Table 1:  Susceptibility of Legionella spp. To Antimicrobial Agents by In Vitro Agar Dilution Method.

Drug/Species	MIC50 (mcg/ml)	MIC90 (mcg/ml)	MIC range (mcg/ml)	References
Erythromycin
L. pneumophila (serogroups 1-9, 12)	0.015-1.0	0.03-2.0	0.008-1.0	(18,29,35,57)(31,32,106)
Legionella spp.	0.10-0.50	0.25-1.0	<0.0015-2.0	(35,44,64,76) (18,32,37) (31) (59, 124,134)
L. micdadei	0.06-1.0	0.25	0.06-1.0	(18,64,73) (26,31,32)
L. bozemanii	0.12-2.0	--	--	(18,64,73)
L. dumoffii	0.25	0.50	0.25-0.50	(31,32,64,73)
L. longbeachae	0.25-1.0	0.50	0.008-0.50	(18,31,32,106)
L. gormanii	0.12	--	--	(64, 73)
Azithromycin
Legionella spp.	0.012-0.50	0.06-2.0	0.016-4.0	(18,31,35,73)
L. pneumophila (serogroups 1,2,5,6)	0.06-01.5	0.50-1.0	0.03-2.0	(18,35,54,106)
L. pneumophila (serogroups 1-9, 12)	0.03-0.12	0.12-0.5	0.008-0.5	(83)
L. longbeachae	0.12-1.0	0.50	0.016-0.50	(18,31,106)
L. micdadei	0.12-1.0	0.25	0.016-0.25	(18,26,31,73)
L. bozemanii	0.50-1.0	--	--	(18,73)
L. dumoffii	0.12-0.25	0.25	0.12-0.25	(31,73)
L. gormanii	0.25	--	--	(73)
Clarithromycin
Legionella spp.	<0.004-0.25	<0.004-2.0	<= 0.004-2.0	(18,32,73) (59,134)
L. pneumophila (serogroups 1,2,5,6)	0.03-0.50	0.06-2.0	0.03-2.0	(18,54,106)
L. pneumophila (serogroups 1-9, 12)	0.016-0.06	0.06	<0.004-0.06	(31)
L. longbeachae	0.06-0.25	0.12	0.008-0.25	(18,31,106)
L. micdadei	0.06-0.50	0.06	0.03-0.12	(18,31,73)
L. bozemanii	0.12-0.50	--	--	(18,73)
L. dumoffii	0.03-0.12	0.06	0.03-0.06	(31,73)
L. gormanii	0.12	--	--	(73)
14-OH Clarithromycin
Legionella spp.	0.06	0.12	0.03-0.50	(73)
L. micdadei	0.12	--	--	(73)
L. bozemanii	0.06	--	--	(73)
L. dumoffii	0.12	--	--	(73)
Dirithromycin
Legionella spp.	1.0	4.0	0.25-4.0	(73)
L. pneumophila (serogroups 1,2,5)	0.50	8.0	0.25-8.0	(106)
L. longbeachae	8.0	8.0	0.25-16	(106)
L. bozemanii	2.0	--	--	(73)
L. dumoffii	4.0	--	--	(73)
L. gormanii	1.0	--	--	(73)
Josamycin
Legionella spp.	0.25-0.50	0.25-1.0	0.0625-1.0	(130)
L. pneumophila	--	--	0.25-0.50	(130)
L. micdadei	--	--	<=0.0313-0.50	(130)
L. bozemanii	--	--	0.125-0.50	(130)
L. dumoffii	--	--	0.125-0.50	(130)
L. longbeachae (serogroups 1,2)	--	--	<=0.0313-.25	(130)
L. gormanii	--	--	<=0.0313-0.0625	(130)
L. jordanis	--	--		(130)
L. wadsworthii	--	--		(130)
Roxithromycin
Legionella spp.	0.06-0.25	0.125-1.0	0.016-2.0	(18,134)
L. pneumophila (1,2,5,6)	0.12-0.50	0.25-2.0	0.06-2.0	(18,81,106)
L. longbeachae	0.06-0.50	0.50	0.12-0.50	(18,106)
L. micdadei	0.125-1.0	--	--	(18)
L. bozemanii	0.12-0.25	--	--	(18,73)
L. dumoffii	0.12	--	--	(73)
L. gormanii	0.25	--	--	(73)
Telithromycin
Legionella spp.	0.015	0.03	<0.004-0.12	(134)
