Community Acquired Pneumonia

1. Community Acquired Pneumonia Dr Vincent Ioos Medical Intensive Care Unit Pakistan Institute of Medical Sciences

2. Definition • Infection of the lung parenchyma that has been acquired in the community • Before hospital admission or within 48 hours • ≠ hospital acquired pneumonia, health care associated pneumonia • ≠ acute bronchitis and exacerbation of COPD • ≠ obstructive pneumonia, TB

3. Diagnosis • Lack of sensitivity of clinical signs and symptoms • But good Positive Predictive value of the presence of crakles • Good Negative Predictive Value of RR>30/mn, HR>100/mn, T°>37,9°C • Fever frequently absent in older patients • CXR • Leucopenia : poor prognosis • Microbiological diagnosis : better treatment when pathogen oriented but contreversies on the value of tests

4. Should we get a CXR ? • Patient with severe infection : presence of pneumonia allows proper empiric antibiotic therapy • If patient is not severely ill : helps in deferentiating CAP from acute bronchitis or exacerbation of COPD, and assess if antibiotics are necessary or not

5. Which pathogens ?

6. Epidemiology • Varies from one country to another • 2 questions : • Pathogens most likely to be responsible for CAP • Pattern of resistance, especially for Streptoccus Pn. • Epidemiological studies difficult : previous use of antibiotics, cost of C/S and serological studies, invasive procedures. • Sentinel surveillance systems for specific pathogens : data from microbiology departments, from disease oriented register.

7. Etiology Outpatients

8. Etiology ward patients

9. Etiology ICU patients

10. In Pakistan • Lack of datas • Neighbooring countries • World surveillance networks • Peadiatric studies

11. Shimia, Himachal Pradesh, India • 70 patients with CAP, blood, sputum and pleural fluid c/s, Mycoplasma Pn. Ab • 75,6 % proven etiology • Streptococcus Pn 35,8% • Klebsiella Pn 22% • Staphylococcus Aureus 17% • Mycoplasma Pn 15% • E. Coli 11% • Beta hemolytic Streptococci 7,5% • GNB 5,9% Bansal S, Indian J Chest Dis Allied Sci. 2004, Jan-March ; 46(1) : 17-22

12. New Delhi • All India Institute of Medical Sciences, April 1997 – December 1998 • 60 patients : blood C/S + Elisa Ab against L. Pneumophila (serogroups 1-7) • 13% “conventional bacterial etiology” • 15% serological evidence of recent infection with L. Pneumophila Chaudhry R, Trop Doct. 2000 Oct ; 30(4):197-200.

13. Shangai • 389 patients with CAP between 2001-2003 • Bacterial culture, PCR, specific immunological assays • Specific pathogen found in 39,8% : • Haemophilus Inflenzae 51%, among them 88,3% amoxicilline S • Mycoplasma Pn. 27% • Chlamydia Pn. 11% • Klebsiella spp. 10% • Streptococcus Pn. 8% among them 75% Peni S, 25%Peni I • Staphylococcus Aureus 4% • Legionella Pn. 1,3% • Moraxella Catharallis 0,6% Huang HH, Eur J Clin Microbiol Infect Dis. 2006 Jun ; 25(6):369-74

14. Iran, Afghanistan • PubMed : country name + “pneumonia”, • Iran : 33 articles, no epidemiological data on CAP • Afghanistan : 12 articles, one on epidemiology datas on CAP… in Russian Soldiers

15. 66 Laboratories in 1997, 81 in 1998 (17 in Asia-Pacific) • Pneumococal isolates from bloodstream and respiratory tract infections • 8252 respiratory tract isolates Hoban DJ, Clin Infect Dis. 2001 May 15;32 Suppl 2:S81-93.

17. Network of microbiology departments in 26 countries • 1998-2000 • Streptococcus Pneumonia (8882 isolates), Haemophilus Influenzae (8523), Moraxella Catharralis (874)

18. Streptococcus Pn. : • 95% Amoxicilline S • Quinolone resistance 1,1% • Haemophilus : Beta Lactamase production 16,9%

19. ARI in children, Pakistan • 87 strains of Streptococcus pneumoniae from blood culture • 97% resistant to at least one drug • 31% R to Cotrimoxazole, • 39% R to Chloramphenicol • All isolates were susceptible to erythromycin, cefaclor, cephalothin, ceftriaxone, cefuroxime, rifampicin, vancomycin, and clindamycin Mastro TD, Lancet 1991 Jan 19 ; 337(8734):156-9.

