Copia (2) de 03 pneumonia guidelines-masterton

1st Asia Pacific Summit

Grand Hyatt, SingaporeGrand Hyatt, Singapore44thth-5-5thth March March

Pneumonia Treatment GuidelinesHospital-acquired Pneumonia (HAP)

Robert G MastertonRobert G MastertonNHS Ayrshire and Arran, UKNHS Ayrshire and Arran, UK

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Why Guidelines?Why Guidelines?

• Evidence-based practiceEvidence-based practice– Best outcome for patientsBest outcome for patients

– Best use of resourceBest use of resource

– Constrains idiosyncratic behaviourConstrains idiosyncratic behaviour

• Legal protectionLegal protection

• Identify research needsIdentify research needs

• A tool for educationA tool for education

• Gain public confidenceGain public confidence

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Why Guidelines for HAP?Why Guidelines for HAP?

• Second commonest hospital-acquired infection (15%)Second commonest hospital-acquired infection (15%)

• 0.5–1% of hospital admissions0.5–1% of hospital admissions

• Ventilator-associated pneumonia (VAP) 5–50% of Ventilator-associated pneumonia (VAP) 5–50% of ventilated patients ventilated patients

• About 50% is E-VAPAbout 50% is E-VAP

• Hazard rate Hazard rate – 3% per day Week 13% per day Week 1

– 2% per day Week 22% per day Week 2

– 1% per day Week 31% per day Week 3

Am J Respir Crit Care Med. 2005;171:388–416.

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Why Guidelines for HAP?Why Guidelines for HAP?

• Mortality Mortality – Crude rate = 20–50%Crude rate = 20–50%– Attributable rate = 30–33% for non-ventilatedAttributable rate = 30–33% for non-ventilated– Attributable rate = 27–43% for ventilatedAttributable rate = 27–43% for ventilated– Relative factor of x2 to x10 in ICURelative factor of x2 to x10 in ICU

• MorbidityMorbidity– >Intubation = 18–22 days for VAP>Intubation = 18–22 days for VAP– >Length of stay x2–3 = circa 13 days for VAP>Length of stay x2–3 = circa 13 days for VAP– USA 1997: 1.75 million hospital bed daysUSA 1997: 1.75 million hospital bed days– Cost USA 1997: $5,800 per case = $1.5 billion in totalCost USA 1997: $5,800 per case = $1.5 billion in total

Adapted from Am J Respir Crit Care Med. 2005;171:388–416.

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The Microbiology of HAPThe Microbiology of HAP

• Gram-negative = 48%Gram-negative = 48%• PseudomonasPseudomonas spp. spp.

• AcinetobacterAcinetobacter spp. spp.

• Klebsiella spp.Klebsiella spp.

• E.coliE.coli

• Gram-positive = 43%Gram-positive = 43%• S. aureusS. aureus

• S. pneumoniaeS. pneumoniae

• Others = 9% (viruses 1%)Others = 9% (viruses 1%)


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Early-onsetEarly-onset Late-onsetLate-onset

pneumoniapneumonia pneumoniapneumonia Others based onOthers based on

(<5 days)(<5 days) (>5 days)(>5 days) specific risksspecific risks

S. pneumoniaeS. pneumoniae P. aeruginosaP. aeruginosa Anaerobic bacteria Anaerobic bacteria

H. influenzaeH. influenzae EnterobacterEnterobacter spp. spp. Legionella pneumophilaLegionella pneumophila

S. aureusS. aureus AcinetobacterAcinetobacter spp. spp.

Enterobacteriaceae Enterobacteriaceae K. pneumoniaeK. pneumoniae

S. marcescensS. marcescens Influenza A and B Influenza A and B E. coliE. coli Respiratory syncytial Respiratory syncytial Other GNB Other GNB virusvirus

S. aureus S. aureus (MRSA) (MRSA)

FungiFungi

The Microbiology of HAPThe Microbiology of HAP

GNB, Gram-negative bacilli; MRSA, methicillin-resistant S.aureus


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HAP GuidelinesHAP Guidelines

• Pulmonary guidelines are increasingly published in Pulmonary guidelines are increasingly published in peer-reviewed journals, but few are tested clinically in peer-reviewed journals, but few are tested clinically in randomised controlled trials (RCTs). randomised controlled trials (RCTs). – There is continued reliance on consensus statements and There is continued reliance on consensus statements and

expert opinion. expert opinion.

