gemifloxacin and Respiratory-Tract-Infections

Respiratory tract infections (RTIs) form a substantial clinical and financial burden, with the increasing complication of antimicrobial resistance. This resistance may compromise the use of many empirically prescribed antimicrobials. The new respiratory fluoroquinolones have been developed to overcome this burgeoning resistance. This group includes gemifloxacin, an enhanced-affinity fluoroquinolone that has been approved for clinical use in several countries and is characterised as a potent dual-acting agent with excellent in vitro activity against Streptococcus pneumoniae (minimum inhibitory concentration for 90% of strains (MIC90)=0.03-0.06 microg/mL). Gemifloxacin given once daily for 5-7 days has been shown to be non-inferior to, or in some instances superior to, comparator agents for the treatment of common lower RTIs. Moreover, it is generally well tolerated and is as safe as many frequently empirically prescribed antimicrobials. In addition, studies have shown gemifloxacin to be a cost-effective agent for some lower RTIs.

Topics: Animals; Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Respiratory Tract Infections

Cutaneous adverse events are seen with many antimicrobials. A signal was observed with gemifloxacin in the original clinical research program, however subsequent studies and analysis demonstrated a mild-moderate self-limited macular-papular rash seen most frequently when the duration of exposure was beyond 7 days, a non-approved duration. Following administration for 5 days for community-acquired respiratory tract infections the rash rate is typically less than 1.5%, a rate similar to that for other fluoroquinolones and lower than other frequently used community antimicrobials. The rash associated with gemifloxacin has not been linked with cross or subclinical-sensitization nor any systemic manifestations such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. This review describes the extensive studies conducted to support the use of this agent for short durations in community infections.

Topics: Clinical Trials as Topic; Exanthema; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Respiratory Tract Infections; Risk Factors; Skin

Community-acquired lower respiratory tract infections (LRTIs) exert a growing clinical and financial burden on healthcare systems and employers. In addition, antimicrobial resistance among pathogens, such as Streptococcus pneumoniae, has compromised the use of commonly prescribed antimicrobial compounds. Newer fluoroquinolones have been developed to meet these emerging demands. Gemifloxacin is a potent, dual-acting fluoroquinolone with excellent activity against S. pneumoniae (MIC(90)0.03-0.06 microg/ml) including those strains demonstrating resistance to other classes of antibiotics. Gemifloxacin demonstrated excellent clinical success in community-acquired lower respiratory infections, has an acceptable safety profile, and is a cost-effective alternative in the management of LRTIs including those caused by resistant pathogens.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cost-Benefit Analysis; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Respiratory Tract Infections; Streptococcus pneumoniae; Treatment Outcome

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.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Drug Interactions; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Naphthyridines; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Respiratory Tract Infections

The fluoroquinolone gemifloxacin has recently been approved for the treatment of acute bacterial exacerbations of chronic bronchitis and mild community acquired pneumonia, including that caused by multidrug-resistant Streptococcus pneumoniae. Owing to the increasing prevalence of multidrug-resistant S. pneumoniae, as well as resistance to other common pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, it is important to have new, potent antimicrobial agents for the treatment of these infections. Gemifloxacin is the most potent antimicrobial agent in vitro for S. pneumoniae, and has excellent activity against the other key pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, including the atypical microorganisms. The clinical trial outcomes of several studies that have evaluated gemifloxacin show a range of superior clinical or bacteriologic outcomes against several current antimicrobials, including levofloxacin, clarithromycin, trovafloxacin and ceftriaxone. The safety profile of gemifloxacin is similar to that of approved agents to treat acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, with a low discontinuation rate of 2.2%. A nonphototoxic rash (usually a mild, maculopapular rash) was observed in 2.8% of patients in clinical studies.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Bronchitis, Chronic; Community-Acquired Infections; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Streptococcus pneumoniae; Treatment Outcome

Levofloxacin, levorotatory isomer of ofloxacine, is the only FQ3G on the belgian market since the middle of 2000 and is a little more efficient than the FQ2G against S. pneumoniae. The FQ4G are in vitro active against the common and atypic respiratory pathogenes and significantly more efficient against the Gram positive cocci, principally against S. pneumoniae. Their long duration of action allows one oral administration a day sufficient to obtain bactericidal levels in the serum. Their secondary effects are located principally at the level of digestive tract, neurologic system or cutaneous area. In the U.S.A., several FQ4G (clina-, grepa-, spar-, trova-floxacin) were withdrawn from use after observance of severe toxicity, while there were being administrated on a large scale. Furthermore, two of these "respiratory" FQ4G (gemi- and moxi-floxacin) should reinforced our therapeutic armoury, moxifloxacin as of 2002 and gemifloxacin as of 2004. The position of FQ3G and 4G are in discussion. In the case of pneumonia acquired in the community and confirmed by X-Ray, our recommendation is to administer a new FQ at the first choice if the patient is allergic to penicillin, debilitated or if a penicillin resistant S. pneumoniae suspected (epidemiology, recent antibiotherapy) and at the second choice if it is resistance to penicillin or to macrolide, in case of atypic pneumonia. Today, the majority of the pneumonia acquired outside the hospital is empirically treated with a betalactam (oral or intravenous), with or without macrolide. The new FQ are important drugs. One must avoid overprescription which leads to bacterial resistance (especially S. pneumoniae).

