gemifloxacin and Bacterial-Infections

Gemifloxacin is a broad-spectrum quinolone antibacterial with enhanced potency against Gram-positive bacteria, including multi-drug resistant Streptococcus pneumoniae, and retained potency against Gram-negative bacilli and bacterial strains resistant to other antibiotics. It has proven particularly effective in respiratory and urinary tract infection. This review presents safety data from 6775 patients included in clinical trials, receiving either the recommended 320 mg once daily oral dose of gemifloxacin, or standard dose of other quinolones, macrolides or beta-lactams (n = 5248). Studies in healthy volunteer and special populations are also reported. Adverse experiences (AEs) were observed in 44.7% of gemifloxacin-treated patients and 47.5% of those who received comparator drugs. Mild gastro-intestinal adverse drug reactions (ADRs) (diarrhoea 5.1%, nausea 3.9%) predominated. Rash, usually maculo-papular and in no case proceeding to more severe eruptions, was observed in 3.6% of those receiving gemifloxacin. A higher incidence of rash (>20%) was observed in young women and was the subject of further study. Adverse drug reactions suspected or probably related to treatment occurred in 17.4% of patients receiving gemifloxacin and in 20% of those receiving comparator antibiotics. Diarrhoea and nausea were experienced by 3.6 and 2.7%, respectively, of gemifloxacin-treated patients (4.6 and 3.2% of comparators), rash by 2.8% (0.6% of comparators) and headache by 1.2% (1.5% of comparators). Gemifloxacin-related vomiting (0.9%), dizziness (0.8%) and taste perversion (0.3%) were uncommon. Treatment discontinuation followed one or more adverse drug reactions in 2.2% of gemifloxacin-treated patients (0.9% due to rash) and 2.1% of comparator-treated patients. A total of 63 deaths (33 receiving gemifloxacin) occurred in the trial population: none were considered related to treatment. A slight prolongation in QT interval (2.56 ms (S.D. +/-24.5)) was observed in gemifloxacin-treated patients: no cardiac arrhythmias were reported. There was a low incidence of liver function tests (LFTs) classified as of potential clinical concern: gemifloxacin (0.4-1.2%), comparators (0.2-1.3%). Serious adverse events (SAEs), occurring during but not necessarily related to therapy, occurred in 3.6% of gemifloxacin-treated patients (4.3% of comparators). SAEs related to treatment agents were rare (0.4% in each group) and included rash (0.1%) and elevated liver enzymes (<0.1%). Gemifloxa

Topics: Administration, Oral; Anti-Infective Agents; Bacterial Infections; Clinical Trials as Topic; Drug Therapy, Combination; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines

Topics: Animals; Anti-Infective Agents; Bacterial Infections; Clinical Trials as Topic; Drug Interactions; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines

Gemifloxacin is a fluoroquinolone antibacterial agent which has an enhanced affinity for topoisomerase i.v.. It has potent activity against most Gram-positive bacteria, particularly Streptococcus pneumoniae. Gemifloxacin is over 30-fold more active than ciprofloxacin and 4- to 8-fold more active than moxifloxacin against this pathogen. Gemifloxacin has excellent activity against Haemophilus influenzae and Moraxella catarrhalis, and is unaffected by beta-lactamase production. It is generally 2-fold less active than ciprofloxacin against most Enterobacteriaceae. Atypical respiratory pathogens (Legionella, Mycoplasma and Chlamydia spp.) are highly susceptible to gemifloxacin. Preliminary results from phase II trials show that oral gemifloxacin 320 mg/day produced bacteriological responses of 94.7% in patients with acute exacerbations of chronic bronchitis and 95% of patients with uncomplicated urinary tract infections. Adverse events included nausea, abdominal pain, headache and mild rash in patients and healthy volunteers treated with gemifloxacin 320 mg/day. Gemifloxacin has a low potential for mild phototoxicity (comparable to that of ciprofloxacin).

Topics: Anti-Infective Agents; Bacterial Infections; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines

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

Gemifloxacin is a broad-spectrum quinolone antibacterial with enhanced potency against Gram-positive bacteria, including multi-drug resistant Streptococcus pneumoniae, and retained potency against Gram-negative bacilli and bacterial strains resistant to other antibiotics. It has proven particularly effective in respiratory and urinary tract infection. This review presents safety data from 6775 patients included in clinical trials, receiving either the recommended 320 mg once daily oral dose of gemifloxacin, or standard dose of other quinolones, macrolides or beta-lactams (n = 5248). Studies in healthy volunteer and special populations are also reported. Adverse experiences (AEs) were observed in 44.7% of gemifloxacin-treated patients and 47.5% of those who received comparator drugs. Mild gastro-intestinal adverse drug reactions (ADRs) (diarrhoea 5.1%, nausea 3.9%) predominated. Rash, usually maculo-papular and in no case proceeding to more severe eruptions, was observed in 3.6% of those receiving gemifloxacin. A higher incidence of rash (>20%) was observed in young women and was the subject of further study. Adverse drug reactions suspected or probably related to treatment occurred in 17.4% of patients receiving gemifloxacin and in 20% of those receiving comparator antibiotics. Diarrhoea and nausea were experienced by 3.6 and 2.7%, respectively, of gemifloxacin-treated patients (4.6 and 3.2% of comparators), rash by 2.8% (0.6% of comparators) and headache by 1.2% (1.5% of comparators). Gemifloxacin-related vomiting (0.9%), dizziness (0.8%) and taste perversion (0.3%) were uncommon. Treatment discontinuation followed one or more adverse drug reactions in 2.2% of gemifloxacin-treated patients (0.9% due to rash) and 2.1% of comparator-treated patients. A total of 63 deaths (33 receiving gemifloxacin) occurred in the trial population: none were considered related to treatment. A slight prolongation in QT interval (2.56 ms (S.D. +/-24.5)) was observed in gemifloxacin-treated patients: no cardiac arrhythmias were reported. There was a low incidence of liver function tests (LFTs) classified as of potential clinical concern: gemifloxacin (0.4-1.2%), comparators (0.2-1.3%). Serious adverse events (SAEs), occurring during but not necessarily related to therapy, occurred in 3.6% of gemifloxacin-treated patients (4.3% of comparators). SAEs related to treatment agents were rare (0.4% in each group) and included rash (0.1%) and elevated liver enzymes (<0.1%). Gemifloxa

Topics: Administration, Oral; Anti-Infective Agents; Bacterial Infections; Clinical Trials as Topic; Drug Therapy, Combination; Fluoroquinolones; Gemifloxacin; Humans; Naphthyridines

In a randomized, open-label, controlled, multicentre study, the clinical and bacteriological efficacy, safety and tolerability of oral gemifloxacin (320 mg once daily, 5 days) was compared with sequential intravenous (i.v.) ceftriaxone (1 g once daily, maximum 3 days) followed by oral cefuroxime axetil (500 mg twice daily, maximum 7 days) in adult hospitalized patients with acute exacerbations of chronic bronchitis (AECB) (n = 274). The clinical success rates at follow-up (21-28 days post-therapy) in the clinical per-protocol population (the primary endpoint) were 86.8% (105/121) for gemifloxacin vs. 81.3% (91/112) for ceftriaxone/cefuroxime (treatment difference = 5.5,95% CI -3.9,14.9). The corresponding clinical results in the clinical intention-to-treat (ITT) population were 82.6% (114/138) vs. 72.1% (98/136), respectively (treatment difference = 10.5,95% CI 0.7, 20.4).Thus, gemifloxacin had significantly higher clinical success rates than ceftriaxone/cefuroxime. The median time to discharge was 9 days in the gemifloxacin group vs. 11 days in the ceftriaxone/cefuroxime group (P = 0.04, Wilcoxon test). At follow-up, 120/138 (87.0%) gemifloxacin-treated patients had been discharged from hospital, compared with 111/136 (81.6%) ceftriaxone/cefuroxime-treated patients in the clinical ITT population. Both treatments were generally well tolerated and there was no significant difference between the treatment groups in the incidence or type of adverse events reported. A 5-day course of oral gemifloxacin was shown by this study to be at least equivalent to sequential i.v. ceftriaxone/cefuroxime axetil (for up to 10 days) in patients with AECB who require hospital treatment.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Bronchitis, Chronic; Ceftriaxone; Cefuroxime; Drug Therapy, Combination; Female; Fluoroquinolones; Forced Expiratory Volume; Gemifloxacin; Hospitalization; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Naphthyridines; Treatment Outcome

