1 / 36

Charles Feldman Professor of Pulmonology Charlotte Maxeke Johannesburg Academic Hospital

Evidence for the Duration of Antibiotic Therapy. Charles Feldman Professor of Pulmonology Charlotte Maxeke Johannesburg Academic Hospital University of the Witwatersrand. Potential COI to Declare. Abbott , Aspen-GSK,Jansen , MSD, Pfızer , Sanofi. Introduction to the Talk.

kaydence-rojas
Download Presentation

Charles Feldman Professor of Pulmonology Charlotte Maxeke Johannesburg Academic Hospital

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Evidence for the Duration of Antibiotic Therapy Charles Feldman Professor of Pulmonology Charlotte Maxeke Johannesburg Academic Hospital University of the Witwatersrand

  2. Potential COI toDeclare • Abbott, Aspen-GSK,Jansen, MSD, Pfızer, Sanofi

  3. Introduction to the Talk • CAP is one of the leading causes of morbidity and mortality throughout the world – 5.6 million cases diagnosed annually • Little consensus on most appropriate duration of antibiotic therapy and recent recognition that prolonged therapy may be related to development of resistance • A range of recommendations are found encompassing courses of between 5 – 14 days

  4. Recommended Duration of Therapy Organisation S. pneumoniae: Treat until afebrile for 72h S. aureus, P. aeruginosa, Klebsiella species, anaerobes and atypical pathogens: ≥ 2 weeks Infectious Diseases Society of America Canadian Infectious Diseases Society and Canadian Thoracic Society 1-2 weeks depending on response of patient American Thoracic Society S. pneumoniae and other bacteria: 7-10d Atypical pathogens: may need 10-14 days With new antimicrobials: may shorten to 5-7 days for outpatients Microbiologically undefined: 7-10 days Legionella species: 14-21 days Atypical pathogens: 14 days Pneumococci: 7 days Staphylococci or gram-negative enteric bacilli: 14-21 days British Thoracic Society

  5. Rationale for Short-Course Therapy • Short course regimens (< 7 days) theoretically useful in reducing antimicrobial resistance and favouring improved patient compliance • Prolonged treatment especially with low-dose antibiotics was associated with increased carriage of PRSP in nasopharynx (3.5 x and 6 x respectively) • Patient compliance decreases after 5 days of treatment and with resolution of symptoms Scalera NM et al. CurrOpin Infect Dis 2007; 20: 177-181

  6. Short Course Therapy - Beta-Lactams • Study recruited 2000 children aged 2 – 59 months with non-severe pneumonia (WHO criteria) • Patients randomly assigned to 3 days or 5 days treatment with oral amoxicillin • Primary outcome was treatment failure and analyses were intention to treat MASCOT Pneumonia Study Group Lancet 2002; 360: 835-841

  7. 1000 allocated to 5 days amoxicillin 1000 allocated to 3 days amoxicillin 980 further analysed 973 further analysed 127 failed 116 failed 857 improved 853 improved 50 failed 45 failed 1 died 2000 patients randomised • 20 excluded • 1 bottle broken • 3 incorrect enrolment • 13 lost to follow-up • 3 treatment changed at home • 27 excluded • 2 bottles broken • 2 incorrect enrolment • 19 lost to follow-up • 4 treatment changed at home Enrolment 1st follow-up (after 3 days) 2nd follow-up (after 5 days) 811 resolved 803 resolved 13 relapsed 12 relapsed 3rd follow-up (after 14 days) 798 cured 791 cured

  8. Treatment of Childhood Pneumonia • Treatment failed in 209 (21%) patients in 3-day group and 202 (20%) patients in 5-day group • Overall 12 (1%) children in 3-day group and 13 (1%) children in 5-day group relapsed • Non-adherence was associated with failure of treatment in 5-day group (p<0.0001) MASCOT Pneumonia Study Group Lancet 2002; 360: 835-841

  9. Treatment of Childhood Pneumonia • Overall failure was most likely in children • that did not adhere to treatment (p<0.0001), • less than 12 months (p<0.0001), • whose illness lasted > 3 days (p=0.004), • whose RR was >10 breaths/min above the age specific cut-off (p=0.004), • with vomiting (p=0.009) MASCOT Pneumonia Study Group Lancet 2002; 360: 835-841