– Pulmonary guideline publications have continued to Pulmonary guideline publications have continued to increase dramatically in number and in importance since increase dramatically in number and in importance since 1974, both on the local level and internationally (13.3% are 1974, both on the local level and internationally (13.3% are about pneumonia)about pneumonia)

Hackner et al. Chest 1999;116:1046–1062

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• SwedenSweden– Patients treated at medical institutions with home-like conditionsPatients treated at medical institutions with home-like conditions

– Patients hospitalised in acute somatic departmentsPatients hospitalised in acute somatic departments

– Post-operative patientsPost-operative patients

• France — VAP onlyFrance — VAP only– Early onset — no prior antibioticsEarly onset — no prior antibiotics

– Early onset — prior antibioticsEarly onset — prior antibiotics

• OROR– Late onset — no prior antibioticsLate onset — no prior antibiotics

– Late onset — prior antibioticsLate onset — prior antibiotics

Mandell et al. Chest 1998;113:188S–193S

29 countries surveyed5 with HAP guidelines2 in Europe

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Which Guideline Is best?Which Guideline Is best?

VariableVariable ATS (1996)ATS (1996) Trouillet (1998)Trouillet (1998)

Predictive accuracy for Predictive accuracy for organismorganism

91%91% 83%83%

Adequacy of treatment Adequacy of treatment recommendationsrecommendations

79%79% 80%80%

Problem organismsProblem organisms PseudomonasPseudomonas spp., spp., AcinetobacterAcinetobacter spp., spp., Stenotrophomonas Stenotrophomonas spp., MRSAspp., MRSA

PseudomonasPseudomonas spp. spp.

Ioanas et al. Eur Respir J 2003;22:876–82

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NameName YearYear CountryCountry TreatmentTreatment PreventionPrevention DiagnosisDiagnosis

BSACBSAC 20062006 UKUK

ATSATS 20052005 USAUSA

GALANNGALANN 20052005 Lat/AmLat/Am

CCCSCCCS 20042004 CanadaCanada

HICPACHICPAC 20042004 USAUSA

GEIH, etc.GEIH, etc. 20042004 SpainSpain (severe)(severe)

CoronaCorona 20032003 ItalyItaly

CollardCollard 20032003 USAUSA

ICCCICCC 20022002 GlobalGlobal

RelloRello 20012001 SpainSpain

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BSAC Work StreamsBSAC Work Streams

Sub-groupSub-group Citations reviewedCitations reviewed Articles reviewedArticles reviewed

PreventionPrevention 971971 350350

DiagnosisDiagnosis 17531753 8585

TreatmentTreatment 38683868 308308

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Classification of EvidenceClassification of Evidence

• Systematic reviews and meta-analyses of RCTs Systematic reviews and meta-analyses of RCTs

• Prospective RCTsProspective RCTs

• Non-randomised intervention studiesNon-randomised intervention studies

• Cohort studiesCohort studies

• Diagnostic studiesDiagnostic studies

• Expert opinionExpert opinion

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BSAC Data QualityBSAC Data Quality

0

10

20

30

40

50

60

70

Prevention Diagnosis Treatment

Syst rev

RCT

Cohort

Case con

Diagnostic

Expert opinion

Percentage of papers reviewed

15 Am J Respir Crit Care Med. 2005;171:388–416

HAP, VAP and Healthcare-associated HAP, VAP and Healthcare-associated pneumonia (HCAP) Guidelinepneumonia (HCAP) Guideline

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HAP, VAP or HCAP suspected

Obtain lower respiratory tract (LRT) sample for culture (quantitative or semi-quantitative) and microscopy

Clinical improvement at 48–72 hours

De-escalate antibiotics, if possible.

Treat selected patients for 7–8 days

and reassess

Search for other pathogens,

complications, other diagnoses or othersites of infection

Days 2 and 3: Check cultures and assess clinical response: (temperature, WBC, chest X-ray, oxygenation, purulent sputum,

haemodynamic changes and organ function)

YESYESNONO

Unless there Is both a low clinical suspicion for pneumonia and negative microscopy of LRT sample, begin empiric antimicrobial therapy using algorithm in Figure 2 and local microbiologic data

Cultures -

Consider stopping

antibiotics

Adjust antibiotic therapy, search for other

pathogens, complications, other diagnoses or other

sites of infection

Cultures +Cultures +Cultures -

Am J Respir Crit Care Med. 2005;171:388–416

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Questions for Treatment PracticeQuestions for Treatment Practice

• What are the optimal empiric and definitive antibiotic What are the optimal empiric and definitive antibiotic therapies for patients with HAP?therapies for patients with HAP?

• Do pharmacodynamic and pharmacokinetic profiles Do pharmacodynamic and pharmacokinetic profiles influence outcomes? influence outcomes?

• Do outcomes depend on whether monotherapy or Do outcomes depend on whether monotherapy or combination therapy is used? combination therapy is used?

• Are data available to support the efficacy of instilled or Are data available to support the efficacy of instilled or nebulised therapy? nebulised therapy?