Ciprofloxacin
L. longbeachae	<=0.004-1.0	0.01-0.06	<=0.004-0.06	(18,31,32,106)
L. pneumophilia	0.03	0.03	0.015-0.03	(114)
L. pneumophilia (serogroups 1-9,12)	<=0.016-2.0	0.016-2.0	<=0.004-4.0	(18,35,57,106) (31,32)
Legionella spp.	0.01-1.0	0.02-2.0	<=0.004-4.0	(35,44,76) (18,32,64,73) (31,59,114,124)
L. micdadei	0.01-1.0	0.03	0.01-0.03	(18,64,73) (31,32)
L. dumoffii	0.01-1.0	0.03	0.01-0.03	(31,32,64,73)
L. bozemanii	0.015-1.0	--	--	(18,64,73)
L. gormanii	0.03	--	--	(64,73)
Enoxacin
L. pneumophila	0.125	--	--	(19)
Fleroxacin
Legionella spp.	0.06	0.06	0.005-0.06	(64)
L. micdadei	0.03	--	--	(64)
L. bozemanii	0.03	--	--	(64)
L. dumoffii	0.03	--	--	(64)
L. gormanii	0.03	--	--	(64)
Grepafloxacin
Legionella spp.	0.015-0.5	0.015-0.5	0.008-2	(59,123)
L.  pneumophila	<0.004-0.016	0.016-0.03	<0.004-0.03	(31)
Gatifloxacin
Legionella spp.	0.03	0.03	0.015-0.03	(114)
L.  pneumophila	0.015	0.03	0.004-0.03	(114)
L. pneumophila (serogroups 1)	0.016	0.016	<0.004-0.03	(30)
L. pneumophila (serogroups 2-9)	0.008	0.016	0.008-0.016	(30)
Levofloxacin
Legionella spp.	0.015-0.12	0.03-0.12	0.008-0.25	(31,59,134)
L.  pneumophila	0.03	--	--	(19)
L. pneumophila (serogroups 1-9, 12)	0.008-0.016	0.008-0.016	<0.004-0.016	(31)
L. dumoffii	0.016	0.016	0.016	(31)
L. micdadei	0.016	0.016	0.008-0.016	(31)
L. longbeachae	0.016	--	0.008-0.016	(31)
Lomefloxacin
Legionella spp.	0.06	0.12	0.03-0.12	(64)
L. micdadei	0.03-0.06	--	--	(64)
L. bozemanii	0.06	--	--	(64)
L. dumoffii	0.12	--	--	(64)
L. gormanii	0.03	--	--	(64)
Ofloxacin
Legionella spp.	0.016-0.5	0.5	<0.004-1	(31,59)
L.  pneumophila	0.015-0.03	0.015	0.015	(19,57,81)
L. pneumophila (serogroups 1-9, 12)	0.016-0.03	0.016-0.3	<0.004-0.03	(31)
L. micdadei	0.03-0.06	0.03	0.03	(31,64)
L. bozemanii	0.03	--	--	(64)
L. dumoffii	0.03-0.06	0.03	0.03	(31,64)
L. longbeachae	0.03	--	0.016-0.03	(31)
L. gormanii	0.03	--	--	(64)
Pefloxacin
L. pneumophila (serogroup 1)	0.50	--	--	(29)
Rufloxacin
L.  pneumophila	0.12	0.25	0.06-0.25	(57)
Sparfloxacin
L. pneumophila (serogroups 1-8)	<0.004	<0.004	<0.004-0.01	(32,44,76)
L. micdadei	<0.004	<0.004	<0.004	(32)
Legionella spp	<0.004-0.50	0.008-1.0	<0.004-2.0	(32,76)
L. dumoffii	0.01	0.01	0.008-0.01	(32)
L. longbeachae	0.008	0.01	<0.004-0.01	(32)
Trovafloxacin
Legionella spp.	<0.004-0.25	0.25	<0.004-1	(31,59)
L. pneumophila (serogroups 1-8)	< 0.004	<0.004	<0.004-0.016	(31,32)
L. micdadei	< 0.004	<0.004	<0.004	(31,32)
L. dumoffii	< 0.004	<0.004	<0.004-0.008	(31,32)
L. longbeachae	< 0.004	<0.004	<0.004	(31,32)
Legionella spp.	< 0.004	<0.004	<0.004	(31,32)