21. Critical microbes • Legionella Pneumophila • Influenza A +B • Avian Influenza • SARS • CA-MRSA  Epidemiological challenges or treatment different from standart regimen

22. Which diagnostic methods ?

24. Blood cultures (pros) • Pretreatment blood cultures positive for a pathogen in 7 to 16 percent of hospitalized patients. • Streptococcus pneumoniae : 2/3 of the positive blood cultures • When positive, the microbial diagnosis is established. • Only diagnostic test done, in most cases : major source of microbiologic data (resistance patterns of S. pneumoniae)

25. Blood cultures (cons) • The blood culture positivity rate is relatively low. • High rate of false positive blood cultures (up to 10 percent). Eg Staphylococcus. • Positive cultures rarely lead to modification or narrowing of antibiotic therapy

26. Sputum : standard quality criterias • Deep cough specimen obtained prior to antibiotics, • To be sampled only if macroscopically purulent sputum, • Cultures performed rapidly after collection, preferably within two hours • « Good" sputum sample : > 25 PMNs / LPF but < 10 SECs/LPF on Gram Stain • Interpretation : Quantitation of growth (heavy, moderate or light, quantitative threshold 107 CFU), clinical correlation, correlation with the Gram's stain

27. Invasive sampling • Protected brush specimen • Bronchalveolar Lavage • In case of failure of the initial treatment • If epidemiology or clinical presentation suggest a specific pathogens that is not covered by usual treatment strategy • If patient is intubated (ICU)

28. Pleural Tap • Rarely positive • Evidences empyema

29. Urinary antigens (pros) • Urine specimens avalable when patients cannot supply expectorated sputum. • Results of urine antigen testing immediately available. • Retains validity even after the initiation of antibiotic therapy. • High sensitivity compared to blood cultures and sputum studies.

30. Urinary antigens (cons) • The sensitivity and specificity may be less in patients without bacteremia. • No microbial pathogen available for antibiotic sensitivity testing.

31. Urinary Antigen LP • Legionella Pneumophila • Only for serotype 1 (the most frequent 80%) • Sensitivity 86%, specificity 93% • Positive 1 to 3 days after the onset of disease

32. Urinary antigen (SP) • Sensitivity 77-89% if CAP with blood culture +, Sensitivity 44-64% if blood culture – • False positive test rare • Rapid diagnosis, still positive after 7 days of antibiotics, persists several weeks.

33. Diagnostic yield of microbiological tests • Prospective study : 262 hospitalized patients with CAP. • Sputum for Gram staining, culture, and detection of pneumococcal antigen; blood for culture and serologic tests; urine for legionella and pneumococcal antigens; and specimens obtained by bronchoscopy. • A pathogen was identified in 158 (60 percent) patients • Adequate sputum samples obtained in only 44 patients : Gram's stain + positive sputum culture in 36/44 patients (82%). Van der Eerden MM, Eur J Clin Microbiol Infect Dis 2005 Apr;24(4):241-9.

34. Diagnostic yield of microbiological tests • S. pneumoniae most commonly identified (97 of 158). • Urinary pneumococcal antigen test positive in 52/97 (54%) patients with pneumococcal pneumonia. • Blood cultures were positive in 40 of 254 (16%) patients. • Bronchoscopy : additive diagnostic value in 18/37 patients (49%) who did not expectorate sputum and in 14 of 27 patients (52 percent) who failed treatment within 72 hours after admission. Van der Eerden MM, Eur J Clin Microbiol Infect Dis 2005 Apr;24(4):241-9.

35. PCR • Multiplex Real-time PCR • Respiratory viruses and atypical bacteria(eg, M. pneumoniae, L. pneumophila, Legionella spp, C. pneumoniae, influenza A and B virus, respiratory syncytial virus, parainfluenza viruses, human rhinovirus, metapneumovirus, adenovirus, and human coronaviruses) • 105 adults : etiology determined • 50% with conventional techniques • 80% with PCR • But increased cost. ? Less antibiotic use. Templeton KE, Clin Infect Dis 2005 Aug 1;41(3):345-51.

36. Minimal approach • 2 blood cultures and Tracheal Aspirate culture if patient is intubated … … before antibiotics are given • Urinary Legionella Pn. Antigen

37. Where should the patient be managed ? • At home • In the ward • In the ICU • « saving lifes and saving money » • Identify low risk patient to « save money » (and hospital beds !) • Identify high risk patient to « save life »

38. Saving lifes : the high risk patient

39. Saving money, avoid unnecessary hospitalisation • Large cohorts for validation (38,039 adults retrospectively, 2,287 adults for prospective validation)

41. Fine scoring system Class Points II  70 III 71 - 90 IV 91 - 130 V > 130 Fine et al. N Engl J Med 1997; 336: 243-50

42. Fine et coll. NEJM 1997

43. Decision • IV, V : admit the patient • I : no admission • II, III : no admission if score results from the age + 1 other criteria. • Admit systematically if : • Hypoxemia SaO2<90% / PaO2<60% • Vomitting prohibiting oral treatment, • immunosupression • Do not forget clinical judgement ! 25 years old pt + hypotension + tachycardia = class II !

44. Curb Index CURB  2 : hospital admission is recomended Derivated indexes : CURB-65, CRB-65

45. Which treatment ?

46. Risk factors for penicillin-resistant S. pneumoniae • Age <2 years or >65 years • Beta-lactam or macrolide therapy within the past six months • Recent hospital stay < 3 months • Medical comorbidities • Immunosuppressive illness or therapy • Exposure to a child in a day care center

47. Treatment options for moderate CAP admitted to hospital

48. Treatment options for patients with severe CAP