CHEST COPD George Dimopoulos, MD, FCCP; Ilias I. Siempos, MD; Ioanna P. Korbila, MD; Katerina G. Manta, MD; and Matthew E. Falagas, MD, MSc, DSc (AECB) ( / ) ( / 2 3 ) AECB Pubmed Cochrane (RCT) 12 RCT (OR 0.51 95%CI 0.34 0.75) (OR 0.64 95%CI 0.25 1.66) (OR 0.56 95%CI 0.22 1.43) (OR 0.75 95%CI 0.39 1.45) (OR 1.58 95%CI 0.74 3.35) AECB / (amoxicillin / clavulanic acid); (COPD); (macrolides); (penicillins); (quinolones); (Streptococcus pneumoniae) AECB = acute exacerbation of chronic bronchitis; CB = chronic bronchitis; CE = clinically evaluable; CI = confidence interval; FEM = fixed-effects model; ITT = intention to treat; ME = microbiologically www.chestjournal.org.cn CHEST 2008 1 5 1 15
evaluable; OR = odds ratio; RCT = randomized controlled trial; REM = random-effects model; SMX = sulfamethoxazole; TMP = trimethoprim (CB) [1,2] CB (AECB) AECB ( ) [3 5] [6,7] (TMP) / (SMX) AECB AECB [8] 2 3 AECB [9] [10,11] AECB AECB From the Critical Care Department (Dr. Dimopoulos), Attikon University Hospital, Athens, Greece; and Alfa Institute of Biomedical Sciences (Drs. Siempos, Korbila, Manta, and Falagas),Athens, Greece. (RCT) PubMed Cochrane COPD 2 (IPK KGM) RCT ( ) (ITT) (CE) (ME) ( RCT ) RCT Jadad [12] RCT 3 1 1 2 1( ) 0( ) +1 ( ) 5 3 RCT Correspondence to: Matthew E. Falagas, MD, MSc, DSc, Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos St, 151 23 Marousi, Greece; e-mail: m.falagas@aibs.gr [8 13] 16
TMP / SMX AECB / ( ) 2 3 () RCT CB 3mo 2y Anthonisen [14] AECB 3 Anthonisen [14] 3 2 3 1 [14] ITT CE ( ) ( ) ITT PubMed Cochrane (RCT) 177 5 4 33 1 3 1 1 1 1 1 triamphenicol 1 supristol 1 124 RCT AECB RCT 97 12 RCT RCT / 1 AECB 5 AECB 5 5 9 1 1 RCT 35 RCT AECB 10 RCT 2 1 RCT TMP / SMX cotrifamole 6 RCT 1 5 RCT TMP / SMX 2 RCT 1 RCT TMP / SMX 5 RCT / 8 RCT / 12 RCT / 2 3 1 RCT www.chestjournal.org.cn CHEST 2008 1 5 1 17
RCT ME ( ) () 3 RCT [19,23,28] RCT 3 RCT [21,22,26] AECB RCT ( ) 1 (S-PLUS version 6.1 Insightful Corp Seattle WA) χ 2 RCT Egger [15] Mantel-Haenszel (FEM) [16] DerSimonian-Laird (REM) [17] OR 95%CI RCT FEM REM QUOROM [18] 1 177 1 80 35 RCT AECB 25 RCT 25 RCT 12 RCT [19 30] / (n =1) [28] TMP / SMX (n =1) [30] (n =5) [19,23 26] (n =2) [20,21] (n =2) [27,29] (n =1) [22] 12 RCT 2 261 1 RCT 3.3 ( 1 5) 10 RCT [19 22,24 26,28 30] 3 9 RCT [20 22,24 27,29,30] 12 RCT 2 RCT [24,30] ITT 2 12 RCT [19 30] CE ( 1 145 CE OR 0.51 95%CI 0.34 0.75 FEM) OR OR 2A 10 RCT [19 22,24 26,28 30] (997 CE OR 0.46 95%CI 0.30 0.70 FEM) 1 RCT [21] (864 CE OR 0.53 95%CI 0.33 0.84 FEM) RCT 1 465 CE OR 0.57 95%CI 0.37 0.89 FEM ( 9 RCT [20 22,24 27,29,30] ) RCT 796 CE OR 0.36 95%CI 0.16 0.81 ( 3 RCT [19,23,28] ) 1991 RCT 1 287 CE OR 0.46 95%CI 0.29 0.73 ( 6 RCT [19 24] ) 1991 RCT 974 CE OR 0.80 95%CI 0.38 1.69 (6 RCT [25 30] ) 1 392 ITT OR 0.64 95%CI 0.25 1.66 FEM (5 RCT [21,26 28,30] ) ( 2B) 1 619 ITT OR 0.75 95%CI 0.39 1.45 REM ( 8 RCT [19 23,25,26,30] ) ( 2C) 1 166 ITT OR 18
