 15(3): 129
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How to manage septic shock? Every medical therapy has potential adverse effects, and selection of patients most likely to benefit is crucial, making more personalized approaches necessary. Immune biomarkers measured on admission and during follow-up can guide/support the clinician s early recognition of sepsis, severity assessment and therapeutic decisions in individual patients. Biomarkers may allow transition from generalizing sepsis care bundles to a more tailored management in individual patients thereby reducing the risk for adverse treatment outcomes in patients who based on their biomarker levels do not likely benefit from therapy. Lactate improves initial risk stratification and prompts early fluid resuscitation. Lactate clearance may be used for assessing a patient s response to fluids. Procalcitonin facilitates assessment of bacterial infection risk. Procalcitonin algorithms for guiding therapeutic decisions about initiation and duration of antimicrobial therapy have shown strong effects in regard to lower antibiotic consumption and appear to be safe regarding the results from interventional trials. Proadrenomedullin is an inflammatory prognostic immune marker that improves early mortality prediction and might improve site-of care decisions in patients with respiratory infections. Autophagy and precisione medicine are the new frontiers?