Tratamiento de la NAC: Importancia de los factores de riesgo

1. Tratamiento de la NAC:
importancia de los factores de riesgo
1
XXV Curso de Avances en Neumología
DR. JORDI ROIG
Pneumologia

2. Enf cardiaca isquémica
Enf cerebrovascular
Infección respiratoria
Enf diarreicas
Trast perinatales
EPOC
Tuberculosis
Sarampión
Accidentes de tráfico
Cáncer de pulmón
3ª
Cáncer gástrico
SIDA
Suicidio
1990 2020
Murray CJ & Lopez AD. Lancet 1997
Mortalidad Global Prevista
4ª

3. Neumonía comunitaria: Mortalidad
Bodi M et al CID 2005;41:1709; Rello J et al ICM 2002;28:1030; BTS Thorax 2001;56
(suppl IV) 1-64; Fine JM et al NEJM 1997;336:243; Marik PE. J Crit Care 2000;15:85
1%
5%
40%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
No Hospitalizada Hospitalizada UCI
Mortalitat

4. S.pneumoniae
S.aureus
Legionella
PA
H.influenzae
Enterobac.
Community Acquired Pneumonia:
Etiology
Angus DC et al . Am J Respir Crit Care Med 2002;166:717-723
“S.pneumoniae is
the principal
microorganism
responsible of
CAP”
“The etiologic
pattern was similar
in both ICU and
non-ICU patients”.

5. ¿Es S. pneumoniae la causa principal de
neumonía de etiología desconocida?
Ruiz-Gonzalez A. A microbiologic study with lung
aspirates in consecutive patients with CAP. Am J
Med 1999.
• n= 109
• Conventional microbial work-up + in 54 cases
(50%) 9 of them S. pneumoniae
• Lung aspiration in remaining 55 provided diagnosis
in 36:
– S. pneumoniae 18
– H. influenzae 6

6. Edad  50 años
o
comorbilidad
o
anomalias en signos
vitales
calcular PSI score
http://pda.ahqr.gov/
Male age (yrs)
Female - 10
Nursing home + 10
cardiac + 10
hepatic + 20
renal + 10
CNS + 10
neoplasia + 20
HR  125/bpm + 10
RR  30/min + 20
SBP < 90 mmHg + 20
Temp. < 35 or  40 C + 15
Confusion + 20
pH < 7.35 + 30
Blood urea nitrogen  30 mg/dl + 20
Sodium < 130 mmol/l + 20
Glucose  250 mg/dl + 10
Hemotocrit < 30% + 10
PaO2 < 60 mmHg + 10
Pleural effusion + 10

7. Fine MJ.NEJM 1997; 336:243 Pneumonia Severity Index PSI

8. Definition of SCAP: PSI Score
Fine MJ et al NEJM 1997; 336:243
COPD?

9. Prevalencia España
En España 1.300.000 personas entre 40 y 69 años padecen una
EPOC. El 78% no estaba diagnosticado.
Leves: 38.3%
Mod.: 39.7%
Graves: 22%
Sobradillo V et al. Chest. 2000 Oct;118(4):981-9.

10. La EPOC en la NAC
que ingresa en UCI
supone mayor
mortalidad (OR 1.58)
10
Rello J et al . Eur Respir J 2006; 27: 1210-6

11. Cillóniz C et al.
Microbial aetiology of community-acquired
pneumonia and its relation to severity.
Thorax. 2011 Jan 21. [Epub ahead of print]
AETIOLOGY PSI I-III
n= 659
(%)
PSI IV
n=500
(%)
PSI V
n=301
(%)
TOTAL
n=1460
(%)
p value
St. pneumoniae 276 (42) 205 (41) 132 (44) 613 (42) 0.728
H. influenzae 27 (4) 28 (6) 15 (5) 70 (5) 0.488
Atypical bacteria
Legionella
Mycoplasma
Chlamydia
Coxiella
163 (25)
54 (8)
51 (8)
31 (5)
27 (4)
77 (15)
50 (10)
12 (2)
13 (3)
2 (0.4)
23 (8)
14 (5)
2 (1)
6 (2)
1 (0.3)
263 (18)
118 (8)
65 (4)
50 (3)
30 (2)
<0.001
0.027
<0.001
0.046
<0.001
Virus 62 (9) 57 (11) 29 (10) 148 (10) 0.511
Mixed 84 (13) 73 (15) 51 (17) 208 (14) 0.217

