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Five-day moxifloxacin therapy compared with 7-day co-amoxiclav therapy for the treatment of acute exacerbation of chronic bronchitis.

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400 mg tablet daily) was compared with that of co-amoxiclav (one 625 mg tablet every 8h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28-35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB.

Adult↗

New real-time PCR-based method for in vitro susceptibility testing of Anaplasma phagocytophilum against antimicrobial agents.

Up to now, only a few isolates of Anaplasma phagocytophilum have been tested for their susceptibility against a small number of antimicrobial agents. In addition, as with other fastidious or intracellular bacteria, the test methods are laborious and neither minimal inhibitory concentration (MIC) definitions, nor the test conditions and the inocula are standardised to date. A new 16S-rDNA-based real-time PCR assay has been developed and used under standardised conditions to analyse the activity of seven antimicrobial agents against two A. phagocytophilum isolates. After 72 h incubation, MICs were determined by software-assisted calculation of bacterial growth in samples and controls from semi-quantitative PCR results. In our study, the rank order of potency on a mg/l basis for the antimicrobial agents with enhanced in vitro activity against A. phagocytophilum was moxifloxacin (MIC: < or = 0.03 mg/l) > doxycycline (MIC: < or = 0.125 mg/l) > ciprofloxacin (MIC: 0.125 mg/l). Gentamicin, ampicillin, azithromycin and cethromycin showed no activity against the isolates tested in this investigation. Our new 16S-rDNA-PCR-based microdilution test system was shown to be sensitive, reproducible and reliable. The assay is capable of testing larger numbers of isolates and antimicrobial agents under standardised and very precise test conditions and may therefore offer a competent technical solution of the difficulties known to be associated with in vitro testing of other bacterial pathogens that grow intracellularly, such as chlamydia or rickettsia.

Ampicillin↗

Bactericidal activity of moxifloxacin against multidrug-resistant Streptoccocus pneumoniae at clinically achievable serum and epithelial lining fluid concentrations compared with three other antimicrobials.

Time-kill studies compared the activities of moxifloxacin with those of levofloxacin, azithromycin and amoxicillin-clavulanate against 10 pneumococcal strains with various drug susceptibilities. Three Streptococcus pneumoniae strains were resistant to moxifloxacin: 6, 7 and 2 strains were resistant to levofloxacin, azithromycin and amoxicillin-clavulanate, respectively. Of these, 1 strain was resistant to all antimicrobial agents studied. Moxifloxacin and amoxicillin-clavulanate were bactericidal after 24h at serum Cmax levels against 9 and 8 strains, respectively, while levofloxacin and azithromycin were bactericidal against 3 and 2 strains, respectively. A higher activity was only observed for amoxicillin-clavulanate for logarithmic phase cultures at 1, 4 and 8h compared with stationary phase organisms. Amoxicillin-clavulanate and moxifloxacin were bactericidal at free serum levels (protein unbound) after 24h against 8 and 3 strains, respectively. Moxifloxacin was bactericidal at epithelial lining fluid levels against all strains at 24h, including one moxifloxacin, amoxicillin-clavulanate and azithromycin-resistant strain; lower levels of bactericidal activity was observed for levofloxacin, azithromycin and amoxicillin-clavulanate against 7, 2 and 4 strains, respectively. This demonstrated the importance of moxifloxacin tissue levels.

Anti-Bacterial Agents↗

In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point.

A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).

Animals↗

A double mutation in the gyrA gene is necessary to produce high levels of resistance to moxifloxacin in Campylobacter spp. clinical isolates.

The aim of this study was to compare different fluoroquinolones against Campylobacter spp., analysing the molecular mechanisms of resistance. Moxifloxacin exhibited the greatest activity of the quinolones tested, being active against isolates carrying a single mutation in the gyrA gene. High resistance levels to moxifloxacin were related to the presence of a double gyrA mutation.

Amino Acid Substitution↗

Susceptibility to moxifloxacin of pneumococci isolated in English hospitals participating in the European Antimicrobial Resistance Surveillance System (EARSS) in 2003.

Susceptibility to moxifloxacin, penicillin and erythromycin was determined for 592 invasive Streptococcus pneumoniae collected from 20 English hospitals participating in the European Antimicrobial Resistance Surveillance System (EARSS) during 2003. Resistance to moxifloxacin, penicillin and erythromycin was observed in 0.8%, 5.4% and 13% of the isolates, respectively. These results show that the large majority of pneumococci were susceptible to moxifloxacin in 2003, the year when it was licensed for clinical use in the UK.

