How to manage and prevent the different faces of pneumonia ...€¦ · Yende S, Am J Respir Crit...
Transcript of How to manage and prevent the different faces of pneumonia ...€¦ · Yende S, Am J Respir Crit...
Session: How to manage and preventSession: How to manage and prevent
the different faces of pneumoniathe different faces of pneumonia
Severe CAPSevere CAP
Garyfallia PoulakouConsultant,
Infectious Diseases4th
Department of Internal
Medicine, Attikon University
Hospital of Athens
Athens 19, 20 November 2015
TRANSPARENCY DECLARATION
No conflicts of interest related to this
presentation
Definition and incidence of sCAP
• CAP is defined as• An acute illness with clinical features of lower
respiratory tract infection, presenting with radiological
infiltrations and no other explanation of the infection
• For sCAP there is not universally accepted
definition
• CAP that requires ICU admission
• (sCAP) represents 10 % of patients hospitalized
with CAP, with an incidence that increases in
recent years
Woodhead M et al, Crit Care. 2006;10(2):S1Mandell et al, Clin Infect Dis 2007; 44(S2): S27‐72
CAP: a disease with important consequences
• CAP is the leading cause of morbidity and mortality from infectious
diseases in developed countries
• It affects more than 5 million adults and accounts for more than
1
million admissions each year in the United States
• Despite effective antibiotic therapy, about 12‐36% patients
admitted to the Intensive Care Unit (ICU) with severe CAP die within
a short period of time
Murray CJ Lancet 1997;349:1498‐504Jemal J, JAMA 2005;294:1255‐9 Fine M, JAMA 1996;275:134‐41
sCAP is on the rise
Data from 17,869 cases in UK: registered in the ICNARC Case Mix Programme
Database
• While sCAP represents a
small proportion of all
ICU admissions, there is a
progressive rise in the
number of admissions
with time (128%)
• Overall mortality (50%
survive to exit hospital)
remains high, especially
in those admitted later in
their hospital stay
Woodhead H et al, Crit Care. 2006;10(2):S1
Mortality of sCAP: stable, worsening or
decreasing over time?• The UK database: stability ~30% ICU mortality• The CAPUCI I (2000‐2002) and II (2008‐2015) studies from Spain and
European centers show a significantly decrease in mortality
• The CAPO International cohort shows increaseCAPO StudyIn-hospital mortality percentage and 95% confidence interval
CAPUCI Studies
Cavallazzi R, Respiratory Medicine (2015) 109, 743e750Woodhead H et al, Crit Care. 2006;10(2):S1, Gattarello S, Crit Care. 2015 Sep 10;19:335
sCAP is a progressive disease
and the most common cause of sepsis and septic shock worldwide
Infection Local extension
Severe sepsis
Sepsis
Septic shock
LRTIMild CAP
LRTIMild CAP
Multiorgan
dysfunction
Multiorgan
dysfunction
Systemic inflammatory responseHypercoagulation
Acute organ dysfunctionHypotensionHypoperfusion
Hypotension non‐responsiveto fluid resuscitation Ewig et al, Eur R J 2006
Beal et al, JAMA 1994Nystrom et al, JAC 1998Rello J, Crit Care 2008
Pulmonary
spreadAcute
respiratory
failure
Acute
respiratory
failure
Why pneumonia remains a lethal condition?
Pathogen Inflammation
• Continuing excess
mortality for
more than 2 years
after surviving an
episode of CAP• Long term
impaired
functional status• Long term
neurologic,
cardiovascular,
cognitive ,
endocrine
consequences
• Pathogen’s
inherent
toxicity• Antimicrobial
resistance• Viral co‐
infections?