12. Cillóniz C et al.
Microbial aetiology of community-acquired
pneumonia and its relation to severity.
Thorax. 2011 Jan 21. [Epub ahead of print]
AETIOLOGY PSI I-III
n= 659
(%)
PSI IV
n=500
(%)
PSI V
n=301
(%)
TOTAL
n=1460
(%)
p value
St. pneumoniae 276 (42) 205 (41) 132 (44) 613 (42) 0.728
H. influenzae 27 (4) 28 (6) 15 (5) 70 (5) 0.488
Moraxella cath.
S. aureus
MSSA
MRSA
GNEnterobact
2 (0.3)
9 (1)
5 (1)
4 (1)
7 (1)
2 (0.4)
10 (2)
5 (1)
5 (1)
9 (2)
1 (0.3)
6 (2)
4 (1)
2 (1)
11 (4)
5 (0.3)
25 (2)
14 (1)
11 (1)
27 (2)
0.961
0.651
0.697
0.731
0.022
Pseudomonas 9 (1) 17(3) 23 (8) 49 (3) <0.001
Others 20 (3) 22 (4) 10 (3) 52 (4) 0.448

13. 46,2
10,1 8,8 8,2 7,6
59,3
4,3
7,6 5,9 8,4
0
10
20
30
40
50
60
70
S.pneumoniae S.aureus L.pneumophila P.aeruginosa H.influenzae
Shock
No Shock
CAP: Etiology (CAPUCI Study)
“The etiologic pattern was similar in both shock and non-
shock patients”.
Bodí M (CAPUCI study). CID 2005

14. Factores que aumentan el riesgo de
infección por S.pneumoniae resistente
-Edad:>65 años o <2 años
-Beta-lactámicos en los últimos 3 meses
-Alcoholismo
-Inmunosupresión
-Comorbilidades
-Contacto con niños en guarderías
- Hospitalización reciente o actual
CAP ATS/IDSA Guidelines 2005

15. Risk factors for multidrug-resistant
pneumococcal pneumonia
Pneumonia Severity Index (PSI) score
Asthma
HIV infection
Previous hospital admission
Nursing home residence
Shock associated with 30-day mortality
Aspa J, Rajas O, et al. Infect Dis Clin Pract 2008.

16. RESISTENCIA NEUMOCOCO
• Historia de antibióticos utilizados
recientemente
– Terapia previa con beta-lactámicos,
macrólidos y quinolonas favorece
resistencia al mismo agente
• Escoger un antibiótico diferente al
indicado la última vez aunque haya
habido éxito terapéutico

17. Ho et al. Risk factors for acquisition of levofloxacin
resistant Streptococcus pneumoniae: a case-control
study. Clin Infect Dis 2001
• Case-control study: 27 with levo-Resist
pneumococci: 10 AECB, 11 pneumonia, 6 colonized;
54 controls (levo-Sens pneumococci)
• Risks for resistance in logistic regression: nursing
home residence (OR= 7.4), COPD (OR=10.3),
nosocomial (OR=16.2), recent hospitalization (OR=
4.6), prior quinolones within 12 months (OR= 10.7),
prior beta-lactam within 6 weeks (OR=14.7)
• 11/14 got prior quinolones (8 with levofloxacin) for
COPD.

18. Puntos clave: resistencia y etiología
• La selección de cepas resistentes se
asocia fuertemente a tratamientos
antimicrobianos subóptimos
• Las pautas de tratamiento cortas
ayudan a reducir la aparición de
bacterias multiresistentes
Rello J & Roig J. In: Respiratory infections. Chapter 40; Hodder
Arnold Pub, London, 2006.

19. 30,1%
21,4%
0%
5%
10%
15%
20%
25%
30%
35%
COPD Non COPD
Mortalityrate(%)
p=0.05
n=176
n=252

20. COPD (%) Non-COPD(%)
Streptococcus
pneumoniae
52 (54.1) 68 (51.5)
P. aeruginosa 13 (13.5) 1 (0.8)
Haemophillus
influenzae
11 (11.4) 7 (5.3)
Legionella spp. 4 (4.1) 15 (11.4)
Staphylococcus aureus 3 (3.1) 12 (9.0)
Enterobacteriaceae 3 (3.1) 9 (6.8)
Microorganismos aislados en pacientes
inmunocompetentes con y sin EPOC con CAP grave
Rello J, Rodriguez A, Torres A, Roig J. ERJ 2006

21. Risk factors for infection with P. aeruginosa
Structural lung disease
Corticosteroid therapy (> 10 mg/d)
Use of broad-spectrum antibiotics
Malnutrition
Leukopenic immunosuppression
Previous hospital admission
Malignancy
Rapid X-ray spread
Weyers CM. Clin Chest Med 2005; Arancibia F. Arch
Intern Med 2002; Bodí M (CAPUCI, CID 2005)

