best therapy of healthcare-associated pneumonia: narrow vs

Best therapy of healthcare-associated pneumonia: narrow vs broad spectrum antimicrobials?

Michele Bartoletti Infectious Diseases Unit S. Orsola Teaching Hospital

ESCMID COURSE - Ferney-Voltaire (France) November 5 -6 2015

“Moving antimicrobial stewardship forward in special patient populations”

ESCMID Online Lecture Library

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CAP

Pneumonia classification


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CAP

HAP



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CAP

HAP

VAP


non-VAP


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CAP

HAP

VAP

HCAPHCAP


non-VAP


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Community onset MDR bloodstream infections

Community onset MRSA bacteremiaMorin and Hadler J Infect Dis 2001

Friedman et al. Ann Intern Med 2002

Tacconelli et al. JAC 2004

Community onset MRSA bacteremia

CAP HAP, VAPATS 1996

HCAP ATS guidelines 2005

Origin of HCAP


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Contact with the health system

Prior hospitalization and/or surgery

IV/wound care at home

Residence in a nursing home or LTCF

Chronic hemodialysisChemotherapy

HCAPFriedman et al. Ann Intern Med 2002


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Pneumonia treated in the internal medicine department: focus on healthcare-associated pneumonia

Giannella M. Clin Microbiol Infect. 2012;18:786-94

CAP

N=148 (%)HCAP

N=65 (%)HAP

N=21 (%)P

Gram-positive

S. pneumoniae

MRSAMSSA

94 (63.5)

1 (0.7)1 (0.7)

25 (38.5)

8 (12.3)1 (1.5)

3 (14.3)

2 (9.5)2 (9.5)

<0.001

<0.0010.03

Gram-negative

Enterobacteriaceae

P. aeruginosa

L. pneumophila

H. influenzae

A. baumannii

17 (11.5)

5 (3.4)11 (7.4)

5 (3.4)

0

8 (12.3)

11 (16.9)2 (3.1)

3 (4.6)

0

5 (23.8)

6 (28.6)0

0

2 (9.5)

0.27

<0.0010.34

0.86

0.008

1002 pts with pneumonia hospitalized in IMDs


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Failure to cover MDR pathogens leads to inadequate initial

antimicrobial coverage and accounts for excess mortality

HCAP patients should be identified and treated with initial

broad-spectrum antibiotic therapy

HCAP presents an etiological pattern

similar to that of HAP

The concept of HCAP


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Prevalence 18-67%

Median age 64-81 years

High rate of comorbidities (CHF, COPD, cerebrovascular

disease)

Poor functional status

Risk factors for aspiration pneumonia

Treatment restrictions

Mortality 18-28%

Kollef et al. Chest 2005; Carratala et al. Arch Intern Med 2007;

Shindo et al Chest 2009; Venditti et al. Ann Intern Med 2009;

Chalmers et al Clin Infect Dis 2011; Jung et al. BMC Infect Dis 2011

HCAP


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HCAP = HAP ?

Aggressive broad-spectrum therapy

HCAP = SEVERE HOSPITALIZED CAP ?

Beta – lactam +

Macrolide

• Increased costs and comsumption of antibiotics

• Incresed risk of MDR pathogens selection

•Increased risk of inadequate empirical therapy

• Increased risk for mortality


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HCAP comprises very heterogeneous conditions, not all

patients need broad spectrum antibiotic therapy

Increased frequency of MDR and increased mortality are

not consistently related

Guideline concordant treatment could not be shown to

be associated with better outcome

Brito V. and Niederman MS. Curr Opin Infect Dis 2009

Ewig S. et al. Lancet Infect Dis 2010

Ewig S. et al. Curr Opin Infect Dis 2012

Criticisms to the HCAP concept


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Predicting MDR risk by HCAP model

Webb BJ et al. Respiratory Med 2014


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Kollef 2005

N=988

Shindo 2009

N=141

Chalmers 2011 N=277

Garcia-Vidal 2011 N=577

Country USA (59 H) Japan UK Spain

Type of study Multicenter retrospective all CP cases

Single center retrospective

Dx=77

Single center prospective

Dx=90

Single center prospective(‘01-’09) Dx=414

S. pneumoniae 7.1% 13.5% 49.4% 45.4%

H. influenzae 5.8% 2.8% 14.6% 6%

Legionella spp. - 0 3.4% 1.6%

Atypical pathogens - 0.7% 3.3% 3.4%

MRSA 26.5% 3.5% 2.2% 0.2%

P. aeruginosa 25.3% 5.7% 2.2% 1.6%

Enterobacteriaceae 16.3% 13.4% 6.7% 3.6%

HCAP


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HCAP comprises very heterogeneous conditions, not all

patients need broad spectrum antibiotic therapy

Increased frequency of MDR and increased mortality are

not consistently related

Guideline concordant treatment are not associated to a

better outcome

Brito V. and Niederman MS. Curr Opin Infect Dis 2009

Ewig S. et al. Lancet Infect Dis 2010

Ewig S. et al. Curr Opin Infect Dis 2012

Criticisms to the HCAP concept


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Impact on mortality of

GLs concordant therapy

Grenier et al.