Topics: Administration, Oral; Anti-Infective Agents; Aza Compounds; Belgium; Biological Availability; Drug Monitoring; Drug Resistance; Fluoroquinolones; Gemifloxacin; Humans; Intestinal Absorption; Levofloxacin; Moxifloxacin; Naphthyridines; Ofloxacin; Patient Selection; Pneumococcal Infections; Quinolines; Respiratory Tract Infections; Streptococcus pneumoniae; Time Factors; Treatment Outcome

The quinolones have evolved from antibacterial agents with a limited spectrum of predominantly anti-gram-negative antimicrobial activity and a restricted number of indications to a class of widely used oral (and, in some cases, intravenous) antibiotics with extensive indications for infections caused by many bacterial pathogens in most body tissues and fluids. This evolutionary pattern has arisen through the development of new core and side-chain structures, with associated improvements in activity, pharmacokinetics and tolerability, and through the selection of molecules that remain useful and well tolerated. This review describes the progress of the quinolones from the first to the third (IIIa and IIIb) generations. Special attention is given to gemifloxacin, currently the most developmentally advanced third-generation quinolone, which has enhanced in vitro gram-positive antimicrobial activity and no troublesome adverse drug reactions. Preliminary data indicate that gemifloxacin should prove to be an important addition to the fluoroquinolone class. Further clinical trial data are awaited with interest.

Topics: 4-Quinolones; Anti-Infective Agents; Bacterial Infections; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Respiratory Tract Infections; Urinary Tract Infections

The incidence of penicillin resistance in pneumococci is increasing in the USA, having risen from <5% before 1989 to >35% in 1997. There has also been a shift in the ratio of intermediate to high-level resistance from 3 or 4:1 to 2 or 1:1. Multidrug resistance and resistance to macrolides and fluoroquinolones in pneumococci is also a matter of concern. The implications for empirical treatment of respiratory tract infections are considerable. The potential of quinolones with activity against respiratory pathogens including pneumococci must be preserved by careful antimicrobial prescribing.

Topics: Adult; Aged; Anti-Infective Agents; Community-Acquired Infections; Drug Resistance, Microbial; Female; Fluoroquinolones; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

We present a case of tendon rupture and subcutaneous bleeding after administration of gemifloxacin for the treatment of lower respiratory tract infection. Fluoroquinolone-induced tendinopathy is a rare but increasingly acknowledged adverse effect of this group of antibiotics. Most of the cases occur in the Achilles tendon and can lead to tendon rupture. Possible predisposing risk factors include steroid use, patients with renal failure or kidney transplantation, old age and being an athlete.

Topics: Achilles Tendon; Anti-Bacterial Agents; Anti-Infective Agents; Fluoroquinolones; Gemifloxacin; Humans; Male; Middle Aged; Respiratory Tract Infections; Risk Factors; Tendinopathy

Gemifloxacin given once daily for 5-7 days has been shown to be non-inferior to, or in some instances superior to, comparator agents for the treatment of common lower respiratory tract infections. Gemifloxacin is generally well tolerated and is as safe as many frequently empirically prescribed antimicrobials.. We report a case of a 46-year-old woman given gemifloxacin for an upper respiratory tract infection who developed allergic myocardial infarction 15 min after taking an oral dose of 320 mg gemifloxacin. To our knowledge, this is the first case of allergic myocardial infarction associated with gemifloxacin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although anaphylactoid/anaphylactic reactions are rare adverse effects of fluoroquinolones, clinicians should be aware of this potentially fatal event. Electrocardiographic interpretation is a critical skill of the emergency physician. Awareness of Kounis syndrome and its specific electrocardiogram findings may help facilitate further testing that will aid in timely diagnosis and interventions. A diagnosis of Kounis syndrome should be considered in young, healthy patients with no atherosclerotic risk factors when they develop an acute coronary syndrome after administration of a potentially allergic agent.

Topics: Anti-Bacterial Agents; Electrocardiography; Emergency Service, Hospital; Female; Gemifloxacin; Humans; Kounis Syndrome; Middle Aged; Respiratory Tract Infections

Novel 7-[7-amino-7-methyl-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]- 8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 2a and 2b were designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Among these, compound 2a possessing (S)-configuration for the asymmetrical carbon on the pyrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens including gram-positive (Streptococcus pneumoniae and Staphylococcus aureus), gram-negative (Haemophilus influenzae and Moraxcella catarrhalis), and atypical strains (Chalmydia pneumoniae and Mycoplasma pneumoniae), as well as multidrug-resistant Streptococcus pneumoniae and quinolone-resistant and methicillin-resistant Staphylococcus aureus). Furthermore, compound 2a showed excellent in vivo activity against the experimental murine pneumonia model due to multidrug resistant Streptococcus pneumoniae (MDRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies.