22. Risk factors for infection with enteric gram-
negative organisms
Nursing home residence
Cardiopulmonary disease
Multiple co-morbidities
Recent antibiotic use
Previous hospital admission
Probable aspiration
Weyers CM. Clin Chest Med 2005. Arancibia F. Arch Intern
Med 2002

23. 0%
10%
20%
30%
40%
50%
60%
Inappropriate Appropriate
COPD PATIENTS WITH SCAP:
MORTALITY RATE / EMPIRIC ATB TREATMENT
Rello J, Rodriguez A, Torres A, Roig J et al. ERJ 2006
p<0.05

24. RISK FACTORS OF TREATMENT FAILURE IN
CAP / MORTALITY RATE
Menéndez R et al. Thorax 2004;59:960
0%
5%
10%
15%
20%
25%
30%
Failure No Failure
p<0.001

25. ¿Es importante la administración
precoz de antibióticos?
• Meehan TP. Quality of care, process, and
outcomes in elderly patients with
pneumonia. JAMA 1997; 278: 2080-84
• Houck PM. Timing of antibiotic
administration and outcomes for
Medicare patients hospitalized with CAP.
Arch Intern Med; 2004; 164: 637-644
8 Horas
4 Horas

26. Tratamiento de la CAP grave
• Escoger apropiadamente antibiótico inicial
9,2%
15,5%
9,9%
16,5%
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
Hospital 30-days
<4 hs
> 4 hs
Houck PM et al. Arch Intern Med 2004;164:637-644
p = 0.04
p = 0.03

27. Early recognition of LD leads to prompt
therapy and low mortality
• Symptoms > 5 days: higher mortality1 in
severe cases
• Adequate Rx < 24 h ICU: 78% survival vs 54%
(p=0.005)2
• Fatality rate11% in outbreaks if delayed
recognition3
• Lower fatality rates (<2%) if early recognition,
as reported in Australia and Murcia, Spain
(n=449)3,4
1Gacouin 2002; 2Lettinga 2002; 3Navarro, Eurosurveillance Weekly 2001;
4Garcia-Fulgueiras 2003

28. COPD PATIENTS: ICU MORTALITY RATE
RISK FACTORS (Cox proportional regression
analysis)
Rello J, Rodriguez A, Torres A, Roig J et al. ERJ 2006

29. DEVELOPMENT OF SHOCK: Risk Factors
CAPUCI Study
.2 .3 .4 .5 .6 .7 .8 .9 1 2 3 4 5
OR
0.3
Previous ATB
APACHE II score >20
3.4
4.4
Rapid X-rays spread

30. Normativa SEPAR de Neumonia
Adquirida en la Comunidad:
actualización de septiembre de 2010.
R. Menéndez, A. Torres, J. Aspa, A. Capelastegui, C. Prat, F.
Rodríguez de Castro
Sociedad Española de Neumología y Cirugía Torácica;
www. separ.es

31. Características del antibiótico ideal
• Alta actividad contra patógenos
potenciales
• Perfil farmacodinámico adecuado (buena
penetración tisular)
• Perfil de seguridad bueno
• Posología fácil
• Relación coste/beneficio favorable

32. Efecto de los antibióticos en la
mortalidad en bacteremia por
neumococo
0
10
20
30
40
50
60
70
80
90
100
0
2
4
6
8
10
12
14
16
18
20
22
Days of illness Austrian and Gold
Ann Int Med 1964
Penicillin (298)
Serum (93)
Untreated (384)

33. Penicillin vs Placebo RT
0
20
40
60
80
100
Mortality
All cases Very Severe
Age Group
Penicillin
None
N=200
Evans and Brim Lancet 1938; 2: 14-19

34. Mortalidad: neumonía por
neumococo
0
5
10
15
20
25
30
35
40
45
50
1920
1926
1932
1938
1944
1950
1956
1962
1968
1974
1980
1986
1992
1998
2004
USA data compiled from published studies and Vital Statistics Reports
%mortality
MORTALITY(%)

35. Antibioterapia combinada es mejor que
monoterapia en neumonía neumocócica
bacteriémica
18,2%
20,0%
55,3%
23,4%
4,3%
6,9%
0%
10%
20%
30%
40%
50%
60%
Waterer Martinez Baddour
Monoth.
Combo
(1) Waterer GW et al. Arch Intern Med 2001;161:1837-42
(2) Martínez JA et al. CID 2003;36:389-395
(3) Baddour LM et al. Am J Respir Crit Care Med 2004; 170:440-444
Mortality rate

