LE GIORNATE LAZIALI DELL’APPROPRIATEZZA IN MEDICINA DI LABORATORIO 2^ Edizione Roma, 20 novembre 2013 ACO San Filippo Neri Le emoculture: indicazioni di appropriatezza prescrittiva indirizzata dal problema diagnostico Bruno Mariani [email protected] RUOLO CLINICO DELLE EMOCOLTURE L’emocoltura rappresenta un esame di laboratorio fondamentale per l’identificazione dell’agente eziologico dal sangue per la diagnosi di infezioni sistemiche, quali infezioni cardiache come endocarditi e pericarditi, infezione da cateteri endovascolari, infezioni endoaddominali, infezioni della cute e tessuti molli, permettendo l’instaurazione precoce di una efficace terapia antimicrobica. Altro vantaggio è il rapporto beneficio/costo se si tiene conto della gravità delle condizioni del paziente che viene sottoposto a tale indagine. Health Protection Agency (2005). Investigation of blood cultures (for organisms other than mycobacterium species).National Standard Method BSOP 37 Emissione 5. http://www.hpastandardmethods.org.uk/pdf_sops.asp. CLASSIFICATION OF BACTEREMIA • • • • Classified by Site of Origin Classified by Place of Acquisition Classified by Duration Classified by Causative Agent Betts,Chapman,Penn: «A pratical approach to infectious diseases» 2003, 5° Ed.- Philadelphia, USA CLASSIFICATION BY SITE OF ORIGIN • Primary Bacteremia – Blood stream or endovascular bacterial invasion with no preceding or simultaneous site of infection with the same microorganism • Secondary Bacteremia – Isolation of a microorganism from blood as well as other site(s) • Fever of Unknown Origin (FUO) – Source unknown July 2013 CDC/NHSN Protocol Clarifications CDC/NHSN Surveillance Definitions for Specific Types of Infections http://www.cdc.gov/nhsn/PDFs/pscManual/17pscNosInfDef_current.pdf Le batteriemie primarie si realizzano in assenza di una fonte d’infezione evidente. (inoculazione diretta) Secondo le definizioni e le raccomandazioni dei “Centers for Disease Control and Prevention” (CDC), le batteriemie primarie comprendono anche le infezioni che insorgono come complicanza dovuta alla presenza di catetere vascolare. July 2013 CDC/NHSN Protocol Clarifications CDC/NHSN Surveillance Definitions for Specific Types of Infections Le batteriemie secondarie sono in relazione a infezioni presenti in altri siti anatomici (polmoniti, infezioni urinarie, ferite infette, ascessi, etc). Ne consegue che lo stesso microrganismo e’ presente sia a livello del sito di infezione che nel sangue. July 2013 CDC/NHSN Protocol Clarifications CDC/NHSN Surveillance Definitions for Specific Types of Infections La pseudobatteriemia è definita come la presenza di un’emocoltura positiva per uno o più microrganismi la cui crescita non si correla con l’evidenza clinica. Questa condizione è spesso chiamata “contaminazione”. Il riconoscimento delle pseudobatteriemie è estremamente importante in quanto fuorvianti per il paziente perche’ causa di ulteriori prelievi di sangue , terapie antibiotiche inutili e una spesa sanitaria inutile. Reese and Betts, 2003, 5° Ed.- Philadelphia, USA CLASSIFICATION BY PLACE OF ACQUISITION • Community-acquired – Defined as a positive blood culture taken on or within 48 hours of admission • Health-care acquired/Nosocomial – Defined as occurring 72 hours post admission July 2013 CDC/NHSN Protocol Clarifications CDC/NHSN Surveillance Definitions for Specific Types of Infections CLASSIFICATION BY DURATION • Transient – Comes and goes – Usually occurs after a procedural manipulation (ex. Infected tissues, Dental procedures) • Intermittent – Can occur from abscesses at some body site that is “seeding” the blood • Continuous Bacteremia – Organisms from an intravascular source that are consistently present in bloodstream