Attualità in tema di polmoniti - SIMI – Società Italiana di … in... · ·...
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Attualitàin tema di polmoniti
MarioVendittiDipartimentodiSanitàPubblica
eMalattieInfettive“Sapienza”UniversitàdiRoma
Confesso di aver ricevuto onorari per…
• Relatore a eventi ECM sponsorizzati: Astellas, Astra Zeneca, Angelini, Basilea, MSD, Pfizer, Gilead, Novartis.
• Partecipazione ad Advisory board: Angelini, MSD, Gilead, Nordic Pharma
Diagnosis of CAP• Typical clinical features, chest x ray documented
pulmonary infiltrate +/- microbiology• Pretreatment blood samples for culture and an
expectorated sputum sample for stain and culture (in patients with a productive cough) should be obtained from hospitalized pts (Moderate recommendation; level I evidence.)
• Pretreatment Gram stain and culture of expectorated sputum should be performed only if a good-quality specimen can be obtained (Moderate recommendation; level II evidence.)
• Pts with severe CAP, should at least have blood cultures, urinary antigen tests for L. pneumophila and S. pneumoniae performed, and sputum samples collected or culture. For intubated pts, an endotracheal aspirate sample should be obtained. (Moderate recommendation; level II evidence.)
IDSA/ATS guidelines Clinical Infectious Diseases 2007; 44:S27–72
•Ex fumatore•Ipertensione arteriosa•Pregresso IMA•Diabete mellito•BPCO, assumeva Ceftriaxone mensilmente a domicilio suconsiglio dello pneumologo curante•Encefalopatia multinfartuale con parkinsonismo, recentericovero•Portatore di mezzo di osteosintesi in sede calcaneale
Anamnesi patologica prossimaM 85 anniGiunge in reparto proveniente dal DEA per la
comparsa di dolore al bacino a seguito di caduta
a terra accidentale senza perdita di coscienza
Caso clinico
Ceftriaxone mensilmente a domicilio su consiglio dellopneumologo curante
caduta a terra accidentale senzaperdita di coscienza
Diagnosis of CAP• Typical clinical features, chest x ray documented
pulmonary infiltrate +/- microbiology• Pretreatment blood samples for culture and an
expectorated sputum sample for stain and culture (in patients with a productive cough) should be obtained from hospitalized pts (Moderate recommendation; level I evidence.)
• Pretreatment Gram stain and culture of expectorated sputum should be performed only if a good-quality specimen can be obtained (Moderate recommendation; level II evidence.)
• Pts with severe CAP, should at least have blood cultures, urinary antigen tests for L. pneumophila and S. pneumoniae performed, and sputum samples collected or culture. For intubated pts, an endotracheal aspirate sample should be obtained. (Moderate recommendation; level II evidence.)
IDSA/ATS guidelines Clinical Infectious Diseases 2007; 44:S27–72
caso clinico• Un uomo di 48 aa, non comorbidità,
giunge a PS per una sindrome di febbre elevata da 72 ore poi riconosciuta come CAP.
• CURB 65: 1. • Sfebbra in 48 ore con ceftriaxone iv
e viene dimesso con ceftriaxoneim,…..
• ....rientrerà dieci giorni dopo con una MOF, Antigenuria per Legionella positiva....guarirà dopo una lunga degenza in UTI......
Età, sesso, rischio
Rx, leucocitosi (L),
iposodiemia (IS)
Coinfezione Rx, esito
54, F, fumo Inf dx, L S. pneumoniae§
Amp/S+Ery, Ok
57, M, fumo Inf bil, IS S. pneumoniae§
Amp/S+Ery, Ok
68, F Inf sin, L, IS S. pneumoniae§
Amp/S, Recidiva
33, F, fumo Inf dx, L S. pneumoniae§
Meropenem, Ok…follow
up?73, M, fumo Inf bil, vers
pleur, LS. pyogenes Amp/S,
Recidiva74, M, cancro Inf bil, L E. cloacae§ Imip+tobra,
Recidiva
Polmonite da Legionella + Infezione concomitanteTan M.J. CID 35: 533, 2002
§ isolati dal sangue +/- espettorato
Epidemiology, Co-Infections, and Outcomes of ViralPneumonia in Adults. An Observational Cohort Study
Crotty et al. Medicine 94(50):e2332, 2015
835 pneumonias34% viral episodes!!!
Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults. An Observational Cohort Study
Crotty et al. Medicine 94(50):e2332, 2015
Viruses Identified in Patients With Viral Pneumonia
Recommended empirical antibiotics for CAPIDSA/ATS guidelines Clinical Infectious Diseases 2007; 44:S27–72
Recommended empirical antibiotics for CAPIDSA/ATS guidelines Clinical Infectious Diseases 2007; 44:S27–72
1. punteggi di gravità.
2. Macrolide vs levofloxacina.
3. Terapia/profilassi per complicanze non infettive della
polmonite che insorge in comunità (CAP & HCAP)?
Expanded CURB-65: a new score system predicts severity of CAP with superior efficiency
Liu J , Xu F ,Zhou H , Wu X , Shi L , Lu R, Farcomeni A , Venditti M , Dong X, & Falcone M Sci Rep. 2016 Mar 18;6:22911.
• Derivation cohort:1640 pts (Zhejiang University); validation cohort: 1164 pts (Sapienza Univerity – Rome).
• Using age ≥ 65 years, LDH > 230 u/L, albumin < 3.5 g/dL, platelet count < 100 × 10(9)/L, confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, low blood pressure, we assembled a new severity score was assembled (expanded-CURB-65).
• The AUCs in the prediction of 30-day mortality in the 1640 chinese pts cohort were 0.826 (95% CI, 0.807-0.844), 0.801 (95% CI, 0.781-0.820), 0.756 (95% CI, 0.735-0.777), 0.793 (95% CI, 0.773-0.813) and 0.759 (95% CI, 0.737-0.779) for the expanded-CURB-65, PSI, CURB-65, SMART-COP and A-DROP, respectively.
• The performance of this bedside score was confirmed in CAP pts of the validation cohort although calibration was not successful in patients with HCAP.
1. punteggi di gravità.
2. Macrolide vs levofloxacina.
3. Terapia/profilassi per complicanze non infettive della
polmonite che insorge in comunità (CAP & HCAP)?
Retrospective Analysis of Azithro vs FQs for Legionella Pneumonia Nagel JL et al P&T, 39: 203, 2014
Clinical outcomes
Nodifferences inpatients demographics, comorbidities, APACHE IIscore,direct admittance inICU,andcomplications
The Association of Antibiotic Treatment Regimen and Hospital Mortality in pts Hospitalized With Legionella PneumoniaGershengorn et al Clinical Infectious Diseases 2015;60(11):e66–79
Comparison of Outcomes of Azithro and Quinolone-Treated pts
Levo vs azithro for treating Legionellapneumonia: a propensity score analysis
Garcia Vidal C et al CMI 2017, in press
Neither univariate nor multivariate analysis showed a significantassociation of levofloxacin vs.
azithromycin on mortality [4(2.3%) vs. 9(5.1%) deaths; p=0.164].
The results did not change afterincorporation of the propensity score
into the models.
1. Punteggi di gravità
2. Macrolide vs levofloxacina.
3. Terapia/profilassi per complicanze non infettive della
polmonite che insorge in comunità (CAP & HCAP)?
One-year outcomes of community-acquired and healthcare-associated pneumonia in the Veterans Affairs Healthcare System
Hsu JL InternJ Infect Dis 2011 on line early
CurvedisopravvivenzaKaplan–MeiersecondoHCAPstatusandcomorbidityscore;tutteledifferenzeHCAP–CAPrisultaronosignificative(p<0.05)
CDQ,Charlson–Deyo–Quancomorbidityindexscore
Cardiovascular Events and Short-Term Mortality Risk in CAP Violi F et al Clin Infect Dis 2017, early on line
Adjusted hazard ratios (HR), based on a Cox proportional hazards model, of intra-hospital CVE according to selected variables.
Cardiovascular Events and Short-Term Mortality Risk in CAP Violi F et al Clin Infect Dis 2017, early on line
Kaplan-Meier estimates of time to 30-days mortality in CAP ptswho experienced or not a CVE during the intra-hospital stay
Platelet Activation Is Associated With Myocardial Infarction in Patients With Pneumonia
Cangemi, R., et al., J Am Coll Cardiol. 2014; 64(18):1917–25.
Potential Mechanisms for Platelet Activation During Pneumonia
Estimated survival during hospitalization of the aspirin group, compared to the nonaspirin group,using Kaplan–Meier survival analysis.