  10. Treatment of Childhood Pneumonia • Randomised, double-blind, multicentre study in children 2 – 59 months of age with non-severe pneumonia showed oral amoxicillin for three days to be as effective as five days • Cochrane database systematic review confirmed the evidence that short course therapy (3 days) was as effective as longer treatment (5 days) in children < 5 years with non-severe CAP Agarwal G et al (ISCAP). BMJ 2004; 328: 791 Haider BA et al. Cochrane Database Syst Rev 2008; Apr 16; (2): CD005976

  11. Treatment of Adult Pneumonia • Prospective study of hospitalised CAP following the implementation of early switch to oral antibiotics and early hospital discharge showed no difference in safety and patient satisfaction compared to historical controls • Prospective, randomised, parallel group study of non-severe CAP which indicated that abbreviated (2-day) course of i.v. antibiotics with rapid oral switch had similar clinical course and cure rates and lower costs Lee RW et al. Respirology 2007; 12: 111-116 Siegel RE et al. Chest 1996; 110: 965-971

  12. Short Course Therapy - Fluoroquinolones • Multicentre, randomised, double-blind study comparing levofloxacin 750mg daily for 5 days versus 500mg daily for 10 days in mild-severe pneumonia • Clinical success rate was 92.4% versus 91.1% and microbiological eradication 93.2% versus 92.4% • Subgroup analysis confirmed benefit in elderly > 65 years Dunbar LW et al. Clin Infect Dis 2003; 37: 752-760 Shorr AF et al. ClinTher 2005; 27: 1251-1259

  13. Duration of Antibiotic Therapy in Severe CAP Patients with community acquired pneumonia: (1883 patients) CURB 3-5: (574 patients) • Excluded from analysis: 162* • ICU within 7 days (99) • Failed to reach clinical stability in 7 days (118) • Died with 7 days (58) • Complicated pneumonia (11) • Organism requiring prolonged treatment (12) Propensity score derived Out-with mutual range of propensity score (84) 7 days (164 patients) >7 days (164 patients) * Subtotals add up to >162 as some patients have >1 factor Choudhury G et al. ClinMicrobiol Infect 2011; 17: 1852-1858

  14. Results of the multivariable analysis Covariate 30-day mortality MV/IS Complicated pneumonia 0.67 (0.21-2.16) p 0.5 Main analysis 7 days vs. >7 days 0.92 (0.27-3.16) p 0.9 0.63 (0.23-1.71) p 0.4 Excluding deaths on treatment 7 days vs. >7 days 0.95 (0.27-3.34) p 0.9 0.92 (0.27-3.14) p 0.9 0.63 (0.23-1.70) p 0.4 Including all patients suitable for matching (N=412) 7 days vs. >7 days 1.20 (0.48-3.02) p 0.7 1.10 (0.57-2.13) p 0.8 0.65 (0.28-1.50) p 0.3 Choudhury G et al. ClinMicrobiol Infect 2011; 17: 1852-1858

  15. Trials excluded from meta-analysis: • Analysed data from previously included trials (n=2) • Did not compare short- vs. extended- course monotherapy (n=18) • Minority of subjects with commonly- acquired pneumonia (n=2) • Pooled analysis of multiple studies with primary data unavailable (n=1) Short Course Therapy – A Meta-analysis Potentially relevant trials identified and screened for retrieval (n=3725) Potentially relevant trials for which full text was retrieved (n=38) Randomised controlled trials included in the meta-analysis (n=15) Li JZ et al. Am J Med 2007; 120: 783-790

  16. Clinical Failure Study Risk Ratio (95% CI) % Weight 0.92 (0.33-2.54) 1.36 (0.64-2.88) 0.80 (0.62-1.03) 1.06 (0.70-1.63) 0.93 (0.68-1.50) 1.09 (0.72-1.65) 0.90 (0.59-1.35) 1.01 (0.56-1.83) 0.12 (0.02-0.89) 0.33 (0.01-2.84) 0.13 (0.03-0.59) 1.16 (0.64-2.14) 1.11 (0.39-3.19) 0.79 (0.31-2.06) 0.04 (0.65-1.37) 0.89 (0.78-1/02) 1.7 2.7 27.8 7.1 7.3 9.9 10.3 5.3 2.0 0.9 3.5 4.0 1.5 2.3 13.6 Bohle et al, 1995 Brion et al, 1990 Dunbar et al, 2003 Kinasewits et al, 1991 Kobayashi et al, 1995 Leophante et al, 2002 Leophante et al, 2002 O’Doherty et al, 1985 Rahav et al, 2004 Rizzato et al, 1995 Schonwald et al, 1994 Schonwald et al, 1990 Sigel et al, 1999 Sopena et al, 2004 Tellier et al, 2004 Overall (95% CI) 0.015412 1 64.8849 Favours short-course Favours extended-course Li JZ et al. Am J Med 2007; 120: 783-790

