Pneumonia: Community- and Hospital-acquired pneumonia · ATHENS 2019 GREECE | 27-29 JUNE Pneumonia:...

ATHENS 2019GREECE | 27-29 JUNE

Pneumonia:Community-andHospital-acquired

pneumoniaAdamantiaLiapikou,MD,PhD

SOTIRIAChestDiseasesHospital,Athens


Conflict of Interest Disclosure

NOTHINGTODECLARE


Community-acquiredpneumonia

§ Epidemiology§ Etiology-Diagnosis§ Prognosis§ Therapy§ Prevention

Clinical Infectious Diseases 2007;44:S27–72

Clinical Microbiology and Infection,Vol17;Sup6,Nov2011

ATHENS 2019GREECE | 27-29 JUNEEPIDEMIOLOGY

ØCAPincidencerangesbetween1,7-11,6/1000cases/yearinadults

ØMorecommoninchildren<5yrsandadults>40yrsØMorecommoninpatientswithcomorbidities

ØPeakincidenceduringwintermonthsØMortalityoutsidethehospitalislow,butin-hospitalmortalityrangesbetween5–10%andreaches30–50%inICUpatients


Overall CAP incidence* in Europe

6

Overall annual CAP incidence: 1.07 (1.04–1.23)/1000 person-years

CAP incidence in men: 1.22 (1.18 – 1.26)

Incidence in >65 Years:14.0 (12.7 – 15.3)

Incidence in COPD:22.4 (21.7 – 23.2)

Incidence in HIV:12.0 (9.9 – 14.0)

CAP incidence in women:0.93 (0.89 – 0.96)

6Torres A, et al. Thorax. 2013;68:1057-65.

*All incidences reported as per 1000 Person Years


Ann Am Thorac Soc. 2016 Sep;13(9):1519-26.

12,127

70,6

134,5

274,1

0

50

100

150

200

250

300

16–44 45–64 65–74 75–84 ≥85

Pneu

mon

ia ho

spita

lizat

ions

(p

er 10

0,000

)

Age (years)

A 2 year, prospective, observational cohort study conducted in a large UK teaching hospital trust. The study included 920 patients with CAP; 366 had pneumococcal CAP.

INCIDENCEACCORDINGTOAGE


28.8%

Mongardon N, et al. Critical Care. 2012, 16:R155.

MortalityinpatientswithseverepneumococcalCAPadmittedtotheICUreaches28.8%


SMOKINGstrongestrik factor!!!


SymptomsandsignsofCAP


Rapidlyprogressive CAP

Rodriguez A, et al. Med Intensiva 2012

ED ICU

6 h after ICU admission

Respiratory failure

ARDS

Refractory hypoxemia

Cardiovascularcomplications

Loubert P,etal.JClin Virol 2016Tayler G,etal.Epidemiol Infect2016Chacko B,etal.JCrit Care 2012


ETIOLOGY


More than 100 microbes can cause CAP. A microbiologic diagnosis wasconfirmed in 38 to 87 percent of cases of CAP in studies that usedspecialized tests to detect various pathogens."Typical" organisms include S. pneumoniae, Haemophilus influenzae,Staphylococcus aureus, group A streptococci, Moraxella catarrhalis,anaerobes, and aerobic gram-negative bacteria."Atypical" pneumonia refers to pneumonia caused by Legionella spp, M.pneumoniae, C. pneumoniae, and Chlamydia psittaci; although imprecise, weuse this term because of its acceptance among clinicians.Polymicrobial aetiology -mixed infection, 2%-13%

ETIOLOGY


PATHOGENSINCAP IN USA:2010-2012ΙΟΙ1Η CAUSE

N Engl J Med 2015; 373:415-427

24,8/10000adults

2259ptswithRXCAP


StreptococcuspneumoniaeasacauseofCAP

ClinicalInfectiousDiseases®2017;XX(00):1–10


PATHOGENSRELATEDTOSEVERITY

OUTPATIENT INPATIENT(NOT ICU)

ICU

S pneumoniae

M pneumoniae

H influenzae

C. pneumoniae

Respir. viruses

S pneumoniae

M. pneumoniae

C. pneumoniae

H influenzae

Legionella spp

Respir. viruses

S pneumoniae

S aureus

Legionella spp

Gram (-) bacilli

H influenzae

17

Clinical Infectious Diseases 2007;44:S27–72


DIAGNOSIS

IMAGING

SensitivityofX-Ray60–70%


CTSCAN?