Falcone et al J Am Heart Assoc. 2015 Jan 6;4(1):e001595
Non Aspirin group
Aspirin group
P= 0.001
aspirinplusmacrolides(A+M)improvessurvivalofptswithcommunity-onsetpneumoniapresentingwithsepticshock
FalconeM,etalIntensiveCareMedicine2016
aspirinplusmacrolides(A+M)improvessurvivalofptswithcommunity-onsetpneumoniapresentingwithsepticshock
FalconeM,RussoA,bertazzoniG,VioliF&VenditttiM,IntensivCareMedicine,2016
Cox regressionanalysis about effects of differentvariables onoverall survival during hospitalization
aspirinplusmacrolidesimprovessurvivalofpatientswithcommunity-onsetpneumoniapresentingwithsepticshock
FalconeM,RussoA,BertazzoniG,Violi F&VendittiMIntensveCareMedicine, 2016
Effect of Corticosteroids on Treatment Failure in pts With Severe CAP and High Inflammatory Response: A Randomized Clinical Trial
Torres et al JAMA, 2015
Clinical Outcomes Using Descriptive Statistics for Per-ProtocolPopulation
Secondary endpoint: no diffences (Los, time to stability…)
IDSAguidelines:maindifferencesbetween2017guidelinesandthe2005version
1. HAP denotes an episode of pneumonia not associated
with mechanical ventilation. Patients with HAP and VAP
belong to 2 distinct groups
2. Removal of the concept of HCAP…..
3. Recommendation for each hospital to generate
antibiograms to guide healthcare professionals with
respect to the optimal choice of antibiotics and to
decrease the unnecessary use of dual gram-negative and
empiricMRSA antibiotic treatment
Rischio di etiologie multiresitenti
CAP HCAP HAP/VAP
Rischio di morte
• Carratalà• Giannella
(Spain)
Shindo(Japan)
KollefMicek(USA)
Venditti(Italy)
HCAPDoesNotAccuratelyIdentifyPotentiallyResistantPathogens:ASystematicReviewandMeta-Analysis
PrevalenceofMultidrug-ResistantPathogensinHCAPandCAPGroups
ChalmersJDetal.ClinInfectDis.2014;58:330-9.
IndividualizingRiskofMDRPathogensinCommunity-OnsetPneumonia
FalconeMetal.PLoSOne.2015;10:e0119528
Etiology of 300 isolations in the study population
Multivariate analysis of factors associated with MDR isolation
Falcone M et al PLOS ONE | DOI:10.1371/journal.pone.0119528, 2015
NEnglJMed2006;355:2619–30
A randomized trial of diagnostic techniquesfor ventilator-associated pneumonia
Thereisnoevidencethatinvasivemicrobiologicalsamplingwithquantitativeculturesimprovesclinicaloutcomescomparedwithnoninvasivesamplingwitheitherquantitativeorsemiquantitativecultures.
ATS2005versus IDSA2016Recommendeduseofnoninvasivesamplingwith
semiquantitativecultures
NoninvasivesamplingqMorerapid
qFewercomplications
qFewerresources
IDSAGuidelines,ClinInfectDis2016:63
Semiquantitative culturesqmorerapidly
qfewerlaboratoryresources
qlessexpertiseneeded
UsefulnessofprocalcitoninforthediagnosisofVAP
LuytCEetal.IntensiveCareMed.2008;34:1434-40
OnDay1nobestPCTcutoffvaluesforVAPdiagnosiscouldbeestablished.Usingathresholdof0.5ng/ml
yielded72%sensitivitybutonly24%specificity
UsefulnessofprocalcitoninforthediagnosisofVAP
LuytCEetal.IntensiveCareMed.2008;34:1434-40
PCTincreasebeforeDay1doesnotreachhighsensitivityandspecificity
PCT,CRP&CPISToDiagnoseVAPAndHAP
…useofclinicalcriteriaalone,ratherthanusingserumPCT+clinicalcriteria,todecidewhetherornot
toinitiateantibioticsstrongrecommendation,moderate-quality evidence
…useofclinicalcriteriaaloneratherthanusingCRP+clinicalcriteria,todecidewhetherornot
toinitiateantibioticsweakrecommendation, low-quality evidence
…useofclinicalcriteriaaloneratherthanusingCPIS+clinicalcriteria,todecidewhetherornot
toinitiateantibioticsweakrecommendation, low-quality evidence
IDSAGuidelines,ClinInfectDis2016:63
Recommentation…
EmpiricTherapyofHAP/VAP
Antibioticselectionforeachpatientbasedon:Timeofonset[late(≥5d)versusearlyonset(<5d)]
ATSGuidelinesAmJRespirCritCareMed,2005
TheriskfactorsforMDR
pathogens
EmpiricTreatmentofHAP-nonVAP
riskofmortality!!