Microbiological Findings and BSIs • CID 2009:48 (Suppl 4) • S239 Red and green arrows indicate the presence and absence, respectively, of bacteria in blood cultures obtained at different time points (in minutes, unless hours [h] is specified). Microbiological Findings and BSIs • CID 2009:48 (Suppl 4) • S239 (Engineering, Montana State University-Bozeman) Common sites of biofilm infection Once biofilm reach the bloodstream they can spread to any moist surface of the human body. The biofilm life cycle in three steps: attachment, growth of colonies (development), and periodic detachment of planktonic cells Intermittent Bacteremia Center for Biofilm Engineering, Montana State University-Bozeman Otitis media, or inflammation of the inner ear, caused by biofilm Center for Biofilm Engineering, Montana State University-Bozeman CLASSIFICATION BY CAUSATIVE AGENT • • • • • Gram positive bacteremia Gram negative bacteremia Anaerobic bacteremia Polymicrobial bacteremia Invasive candidiasis Reese and Betts, 2003, 5° Ed.- Philadelphia, USA Bacteremia Complications • Septic shock – Results from body’s reactions to bacterial bi-products • Endotoxins: lipopolysaccharide • Exotoxins – Disrupts many body functions • Hemodynamic changes, decreased tissue perfusion and compromised organ & tissue function SCCM/ACCP/ Consensus Conference. Definitions for sepis and organ failure 1992. SIRS La SIRS (Sindrome da Risposta Infiammatoria Sistemica) definisce la risposta infiammatoria aspecifica dell’organismo caratterizzata da cause infettive e non infettive che determinano la liberazione di sostanze endogene: i mediatori infiammatori. La diagnosi di SIRS richiede la presenza di almeno due dei seguenti segni clinici: temperatura > 38 °C o < 36 °C frequenza cardiaca > 90 bpm frequenza respiratoria > 20 apm o PaCO2 < 32 mmHg numero di globuli bianchi > 12.000/mm3, < 4.000/mm3 o presenza > 10% di forme immature (band) SCCM/ACCP/ Consensus Conference. Definitions for sepis and organ failure 1992. SEPSI E’ caratterizzata dalla massiccia produzione di elevate quantità di fattori infiammatori (PGs, TNFs, IL1, IL6, IL8, IL12) Le citochine proinfiammatorie innescano: • alterazione degli endoteli vascolari con collasso ipotensivo (sepsi ipotensiva) • la cascata della coagulazione con la formazione di diffuse coagulazioni intravasali (DIC: disseminated intravascular coagulation) • estesi fatti emorragici con la grave compromissione di diversi organi (Shock settico) ed effetti fatali per il paziente Mosnier at al. Blood 2007 Critical Care Medicine- February 2013 • Volume 41 • Number 2 Table 5. Recommendations: Initial Resuscitation and Infection Issues B. Screening for Sepsis and Performance Improvement 1. Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy (grade 1C). 2. Hospital–based performance improvement efforts in severe sepsis (UG). C. Diagnosis 1. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade 1C). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted (grade 1C). 2. Use of the 1,3 beta-D-glucan assay (grade 2B), mannan and anti-mannan antibody assays (2C), if available and invasive candidiasis is in differential diagnosis of cause of infection. 3. Imaging studies performed promptly to confirm a potential source of infection (UG). Critical Care Medicine- February 2013 • Volume 41 • Number 2 SOURCE CONTROL 1. We recommend that a specific anatomical diagnosis of infection requiring consideration for emergent source control (eg, necrotizing soft tissue infection, peritonitis, cholangitis, intestinal infarction) be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible (grade 1C). 