• Are there clear criteria available for the initiation of Are there clear criteria available for the initiation of step-down therapy, eg intravenous to oral?step-down therapy, eg intravenous to oral?

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Treatment — Volume of Evidence (1)Treatment — Volume of Evidence (1)

• There is a large body of evidence from RCTs over the There is a large body of evidence from RCTs over the past three decadespast three decades

• Earlier studies evaluated antibiotics that are no longer Earlier studies evaluated antibiotics that are no longer regarded as appropriate empiric therapy for HAP regarded as appropriate empiric therapy for HAP particularly late-onset — due to dramatic changes in particularly late-onset — due to dramatic changes in the nature and susceptibility patterns of the pathogensthe nature and susceptibility patterns of the pathogens

• No well-conducted studies for pharmacoeconomic or No well-conducted studies for pharmacoeconomic or health economic evaluationshealth economic evaluations

www.bsac.org.uk

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• Only four studies were randomised double-blind Only four studies were randomised double-blind studiesstudies

• In several studies so few patients were enrolled that In several studies so few patients were enrolled that the likelihood of a type II error is high the likelihood of a type II error is high

• No studies addressed patient demography and risk No studies addressed patient demography and risk factors or assessed empiric or definitive treatment in factors or assessed empiric or definitive treatment in relation to severity of illness or duration of relation to severity of illness or duration of hospitalisationhospitalisation

• Limited data concerning the influence of appropriate Limited data concerning the influence of appropriate therapy on duration of hospital stay, particularly length therapy on duration of hospital stay, particularly length of time on a ventilator, and costof time on a ventilator, and cost

www.bsac.org.uk

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• Few studies compared >2 therapeutic optionsFew studies compared >2 therapeutic options

• Almost all studies had insufficient power to Almost all studies had insufficient power to demonstrate superiority of one regimen over another demonstrate superiority of one regimen over another

• A limitation is that the primary microbiological A limitation is that the primary microbiological evaluations are invariably related to pathogens that are evaluations are invariably related to pathogens that are susceptible to the trial antibioticssusceptible to the trial antibiotics

• Only six studies recruited ≥200 patients to both Only six studies recruited ≥200 patients to both treatment and comparator arms treatment and comparator arms

www.bsac.org.uk

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And the Evidence Shows …And the Evidence Shows …

• Whereas the pathogens and their susceptibility in late-Whereas the pathogens and their susceptibility in late-onset HAP are highly variable, those in early-onset onset HAP are highly variable, those in early-onset HAP are limitedHAP are limited

Evidence grade = 2+Evidence grade = 2+

• Infections caused by Infections caused by P. aeruginosaP. aeruginosa are associated are associated with a significantly higher incidence of treatment failure with a significantly higher incidence of treatment failure than those caused by other organismsthan those caused by other organisms

Evidence grade = 1+Evidence grade = 1+

www.bsac.org.uk

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Treatment RecommendationTreatment Recommendation

• The choice of empiric antibiotic therapy for patients The choice of empiric antibiotic therapy for patients with HAP in an individual unit should be based on with HAP in an individual unit should be based on knowledge of the nature and susceptibility patterns of knowledge of the nature and susceptibility patterns of the pathogens that are prevalent in that unit andthe pathogens that are prevalent in that unit and– Should also take account of such variables as duration of Should also take account of such variables as duration of

hospital stay (ie, early- or late-onset infection), recent hospital stay (ie, early- or late-onset infection), recent administration of antibiotic therapy and co-morbidities.administration of antibiotic therapy and co-morbidities.

– Similarly, definitive therapy should be determined by culture Similarly, definitive therapy should be determined by culture and susceptibility test results and susceptibility test results

Recommendation grade = ARecommendation grade = A

www.bsac.org.uk

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Treatment Recommendation (2)Treatment Recommendation (2)

• Treatment with an appropriate antibiotic should be Treatment with an appropriate antibiotic should be started as soon as possible in order to reduce mortalitystarted as soon as possible in order to reduce mortality

Recommendation grade = ARecommendation grade = A

http://www.bsac.org.uk/

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Good Practice PointsGood Practice Points

• For patients with early-onset infections (For patients with early-onset infections (<5<5 days after days after admission to hospital) who have not previously admission to hospital) who have not previously received antibiotics and in the absence of other risk received antibiotics and in the absence of other risk factors, the use of amoxicillin/clavulanate or factors, the use of amoxicillin/clavulanate or cefuroxime would be appropriatecefuroxime would be appropriate

• For patients with early-onset infections (For patients with early-onset infections (<5<5 days days following admission to hospital) who have recently following admission to hospital) who have recently received antibiotics and/or have other risk factors, a received antibiotics and/or have other risk factors, a third-generation cephalosporin (cefotaxime or third-generation cephalosporin (cefotaxime or ceftriaxone) or a fluoroquinolone, or ceftriaxone) or a fluoroquinolone, or piperacillin/tazobactam would be appropriatepiperacillin/tazobactam would be appropriate

www.bsac.org.uk

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ATS Treatment GuidanceATS Treatment Guidance

• Select empiric therapy based on the absence or presence of risk factors for MDR pathogens.