  17. Mortality Study Risk Ratio (95% CI) % Weight 3.6 11.9 33.8 6.8 12.0 19.6 2.0 10.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Bohle et al, 1995 Brion et al, 1990 Dunbar et al, 2003 Kinasewits et al, 1991 Leophante et al, 2004 Leophante et al, 2002 Siegal et al, 2999 Tellier et al, 2004 Kobayashi et al, 1995 O’Doherty et al, 1988 Rahav et al, 2004 Rizzato et al, 1995 Schonwald et al, 1994 Schonwald et al, 1990 Sopena et al, 2004 Overall (95% CI) 1.10 (0.07-16.45) 0.83 (0.20-4.38) 0.58 (0.20-1.69) 9.62 (0.06-6.68) 1.22 (0.28-5.37) 0.76 (0.21-2.77) 0.79 (0.12=65.38) 0.72 (0.12-4.29) (Excluded) (Excluded) (Excluded) (Excluded) (Excluded) (Excluded) (Excluded) 0.81 (0.48-1.43) 0.015294 1 5.3844 Favours short-course Favours extended-course Li JZ et al. Am J Med 2007; 120: 783-790

  18. Clinical Implications of The Study • Adults with mild-moderate community-acquired pneumonia can be effectively treated with an antibiotic regimen of 7 days or less • This result is consistent among the 4 antibiotic classes studies (macrolide, fluoroquinolone, beta-lactam, and ketolide) • There is a trend toward decreased adverse events with antibiotic regimens of 7 days or less Li JZ et al. Am J Med 2007; 120: 783-790

  19. Potentially relevant articles retrieved from MEDLINE database (n=381) Articles selected for further evaluation after screening title and abstract (n=34) Excluded articles (n=28) after detailed review: Potentially relevant articles retrieved from the Cochrane database (n=287) Articles selected for further evaluation after screening title and abstract (n=17) Excluded articles (n=13) after detailed review: • Comparing different duration courses for different antibacterial regimens (n=17) • Subgroup analysis of another trial (n=5) • Comparing different dose regimens (n=3) • In children < 2 months of age (n=2) • Not an RCT (n=1) • Comparing different duration courses for different antibacterial regimens (n=9) • Subgroup analysis of another trial (n=2) • Comparing different dose regimens (n=1) • In children < 2 months of age (n=2) • Not an RCT (n=1) Six relevant RCTs identified Four relevant RCTs identified (subset of those identified with the MEDLINE search) One more RCT identified by reviewing reference lists Total of Seven studies selected for inclusion in our meta-analysis Dimopolous G et al. Drugs 2008; 68: 1841-1854

  20. Clinical Success – End of Therapy Study or Sub-Category Short course (n/N) Long course (n/N) OR (fixed) 95% CI Weight (%) OR (fixed) (95% CI) Year Studies including adult patients Leophonte et al Tellier et al El Moussaoui et al File et al Subtotal (95% CI) Total events: 510 (short course), 506 (long course) Test for heterogeneity: chi2 = 0.46, df = 3 (p = 093), I2 = 0% Test for overall effect: Z = 0.10 (p = 0.746) 82/91 142/159 50/54 236/247 551 81/87 143/161 56/60 226/236 544 3.48 6.46 1.67 4.38 15.99 0.67 (0.23-1.98) 1.05 (0.52-2.12) 0.89 (0.21-3.76) 0.85 (0.40-2.28) 0.92 (0.58-1.47) 2002 2004 2006 2007 Studies including paediatric patients MASCOT Agarwal et al Subtotal (95% CI) Total events: 1783 (short course), 1794 (long course) Test for heterogeneity: chi2 = 0.22, df = 1 (p = 0.64), I2 = 0% Test for overall effect: Z = 0.747 (p = 0.46) 803/980 980/1033 2013 811/973 983/1026 1999 62.50 21.51 84.01 0.91 (0.72-1.15) 0.81 (0.54-1.22) 0.88 (0.72-1.08) 2002 2004 Total (95% CI) Total events: 2293 (short course), 2300 (long course) Test for heterogeneity: chi2 = 0.72, df = 5 (p = 0.98), I2 = 0% Test for overall effect: Z = 1.25 (p = 0.21) 2564 2543 100.00 0.89 (0.74-1.07) 0.1 0.2 0.5 1 2 5 10 Favours short course Favours long course Dimopolous G et al. Drugs 2008; 68: 1841-1854