Moxifloxacin
Legionella spp.	0.008-0.03	0.018	0.008-0.12	(31,124,134)
L. pneumophila (serogroups 1-9, 12)	<0.004-0.016	0.008-0.016	<0.004-0.03	(31)
L. dumoffii	0.03	0.03	0.008-0.03	(31)
L. micdadei	0.016	0.03	0.008-0.03	(31)
L. longbeachae	0.016	--	0.008-0.03	(31)
Gemifloxacin
Legionella spp.	0.03-1	1	0.016-4	(31,59)
L. pneumophila (serogroups 1-9, 12)	0.008-0.03	0.016-0.03	0.008-0.03	(31)
L. dumoffii	0.06	0.06	0.06	(31)
L. micdadei	0.016	0.03	0.008-0.03	(31)
L. longbeachae	0.06	--	0.016-0.03	(31)
Amoxicillin
L. pneumophila (serogroups 1,2,5)	0.25-0.50	2.0	0.12-2.0	(106)
L. longbeachae	0.50-1.0	>2.0	0.25-2.0	(106)
Amoxicillin/Clavulanate
L. pneumophila (serogroups 1,2,5)	0.06-0.25	0.25	0.06-0.50	(106)
L. longbeachae	0.25-0.50	1.0	0.25-1.0	(106)
Piperacillin/Tazobactam
L. longbeachae	0.06	0.12	0.015-0.12	(106)
L. pneumophila (serogroups 1,2,5)	0.25	0.50	0.06-0.50	(106)
Imipenem
L. longbeachae	<0.03	0.03	0.015-0.06	(18,106)
L. pneumophila (serogroups 1,2,5)	0.03-0.125	0.06	<0.015-0.25	(18,106)
Legionella spp	0.03-0.50	0.06-1.0	<0.03-2.0	(18,64)
L. micdadei	0.125-0.25	--	--	(18,64)
L. bozemanii	0.25-1.0	--	--	(18,64)
L. dumoffii	4.0	--	--	(64)
Imipenem
L. gormanii	1.0	--	--	(64)
Meropenem
Legionella spp.	<0.06	0.12	<0.06-0.125	(73)
L. micdadei	<0.06	--	--	(73)
L. bozemanii	<0.06	--	--	(73)
L. dumoffii	0.12	--	--	(73)
L. gormanii	0.12	--	--	(73)
Rifampicin
Legionella spp.	<0.0005-0.03	<0.002-0.03	<0.0005-0.03	(63,73,76) (18,32) (31,134) (124)
L. pneumophila (serogroups 1-9,12)	<0.002-0.004	<0.004-0.008	<0.0004-0.008	(18,81.106) (31,32)
L. micdadei	0.008	0.008	0.008	(18,64,73) (31,32)
L. dumoffii	0.008-0.15	0.01	<0.004-0.03	(18,106) (31,32)
L. longbeachae	<0.002-0.004	0.01	<0.004-0.06	(64,73) (18,32)
L. bozemanii	<0.002-0.004	--	--	(64,73)
Clindamycin
Legionella spp.	4.0-8.0	8.0	1.0-16	(73,134)
L. micdadei	4.0-8.0	--	--	(73)
L. bozemanii	4.0	--	--	(73)
L. dumoffii	4.0	--	--	(73)
L. gormanii	4.0	--	--	(73)
Trimethoprin/Suflamethaxazole
Legionella spp.	0.50	0.50	<0.03-1.0	(73)
L. micdadei	0.50	--	--	(73)
L.bozemanii	<0.03	--	--	(73)
L. dumoffii	<0.03	--	--	(73)
L. gormanii	<0.03	--	--	(73)
Doxycycline
Legionella spp.	1.0-4.0	2.0-8	0.12-8.0	(73,134)
L. micdadei	0.12-025	--	--	(73)
L.bozemanii	1.0	--	--	(73)
L. dumoffii	1.0	--	--	(73)
L. gormanii	2.0	--	--	(73)
Tetracycline
Legionella spp.	8.0	8.0	1.0->8.0	(73)
L. micdadei	0.25-1.0	--	--	(73)
L.bozemanii	4.0	--	--	(73)
L. dumoffii	4.0	--	--	(73)
L. gormanii	4.0	--	--	(73)
Dalfopristin-Quinupristin
Legionella  spp.	0.25	0.5	0.12-1	(134)
Linezolid
Legionella spp.	4	8	4.0-8	(134)