1 RCT 1 / / / /% (2) ( ) AECB ITT 1 2 (2) (3) Schouenbourg [19] / MC SB RCT 18 CB Anthonisen 61 59 / 49 49 700 mg 500 mg NA 239 98 138 3 2000 / AECB q12h (10 d) q24h (3 d) Chodosh [20] / MC DB RCT 18 CB 65 65 / 23 41 500 mg 400 mg NA 194 92 102 4 1993 / Anthonisen AECB q8h (7 d) q24h (7 d) Ulmer [21] / MC DB RCT 18 CB 63 63 / 34 35 500 mg 400 mg 625 310 313 4 1993 / Anthonisen AECB q8h (7 d) q24h (7 d) De Vlieger [22] / MC DB RCT 18 CB Anthonisen 58 62 / 48 37 200 mg 300 mg 76 33 41 4 1992 / AECB q24h (7 14 d) q24h (7 14 d) Guay [23] / MC SB RCT 18 CB Anthonisen 54 58 / 46 42 500 mg 500 mg NA 103 50 53 1 1992 / AECB q6h ( 14 d) q12h ( 14 d) Mertens [24] / DB RCT CB Anthonisen 58 65 / 56 79 500 mg 500 mg NA 50 25 25 4 1992 / AECB q8h (5 d) q24h (3 d) Aldons [25] / MC DB RCT 18 CB Anthonisen 58 60 / 43 45 250 mg 250 mg NA 125 65 60 5 1991 / AECB q6h (7 14 d) q12h (7 14 d) Bachand [26] / MC DB RCT 18 COPD 56 55 / 42 41 250 mg 250 mg 225 114 111 4 1991 / q6h (10d) q12h (10 d) AECB (4) Trigg [27] / DB RCT 46 COPD 71 68 / 79 30 500 mg 500 mg NA 51 25 26 2 1991 / Anthonisen AECB q8h (7 d) q8h (7 d) McGhie [28] / SB RCT 18 CB AECB (4) 49 52 / 50 43 250 mg 250 mg NA 454 230 224 3 1986 / 200 mg 125 mg q12h (10 d) q8h (10 d) Law [29] / DB RCT 55 CB 66 65 / 20 15 500 mg 500 mg NA 80 40 40 3 1983 / Anthonisen AECB q8h (10 d) q8h (10d) Anderson [30] / DB RCT 48 CB AECB (4) 66 64 / 16 25 TMP 80 mg / SMX 500 mg NA 39 19 20 3 1981 / 400 mg q24h (7 d) q8h (7 d) (1) MC SB DB NA (2) (3) Jadad (4) Anthonisen AECB www.chestjournal.org.cn CHEST 2008 1 5 1 19
2 RCT (1) / TOCV ITT TOCV CE Schouenbourg [19] /2000 NA 79 / 92 (86) 124 / 133 (93) NA 22 / 98 (22) 20 / 138 (14) 5 / 98 (5) 3 / 138 (2) 11 / 98 (11) 7 / 138 (5) Chodosh [20] / 1993 NA 22 / 29 (76) 21 / 22 (95) NA 14 / 92 (15) 42 / 102 (41) 5 / 92 (5) 13 / 102 (13) NA Ulmer [21] /1993 NA 111 / 136 (81) 131 / 145 (89) 3 / 310 (1) 3 / 313 (1) 27 / 310 (9) 61 / 313 (19) 7 / 310 (2) 20 / 313 (6) NA De Vlieger [22] / 1992 NA 20 / 25 (80) 30 / 37 (81) NA 7 / 33 (21) 4 / 41 (10) 3 / 33 (9) 0 / 41 (0) NA Guay [23] /1992 NA 46 / 47 (98) 53 / 53 (100) NA 10 / 50 (20) 8 / 53 (15) NA 3 / 50 (6) 3/53 (6) Mertens [24] /1992 20 / 25 (80) 24 / 25 (96) 20 / 25 (80) 24 / 25 (96) NA NA NA NA Aldons [25] / 1991 NA 21 / 23 (91) 27 / 28 (96) NA 1 / 65 (2) 7 / 60 (12) 1 / 65 (2) NA 0 / 65 (0) 0/60 (0) Bachand [26] /1991 NA 31 / 34 (91) 28 / 29 (97) 1 / 114 (1) 1 / 111 (1) 36 / 114 (32) 34 / 111 (31) NA NA Trigg [27] /1991 NA 13 / 25 (52) 11 / 23 (48) 2 / 25 (8) 4 / 26 (15) NA NA 1 / 25 (4) 2/26 (8) McGhie [28] / 1986 NA 51 / 55 (93) 49 / 49 (100) 0 / 230 (0) 2 / 224 (1) NA NA NA Law [29] / 1983 NA 33 / 36 (92) 36 / 38 (95) NA NA NA NA Anderson [30] /1981 15 / 19 (79) 15 / 20 (75) 15 / 17 (88) 15 / 19 (80) 1 / 19 (5) 1 / 20 (5) 0 / 19 (0) 0 / 20 (0) 0 / 19 (0) 0 / 20 (0) 0 / 19 (0) 0/20 (0) (1) / (%) TOCV ( 1 7 d) 1 0.61 95%CI 0.35 1.06 FEM ( 5 RCT [19 22,30] ) 554 ITT OR 1.58 95%CI 0.74 3.35 FEM ( 5 RCT [19,23,25,27,30] ) ( 4 RCT [19,21 23] ) ( 1 RCT) ( 4 RCT [20,21,23,25] ) ( 2 RCT [19,22] ) ( 1 RCT) 3 9 RCT [19 23,25 27, 30] ME ( 638 ME OR 0.56 95%CI 0.22 1.43 REM) ( 2D) 7 RCT [20,21,23 26, 30] 3 ( ) (241 OR 0.62 95%CI 0.29 1.29 FEM) (98 OR 0.33 95%CI 0.07 1.53 FEM) (137 OR 1.86 95%CI 0.67 5.20 FEM) ( ) ( / ) RCT CE 943 CE OR 0.46 95%CI 0.30 0.72 FEM ( 9 RCT [19 21,23 27,29] ) ME 610 ME 20
A ( ) Schouenborg Chodosh Ulmer De Vlieger Guay Mertens Aldons Bachand Trigg Mc Ghie Law Anderson Combined 0.01 1.00 164.89 OR () C ( ) Schouenborg Chodosh Ulmer De Vlieger Guay Aldons Bachand Anderson Combined B ( ) Ulmer Bachand Trigg Mc Ghie Anderson Combined D ( ) Schouenborg Chodosh Ulmer De Vlieger Guay Aldons Bachand Trigg Anderson Combined 0.001 1.00 108.50 OR () 0.01 1.00 70.89 OR () 0 1.00 391.68 OR () 2 AECB RCT OR A CE B C D ME OR ( ) RCT OR 95%CI OR 0. 35 95%CI 0.20 0.60 FEM ( 7 RCT [19 21,23,25 27] ) ( ) [21,26,27] [19 21,23,25,26] [19,23,25,27] [19 21] [20,21,23 26] ( ) RCT CE 489 CE OR 0. 36 95%CI 0.17 0.75 FEM (5 RCT [19,23 26] ) [19,23,25,26] [19,23,25] ME [19,23,25,26] [23 26] ( ) www.chestjournal.org.cn CHEST 2008 1 5 1 21
3 RCT (1) / (3) ( ) (2) Schouenbourg [19] / 32 / 37 (86) 49 / 54 (91) NA NA NA 2000 Chodosh [20] /1993 18 / 30 (60) 21 / 22 (95) 7 / 11 (64) 10 / 10 (100) 5 / 5 (100) 6 / 6 (100) 0 / 1 (0) 1/1 (100) l U 8 De Vlieger [22] /1992 6 / 7 (86) 5 / 5 (100) NA NA NA Guay [23] / 1992 12 / 12 (100) 23 / 23 (100) 10 / 10 (100) 10 / 10 (100) 11 / 11 (100) 11 / 11 (100) 20 / 20 (100) 19 / 19 (100) Mertens [24] / 1992 NA 7 / 11 (64) 8 / 12 (67) 2 / 2 (100) 6 / 6 (100) 6 / 7 (86) 3 / 4 (75) Aldons [25] /1991 24 / 24 (100) 28 / 29 (96) 17 / 17 (100) 19 / 20 (95) 1 / 1 (100) 6 / 6 (100) 6 / 6 (100) 2/2 (100) Bachand [26] /1991 32 / 34 (94) 25 / 29 (86) 18 / 21 (86) 7 / 11 (64) 1 / 2 (50) 6 / 7 (86) 7 / 7 (100) 11 / 11 (100) Trigg [27] /1991 5/15 (33) 9 / 15 (60) NA NA NA McGhie [28] /1986 NA NA NA NA Law [29] /1983 NA NA NA NA Anderson [30] /1981 8 / 8 (100) 4 / 8 (50) 5 / 5 (100) 4 / 6 (67) NA 3 / 3 (100) 0/2 (0) (1) 1 (2) / (%) (3) / (%) 6 RCT [20,21,24,27,29,30] 4 RCT [19,23,25,26] 540 CE OR 0. 