Topics: Animals; Anti-Bacterial Agents; Drug Design; Fluoroquinolones; Haemophilus influenzae; Male; Mice; Microbial Sensitivity Tests; Quinolones; Rats; Respiratory Tract Infections; Spiro Compounds; Staphylococcus aureus; Streptococcus pneumoniae

Gemifloxacin is a recently introduced fluoroquinolone antibiotic frequently used for its broad spectrum and once-daily dosing. Fluoroquinolones are associated with various neuropsychiatric side effects, such as seizures, insomnia, confusion, lightheadedness, psychosis, paranoia and hallucinations. We report a case of a 36-year-old woman given gemifloxacin for an upper respiratory tract infection who developed acute dystonia on the third day following therapy initiation. The clinical implications are discussed.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Dystonia; Female; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines; Respiratory Tract Infections

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Fluoroquinolones; Gemifloxacin; Humans; Ireland; Naphthyridines; Pneumococcal Infections; Population Surveillance; Respiratory Tract Infections; Streptococcus pneumoniae; United Kingdom

This study was undertaken to assess the in vitro activity of gemifloxacin, five other fluoroquinolone antimicrobial agents (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin and ofloxacin) and other non-quinolone comparator agents (ampicillin, erythromycin, clindamycin, doxycycline, penicillin and trimethoprim/sulphamethoxazole) against Streptococcus pneumoniae collected in the United States. Susceptibility testing of 550 S. pneumoniae, 290 Haemophilus influenzae and 205 Moraxella catarrhalis showed that 38.2% of pneumococci were penicillin nonsusceptible, while 26.2 and 95.6% of H. influenzae and M. catarrhalis, respectively, produced beta-lactamase. Overall new fluoroquinolones were the most active agents. The in vitro activity (based on MIC90 in mg/l) of the six fluoroquinolones was gemifloxacin>moxifloxacin>gatifloxacin>levofloxacin>ciprofloxacin and ofloxacin.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactamases; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Naphthyridines; Respiratory Tract Infections; Streptococcus pneumoniae; United States

The in vitro susceptibility to trovafloxacin and gemifloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin (MIC > or =2 microg/ml; 30 strains with intermediate resistance [MIC 2 microg/ml] and 43 strains with complete resistance [MIC > or =4 microg/ml]) was determined. Seventy-three strains collected in a surveillance study carried out from May 1996 to April 1997 in Spain (prior to commercialisation of trovafloxacin and gemifloxacin) from patients with respiratory tract infections were tested. The antibacterial activity of gemifloxacin was affected to a lesser extent than that of trovafloxacin by the increase in the MIC of ciprofloxacin, with gemifloxacin showing significantly (P< or =0.001) better antibacterial activity than trovafloxacin in all ciprofloxacin MIC categories (MIC50/MIC90 values of 0.015/0.03, 0.015/0.06, 0.03/0.06 and 0.12/0.25 microg/ml for gemifloxacin vs. 0.12/0.12, 0.12/1, 0.25/0.5 and 2/4 microg/ml for trovafloxacin in the 2, 4, 8 and > or =16 microg/ml ciprofloxacin MIC categories, respectively). Nine (12.3%) of these 73 strains exhibited decreased susceptibility to trovafloxacin (> or =2 microg/ml), whereas all strains were inhibited by 0.25 microg/ml of gemifloxacin.

Topics: Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Microbial Sensitivity Tests; Naphthyridines; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral gemifloxacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin- clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than gemifloxacin: these agents reduced bacterial numbers by < or =3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of gemifloxacin against these organisms. This indicates that gemifloxacin may be of significant benefit in the treatment of RTI.

Topics: Animals; Anti-Infective Agents; Fluoroquinolones; Gemifloxacin; Haemophilus Infections; Haemophilus influenzae; Male; Naphthyridines; Pneumococcal Infections; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections

European isolates collected in 1998 for the Alexander Project were tested for their susceptibility to ciprofloxacin, ofloxacin and a novel fluoroquinolone, gemifloxacin, which has a spectrum of activity including common and atypical respiratory pathogens. MIC90s of gemifloxacin for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were 0.03, 0.06 and 0.015 mg/L, respectively. On the basis of MIC90s, gemifloxacin was the most potent antimicrobial tested against S. pneumoniae and M. catarrhalis. Against H. influenzae, gemifloxacin was one tube dilution more potent than ofloxacin and one tube dilution less potent than ciprofloxacin. As resistance to currently available antimicrobial agents increases, gemifloxacin offers potential as a promising new agent for the treatment of respiratory tract infection.

Topics: Anti-Infective Agents; Community-Acquired Infections; Drug Resistance, Microbial; Europe; Fluoroquinolones; Gemifloxacin; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Naphthyridines; Respiratory Tract Infections; Streptococcus pneumoniae