  21. Study or sub-category Short course (n/N) Long course (n/N) OR (fixed) 95% CI Weight (%) OR (fixed) (95% CI) Year Studies including adult patients Siegel et al Leophonte et al El Moussaoui et al File et al Subtotal (95% CI) Total events: 367(short course), 345 (long course) Test for heterogeneity: chi2 = 1.23, df = 3 (p = 0.74), I2 = 0% Test for overall effect: Z = 0.92 (p = 0.36) 21/24 69/94 47/52 230/242 412 20/22 67/92 49/56 209/227 397 1.37 9.56 2.38 5.62 18.84 0.70 (0.11-4.64) 1.03 (0.54-1.97) 1.34 (0.40-4.53) 1.65 (0.78-3.51) 1.23 (0.79-1.91) 1999 2002 2006 2007 Studies including paediatric patients MASCOT Subtotal (95% CI) Total events: 791 (short course), 798 (long course) Test for heterogeneity: not applicable Test for overall effect: Z = 0.747 (p = 0.46) 791/980 980 798/973 973 81.16 81.16 0.92 (0.73-1.15) 0.92 (0.73-1.15) 2002 Total (95% CI) Total events: 1158 (short course), 1143 (long course) Test for heterogeneity: chi2 = 2.56, df = 4 (p = 0.37), I2 = 0% Test for overall effect: Z = 0.23 (p = 0.82) 1392 1370 100.00 0.98 (0.80-1.20) 0.1 0.2 0.5 1 2 5 10 Favours short course Favours long course Clinical Success – Late Follow-up Dimopolous G et al. Drugs 2008; 68: 1841-1854

  22. Mortality Study or sub-category Short course (n/N) Long course (n/N) OR (fixed) 95% CI Weight (%) OR (fixed) (95% CI) Year Studies including adult patients Sigel et al Leophonte et al Tellier et al El Moussaoui et al File et al Subtotal (95% CI) Total events: 6 (short course), 10 (long course) Test for heterogeneity: chi2 = 1.08, df = 3 (p = 0.78), I2 = 0% Test for overall effect: Z = 1.03 (p = 0.30) 1/23 4/125 1/193 0/56 654 0/22 7/119 2/195 0/53 1/254 643 3.94 55.90 15.94 12.10 87.88 2.87 (0.11-74.26) 0.53 (0.15-1.86) 0.50 (0.05-5.59) Not estimable 0.33 (0.01-8.12) 0.60 (0.23-1.85) 1999 2002 2004 2006 2007 Studies including paediatric patients MASCOT Argarwal et al Subtotal (95% CI) Total events: 0 (short course), 1 (long course) Test for heterogeneity: not applicable Test for overall effect: Z = 0.68 (p = 0.50) 0/980 0/1095 2075 1/973 0/1093 2066 12.12 12.12 0.33 (0.01-8.13) Not estimable 0.33 (0.01-8.13) 2002 2004 Total (95% CI) Total events: 6 (short course), 11 (long course) Test for heterogeneity: chi2 = 1.20, df = 4 (p = 0.88), I2 = 0% Test for overall effect: Z = 1.20 (p = 0.23) 2729 2709 100.00 0.57 (0.23-1.43) 0.01 0.1 1 10 100 Favours short course Favours long course Dimopolous G et al. Drugs 2008; 68: 1841-1854