• Antibiotic
development
Most hospital deaths occur after eradication of bacteria
Bordon J, Chest. 2010;138:279–83Iwashyna TJ, JAMA. 2010;304:1787–9Yende S, Am J Respir Crit Care Med. 2008;177:1242–74
Johnstone, Medicine. 2008;87:329–34Waterer GW, Am J Respir Crit Care Med. 2004;169:910–4
IDSA / ATS Criteria for ICU admission
Major criteria (1 or more)Invasive mechanical ventilationSeptic shock with the need for vasopressorsMinor criteria (3 or more)Respiratory rate ≥30 breaths/minPaO2
/FiO2
≤250Multilobar infiltratesConfusion-disorientationUremia (BUN level≥20 mg/dL)Leucopenia (WBC count <4×109/L)Thrombocytopenia (platelet count <100×109/L)Hypothermia (core temperature <36 °C)vHypotension (SBP <90 mmHg) requiring aggressive fluid resuscitation
Delayed ICU transfer for
respiratory arrest or shock is
associated with 2–2.6‐fold
increased risk for hospital
mortality compared with direct
admission from the emergency
department
Renaud B, Crit CareMed. 2009;37:2867–74Restreppo MI, Chest. 2010;137:552–7Leroy O, Intensive Care Med. 1995;21(1):24–31.
PSI for admission decisions in CAP
DEMOGRAPHICSAge
GenderNursing home
COMORBIDITIESNeoplasia
Liver DiseaseCHF
Cerebrovascular diseaseRenal Disease
PHYSICAL EXAMMental confusionRespiratory Rate
SBPHeart RateTemperature
LABORATORY/IMAGINGBUN,Glucose
Sodium, HematocritPleural effusion
Arterial PhOxygenation
Risk Class Mortality Admission recommendation
I 0.1 Outpatient
II 0.6 Outpatient
III 2.8 Outpatient or Brief Inpatient
IV 8.2 Inpatient
V 29.2 Inpatient Woodhead Eur R J 2005Fine, NEJM 1997
Restrepo and Anzueto Curr Opin Infect Dis 2006
CURB‐65 for admission decisions in CAP
• C
onfusion• U
rea (>7mmol/L)• R espiratory rate ≥30/min• B
P (SBP ≤90mmHg or DBP ≤60mmHg• 65
(Age ≥65 years)1 point each
Score/ Risk
ClassMortality Admission recommendation
0 0.7 Outpatient
1 2.1 Outpatient
2 7.2 Short Hospital stay/Supervised outpatient
3 14.5 Hospital, assess for ICU admission
4 40 Hospital, assess for ICU admission
5 57 Hospital, assess for ICU admissionMcFarlane et al, Thorax 2001; 56(S IV): 1‐96
Comparison of PSI and CURB‐65
PSI• Well validated• Reduces admissions and costs
• Rather complex to calculate• Not based on severity of disease• Age bias against young without
comorbidities
CURB‐65• Easy to remember• Easy to calculate• Disease severity; no comorbidities
• BUN?• Underestimates risk in elderly with
comorbidities
Mandell et al, Clin Infect Dis 2007; 44(S2): S27‐72Woodhead Eur R J 2005, Rello J Crit Care 2009
Adapted PIRO score for sCAP
Rello J, et al, Crit Care Med. 2008Rello J et al, Eur Respir J. 2006;27:1210–1216Opal S, Pediatr Crit Care Med. 2005;6(suppl):S55–S60
The PIRO conceptAnalogy to the TNM cancer
classificationP
redispositionI
nfectionR
esponseO
rgan dysfunction
PIRO score for community‐acquired pneumonia: results
fro the CAPUCI I study
Length of stay (LOS) in intensive care unit
(ICU) and mechanical ventilation (MV) days
on survivors according to PIRO score
Rello J et al, Critical Care Medicine 2009; 37(2):456‐462
Twenty‐eight‐day mortality rate according
PIRO score
The SMART‐COP score• A tool developed in the Australian CAP Study for the prediction of which
patients will require intensive respiratory or vasopressors support. • Systolic blood pressure, • Multilobar chest radiography, • low Albumin levels, • Respiratory rate (age adjusted), • Tachycardia, • Confusion, • low Oxygen (age‐adjusted), • and arterial pH (<7.35)
Charles PG, Clin Infect Dis 2008;47(3):375-84
Newly introduced scores
aiming to predict ICU referralThe SCAP score•Variables of the score grouped in six minor criteria
• (confusion, urea >30 mg/dl, respiratory rate >30/ min, multilobar bilateral infiltrates, PaO2
<54 mmHg or PaO2/FiO2 <250 and age >80 years) and •two major criteria
• (arterial pH <7.35 or systolic blood pressure <90 mmHg) •At least, two minor criteria or one major criterion predicted SCAP with
sensitivity of 84% and specificity of 60%The REA‐ICU index •11 criteria : male gender, age <80 years, comorbid conditions, respiratory rate
>30 breaths/min, heart rate >125 beats/min, multilobar infiltrate or pleural
effusion, WBC <3 or >20 G/l, hypoxemia [SO2 <90% or PaO2<60 mmHg], blood
urea nitrogen >11 mmol/l, pH < 7.35 and Na<130 mEq/l.
