Pharmacological properties
Pharmacodynamics. Levofloxacin is a synthetic antibacterial drug from the group of fluoroquinolones, which is the s-enantiomer of the racemic mixture of ofloxacin.
Mechanism of action
Levofloxacin acts on the DNA-DNA gyrase complex and topoisomerase IV.
Pharmacokinetics/pharmacodynamics relationship
The degree of bacterial activity of levofloxacin depends on the ratio of C max in blood plasma or AUC and MIC.
resistance mechanism
The main mechanism of resistance is due to mutations in the gyr-A gene. In vitro, there is cross-resistance between levofloxacin and other fluoroquinolones. Due to its mechanism of action, cross-resistance between levofloxacin and other classes of antibacterial agents is not usually observed.
Breakpoints The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommended MIC breakpoints for levofloxacin, which separate susceptible from intermediately susceptible (moderately resistant) organisms and intermediately susceptible from resistant organisms, are presented in the MIC testing table (mg/L).
EUCAST clinical MIC breakpoints for levofloxacin (20.06.2006)
| pathogen | Sensitive, mg/l | Resistant, mg/l |
| Enterobacteriaceae | ≤1 | 2 |
| Pseudomonas spp. | ≤1 | 2 |
| Acinetobacter spp. | ≤1 | 2 |
| Staphylococcus spp. | ≤1 | 2 |
| S. pneumoniae 1 | ≤2 | 2 |
| Streptococcus A, B, C, G | ≤1 | 2 |
| H. influenzae M. catarrhalis 2 | ≤1 | 2 |
| Limit values not related to species 3 | ≤1 | 2 |
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1 The MIC breakpoint between susceptible and intermediately susceptible (moderately resistant) strains was raised from 1.0 to 2.0 to inhibit the growth of wild-type strains of this organism, demonstrating the variability of this parameter. The breakpoints apply to high-dose therapy.
2 Strains with MIC values above the breakpoint between susceptible and intermediately susceptible (moderately resistant) strains are very rare or have not been reported. Identification and antimicrobial susceptibility testing should be repeated on any such isolate and, if confirmed, sent to a reference laboratory.
3 Non-species MIC breakpoints have been derived primarily from pharmacokinetic/pharmacodynamic data and are independent of the MIC distribution of specific species. They are used only for species for which no species-specific breakpoint has been established and are not used for species where susceptibility testing is not recommended or for which there is insufficient evidence for questionable species (Enterococcus, Neisseria, Gram-negative anaerobes).
The CLSI (Clinical and Laboratory Standards Institute, formerly NCCLS) recommended MIC breakpoints for levofloxacin that separate susceptible from intermediately susceptible organisms, and intermediately susceptible from resistant organisms, are presented in the table below for MIC testing (µg/mL) or the disk diffusion method (zone diameter (mm) using a 5 µg levofloxacin disk).
Recommended CLSI MIC and disk diffusion method breakpoints for levofloxacin (M100-S17, 2007):
| pathogen | sensitive | resistant |
| Enterobacteriaceae | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| He Enterobacteriaceae | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| Acinetobacter spp. | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| Stenotrophomonas maltophilia | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| Staphylococcus spp. | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| Enterococcus spp. | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| H. influenzae M. catarrhalis 1 | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| Streptococcus pneumoniae | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
| β-hemolytic Streptococcus | ≤2 μg/ml ≥17 mm | ≥8 μg/ml ≤13 mm |
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1 The absence or infrequent occurrence of resistant strains pre-empts the determination of any result categories other than “susceptible.” For strains that yield results that suggest a nonsusceptible category, the identification of the organisms and the results of antimicrobial susceptibility tests should be confirmed by a reference laboratory using the CLSI reference dilution method.
antibacterial spectrum
The prevalence of resistance may vary geographically and over time for selected species; and it is desirable to obtain
