1、Clinical Infectious DiseasesIDSA GUIDELINEManagement of Adults With Hospital-acquired andVentilator-associated Pneumonia: 2016 Clinical PracticeGuidelines by the Infectious Diseases Society of Americaand the American Thoracic SocietyAndre C. Kalil,1,aMark L. Metersky,2,aMichael Klompas,3,4John Musce
2、dere,5Daniel A. Sweeney,6Lucy B. Palmer,7Lena M. Napolitano,8Naomi P. OGrady,9John G. Bartlett,10Jordi Carratal,11Ali A. El Solh,12Santiago Ewig,13Paul D. Fey,14Thomas M. File Jr,15Marcos I. Restrepo,16Jason A. Roberts,17,18Grant W. Waterer,19Peggy Cruse,20Shandra L. Knight,20and Jan L. Brozek211Dep
3、artment of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha;2Division of Pulmonary and Critical Care Medicine, University of ConnecticutSchool of Medicine, Farmington;3Brigham and Womens Hospital and Harvard Medical School, and4Harvard Pilgrim Health C
4、are Institute, Boston, Massachusetts;5Department of Medicine,Critical Care Program, Queens University, Kingston, Ontario, Canada;6Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego;7Department of Medicine,Division of Pulmonary Critical Care and Sleep Medicin
5、e, State University of New York at Stony Brook;8Department of Surgery, Division of Trauma, Critical Care and Emergency Surgery,University of Michigan, Ann Arbor;9Department of Critical Care Medicine, National Institutes of Health, Bethesda, and10Johns Hopkins University School of Medicine, Baltimore
6、, Maryland;11Department of Infectious Diseases, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute, Spanish Network for Research in Infectious Diseases, University of Barcelona,Spain;12Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Universit
7、y at Buffalo, Veterans Affairs Western New York Healthcare System, New York;13Thoraxzentrum Ruhrgebiet, Department of Respiratory and Infectious Diseases, EVK Herne and Augusta-Kranken-Anstalt Bochum, Germany;14Department of Pathology and Microbiology,University of Nebraska Medical Center, Omaha;15S
8、umma Health System, Akron, Ohio;16Department of Medicine, Division of Pulmonary and Critical Care Medicine, South Texas VeteransHealth Care System and University of Texas Health Science Center at San Antonio;17Burns, Trauma and Critical Care Research Centre, The University of Queensland,18Royal Bris
9、bane andWomens Hospital, Queensland, and19School of Medicine and Pharmacology, University of Western Australia, Perth, Australia;20Library and Knowledge Services, National Jewish Health,Denver, Colorado; and21Department of Clinical Epidemiology and Biostatistics and Department of Medicine, McMaster
10、University, Hamilton, Ontario, CanadaIt is important to realize that guidelines cannot always account for individual variation among patients. They are not intended tosupplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to theseguid
11、elines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the lightof each patients individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia(HAP) a
12、nd ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, andsurgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomialpneumonia. The panels recommendations f
13、or the diagnosis and treatment of HAP and VAP are based upon evidence derived fromtopic-specic systematic literature reviews.EXECUTIVE SUMMARYIn this 2016 guideline, the term “hospital-acquired pneumo-nia” (HAP) denotes an episode of pneumonia not associatedwith mechanical ventilation. Thus, patient
14、s with HAP andventilator-associated pneumonia (VAP) belong to 2 distinctgroups. The major differences between this guideline andthe 2005 version 1 include the following: the use of theGrading of Recommendations Assessment, Developmentand Evaluation (GRADE) methodology for the evaluation ofall availa
15、ble evidence (Table 1)2; the removal of the conceptof healthcare-associated pneumonia (HCAP); and the recom-mendation that each hospital generate antibiograms to guidehealthcare professionals with respect to the optimal choice ofantibiotics. In an effort to minimize patient harm and expo-sureto unne
16、cessaryantibiotics and reduce the development ofantibiotic resistance, we recommend that the antibiogramdata be utilized to decrease the unnecessary use of dualgram-negative and empiric methicillin-resistant Staphylococ-cus aureus (MRSA) antibiotic treatment. We also recommendshort-course antibiotic
17、 therapy for most patients with HAPorVAP independent of microbial etiology, as well as antibioticde-escalation.Summarized below are the recommendations made inthe 2016 guideline. A detailed description of the methods,background, and evidence summaries that support each ofthe recommendations can be f
18、ound in the full text of thisguideline.Received 17 May 2016; accepted 18 May 2016.aA. C. K. and M. L. M. contributed equally to this work.Correspondence: A. C. Kalil, Department of Internal Medicine, Division of Infectious Diseas-es, University of Nebraska Medical Center, Omaha, NE 68198-5400 (akali