36. Tipo de Combinación / Mortalidad
OR: 2.7
Mortensen EM et al. Crit Care 2006;10:R8 p=0.004

37. 20-year longitudinal study of Bacteremic pneumococcal
pneumonia in Huntington, West Virginia
0
2
4
6
8
10
12
14
16
18
20
1978-1982 1983-1987 1988-1992 1993-1997
Pen alone
Pen+Mac
Mufson MA & Stanek RJ. Am J Med 1999
p<0.001

38. 806040200
DAYS
1,0
0,8
0,6
0,4
0,2
0,0
CumulatedSurvival
MONOTHERAPY-
censured
COMBINED-
censured
MONOTHERAPY
COMBINED RX
Severe LD(Capuci): Kaplan – Meier survival curve
P=0.203
(Log Rank)

39. HRCT in patients with dyspnea, fever of unknown origin
and normal X-ray
Brown MJ. Acute lung disease in the immunocompromised host:
CT and pathologic findings. Radiology 1994
Ramila E. Bronchoscopy guided by HRCT for the diagnosis of
pulmonary infections in patients with hemathologic malignancies
and normal plain chest X-rays. Haematologica 2000
• Immunocompromise, severe emphysema
• May detect an unsuspected alveolar infiltrate
or a subtle interstitial pattern
• Guide for FOB techniques ► better yield

40. Epidemiological features
• Travel or residence in high-risk areas for
some pathogens: rickettsiosis, fungal
infection, viral hemorrhagic pneumonia
• Occupational risk: F. tularensis, Coxiella
burnetti, Leptospira, Adenovirus
• Family illness: Mycoplasma, C. pneumoniae
• Bioterrorism setting
• Close contact (schools,…): H1N1

41. Acinetobacter as causative agent of SCAP
•Marik PE. The clinical features of SCAP
presenting as septic shock. Norasept II Study
Investigators. J Crit Care 2000; 15:85-90.
•Anstey NM. Community-acquired bacteremic
Acinetobacter pneumonia in tropical Australia is
caused by diverse strains of A. baumannii, with
carriage in the throat in at-risk groups. J Clin
Microbiol 2002; 40: 685-686.
•Lee K. Novel acquired metallo-β-lactamase gene,
in a class 1 integron from A. baumannii clinical
isolates from Korea. AAC 2005; 49: 4485-4491.
•Leung W. Fulminant A. baumannii CAP as a
distinct clinical syndrome. Chest 2006; 129:102-9.

42. S. aureus infection in healthy patients
•Gillet Y. Association between S. aureus strains
carrying gene for Panton-Valentine leukocidin and
highly lethal necrotising pneumonia in young
immunocompetent patients. Lancet 2002;359:753-
59.
•Boussaud V. Life-threatening hemoptysis in
adults with CAP due to PV leukocidin-secreting S.
aureus. Intensive Care Med 2003;29:1840-3.
•Francis J. Severe Community-onset pneumonia
in healthy adults caused by methicillin-resistant S.
aureus carrying the PV leukocidin genes. CID
2005; 40: 100-7.

43. 221.200
Mercè Agustí
Jordi Roig
157.200
165.138
73.800 40.000
231.468
Jordi Almirall
Eugènia Carandell
Imma Hospital
Pilar Ayuso Andreu Estela
Población diana: 888.806 habitantes
Almirall J et al. New evidence of risk factors for
CAP: a population-based study. PACAP group.
Eur Respir J 2008

44. 269/267
353/376
232/230
129/127 79/80
159/171
115/75
N: 1336/1326

45. OR P
DENTISTA 0.69 0.02
VACUNA NEUMOCOCO 0.54 0.003
PREVIA NAC 1.48 0.001
TABAQUISMO
<150 paq/año
>150 paq/año
1.01
1.46
0.006
BRONQUITIS CRÓNICA 1.81 0.006
OXÍGENO 2.42 0.01
INHALADORES 1.57 0.03
HALADORES
New evidence of risk factors for CAP:
a population-based study
Almirall J et al. PACAP group. Eur Respir J 2008

46. OR P
CORTICOIDES INH 7.44 0.05
BETA-2 1.17 0.45
IPRATROPIO 2.30 0.002
OXIGENOTERAPIA 5.04 0.014
INHALADORES
Con cámara
Sin cámara
2.28
1.39
0.01
ANÁLISIS MULTIVARIANTE
(tratamiento)
casos n=473; controles
n=235

47. Prevención de la CAP
Vacunación antigripal
Vacuna antineumocócica:
Johnstone J.Effect of pneumococcal vaccination
in hospitalized adults with CAP. Arch Intern Med
2007. OR of death or ICU was 0.62
Tabaco ↑ riesgo adquisición y muerte.
Nuorti JP. Cigarette smoking and invasive
pneumococcal dis. NEJM2000
Control odontólogo  riesgo de adquisición
Cambio brusco Tª ↑ riesgo

