PATOLOGIA RESPIRATORIA ACUTA INFETTIVA S.A. Marsico Dipartimento di Scienze Cardio-Toraciche e Respiratorie Seconda Università degli Studi di Napoli Respiratory Infections Acute Bronchitis Exacerbation of chronic bronchitis Community Acquired Pneumonia classical CAP Health care associated Pneumonia (HCAP) Nosocomial Pneumonia Hospital acquired Pneumonia (HAP) Ventilator t associated Pneumonia (VAP) Pneumonia in immunocompromised patients Rare Causes of Infectious Diseases scaricato da www.sunhope.it 1
CAP: Community Acquired Pneumonia Acute Pulmonary Infection in a patient who is not hospitalized or resting in a long-term facility 14 or more days prior to presentation HCAP : Health Care Acquired Pneumonia Hospitalization in an acute care hospital for two or more days in the preceding 90 days Residence in a nursing home or long-term care facility Home intravenous therapy ( including antibiotics) or home wound care within the past 30 days of the current infection Long term dialysis within 30 days American Thoracic Society Documents. Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia. Am J Respir Crit Care Med 171 (4):388-416, 2005. scaricato da www.sunhope.it 2
HOSPITAL ACQUIRED PNEUMONIA HAP: Hospital Acquired Pneumonia New Infection occurring 48 or more hours after hospital admission VAP: Ventilator Associated Pneumonia New infection occurring 48 or more hours after endotracheal intubation Community Acquired Pneumonia scaricato da www.sunhope.it 3
CAP EPIDEMIOLOGIA USA: 5 milioni di morti/anno 1 a causa infettiva di morte 6 a causa di morte ITALIA: epidemiologia simile a quella negli USA 13 morti per 100.000 abitanti Polmonite extraospedaliera (CAP) Incidenza ( x 1000/ anno ) 30 25 20 15 10 5 EPIDEMIOLOGIA 0 0 5 10 15 20 25 60 65 70 75 Età (anni) scaricato da www.sunhope.it 4
CAP Management in Adults Diagnostic approach Site-of-Care Decisions Diagnostic Testing Antibiotic Treatment Other Treatment Considerations Management of Nonresponding Pneumonia Prevention CAP Management in Adults Diagnostic approach: TYPICAL PNEUMONIA ATYPICAL PNEUMONIA scaricato da www.sunhope.it 5
CARATTERISTICHE DIFFERENZIALI Forme tipiche Batteriche Accumulo di polimorfonucleati negli alveoli Esordio brusco Febbre elevata Dolore toracico Tosse produttiva Reperto obiettivo di rantoli consolidamento polmonare Infiltrazione lobare o segmentaria all Rx Leucocitosi Herpes labiale Forme atipiche Virali e simil-virali Infliltrazione di cellule mononumononucleate nell interstizio nell interstizio polmonare p. Inizio graduale Prodromi simil -influenzali (astenia, malessere generale, cefalea, febbre modesta) Tosse non produttiva Reperto obiettivo assente o modesto Tenui infiltrati o interessamento dell interstizio peribronchiale all Rx Assenza di leucocitosi Polmonite del lobo inferiore destro scaricato da www.sunhope.it 6
Polmonite pneumococcica del lobo superiore destro Dopo antibioticoterapia Polmonite destra da entercoccoo Anni 74 Dopo antibioticoterapia scaricato da www.sunhope.it 7
5-5-2002 5-5-2002 7-6-2002 7-6-2002 Anni 34, non fattori di rischio: Polmonite del lobo inf. sn con versamento pleurico Fattori di rischio (diabete, hiectasiebronc) Polmonite da Pseudomonas Insufficienza respiratoria scaricato da www.sunhope.it 8
Polmonite da Mycoplasma pneumoniae Polmonite da Mycoplasma Pneumoniae scaricato da www.sunhope.it 9
scaricato da www.sunhope.it 10
Polmonite bilaterale: anni 49, non fattori di rischio 29-8-2001 11-9-2001 Polmonite ascessualizzata del lobo inferiore sinistro Donna di 43 anni, senza fattori di rischio ascessualizzazione del lobo inferiore sinistro. Ampia Quadro TAC all ingresso Quadro TAC alla dimissione scaricato da www.sunhope.it 11