 

Table 2:  Susceptibility of Legionella spp. To Antimicrobial Agents by In Vitro Broth Dilution Method

Drug/Species	MIC50 (mcg/ml)	MIC90 (mcg/ml)	MIC range (mcg/ml)	References
Erythromycin
L. pneumophila	0.125-0.25	0.25-1	0.016-1.0	(35,44,81) (37,57) (121,142)
Legionella spp.	0.5-0.06	0.5-0.10	0.032-1.0	(35,37,39) (40,58)
L. micdadei	--	0.25	1.0	(26,135,142)
L. bozemanii	--	0.25	0.25	(26,135,142)
L. longbeachae	0.06	0.12-0.25	0.06-0.12	(63,135)
L. gormanii	0.12	0.5	0.06-0.5	(63)
L. dumoffii	0.12	0.5	0.12-0.5	(63)
Azithromycin
L. pneumophila	0.06-1.39	0.5-2.77	0.016-7.80	(35,121) (63,142) (135)
L. micdadei	--	0.25	0.50	(135,142)
L. bozemanii	--	0.125	0.25q	(135,142)
L. longbeachae	0.12	0.25	0.06-0.25	(63,135)
L. gormanii	0.25	0.5	0.12-1.0	(63)
L. dumoffiii	0.25	0.5	0.12-0.5	(63)
Clarithromycin
Legionella spp.	0.007-0.032	0.015-0.5	0.0004-2	(40,58) (49,92)
L. pneumophila	0.007-0.032	0.008-0.06	<0.001-0.125	(93,121,142) (40,135)
L. micdadei	--	0.03	0.125	(135,142)
L. bozemanii	--	<0.03	0.03	(135,142)
L. longbeachae	--	0.125	--	(135)
14-Hydroxyclarithromycin
Legionella spp.	--	--	0.004-0.03	(93)
Dirithromycin
L. pneumophila	--	--	0.50-8.0	(142)
L. micdadei	--	--	4.0	(142)
L. bozemanii	--	--	8.0	(142)
Roxithromycin
L. pneumophila	0.0625	--	0.06-0.25	(81,142)
L. micdadei	--	--	4.0	(142)
L. bozemanii	--	--	8.0	(142)
Telithromycin
Legionella spp.	0.062	0.125	0.004-0.250	(40)
L. pneumophila	0.032	0.125	0.016-0.344	(40,135)
L. micdadei	--	<0.03	--	(135)
L. longbeachae	--	<0.03	--	(135)
L. bozemanii	--	<0.03	--	(135)
ABT 773
L. pneumophila	--	0.03-0.06	--	(135)
L. micdadei	--	0.03	--	(135)
L. longbeachae	--	0.25	--	(135)
L. bozemanii	--	0.03	--	(135)
Ciprofloxacin
Legionella spp	0.007-0.016	0.015-0.06	0.0018-0.25
L. pneumophila	0.0079-0.06	0.03-0.06	0.016-0.25
L. longbeachae	0.016	0.03	0.008-0.03
L .gormanii	0.016	0.03	0.016-0.03
L. dumoffii	0.03	0.03	0.01-0.03
L. micdadei	--	0.008	--
L. bozemanii	--	0.015	--
Levofloxacin
Legionella spp	0.007-0.032	0.016-0.063	0.0039-0.5	(40,42) (58,92) (146)
L. pneumophila	0.016-0.062	0.016-0.063	0.008-0.063	(63,99) (40,135)
L. longbeachae	0.016	0.016	0.008-0.016	(63,135)
L. micdadei	--	0.015	--	(135)
L. bozemanii	--	0.03	--	(135)
L. gormanii	0.016	0.016	0.008-0.016	(63)
L. dumoffii	0.016	0.016	0.008-0.016	(63)
Ofloxacin