The magnitude and time course of effect of an acute exacerbation of chronic bronchitis (AECB) on health status are not known. Data from the GLOBE study, a randomised double blind trial of antibiotic therapy, were used to investigate these effects.. 438 patients with AECB received either gemifloxacin 320 mg once daily for 5 days (214 patients) or clarithromycin 500 mg twice daily for 7 days (224 patients) and were followed up for 26 weeks. St George's Respiratory Questionnaire (SGRQ) scores were obtained at baseline and after 4, 12, and 26 weeks.. At presentation during an exacerbation SGRQ scores were worse (Total score difference 5.4 units, 95% CI 1.9 to 8.8, p=0.002) in patients who had a subsequent exacerbation during follow up. The greatest improvement in SGRQ score occurred within the first 4 weeks (mean 8.9 units, 95% CI 6.5 to 11.5, p<0.0001). Subsequently, scores improved more rapidly in patients with no further exacerbations. At 26 weeks the difference between the two groups was 9.6 units (95% CI 5.7 to 13.4, p<0.0001). In patients with no further exacerbations the SGRQ score improved between 4 and 12 weeks by a further 4.1 units (95% CI 2.2 to 5.9, p<0.0001).. A single infective AECB has a sustained effect on health status. The recovery period is long even in patients who have no further exacerbations. A second episode within 6 months limits recovery markedly. Treatments that reduce exacerbation frequency could have a significant impact on health status.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Area Under Curve; Bacterial Infections; Bronchitis; Chronic Disease; Double-Blind Method; Female; Fluoroquinolones; Gemifloxacin; Health Status; Humans; Macrolides; Male; Naphthyridines; Smoking; Treatment Outcome

The primary objective of this study was to demonstrate the clinical and radiologic efficacy of 5 days compared with 7 days of gemifloxacin therapy in the treatment of acute bacterial rhinosinusitis (ABRS).. In this prospective, double-blind, multicenter, parallel-group study, adult patients presenting with ABRS were randomized to receive gemifloxacin 320 mg once daily for either 5 days (n = 218) or 7 days (n = 203).. For the primary efficacy end point, clinical response to therapy at follow-up, 5 days of therapy with gemifloxacin was as effective as 7 days of therapy (per-protocol population; treatment difference 0.44%; 95% confidence interval [CI], -6.54 to 7.41). Five and 7 days of treatment with gemifloxacin were well tolerated.. The clinical efficacy of gemifloxacin 320 mg daily for 5 days is at least as good as the efficacy of gemifloxacin 320 mg daily for 7 days in the treatment of ABRS.

Topics: Acute Disease; Administration, Oral; Adult; Anti-Infective Agents; Bacterial Infections; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluoroquinolones; Follow-Up Studies; Gemifloxacin; Humans; Male; Middle Aged; Naphthyridines; Probability; Prospective Studies; Rhinitis; Sinusitis; Treatment Outcome

LCB01-0371 is a new oxazolidinone with cyclic amidrazone. In vitro activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens. In vivo activity of LCB01-0371 against systemic infections in mice was also evaluated. LCB01-0371 was more active than linezolid against these systemic infections. LCB01-0371 showed bacteriostatic activity against Staphylococcus aureus.

Topics: Acetamides; Animals; Anti-Bacterial Agents; Bacterial Infections; Gram-Positive Bacteria; Linezolid; Male; Mice; Mice, Inbred ICR; Oxazolidinones; Staphylococcus aureus; Vancomycin

The in vitro activity of gemifloxacin against 1,000 clinical isolates of 147 Streptococcus pneumoniae (115, penicilin susceptible; 26, intermediate penicillin-resistant and 6, penicillin-resistant), 127 Hemophilus influenzae (109, beta lactamasa non-producer; 18, beta lactamase producers), 95 Streptococcus pyogenes (6, azytromycin-resistant), 84 Moraxella catarrhalis (79, beta lactamase producers), 110 Staphilococcus aureus (89, methicillin-susceptible; 21, methicilin-resistant), 98 Eenterococcus faecalis and 339 Enterobacteriacea, (recovered from patients with respiratory tract infection; skin and soft tissue infection and urinary tract infection), was compared with the activities of four fluorquinolones and five other antimicrobial agents. Of the quinolones tested, gemifloxacin was the most potent against Streptococcus pneumoniae, including penicillin intermediate and resistant strains. Mic(90) values obtained for gemifloxacin, ciprofloxacin, ofloxacin, levofloxacin and trvafloxacin were 0.03, 2, 2, 1 and 0.25 mg/L respectively. Gemifloxacin was 16 fold more potent than ciprofloxacin against methicillin-susceptible Staphylococcus aureus and 32 fold more potent than ciprofloxacin against Streptococcus pyogenes. When tested against Hemophilus influenzae, Moraxella catarrhalis and Enterobacteriaceae, all the quinolones showed similar activity. Our results demonstrate that gemifloxacin has similar activity than the other quinolones tested against Gram-negative organisms and is considerably more potent against Gram-positive organisms.

