Gemifloxacin for the Treatment of Respiratory Tract Infections: In Vitro Susceptibility, Pharmacokinetics and Pharmacodynamics, Clinical Efficacy, and Safety

Abstract

Gemifloxacin is a synthetic fluoroquinolone antimicrobial agent exhibiting potent activity against most gram-negative and gram-positive organisms, such as the important community-acquired respiratory pathogens Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae , and Moraxella catarrhalis . The agent's mechanism of action involves dual targeting of two essential bacterial enzymes: DNA gyrase and topoisomerase IV. Gemifloxacin was approved by the Food and Drug Administration in April 2003 for treatment of community-acquired pneumonia and acute bacterial exacerbation of chronic bronchitis. The drug has an oral bioavailability of approximately 71%. Approximately 20-35% of gemifloxacin is excreted unchanged in the urine after 24 hours. The elimination half-life of gemifloxacin is 6-8 hours in patients with normal renal function, supporting once-daily dosing. The 24-hour free-drug area under the plasma concentration-time curve:minimum inhibitory concentration ratio (fAUC(0-24):MIC) associated with efficacy, based on results from in vitro and animal models of infection, is approximately 30. With a mean fAUC(0-24) of approximately 3 microg*hour/ml (35% of total AUC(0-24) of 8.4) and a median S. pneumoniae MIC for 90% of tested strains of 0.03, a fAUC(0-24):MIC ratio of 100 would be expected after standard dosing (320 mg once/day). In clinical studies involving both hospitalized and outpatient populations, gemifloxacin has been highly effective in the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis. Clinical success rates ranged from 93.9-95.9% in patients with community-acquired pneumonia and 96.1-97.5% in those with acute exacerbation of chronic bronchitis. Gemifloxacin is well tolerated; the frequency of adverse events with this agent is low. Most adverse events are mild-to-moderate in severity, with diarrhea (< 4%), nausea and rash (< 3%), and headache (< 2%) most commonly reported. Drug interactions with gemifloxacin are not common, although absorption is greatly reduced when given with divalent and trivalent cation-containing compounds, such as antacids. Due to its potent activity against many common gram-positive and gram-negative respiratory pathogens, its proven clinical efficacy, and its favorable safety profile, gemifloxacin is a highly effective empiric treatment for community-acquired lower respiratory tract infections.

Duration of Antimicrobial Therapy in Community Acquired Pneumonia: Less Is More

“…Gemifloxacin, a fluoroquinolone approved for the treatment of CAP, displays a concentration-dependent killing activity, which appears favorable to short-course, high-dose antimicrobial regimens [21]. File Jr. et al tested the efficacy of 320 mg once daily gemifloxacin short-course therapy for the outpatient treatment of mild-to-moderate CAP [22]; the investigators compared a 5-day and a 7-day regimen in a multicentre, double-blind, randomized study of 510 adults, including those having known risk factors, such as a history of cardiac conditions (hypertension, ischaemic heart disease, and congestive heart failure) or other diseases known to adversely affect pneumonia outcome (e.g., diabetes) [22].…”

Gemifloxacin

“…It is well known that Streptococcus pneumoniae has been showed mutations in both DNA gyrase and TOPO IV (double mutants), and they are resistant to most fluoroquinolones [8]. Thus, gemifloxacin is considered the only fluoroquinolone which has the ability to inhibit both enzyme systems (dual targeting of both DNA Gyrase and TOPO IV) at therapeutically relevant drug levels in S. pneumoniae [7][8][9]. Further, it has a minimum inhibitory concentration values that are still in the susceptible range for some of these double mutants.…”

“…Further, it has a minimum inhibitory concentration values that are still in the susceptible range for some of these double mutants. The main advantage of gemifloxacin over the older agents of fluoroquinolones is retaining the excellent activity against Gram-negative bacilli and improving Gram-positive activity (including S. pneumoniae and Staphylococcus aureus) [9,10]. Therefore, gemifloxacin was approved by the Food and Drug Administration (FDA) in April 2003 for treatment of acute bacterial exacerbation of chronic bronchitis, mild-to-moderate pneumonia, and multidrug resistant S. pneumoniae as well as community-acquired pneumonia [9,11,12].…”

Strategies to Address Appropriate Fluoroquinolone Use in the Hospital

“…Gemifloxacin, levofloxacin, and moxifloxacin are commonly referred to as respiratory fluoroquinolones because they demonstrate excellent activity against the most common etiologic agents in CAP (S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae). 16,19,[23][24][25][26] Moxifloxacin is the only clinically available fluoroquinolone in the United States with meaningful anaerobic activity. 17,24 Because fluoroquinolones readily penetrate many body sites, they are used for a wide array of infections including those of the urinary tract, pulmonary, soft tissue, bone, and bloodstream.…”

“…17,24 Because fluoroquinolones readily penetrate many body sites, they are used for a wide array of infections including those of the urinary tract, pulmonary, soft tissue, bone, and bloodstream. 18,19,[24][25][26][27] Furthermore, fluoroquinolones possess excellent bioavailability providing an oral option to treat even serious infections.…”