4. If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established (UG). Critical Care Medicine- February 2013 • Volume 41 • Number 2 EVOLUZIONE SEPSI: SHOCK SETTICO Termine che definisce una serie di eventi fisiopatologici ai danni del sistema cardiocircolatorio che determinano la sindrome da insufficienza multipla di organi (MOFS) che può provocare il decesso del paziente. SCCM/ACCP/ Consensus Conference. Definitions for sepis and organ failure 1992. Bone et al. Chest 1992;101:1644 Le dimensioni del problema Casi accertati stabiliscono che in tutto il mondo l'incidenza di sepsi è 1,8 milioni di casi ogni anno, ma questo numero è sottostimato per una controversa diagnosi che prevede diversi criteri di valutazione nei differenti paesi. “Surviving Sepsis Campaign” stima che, con una incidenza del 3 ‰, il numero reale dei casi ogni anno raggiunge i 18 milioni con un tasso di mortalità di quasi il 30% diventando cosi’ una delle principali cause di morte *1,2+. L'incidenza è destinata ad aumentare con l'invecchiamento della popolazione, essendo gli anziani i più colpiti [1]. I costi della sepsi sono in media US $ 22 000 per paziente e il suo trattamento ha un grande impatto sulle risorse finanziarie degli ospedali: negli Stati Uniti ammonta complessivamente a circa 16,7 miliardi dollari ogni anno [1]. Il costo del trattamento di un paziente con sepsi ricoverato in ICU è sei volte maggiore di quella di un paziente senza sepsi [3]. 1. Angus DC, et all: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001, 29:1303-1310. 2. Hoyert DL, Anderson RN: Age-adjusted death rates: trend data based on the year 2000 standard population. Natl Vital Stat Rep 2001, 49:1-6. 3. Edbrooke DL, et all: The patient-related costs of care for sepsis patients in a United Kingdom adult general intensive care unit. Crit Care Med 1999, 27:1760-1767. Mortalità per sepsi in Italia In uno studio epidemiologico pan-Europeo* del 2006, la mortalità intraospedaliera dei pazienti con sepsi grave/shock settico nelle 24 ICU italiane partecipanti alla ricerca era del 45%. Secondo studi recenti, inoltre, l’incidenza della condizione è in aumento per effetto dell’invecchiamento della popolazione e della conseguente maggior comorbidità, del crescente numero di pazienti infettati da microrganismi resistenti al trattamento, dell’aumento del numero di pazienti immunocompromessi o che subiscono interventi chirurgici ad alto rischio. • Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units : Results of the SOAP study. Crit Care Med 2006;34:344353. SEPSI: Fattori di rischio • Fattori epidemiologici: aumento dell’età media e delle patologie associate ad un maggior rischio di infezioni (neoplasie, AIDS, interventi chirurgici, malattie croniche) • Fattori iatrogeni: diffuso uso di mezzi invasivi (cateteri venosi centrali, ventilazione meccanica), antibiotici a largo spettro e corticosteroidi • Fattori ambientali: mancanza di barriere fisiche tra i pz e inosservanza delle norme igieniche Diagnosi microbiologica Emocolture: strumento essenziale per la diagnosi di sepsi. Emocolture realmente positive costituiscono il miglior criterio per la definizione di sepsi e della sua causa. Purtroppo in un rilevante numero di pazienti con sepsi le emocolture sono negative, molti fattori ostacolano la resa diagnostica delle emocolture: Volume prelievo di sangue. Numero delle emocultere. Tempo di raccolta prelievi. Durata incubazione flaconi. Contesto clinico. EMOCOLTURE: QUANDO ESEGUIRLE? Febbre (> 38°C) Ipotermia (< 36°C) Leucocitosi(> 10.000/μl) Granulocitopenia(< 1.000/μl) Ipotensione Infezioni , sospette o comprovate (meningiti, polmoniti, endocarditi, ascessi, SSTIs, etc..) Insufficienza renale Alterato stato mentale Pazienti immunoconpromessi CUMITECH Blood Cultures IV, ASM Press 2005 Mylotte and Tayara EJCMID 2000 Indications for