Claessens Y-E et al. AJRCCM ,2015


Ø >65 years (dpt internal

medicine), suspected

pneumonia

ØChest X-ray and CT-scan / 72h

Ø probability pneumonia (Likert

scale)

Ø before and after CT-scan

ØGold standard adjudication

committee

Change in 90 (45%) pts60 (30%)downgraded30 (15%) upgraded


Our initial search strategy yielded 10 377 studies, of which 17 (0.2%) were eligible. These studies provided a combined sample size of 5108participants.


MICROBIOLOGICALDIAGNOSIS

Waterer GW, RespMed 2001;95(1)78-82Campell SG,Chest2003;123:1142


Sputum: Gram staining and culture Expectorated sputum should be deep cough specimen obtained before antibiotic treatmentand it should be rapidly transported and processedwithin a few hours of collection.

Blood cultures (2 sets)2 sets of blood cultures should be drawn before initiation of antibiotic therapy during thefirst 24 hours.

Clinical Infectious Diseases 2007; 44:S27–72


URINEANTIGEN

§ ΑgSpneumoniae shouldbeperformedin patientsadmittedtothehospitalforreasonsofillnessseverityand wheneverapleural fluidsampleisobtainedinthesettingofaparapneumonic effusion

§ UrineL.pneumophilaserogroup1Αgdetectionshould beperformedinpatientsadmittedtothehospitalforreasonsofseverityandinotherpatientswherethisinfectionis clinicallyorepidemiologicallysuspected

§ Thetestretainsvalidityevenaftertheinitiationofantibiotictherapy

Clin Microbiol Infect 2011; 17(Suppl. 6): E1–E59


Ø Ofthese,78%hadabacterialpathogendetectedbyPCRbutonly32%wereculture-positive(p<.0001)

Ø Viruseswerepresentin30%ofcases;82%ofthesewereco-detectionswithbacteria

Ø Moleculartestinghadthepotentialtoenablede-escalationinnumberand/orspectrumofantimicrobialsin77%ofpatients.

Fast multiplex real-time polymerase-chain reaction (PCR) assays for 26 respiratory bacteria and viruses.

S. pneumoniae in 36%,H. influenzae in 40%,

Moraxella in 14%, S. aureus in 10%, Klebsiella in 4%,

Pseudomonas in 3%, Mycoplasma or Legionella

in <2% each


Clinical Parameter Scoring

Age in years Example

For Men (Age in yrs) 50

For Women (Age -10)

(50-10)

NH Resident 10 points

Co-morbid Illnesses

Neoplasia 30 points

Liver Disease 20 points

CHF 10 points

CVD 10 points

Renal Disease (CKD) 10 points

Clinical Parameter Scoring

Clinical Findings

Altered Sensorium 20 points

Respiratory Rate > 30 20 points

SBP < 90 mm 20 points

Temp < 350 C or > 400 C 15 points

Pulse > 125 per min 10 points

Investigation Findings

Arterial pH < 7.35 30 points

BUN > 30 20 points

Serum Na < 130 20 points

Hematocrit < 30% 10 points

Blood Glucose > 250 10 points

Pa O2 10 points

X Ray e/o Pleural Effusion

10 points

PSI


Minor criteriaØ RR ≥30 /minØ PaO2/FiO2 ≤250 *Ø Multilobar InvolvementØ ConfusionØ Uremia (BUN ≥20 mg/dL)Ø Leucopenia (<4x109/L)Ø Thrombocytopenia(<100x109/L)Ø Hypothermia (Θ<36ºC)Ø Hypotension requiring aggressive fluid resuscitation

Major criteriaØ Mechanical VentilationØ Septick shock with the need for vasopressors

