Question 5

How does the antibacterial activity of high-dose levofloxacin compare to other fluoroquinolones?

A few notable differences exist between the antibacterial activity of the fluoroquinolones (Table 2 and Table 3). While levofloxacin and moxifloxacin have equivalent bacterial killing activities against S. pneumoniae (39) the activity of ciprofloxacin is lower, resulting in a greater likelihood of resistance developing compared with levofloxacin or moxifloxacin (40). In fact, according to ciprofloxacin prescribing information, ciprofloxacin is not a drug of first choice in pneumonia known or suspected to be caused by S. pneumoniae (41). In regard to the enteric Gram-negatives, levofloxacin and ciprofloxacin have similar MIC₉₀ values for E. coli and are 2- to 4-fold more active in vitro than moxifloxacin (42-44). K. pneumoniae, P. mirabilis, Serratia marcescens, Citrobacter freundii, Morganella morganii are more sensitive to levofloxacin than ciprofloxacin, and the MIC values are 2- to 4- fold more active than moxifloxacin (44). Finally, the 750 mg levofloxacin regimen dose has a low potential to select for resistance in E. coli and K. pneumoniae (45).

Table 2. In vitro antibacterial activity of levofloxacin and other quinolones against Gram-positive bacteria

Species (no. of isolates)		LVFX		CPFX		GAT		MOX		References
		MIC90 (mg/l)	S %	MIC90 (mg/l)	S %	MIC90 (mg/l)	S %	MIC90 (mg/l)	S %
Enterococcus faecalis(114)		1-32c	NR	32c	NR	≥ 16		8		15-18
	vancomycin-susceptible (207)	8 to ≥ 32	65	≥ 32	46	≥ 16	NR	8	NR	19,20
	vancomycin-resistant (8)	> 32	NR	> 32	0	NT		NT		19
Staphylococcus aureus (6,828)		10.25 to ≥64 c	51.7-71.4	0.5 to > 2c	70.3	4	71.7	4	70.3	16,17,21,22
	meticillin/oxacillin-susceptible (4,247)	0.25-4	87.6-96.2	0.5-4	87.9-95.6	0.12-0.5	94.8-96.7	0.06	95.6	15,21-23
	meticillin/oxacillin-resistant (2,689)	> 4 to ≥ 64	3.8-20.8	> 4	1.9-19.1	> 4-8	21.1-24	> 4	23.1	15,21-23
Streptococcus pneumoniae (79,367) d,e		0.5-16c	97.6-99.4	2c	84.9	0.25-0.5	98.5-99.2	0.12-0.25	98.5-99.3	16,17,24-31
	penicillin-susceptible (14,429)	1	96.9-100	2	NR	0.5	99.5-100	0.25	98	15,23,24,26,27
	penicillin-intermediate (4,706)	1	97.3-100	2	NR	0.5	97.9-100	0.12-0.25	100	15,23-27
	penicillin-resistant (7,265)	1	94.6-100	2	NR	0.25-1	98.1-100	0.12-0.25	97.3	15,23-27
In vitro antibacterial activity of levofloxacin and other quinolones against Gram-positive bacteria that are the causative pathogens for CAP, ABS and are indicated for treatment in the United States with levofloxacin 750 mg or 500 mg once daily for 5 or 10 days. Dataa are from large surveillance studies (1997-2005) (21, 22, 24-30) and recent studies (2002-2006) (15-17, 23, 31) conducted worldwide (21, 24, 28) and in North America (15, 17, 22, 23, 25-27, 29-31) comparing the activity of antibacterial agents against clinical isolates.b Data from older studies have been included where more recent data were limited or unavailable (18-20). a MIC90 values and percentage of susceptible isolates. NCCLS (CLSI) susceptibility breakpoints were ≤ 2 mg/l for levofloxacin and ≤ 1 mg/l for gatifloxacin and moxifloxacin. b In two studies, reference strains were included in addition to clinical isolates (15, 17). c The MIC90 values from one study (17) are from a small number of quinolone-susceptible isolates (n = 13-29). d Penicillin NCCLS breakpoints for S. pneumoniae were ≤ 0.06 mg/l (susceptibility), 0.12-1 mg/l (intermediate susceptibility) and ≥ 2 mg/l (resistance). e Causative pathogen for ABS and CAP and is indicated for treatment with levofloxacin 750 mg once daily for 5 days (US). Abbreviations: LVFX = levofloxacin, CPFX = ciprofloxacin, GAT = gatifloxacin, MOX = moxifloxacin, MIC90 = minimum inhibitory concentration at which 90% of isolates are inhibited, S = susceptible isolates, NR = not reported, NT = not tested, CAP = community-acquired pneumonia, ABS = acute bacterial sinusitis, NCCLS = National Committee for Clinical Laboratory Standards, CLSI = Clinical and Laboratory Standards Institute. Adapted from reference (32).

