Session: How to manage and prevent the different faces of pneumonia Severe CAP

Transcription

1 Athens 19, 20 November 2015 Garyfallia Poulakou Consultant, Infectious Diseases 4 th Department of Internal Medicine, Attikon University Hospital of Athens Session: How to manage and prevent the different faces of pneumonia Severe CAP

2 TRANSPARENCY DECLARATION No conflicts of interest related to this presentation

3 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):S1 Mandell et al, Clin Infect Dis 2007; 44(S2): S27 72

4 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: Jemal J, JAMA 2005;294: Fine M, JAMA 1996;275:134 41

5 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

6 Mortality of scap: stable, worsening or decreasing over time? The UK database: stability ~30% ICU mortality The CAPUCI I ( ) and II ( ) studies from Spain and European centers show a significantly decrease in mortality The CAPO International cohort shows increase CAPO Study In-hospital mortality percentage and 95% confidence interval CAPUCI Studies Cavallazzi R, Respiratory Medicine (2015) 109, 743e750 Woodhead H et al, Crit Care. 2006;10(2):S1, Gattarello S, Crit Care Sep 10;19:335

7 scap is a progressive disease and the most common cause of sepsis and septic shock worldwide Infection Local extension LRTI Mild CAP Systemic inflammatory response Hypercoagulation Acute organ dysfunction Hypotension Hypoperfusion Sepsis Severe sepsis Pulmonary spread Multiorgan dysfunction Acute respiratory failure Hypotension non responsive to fluid resuscitation Ewig et al, Eur R J 2006 Beal et al, JAMA 1994 Septic shock Nystrom et al, JAC 1998 Rello J, Crit Care 2008

8 Why pneumonia remains a lethal condition? Pathogen s inherent toxicity Antimicrobial resistance Viral coinfections? Antibiotic development Most hospital deaths occur after eradication of bacteria Pathogen Bordon J, Chest. 2010;138: Iwashyna TJ, JAMA. 2010;304: Yende S, Am J Respir Crit Care Med. 2008;177: 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 Johnstone, Medicine. 2008;87: Waterer GW, Am J Respir Crit Care Med. 2004;169:910 4

9 IDSA / ATS Criteria for ICU admission Major criteria (1 or more) Delayed ICU transfer for Invasive mechanical ventilation respiratory arrest or shock is Septic shock with the need for vasopressors associated with fold Minor criteria (3 or more) increased risk for hospital Respiratory rate 30 breaths/min PaO2/FiO2 250 mortality compared with direct Multilobar infiltrates admission from the emergency Confusion-disorientation department Uremia (BUN level 20 mg/dl) Leucopenia (WBC count <4 109/L) Thrombocytopenia (platelet count < /L) Hypothermia (core temperature <36 C) vhypotension (SBP <90 mmhg) requiring aggressive fluid resuscitation Renaud B, Crit CareMed. 2009;37: Restreppo MI, Chest. 2010;137:552 7 Leroy O, Intensive Care Med. 1995;21(1):24 31.

10 PSI for admission decisions in CAP DEMOGRAPHICS Age Gender Nursing home COMORBIDITIES Neoplasia Liver Disease CHF Cerebrovascular disease Renal Disease PHYSICAL EXAM Mental confusion Respiratory Rate SBP Heart Rate Temperature LABORATORY/ IMAGING BUN,Glucose Sodium, Hematocrit Pleural effusion Arterial Ph Oxygenation 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 2005 Fine, NEJM 1997 Restrepo and Anzueto Curr Opin Infect Dis 2006

11 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 McFarlane et al, Thorax 2001; 56(S IV): 1 96 Score/ Risk Class Mortality Outpatient Outpatient Admission recommendation Short Hospital stay/supervised outpatient Hospital, assess for ICU admission 4 40 Hospital, assess for ICU admission 5 57 Hospital, assess for ICU admission

12 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 72 Woodhead Eur R J 2005, Rello J Crit Care 2009

13 Adapted PIRO score for scap The PIRO concept Analogy to the TNM cancer classification P redisposition I nfection R esponse O rgan dysfunction Rello J, et al, Crit Care Med Rello J et al, Eur Respir J. 2006;27: Opal S, Pediatr Crit Care Med. 2005;6(suppl):S55 S60

14 PIRO score for community acquired pneumonia: results fro the CAPUCI I study Rello J et al, Critical Care Medicine 2009; 37(2): Twenty eight day mortality rate according PIRO score Length of stay (LOS) in intensive care unit (ICU) and mechanical ventilation (MV) days on survivors according to PIRO score

15 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

16 Newly introduced scores aiming to predict ICU referral The 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): Renaud et al Crit Care Med 2009;37(11):

17 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* Neuhaus and Ewig, Med Clin North Am. 2001;85: Rello et al Chest. 2003;123: Liapikou and Torres 2014 Alcoholics Account for 85% of CAP causes 2/3 of deaths are attributed to pneumococcus * Lethal pathogens 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)

18 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 days Woodhead CMI 2011

19 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 72 Woodhead et al, Clin Microbiol Infect. 2011;17(6):E1 59

20 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): Am J Respir Crit Care Med 2004;170(4): Antimicrob Agents Chemother 2007;51(11):

21 13 studies 5 prospective 7 included ICU patients O Brien E et al, Respir Investigation 2015

22 Combined therapy provided a survival benefit in CAPUCI study Gatarello S et al, Chest 2014 Jul 1;146(1):22e31

23 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

24 Combination therapy is associated with better survival in scap: CAPUCI study, non pneumococcal scap Gattarello S et al Crit Care 2015 Courtesy S. Gattarello and J. Rello

25 Prompt administration of antibiotics is associated with better survival curves : CAPUCI study, non pneumococcal scap Gattarello S et al Crit Care 2015

26 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 inhospital 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): Schuez P et al, Care 2013;17(3):R115

27 Corticosteroids in scap For 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

28 Author / year Confalonieri et al./ 2005 Mikami et al./ 2007 (open label) Snijders et al./ 2010 Fernandez Serrano/ 2011 Sabry et al. / 2011 Meijvis et al./ 2011 Torres et al/ 2015 Blum et al/ 2015 SUMMARY OF RANDOMISED CONTROLLED TRIALS OF CORTICOSTEROIDS IN CAP Adapted from Sibila O, Minerva Anestesiol 2014;80: No patients Disease 48 CAP requiring ICU 31 Hospitalized CAP 213 Hospitalized CAP 56 Hospitalized CAP 80 Hospitalized CAP 304 Hospitalized CAP 112 scap and high inflammatory response Type of corticosteroid, dosage Hydrocortisone, 240 mg/d Duration of treatment Main outcome 7 days Decrease mortality Prednisolone 40 mg/d 3 days Early stabilization vital signs Prednisolone 40 mg/d 7 days Increase late failure Methylprednisolone, 620 mg 9 days Gradual withdrawal Decrease length of stay Hydrocortisone 300 mg/d 7 days Decreased duration of mechanical ventilation Dexamethasone 5 mg/d 4 days Reduced length of stay Hyperglycemia 0.5 mg/kg per 12 hours of methylprednisolone 5 days Decreased treatment failure 785 Mild and scap Prednisone 50 mg daily 7 days Shorter median time to clinical stability Hyperglycemia

29 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 Sep 16;5:14061.

30 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 Sep 16;5:14061.

31 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 mg kg 1 day 1 (or an equivalent dose of dexamethasone, hydrocortisone, prednisolone or betamethasone)] Tagami T, Eur Respir J 2015; 45:

32 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

33 Thank you for your attention Athena, the ancient Greek Goddess of wisdom and justice