Topics: Anti-Infective Agents; Argentina; Bacterial Infections; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Naphthyridines

Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), gemifloxacin reduced bacterial numbers significantly (P < 0.01) compared with no treatment. No comparator agent had a greater effect than gemifloxacin. Notably, grepafloxacin and azithromycin were significantly less effective (P < 0.01) than gemifloxacin against E. coli pyelonephritis, and amoxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0.01) against P. mirabilis infection. In the S. pyogenes wound infection model, gemifloxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduced bacterial numbers significantly compared with controls (P < 0.01). Results for the comparator quinolones were not significantly different from untreated controls (P > 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than gemifloxacin (P < 0.01). No comparator agent had greater activity than gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

Topics: Animals; Anti-Infective Agents; Bacterial Infections; Escherichia coli Infections; Fluoroquinolones; Gemifloxacin; Humans; Male; Naphthyridines; Proteus Infections; Pyelonephritis; Rats; Rats, Sprague-Dawley; Staphylococcal Infections; Streptococcal Infections; Wound Infection

A total of 5499 contemporary clinical bacterial isolates were tested for susceptibility to gemifloxacin and four comparison agents by the broth microdilution method. Gemifloxacin activity against Enterobacteriaceae was generally comparable to that of ciprofloxacin and trovafloxacin, but because the gemifloxacin susceptible MIC breakpoint is lower, the percent susceptible to gemifloxacin was less than that to the other quinolones for some species. All agents were less active against Pseudomonas spp. Gemifloxacin was the most active agent tested against Gram-positive species, though Corynebacterium jeikeium and vancomycin-resistant enterococci were uniformly resistant to all agents tested. With staphylococci, a bimodal distribution of gemifloxacin MICs corresponded with susceptibility or resistance to ciprofloxacin. The significance of ciprofloxacin-resistant staphylococci that have susceptible gemifloxacin MICs is not known at this time. Disk diffusion tests were performed simultaneously with gemifloxacin and trovafloxacin as a control drug. Gemifloxacin MIC-zone diameter scattergrams indicated that interpretive discrepancy rates based on previously proposed criteria when using < or = 0.5 microg/ml as the susceptible MIC breakpoint was within acceptable limits. However, with the currently proposed MIC breakpoint of < or = 0.25 microg/ml, tentative zone diameter breakpoints of > or = 22 mm for susceptible, 19-21 mm for intermediate and < or = 18 mm for resistant are proposed.

Topics: Anti-Infective Agents; Bacterial Infections; Fluoroquinolones; Gemifloxacin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Naphthyridines; North America; Quality Control

The activities of gemifloxacin (SB 265805, LB20304) and comparator agents were determined by an agar dilution method against 419 clinical strains of less-commonly identified species of anaerobes. Gemifloxacin was generally more active than trovafloxacin against gram-positive strains by one to two dilutions. Peptostreptococci (Peptostreptococcus asaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus micros, and Peptostreptococcus prevotii) and Porphyromonas spp. (Porphyromonas asaccharolytica, Porphyromonas canoris, Porphyromonas gingivalis, and Porphyromonas macacae) were all susceptible to /=4 microgram/ml).

Topics: Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; Colony Count, Microbial; Fluoroquinolones; Gemifloxacin; Humans; Microbial Sensitivity Tests; Naphthyridines

The in-vitro activity of gemifloxacin, a new fluoroquinolone, against a wide range (c. 700) of recent clinical isolates, was compared with that of three other fluoroquinolones and other relevant agents. Gemifloxacin inhibited 90% of the Enterobacteriaceae strains at 0.5 mg/L or less, exceptions being Serratia spp. (MIC(90) 1 mg/L) and strains possessing a putative mechanism of resistance to fluoroquinolones. Ninety per cent of Pseudomonas aeruginosa were inhibited by 4 mg/L. Gemifloxacin had good activity against respiratory pathogens, with 90% of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis being inhibited by 0.06 mg/L or less. Staphylococcus aureus (MSSA) were highly susceptible (MIC(90) 0.06 mg/L) but MRSA less susceptible (MIC(90) 8 mg/L) to gemifloxacin. Enterococcus spp. were markedly more susceptible to the study agent than to ciprofloxacin. Gemifloxacin showed good activity against Bacteroides fragilis (MIC(90) 0.5 mg/L) and anaerobic cocci. A tentative in-vitro breakpoint of 0.5 mg/L was studied using a 1 microg disc content for all genera except Pseudomonas where a 5 microg disc content was employed. The false sensitivity reporting rate was 0.5% and false resistance rate was 6.0%, which was considered acceptable. In conclusion, gemifloxacin is a highly active fluoroquinolone that should prove clinically useful in the treatment of a wide range of infections. Susceptibility testing criteria have been developed that should prove robust in a clinical laboratory.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Bacterial Infections; Evaluation Studies as Topic; Fluoroquinolones; Gemifloxacin; Humans; Microbial Sensitivity Tests; Naphthyridines