55 95%CI 0.33 0.90 FEM ( 6 RCT [20,21,24,27,29,30] ) 439 CE OR 0. 41 95%CI 0.19 0.90 REM ( 4 RCT [19,23,25,26] ) AECB CE AECB CE ( ME AECB ) ( ) RCT RCT RCT AECB 65 FEV 1 50% 1y AECB 3 [8] [31,32] RCT [20,21,24,27,29,30] AECB CE RCT [21] RCT [19 22,24 26,28 30] RCT [20 22,24 27,29,30] 1991 RCT [19 24] 1991 RCT [25 30] 22
[1,33] Anthonisen ( ) AECB [13] RCT ( ) RCT RCT ( TMP / SMX / ) AECB RCT TMP / SMX ( [13] AECB ) RCT [34] / AECB ITT 2 RCT [24,30] AECB AECB AECB RCT 1991 AECB β β AECB 1 Miravitlles M, et al. Chest 2002;121:1449 1455 2 Niederman MS, et al. Clin Ther 1999;21:576 591 3 Sethi S, et al. N Engl J Med 2002;347:465 471 4 Patel IS, et al. Thorax 2002;57:759 764 5 Martinez FJ, et al. Am J Med 2005;118(Suppl):39S 44S 6 Adams SG, et al. Cleve Clin J Med 2000;67:625 628, 631 633 7 Anzueto A. Semin Respir Crit Care Med 2000;21:97 106 8 Balter MS, et al. Can Respir J 2003;10(Suppl):3B 32B 9 Miravitlles M, et al. Chest 1999;116:40 46 10 Sethi S. Clin Infect Dis 2005;41(Suppl):S177 S185 11 Miravitlles M, et al. Chest 2004;125:953 964 12 Moher D, et al. Lancet 1998;352:609 613 13 Woodhead M, et al. Eur Respir J 2005;26:1138 1180 14 Anthonisen NR, et al. Ann Intern Med 1987;106:196 204 15 Egger M, et al. BMJ 1997;315:629 634 16 Mantel N, et al. J Natl Cancer Inst 1959;22:719 748 17 DerSimonian R, et al. Control Clin Trials 1986;7:177 188 18 Moher D, et al. Lancet 1999;354:1896 1900 www.chestjournal.org.cn CHEST 2008 1 5 1 23
19 Schouenborg P, et al. J Int Med Res 2000;28:101 110 20 Chodosh S. Am J Med 1993;94(Suppl):131S 135S 21 Ulmer W. Am J Med 1993;94(Suppl):136S 141S 22 De Vlieger A, et al. Diagn Microbiol Infect Dis 1992;15(Suppl): 123S 127S 23 Guay DR, et al. J Intern Med 1992;231:295 301 24 Mertens JC, et al. Antimicrob Agents Chemother 1992;36: 1456 1459 25 Aldons PM. J Antimicrob Chemother 1991;27(Suppl):101 108 26 Bachand RT Jr. J Antimicrob Chemother 1991;27(Suppl):91 100 27 Trigg CJ, et al. Respir Med 1991;85:301 308 28 McGhie D, et al. J Int Med Res 1986;14:254 260 29 Law MR, et al. J Antimicrob Chemother 1983;11:83 88 30 Anderson G, et al. J Antimicrob Chemother 1981;8:487 489 31 Wilson R, et al. Thorax 2006;61:337 342 32 Wilson R, et al. Chest 2004;125:953 964 33 Sportel JH, et al. Thorax 1995;50:249 253 34 Siempos, et al. Eur Respir J 2007;29:1127 1137 CHEST 2007;132:447 455 24