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Procalcitonin and CRP in Lower Respiratory Tract Infections

Procalcitonin and CRP in Lower Respiratory Tract Infections. Doç. Dr. Aykut Çilli Akdeniz Üniversitesi Tıp Fakültesi Göğüs Hastalıkları Anabilim Dalı, Antalya. Studies related with CRP and PCT. Fungal infections HIV Transplantation Febril neutropenia Sepsis VAP TB SARS Children. Plan.

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Procalcitonin and CRP in Lower Respiratory Tract Infections

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  1. Procalcitonin and CRP in Lower Respiratory Tract Infections Doç. Dr. Aykut Çilli Akdeniz Üniversitesi Tıp Fakültesi Göğüs Hastalıkları Anabilim Dalı, Antalya

  2. Studies related with CRP and PCT • Fungal infections • HIV • Transplantation • Febril neutropenia • Sepsis • VAP • TB • SARS • Children

  3. Plan • Introduction • Usefulness of PCT and CRP as a diagnostic tool in LRTI • CRP and PCT as a predictor of etiology and prognosis in CAP • PCT in severe CAP • Procalcitonin-guided treatments • Limitations • Conclusions

  4. CRP • Acute phase protein produced in the liver. • Increased production is triggered by cytokines released by infection or tissue damage. • Serum concentration is usually <3 mg/L, but can increase to 500 mg/L.

  5. Procalcitonin (PCT) • Precursor peptide of the hormone procalcitonin. • PCT is a small (13 kd) protein that is normally undetectable in plasma. • PCT increases markedly in bacterial infections. COOH NH3 Katakalsin Kalsitonin Sinyal dizisi Aminokalsitonin PROCALCİTONİN

  6. For the diagnosis of infections, the diagnostic accuracy of PCT and its optimum cut-offs are completely dependent on the use of a sensitive assay.

  7. The usefulness of PCT and CRP as a diagnostic tool in LRTI

  8. Aim: To evaluate the diagnostic and prognostic accuracy of clinical signs, symptoms and biomarkers for CAP 373 CAP 545 patients with suspected LRTI 132 other RTI 40 other diagnosis Müller B et al, BMC Infect Dis 2007

  9. ROC of different parameters for the diagnosis of pneumonia A. Diagnostic accuracy to predict CAP without XR B. Diagnostic accuracy to predict radiographically defined CAP PCT > CRP, p=0.36 PCT, CRP > temp,WBC,chest ausc,sputum p<0.001 PCT > CRP, p=0.04 PCT > temp,WBC,chest ausc,sputum p<0.001 Müller B et al, BMC Infect Dis 2007

  10. ROC of different parameters for the diagnosis of pneumonia C. Diagnostic accuracy to predict radiographically suspected CAP (included non-infectious origin) D. Diagnostic accuracy to predict bacteremic CAP PCT>CRP, p=0.01 PCT>CRP, p<0.001 Müller B et al, BMC Infect Dis 2007

  11. Müller B et al, BMC Infect Dis 2007

  12. Diagnostic accuracy of C reactive protein in detecting radiologically proved pneumonia Systematic review: 6 studies, N=1178 Sensitivities: 10% to 98% Specificities: 44% to 99% Testing for C reactive protein is neither sufficiently sensitive to rule out nor sufficiently specific to rule in an infiltrate on chest radiograph and bacterial aetiology of lower respiratory tract infection. van der Meer V, et al. BMJ  2005

  13. CRP and PCT as a predictor of etiology and prognosis in CAP

  14. One-year, population-based, prospective study • 185 adult patients with CAP • Patients were classified according to microbial diagnosis, PSI and PCT levels Masia M et al, Chest 2005

  15. Masia M et al, Chest 2005

  16. Low PSI risk classes (I-II) Higher PSI risk classes (III-V) p=0.08 Masia M et al, Chest 2005

  17. Aim: Diagnostic value of admission serum levels of PCT and CRP as indicators of etiology and prognosis • 96 patients with CAP • All patients had elevated CRP levels (>10 mg/l) • Only 60 patients had elevated PCT levels (>0.1 µg/l) • APACHE II score was strongly associated with PCT (p=0.006), but not with CRP Hedlund J et al, Infection 2000

  18. p<0.03 Hedlund J et al, Infection 2000

  19. 116 patients with mild CAP • Aetiology was established • for 62 patients • PCT levels seems to be a • useful tool to rule out an • atypical aetiology. P<0.0001 P=0.021 Beovic et al, CMI 2005

  20. Objective: To assess the usefulness of serum CRP in patients with CAP, identify etiologic diagnosis and to predict severity outcome • Population-based case-control study • 201 patients with CAP and 84 controls Almirall J et al, Chest 2004

  21. Table 1. Serum CRP values in 89 patients with CAP according to causative pathogen Almirall J et al, Chest 2004

  22. Table 2. Serum CRP values patients with CAP according to site of care • Considering a cut point of 106 mg/L in men and 110 mg/L in women for deciding about the appropriateness of inpatient care, CRP levels showed a sensitivity of 80.5% and a specificity of 80.7% Almirall J et al, Chest 2004

