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2 CID Sept 2016 (previous 2005). Littérature: jusque nov experts dont un Espagnol ( J Carratalà), un Allemand (S Ewig) et un Australien (JA Roberts). ATS/IDSA/SHEA/SCCM 25 items; 50 pages Sept 2017 (previous 2009). Littérature: jusque Sept experts dont 3 Américains: Michael S. Niederman, Marin Kollef and Richard Wunderink. ERS/ESICM/ESCMID/ALAT 7 items; 26 pages

3 CID Sept 2016 (previous 2005). Littérature: jusque nov experts dont un Espagnol ( J Carratalà), un Allemand (S Ewig) et un Australien (JA Roberts). ATS/IDSA/SHEA/SCCM 25 items; 50 pages Méthodologie: GRADE + PICO Sept 2017 (previous 2009). Littérature: jusque Sept experts dont 3 Américains: Michael S. Niederman, Marin Kollef and Richard Wunderink. ERS/ESICM/ESCMID/ALAT 7 items; 26 pages Méthodologie: GRADE + PICO Not for patients with immunosuppression.

4 USA: The major differences between this guideline and the 2005 version: 1. méthodologie GRADE/PICO 2. Disparition du concept HCAP Europe: not covered. There is increasing evidence from a growing number of studies that many patients defined as having HCAP are not at high risk for MDR pathogens.

5 USA: The major differences between this guideline and the 2005 version: 3. each hospital generate antibiograms to guide healthcare professionals with respect to the optimal choice of antibiotics: to decrease the unnecessary use of dual gram-negative and empiric methicillin-resistant Staphylococcus aureus (MRSA) antibiotic treatment. 4. short-course antibiotic therapy for most patients with HAP or VAP independent of microbial etiology. 5. antibiotic de-escalation.

6 the definitions of HAP and VAP, same as delineated in the 2005 guidelines: new lung infiltrate plus clinical evidence that the infiltrate is of an infectious origin, which include the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation. HAP is defined as a pneumonia not incubating at the time of hospital admission and occurring 48 hours or more after admission. VAP is defined as a pneumonia occurring >48 hours after endotracheal intubation. In fact, the concept of early vs late VAP should be based on hospital admission as the starting point, rather than intubation.

7 For VAP: colonization patterns in the upper and lower airways changed within the first 3 4 days from a communitylike to a typical nosocomial pattern. Others found that the threshold may also be extended to 7 days (Chastre et Trouillet 1998). the presence of risk factors for MDR should take precedence over the distinction between early- and late-onset pneumonia. With regard to the early vs late pneumonia concept, no data are available for HAP.

8 Most studies analyzed risk factors for MRSA colonization. patients with cystic fibrosis and bronchiectasis potential other risk factors, the published evidence is scarce and of low quality. FR pour MRSA ou Pseudomonas spécifique pour VAP ou HAP: voir + loin.

9 Early-onset HAP and VAP, defined as occurring within the first 4 days of hospitalization. Late-onset HAP and VAP ( 5 days of hospitalisation).

10 Diagnostic: VAP: Cultures of respiratory secretions would be obtained from all patients with suspected VAP before starting/changing ATB. HAP: We suggest noninvasive sampling with semiquantitative cultures to diagnose VAP (weak recommendation, lowquality evidence). Respiratory samples obtained noninvasively.

11 We recommend obtaining a lower respiratory tract sample (distal quantitative or proximal quantitative or qualitative culture) to focus and narrow the initial empiric antibiotic therapy. (Strong recommendation, low quality of evidence.) We suggest obtaining distal quantitative samples (prior to any antibiotic treatment) in order to reduce antibiotic exposure in stable patients with suspected VAP and to improve the accuracy of the results. (Weak recommendation, low quality of evidence.)

12 USA: The panel recognizes that invasive quantitative cultures will occasionally be performed by some clinicians. For patients with suspected VAP whose invasive quantitative culture results are below the diagnostic threshold for VAP, we suggest that antibiotics be withheld rather than continued (weak recommendation, very low quality evidence).

13 Remarks: Clinical factors should also be considered because they may alter the decision of whether to withhold or continue antibiotics. These include: the likelihood of an alternative source of infection, prior antimicrobial therapy at the time of culture, degree of clinical suspicion, signs of severe sepsis, and evidence of clinical improvement. Justifier dans dossier son attitude. Quid si AET < 10 5 CFU/mL? Stop?

14 approximately 15% of patients with VAP are bacteremic. at least 25% of positive blood cultures in suspected VAP patients are from a nonpulmonary source. blood culture results may provide further guidance for both antibiotic treatment and treatment de-escalation for HAP and VAP.

