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Diagnostik und Therapie der Beatmungspneumonien M. Raffenberg, H. Lode Zentralklinik Emil von Behring, Berlin-Zehlendorf Lungenfachklinik Heckeshorn akadem.

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Präsentation zum Thema: "Diagnostik und Therapie der Beatmungspneumonien M. Raffenberg, H. Lode Zentralklinik Emil von Behring, Berlin-Zehlendorf Lungenfachklinik Heckeshorn akadem."—  Präsentation transkript:

1 Diagnostik und Therapie der Beatmungspneumonien M. Raffenberg, H. Lode Zentralklinik Emil von Behring, Berlin-Zehlendorf Lungenfachklinik Heckeshorn akadem. Lehrkrankenhaus der FU Berlin

2 Inzidenz: % bzw. 5-34/1000 Tage VAP-Rate: 1-3 % pro Beatmungstag ICU-Therapie:+6d - +13d Beatmung:+10d - +23d Letalität: % Epidemiologie der Beatmungspneumonie Craven DE, Steger KA. Epidemiology of nosocomial pneumonia. Chest 1995:108:1S-16S Fagon JY et al. Nosocomial pneumonia and mortality among pts in ICU. JAMA 1996;275:866-9 Cook DJ et al. Incid. of and risk factors for VAP in critically ill pts. Ann Intern Med 1998;129: Fagon JY et. al. Nosocomial Pneumonia. in: Schoemaker. Crit Care Med. 4th Ed. 2000:

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4 The Mechanically Ventilated Patient mod. Francoli. CMI 1997; 3(1) environment other patients nursing stuff endogenous flora distant focus of infection blood catheter, tube oropharyngeal flora microaspiration lower respiratory tract pneumonia enteral nutrition stomach, bowel air direct contact

5 Supine Body Position as a Risk Factor for Nosocomial Pneumonia in Mechanically Ventilated Patients: A Randomized Trial (I) Background:Can the incidence of nosocomial pneumonia be reduced by a semirecumbent body position in ICU-patients? Design:Prospective randomized study in 130 patients at 2 ICU in Hospital Clinic Barcelona. Methods:Analysis of clinically suspected and micro- biologically confirmed nosocomial pneumonia (clinical + quantitative bacteriological criteria). Drakulovic MB, Torres A et al. Lancet 1999; 354:

6 Supine Position in Mechanically Ventilated Patients (II) Results: Clinic. suspected nosocomial pneumonia - semirecumbent group: 3/39 (8%) - supine group: 16/47 (34%); p = Microbiologically confirmed pneumonia - semirecumbent group: 2/39 (5%) - supine group: 11/47 (23%); p = Highest risk: Supine body position plus enteral nutrition: 14/28 (50%) Conclusions: Semirecumbent body position reduces frequency and risk of nosocomial pneumonia especially in patients who receive enteral nutrition. Drakulovic MB, Torres A et al. Lancet 1999; 354:1851

7 Infektionsraten bei nicht invasiver Beatmung Pneumonie % Ergebnisse randomisierter kontrollierter Studien Brochard 1995 n=43/42 Kramer 1995 n=16/15 Antonelli 1998 n=32/32 Wood 1998 n=16/11 Confalonieri 1999 n=28/28 Antonelli 2000 n=20/20 Nava 1998 n=25/25

8 Ventilator-Associated Pneumonia Variables Independently Associated with VAP by Log. Regress. Analysis VariableAdjustedOR95% Clp OSFI > < Pat. age > 60 yrs Prior antibiotics Pat. head position Kollef MH. JAMA 1993; 270:1965

9 Ventilator-associated Pneumonia Caused by Potentially Drug-resistant Bacteria Design:Risk factor analysis of 135 consecutive episodes of VAP in a single ICU over 25 months in terms of potentially drug- resistant bacteria Technique: VAP was diagnosed by PSB and BAL Results:77 VAP by potent. resist. bacteria 58 VAP by other organisms Trouillet JL, Chastre J et al. AJR CCM 1998; 157:531

10 Ventilator-associated Pneumonia Results: Potentially-resistant bacteria: S. aureus (MRSA), P. aeruginosa, A. baumannii, S. maltophilia Riskfactors: Duration of MV (> 7d/OR=6.0) Prior antibiotic use (OR=13.5) Prior use of broad - sp. ant. (OR=4.1) Conclusions: Considering these risk factors may provide a more rational basis for selecting the initial therapy of VAP Trouillet JL et al. AJR CCM 1998; 157:531