  23. ¥ With suggestive symptoms of CAP, serum CRP > 33 mg/L is a useful marker. ¥ Serum CRP levels are greater when S pneumoniae or L pneumophila are the causative pathogens. ¥ CRP > 106 mg/L seem to predict severity of illness. Almirall J et al, Chest 2004

  24. Aim: To evaluate the diagnostic value of CRP as an indicator of the aetiology of CAP • A cohort of 1222 patients with CAP was assessed. • CRP levels were analysed in 258 patients. Vazquez EG et al, Eur Respir J 2003

  25. Table 1. CRP levels and aetiological diagnosis *p=0.0002 Vazquez EG et al, Eur Respir J 2003

  26. Table 2. CRP levels and aetiological diagnosis: multivariate analysis Vazquez EG et al, Eur Respir J 2003

  27. Procalcitonin in Severe CAP

  28. Aim: To determine diagnostic and prognostic values of PCT for severe CAP • 110 patients admitted to ICU 50% PCT ≥ 2 ng/ml 30% 0.5 ≤ PCT < 2 ng/ml 20% PCT ≤ 0.5 ng/ml Boussekey N et al, Infection 2005

  29. Boussekey N et al, Infection 2005

  30. Boussekey N et al, Infection 2005

  31. Aim: To evaluate prognostic value of PCT in severe CAP patients • Prospective observational study in ICU • 100 critically-ill patients with CAP Boussekey N et al, Intensive Care Med 2006

  32. P<0.001 P=0.03 PCT increased in nonsurvivors and decreased in survivors (p=0.01) Boussekey N et al, Intensive Care Med 2006

  33. Can CRP be used as a marker of infection in COPD exacerbation?

  34. 116 consecutive patients with exacerbation of COPD • Patients with exacerbation of COPD with and without pneumonia were compared Weis N et al, Eur J of Intern Med 2006

  35. Chest x-ray with changes compatible with pneumonia Chest x-ray without changes compatible with pneumonia a Antonisen score 1 less than score 2 or 3 (p<0.001) b CRP significantly higher for patients with pneumonic infiltration than for those without pneumonic infiltration (p<0.001) * CRP values are normal in nearly 50% of patients admitted due to exacerbation of COPD Weis N et al, Eur J of Intern Med 2006

  36. P<0.001 I: 64 patients without pneumonia and without increased sputum purulence II: 51 patients without pneumonia and with increased sputum purulence III: 51 patients with pneumonia Weis N et al, Eur J of Intern Med 2006

  37. Procalcitonin-guided treatment on antibiotic use

  38. PCT-guided treatment in LRTI • Prospective, controlled, cluster randomised, single-blinded intervention trial • 243 patients admitted with suspected LRTI • Baseline characteristics were similar Christ-Crain M, et al. Lancet 2004

  39. 124 PCT-guided group 42 Pneumonia 29 AECOPD 28 Bronchitis 10 Asthma 15 Others 243 patients with suspected LRTI 119 standard-treated group 45 Pneumonia 31 AECOPD 31 Bronchitis 3 Asthma 9 Others Christ-Crain M, et al. Lancet 2004

  40. PCT (ng/ml) < 0,1 Absence of bacterial infection Use of AB strongly discouraged 0,1 – 0,25 Bacterial infection unlikely Use of AB discouraged 0,25 – 0,5 Bacterial infection probable Antibiotcs recommended > 0,5 Presence of bacterial infection Antibiotcs strongly recommended PCT-Algorithm Christ-Crain M, et al. Lancet 2004

  41. *The risk of antibiotic exposure was reduced by 50% (without compromising clinical and laboratory outcome) Christ-Crain M, et al. Lancet 2004

  42. PCT-guidance of antibiotic therapy in CAP • Randomized intervention trial • 302 consecutive patients with CAP • Baseline characteristics (clinical, laboratory, microbiological and PSI) were similar. Control group (n=151) Procalcitonin group (n=151) Christ-Crain M, et al. AJRCCM 2006

  43. Median AB treatment duration=12 days (control) Median AB treatment duration=5 days (procalcitonin) *(P<0.05) Christ-Crain M, et al. AJRCCM 2006

  44. PCT-guided treatment of exacerbations of COPD • A randomized, controlled trial comparing procalcitonin-guidance with standard therapy • Single center, single-blinded study 102 procalcitonin group 208 patients requiring hospitalization 106 standard group Stolz D, et al. Chest 2007

  45. 51% < 0.1 ng/ml 29% 0.1-0.25 ng/ml 20% > 0.25 ng/ml Stolz D, et al. Chest 2007

  46. PCT guidance significantly reduced antibiotic prescribtions (40% vs 72 %, p<0.0001) Stolz D, et al. Chest 2007

  47. Stolz D, et al. Chest 2007

  48. Stolz D, et al. Chest 2007

  49. Stolz D, et al. Chest 2007

  50. Potential limitations

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