Table 3. In vitro antibacterial activity of levofloxacin and other quinolones against Gram-negative bacteria

Species (no. of isolates)		LVFX		CPFX		GAT		MOX		References
		MIC90 (mg/l)	S %	MIC90 (mg/l)	S %	MIC90 (mg/l)	S %	MIC90 (mg/l)	S %
Enterobacter cloacae (427)		0.25-1	94-94.5	≤ 0.06-1	90.9-91	1	94.5	NT		15,19,20,23,33,34
Escherichia coli (2,562)c		≤ 0.06 to > 8	80.4.94.5	≤ 0.03 to > 2	80.1-94.4	0.06 to > 4	80.8-92.3	> 4	NR	15,21,23,33-35
Haemophilus influenzae(35,163)c		0.008 to ≤ 0.06	99.7-100	0.008-0.03	> 99.9-100	0.015-0.03	99.7-100	≤ 0.03	99.7 to > 99.9	17,23-28,36-38
	β-lactamase negative (14,669)	0.015-0.06	99.6 to > 99.9	0.015-0.12	> 99.9	0.015-0.03	99.9	≤ 0.03-0.06	99.9	15,24-27
	β-lactamase positive (4,606)	0.015-0.06	99.9-100	0.015-0.12	100	≤ 0.03	99.6	≤ 0.03	99.6	15,24-27
Haemophilus parainfluenzae(112)c		≤ 0.06	100							38
Klebsiella pneumoniae(458)c		0.5 to > 8	95-100	0.25-1	95-98	0.5-1	100	NT		15,19,23,33,34
Moraxella catarrhalis(10,088)c		0.03-0.06	> 99.5-100	0.015-0.25	> 99.9-100	≤ 0.03	100	0.06	> 99.0-100	17,23,24,28,36-38
	β-lactamase negative (269)	0.06	NR	≤ 0.03	NR	0.06	NR	NT		15,24
	β-lactamase positive (5,151)	0.06	NR	≤ 0.03	NR	0.06	NR	NT		15, 24
Proteus mirabilis(428)c		≤ 0.05.2	91.6	0.12-2	85.9	4	86.6	> 4	NR	15,17,21,33
Pseudomonas aeruginosa(1,515)		0.5-64	71-94.2	0.25 to > 2	72.5	2-64	69.3-90.4	> 4	NR	15,17,21,23,33,34
In vitro antibacterial activity of levofloxacin and other quinolones against Gram-negative bacteria that are the causative pathogens for CAP, ABS, cUTI and AP, and are indicated for treatment in the United States with levofloxacin 750 mg or 500 mg once daily for 5 or 10 days. Dataaare from surveillance studies (1997-2005) (21, 25-28, 36-38) and recent studies (2002-2006) (15, 17, 23, 24, 34, 38) conducted worldwide (21, 24, 28, 38) and in North America (15, 17, 23, 25-27, 34-37) comparing the activity of antibacterial agents against clinical isolates.b Data from older studies have been used where small numbers of isolates were tested in recent studies (19, 20). a MIC90 values and percentage of susceptible isolates. NCCLS (CLSI) susceptibility breakpoints were ≤ 2 mg/l for levofloxacin and ≤ 1 mg/l for gatifloxacin and moxifloxacin. Pharmacokinetic/pharmacodynamic susceptibility breakpoints (with the same values as NCCLS breakpoints) were used in one study against M. catarrhalis (28). b In two studies, reference strains were included in addition to clinical isolates (15, 17). c Causative pathogen for one or more of the following indications: CAP, ABS, cUTI or AP, and is indicated for treatment with levofloxacin 750 mg once daily for 5 days (US). Abbreviations: LVFX = levofloxacin, CPFX = ciprofloxacin, GAT = gatifloxacin, MOX = moxifloxacin, MIC90 = minimum inhibitory concentration at which 90% of isolates are inhibited, S = susceptible isolates, NT = not tested, NR = not reported, CAP = community-acquired pneumonia, ABS = acute bacterial sinusitis, cUTI = complicated urinary tract infection, AP = acute pyelonephritis, NCCLS = National Committee for Clinical Laboratory Standards, CLSI = Clinical and Laboratory Standards Institute. Adapted from reference (32).