Moxifloxacin

Abstract

Moxifloxacin is an extended-spectrum fluoroquinolone which has improved coverage against Gram-positive cocci and atypical pathogens compared with older fluoroquinolone agents, while retaining good activity against Gram-negative bacteria. The antibacterial spectrum of moxifloxacin includes all major upper and lower respiratory tract pathogens; it is one of the most active fluoroquinolones against pneumococci, including penicillin- and macrolide-resistant strains. In in vitro studies, emergence of bacterial resistance was less common with moxifloxacin than with some other fluoroquinolones, but this requires confirmation in large-scale clinical studies. As with other fluoroquinolones, moxifloxacin achieves good penetration into respiratory tissues and fluids. It shows a low potential for drug interactions and dosage adjustment is not required for patients of advanced age or those with renal or mild hepatic impairment. The efficacy of oral moxifloxacin has been demonstrated in large, well-designed clinical trials in patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis. Moxifloxacin 400mg once daily achieved bacteriological and clinical success rates of approximately 90% or higher. It was as effective as, or more effective than, comparators including clarithromycin, cefuroxime axetil and high dose amoxicillin in these trials. The most commonly reported adverse events in patients receiving moxifloxacin are gastrointestinal disturbances. Moxifloxacin is also associated with QTc prolongation in some patients; there are, as yet, no data concerning the possible clinical sequelae of this effect in high-risk patients. Moxifloxacin has a low propensity for causing phototoxic reactions relative to other fluoroquinolones, and animal data suggest that it has a low potential for causing excitatory CNS and hepatotoxic effects. Conclusions: As an extended-spectrum fluoroquinolone, moxifloxacin offers the benefits of excellent activity against pneumococci, once daily administration and a low propensity for drug interactions. Although studies are needed regarding its tolerability in at-risk patients with QT interval prolongation, available data suggest that moxifloxacin is likely to become a first-line therapy option for the treatment of community-acquired lower respiratory tract infections, particularly in areas where drug-resistant S. pneumoniae or H. influenzae are common. Moxifloxacin is an extended-spectrum fluoroquinolone which has an antibacterial spectrum that covers all of the major respiratory tract pathogens. It is one of the most active fluoroquinolones against Streptococcus pneumoniae (mean weighted MIC₉₀32 mg/L) against Pseudomonas aeruginosa. Moxifloxacin also demonstrates good activity against the atypical respiratory tract pathogens Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp. (MIC₉₀ ≤1 mg/L). Minimum bactericidal concentrations of moxifloxacin were equal to, or within 1 dilution of, MIC values. Postantibiotic effects of >1 hour have been demonstrated against a range of respiratory pathogens. Moxifloxacin was active in experimental lung infections in animals, eradicating or markedly reducing the number of M. pneumoniae, S. pneumoniae, C. pneumoniae or L. pneumophila in the lung and protecting against death or dissemination of Legionella infection. Moxifloxacin has similar inhibitory activity against both of the bacterial enzymatic targets of fluoroquinolones, topoisomerase IV and DNA gyrase. The inhibitory activity of moxifloxacin appears to be little affected by characterised single genetic mutations or by the presence of the NorA efflux mechanism, and emergence of bacterial resistance among Gram-positive pathogens in vitro studies was less common with moxifloxacin than with other fluoroquinolones tested. Moxifloxacin is almost completely (≈90%) absorbed after oral administration. Thus, maximum plasma concentration (C_max) and area under the concentrationtime curve (AUC) values are only slightly lower than after administration of the same dose by the intravenous route (as a 60-minute infusion). Oral absorption is not affected by food intake (including dairy products). The pharmacokinetics of moxifloxacin are linear within the 50 to 800mg dose range. An oral dose of 400mg generally achieves a mean C_max of approximately 2.5 to 5 mg/L within 1 to 2 hours (t_max) and an AUC of approximately 27 to 45 mg/L · h. In common with other fluoroquinolones, moxifloxacin exhibits a high volume of distribution (2 to 3.5 L/kg), relatively low binding to plasma proteins (39%) and penetrates well into respiratory tissues and fluids. Concentrations achieved in bronchial mucosa, epithelial lining fluid, sinus tissues and alveolar macrophages exceed concurrent plasma concentrations and are ≥1 mg/L (or mg/kg) 24 hours after a 400mg dose(s). Evidence from animal studies suggests that moxifloxacin penetrates the placental and blood-brain barriers and into breast milk. Moxifloxacin is metabolised to a sulfo- (M1) and a glucuronide (M2) derivative. The cytochrome P450 system is not involved in the metabolism of the agent. Approximately 15 to 22% of a dose is found unchanged in the urine, with a similar amount in the faeces. The terminal elimination half-life of moxifloxacin ranges from approximately 8 to 16 (median 12.4) hours. Plasma clearance ranges from 9 to 15 L/h and renal clearance from 1.3 to 3 L/h. The pharmacokinetics of moxifloxacin do not appear to be affected by advanced age, gender, race, renal impairment or mild hepatic impairment. Oral moxifloxacin 400mg once daily was effective in the treatment of patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis, achieving bacteriological and clinical success/resolution rates of...