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Community-Acquired Pneumonia
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Treatment 2017
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Jordi Carratalà

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Department of Infectious Diseases
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Hospital Universitari de Bellvitge

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 Key points in the treatment of CAP
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Time to initiation of antibiotic therapy

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Initial antibiotic treatment
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Antibiotic de-escalation

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Switching from IV to oral antibiotic therapy
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Duration of antibiotic treatment
 Key points in the treatment of CAP
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Time to initiation of antibiotic therapy

D t
Initial antibiotic treatment
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M a
Antibiotic de-escalation

C y
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Switching from IV to oral antibiotic therapy
E• ©
Duration of antibiotic treatment
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Studies assessing initiation of antibiotic therapy within various thresholds

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and short-term mortality for hospitalized patients with CAP

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Lee JS. JAMA 2016
 Key points in the treatment of CAP
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Time to initiation of antibiotic therapy

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Initial antibiotic treatment
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Antibiotic de-escalation

C y
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S b
Switching from IV to oral antibiotic therapy
E• ©
Duration of antibiotic treatment
Recommended empirical antibiotic therapy for CAP
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IDSA/ATS Guidelines on the Management of CAP. CID 2007
Improving outcomes in elderly patients with CAP
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by adhering to national guidelines
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Aim: to define whether elderly patients hospitalized with CAP had better

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outcomes if they were were treated with empirical antimicrobial therapy
adherent the 2007 IDSA/AST guidelines
Design: secondary analysis of the CAPO database. 43 centers in 12
countries

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Patients: 1649 (975 regimen adherent, 465 undertreated, 195 overtreated)

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Outcome

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Clinical stability by 7 days
Adherence

71 %
Nonadherence

57 %
P

<.01

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Length of stay, days 8 10 <.01

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Overall in-hospital mortality 8% 17 % <.01

Arnold FW. Arch Intern Med 2009

 Macrolide-based regimens and mortality in hospitalized
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patients with CAP: a systematic review and meta-analysis

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- 23 studies and 137574 patients were included.

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- Overall, macrolide use was associated with a significant mortality reduction
compared with nonmacrolide use (3.7% vs 6.5%; RR .78, 95% CI .64-.95; P= .01)

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- There was no survival advantage when analysis were restricted to RCTs or to
patients treated with guideline-concordant antibiotics.

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© RCTs

Asadi L. Clin Infect Dis 2012

 Macrolides and mortality in critically ill patients with CAP:
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a systematic review and meta-analysis

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- 28 observational studies (no RCTs) of almost 10,000 critically ill pts with CAP.

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- Overall, macrolide use was associated with lower mortality compared with

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nonmacrolides (21% vs. 24%; RR .82, 95% CI .70-.97; P= .02)
- When broadly guideline-concordant regimens were compared, no significant

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difference in mortality was found (20% betalactam/macrolide vs. 23% betalactam/
fluoroquinolone; RR .83, 95% CI .67-1.03; P= .09)

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Sligl WI. Crit Care Med 2014
 β-Lactam Monotherapy vs β-Lactam–Macrolide
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Combination Treatment in Moderately Severe CAP
A Randomized Noninferiority Trial

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© Garin N. JAMA Intern Med 2014
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Outcome
I D ut β-lactam β-lactam-macrolide (n= Fluoroquinolone (n=

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90-day mortality

y a (n= 656)
9.0 %
739)
11.1 %
888)
8.8 %

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Time to starting 4 (3 – 5) 4 (3 – 5) 3 (0 – 4)
oral ATB therapy
LOS
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Complications
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6 (4 – 8)
16.2 %
6 (4 – 10)
17.3 %

Cluster-randomized, crossover trial with strategies rotated

6 ( 4 – 8)
17.4 %

in 4-month periods; 7 hospitals in the Netherlands Postma DF. New Engl J Med 2015
Levofloxacin vs. azithromycin for treating Legionella pneumonia
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Observational retrospective multicenter study of 446 consecutive patients
with Legionella pneumonia requiring hospitalization (2000 – 2014)

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Variable
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Time to defervescence
(n= 175)

2 (1 – 4)
(n= 177)

2 (1 – 3) 0.45

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Time to clinical stability 3 (2 – 5) 3 (2 – 5) 0.48

LOS
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Length of IV therapy 3 (2 – 5)

7 (5 – 10)
4 (3 – 6)

6 (5 – 9)
0.58

0.88

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30-day mortality 2.3 % 5.1 % 0.16

Garcia-Vidal C. Clin Microbiol Infect 2017

 Key points in the treatment of CAP
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• e ho r
Time to initiation of antibiotic therapy

D t
Initial antibiotic treatment
I u
•
M a
Antibiotic de-escalation

C y
•
S b
Switching from IV to oral antibiotic therapy
E• ©
Duration of antibiotic treatment
 Key points in the treatment of CAP
r y
r a
•
L ib
• e ho r
Time to initiation of antibiotic therapy

D t
Initial antibiotic treatment
I u
•
M a
Antibiotic de-escalation

C y
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Switching from IV to oral antibiotic therapy
E• ©
Duration of antibiotic treatment
 Studies evaluating antibiotic de-escalation in CAP
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Study

L ib Population De-escalation Results

Khasawneh
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60 pts with bacteremic CAP
n (%)
33 (55.5) No differences in
mortality and LOS

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Inf Drug Res 2014
261 pts with bacteremic CAP 165 (63.2) Higher mortality

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Carugati
in the non-DE

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group

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CMI 2015

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Yamana 11159 pts with CAP 1258 (11.3) No differences in
5-day and in-

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J Infect 2016

Viasus

JAC 2016
© 1410 pts with CAPP 166 (11.7)
hospital mortality
No differences in
30-day mortality
Shorter LOS in DE
 Key points in the treatment of CAP
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Time to initiation of antibiotic therapy

D t
Initial antibiotic treatment
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Antibiotic de-escalation

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Switching from IV to oral antibiotic therapy
E• ©
Duration of antibiotic treatment
 Effectiveness of early switch from intravenous to oral
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antibiotics in severe CAP: a multicentre randomised trial
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Setting: 7 teaching hospitals in the Netherlands.