49. FUMADOR
ACTIVO
Pacientes
n (%)
Controles OR
ajustada
p
Nº cig
0/ dia 92 (42) 224 (76) 1.0
1-14/dia 48 (22) 39 (13) 2.3 (1.3-
4.3)
0.006
15-24/dia 41 (19) 19 (6) 3.7 (1.8-
7.8)
<0.001
> 25/dia 37 (17) 13 (4) 5.5 (2.5-
12.9)
<0.001
Nuorti JP. Cigarrette smoking and invasive pneumococcal
disease. NEJM 2000

50. No
FUMADOR
Pacientes
n (%)
Controles OR
ajustada
p
No
exposición
40 (59) 125 (80) 1.0
1-4h /dia 16 (24) 25 (16) 2.4 (0.9-
6.3)
0.08
> 4h /dia 12 (18) 7 (4) 3.9 (1.0-
16)
0.05
Nuorti JP. Cigarrette smoking and invasive pneumococcal
disease. NEJM 2000

51. Effect of nicotine on L. pneumophila growth
in alveolar macrophages024
control nicotine 0.1 nicotine 1 nicotine 10
24h after
infection
48h after
infection
Matsunaga K et al. J Immunol 2001

52. Estudio TORCH
6.112 pacientes EPOC y
FEV1<60%
Salmeterol+fluticasona
Fluticasona
Salmeterol
Placebo
52
Calverley P et al. N Engl J Med 2007; 356: 775-789

53. Estudio TORCH
NEUMONÍA
Salmeterol+fluticasona 19.6%
Fluticasona 18.3%
Placebo 12.3%
(P<0.001)
53
Calverley P et al. N Engl J Med 2007; 356: 775-789

54. Inhaled drugs as risk factors for
community-acquired pneumonia
J. Almirall, I. Bolíbar, M. Serra-Prat, E. Palomera, J. Roig, I.
Hospital, E. Carandell, M. Agustí, P. Ayuso, A. Estela, A. Torres
and the Community-Acquired Pneumonia in Catalan Countries
(PACAP)
Eur Respir J 2010; 36: 1080–1087

55. COPD OR p
Upper respiratory tract infection in the
past month
2.25 (0.84–6.01) 0.107
Oxygen therapy 1.18 (0.19–7.39) 0.863
Inhaled steroids 3.26 (1.07–9.98) 0.038
Inhaled β-agonists 0.68 (0.23–2.02) 0.483
Inhaled anticholinergics 1.19 (0.39–3.63) 0.757
Asthma 1.00 (0.38–2.62) 0.998
Oral corticosteroids 1.30 (0.31–5.47) 0.718
Smoking history pack-yrs
0 1 0.081
1–150 4.23 (1.07–16.7) 0.039
>150 2.44 (0.83–7.21) 0.105
Influenza vaccine 0.39 (0.12–1.27) 0.118
Table 3– Association between inhaled drug treatments and the risk of CAP adjusted for
respiratory comorbidity and its severity, respiratory treatments and other non-respiratory
risk factors, by strata of patients with specific respiratory diseases

56. Table 3– Association between inhaled drug treatments and the risk of CAP adjusted for
respiratory comorbidity and its severity, respiratory treatments and other non-respiratory
risk factors, by strata of patients with specific respiratory diseases
Asthma alone OR p
Upper respiratory tract infection
in the past month
1.46 (0.92–2.30) 0.105
Inhaled steroids 1.10 (0.40–3.00) 0.857
Inhaled β-agonists 1.24 (0.58–2.67) 0.582
Inhaled anticholinergics 8.80 (1.02–75.7) 0.048
Influenza vaccine 0.67 (0.42–1.08) 0.096
Pneumococcal vaccine at any
time of life
0.35 (0.14–0.84) 0.020
N-Acetylcysteine 0.23 (0.03–1.87) 0.168
Depression 0.70 (0.40–1.21) 0.200

57. 5,81
0,73
4,52
3,02
1,19
5,16
0
1
2
3
4
5
6
7
Biologic Adoptive
Infection
Vascular
Cancer
Sorenson TI et al N Engl J Med 1988
Dying from infection is hereditary

58. Sorenson et al N Engl J Med 1988

59. Pathogen coverage Timely initiation
Correct dose Correct route
Optimal
therapy
Increased survival
Pea F et al. Clin Infect Dis. 2006;42:1764-1771; Rello J et al. Chest.
2006;130:938
Tratamiento “OPTIMO”
Inmunomodulación?