Polmonite virale ASPETTI RADIOLOGICI DELLE POLMONITI Pattern Alveolare una o più aree di opacità omogenea, a varia estensione, con broncogramma aereo nei casi tipici l addensamento è a limiti lobari (raro!) concordanza tra rilievi clinici e radiologici Pattern Interstiziale accentuazione diffusa o circoscritta della trama interstiziale alveolare infiltrato peri-ilare bilaterale quadro reticolo-nodulare diffuso tenue addensamento monolaterale discrepanza fra obiettività clinica e quadri radiologici scaricato da www.sunhope.it 12
Anni 45 (non fattori di rischio) Ascesso Stafilococcico Polmonite acquisita in comunità DIAGNOSI Sospetta polmonite Esame obiettivo Rx Torace Diagnosi di polmonite Valutazione della gravità Paziente ospedalizzato Paziente ambulatoriale scaricato da www.sunhope.it 13
Infezione polmonare da S. aureus Anni 21, non fattori di rischio. Micetoma endocavitario scaricato da www.sunhope.it 14
CAP Management in Adults Diagnostic approach Site-of-Care Decisions Diagnostic Testing Antibiotic Treatment Other Treatment t Considerations Management of Nonresponding Pneumonia Prevention Site-of-Care Decisions Initial assessment of severity Outpatient Hospital General ward ICU Clin Infectious Disease 2007 scaricato da www.sunhope.it 15
Site-of-Care Decisions Hospital admission decision USA: Prognostic model Pneumonia severity Index (PSI) British Thoracic Society: Severity of illness scores CURB-65 criteria CRB-65 NEJM 1997 scaricato da www.sunhope.it 16
CAP: Stratificazione del rischio prognostico Classe di rischio Punteggio Mortalità (%) Luogo di cura I * 0,1 Domicilio II 70 0,6 Domicilio III 71-90 2,8 Domicilio o breve ricovero IV 91-130 8,2 Ospedale V > 130 29,22 Ospedale * pazienti di età < di 50 anni, senza comorbilità (neoplasie, epatopatie, nefropatie, insufficienza cardiaca congestizia) e senza compromissione dei segni vitali Fine et al. 1997 Pneumonia Severity Index Il paziente ha più di 50 anni? No Il paziente presenta fattori di rischio? SI Assegnare alle classi II-V No Assegnare alla classe I Fine M.J. et al. New Engl J Med, 1997 scaricato da www.sunhope.it 17
CURB-65 BTS Criteria Confusion BUN level > 7 mmol/l (20 mg/dl) Respiratory p yrate > 30 breaths/min Blood pressure (systolic < 90 mm Hg; or diastolic < 60 mmhg) Age > 65 years Score 0-1 treated as outpatients 2 admitted to the wards > 3 ICU care CRB-65: a simplified version, which does not require testing for BUN level, may be appropriate for decision making in a primary care practitioner s office. CURB-65 BTS Criteria Confusion BUN level > 7 mmol/l (20 mg/dl) Respiratory p yrate > 30 breaths/min Blood pressure (systolic < 90 mm Hg; or diastolic < 60 mmhg) Age > 65 years Score 0-1 treated as outpatients 2 admitted to the wards > 3 ICU care CRB-65: a simplified version, which does not require testing for BUN level, may be appropriate for decision making in a primary care practitioner s office. scaricato da www.sunhope.it 18
Confusion Respiratory Blood-age 65 CRB-65 score Confusion Respiratory rate 30/min Blood pressure (SBP <90 mmhg or DPB 60 mmhg) Age 65 Years 0 or 1 1 or 2 3 or 4 Treatment options GROUP 1 Mortality low (1,2%) (n.=167, died =2) GROUP 2 Mortality intermediate (8,15%) (n.= 455, died = 37) GROUP 3 Mortality high (31%) (n. 96, died = 30) Likely suitable for home treatment Likely need hospital referral and assessment Urgent hospital ammission Lim, W S et al. Thorax 2003;58:377-382 CURB65 SEVERITY SCORE IN CAP Mortality % Confusion Urea > 7 Resp Rate 30 sbp < 90 or dbp 60Age 65 Lim et al Thorax 2003;58:377-382 N. of features scaricato da www.sunhope.it 19