Anti-Bacterial Agents↗

Microbiological rationale for the utilisation of prulifloxacin, a new fluoroquinolone, in the eradication of serious infections caused by Pseudomonas aeruginosa.

Minimal inhibitory concentrations (MICs) of prulifloxacin were evaluated in comparison with ciprofloxacin, levofloxacin and moxifloxacin against a large collection (N = 300) of Pseudomonas aeruginosa strains characterised according to the CLSI/NCCLS microdilution method. Additional in vitro tests (time-kill curves and mutant prevention concentration (MPC) determinations) were carried out. Assuming a susceptibility breakpoint for prulifloxacin identical to that of ciprofloxacin, the new fluoroquinolone emerged as the most potent antibiotic (72% of susceptible strains versus 65%, 61% and 23% for ciprofloxacin, levofloxacin and moxifloxacin, respectively). Time-kill tests at 4x MIC confirmed the pronounced bactericidal potency of the drug against P. aeruginosa. Amongst the members of the fluoroquinolone class assessed, prulifloxacin produced the lowest MPC values (< or = 4 mg/L). Our in vitro results indicate that prulifloxacin represents the most powerful antipseudomonal drug available today.

Anti-Bacterial Agents↗

Sequential intravenous/oral moxifloxacin versus intravenous piperacillin-tazobactam followed by oral amoxicillin-clavulanate for the treatment of complicated skin and skin structure infection.

In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7-14 days. Clinical cure rates at the test-of-cure visit (10-42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, -12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.

Administration, Oral↗

Correlation between in vitro and in vivo activity of levofloxacin and moxifloxacin against pneumococcal strains with different susceptibilities to fluoroquinolones.

In vitro and in vivo models were developed to evaluate the efficacy of levofloxacin and moxifloxacin against three serotype 3 pneumococcal strains with different susceptibilities to fluoroquinolones (wild-type, parC mutant, and parC, parE and gyrA mutant). Levofloxacin and moxifloxacin reduced the bacterial burden in the in vitro pharmacodynamic and animal models for the wild-type strain but had very little activity against the fully resistant strain (parC, parE and gyrA mutant). Levofloxacin showed very little activity both in the in vitro pharmacodynamic model and in the animal model for the strain having a mutation in parC (levofloxacin and moxifloxacin minimum inhibitory concentrations, 2mg/L and 0.25mg/L, respectively). However, moxifloxacin still had a significant in vitro and in vivo activity against this strain.

Animals↗

Treatment of implant-associated infections with moxifloxacin: an animal study.

The efficacy of moxifloxacin in the treatment of an implant-associated infection by Staphylococcus aureus was compared with vancomycin in an animal study. The femoral medullary cavity of 36 Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted. After treatment for 14 days with moxifloxacin (2 x 10 mg/kg/day) or vancomycin (2 x 15 mg/kg/day), the bacterial counts (colony-forming units) in the periprosthetic bone, the soft tissue and the implant-associated biofilm were measured. Compared with the control group, moxifloxacin achieved a highly significant decrease in the microbial counts in the bone and soft tissue and in the biofilm (P<0.001). Moreover, the efficacy of moxifloxacin was significantly greater than that of vancomycin (P<0.01). Vancomycin did not reduce the microbial count significantly compared with the control group (P>0.05). The results justify further investigations of the treatment of implant-associated infections due to S. aureus with moxifloxacin.

Animals↗

Treatment of murine pneumonic Francisella tularensis infection with gatifloxacin, moxifloxacin or ciprofloxacin.

The efficacies of gatifloxacin and moxifloxacin were assessed in a BALB/c mouse model of pneumonic tularemia and compared with the efficacy of ciprofloxacin. The rate of relapse following dexamethasone treatment was also investigated. Mice were given 100 mg/kg of the antibiotic by oral administration twice daily for 14 days following an aerosol challenge. All three fluoroquinolones prevented disease during the treatment period, but significant failure rates occurred after the cessation of therapy. Both gatifloxacin and moxifloxacin were more effective than ciprofloxacin at reducing late mortality. Fluoroquinolones may therefore be considered useful candidates for the treatment of pneumonic tularemia.

Animals↗

Comparative elution of moxifloxacin from Norian skeletal repair system and acrylic bone cement: an in vitro study.