  23. Adverse Events Study or sub-category Short course (n/N) Long course (n/N) OR (fixed) 95% CI Weight (%) OR (fixed) (95% CI) Year Studies including adult patients Leophonte et al Tellier et al El Moussaoui et al File et al Subtotal (95% CI) Total events: 207 (short course), 205 (long course) Test for heterogeneity: chi2 = 2.94, df = 3 (p = 0.40), I2 = 0% Test for overall effect: Z = 0.12 (p = 0.90) 100/125 47/193 6/56 54/256 630 98/119 41/195 13/63 53/254 631 12.67 19.46 6.89 26.48 65.50 0.86 (0.45-1.63) 1.21 (0.75-1.95) 0.46 (0.16-1.31) 1.01 (0.66-1.55) 0.98 (0.75-1.29) 2002 2004 2006 2007 Studies including paediatric patients MASCOT Subtotal (95% CI) Total events: 43 (short course), 57 (long course) Test for heterogeneity: not applicable Test for overall effect: Z = 1.47 (p = 0.14) 43/980 980 57/973 973 34.50 34.50 0.74 (0.49-1.11) 0.74 (0.49-1.11) 2002 Total (95% CI) Total events: 250 (short course), 262 (long course) Test for heterogeneity: chi2 = 4.30, df = 4 (p = 0.37), I2 = 6.9% Test for overall effect: Z = 0.93 (p = 0.35) 1610 1604 100.00 0.90 (0.72-1.13) 0.1 0.2 0.5 1 2 5 10 Favours short course Favours long course Dimopolous G et al. Drugs 2008; 68: 1841-1854

  24. Potentially relevant articles identified from PubMed (n=381) • Articles excluded (n=689) because they were: • letters (n=59) • irrelevant (n=239) • review (n=270) • guidelines (n=61) • paediatric population (n=29) • experimental (n=3) • non-RCTs (n=14) • case reports (n=7) • meta-analysis (n=3) • not CAP infection (n=13) RCTs eligible for further meta-analysis (n=5) Scopus search: 1 additional RCT RCTs included in further meta-analysis (n=6) Athanassa Z et al. Drugs 2008; 68: 2469-2481

  25. Treatment Success Study or sub-category Early switch (n/N) IV treatment (n/N) OR (fixed) [95% CI] Weight (%) OR (fixed) [95% CI] 3.68 39.45 4.84 20.10 3.75 28.28 100.00 [0.05, 6.81] [0.62, 2.14] [0.05, 5.09] [0.01, 0.66] [0.24, 10.30] [0.59, 2.54] [0.62, 1.39] Siegel et al Norrby et al Omidvari et al Castro-Guardiola Yacub et al Oosterheert et al Total (95% CI) Total events: 333 (early switch), 341 (IV treatment) Test for heterogeneity: chi2 = 6.96, df = 5 (p = 0.22) I2 = 28.2% Test for overall effect: Z = 0.39 (p = 0.69) 18/20 105/127 55/58 39/48 23/25 93/108 386 16/17 112/139 36/37 54/55 22/25 101/121 394 0.56 1.15 0.51 0.08 1.57 1.23 0.92 0.01 0. 1 1 10 100 Favours IV treatment Favours early switch Athanassa Z et al. Drugs 2008; 68: 2469-2481

  26. Mortality Study or sub-category Early switch (n/N) IV treatment (n/N) OR (fixed) [95% CI] Weight (%) OR (fixed) [95% CI] 61.34 10.42 1.33 4.33 22.58 100.00 [0.50, 1.71] [0.06, 2.55] [0.14, 88.08] [0.01, 8.25] [0.20, 1.93] [0.49, 1.33] Norrby et al Omidvari et al Castro-Guardiola Yacub et al Oosterheert et al Total (95% CI) Total events: 29 (early switch), 34 (IV treatment) Test for heterogeneity: chi2 = 2.04, df = 4 (p = 0.73) I2 = 0% Test for overall effect: Z = 0.84 (p = 0.40) 21/314 2/58 1/48 0/25 5/132 577 22/305 3/37 0/55 1/25 8/133 555 0.92 0.40 3.51 0.32 0.62 0.81 0.01 0. 1 1 10 100 Favours IV treatment Favours early switch Athanassa Z et al. Drugs 2008; 68: 2469-2481