Criteria for severe CAP Clin Infectious Disease 2007 Site-of-Care Decisions ICU admission decision Direct admission to an ICU is required for patients with septic shock requiring vasopressor or with acute respiratory failure requiring intubation and mechanical ventilation. Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP. Clin Infectious Disease 2007 scaricato da www.sunhope.it 20
IDSA/ATS Guidelines for CAP in Adults Implementation of Guideline Recommendations Site-of-Care Decisions Diagnostic Testing Antibiotic Treatment Other Treatment Considerations Management of Nonresponding Pneumonia Prevention Clin Infectious Disease 2007 IDSA/ATS Guidelines for CAP in Adults Antibiotic treatment Likely pathogens in CAP Antibiotic resistance issues Empirical antimicrobial therapy Pathogen-directed therapy Time to first antibiotic dose Switch from intravenous to oral therapy Duration of antibiotic therapy Clin Infectious Disease 2007 scaricato da www.sunhope.it 21
IDSA/ATS Guidelines for CAP in Adults Clin Infectious Disease 2007 Clin Infectious Disease 2007 scaricato da www.sunhope.it 22
IDSA/ATS Guidelines for CAP in Adults Antibiotic treatment Likely pathogens in CAP Antibiotic resistance issues Empirical antimicrobial therapy Pathogen-directed therapy Time to first antibiotic dose Switch from intravenous to oral therapy Duration of antibiotic therapy Clin Infectious Disease 2007 SEMPRE Surveillance Study (2000-2002) Antibiotic susceptibility of S. Pneumoniae PEN CEF CLAR LEV % R % I % S TETRA 0 20 40 60 80 100 A. Marchese et al, Intern J Antimicrobial Agents 2005 scaricato da www.sunhope.it 23
PROTEKT Study: susceptibility of S. Pneumoniae to penicillin and azithromycin 45 Italy 40 35 30 25 20 15 10 5 0 2000 2001 2002 2003 25 UK 20 15 10 5 0 2000 2001 2002 2003 PEN-I PEN-R AZY-R 45 Spain 40 35 30 25 20 15 10 5 0 2000 2001 2002 2003 70 France 60 50 40 30 20 10 0 2000 2001 2002 2003 G.C. Schito, D. Felmingham, Intern J Antimicrobial Agents 2005 EARSS DATA Susceptibility results for S. pneumoniae isolates in Italy % 100 90 80 70 60 50 40 30 20 10 0 1999 2000 2001 2002 2003 2004 2005 PEN RES PEN INT PEN SUSC http://www.rivm.nl/earss/database/ scaricato da www.sunhope.it 24
EARSS DATA Susceptibility results for S. pneumoniae isolates in Italy % 40 35 30 25 20 15 10 5 0 1999 2000 2001 2002 2003 2004 2005 ERY RES PERCENTAGE http://www.rivm.nl/earss/database/ IDSA/ATS Guidelines for CAP in Adults Antibiotic treatment Likely pathogens in CAP Antibiotic resistance issues Empirical antimicrobial therapy Pathogen-directed therapy Time to first antibiotic dose Switch from intravenous to oral therapy Duration of antibiotic therapy Clin Infectious Disease 2007 scaricato da www.sunhope.it 25
IDSA/ATS Guidelines for CAP in Adults Appropriate drug selection is dependent on the causative pathogen and its antibiotic susceptibility. Acute pneumonia may be caused by a wide variety of pathogens. However, until more accurate and rapid diagnostic methods are available, the initial treatment for most patients will remain empirical. Clin Infectious Disease 2007 IDSA/ATS Guidelines for CAP in Adults Outpatient treatment Clin Infectious Disease 2007 scaricato da www.sunhope.it 26
IDSA/ATS Guidelines for CAP in Adults Inpatients, non ICU treatment Inpatients, ICU treatment Clin Infectious Disease 2007 IDSA/ATS Guidelines for CAP in Adults Special concerns Clin Infectious Disease 2007 scaricato da www.sunhope.it 27
Prevalenza di P. aeruginosa multiresistente Osp. Monaldi (2002 2003) N 131 62 59 100 5 58 80 60 73 68 63 46 54 ESBL IMIP-R CIP-R 40 20 36 24 21 20 36 27 0 0 scaricato da www.sunhope.it 28
IDSA/ATS Guidelines for CAP in Adults Antibiotic treatment Likely pathogens in CAP Antibiotic resistance issues Empirical antimicrobial therapy Pathogen-directed therapy Time to first antibiotic dose Switch from intravenous to oral therapy Duration of antibiotic therapy Clin Infectious Disease 2007 scaricato da www.sunhope.it 29
