Ventilator Associated Pneumonia (VAP) or Hospital Acquired Pneumonia (HAP)
New Developments in Community Onset Pneumonia
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Transcript of New Developments in Community Onset Pneumonia
New Developments in Community-
Onset Pneumonia
Richard G. Wunderink MD
Northwestern University Feinberg School of Medicine
Chicago, IL, USA
Conflicts of Interest
• bioMerieux – investigator-initiated grant
• Pfizer – data safety monitoring board
• Accelerate Diagnostics
• Curetis
• Genmark
• Nabriva
• Arsanis
Diagnostics companies
US Causes of Death
1
10
100
1000
Dea
ths
per
100,0
00 p
op
ula
tion
Pneumonia Tuberculosis Sepsis AIDS 20/100K
Pediatric
Conjugate
Vaccine
Clinical use of penicillin starts
Effective anti-TB drugs
US Causes of Death
1
10
100
1000
Dea
ths
per
100,0
00 p
op
ula
tion
Pneumonia Tuberculosis Sepsis AIDS 20/100K
CMS Public
reporting/Pediatric
ConjugateVaccine
Clinical use of penicillin starts
Effective anti-TB drugs
Paradigm change #1:
Outcome of many critical
illnesses, including CAP,
is determined by the
timely provision of
appropriate antibiotic(s)
Time to First Antibiotic Dose
in Septic Shock
Kumar, Crit Care Med, 2006
7.6%/hr increase
in mortality
ARDS Prevention Strategies:
Appropriate Antibiotics
Levitt JE and Matthay MA. Critical Care
2012;1:223
Septic
Shock
Pneumonia
Iscimen et
al,
Crit Care
Med
2008;36:151
8- 1522
Kojicic et al
Crit Care
2012;16:R46
“It’s the antibiotics,
stupid.”
What is (are) the correct
antibiotic(s)?
What is (are) the correct
antibiotic(s) in the era of
antibiotic stewardship?
JAMA, 2014
JAMA, 2014
July 14, 2015
CDC Etiology of Pneumonia in the
Community (EPIC) Study
Both children (< 18
years) and adults
4 sites: Chicago,
Nashville, Memphis,
Salt Lake City
January 1, 2010 –
June 30, 2012
2320 adults with
radiographic
pneumonia
Objective: Determine US population-based incidence
and etiology of CAP
Am J Respir Crit Care Med, 2015
319 patients with clinically suspected CAP in 4 EDs
87% prior to
antibiotics
CDC EPIC Diagnostic Algorithm
CDC-EPIC Etiology of CAP:
Etiology Results
77
27
10 11
18
64
0
10
20
30
40
50
60
70
80
90
Pediatric Adult
Perc
en
t o
f p
ati
ents
ViralBacterialNone
Only 52/2320 (2%) of adults
enrolled in EPIC died
Slightly higher in eligible, un-
enrolled patients (4% at most)
Trends in Adult Community-
Acquired Pneumonia
Smith et al, JAMA Int Med, 2014
EPIC
3rd Gen Cephalo
Aminoglycoside
B-lactam+Macro
Cephalo+Macro
Quinolone
Treatment Outcomes Data
Gleason, Arch
Intern Med, 1999
Macrolide Combination Therapy
0
2
4
6
8
10
Ceftriaxone Other Ceph Penicilln Quinolone
6.31
5.11
8.15
4.94
2.762.16 2.46
2.91
Mo
rtali
ty (
%)
Monotherapy Macrolide Combination
p < 0.0001 p < 0.05
Brown, Chest, 2003
18,500 16,000 4,500 1800
Presumption of proponents of
narrow-spectrum therapy e.g.
β-lactam monotherapy, is that
S. pneumoniae is the
overwhelming cause of CAP
EPIC – Adult Pathogen
Detections
0
20
40
60
80
100
120
140
160
180
200
HRV Flu S. pn. HMPV RSV PIV G. ng.* CoV M. pn. S. au. AdV Leg. Strep
sp.Other†
115/2320 (5%) S. pneumoniae
Changing Etiology of CAP
PCV7
CAP-START
Postma et al, NEJM, 2015
CAP-START Primary Endpoint :
90 Day Mortality
Postma et al, NEJM, 2015
CAP-START Endpoints
9 8.8
11.1
6.1
8.8
3.7
0
2
4
6
8
10
12
90-DayMortality Add Abs for failure
%
B-Lactam
BL/Macro
Quinolone
Postma et al, NEJM, 2015
JAMA Intern Med 2014
TCS difference at 7 days –
7.6% (95%CI:-0.8 to 16, p = .07)
HR PSI IV = 0.81 (0.59-1.10)
HR CURB65 >2 = 0.80 (0.61-1.06)
ICU transfer: 3 (Legionella) vs. 0
Death 2 (Mycoplasma) vs. 0
Significantly more readmissions
Viruses are a common cause
of adult CAP
Paradigm Change #2
EPIC – Pathogen Detections
0
20
40
60
80
100
120
140
160
180
200
HRV Flu S. pn. HMPV RSV PIV G. ng.* CoV M. pn. S. au. AdV Leg. Strep
sp.Other†
RCT of PCT in LRTI
Christ-Crain, Lancet, 2004
Admission Procalcitonin in EPIC
< .25 ng/dl,
1042, 59%
> .25 ng/dl,
728, 41%
Admission Procalcitonin in EPIC
Viral