15 THE USE OF BIOMARKERS AND THE CLINICAL PULMONARY INFECTION SCORE TO DIAGNOSE VAP AND HAP: Clinical criteria alone Pas PCT serum PCT plus clinical criteria can diagnose HAP/VAP with a sensitivity and specificity of 67% and 83%, respectively: FN: 33% FP: 17%» Unnecessary ATB» Efforts to find the correct diagnosis may cease. Pas CRP

16 THE USE OF BIOMARKERS AND THE CLINICAL PULMONARY INFECTION SCORE TO DIAGNOSE VAP AND HAP: Clinical criteria alone Pas PCT serum PCT plus clinical criteria can diagnose HAP/VAP with a sensitivity and specificity of 67% and 83%, respectively: FN: 33% FP: 17%» Unnecessary ATB PCT: pas pour suivi ni pour stop si basé sur 7j de traitement. - USA et Europe.» Efforts to find the correct diagnosis may cease. Pas CRP

17 THE USE OF BIOMARKERS AND THE CLINICAL PULMONARY INFECTION SCORE TO DIAGNOSE VAP AND HAP: Clinical criteria alone Pas CPIS modifié Sensibilité 65% Spécificité 64% FN 35% FP 36%

18 VAT: Traitement: fever with no other recognizable cause, with new or increased sputum production, positive ETA culture (>10 6 CFU/mL) yielding a new bacteria, and no radiographic evidence of nosocomial pneumonia In patients with VAT, we suggest not providing antibiotic therapy (weak recommendation, lowquality evidence).

19 Traitement: VAT: fever with no other recognizable cause, with new or increased sputum production, positive ETA culture (>10 6 CFU/mL) yielding a new bacteria, and no radiographic evidence of nosocomial pneumonia In patients with VAT, we suggest not providing antibiotic therapy (weak recommendation, low-quality evidence). in conjunction with new systemic signs of infection plus worsening oxygenation and/or increasing ventilator settings, antibiotic treatment may be considered even in the absence of new or progressive persistent infiltrates on portable chest radiographs; the rationale for that is because of the high likelihood of a new VAP.

20 VAP: Traitement empirique: 1. We recommend that all hospitals regularly generate and disseminate a local antibiogram, ideally one that is specific to their intensive care population(s) if possible. 2. We recommend that empiric treatment regimens be informed by the local distribution of pathogens associated with VAP and their antimicrobial susceptibilities (or failing that, specific for ICU patients).

21 In patients with suspected VAP, we recommend including coverage for S. aureus, P. aeruginosa, and other gram negative bacilli in all empiric regimens (strong recommendation, low-quality evidence). VAP in the United States are S. aureus (approximately 20% 30% of isolates), P. aeruginosa (approximately 10% 20% of isolates), enteric gram-negative bacilli (approximately 20% 40% of isolates), and Acinetobacter baumannii (approximately 5% 10% of isolates)

22 CHU: VRI USI 2009 à 2014 Colonisation vs infection: 4793 bactéries Enterobactéries: 54,7% E coli: 17,3% Klebs spp: 18,6% Enterobacter spp: 18,1% H influenzae: 14,3% Non fermentants: 26,3% Pyo: 69% 18,2% du total Gram + : 19% St aureus: 75% 14,2% du total 23% = MRSA Pneumo: 21,4% MRSA AET USI 2016 et 2017: 20 et 25% LBA + St aureus: 4 en 2 ans: 100% MSSA

23 We suggest including an agent active against MRSA for the empiric treatment of suspected VAP only in patients with any of the following: a risk factor for antimicrobial resistance (Table 2), patients being treated in units where >10% 20% of S. aureus isolates are methicillin resistant, and patients in units where the prevalence of MRSA is not known. (weak recommendation, very low-quality evidence). MRSA: we recommend either vancomycin or linezolid. MSSA: piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem. Target: 95% empiric is active. CHU

24 We suggest prescribing 2 antipseudomonal antibiotics from different classes for the empiric treatment of suspected VAP only in patients with any of the following: a risk factor for antimicrobial resistance (Table 2), patients in units where >10% of gram-negative isolates are resistant to an agent being considered for monotherapy, and patients in an ICU where local antimicrobial susceptibility rates are not available (weak recommendation, low-quality evidence). CHU Target: 95% empiric is active.

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28 The rationale for including 2 gram-negative agents in empiric regimens is to increase the probability that at least one agent will be active against the patient s pathogen. The generally recommended compromise is to pair early and aggressive treatment with early and aggressive de-escalation.