11 Characteristics of Patients Who Died from VAP Case/Age[yr]/ Sex Diagnosis pATBMicroorganisms 1 / 43 / M Heart transplant YesAspergillus species, Candida sp. 2 / 59 / M COPD YesPseudomonas aeruginosa 3 / 33 / M Heart transplant YesP. aeruginosa, S marcescens 4 / 76 / M CET YesP. aeruginosa 5 / 75 / M Cardiogenic shock YesAspergillus species 6 / 62 / M CAP YesP. aeruginosa, S. marcescens 7 / 70 / M COPD Yes Acinetobacter, A. calcoacetius 8 / 74 / M COPD YesP. aeruginosa 9 / 71 / F COPD YesA. calcoacetius 10 / 46 / M Asthma Yes P. aeruginosa 11 / 65 / M Cardiac surgery YesP. aeruginosa 12 / 72 / F Pancreatitis YesP. aeruginosa 13 / 54 / M Septic shock YesProteus mirabilis 17 / 51 / M Multiple trauma NoS. marcescens 18 / 71 / M Thoracic surgery NoP. aeruginosa Rello J et al. Chest 1993; 104:1230

12 Ventilator-Associated Nosocomial Pneumonia 1. Protected specimen brushing (PSB) - No wedging into a peripheral position - >10 3 CFU/ml significant bacterial level International Consensus Conference, Memphis, May Chest 102(1) 1992 Recommendations for Diagnostic Bronchoscopic Techniques 2. Bronchoalveolar lavage (BAL) - Total amount of fluid >140 ml - >10 4 CFU/ml significant bacterial level Controversy: Diagnostic value of PSB/BAL in patients receiving antibiotics

13 Evaluation of Diagnosis of Pneumonia Sensitivity [%] Specificity [%] authors year PSB BAL PSB BAL Torres Marquette Chastre Papazian Lode H et al. Crit Care Clinics 1998; 14(1): Operative values of protected specimen brush (PSB) and broncho- alveolar lavage (BAL) in four recent studies systematically referring to histology

14 Invasive and Noninvasive Strategies for Management of Suspected Ventilator-associated Pneumonia (I) Background: Optimal management of patients with clinically suspected VAP is a controversial issue Design: Multicenter, randomized trial in 31 french ICU including 413 patients Interventions:- Invasive Management Bronchoscopy with quantitative cultures of BAL or PSB - Noninvasive Management Clinical criteria and nonquantitative analysis of endotracheal aspirates Fagon JY et al. Ann Intern Med 2000; 132:621-30

15 Actuarial 28-day Survival Among 413 Patients Assigned to the Invasive (solid line) or Clinical (dashed line) Management Strategy Fagon JY et al. Annals of Internal Medicine 2000; 132:621-30

16 Invasive and Noninvasive Strategies for Management of Suspected Ventilator-associated Pneumonia (II) Measurements:- Death from any cause - Quantification of organ failure - Antibiotic use at 14 / 28 days Interventions:- Reduced mortality at day 14 (16.2% vers. 25.8%; p = 0.02) - Decreased Sepsis-related Organ Failure Assessm. Score on day 3 / 7 - Decreased antibiotic use on day 14 / 28 (11.5 vers. 7.5 antib.-free days on day 28) Fagon JY et al. Ann Intern Med 2000; 132:621-30

17 Nosokomiale Pneumonie Diagnose und Therapie nach Singh et al (2000) Chastre J, Fagon JY (2002) AJRCCM 165: Klinischer Verdacht auf Infektion Erneute Bewertung am 3. Tag: CPIS > 6 Erneute Bewertung am 3. Tag: CPIS > 6 Antibiotika für Tage ja Ciprofloxacin absetzen nein 3 Tage Ciprofloxacin nein Keine weitere Untersuchung, beobachten nein Als Pneumonie behandeln ja CPIS (clinical pulmonary infection score): > 6 ja

18 Nosokomiale Pneumonie Diagnose und Therapie invasive Strategie Klinischer Verdacht auf Infektion ja sofort gezielte AB-Therapie Keine weiteren Untersuchungen beobachten nein Direktpräparat: Bakterien? sofort PSB/BAL ja nein Beobachten, anderen Herd suchen Bakterienkultur positiv? nein ja Beobachten, anderen Herd suchen gezielte AB-Therapie ja Schwere Sepsis? nein Bakterienkultur positiv? Antibiotika anpassen ja AB fortsetzen od. anpassen, anderen Herd suchen nein Chastre J, Fagon JY (2002) AJRCCM 165:

19 Invasives Vorgehen: Vorteile Höhere Sicherheit bei der Diagnosestellung Durch Erregernachweis zielgerichtete Antibiotikatherapie möglich Kontaminationen mit der Flora aus den oberen Atemwegen werden vermieden Bewirkt restriktiven Einsatz von Antibiotika und dadurch eine geringere Resistenzentwicklung Weniger Todesfälle Schnellere Normalisierung von Organdysfunktionen, Geringerer Antibiotikaverbrauch Fagon et al (2000) Ann Intern Med