The objective of this study was to evaluate the efficacy of Norian skeletal repair system (SRS), a novel biodegradable and injectable form of calcium phosphate cement with a composition similar to that of cancellous bone, as a carrier for moxifloxacin, which is the most potent quinolone agent against staphylococci and Enterobacteriaceae. Norian SRS was mixed with moxifloxacin at a ratio of ca. 100:3 at room temperature and solidified in the bottom of a cylindrical vial. The same procedure was followed for acrylic bone cement. A total of five vials were prepared per system. Mueller-Hinton broth was placed over the free surface of both systems and the vials were transferred to a 37 degrees C incubator. The broth was replaced daily until visual degradation of both systems. Moxifloxacin was measured in aliquots of broth after passage through a high-performance liquid chromatography system. Optical degradation of both systems occurred after 450 days. Until Day 17, concentrations eluted from both systems were similar. After Day 18 until degradation, concentrations eluted by Norian SRS were statistically higher than those eluted by acrylic bone cement and ranged between 100 mg/L and 800 mg/L. The mean area under the concentration-time curve (AUC) over 450 days of sampling was 241 935.0 mg/L day for Norian SRS and 18 300.0 mg/L day for the acrylic bone cement system (P=0.043). Norian SRS is a novel biodegradable system providing excellent strength and mineralisation to bone. It was shown that this system allows in vitro elution of moxifloxacin at significant concentrations, making it a promising candidate for the therapy of chronic osteomyelitis.

Absorbable Implants↗

Penetration of moxifloxacin into sternal bone of patients undergoing routine cardiopulmonary bypass surgery.

This study investigated plasma and bone concentrations of moxifloxacin following a single intravenous dose of 400mg to consider its potential role in the treatment of osteomyelitis. Eight patients who underwent routine cardiopulmonary bypass surgery were enrolled in the study. Plasma and bone samples were collected 2h and 5h after the end of infusion. High performance liquid chromatography was used for the determination of moxifloxacin concentrations. Mean plasma concentrations were 3.36 microg/mL and 2.93 microg/mL at 2h and 5h after the end of infusion. The concentrations in the body and manubrium of the sternal bone were 1.65 microg/g and 1.64 microg/g at 2h and 1.4 microg/g and 1.45 microg/g at 5h, respectively. Moxifloxacin showed good penetration into bone and could be considered for the treatment of osteomyelitis.

Aged↗

Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis.

Antibiotic therapy is of clinical benefit in certain patients with acute exacerbations of chronic bronchitis (AECB). In this randomised, investigator-blinded, multicentre trial, azithromycin (500mg once a day (qd) for 3 days) was compared with moxifloxacin (400mg qd for 5 days) for the treatment of outpatients with AECB (forced expiratory volume in 1s (FEV(1)) >35%). Of 342 patients randomised to either treatment, 169 received azithromycin and 173 received moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4 years and 55.5 years, respectively. In the intent-to-treat analysis, clinical success rates for azithromycin and moxifloxacin were comparable at Days 10-12 (90% versus 90%, respectively) and Days 22-26 (81% versus 82%, respectively). Among patients who were culture-positive at baseline for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10-12 was 93% versus 84%, respectively, and at Days 22-26 it was 89% versus 73%, respectively. The incidence of at least one treatment-related adverse event (AE) in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively. The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most treatment-related AEs were of mild or moderate severity, with no serious treatment-related AEs. One subject in the moxifloxacin group discontinued treatment owing to a treatment-related AE (precordial pain and dry throat). Compliance with both regimens was >90%. Three-day azithromycin and 5-day moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB in outpatients.

Abdominal Pain↗

The effect of treatment with moxifloxacin or azithromycin on acute bacterial rhinosinusitis in mice.

OBJECTIVE: Acute bacterial rhinosinusitis, which is a major health problem, is treated with antibiotics. We developed a mouse model of acute bacterial rhinosinusitis to gain a better understanding of the pathophysiology of the disease. Our goal was to investigate the response to acute rhinosinusitis when treated with either a bactericidal or a bacteriostatic antibiotic. METHODS: C57BL/6 mice were infected intranasally with Streptococcus pneumoniae. One day after inoculation, the mice were treated with either moxifloxacin (bactericidal) or azithromycin (bacteriostatic). Different groups were euthanized during the first five days post-inoculation. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were evaluated by flow cytometry. RESULTS: Azithromycin led to rapid clearance of the bacteria and of the inflammation in contrast to placebo. Surprisingly, moxifloxacin showed a limited effect. Investigations of this limited effect of moxifloxacin suggested a high metabolic clearance, a low concentration at the site of infection, and low persistent post-antibiotic effects of moxifloxacin in mice. CONCLUSION: Our animal model of acute sinusitis has great utility for studying the disease, but the difference between mice and man must always be considered in making extrapolations from animal experiments to the human experience.

Acute Disease↗