31

Mandell et al, Clin Infect Dis 2007; 44 (S2):S27-S72

3 of minors

1 of majors

Mandell et al, Clin Infect Dis 2007; 44 (S2):S27-S72

ICUADMISSION


THERAPY


I. CAP– outpatienttreatmentØPreviouslyhealthyandnoriskfactorsforPRSP

MacrolideDoxycycline

Presenceofcomorbidities (CHF,renal-respiratoryorhepaticdisease,diabetesmelitus,alcoholism,asplenia, malignancies,immunosuppressingconditionsormedication),useofantimicrobialswithintheprevious3months:RespiratoryfluoroquinoloneΒ-lactam +macrolide- highdoseamoxicillinoramoxicillin-clavulanate

ATHENS 2019GREECE | 27-29 JUNETHERAPYOFCAP

MODERATEØAminopenicillin± macrolideØAminopenicillin/β-lactamaseinhibitor ± macrolide

ØNon-antipseudomonalcephalosporin

ØCefotaxime or ceftriaxone ±macrolide

ØLevofloxacinØMoxifloxacinØPenicillinG± macrolide

ØNon-antipseudomonal cephalosporin III+macrolideØmoxifloxacin or levofloxacin ± non-antipseudomonal cephalosporin IIIRiskfactor for PsAØAntipseudomonal cephalosporinØOr acylureidopenicillin/β-lactamaseinhibitor

Øor carbapenemPLUS

ØCiprofloxacinORPLUS

ØMacrolide +aminoglycoside

Woodhead M. et al., Clin Microbiol Infect 2011

SEVERE


DURATIONOFTHERAPY

- In clinical practice, a standard 10-14 days approach is still used to decide duration of antibiotic therapy in CAP patients.

- ATS/IDSA 2007 and ERS 2011 guidelines recommendations suggest to individualize duration of antibiotic therapy on patients’ characteristicsnicalpractice, a standard 10-14 days approach is still used to decide duration of

antibiotic therapy in CAP patients.

- ATS/IDSA 2007 and ERS 2011 guidelines recommendations suggest to individualize duration of antibiotic therapy on patients’ characteristics.

Woodhead M, Clin Microbiol Infect 2011Mandell LA, CID 2007

ERJ 2010; 36(1):128–34

- Patients with CAP should be treated for a minimum of 5 days (level I evidence), should be afebrile for 48–72 h, and should have no more than 1 CAP-associated sign of clinical instability before discontinuation of therapy (level

II evidence).


Ø Inthismulticenterstudy,1182patientshospitalizedforCAPwereprospectivelyfollowedforupto30days

aftertheirhospitalizationforthisinfection.

Ø 380(32.2%)patientsexperiencedintrahospitalcardiovascularevents(CVEs)including281(23.8%)withheart

failure,109(9.2%)withatrialfibrillation,89(8%)withmyocardialinfarction,11(0.9%)withischemicstroke,

and1(0.1%)withdeepvenousthrombosis;28patients(2.4%)diedforcardiovascularcauses.

Ø 30dayυmortalitywassignificantlyhigherinpatientswhodevelopedCVEscomparedwiththosewhodidnot

(17.6%vs4.5%,P<.001).


38

PREVENTION

ØSmokingCessationØΕμβολιασμόςØ InfluenzaØ Inactivatedvaccineforpeople>50yo,thoseatriskforinfluenzacomplications,pregnancy,householdcontactsofhigh-riskpersonsandhealthcareworkers

Ø Intranasallive,attenuatedvaccine:5-49 yo withoutchronicunderlyingdz

Ø Pneumococcal(PPV23,PCV13)Immunocompetent≥65yo,chronicillnessandimmunocompromised≤64yo


Hospital-acquiredpneumonia

NewGuidelines(2016fromATS,2017fromERS)• Definitions• Pathogenesis• Etiology• Diagnosis:invasiveornon-invasivetechniques• Therapy§

ATHENS 2019GREECE | 27-29 JUNEHAP

NNVAP NIV

MVHAP


MAINFOCUS(2005)

Ø HCAP(HEALTHCAREASSOCIATEDPNEUMONIA)

Ø MDR(MULTIDRUGRESISTANTBACTERIA)

Pseudomonasaeruginosa,Acinetobacterspp.,Staphylococcusaureus

ATHENS 2019GREECE | 27-29 JUNEEPIDEMIOLOGY

§ HAP/VAPtogetheraccountfor22%ofallhospital-associatedinfections

▸ HAP:5- 20cases/1000admissions,higherratesamongimmunocompromised,surgery &elderly.