20 Invasives Vorgehen: Nachteile Invasive Methoden mit Risiken behaftet Kosten Technische Grenzen der Kulturverfahren Verzögerung der initialen Antibiotikatherapie Bei einem negativen Resultat, das evtl. falsch ist, erhält der Patient keine Therapie Ergebnis erst verfügbar, wenn der Verlauf der Infektion nicht mehr beeinflusst werden kann Fagon et al (2000) Ann Intern Med

21 Diagnosis of Nosocomial Pneumonia Bronchoscopy: PSB or BAL quantitative moderatesevere VAP (sputum), serology, blood cultures, Legionella-antigen therapy progress Nosocomial Pneumonia

22 Bacteriology of Hospital-Acquired Pneumonia Early-Onset Late-Onset Pneumonia Pneumonia Other S. Pneumoniae P. aeruginosa Anaerobic bacteria H. Influenzae Enterobacter spp. Legionella pneumophila Moraxella catarrhalis Acinetobacter spp. Influenza A and B S. aureus K. pneumoniae Respiratory syncitial virus Aerobic gram-negative bacilli* S. marcescens Fungi E. coli Other gram-negative bacilli S. aureus** Francioli et al.Clin Microbiol Infect 1997; 3(suppl 1):61-76 *in patients with risk factors, **including methicillin-resistant S. aureus

23 Kennzahlen Untersuchungszeitraum: Juli 1997 bis Juni Aufnahmen auf die ITS (8 Betten) 111 Pat. in die Studie eingeschlossen (31 w, 80 m, 58 ±13,3 J.) 65/111 Pat. (59%) mit signifikantem Nachweis pathogener Erreger in den Untersuchungsmaterialien. 16 Pat. (14%) mit Stenotrophomonas-Nachweis (2 w, 14 m) im Bronchialsekret (68%), Sputum (19%), Pleuraexsudat (13%) Stenotrophomonas maltophilia Studie

24 Stenotrophomonas-Infektionen auf der Intensivstation - Epidemiologie A´Court et al. : SMA verantwortlich für 5% der nosokomialen Pneumonien auf der ITS Thorax 1992,47, Ibrahim EH, Ward S, Sherman G, Kollef MH.: Vergleichende Analyse von Intensivpatienten mit early-onset und late-onset Pneumonien Intensivpatienten (internistisch und chirurgisch) 420 nosokomiale Pneumonien (11,5%) 235 early onset185 late onset pneumonia P. aeruginosa (38,4%) ORSA (21,1%) S. maltophilia (11,4%)OSSA (10,8%) Gesamtletalität:41% Chest 2000,117,

25 Antibiotic Therapy in Nosocomial Pneumonia MonotherapyAntibiotic combination Lower cost Higher cost Lower risk of side-effects Possible lower risk of emergence of resistance? No antagonistic effect Synergistic effect of antibiotics No pharmacologic interactions Wider spectrum Equal efficacy? Lower antibiotic dose versus

26 Antibiotic Monotherapy in HAP Reference Drugs Results Comments (Cure/Improv.) R.D. Manji et al Cefoperazone Cefoper.: 87% Lower costs AJM 1988 versus Combin.: 72% for monotherapy Cefazol/Gentamycin M.P. Fink et al Ciprofloxacin Ciprofloxacin: 64% Imipenem: 6% seizures AAC 1994 versus Imipenem: 56% Ciprofloxacin: 1% Imipenem A. Cometta etal Imipenem Imipenem: 80% Combination: 11 AAC 1994 versus Combination: 86% nephrotoxic reaction Imipenem/Netilmicin E. Rubinstein, Ceftazidime Ceftazidime: 85% Combination: 9 H. Lode et al versus Combination: 77% nephrotoxic reaction CID 1995 Ceftriaxone/Tobramycin

27 Combination Therapy as a Tool to Prevent Emergence of Bacterial Resistance Design:Overview of experimental data analysing antimicrobial mono-versus combination therapy. Results:In vitro Pk and animal data indicate that emergence of resistance with combination therapy is less common. Problems:- Demonstrated only in P. aeruginosa infections - No strong clinical trials Mouton JW. Infection 1999

28 Mean Change (log values) of MIC for Ceftazidime of Pseudomonas aeruginosa During Monotherapy or Combined With Tobramycin in a in vitro Pharmacokinetic Model Mouton JW h16 h 8 h0 h mean increase factor MIC ceftazidime ceftazidime + tobramycin