19、lunmc.edu).Clinical Infectious Diseases2016;63(5):57582 The Author 2016. Published by Oxford University Press for the Infectious Diseases Societyof America. All rights reserved. For permissions, e-mail .DOI: 10.1093/cid/ciw504Management of Adults With HAP/VAP CID 2016:63 (1 September) 575at KOREA UN
20、IVERSITY MEDICAL LIBRARY on August 17, 2016http:/cid.oxfordjournals.org/Downloaded from MICROBIOLOGICMETHODSTODIAGNOSEVAPANDHAPI. Should Patients With Suspected VAP Be Treated Based on the Resultsof Invasive Sampling (ie, Bronchoscopy, Blind Bronchial Sampling)With Quantitative Culture Results, Noni
21、nvasive Sampling (ie,Endotracheal Aspiration) With Quantitative Culture Results, orNoninvasive Sampling With Semiquantitative Culture Results?Recommendation1. We suggest noninvasive sampling with semiquantitative culturesto diagnose VAP, rather than invasive sampling with quantitativecultures and ra
22、ther than noninvasive sampling with quantitativecultures (weak recommendation, low-quality evidence).Remarks: Invasive respiratory sampling includes broncho-scopic techniques (ie, bronchoalveolar lavage BAL, protect-ed specimen brush PSB) and blind bronchial sampling(ie, mini-BAL). Noninvasive respi
23、ratory sampling refers toendotracheal aspiration.II. If Invasive Quantitative Cultures Are Performed, Should Patients WithSuspected VAP Whose Culture Results Are Below the Diagnostic Thresholdfor VAP (PSB With 10%20%of S. aureus isolates are methicillin resistant, and patients inunits where the prev
24、alence of MRSA is not known (weakrecommendation, very low-quality evidence).ii. We suggest including an agent active against methicillin-sensitive S. aureus (MSSA)(andnotMRSA) fortheempirictreatment of suspected VAP in patients without risk factorsfor antimicrobial resistance, who are being treated
25、in ICUswhere 10% of gram-negative isolates are resistant to an agentbeing considered for monotherapy, and patients in an ICUwhere local antimicrobial susceptibility rates are not available(weak recommendation, low-quality evidence).5. We suggest prescribing one antibiotic active against P. aer-ugino
26、sa for the empiric treatment of suspected VAP in pa-tients without risk factors for antimicrobial resistance whoare being treated in ICUs where 10% of gram-negative iso-lates are resistant to the agent being considered for mono-therapy (weak recommendation, low-quality evidence).6. In patients with
27、suspected VAP, we suggest avoiding amino-glycosides if alternative agents with adequate gram-negativeactivity are available (weak recommendation, low-qualityevidence).7. In patients with suspected VAP, we suggest avoiding colistinif alternative agents with adequate gram-negative activity areavailabl
28、e (weak recommendation, very low-quality evidence).Values and Preferences: These recommendations are a com-promise between the competing goals of providing early ap-propriate antibiotic coverage and avoiding superuoustreatment that may lead to adverse drug effects, Clostridiumdifcile infections, ant
29、ibiotic resistance, and increased cost.Remarks: Risk factors for antimicrobial resistance are pro-vided in Table 2. The 10%20% threshold for decidingwhether or not to target MRSA and the 10% threshold fordeciding whether or not to prescribe 1 antipseudomonalagent or 2 were chosen by the panel with a
30、 goal of tryingto assure that 95% of patient receive empiric therapy ac-tive against their likely pathogens; when implementingthese recommendations, individual ICUs may elect to mod-ify these thresholds. If patient has structural lung disease in-creasing the risk of gram-negative infection (ie,bronc
31、hiectasis or cystic brosis), 2 antipseudomonal agentsare recommended.XI. Should Selection of an Empiric Antibiotic Regimen for HAP(Non-VAP) Be Guided by Local Antibiotic Resistance Data?Recommendations1. We recommend that all hospitals regularly generate and dis-seminate a local antibiogram, ideally
32、 one that is tailored totheir HAP population, if possible.2. We recommend that empiric antibiotic regimens be basedupon the local distribution of pathogens associated withHAP and their antimicrobial susceptibilities.Remarks: The frequency with which the distribution of path-ogens and their antimicro
33、bial susceptibilities are updatedshould be determined by the institution. Considerationsshould include their rate of change, resources, and theamount of data available for analysis.Table 3. Suggested Empiric Treatment Options for Clinically Suspected Ventilator-Associated Pneumonia in Units Where Em
34、piric Methicillin-ResistantStaphylococcus aureus Coverage and Double Antipseudomonal/Gram-Negative Coverage Are AppropriateA. Gram-Positive Antibiotics WithMRSA ActivityB. Gram-Negative Antibiotics WithAntipseudomonal Activity: -LactamBased AgentsC. Gram-Negative Antibiotics With AntipseudomonalActi