Ølesssevere,butseriouscomplicationsstilloccurin~50%ofpatientswith20%requireICUadmission

▸VAP ~10%incidenceofVAPinpatientsrequiringventilation

▸ All-causemortality inpatientswithVAP20-50%,attributablemortality13%

▸ prolongslengthofventilationby7.6- 11.5days

▸ prolongshospitalizationby11.5- 13.1days

▸ $40Kexcesscostperpatient(USdata)

▸ $46millionexcesscostannually(Canadiandata)

Clin Infect Dis 2016; 63: e61-e111Giuliano KK: 2018, Davies G: Pa Patient Saf Advis 2012,Baker D:2018


Patient Surgery Drugs Invasive devices

Respiratory devices

Gastric colonization

oropharyngeal colonization

ASPIRATIONΒacterialVirulence

Lung Immunitycellular / humoral Translocation

Bacteremia

VAP

Previous antbs

45 PATHOGENESIS


MICROBIOLOGYOFHAP/VAPCorepathogensStr. pneumoniaeMethicillin-susceptibleStaphylococcusaureus(MSSA)Haemophilus influenzaeGram(-)EnterobacteriaeceaeEscherichiacoliKlebsiellapneumoniaeEnterobacterspp.Proteusspp.Serratiamarcescens

American Thoracic Society. GuidelinesAm J Respir Crit Care Med 2005


MDRs

Ø Methicillin-resistantS.aureus (MRSA)Ø Pseudomonasaeruginosa resistanttoantipseudomonalpenicillins,cephalosporins,carbapenems,andquinolones

Ø Acinetobacterbaumanii

Ø Vancomycin-resistantEnterococcusØ Enterobacteriaceaeproducingextended-spectrumB-lactamases(ESBL)

Rello J, 2011 ERJ

Mortality rates according to pathogens found in 224 HAP and 465 VAP episodes


DIAGNOSTICSTRATEGY

NOGOLDSTADARD


50

???


ClinicalDiagnosticStrategy

ClinicalsuspicionØ PatientonMV+infiltrateCXR

Ø+2/3findingsØ Symptomsà infection:

Ø(1)Fever,(2)purulenttrachealsecretions

Ø Laboratoryà infection:

Ø(3)Leukocytosis orleukopenia

ØHypoxemia

DifferentialdiagnosisPChemicalaspirationwithoutinfection

PAtelectasis

PPulmonaryembolism

PARDS

PPulmonaryhemorrhage

PLungcontusion

PDrugreaction

POther


InPatientsWithSuspectedHAP(Non-VAP),ShouldTreatmentBeGuidedbytheResultsofMicrobiologicStudiesPerformedonRespiratorySamples,orShouldTreatmentBeEmpiric?

ØTreataccordingtotheresultsofmicrobiologicstudiesperformedonrespiratorysamplesobtainednoninvasively, ratherthanbeingtreatedempirically(weakrecommendation,verylow-qualityevidence).

ØRemarks:Non-invasivemethodstoobtainrespiratorysamplesincludethefollowing:

Ø spontaneousexpectoration,

Ø sputuminduction,

Ø naso-trachealsuctioninginapatientwhoisunabletocooperatetoproduceasputumsample,and

Ø endotrachealaspirationinapatientwithHAPwhosubsequentlyrequiresmechanicalventilation.


Non-invasivesamplingwithsemi-quantitativeculturestodiagnose

VAP(weakrecommendation,low-qualityevidence).

Remarks:Invasiverespiratorysamplingincludesbronchoscopictechniques(ie,bronchoalveolarlavage[BAL],protectedspecimenbrush[PSB])andblindbronchialsampling(ie,mini-BAL).Noninvasiverespiratorysamplingreferstoendotrachealaspiration.