29 We suggest using narrow-spectrum antibiotics (ertapenem, ceftriaxone, cefotaxime, moxifloxacin or levofloxacin) in patients with suspected low risk of resistance and early-onset HAP/VAP. (Weak recommendation, very low quality of evidence.) low risk patients: without septic shock, with no other risk factors for MDR pathogens and those who are not in hospitals with a high background rate of resistant pathogens. A prevalence of resistant pathogens in local microbiological data >25% is considered a high background rate (the rate of resistance in the ICU caring for the patient (not the hospital as a whole) is the relevant factor to consider).

30 We suggest using narrow-spectrum antibiotics (ertapenem, ceftriaxone, cefotaxime, moxifloxacin or levofloxacin) in patients with suspected low risk of resistance and earlyonset HAP/VAP. (Weak recommendation, very low quality of evidence.) low risk patients: without septic shock, with no other risk factors for MDR pathogens and those who are not in hospitals with a high background rate of resistant pathogens. A prevalence of resistant pathogens in local microbiological data >25% is considered a high background rate (the rate of resistance in the ICU caring for the patient (not the hospital as a whole) is the relevant factor to consider). - The percentage of potentially MDR pathogens is significant even in early-onset HAP/VAP. - At the present time, the number of patients with early-onset HAP who can safely receive empiric narrow-spectrum therapy is limited.

31 We recommend initial empiric combination therapy for high-risk HAP/VAP patients to cover Gram-negative bacteria and include antibiotic coverage for MRSA in those patients at risk. (Strong recommendation, moderate quality of evidence.) high-risk HAP/VAP : patients with septic shock and/or the following risk factors for potentially resistant microorganisms: hospital settings with high rates of MDR pathogens (i.e. a pathogen not susceptible to at least one agent from three or more classes of antibiotics): a prevalence of resistant pathogens in local microbiological data >25% represents a high-risk situation (including Gram-negative bacteria and MRSA). previous antibiotic use, recent prolonged hospital stay (>5 days of hospitalisation) and previous colonisation with MDR pathogens. consider selected patients at high risk for MDR pathogens for initial empiric monotherapy, if there is a single-antibiotic therapy that is effective against >90% of Gram-negative bacteria according to the local antibiogram.

32 Empiric antibiotic treatment algorithm for hospital-acquired pneumonia (HAP)/ventilatorassociated pneumonia (VAP). Antoni Torres et al. Eur Respir J 2017;50: by European Respiratory Society

33 Traitement empirique HAP: We recommend that all hospitals regularly generate and disseminate a local antibiogram, ideally one that is tailored to their HAP population, if possible. 2. We recommend that empiric antibiotic regimens be based upon the local distribution of pathogens associated with HAP and their antimicrobial susceptibilities. Pas disponible au CHU

34 24 études analysées: Non fermentants: 19% Enterobactéries: 16% St aureus: 16 % (10 % MRSA) Pas de différence précoce vs tardive.

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36 Traitement adapté: Aérosols: Que amino ou coli si souche que S à une molécule (faire IV + aérosol). Pseudomonas: bithérapie poursuivie que si choc (stop quand choc OK) Haut risque de mortalité (> 25%) ESBL: selon ATBgramme (pas carba exclusif) Acineto: carba ou ampi/sulbactam Pas ajouter rif Pas tige

37 If initial combination therapy is started, we suggest continuing with a single agent based on culture results. Only consider maintaining definitive combination treatment based on sensitivities in patients with: extensively drug-resistant (XDR; i.e. susceptible to only one or two classes of antibiotics)/pan-drug-resistant (PDR; i.e. not susceptible to any antibiotics) nonfermenting Gram-negative bacteria and carbapenem-resistant Enterobacteriaceae (CRE) isolates. (Weak recommendation, low quality of evidence.)

38 Durée de traitement: For patients with VAP, we recommend a 7-day course of antimicrobial therapy rather than a longer duration (strong recommendation, moderate-quality evidence). For patients with HAP, we recommend a 7- day course of antimicrobial therapy (strong recommendation, very lowquality evidence)

39 We suggest using a 7 8-day course of antibiotic therapy in patients with VAP without: immunodeficiency, cystic fibrosis, empyema, lung abscess, cavitation or necrotising pneumonia and with a good clinical response to therapy.

40 Désescalade: For patients with HAP/VAP, we suggest that antibiotic therapy be de-escalated rather than fixed: De-escalation refers to changing an empiric broadspectrum antibiotic regimen to a narrower antibiotic regimen by changing the antimicrobial agent or changing from combination therapy to monotherapy.

41 Prévention VAP A: pas de détails E : SOD si résistances < 5% et si consommation antibiotiques < 1000 DDD/1000 JH attention à la chlorhexidine

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43 Chlorhexidinevscontrol BMJ 2014 Price R et al

44 Roquilly et al CID 2015

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