Legionella spp.	0.015-0.032	0.03-0.64	0.007-0.25	(39,42,81) (49,58)
L. pneumophila (serogroups 1)	0.02-0.06	0.06-0.12	0.01-0.25	(42,63,81)
L. longbeachae	0.016	0.03	0.008-0.03	(63)
L. gormanii	0.03	0.06	0.03-0.06	(63)
L. dumoffii	0.03	0.06	0.03-0.06	(63)
Sparfloxacin
Legionella spp.	0.19	0.38	0.03-1.0	(21) (92)
L. pneumophila (serogroup 1)	<=0.003	--	--	(44)
Trovafloxacin
Legionella spp.	0.0018-0.125	0.0018-0.5	0.004-0.38	(21) (92) (146)
L. pneumophila	<0.004	<0.004-0.008	0.004-0.008	(63, 135)
L. longbeachae	--	0.004-0.008	<0.004-0.004	(63,135)
L. bozemanii	--	0.008	--	(135)
L. micdadei	--	0.008	--	(135)
L. gormanii	0.004	0.004	<0.004-0.008	(63)
L. dumoffii	<0.004	0.008	0.004-0.008	(63)
Gatifloxacin
Legionella spp.	0.19	0.38	0.125-0.5	(21)
Grepafloxacin
Legionella spp.	0.007	0.007-0.03	0.0018-0.5	(49,58) (92)
L. pneumophila	--	0.03-0.06	--	(135)
L. micdadei	--	0.015	--	(135)
L. longbeachae	--	0.125	--	(135)
L. bozemanii	--	0.03	--	(135)
T-3811 DES-F(6)-Quinolone
Legionella spp.	0.0156	0.0313	0.002-0.0313	(146)
Gemifloxacin
Legionella spp.	0.003	0.003	0.0009-0.03	(58)
L. pneumophila		0.03		(135)
L. micdadei		0.015		(135)
L. longbeachae		0.06		(135)
L. bozemanii		0.03		(135)
Moxifloxacin
Legionella spp.	--	0.06	0.03-0.25	(92)
L. pneumophila	0.008-0.016	0.016-0.06	0.004-0.03	(63,135)
L. longbeachae	0.016	0.016-0.03	0.008-0.03	(63,135)
L. gormanii	0.0016	0.016	0.008-0.03	(63)
L. dumoffii	0.016	0.03	0.008-0.003	(63)
L. micdadei	--	0.03	--	(135)
L. bozemanii	--	0.03	--	(135)
Amoxicillin
L. pneumophila	0.5	1	<0.063-1	(99)
Cefdinir
L. pneumophila	8	8	0.25-8	(99)
Cefditoren
L. pneumophila	8	16	0.25-16	(99)
Piperacillin
L. pneumophila (serogroup 1)	0.25	--	--	(81)
Imipenem
L. pneumophila	<0.063-0.0157	<0.0063	<0.063	(81) (99)
Faropenem
L. pneumophila	<0.063	<0.063	<0.063	(99)
L-036 (carbapenem)
L. pneumophila	<0.063	<0.063	<0.063	(99)
Rifampicin
Legionella spp.	0.008	0.008	<0.004-0.06	(49)
L. pneumophila	0.0000043-0.004	0.000012-0.004	<0.001-0.062	(81) (63,121)
L. longbeachae	0.008	0.03	<0.004-0.03	(63)
L. gormanii	0.004	0.004	<0.004-0.008	(63)
L. dumoffii	0.008	0.016	<0.004-0.016	(63)
Doxycycline
L. pneumophila	1.76-2.48	3.65-4.95	0.24-31.25	(121)
Minocycline
L. pneumophila (serogroup 1)	0.0313	--	--	(81)
Quinupristin/Dalfopristin
Legionella  spp.	0.25	0.50	0.125-0.50	(41)

 