IDSAGuidelines,ClinInfectDis2016:63
Itshouldbebasedon…
Needforventilatorysupportduetopneumonia
Septicshock
EmpiricTreatmentofHAP-nonVAP
NoHighRiskofMortalityvnoneedforventilatorysupport
vnosepticshock
NoincreasedLikelihoodofMRSAvNoivantibiotictherapywithin90d
vunitwhereMRSArate<20%
AND
Oneofthefollowing:•Piperacillin-tazo4.5gIVq6h
•Cefepime2gIVq8h
•Levofloxacin750mgIVdaily
•Imipenem500mgIVq6h
•Meropenem1gIVq8h
IncludeCoverageforMSSAandP.aeruginosa
IDSAGuidelines,ClinInfectDis2016:63
ONEAGENT!!
EmpiricTreatmentofHAP-nonVAP
IncreasedLikelihoodofMRSAvIvantibiotictherapywithin90d
vunitwhereMRSArate>20%or
prevalencenotknown
AND
Oneofthefollowing:•Piperacillin-tazo4.5gIVq6h•Cefepime2gIVq8h•Levofloxacin750mgIVdaily•Ciprofloxacin400mgIVq8h•Imipenem500mgIVq6h•Meropenem1gIVq8h
IncludeCoverageforMRSAandP.aeruginosa
IDSAGuidelines,ClinInfectDis2016:63
Vanco15mg/kgIVq8-12hwiththegoaltotarget15-20mg/mLtrough
level
Linezolid600mgIVq12h
OR
TWOAGENTS!!
NoHighRiskofMortalityvnoneedforventilatorysupport
vnosepticshock
EmpiricTreatmentofHAP-nonVAP
HighRiskofMortalityvNeedforventilatorysupport
vSepticshock
FactorsincreasingthelikelihoodforP.
aeruginosa orotherGram-negativebacilliPriorantibioticusewithin90days
AND
Two ofthefollowing,avoiding2β-lactams•Piperacillin-tazo4.5gIVq6h•Cefepime2gIVq8h•Levofloxacin750mgIVdaily•Ciprofloxacin400mgIVq8h•Imipenem500mgIVq6h•Meropenem1gIVq8h•Amikacin15-20mg/kgIVdaily•Gentamicin5-7mg/kgIVdaily•Tobramycin5-7mg/kgIVdaily
IncludeCoverageforMRSAandP.aeruginosa
IDSAGuidelines,ClinInfectDis 2016:63
Vancomycin15mg/kgIVq8-12hwiththegoaltotarget15-20mg/mL
troughlevel
Linezolid600mgIVq12hOR
THREEAGENTS
EmpiricTherapyofVAP
EnsurecoverageforS.aureus,Pseudomonasaeruginosa,andothergram-negativebacilliinallempiricregimens
strongrecommendation, low-qualityevidence
Riskfactorforantimicrobialresistance•priorIVantibioticusewithin90d•septicshockattimeofVAP•ARDSprecedingVAP•5omoredaysofhospitalizationpriortotheoccurrenceofVAP•acuterenalreplacementtherapypriortoVAPonset
PatientsbeingtreatedinunitswhereMRSArate>10%–20%orinunitswheretheprevalenceofMRSAisnotknown
IncludeMRSAcoverage
IDSAGuidelines,ClinInfectDis 2016:63
EnsurecoverageforS.aureus,Pseudomonasaeruginosa,andothergram-negativebacilliinallempiricregimens
strongrecommendation, low-qualityevidence
Riskfactorforantimicrobialresistance•priorIVantibioticusewithin90d
•septicshockattimeofVAP•ARDSprecedingVAP
•5omoredaysofhospitalizationpriortotheoccurrenceofVAP•acuterenalreplacementtherapypriortoVAPonset
Patientsbeingtreatedinunitswhere>10%ofgram-negativeisolatesareresistant toanagentbeingconsideredformonotherapy
Use2antipseudomonal agents
IDSAGuidelines,ClinInfectDis 2016:63EmpiricTherapyofVAP
Avoidaminoglycosidesifalternativeagentswithadequategram-negative
activityareavailable(weakrecommendation,low-qualityevidence).