Blood Cultures Indications Cultures PRINCIPALI SITUAZIONI CLINICHE IN CUI È IMPORTANTE ESEGUIRE IL TEST E % ATTESA DI POSITIVITÀ. Endocarditi e infezioni endovascolari Epiglottite acuta Meningite batterica Pielonefrite ascendente Osteomielite ematogena Polmonite batterica Ascessi endoaddominali Febbre di natura non determinata 85-95 % 80-90 % 50-80 % 30-50 % 30-50 % 5-30 % varia varia Estratto da:”TRACCIA PER LA FORMULAZIONE DI LINEE GUIDA PER L’EMOCOLTURA” Elaborazione a cura di AMCLI (CoSBat) e APSI” Health Protection Agency (2005). Investigation of blood cultures (for organisms other than mycobacterium species). National Standard Method BSOP 37 Emissione 5. Downloaded from http://cid.oxfordjournals.org/ at IDSA member on July 11, 2013 A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)a Consensus guidelines and expert panels recommend peripheral venipuncture as the preferred technique for obtaining blood for culture based on data showing that blood obtained in this fashion is less likely to be contaminated than blood obtained from an intravascular catheter or other device. Several studies have documented that iodine tincture, chlorine peroxide, and chlorhexidine gluconate (CHG) are superior to povidone-iodine preparations as skin disinfectants for blood culture. Iodine tincture and CHG require about 30 seconds to exert an antiseptic effect compared with 1.5–2 minutes for povidone-iodine preparations. CHG is NOT recommended for use in infants less than 2 months of age. Clinical Infectious Diseases Advance Access published July 10, 2013 A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)a Clinical Infectious Diseases Advance Access published July 10, 2013 Washington, J. A. II 1975. Mayo Clin. Proc. 50:91–98. Weinstein, M. P., et al. 1983. Rev. Infect. Dis. 5:35–53. Cockerill, F. R., et al. 2004. Clin. Infect. Dis. 38:1724–1730. Lee, A. S., et al. 2007. J. Clin. Microbiol. 45:3546–3548 SUSPECTED CATHETER SEPSIS 1. Draw two blood culture sets. 2. One set is obtained from the suspected catheter. 3. At the same time, a second set must be from a separate peripheral site. 4. Time of collection should be noted for both specimens. 5. If the catheter is removed, a section of about 1 inch in length from an intradermal portion is to be cut aseptically and sent to Microbiology in a dry sterile container. Do not send catheter tip without sending concomitant blood cultures. In such cases the catheter tip will not be cultured. Clinical Infectious Diseases Advance Access published July 10, 2013 Johns Hopkins Medical Microbiology Specimen Collection Guidelines – Updated 6/2013 ACUTE ENDOCARDITIS 1. Draw 2-3 culture sets from separate sites within 30 minutes of each other and before beginning antimicrobial therapy. 2. Begin therapy after cultures are obtained. SUBACUTE ENDOCARDITIS 1. Draw 2-3 blood culture sets on day 1, spaced 30-60 minutes apart. This may help to document a continuous bacteremia. 2. If all are negative additional sets can be drawn on days 2 and 3 (no more than 4 sets in a 24 hour period). 3. Immediate antibiotics are less important than establishing a specific microbial diagnosis. C. I. D.: July 10, 2013 J. H. M. M.: Updated 6/2013 Blood cultures are the preferred sample for the diagnosis of epiglottitis Clinical Infectious Diseases Advance Access published July 10, 2013 LOWER RESPIRATORY TRACT INFECTIONS Clinical Infectious Diseases Advance Access published July 10, 2013 Lacroix et al. Critical Care 2013, 17:R24 Results: We included 54 patients with HCAP. Pathogens were identified in 46.3% of cases using mini-BAL and in 11.1% of cases using blood cultures (P <0.01). When the patient did not receive antibiotic therapy before the procedure, pathogens were identified