Espan˜a PP, J Infect 2010;60(2):106-13Renaud et al Crit Care Med 2009;37(11):2867-74
Microbiology of sCAP
• Streptococcus pneumoniae*• Legionella pneumophila*• Haemophilus influenza• Klebsiella pneumoniae• Viral infections (up to 1/3)• Mixed infections (up to 20%)• Anaerobes• Pseudomonas aeruginosa*
Risk factors•Severe COPD with frequent hospitalizations,
Bronchiectasis, •Cystic fibrosis,•Those taking antibiotics for a long time(>10 mg for >1
month)•Immunosuppressed patients (HIV, corticosteroid
therapy, malnutrition)
• Account for 85% of CAP
causes• 2/3 of deaths are attributed
to pneumococcus
Alcoholics* Lethal pathogens
Neuhaus and Ewig, Med Clin North Am. 2001;85:1413–1425Rello et al Chest. 2003;123:174–180Liapikou and Torres 2014
Antibiotic treatment in sCAP
Speed matters
• Antimicrobial treatment for sCAP remains largely empirical,
targeting the most likely pathogens
• Before the initiation of antibiotics, at least two samples of blood
cultures should be obtained, one intravenous and the other from a
vascular catheter
• Total duration of 7‐10 daysWoodhead CMI 2011
Recommended treatment for sCAP• Patients without pseudomonal risk: an intravenous β‐
lactam plus
either a macrolide or a respiratory fluoroquinolone
• Patients with pseudomonas risk: • an antipseudomonal β‐lactam combined with either levofloxacin or
ciprofloxacin or• the antipseudomonal β‐lactam can be combined with both an
aminoglycoside and either azithromycin or a respiratory quinolone
• Anaerobic coverage (a cephalosporin with clindamycin) is indicated
only in patients with a risk for aspiration, such as alcoholism,
loss of
consciousness and oropharyngeal dysphagia due to neurological
disease
Mandell LA, et al Clin InfectDis. 2007;44 Suppl 2:S27–72Woodhead et al, Clin Microbiol Infect. 2011;17(6):E1–59
Combination treatments and the role of
macrolides• From several studies, it has been reported that the benefit of
combination therapy in patients with SCAP and septic shock is seen
only when a macrolide is part of the regimen
• This effect is probably attributed to the anti‐inflammatory properties of
macrolides
• In one US study of patients with Pneumonia Severity Index class V,
quinolone monotherapy had twice as high a mortality as the use of
a b‐lactam/macrolide combination
Eur Respir J 2009;33(1): 153-9, Intensive Care Med 2010;36(4):612-20Am J Respir Crit Care Med 2004;170(4): 440-4 Antimicrob Agents Chemother 2007;51(11):3977-82
• 13 studies• 5 prospective• 7 included ICU
patients
O’
Brien E et al, Respir Investigation 2015
Combined therapy provided a survival benefit in
CAPUCI study
Gatarello S et al, Chest 2014 Jul 1;146(1):22e31
Early initiation of treatment was associated
with a survival benefit in the CAPUCI study
Gatarello S et al, Chest 2014 Jul 1;146(1):22e31
Combination therapy is associated with better survival in
sCAP: CAPUCI study, non pneumococcal sCAP
Courtesy S. Gattarello and J. RelloGattarello S et al Crit Care 2015
Prompt administration of antibiotics is associated with better
survival curves : CAPUCI study , non pneumococcal sCAP
Gattarello S et al Crit Care 2015
Biomarkers as tools for treatment duration
and prognosis in sCAP• The SCC and ESCMID guidelines now include the use of biomarkers,
especially PCT, to assist in decisions regarding discontinuation
of empiric
antibiotics (grade 2C). • The largest randomized trial published to date reported that a PCT
guided strategy to treat suspected bacterial infections could reduce
antibiotic exposure • Moreover, PCT kinetics could be a tool for assessing the evolution of
severe sepsis and septic shock• In their study, Schuetz and colleagues concluded that for ICU and in‐