J Antimicrob Chemother 2011

NO

Chalmers et al.

Clin Infect Dis 2011

NO

Attridge et al.

Eur Respir J 2011

NO

Falcone et al.

Intern Emerg Med 2012

YES

Webb BJ et al.

Respiratory Medicine 2012

NO

Rotheberg et al.

J Abtimicrob Chemother 2015

NO

GLs concordant therapy in HCAP


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Clinical prediction models for CAP-DRP

Webb BJ et al. Respiratory Med 2014


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1. Identify patients at risk for CAP caused by DRP.


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Risk Factors for Drug-Resistant Pathogens in Community-acquired and Healthcare-associated Pneumonia

Objectives: to clarify risk factors for drug-resistant pathogens

(DRPs) in patients with CAP and HCAP.

Methods: prospective observational study conducted in

hospitalized patients with pneumonia at 10 institutions in Japan.

Pathogens identified as not susceptible to ceftriaxone, ampicillin-

sulbactam, macrolides, and respiratory fluoroquinolones were

defined as CAP-DRPs.

Y Shindo et al. AM J Resp Crit Care Med 2013


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Main Results:1,413 patients (887 CAP and 526 HCAP) were analyzed.

Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP.

These included:

o prior hospitalization (AOR 2.06; 95% CI, 1.23–3.43),

o immunosuppression (AOR, 2.31; 95% CI, 1.05–5.11),

o previous antibiotic use (AOR,2.45;95%CI,1.51–3.98),

o use of gastric acid–suppressive agents (AOR, 2.22; 95%CI, 1.39–3.57),

o tube feeding (AOR, 2.43; 95% CI, 1.18–5.00),

o nonambulatory status (AOR, 2.45; 95% CI, 1.40–4.30)7


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When no risk factors or only one risk factor is observed in a

pneumonia patient (86% of patients with CAP and 36% of

patients with HCAP in the current study), CAP-DRPs are low

(<10%) .


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2. Stratify for disease severity.


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A New Strategy for Healthcare-Associated Pneumonia: A 2-Year Prospective MulticenterCohort Study Using Risk Factors for Multidrug- Resistant Pathogens to Select InitialEmpiric Therapy. T.Maruyama et al. Clin Infect Dis 2013

124 CAP

321 HCAP

n=110 n=92 n=41 n=78

93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, 92.9% received appropriate therapy for the identified pathogen


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2. Stratify for disease severity.

3. Discontinue unecessary

antibioticsESCMID Online Lecture Library

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De-escalation therapy among bacteraemic patients withcommunity-acquired pneumonia

Carugati M Clin Microbiol Infect 2015; 21: 936.e11–936.e18

METHODS:Secondary analysis of the Community-Acquired Pneumonia Organization database

DET was defined as changing an appropriate empirical broad-spectrum regimen toa narrower-spectrum regimen according to culture results within 7 days from hospital admission

Study population: 261 patients with bacteriemic CAP

165 DET gropup 96 N-DET gropup

There was a significantly lower 30-day mortality rate in the DET group than in the N-DET group in univariate analysis ( 15.1% vs. 25.0%, p 0.04)

After adjustment for confounders, DET was not associated with an increased risk of 30-day mortality RR 0.78 (95% CI 0.47–1.27), p 0.32)


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Retrospective study, 2007-2009, 102 HCAP

77 NC, 29 PC

De-escalation in 55/77 NC within median 4 days

Schlueter et al. Infection 2010


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De-escalation of empirical therapy is associated with lowermortality in patients with severe sepsis and septic shock

A total of 628 patients with severe sepsis or septic shock at ICU admission were treated empirically with broad-spectrum antibiotics.

De-escalation was applied in 219 patients (34.9 %).