18%
Unknown
36%
Atypical
2%Bacterial
2%
Bacterial
7%
Atypical
2%
Unknown
25%
Viral
8%
< .25 ng/dl> .25 ng/dl
Antibiotics in CHF Admissions
Maisel et al, Eur J Heart Fail, 2011
Antibiotics in CHF Admissions
Maisel et al, Eur J Heart Fail, 2011
Phase III RCT of Daptomycin
vs. Ceftriaxone in CAP
• Daptomycin subsequently found to be inactivated by pulmonary surfactant
• Essentially placebo-controlled study of ceftriaxone
• Re-analyzed based on whether received prior antibiotic dose
– usually cephalosporin60
65
70
75
80
85
90
95
All Prior No Prior
79.4
90.7
75.4
87.9 88 87.8
Cli
nic
al
Su
cces
s (%
)
Daptomycin Ceftriaxone
Pertel, Clin Infect Dis, 2008 Clinically Evaluable
It is OK to avoid or use
ultra-short course antibiotics
for some suspected CAPs
Paradigm Change #3
10 days 5 days
• Antibiotic of
physician’s choice
• Placebo after 5 days
10 days 5 daysHigher
readmissions in
10-day treatment
also
Sept 2016
Healthcare-Associated
Pneumonia (HCAP)
HCAPHospital
-acquired
Community
-acquired
Epidemiology Of HCAPCulture-positive cases from large database
0
5
10
15
20
25
30
MRSA Pseudomonas Acinetobacter Enterics
8.9
17.1
1.6
21.3
26.525.3
2.6
25.8
22.9
18.4
2
19.8
14.6
21.2
3
26.6
CAP HCAP HAP VAP
Kollef, Chest, 2005
% o
f is
ola
tes
7
22.6
37.8
4
9.9
19.8
5
20.1
32.7
0
5
10
15
20
25
30
35
40
LOS 30-Day 90-Day
GC-HCAP
GC-CAP
Non-GC
Mortality
p = 0.001
p = 0.001
p = 0.001
EPIC Adult Exclusions
Recent hospitalization
30 days for immunocompetant
90 days for immunosuppressed
Functionally dependent nursing home
patients
Tracheostomy or PEG
Cystic Fibrosis
Severe immunosuppression
Language barrier to consent
EPIC:
Severe Immunosuppression
Cancer with neutropenia
Solid organ or stem cell transplant
within 90 days
Graft vs. Host Disease or Bronchiolitis
obliterans
HIV with CD4 < 200 mm3
EPIC – Pathogen Detections
0
20
40
60
80
100
120
140
160
180
200
HRV Flu S. pn. HMPV RSV PIV G. ng.* CoV M. pn. S. au. AdV Leg. Strep
sp.Other†
7/2320 (0.3%) Pseudomonas
38/2320 (1.6%) S. aureus
115/2320 (5%) S. pneumoniae
CAP-Drug Resistant Pathogens
618
36%
219
57120
162
74
286
1479
5%
22 77
Unknown
S. pneumoniae
Other Strep
MSSA
H. flu/Morax
Atypicals
GNB - sens
GNB - resist
Pseudo
Other Nonferm
MRSA
Shindo, Am J Respir Crit Care Med, 2013
Independent Risk Factors for Pneumonia Secondary to:
CAP-DRP MRSAHospitalization > 2 days in
previous 90 days
Hospitalization > 2 days in
previous 90 days
Use of antibiotics in
previous 90 days
Use of antibiotics in
previous 90 days
Immunosuppression Chronic hemodialysis in
previous 30 days*
Non-ambulatory status Prior MRSA colonization*
Tube feedings Congestive heart failure*
Gastric acid suppression Gastric acid suppression
* MRSA- specific risk factors
Shindo, Am J Respir Crit Care Med, 2013
2/12
Gross Findings: The Lung
Wunderink RG, Waterer GW. N Engl J Med
2014;370:543-551.
Risk for CAP-Drug Resistant
Pathogens
439 122 57
20
25
32
12
9
32
0
50
100
150
200
250
300
350
400
450
500
<=1 2 >=3
CAP-DRP Risk Factors
Negative
MRSA
Other CAP-DRPs
Shindo, Am J Respir Crit Care Med, 2013
Treatment Response for Patients
with < 1 Risk for CAP-DRPs
2.1
10.2
13.2
9.7
0
2
4
6
8
10
12
14
CAP Mono β-lactam Broad Spec Inappropriate
Mo
rta
lity
Empirical Treatment
p = 0.00001
284 380 266 72
Shindo, Am J Respir Crit Care Med, 2013
Paradigm Change #4:
Should have good reasons to not
treat with traditional CAP drugs
CAP-DRG make up 13.6% of all CAP
Increased mortality in HCAP is likely not
due to inappropriate antibiotics alone
Summary
Falling CAP mortality rates can result from:
Pneumococcal conjugate vaccine
Early traditional CAP antibiotics
Avoiding overtreatment of patients at low risk for DRPs
Viral CAP is much more common than previously
believed
Greater availability of multiplex RVPs
Procalcitonin may identify patients at low risk for
deterioration with extremely short course antibiotics
“Not everything that counts can
be measured and not everything
that can be measured counts.”
Albert Einstein