IDSA/ATS Guidelines for CAP in Adults Clin Infectious Disease 2007 Clinically relevant outome parameters in CAP Clin Infectious Disease 2007 scaricato da www.sunhope.it 30
Acute Exacerbations of COPD COPD exacerbation An exacerbation is a sustained worsening of the patient s symptoms from his or her usual stable state that is beyond normal day-to-day variations, and is acute in onset. BTS 2004 An exacerbation of COPD is an event in the natural course of the disease caracterized by a change in the patient baseline dyspnea, cough and/or sputum beyond day to day variability to warrant a change in management. ATS/ERS 2004 scaricato da www.sunhope.it 31
COPD exacerbation Pathophysiology - Current Hypothesis Chronic Inflammation Viral Infection 25% Unknown 20% Bacterial Infection 50% Acute Inflammation Exacerbation Air Pollution 5% Relative frequency of bacterial pathogens isolated from 14 recent antibiotic comparison trials in acute exacerbations of COPD Sethi S, Proc Am Thorac Soc, 2004 scaricato da www.sunhope.it 32
Patogeni isolati in soggetti con riacutizzazione di BPCO % 70 60 50 40 30 S. pneumoniae e cocchi Gram-pos. Haemophilus i./moraxella c. Enterobacteriaceae/ Pseudomonas spp. 20 Gruppo I: FEV 1 >50% del predetto Gruppo II: FEV 1 <50%>35 del pred. 10 Gruppo III: FEV 1 <35% del predetto 0 Gruppo I Gruppo II Gruppo III J Eller, Chest 1998 Miravitlles M, Chest 1999 scaricato da www.sunhope.it 33
scaricato da www.sunhope.it 34
S. pneumoniae: prevalenza dei ceppi resistenti nel periodo 2000-2001 Pen-R Mac-R Cef-R FQ-R (moxifloxacina) UK 3 12 4 0 Germania 2 16 3 0 Francia 27 58 41 0 Grecia 18 16 26 0 Spagna 28 37 39 0 Italia 5 30 6 0 NCCLS 2002 Breakpoints ME Jones et al., Clin Microbiol Infect 2003 Produzione di -lattamasi in H. influenzae e H. parainfluenzae in Italia Haemophilus influenzae 1997 1998 1999 Haemophilus parainfluenzae 40 37 Ce eppi resistenti (%) 30 20 10 16 12 5 4 8 13 26 11 6 9 20 17 5 13 22 2 10 9 12 6 9 16 20 0 Italia Nord Centro Sud Italia Nord Centro Sud Nicoletti et al., 2000 scaricato da www.sunhope.it 35
Resistenze nel mondo ai betalattamici in ceppi di Haemophilus influenzae SENTRY Antimicrobial Surveillance Program, 1997-1999 Amoxicillina Amoxi/clav Cefprozil Cefixime Cefuroxime 32 31,5 27 Ce eppi resistenti (%) 24 16 10 10 12,5 11,8 16,2 8 0 0,3 0,1 0,6 0,3 0 0,9 0 1,1 0 0 0,2 1 0 0 0 1,4 0 0,4 Stati Uniti Canada America Latina Europa Asia Pacifico N. ceppi: 8252; break point di sensibilità secondo NCCLS Hoban et al., 2001 Resistenze nel mondo ai -lattamici in ceppi di Moraxella catarrhalis SENTRY Antimicrobial Surveillance Program, 1997-1999 100 Amoxicillina Amoxi/clav Cefprozil Cefixime Cefuroxime 96 96,9 97,6 95,3 97 Ceppi resistenti (%) 12 8 4 3,4 0 0,1 0,8 0,30,1 0 0,6 0 0 0,4 0 0 0 0 0 0 0,2 0 0 0 Stati Uniti Canada America Latina Europa Asia Pacifico N. ceppi: 8252; break point di sensibilità secondo NCCLS Hoban et al., 2001 scaricato da www.sunhope.it 36
Produzione di -lattamasi in M. catarrhalis saggiati in Italia 1998 1999 100 80 84 87 81 88 75 77 98 92 (%) 60 40 20 0 Italia Nord Centro Sud Nicoletti et al., 2000 Emergence and epidemiology of fluoroquinolone-resistant Streptococcus pneumoniae strains from Italy: report from the SENTRY Antimicrobial i Surveillance Program (2001 2004) Lalitagauri M. Deshpande, Helio S. Sader, Eugenio Debbia, Giuseppe Nicoletti, Giovanni Fadda and Ronald N. Jones Diagnostic Microbiology and Infectious Disease, 2006 scaricato da www.sunhope.it 37
INDAGINI DI LABORATORIO Immunochromatographic urinary antigen test t for S.Pneunoniae Immunochromatographic urinary antigen test for L.Pneumophila serogroup 1 Serologic Tests Molecular Tests (real-time quantitative PCR) scaricato da www.sunhope.it 38