• Choice of agents dictated by local microbiology, cost, availability, and formulary restrictions.

• Patients with HCAP should be treated for potentially drug-resistant organisms

• Inappropriate therapy is a major risk factor for excess mortality and length of stay and antibiotic-resistance is most commonly associated with inappropriate therapy.

• In empiric therapy where recent antibiotic used select from a different antibiotic class.

• Initial antibiotic therapy should be given promptly because delays in administration may add to excess mortality resulting from VAP.

• Initial empiric therapy is more likely to be appropriate if a protocol for antibiotic selection is developed.


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ATS Guidance against Late HAPATS Guidance against Late HAP

Potential Pathogens Combination Antibiotic Therapy

Late HAP & MDR pathogens

Pseudomonas aeruginosa or

Klebsiella pneumoniae (ESBL)

Acinetobacter species

MRSA

Legionella pneumophila

Antipseudomonal cephalosporin (cefepime, ceftazidime)

Antipseudomonal carbepenem

(imipenem or meropenem)

or beta-Lactam/-lactamase inhibitor (piperacillin–tazobactam) plus Antipseudomonal fluoroquinolone†

(ciprofloxacin or levofloxacin) or Aminoglycoside

(amikacin, gentamicin, or tobramycin)

plus

Linezolid or vancomycin


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HAP Treatment ConsensusHAP Treatment Consensus

• Risk assessment approachRisk assessment approach

• Early versus late antibiotic selectionEarly versus late antibiotic selection

• Empiric late treatment driven by local surveillanceEmpiric late treatment driven by local surveillance

• Hit hard and hit earlyHit hard and hit early

• As short a duration as possibleAs short a duration as possible

• De-escalate when and where possibleDe-escalate when and where possible

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Do Great Minds Think Alike …?Do Great Minds Think Alike …?

BSACBSAC ATSATS

PreventionPrevention

SDDSDD

Effective, cost- Effective, cost- effective, no effective, no resistance riskresistance risk

HAP but HAP but discourage use due discourage use due to resistanceto resistance

DiagnosisDiagnosis

MicrobiologyMicrobiology

Treat and testTreat and test Test and treatTest and treat

TreatmentTreatment

MRSA — linezolidMRSA — linezolid

No recommendation No recommendation can be madecan be made

Superiority needs Superiority needs validationvalidation

May be preferredMay be preferred

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VAP Guideline AdherenceVAP Guideline Adherence

• The overall non-adherence rate was 37.0% The overall non-adherence rate was 37.0% • The non-adherence rate was 25.2% for clinical use The non-adherence rate was 25.2% for clinical use

strategies, and 45.6% for less effective strategiesstrategies, and 45.6% for less effective strategies• Pharmacological strategies had a higher degree of –Pharmacological strategies had a higher degree of –

non-adherence than non-pharmacological strategiesnon-adherence than non-pharmacological strategies• Non-adherence to recommendations did not relate to Non-adherence to recommendations did not relate to

the weight of evidencethe weight of evidence

• Commonest reasons for non-adherence were:Commonest reasons for non-adherence were:– Disagreement with interpretation of clinical trials (35%)Disagreement with interpretation of clinical trials (35%)– Unavailability of resources (31.3%)Unavailability of resources (31.3%)– Costs (16.9%)Costs (16.9%)

Rello et al. Chest 2002;122:656–661

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Do Guidelines Work in VAP?Do Guidelines Work in VAP?

• ICU imipenem-based regimenICU imipenem-based regimen

• After D3 therapy based on susceptibility resultsAfter D3 therapy based on susceptibility results

• Better empirical cover (81 vs 46%; p<0.01)Better empirical cover (81 vs 46%; p<0.01)

• No change in imipenem resistance ratesNo change in imipenem resistance rates

Soo Hoo et al. Chest 2005;128:2778-87

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The Future for HAP GuidelinesThe Future for HAP Guidelines

• Production of a guideline model for all to follow easilyProduction of a guideline model for all to follow easily

• Holistic guidelinesHolistic guidelines

• Production of care-path bundleProduction of care-path bundle

• Cost-effectiveness evaluationCost-effectiveness evaluation

• A single set of recommendationsA single set of recommendations

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1st Asia Pacific Summit

Grand Hyatt, SingaporeGrand Hyatt, Singapore44thth-5-5thth March March

Health & Medicine

Copia (2) de 03 pneumonia guidelines-masterton