-739patients with VAP

-Randomized to quantitative BALvsqualitative EA

-Randomized to Meropenem+Ciprofloxacin or Meropenemalone

-Antibiotics adjusted by cultureandsensitivity reports

-Exclusion of infected or colonizedby Paeruginosa or MRSA


Using clinicalcriteriaalone,ratherthanusingserumPCT plusclinicalcriteria,todecidewhetherornottoinitiateantibiotictherapy(strongrecommendation,moderate-qualityevidence)

Usingclinicalcriteriaalone,ratherthanusingCPIS plusclinicalcriteria,todecidewhetherornottoinitiateantibiotictherapy(weakrecommendation,low-qualityevidence).

Usingclinicalcriteriaalone,ratherthanusingbroncho-alveolarlavagefluid(BALF)sTREM-1plusclinicalcriteria,todecidewhetherornottoinitiateantibiotictherapy(strongrecommendation,moderate-qualityevidence).

Kalil 2016, Torres 2017

BIOMARKERS

ATHENS 2019GREECE | 27-29 JUNETHERAPY

Whatchanged?ØEmpirictreatmentshouldcoverMDRpathogensinanypatientwithriskfactorsregardlessofthetimeofonsetofinfection

ØEachhospitalgenerateantibiogramstoguidehealthcareprofessionalswithrespecttotheoptimalchoiceofantibiotics.


INITIALEMPIRICTREATMENT

ØTakeintoconsiderationthelocalmicrobiologypatternsofICUorhospital

ØTheinitialantibiotictreatmentismostlikelytobeappropriatewhengivenbaseduponaprotocoladjustedtothelocalresistancepatterns

ØPatientsinwhomHAP/VAPissuspectedshouldbeadministeredinitialempiricaltreatmentaftersamplesformicrobiologicalculturesarecollected.


MDRs


THERAPYVAP

Kalil etal,CID2016


62

VAPTHERAPY


HAPTHERAPY


EMPIRICALTHERAPYFORHAP

§ MRSAcoveragewhenwehaveriskfactorforresistanceorhighriskformortality(needforventilatorysupportorsepticshock) (weakrecommendation,verylow-qualityevidence)

ØPseud.aeruginosa coveragewith2antbs whenwehaveriskfactorforresistanceorhighriskformortality(strongrecommendation, verylow-qualityevidence)

ØNOTusingaminoglycoside asthesoleantb agent


ImpactofEarlyAntibioticTreatmentonMortality

Seymour CW. al. N EnglJ Med 2017

ATHENS 2019GREECE | 27-29 JUNEDURATIONOFTHERAPY

Before2005

• 14-21days2005

• 7daysforclinicalimprovement

• 14daysforPseudaerugHAP/VAP

2016• 7daysforall

▸“Werecommenda7-daycourseofantimicrobialtherapyratherthanalongerduration”(strongrecommendation,moderate-qualityevidence)


ForpatientswithHAP/VAP,wesuggestusingPCT levelsplusclinicalcriteria toguidethediscontinuationofantibiotictherapy,ratherthanclinicalcriteriaalone

Kalil et al, CID 2016,Torres 2017

WedonotrecommendtheroutinemeasurementofserialserumPCT levelstoreducedurationoftheantibioticcourseinpatientswithHAP/VAPwhentheanticipateddurationis7–8days.


ForpatientswithVAPduetoGNBthataresusceptibletoonlyaminoglycosidesorpolymyxins(colistin orpolymyxinB),wesuggestbothinhaledandsystemicantibiotics,ratherthansystemicantibiotics alone (weakrecommendation,verylow-quality

evidence).

Kalil et al, CID2016


§ 68 years old male with history of COPD (GOLD IV) is intubated due to hypercapnic coma

§ On day 4 of hospitalization, he developed fever(38° C), hypotension and a new left-sided infiltrate

§ ICU has an incidence of MRSA >20%

WHICH IS THE RECOMMENDED ANTIBIOTIC THERAPY?

QUESTION


A. MeropenemB.Ciprofloxacin+linezolidC.AminoglycosideD.Vancomycinandcefepime +ciproxinE.Noneoftheabove


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