Avoidcolistinifalternativeagentswithadequategram-negative
activityareavailable(weakrecommendation,verylow-qualityevidence).
IDSAGuidelines,ClinInfectDis2016:63EmpiricTherapyofVAP
Malattia da Aspergillus
• Sudbdola e indolente à capace di accellerare in una progressione fatale
• Necessità e possibilità di diagnosi precoce con surrogati marker?
• Nuove categorie a rischio• Prospettive terapeutiche….
Chest radiographs performed at day 1 (left) showing bilateral reticular-nodular infiltrates, and at day 10 (right) showing
extensive bilateral consolidations.
Fatal Invasive Pulmonary Aspergillosis Complicating Influenza A (H1N1)v Infection
Carfagna P, Brandimarte P, Caccese R, Campagna D, Brandimarte C, Venditti M.Mycoses on line early, 2011
OtherrecommendationsPK/PDOPTIMIZATION
OFANTIBIOTICTHERAPY
ROLEOFINHALEDANTIBIOTIC
THERAPY
IDSAGuidelines,CID2016:63
MeropenemfortreatingKPC-producingKlebsiellapneumoniae bloodstreaminfections:Shouldwe
gettothePK/PDrootoftheparadox?DelBonoetal.Virulence 2017;8:66-73
Univariate logistic regression analysis of variables associated with clinical cure from KPC-producing Klebsiella
pneumoniae-related infections (n = 30 patients)Pea F et al IJAA, 2017
Variable OR (95% CI) P-value Age 1.032 (0.969–1.100) 0.322 Male sex 1.154 (0.218–6.097) 0.866 CCI ≥ 4 0.158 (0.025–0.999) 0.050 Length of therapy 1.091 (0.936–1.271) 0.264 Mero Css/MIC ³1 10.556 (1.612–69.122) 0.014 * Mero Css/MIC ³4 12.250 (1.268–118.361) 0.030 * Mero MIC 0.965 (0.930 – 1.003) 0.068 Site of infection .................No. of co-administered antimicrobials 1 active drug 3.267 (0.334–31.914) 0.309 2 active drugs 0.952 (0.179–5.081) 0.954 3 active drugs 2.059 (0.202–20.959) 0.542 ≥4 active drugs 0.167 (0.022–1.282) 0.085
BoissonMetalAntimicrobAgentsChemother2014;587331-7339
Comparison of Intrapulmonary and Systemic Pharmacokinetics of Colistin Methanesulfonate (CMS) and Colistin after Aerosol Delivery and
Intravenous Administration of CMS in Critically Ill Patients
Effect of Aerosolized Colistin as Adjunctive Treatment on the Outcomes of Microbiologically Documented VAP Caused by Colistin-Only
Susceptible Gram-Negative Bacteria Tumbarello M et al Chest 2015
Multivariate Analysis of Factors Associated With Clinical Cure in ptsWith VAP Caused by Colistin-Only Susceptible Gram-Negative Bacteria
P=0.001
caso• 63 anni, diabete tipo I e cirrosi CP:
B8àC• Profilassi con norfloxacina per
profilassi recidiva di peritonite primaria• Terapia con inibitori di pompa…• Piastrinopenia & IRCàIRA• Polmonite a insorgenza comunitaria
con criteri HCAP (frequenti ricoveri)• Terapia empirica?
Nuovi antibioticiAgente tipo di spettroCeftarolina ceftriaxone+MRSACeftibrolo cefepime+MRSA Ceftolozano/tazo pip/tazo + P aeruginosa MDRCeftazidime-avibactam ceftazidime+ KPC & ESBLTedizolid <tossico e >PK/PD di linezolidFosfomicina iv partner àMRSA,
ESBL, KPC & P aeruginosa MDR
ProcalcitonintoGuideInitiationandDurationofAntibioticTreatmentinAcuteRespiratoryInfections:
AnIndividualPatientDataMeta-Analysis
SchuetzPetal.ClinInfectDis.2012;55:651-62