Levaquin Clinical Pharmacology

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Levaquin - Clinical Pharmacology [Levofloxacin]

Aerobic gram-negative microorganisms Enterobacter cloacae Klebsiella pneumoniae Pseudomonas aeruginosa

Escherichia coli Legionella pneumophila Serratia marcescens
Haemophilus influenzae Moraxella catarrhalis
Haemophilus parainfluenzae Proteus mirabilis

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin. Other microorganisms Chlamydia pneumoniae Mycoplasma pneumoniae

The following in vitro data are available, but their clinical significance is unknown.

Levofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 痢/ mL or less against most ( 90%) strains of the following microorganisms; however, the safety and effectiveness of levofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials. Aerobic gram-positive microorganisms Staphylococcus haemolyticus Streptococcus (Group G) Streptococcus milleri

Streptococcus (Group C/ F) Streptococcus agalactiae Viridans group streptococci Aerobic gram-negative microorganisms Acinetobacter baumannii Enterobacter aerogenes Proteus vulgaris

Acinetobacter lwoffii Enterobacter sakazakii Providencia rettgeri Bordetella pertussis Klebsiella oxytoca Providencia stuartii Citrobacter (diversus) koseri Morganella morganii Pseudomonas fluorescens Citrobacter freundii Pantoea (Enterobacter) agglomerans
Anaerobic gram-positive microorganisms Clostridium perfringens

Susceptibility Tests Susceptibility testing for levofloxacin should be performed, as it is the optimal predictor of activity.

Dilution techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC values). These MIC values provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC values should be determined using a standardized procedure. Standardized procedures are based on a dilution method 1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of levofloxacin powder. The MIC values should be interpreted according to the following criteria:

For testing Enterobacteriaceae, Enterococci, Staphylococcus species, and Pseudomonas aeruginosa:
MIC (痢/ mL) Interpretation
2 Susceptible (S) 4 Intermediate (I)

8 Resistant (R) For testing Haemophilus influenzae and Haemophilus parainfluenzae: a MIC (痢/ mL) Interpretation
2 Susceptible (S) a These interpretive standards are applicable only to broth microdilution susceptibility testing with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium.
1 The current absence of data on resistant strains precludes defining any categories other than "Susceptible." Strains yielding MIC results suggestive
of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

For testing Streptococcus spp. including S. pneumoniae: b MIC (痢/ mL) Interpretation

2 Susceptible (S) 4 Intermediate (I)

8 Resistant (R) b These interpretive standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.

A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the con-centrations usually achievable.

A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation.

A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of labora-tory control microorganisms to control the technical aspects of the laboratory procedures. Standard levofloxacin powder should give the following MIC values:

Microorganism MIC (痢/ mL)
Enterococcus faecalis ATCC 29212 0.25-2 Escherichia coli ATCC 25922 0.008-0.06

Escherichia coli ATCC 35218 0.015-0.06 Haemophilus influenzae ATCC 49247 c 0.008-0.03
Pseudomonas aeruginosa ATCC 27853 0.5-4 Staphylococcus aureus ATCC 29213 0.06-0.5
Streptococcus pneumoniae ATCC 49619 d 0.5-2 c
This quality control range is applicable to only H. influenzae ATCC 49247 tested by a broth microdilution procedure using Haemophilus

Test Medium (HTM). 1 d
This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a broth microdilution procedure using cation-adjusted

Mueller-Hinton broth with 2-5% lysed horse blood.

Diffusion techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the suscepti-bility of bacteria to antimicrobial compounds. One such standardized procedure 2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5-痢 levofloxacin to test the susceptibility of microorganisms to levofloxacin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5-痢 levofloxacin disk should be interpreted according to the following criteria: For testing Enterobacteriaceae, Enterococci, Staphylococcus species, and Pseudomonas aeruginosa:

Zone diameter (mm) Interpretation
17 Susceptible (S) 14-16 Intermediate (I)

13 Resistant (R) For Haemophilus influenzae and Haemophilus parainfluenzae: e

Zone diameter (mm) Interpretation
17 Susceptible (S) e These interpretive standards are applicable only to disk diffusion susceptibility testing with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium. 2 The current absence of data on resistant strains precludes defining any categories other than "Susceptible." Strains yielding zone diameter results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing.

For Streptococcus spp. including S. pneumoniae: f
Zone diameter (mm) Interpretation

17 Susceptible (S) 14-16 Intermediate (I)

13 Resistant (R) f These zone diameter standards for Streptococcus spp. including S. pneumoniae apply only to tests performed using Mueller-Hinton agar supplemented with 5% sheep blood and incubated in 5% CO2 .

Interpretation should be as stated above for results using dilution tech-niques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for levofloxacin.
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5-痢 levofloxacin disk should provide the following zone diameters in these laboratory test quality control strains:
Microorganism Zone Diameter (mm)
Escherichia coli ATCC 25922 29-37 Haemophilus influenzae ATCC 49247 g 32-40
Pseudomonas aeruginosa ATCC 27853 19-26 Staphylococcus aureus ATCC 25923 25-30
Streptococcus pneumoniae ATCC 49619 h 20-25 g
This quality control range is applicable to only H. influenzae ATCC 49247 tested by a disk diffusion procedure using Haemophilus Test Medium (HTM). 2 h
This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a disk diffusion procedure using Mueller-Hinton agar supplemented with 5% sheep blood and incubated in 5% CO2 .