35、vity: Non-LactamBased AgentsGlycopeptidesaVancomycin 15 mg/kg IV q812h(consider a loading dose of 2530mg/kg1 for severe illness)Antipseudomonal penicillinsbPiperacillin-tazobactam 4.5 g IV q6hbFluoroquinolonesCiprofloxacin 400 mg IV q8hLevofloxacin 750 mg IV q24hOR OR OROxazolidinonesLinezolid 600 m
36、g IV q12hCephalosporinsbCefepime 2 g IV q8hCeftazidime 2 g IV q8hAminoglycosidesa,cAmikacin 1520 mg/kg IV q24hGentamicin 57 mg/kg IV q24hTobramycin 57 mg/kg IV q24hOR ORCarbapenemsbImipenem 500 mg IV q6hdMeropenem 1 g IV q8hPolymyxinsa,eColistin 5 mg/kg IV1 (loading dose) followed by 2.5mg(1.5CrCl+3
37、0) IV q12h (maintenance dose) 135Polymyxin B 2.53.0 mg/kg/d divided in 2 daily IV dosesORMonobactamsfAztreonam 2 g IV q8hChoose one gram-positiveoption from column A, one gram-negative optionfrom column B, and one gram-negativeoption from column C. Note that the initial dosessuggested in thistable m
38、ayneed to be modified for patients with hepatic or renal dysfunction.Abbreviations: CrCl, creatinine clearance; IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus.aDrug levels and adjustment of doses and/or intervals required.bExtended infusions may be appropriate. Please see section
39、 XIII on pharmacokinetic/pharmacodynamic optimization of antibiotic therapy.cOn meta-analysis, aminoglycoside regimens were associated with lower clinical response rates with no differences in mortality.dThe dose may need to be lowered in patients weighing 20% of S. aureus isolates are meth-icillin
40、resistant, orthe prevalence ofMRSA isnot known, orwho are at high risk for mortality, we suggest prescribing anantibiotic with activity against MRSA (weak recommenda-tion, very low-quality evidence). (Risk factors for mortalityinclude need for ventilatory support due to HAP and septicshock).ii. For
41、patients with HAP who require empiric coverage forMRSA, we recommend vancomycin or linezolid ratherthan an alternative antibiotic (strong recommendation,low-quality evidence).iii. For patients with HAP who are being treated empirical-ly and have no risk factors for MRSA infection and arenot at high
42、risk of mortality, we suggest prescribing anantibiotic with activity against MSSA. When empiric treat-ment that includes coverage for MSSA (and not MRSA) isindicated, we suggest a regimen including piperacillin-tazo-bactam, cefepime, levooxacin, imipenem, or meropenem.Table 4. Recommended Initial Em
43、piric Antibiotic Therapy for Hospital-Acquired Pneumonia (Non-Ventilator-Associated Pneumonia)Not at High Risk of Mortalityaand noFactors Increasing the Likelihood ofMRSAb,cNot at High Risk of Mortalityabut With FactorsIncreasing the Likelihood of MRSAb,cHigh Risk of Mortality or Receipt of Intraven
44、ousAntibiotics During the Prior 90 da,cOne of the following: One of the following: Two of the following, avoid 2 -lactams:Piperacillin-tazobactamd4.5 g IV q6h Piperacillin-tazobactamd4.5 g IV q6h Piperacillin-tazobactamd4.5 g IV q6hOR OR ORCefepimed2 g IV q8h Cefepimedor ceftazidimed2 g IV q8h Cefep
45、imedor ceftazidimed2 g IV q8hOR OR ORLevofloxacin 750 mg IV daily Levofloxacin 750 mg IV daily Levofloxacin 750 mg IV dailyCiprofloxacin 400 mg IV q8h Ciprofloxacin 400 mg IV q8hOR ORImipenemd500 mg IV q6h Imipenemd500 mg IV q6h Imipenemd500 mg IV q6hMeropenemd1 g IV q8h Meropenemd1 g IV q8h Meropen
46、emd1 g IV q8hOR ORAztreonam 2 g IV q8h Amikacin 1520 mg/kg IV dailyGentamicin 57 mg/kg IV dailyTobramycin 57 mg/kg IV dailyORAztreoname2 g IV q8hPlus:Vancomycin 15 mg/kg IV q812h with goal to target1520 mg/mL trough level (consider a loadingdose of 2530 mg/kg1 for severe illness)Plus:Vancomycin 15 m
47、g/kg IV q812h with goal to target 1520 mg/mLtrough level (consider a loading dose of 2530 mg/kg IV1 forsevere illness)OR ORLinezolid 600 mg IV q12h Linezolid 600 mg IV q12hIf MRSA coverage is not going to be used, include coverage for MSSA.Options include:Piperacillin-tazobactam, cefepime, levofloxa
48、cin, imipenem,meropenem. Oxacillin, nafcillin, and cefazolin are preferred for thetreatment of proven MSSA, but would ordinarily not be used in anempiric regimen for HAP.If patient has severe penicillin allergy and aztreonam is going to be usedinstead of any -lactambased antibiotic, include coverage
49、 for MSSA.Abbreviations: HAP, hospital-acquired pneumonia; IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus.aRisk factors for mortality include need for ventilatory support due to pneumonia and septic shock.bIndications for MRSA coverage include intravenous antibiotic treatment during the prior 90 days,and treatment in a unit where the prevalence of MRSA among S. aureus isolates is not knownor is 20%. Prior detection of MRSA by culture or n