Table 3:  Activity of Antimicrobial Agents Using In Vivo Animal Model 

Species	Antimicrobials	Animal model*	Effect	References
L. pneumophila, serogroup 1
	erythromycin	gp pneumonia gp peritonitis rat pneumonia	10-90% survival 33-100% survival Significant decrease in bacterial load in lung	(44,58,82,108,128,130) (56) (140)
	erythromycin + rifampicin (po)	gp pneumonia	20% survival	(58)
	azithromycin	gp pneumonia A/J mice pneumonia	100% survival 92% survival	(54,122) (15)
	clarithromycin	gp pneumonia	100% survival	(54)
	josamycin	gp pneumonia	0-20% survival	(82,130)
	telithromycin	gp pneumonia	100% survival	(40)
	ABT 773	gp pneumonia	66% survival **	(45)
	ciprofloxacin	gp pneumonia	50-80% survival	(128,129)
	levofloxacin	gp pneumonia	91-100%	(42,46)
	ofloxacin	pg pneumonia A/J mice pneumonia	70-100% survival 92% survival	(42,43,128,130) (15)
	pefloxacin	gp peritonitis gp pneumonia	100% survival 87.5% survival	(29) (108)
	sparfloxacin	gp pneumonia	100% survival	(44,128)
	trovafloxacin	gp pneumonia	100% survival	(43)
	alatrofloxacin	gp pneumonia	100% survival	(58)
	amoxifloxacin	gp pneumonia	Significant decrease in bacterial load in lung	(88)
L. pneumophila, Serogroup 1
	gemifloxacin	gp pneumonia	92% survival	(46)
	rifampicin	gp pneumonia gp peritonitis	62.5-90% survival 67-100% survival	(108,130) (140)
	amoxicillin/clavulanate	rat pneumonia	significant decrease in bacterial load in lung	(140)
	amoxicillin/clavulanate	rat pneumonia	significant decrease in bacterial load in lung	(139)
	ticarcillin/clavulanate	rat pneumonia	significant decrease in bacterial load in lung	(140)
	amoxicillin	rat pneumonia	no decrease in bacterial load in lung	(140)
	ticarcillin	rat pneumonia	no decrease in bacterial load in lung	(140)
	minocycline	gp pneumonia gp peritonitis	75 - 87.5% survival 33-67% survival	(108) (104)
	doxycycline	gp pneumonia	75% survival	(108)
	tetracycline	gp peritonitis	17% survival	(56)
	chloramphenicol	gp peritonitis	33% survival	(56)
	penicillin	gp peritonitis	0% survival	(56)
	aminoglycosides	gp peritonitis	0-33% survival	(56,104)
L. micdadei
	erythromycin	gp pneumonia	70% survival	(110)
	rifampicin	gp pneumonia	60% survival	(110)
	trimethoprim-sulfamethoxazole	gp pneumonia	60% survival	(110)
	doxycycline	gp pneumonia	40% survival	(110)
	penicillin	gp pneumonia	30% survival	(110)
	cefazolin	gp pneumonia	30% survival	(110)
	chloramphenicol	gp pneumonia	20% survival	(110)
	gentamicin	gp pneumonia	20% survival	(110)
	cefoxitin	gp pneumonia	0% survival	(110)

**All of the ABT 773 treated animals that died appeared to do so because of drug-induced peritonitis rather than overwhelming pneumonia (45).

 

Table 4:  Antibiotic Doses for Legionella Infection [Download PDF]

Antimicrobial Agent	Dosage*
Azithromycin**	500mg*** orally or intravenously every 24 hours
Clarithromycin	500mg orally or intravenously† every 12 hours
Roxithromycin	500mg orally every 12 hours
Erythromycin	1000mg intravenously every 6 hours 500mg orally every 6 hours
Dirithromycin	500mg orally every 24 hours
Levofloxacin	500mg*** orally or intravenously every 24 hours
Ciprofloxacin	400mg intravenously every 8 hours 750mg orally every 12 hours
Ofloxacin	400mg orally or intravenously every 12 hours
Moxifloxacin	400mg ***orally every 24 hours
Doxycycline	100mg*** orally or intravenously every 12 hours
Minocycline	100mg*** orally or intravenously every 12 hours
Tetracycline	500mg orally or intravenously every 6 hours
Trimethoprim-sulfamethoxazole	160 and 800mg intravenously every 8 hours 160 and 800mg orally every 12 hours
Rifampin	300 to 600mg orally or intravenously   every 12 hours

*The dosages are based on clinical experience and not on controlled trials.

**Intravenous form not available in some European countries.

***We recommend doubling the first dose.

† Intravenous form not available in the United States.