29 Clinical Indications of Combinations Difficult to treat Gram-nagatives Clinical Arguments Avoid mutation Obtain synergistic effect Possible prevention of the emergence of resistance Extend the spectrum of antibacterial activities: against enterococci (using penicillin) against anaerobes (using metronidazole) Bergogne-Bérézine. Phoenix 1995 Enterobacter Pseudomonas Acinetobacter

30 PK/PD Parameters: A First Sight Serum Concentration varying with time Peak Through Area under the curve time concentration peak through area under the curve

31 Forrest A et al. Antimicrob Agents Chemother 1993;37: AUIC Prediction of Clinical and Microbiological Outcome in RTI

32 Pharmacodynamic Evaluation of Factors Associated With the Development of Bacterial Resistance in Acutely Ill Patients During Therapy Design:Analysis of 107 pat. suffering from LRTI; 128 pathogens and 5 antimicrobial regimes. Parameters:- MIC - before/after treatment - AUC PK/PD model (Hill equation) Thomas JK et al. AAC 1998; 42:521-27

33 AUIC versus Resistance Thomas JK et al. AAC 1998

34 Scheduled Change of Antibiotic Classes (I) Study design: Prospective before - after study Patients: 680 with cardiac surgery Location: ICU-St. Louis, Missouri Barnes-Jewish Hospital (900 beds) Intervention: During 12-months period (8/95-8/96) empiric treatment - first 6-months period: ceftazidime - second 6-months period: ciprofloxacin Kollef MH. AJRCCM 1997; 156:1040 A strategy to decrase the incidence of ventilator-associated pneumonia

35 Kollef et al.AJRCCM 1997:165:

36 Scheduled Change of Antibiotic Classes (II) Incidence of VAP: Before 11.6% (n = 327) After 6.7% (n = 353) VAP with resist. GNB:4.0% versus 0.9% Bacteremia due to ARGNB: 1.7% versus 0.3% Conclusion: These data suggest that a scheduled change of antibiotic classes can reduce the incidence of VAP attributed to ARGNB. Kollef MH. AJRCCM 1997; 156:1040 Results

37 Group 1Group 3 Group 2 mild to moderate Classifying Patients With Hospital-acquired Pneumonia Consensus Statement of the American Thoracic Society: Am J Respir Crit Care Med 1996; 153: Severity of illness severe no risk factors with risk factors Group 1 late onset early onset onset any time

38 Patients with mild to moderate hospital-acquired pneumonia, no unusual risk factors, onset any time or patients with severe hospital acquired pneumonia with early onset* Core organismsCore antibiotics Enteric gram-negative bacilliCephalosporin (Non-Pseudomonal)second generation or Enterobacter spp.Nonpseudomonal third generation E. coli Klebsiella spp.Beta-lactam / beta-lactamase- Proteus spp. inhibitor combination Serratia marcescens Haemophilus influenzaeIf allergic to penicillin: S. aureus (Methicillin-sensitive)Fluoroquinolone or Streptococcus pneumoniaeClindamycin + aztreonam Group 1 *Excludes patients with immunosuppression Consensus Statement of the American Thoracic Society: Am J Respir Crit Care Med 1996; 153:

39 Patients with mild to moderate hospital-acquired pneumonia, with risk factors, onset any time* Core organisms plus:Core antibiotics plus: AnaerobesClindamycin (recent abdomial surgery)or beta-lactam / beta- lactamase- witnessed aspiration)inhibitor (alone) Staphylococcus aureus+/- Vancomycin (coma, head trauma, diabetes(until methicillin- resistant mellitus, renal failure)S. aureus is ruled out) LegionellaErythromycin +/- Rifampicin ** (high dose steroids) Pseudomonas aeruginosaTreat as severe hospital-acquired (prolonged ICU stay, steroids,pneumonia (Group 3) antibiotics, structural lung disease) *Excludes patients with immunosuppression; ** Rifampicin may be added if Legionella species is documented Consensus Statement of the American Thoracic Society: Am J Respir Crit Care Med 1996; 153: Group 2

40 Patients with severe hospital-acquired pneumonia, with risk factors, early onset or patients with severe hospital acquired pneumonia with late onset* Core organisms plus:Therapy P. aeruginosaAminoglycoside or ciprofloxacin Acinetobacter spp. plus one of the following: Consider MRSA Antipseudomonal penicillin beta-lactam / beta-lactamase inhibitor Ceftazidime or cefoperazone Imipenem Aztreonam** +/- Vancomycin *Excludes patients with immunosuppression ** Aztreonam efficacy is limited to enteric gram-negative bacilli and should not be used in combination with aminoglycoside if gram-positive or H. influenzae infection is of concern Consensus Statement of the American Thoracic Society: Am J Respir Crit Care Med 1996; 153: Group 3


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