Garnacho-Montero J Intensive Care Med 2014; 40 (1):32-40

Patients with adequated empirical therapy

In terms of survival de-escalation therapy was a protective factor (OR0.54; 95 % CI 0.33–0.89). PS adjusted analysis confirmed this finding.


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Safety and clinical outcomes of carbapenem de-escalation as part ofan antimicrobial stewardship programme in an ESBL-endemic setting

Lew KY et al JAC. 2015 Apr;70(4):1219-25

Criteria for de-escalation

Empirical therapy Definitive therapy

•Afebrile

•Not on inotropes

•Systolic blood pressure returned to baseline

•Not mechanically ventilated or fraction of inspired oxygen ≤0.4

•Respiratory rate < 25 bpm

Microbiology-driven

Patients receiving meropenem or imipenem underwent a prospective ASP review for eligibility for de-escalation.

Patients in whom carbapenem was de-escalated or not de-escalated, representing the acceptance and rejection of the ASP recommendation, respectively, were compared


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Safety and clinical outcomes of carbapenem de-escalation as part ofan antimicrobial stewardship programme in an ESBL-endemic setting

Lew KY et al JAC. 2015 Apr;70(4):1219-25

De escalated patients

N= 204

Non de-escalated patients

N=96

P

Respiratory infections 60(29) 29(30) 0.84

Culture-negative infections 46(22) 27(28) 0.47

ESBL producing strain 35(22) 25(26) 0.20

Outcome

Survival at discharge 173 (84.8) 79 (82.3) 0.54

Duration of carbapenem use (days)

6 (4-8) 8 (7-11) <0.001

Incidence of CDAD 2 (1) 4 (4) 0.08

Incidence of XDR A.baumannii at 30 days

4(2) 7 (7.3) 0.04


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Predictive Value of Methicillin-Resistant Staphylococcusaureus (MRSA) Nasal Swab PCR Assay for MRSA Pneumonia

Dangerfield B. et alAntimicrob Agents Chemother. 2014;58(2):859-64

All patients with confirmed pneumonia who had both a nasal swab MRSA PCR test and a bacterial culture within predefined time intervals were included in the study

435 patients enrolled

54% cases were calssified as HCAP

14% of cases had a nasal swab culturepositive for MRSA

5.7% of cases had bloodculture or sputum positive for MRSA

Ability of nasal swab MRSA PCR assay in predicting MRSA pneumonia

SE SP PPV NPV

88.0% 90.1% 35.4% 99.2%


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Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia andPrior Receipt of Influenza Vaccination

Grijalva G et al JAMA. 2015;314(14):1488-1497.

METHODSThe Etiology of Pneumonia in the Community (EPIC) study was a prospectiveobservational multicenter study of hospitalizations for community-acquiredpneumonia

In this case-control study, authors used EPIC data from patients 6 months or older withlaboratory-confirmed influenza infection and verified vaccination status during theinfluenza seasons

RESULTSOverall, 2767 patients hospitalized for pneumonia were eligible for the study; 162(5.9%) had laboratory-confirmed influenza. Twenty-eight of 162 cases (17%) withinfluenza-associated pneumonia and 766 of 2605 controls (29%) with influenza-negativepneumonia had been vaccinated.

The adjusted odds ratio of prior influenza vaccination between cases and controlswas 0.43 (95% CI, 0.28-0.68; estimated vaccine effectiveness, 56.7%; 95% CI, 31.9%-72.5%).


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Antimicrobial stewardship:Reduction of unecessary antibiotic use for patients with pneumoniae

DE-ESCALATION: microbiological and clinically driven approach

No RF for MDR pathogens

Bloodcultures, culture of respiratory samples, urinary antigens, sample for respiratory viruses and influenza

β-lactam + macrolide

Etiologial diagnosis

De-escalation narrowing the antimicrobial spectrum

RF for MDR pathogens

Bloodcultures, culture of respiratory samples, urinary antigens, sample for respiratory viruses and influenza, nasal swab for MRSA

Pip/tzb + quinolone + anti MRSA*

Culture-negative and no clinical improvement

Repeat diagnostc work-up

SEVERE CAP/HCAP

Cultures-negative but clinical improvement

Switch to Oral intake(if possible)

72 h


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Take home messages

Clinical severity, patient risk factors for DRP, and local epidemiology should be considered in the choice of empirical therapy for pneumonia

Attempt to etiological diagnosis is mandatory in hospitalized patients with pneumonia

Antimicrobial stewardship programs focused on de-escalation and reduction of length of therapy for pneumonia treated in IMDs should be implemented


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best therapy of healthcare-associated pneumonia: narrow vs

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