hospital mortality, a 72‐h PCT decrease >80% had a negative predictive
value of 91%, and no decrease or an increase in PCT over 72 h had a
positive predictive value of 48%.Bouadma L et al, Lancet 2010;375(9713):463-74Schuez P et al, Care 2013;17(3):R115
Corticosteroids in sCAPFor patients with sCAP, risk assessment should take into
consideration patients with severe chronic obstructive pulmonary
disease and asthma that may have received intermittent treatment
with steroids before their septic episode, and, therefore, have
iatrogenic adrenal insufficiency,
needing steroid replacement
Mandel L, Clin Infect Dis 2007; 44(S2); S27‐72
Author /
yearNo
patientsDisease Type of corticosteroid,
dosageDuration of
treatmentMain outcome
Confalonieri et
al./
200548 CAP requiring
ICUHydrocortisone,240 mg/d
7 days Decrease mortality
Mikami et al./
2007 (open label)31 Hospitalized
CAPPrednisolone 40 mg/d 3 days Early stabilization vital signs
Snijders et al./
2010213 Hospitalized
CAPPrednisolone 40 mg/d 7 days Increase late failure
Fernandez‐
Serrano/ 201156 Hospitalized
CAPMethylprednisolone, 620 mg 9 days
Gradual
withdrawal
Decrease length of stay
Sabry et al.
/
201180 Hospitalized
CAPHydrocortisone 300 mg/d 7 days Decreased duration of
mechanical ventilation
Meijvis et al./
2011304 Hospitalized
CAPDexamethasone 5 mg/d 4 days Reduced length of stay
Hyperglycemia
Torres et al/
2015112 sCAP and high
inflammatory
response
0.5 mg/kg per 12 hours of
methylprednisolone5 days Decreased treatment failure
Blum et al/
2015785 Mild and sCAP Prednisone 50 mg daily 7 days Shorter median time to clinical
stability Hyperglycemia
SUMMARY OF RANDOMISED CONTROLLED TRIALS OF CORTICOSTEROIDS IN CAPAdapted from Sibila O, Minerva Anestesiol 2014;80:1336‐44
Results of the most recent meta‐analysis
(10 eligible RCTs comprising 1780 cases)
(i) corticosteroids shorten
length of hospital stay for CAP,(ii) corticosteroids shorten
length to clinical stability for
CAP, and (iii) corticosteroids lower
mortality for severe CAP
Horita N et al, Sci Rep. 2015 Sep 16;5:14061.
• According to the most recent
meta‐analysis corticosteroids
lower mortality for severe
CAP
• The incidence of major
complications was not
greatly increased
Horita N et al, Sci Rep. 2015 Sep 16;5:14061.
A large scale observational study from Japan
Low‐dose* corticosteroid use may be
associated with reduced 28‐day mortality in
patients with septic shock complicating CAP *[defined as intravenous infusion of
methylprednisolone 0.5–2.5 mg∙kg−1∙day−1 (or
an equivalent dose of dexamethasone,
hydrocortisone, prednisolone or betamethasone)]
Tagami T, Eur Respir J 2015; 45: 463–472
Conclusions• Despite the advent of new antibiotics and better treatment modalities in
the ICU, sCAP still carries a significant mortality • The use of severity scores to guide ICU admission remains a priority,
because delayed ICU admission is associated with higher mortality;
however still do not have the ideal score for this purpose • Clinical experience and judgment should not be underestimated in
this setting• Early administration of combination antibiotic treatment represents a
milestone in the management of sCAP; the combination of a β‐
lactam
plus a macrolide showed survival benefits in the recent literature• Although several RCTs have been performed in the last years with
promising results, the use of corticosteroids in CAP remains controversial
in clinical practice• Patients with severe CAP, septic shock and a high inflammatory response could be
the most likely to benefit of adjuvant corticosteroid treatment
Thank you for your attention
Athena, the ancient Greek Goddessof wisdom and justice