Fluoroquinolones in the Management of Community-acquired Pneumonia in Primary Care

Brian Wispelwey; Katherine R Schafer


Expert Rev Anti Infect Ther. 2010;8(11):1259-1271. 

In This Article

Fluoroquinolones & Site Penetration

When the MIC90 profiles of the three fluoroquinolones against various common CAP pathogens are compared, as shown in Table 5, gemifloxacin exhibits the lowest MIC90 against S. pneumoniae, followed by moxifloxacin.[45,50] Penetration to the site of infection is also an extremely important factor, and MICs should be considered within this context. Both moxifloxacin and levofloxacin have good penetration into epithelial lining fluid (ELF) and alveolar macrophages.[51,52] Steady-state intrapulmonary concentrations for moxifloxacin, levofloxacin, and azithromycin were assessed over a 24-h dosing interval in a study conducted in older adults undergoing bronchoscopy. Patients were given five doses of antibiotic and tests were conducted after the last dose was received at 4, 8, 12 and 24 h. All three agents were highly concentrated in alveolar macrophages and ELF, relative to plasma.[51] Moxifloxacin concentrations exceeded the S. pneumoniae susceptibility breakpoint (1.0 µg/ml) at all time points. However, azithromycin concentrations in ELF were not adequate to reliably eradicate S. pneumoniae based on the drug's MIC profile. Although tissue concentrations for most patients receiving levofloxacin were adequate for eradication of S. pneumoniae, 13% of patients who received levofloxacin did not maintain concentrations above the breakpoint (2.0 µg/ml) at 24 h.[51] On the other hand, azithromycin achieved the highest mean concentration in alveolar macrophages of all three drugs, with significant differences occurring at 24 h compared with moxifloxacin (p = 0.02) and at 12 h (p = 0.04) and 24 h (p = 0.02) compared with levofloxacin.[51] In a separate study, gemifloxacin also achieved higher concentrations within alveolar macrophages than the other two fluoroquinolones 1.5–2 h after a fifth dose. However, plasma and ELF concentrations were considerably lower with gemifloxacin at 1.5–2 h than with either levofloxacin or moxifloxacin at 4 h post-dose.[45]

High penetration of lung tissue was noted for moxifloxacin in a study conducted in patients with CAP. Maximum lung concentrations of 12.37 and 16.21 µg/g were found for intravenous and oral administration, respectively, with tissue concentrations far above the MIC90 values for most common CAP pathogens.[53] With levofloxacin, the highest levels of lung tissue concentrations were found 4–6 h after a 500 mg oral dose was received, with a maximum lung concentration of 11.28 µg/g and a trough concentration at 24 h of 2.43 µg/g.[52] It should be noted that this is below the current recommended levofloxacin dose of 750 mg for CAP. Furthermore, these concentrations were all well above the MIC90 for S. pneumoniae, H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae and L. pneumophila for all three fluoroquinolones with the exception of levofloxacin at 24 h (lung tissue concentration 2.43 µg/g) for S. pneumoniae (MIC90 1–2 µg/g) and C. pneumoniae (MIC90 1 µg/g).[50–52]

A recent analysis compared garenoxacin, gemifloxacin and moxifloxacin pharmacodynamics in CAP caused by S. pneumoniae. Using a Monte Carlo simulation analysis of S. pneumoniae in serum and ELF of hospitalized patients with CAP, the investigators found that moxifloxacin, gemifloxacin and garenoxacin achieved target serum and ELF concentrations for eradication of this pathogen. Importantly, the simulation indicated that these fluoroquinolones exhibited a low potential to select for resistance.[54] Garenoxacin is not approved for use in the USA.


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