  27. Hospitalisation Study or sub-category N Early switch mean (SD) N IV treatment mean (SD) WMD (random) [95% CI] Weight (%) WMD (random) [95% CI] Siegel et al Omidvari et al Gastro-Guardiola Yacub et al Oosterheert et al Total (95% CI) Test for heterogeneity: chi2 = 34.86, df = 4 (p<0.00001), I2 = 88.5% Test for overall effect: Z = 6.03 (p <0.00001) 20 58 48 25 108 259 8.00 (4.00) 7.30 (0.80) 6.00 (4.00) 4.10 (0.92) 9.00 (4.70) 17 37 55 25 133 267 13.70 24.85 18.05 23.89 19.50 100.00 -3.00 (-4.99, -1.01) -2.40 (-2.76, -2.04) -5.00 (-6.38, -3.62) -4.10 (-4.66, -3.54) -2.30 (-3.49, -1.11) -3.34 (-4.42, -2.25) 11.00 (2.00) 9.70 (0.90) 11.00 (3.00) 8.20 (1.10) 11.30 (4.70) -10 -5 0 5 10 Early switch IV treatment Athanassa Z et al. Drugs 2008; 68: 2469-2481

  28. Recurrent Infection Study or sub-category Early switch mean (SD) IV treatment (nN) OR 9fixed)) [95% CI] Weight (%) OR (fixed) [95% CI] Siegel et al Norrby et al Omidvari et al Gastro-Guardiola Yacub et al Total (95% CI) Test for heterogeneity: chi2 = 3.94, df = 4 (p= 0.041), I2 = 0% Test for overall effect: Z =1.22 (p = 0.22) 1/20 3/69 2/42 4/48 0/10 189 7.73 53.01 8.35 6.55 24.35 100.00 2.69 (0.10, 40.49) 0.92 (0.20, 4.25) 3.89 (0.18, 83.93 11.22 (0.59, 214.08) 0.24 (0.01, 6.69) 1.81 (0.70, 4.72) 0/17 4/85 0/31 0/55 1/8 196 0.001 0.01 0.1 0 10 100 1000 IV treatment Early switch Athanassa Z et al. Drugs 2008; 68: 2469-2481

  29. Bacteremia MEDLINE 1445 EMBASE 2771 Cochrane 1057 Peritonitis MEDLINE 664 EMBASE 20231 Cochrane 1055 CRBSI MEDLINE 302 EMBASE 1499 Cochrane 1292 Pneumonia MEDLINE 3587 EMBASE 15604 Cochrane 2000 Pyelonephritis MEDLINE 220 EMBASE 825 Cochrane 325 SSTI MEDLINE 673 EMBASE 4312 Cochrane 827 5273 records screened 3743 records screened 3093 records screened 21195 records screened 1368 records screened 5812 records screened 1 study included 3 studies included 0 studies included 13 studies included 6 studies included 1 study included 24 studies included in systematic review 1 study with bacteremic patients excluded 8 studies unclear whether bacteremic patients included 15 studies included bacteremic patients 7 studies with data on bacteremic patient outcomes Havey TC et al. Critical Care 2011, 15:R267

  30. 0.88 1.00 0.24 1.00 0.88 [0.75, 1.02] [0.68, 1.46] [0.02, 3.19] [0.83, 1.21] [0.77, 1.01] 0. 01 0. 1 10 100 1 Favours long duration Favours short duration Outcome – ClinicalCure Short Duration Long Duration Weight (%) Risk Ratio M-H, Fixed, 95% CI Study or subgroup Events Total Events Total 28 5 0 12 45 33 5 2 12 52 32 4 3 8 47 33 4 4 8 49 64.5 9.9 5.3 20.3 100.0 Chowdhary Jernelius Siegel Teller Total (95% CI) Total events: 29 (early switch), 34 (IV treatment) Test for heterogeneity: chi2 = 3.15, df = 3 (p = 0.37) I2 = 5% Test for overall effect: Z = 1.86 (p = 0.06) Havey TC et al. Critical Care 2011, 15:R267