in 72.6% of cases using mini-BAL and in 9.5% of cases using blood cultures (P <0.01). We noted multidrugresistant pathogens in 16% of cases. All bronchoscopic procedures could be performed in patients without complications. INTRA-ABDOMINAL INFECTIONS Blood cultures are rarely positive in cases of PDAP Clinical Infectious Diseases Advance Access published July 10, 2013 Clinical Infectious Diseases Advance Access published July 10, 2013 BONE AND JOINT INFECTIONS Osteomyelitis may arise as a consequence of hematogenous seeding of bone from a distant site, extension into bone from a contiguous soft tissue infection, extension into bone from a biofilm on a contiguous prosthesis, or direct traumatic inoculation. Similarly, joint infections may develop by any of these routes, but occur most often by hematogenous seeding. From the perspective of pathophysiology, specific nature of infection and to at least some extent, clinical course, it is useful to classify bone infections based on pathogenesis. With joint infections, a classification scheme based on specific site of involvement and tempo of disease is most instructive; ie, acute versus chronic arthritis and septic bursitis. With few exceptions, bone and joint infections are usually monomicrobic. Rarely, such infections are polymicrobic Clinical Infectious Diseases Advance Access published July 10, 2013 BONE AND JOINT INFECTIONS blood cultures collected during febrile episodes are recommended for the evaluation of patients suspected of having secondary bacteremia or fungemia. Concomitant blood cultures are indicated for detection of some systemic agents of osteomyelitis and joint infections, but not for prosthetic joint infection. Clinical Infectious Diseases Advance Access published July 10, 2013 GENITAL INFECTIONS Clinical Infectious Diseases Advance Access published July 10, 2013 SKIN AND SOFT TISSUE INFECTIONS Blood cultures should be collected for detection of systemic disease secondary to the wound. SKIN AND SOFT TISSUE INFECTIONS Clinical Infectious Diseases Advance Access published July 10, 2013 SKIN AND SOFT TISSUE INFECTIONS Clinical Infectious Diseases Advance Access published July 10, 2013 SKIN AND SOFT TISSUE INFECTIONS Clinical Infectious Diseases Advance Access published July 10, 2013 Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases WHAT ARE THE BEST TESTS FOR DIAGNOSING CANDIDAEMIA? Clinical Microbiology and Infection ª2012 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18 (Suppl. 7), 9–18 TABLE 2. Summary of recommendations by Candida disease, specimen and test evaluated Disease Specimen Test Recommendation Candidaemia Invasive candidiasis Chronic disseminated candidiasis Blood Blood culture Essential investigation Serum Mannan/anti-mannan B-D-glucan Recommended Recommended Blood Blood culture Essential investigation Serum Mannan/anti-mannan B-D-glucan Recommended Recommended Blood Blood culture Essential investigation Serum Mannan/anti-mannan B-D-glucan Recommended Recommended Essential investigation means it must be done if possible. Recommended Technique is accurate in 50–70% of cases (reasonable number) BLOOD CULTURES (BC) ARE ESSENTIAL FOR DIAGNOSING CANDIDAEMIA The number of BC recommended in a single session is 3 set with a total volume varying according to the age of the patient: 40–60 mL for adults, 2–4 mL for children under 2 kg, 6 mL between 2 and 12 kg, and 20 mL between 12 and 36 kg. The timing for obtaining the BC is one right after the other from different sites, and venipuncture remains the technique of choice. A BC set comprises of 60 mL blood for adults obtained in a single session within a 30-min period and divided in 10-mL aliquots among three aerobic and three anaerobic bottles. The frequency recommended is daily when candidaemia is suspected, and the incubation period must be at least 5 days. Clinical Microbiology and Infection ª2012 ESCMID Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated Reviews Series). 