Moxifloxacin

Moxifloxacin (Avelox®) is a fluoroquinolone antibacterial with a methoxy group in the C-8 position and a bulky C-7 side chain. Moxifloxacin is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP), acute bacterial sinusitis and uncomplicated skin and skin structure infections (approved indications may differ between countries).

In vitro, moxifloxacin is active against clinically relevant Gram-positive and -negative organisms, as well as atypical organisms and anaerobes. In vitro studies revealed that with moxifloxacin, the minimum concentration inhibiting 90% of strains (MIC90) was ≤0.5 μg/mL for S. pneumoniae, including strains with intermediate- and high-level penicillin resistance, S. pyogenes, meticillin-susceptible Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis and Mycoplasma pneumoniae.

The bactericidal activity of moxifloxacin against these clinically relevant pathogens has been shown in vitro. In addition, pharmacodynamic models simulating the pharmacokinetics of moxifloxacin showed that the drug is associated with favourable area under the concentration-time curve: MIC and peak plasma concentration (C_max): MIC ratios. Moxifloxacin retained greater activity against mutant bacterial strains than older fluoroquinolones such as levofloxacin and ciprofloxacin, and had a lower potential to select for resistant mutants.

Moxifloxacin was associated with slight QT interval prolongation in both healthy volunteers and patients, although the risk of cardiac toxicity is minimal when prescribing recommendations are adhered to.

Oral moxifloxacin has an absolute bioavailability of =90%. With oral moxi-floxacin 400mg once daily, a mean steady-state Cmax of 3.2–4.5 mg/L was reached in ≈1.5 hours. Mean C_max with intravenous moxifloxacin was 4.2 mg/L. Moxifloxacin is widely distributed throughout the body. Concentrations of the drug in clinically relevant tissues and fluids (e.g. lung tissue, epithelial lining fluid, alveolar macrophages, sinus mucosa and adipose tissue) exceeded MIC90 values of clinically relevant pathogens. At steady state, the mean elimination half-life of oral or intravenous moxifloxacin 400mg once daily was 12.0–15.1 hours. The extent and rate of moxifloxacin absorption were reduced by the concomitant administration of an aluminium- and magnesium-containing antacid, an iron supplement or sucralfate.

The efficacy of oral moxifloxacin 400mg once daily has been examined in well designed clinical trials in the treatment of AECB, CAP, acute bacterial sinusitis and uncomplicated skin and skin structure infections. In addition, sequential therapy with intravenous then oral moxifloxacin 400mg once daily was examined in CAP. The duration of therapy varied according to the indication/study. In most studies, the primary endpoint was the clinical success rate at the test-of-cure (TOC) visit.

In patients with AECB, the clinical success rate at the TOC visit was 85–96% in patients receiving short-course treatment with moxifloxacin and 81–94% in patients receiving clarithromycin, azithromycin, ceftriaxone, cefuroxime axetil, levofloxacin, amoxicillin or amoxicillin/clavulanic acid. The bacteriological success rate at the TOC visit was 77–96% in moxifloxacin recipients versus 62–96% in patients receiving comparator antibacterials; moxifloxacin was shown to be superior to clarithromycin or the comparator antibacterials amoxicillin, clarithromycin or cefuroxime axetil in two studies.

Sequential intravenous/oral therapy with moxifloxacin was at least as effective as comparator antibacterials in patients with CAP. Clinical success rates at the TOC visit were 83–93% in moxifloxacin recipients versus 80–89% in patients receiving alatrofloxacin/trovafloxacin or levofloxacin, amoxicillin/clavulanic acid with or without clarithromycin, ceftriaxone with or without erythromycin and ceftriaxone/cefuroxime axetil with or without azithromycin. Moxifloxacin was considered superior to amoxicillin/clavulanic acid with or without clarithromycin. The bacteriological success rate was significantly higher with moxifloxacin than with amoxicillin/clavulanic acid with or without clarithromycin at the TOC visit (94% vs 82%).

Continuous therapy with oral moxifloxacin had similar efficacy to comparator antibacterials in patients with CAP. At the end-of-therapy (EOT), TOC and follow-up visits, clinical success rates were 92–97%, 87–94% and 89–98%, respectively, with moxifloxacin and 90–95%, 87–94% and 89–99% with comparators (clarithromycin, amoxicillin/clavulanic acid plus roxithromycin, amoxicillin, or amoxicillin and/or clarithromycin). Bacteriological success rates at the EOT, TOC and follow-up visits were 79–97%, 77% and 53–94%, respectively, in moxifloxacin recipients and 71–96%, 74% and 68–93% in recipients of comparator antibacterials.

In patients with acute bacterial sinusitis, clinical success rates at the EOT or TOC visit were 86–97% in moxifloxacin recipients versus 84–92% in recipients of amoxicillin/clavulanic acid, trovafloxacin or cefuroxime axetil. In terms of bacteriological success rates, moxifloxacin was shown to be superior to cefurox-ime axetil (95% vs 84%).

In patients with uncomplicated skin and skin structure infections, the clinical success rate was 90–100% in moxifloxacin recipients and 89–93% in cefalexin recipients. Bacteriological success rates of 80–91% occurred with moxifloxacin and 80–94% with cefalexin.

Moxifloxacin is generally well tolerated, with most adverse events being of mild-to-moderate severity. In a meta-analysis of clinical trial data, the most commonly reported adverse effects (e.g. nausea, diarrhoea, dizziness and abdominal pain) were associated with gastrointestinal or CNS intolerance. Liver function test abnormalities seen with moxifloxacin were usually mild elevations in trans-aminase levels that resolved following cessation of therapy.

Moxifloxacin recipients do not appear to have an increased risk of relevant cardiac arrhythmias. No cases of torsade de pointes have been reported in clinical or postmarketing studies. Moxifloxacin is not associated with phototoxicity or severe/extensive joint disorders and does not have a clinically relevant effect on blood glucose homeostasis.