  31. 1.15 1.04 1.00 1.05 [0.79, 1.68] [0.85, 1.26] [0.83, 1.21] [0.91, 1.21] 0. 01 0. 1 10 100 1 Favours long duration Favours short duration Outcome – MicrobiologıcalCure Short Duration Long Duration Study or subgroup Weight (%) Risk Ratio M-H, Fixed, 95% CI Risk Ratio M-H, Fixed, 95% CI Events Total Events Total 7 9 12 28 7 9 12 28 6 16 8 30 7 17 8 32 22.9 41.6 35.5 100.0 Dunbar Runyon Teller Total (95% CI) Total events: Heterogeneity: chi2 = 0.51, df = 2 (p = 0.78) I2 = 0% Test for overall effect: Z = 0.69 (p = 0.49) Havey TC et al. Critical Care 2011, 15:R267

  32. Short Duration Long Duration Study or subgroup Weight (%) Risk Ratio M-H, Fixed, 95% CI Risk Ratio M-H, Fixed, 95% CI Events Total Events Total 5 9 1 28 6 9 2 28 7 15 4 30 8 17 4 32 29.3 54.1 16.5 100.0 Chaudhry Runyon Siege Total (95% CI) Total events: Heterogeneity: chi2 = 2.07, df = 2 (p = 0.36) I2 = 3% Test for overall effect: Z = 0.26 (p = 0.79) 0.95 1.10 0.56 0.97 [0.61, 1.48] [0.87, 1.39] [0.17, 1.79] [0.97, 1.23] 0. 01 0. 1 10 100 1 Favours long duration Favours short duration Outcome – Survival Havey TC et al. Critical Care 2011, 15:R267

  33. Control PCT after 6 - 24 hours • Initial antibiotics can be considered in case of: • Respiratory or hemodynamic instability • Need for ICU admission • PCT <0.1 µg/l • PCT <0.25 µg/l • Localised injection (abscess, empyema) • Compromised host defence (e.g. Immuno- suppression other than corticosteroids) • Concomitant infection in need of antibiotics CAP with PSI V or CURB >3 COPD with GOLD VI CAP with PSI ≥IV or CURB >2 COPD with GOLD >III Procalcitonin (PCT) algorithm for stewardship of antibiotic therapy in patients with LRTI <0.1 µg/l 0.1 -0.25 µg/l >0.25 – 0.5 µg/l >0.5 µg/l Bacterial etiology very unlikely Bacterial etiology unlikely Bacterial etiology likely Bacterial etiology very likely NO antibiotics! No antibiotics Antibiotics yes Antibiotics YES! Consider the course of PCT • If antibiotics are initiated: • Repeated measurement of PCT on days 3, 5, 7 • Stop antibiotics using the same cut-offs above • If initial PCT levels are >5-10 µg/l, then stop when 80-90% decrease of peak PCT • If initial PCT remains high, consider treatment failure (e.g. resistant strain, emypema, ARDS) • Outpatients: duration of antibiotics according to the last PCT results >0.26 - 0.6 µg/l >0.6 - 1.0 µg/l >1.0 µg/l : 3 days : 5 days : 7 days Schuetz P et al. Eur J ClinMico Infect Dis 2010; 29: 269-277

  34. 287 outpatients with CAP assessed for eligibility 115 excluded (not eligible) 172 randomised 86 randomised to PCT group 86 randomised to control group 4 lost to follow-up 4 withdrew 1 lung cancer 2 lost to follow-up 4 withdrew 2 pulmonary TB 77 completed interview at 28 days 77 in per-protocol analysis 81 in intention-to-treat analysis 79 completed interview at 28 days 79 in per-protocol analysis 81 in intention-to-treat analysis Long W et al. Respirology 2011; 16: 819-824

  35. Common Recommendations • Patients with CAP should be treated for a minimum of 5 days, should be afebrile for 48 – 72h and should have no more than one CAP-associated sign of clinical instability • Longer duration for certain infections such as S. aureus pneumonia because of risk of endocarditis and deep-seated infections, Pseudomonas aeruginosa infections and atypical pathogens Siegel RE et al. Am J Therapeutics 1999; 6: 217-222

  36. Concluding Comments • It is reasonable to treat patients with CAP for 5-7 days, if the patient has been afebrile for > 48 hours, has no more than one of CAP-associated signs of clinical instability, and complications of CAP are absent Lim WS et al – BTS Guideline. Thorax 2009 Mandell LA et al – IDSA/ATS Guideline. Clin Infect Dis 2007 Hoffken G et al. Pneumologie 2010

More Related