2007 Microbiological Findings and BSIs • CID 2009:48 (Suppl 4) • S239 ULCERA DA PRESSIONE Viene definita ulcera da pressione, una lesione a livello tissutale causata da prolungata pressione e/o ripetuta frizione tra il piano d’appoggio e la superficie ossea di un soggetto immobilizzato per età avanzata e/o grave compromissione della funzionalità neuromotoria. Il fenomeno interessa la cute, il derma e gli strati sottocutanei, fino a coinvolgere, nei casi più gravi, la muscolatura e le ossa. La compressione tissutale, indicata come principale fattore patogenetico, diventa lesiva quando supera la soglia dei 32 mmHg che rappresenta appunto il valore pressorio normale della circolazione capillare arteriosa. Lo stress meccanico e la concomitante riduzione della circolazione ematica locale, con conseguente ischemia e ipossia sono alla base dell’evoluzione necrotica delle ulcere. Donelli, et al Istituto Superiore di Sanità 2005, iii, 23 p. Rapporti ISTISAN 05/41 Le ulcere da pressione possono essere classificate secondo criteri clinici, topografici, e di stato. Nell’ambito dei criteri clinici l’European Pressure Ulcer Advisory Panel (EPUAP) e l’Agency for Health Care Policy and Research (AHCPR) forniscono indicazioni universalmente accettate che permettono di classificare le ulcere da pressione in quattro distinti stadi clinici ai quali l’NPUAP (National Pressure Ulcer Advisory Panel) ha aggiunto, per gli USA, due ulteriori stadi riguardanti il sospetto danno degli strati tissutali profondi e le lesioni non stadiabili R. Bernabei, et al: G Gerontol 2011;59:237-243 R. Bernabei, et al: G Gerontol 2011;59:237-243 SERVIZIO SANITARIO REGIONALE EMILIA-ROMAGNA Azienda Ospedaliero – Universitaria di Ferrara Altri dati epidemiologici emersi dallo studio Sedi interessate Sacro Occipite Trocantere Ischio Malleolo Tallone Altro 41,3% 1,4% 5,4% 2,7% 3,1% 35,9% 10,2% febbraio 2013 EMOCOLTURE 2° QUESTIONARIO SU ALCUNI ASPETTI RELATIVI ALLA APPLICAZIONE DELLA APPROPRIATEZZA PRESCRITTIVA, DI REFERTAZIONE e ORGANIZZATIVA struttura tipologia 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 MV BM MV BM BM BM BM BM BM BM BM MV BM BM BM BM LG LG Prelievo Clinica 1 0 1 1 0 1 1 0 0 1 1 0 0 0 0 1 0 1 1 0 0 1 0 0 0 1 0 0 0 0 P.S. EMATOL. DIALISI TERAPIA INTENSIVA CAMERA OPERAT. T.I. NEONAT. 1 1 1 0 1 1 0 1 0 0 1 0 0 1 1 1 0 0 1 0 1 0 0 0 1 0 1 0 0 0 0 1 0 1 1 1 1 0 0 1 0 0 1 0 0 1 1 1 1 1 1 0 1 1 1 1 0 0 1 1 0 1 0 1 1 1 1 1 1 1 1 1 1 0 1 1 0 1 1 1 1 0 1 0 1 0 0 0 0 0 1 0 0 0 0 1 LG Prelievo: linee guida concordate per le tecniche di prelievo delle Emocolture: asepsi, volume appropriato, etc. LG Clinica: protocolli concordati e condivisi delle Emocolture in base al sospetto diagnostico: numero e ritmo dei prelievi. 1 ; 0: Rispettivamente presenza, assenza. Ringraziamenti Ai colleghi dei Laboratori contattati che, compilando e restituendo il questionario, hanno reso possibile l’indagine. Un sentito ringraziamento ai colleghi del Gruppo di Lavoro AdAMeL: Dott.ssa Marina Vitillo (ACO S. Filippo Neri) Dott.ssa Maria Teresa Muratore (Osp. Belcolle VT-Del. Lazio SIBioC) Dott.ssa Fiorella Bottan (AO S. Giovanni Addolorata) Dott.ssa Alessandra Amendola (INMI Spallanzani) Dott. Francesco Bondanini (Osp. S. Pertini) Dott. M. Daniele Naim (Pol. Di Liegro) Prof. MaurizioMuraca (Osp. Ped. Bambino Gesù) Dott. Sebastiano La Rocca (ACO S. Filippo Neri) Ringrazio per i dati forniti la Dott.ssa Gabriella Parisi U.O.C Lab. Micr. e Virol. S. Camillo-Forlanini. Sez. Emocolture