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Participants: 265 pts in non-intensive care wards with severe CAP.
Intervention: 3 days of iv antibiotics followed, when clinically stable,

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by oral antibiotics or 7 days of iv antibiotics.

Outcome

C M y a Intervention
(n= 132)
Control
(n= 133)
Mean difference
(95% CI)

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Clinical cure
b 110 (83) 113 (85) 2% (-7% to 10%)

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Mean (SD) LOS, days 9.6 (5.0) 11.5 (4.9) 1.9 (0.6 to 3.2)

Oosterheert JJ. BMJ 2006

 Effect of a 3-step critical pathway to reduce duration of
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intravenous antibiotic therapy and length of stay in CAP

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Objective: to determine whether the use of a 3-step critical pathway

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is safe and effective in reducing duration of iv antibiotic therapy and
LOS in hospitalized adults with CAP

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Design: randomized controlled trial (ISRCTN 17875607)

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Setting: 2 tertiary hospitals in Barcelona
Intervention: 3-step critical pathway or usual care

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Primary end point: LOS

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Secondary end points: duration of iv antibiotic therapy, adverse drug
reactions, need for readmission, and overall case-fatality rate
Carratalà J. Arch Intern Med 2012
 3-Step Critical Pathway in CAP
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1 EARLY MOBILIZATION

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Movement out of bed:

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> 20´ during the first 24 hours of hospitalization
progressive movement each subsequent day

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2 SWITCH TO ORAL ANTIBIOTIC THERAPY

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Ability to maintain oral intake, stable vital signs (temperature 37.8ºC,
RR 24´, SBP ≥90 mmHg) and absence of exacerbated comorbidities

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3 HOSPITAL DISCHARGE

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Meeting criteria for oral antibiotic therapy, baseline mental status,
and adequate oxygenation on room air (PaO2 ≥60 mmHg or pulse
oximetry ≥90%)
Carratalà J. Arch Intern Med 2012
 Effect of a 3-step critical pathway to reduce duration of
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intravenous antibiotic therapy and length of stay in CAP

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Outcomes

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Primary end pointe ho r (n= 200) (n= 201)

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Length of stay, median, days 3.9 6.0 <.001

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Secondary end points

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Length of iv antibiotic therapy 2.0 4.0 <.001

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Adverse drug reactions 5% 16 % <.001
Phlebitis
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Subsequent admission
4%
9%
10 %
8%
.02
.59
Overall case-fatality rate 2% 1% .45
 Key points in the treatment of CAP
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L ib
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Time to initiation of antibiotic therapy

D t
Initial antibiotic treatment
I u
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M a
Antibiotic de-escalation

C y
•
S b
Switching from IV to oral antibiotic therapy
E• ©
Duration of antibiotic treatment
 Efficacy of short-course antibiotic regimens for
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community-acquired pneumonia: a meta-analysis
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15 randomized controlled trials (1980-2006); mild/moderate CAP.
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Short-course (≤ 7 days) versus extended-course (>7 days).

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Short-course: azithro (10), β-lactams (2), FQ (2), ketolides (1).

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Outcome I Relative risk, 95% CI

C y a
Clinical failure 0.89, 0.78 – 1.02

S
Mortality

E b 0.81, 0.46 – 1.43

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Bacteriologic eradication 1.11, 0.76 – 1.62

Li JZ. Am J Med 2007

 Duration of antibiotic treatment in CAP
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A multicenter randomized clinical trial

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Multicenter, noninferiority, RCT. Four spanish teaching hospitals (2012 - 2013)

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A total of 312 pts were randomized at day 5 to an intervention (ATBs for 5 days)

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or control group (duration of ATBs determined by physicians).

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Outcome Control Intervention P value

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Intent-to-treat analysis
Clinical success, n (%)

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n= 150 n= 162

At day 10

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At day 30

y a 71 (49)
132 (89)
90 (56)
147 (92)
0.18
0.33

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CAP symptom questionnaire

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score, mean (SD)
At day 5

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At day 30
24.7 (11)
18.6 (9.0)
27.2 (12)
17.9 (8)
0.10
0.69

Uranga A. JAMA Intern Med 2016

The new antibiotic mantra “Shorter is Better”
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Infections for which short-course therapy has been shown

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to be equivalent in efficacy to longer therapy

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Spellberg B. JAMA Intern Med 2016
 Summary r y
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Antibiotic therapy based on current guideline
recommendations should be initiated within 4

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to 8 hours of hospital arrival for patients with

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confirmed CAP.

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Antibiotic de-escalation is effective in reducing
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LOS and does not negatively affect outcomes.
 Summary r y
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Objective measures of clinical stability can

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promote rapid transition from IV to oral

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antibiotic therapy, without compromising

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outcomes, while decreasing LOS.

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Duration of therapy in most patients can be

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safely shortened to 5 days without increased
risk of treatment failure or mortality.
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Thank you very much for your attention!

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© Santa Caterina Market, Barcelona