Moxifloxacin Group Research Articles

Clinical efficacy and safety of moxifloxacin versus levofloxacin plus metronidazole for community-acquired pneumonia with aspiration factors

Background Community-acquired pneumonia (CAP) is a common infectious disease throughout the world and the incidence continues to grow as the population ages. Aspiration is an important pathogenic mechanism for pneumonia in the elderly and the management of patients with community-acquired pneumonia with aspiration factors is a major medical problem. Our study aimed to assess whether moxifloxacin in comparison to levofloxacin plus metronidazole are effective and safe in the treatment of community-acquired pneumonia with aspiration factors. Methods In this prospective, multicenter, open-label, randomized controlled trial, 77 patients with mild-to-moderate community-acquired pneumonia with aspiration factors were enrolled and randomly assigned to receive moxifloxacin or levofloxacin plus metronidazole. The primary efficacy variables were clinical outcomes in evaluable patients at a follow-up visit 7 to 14 days after the end of therapy. Results Seven days after the end of therapy a clinical cure was achieved for 76.7% (23 of 37) of efficacy-evaluable patients in the moxifloxacin group and 51.7% (15 of 40) of patients in the levofloxacin plus metronidazole group. There was a significant difference between the two groups (○2=4.002, P <0.05). Bacteriological success rates were similar in the moxifloxacin group (93.3%) and levofloxacin plus metronidazole group (96.4%), there was no significant difference between the two groups (P >0.05). The overall adverse event rate was 10.8% (4/37) in the moxifloxacin group versus 17.5% (7/40) in the levofloxacin plus metronidazole group, there was no significant difference between the two groups (P >0.05). No serious adverse events were observed. Conclusions Moxifloxacin is effective and safe for treatment of community-acquired pneumonia with aspiration factors. And the regimen of moxifloxacin monotherapy is more convenient compared with levofloxacin plus metronidazole.

Cardiac Repolarization With Gabapentin Enacarbil in a Randomized, Double-Blind, Placebo- and Active-Controlled, Crossover Thorough QT/QTc Study in Healthy Adults

BackgroundGabapentin enacarbil (GEn) is a prodrug of gabapentin and is approved in the United States in adults for the management of postherpetic neuralgia and in the United States and Japan for the treatment of moderate-to-severe primary restless legs syndrome. ObjectiveThis study examined the lack of effect of GEn on cardiac repolarization in accordance with International Conference on Harmonisation E14 guidance. MethodsThis was a randomized, double-blind, double-dummy, placebo- and active- controlled, crossover study in healthy adults (age range, 18–50 years). Study participants received the following in randomized order with a minimum 7-day washout period between treatments: placebo at 0 hours and GEn 1200 mg at 2 hours (GEn 1200 mg group), placebo at 0 hours and GEn 6000 mg at 2 hours (GEn 6000 mg group), placebo at 0 and 2 hours (placebo group), moxifloxacin 400 mg (active control group) at 0 hours, and placebo at 2 hours (moxifloxacin group). Dose offsetting permitted moxifloxacin to be administered in the fasted state and GEn to be administered in the fed state. Assessments included continuous ECG monitoring, pharmacokinetic parameters, and safety and tolerability profiles. The primary end point was the change from baseline in the Fridericia corrected QT interval, at each time point, for the GEn 6000 mg and placebo groups. ResultsOf 52 adults enrolled (mean [SD] age, 30.8 [8.55] years; 50% women), 44 adults (85%) completed the study. Forty-nine adults received GEn 1200 mg, 47 received GEn 6000 mg, 48 received placebo, and 47 received moxifloxacin. The highest estimated (upper limit of the 95% CI) model-adjusted difference in mean change from baseline in the Fridericia corrected QT interval between GEn and placebo was 3.55 (5.66) msec for 1200 mg and 1.20 (3.32) msec for 6000 mg. Assay sensitivity was confirmed with moxifloxacin 400 mg. The geometric mean (%CV) Cmax (between-subject coefficient of variation) was 7.49 (21.2) μg/mL for GEn 1200 mg, 32.46 (23.9) μg/mL for GEn 6000 mg, and 2.08 (24.5) μg/mL for moxifloxacin 400 mg. The most frequently reported adverse events with GEn 6000 mg were dizziness (30%), feeling drunk (26%), nausea (15%), headache (13%), and vomiting (13%). ConclusionSingle doses of GEn, up to 6000 mg, had no effect on cardiac repolarization in this thorough-QT study and are unlikely to cause clinically relevant QT prolongation in clinical use. Assay sensitivity was confirmed with moxifloxacin as an active control. ClinicalTrials.gov identifier: NCT01516372.

Resistance of M. leprae to Quinolones: A Question of Relativity?

Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assessed. Our objective was to measure the impact of a DNA gyrase mutation whose implication in fluoroquinolone resistance has been previously demonstrated through biochemical studies, on the in vivo activity of 3 fluoroquinolones: ofloxacin, moxifloxacin and garenoxacin.Methodology/Principal FindingsWe used the proportional bactericidal method. 210 four-week-old immunodeficient female Nude mice (NMRI-Foxn1nu/Foxn1nu) were inoculated in the left hind footpad with 0.03 ml of bacterial suspension containing 5×103, 5×102, 5×101, and 5×100 M. leprae AFB organisms of strain Hoshizuka-4 which is a multidrug resistant strain harboring a GyrA A91V substitution. An additional subgroup of 10 mice was inoculated with 5×10−1 bacilli in the untreated control group. The day after inoculation, subgroups of mice were treated with a single dose of ofloxacin, moxifloxacin, garenoxacin or clarithromycin at 150 mg/kg dosing. 12 months later mice were sacrificed and M. leprae bacilli were numbered in the footpad. The results from the untreated control group indicated that the infective inoculum contained 23% of viable M. leprae. The results from the moxifloxacin and garenoxacin groups indicated that a single dose of these drugs reduced the percentage of viable M. leprae by 90%, similarly to the reduction observed after a single dose of the positive control drug clarithromycin. Conversely, ofloxacin was less active than clarithromycin.Conclusion/SignificanceDNA gyrase mutation is not always synonymous of lack of in vivo fluoroquinolone activity in M. leprae. As for M. tuberculosis, in vivo studies allow to measure residual antibiotic activity in case of target mutations in M. leprae.

Comparison of Levofloxacin versus Moxifloxacin for Multidrug-Resistant Tuberculosis

Levofloxacin (LFX) and moxifloxacin (MXF) are the two most frequently recommended fluoroquinolones for treatment of patients with multidrug-resistant tuberculosis (MDR-TB). However, studies comparing the effectiveness of LFX and MXF among patients with MDR-TB are lacking. To compare the effectiveness of LFX and MXF in terms of culture conversion after 3 months of treatment for MDR-TB. In this prospective multicenter randomized open label trial, we randomly assigned 182 patients with MDR-TB (sensitive to LFX and MXF) to receive either LFX (750 mg/day; 90 patients) or MXF (400 mg/day; 92 patients) with a background drug regimen. The primary outcome was the proportion of patients who achieved sputum culture conversion at 3 months of treatment. Secondary outcomes were time to culture conversion and time to smear conversion, with data censored at 3 months, and the proportions of adverse drug reactions. At 3 months of treatment, 68 (88.3%) of the 77 patients in the LFX group and 67 (90.5%) of the 74 in the MXF group showed conversion to negative sputum cultures (odds ratio for LFX compared with MXF, 0.78; 95% confidence interval, 0.27-2.20). Adverse drug reactions were reported in six patients (7.7%) in the LFX group and four (5.2%) in the MXF group (P = 0.75). The choice of LFX or MXF for treatment of patients with MDR-TB may not affect sputum culture conversion at 3 months of treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 01055145).

Pharmacokinetics of sunitinib in combination with fluoroquinolones in rabbit model

BackgroundFluoroquinolones are widely prescribed antibiotics. Ciprofloxacin is a well-known inhibitor of cytochrome P450 CYP3A4 and causes numerous drug interactions that are not found for levofloxacin and moxifloxacin. CYP3A4 is involved in the metabolism of the new oral multikinase inhibitor sunitinib which is indicated for the treatment of gastrointestinal stromal tumor (GIST) and advanced renal cell carcinoma (RCC). This study investigated the effects of single intravenous dose of ciprofloxacin, levofloxacin or moxifloxacin on the pharmacokinetics of sunitinib. MethodsRabbits were subjected to one of four study drug groups: sunitinib + ciprofloxacin (n=6), sunitinib + levofloxacin (n=6), sunitinib + moxifloxacin (n=6), or sunitinib alone (n=6). The rabbits were treated with sunitinib in the oral dose of 25mg. The antibiotics were administered intravenously at the doses of 20, 25 and 20mg/kg, respectively. Plasma concentrations of sunitinib and active metabolite (SU12662) were measured with validated HPLC method with UV detection. ResultsThe comparison of sunitinib Cmax for the sunitinib + ciprofloxacin, sunitinib + levofloxacin, sunitinib + moxifloxacin group and that for the sunitinib group gave ratios of 1.81 (90% CI 1.33, 2.44), 1.59 (90% CI 1.18, 2.16), 1.06 (90% CI 0.79, 1.44), respectively. The comparison of sunitinib AUC0-∞ for the sunitinib + ciprofloxacin, sunitinib + levofloxacin, sunitinib + moxifloxacin group and that for the sunitinib group gave ratios of 2.90 (90% CI 1.32, 6.37), 2.45 (1.11, 5.39), 1.58 (0.70, 1.56), respectively. The mean sunitinib tmax was similar for all four groups. The mean Cmax for SU12662 was similar for both the sunitinib + moxifloxacin and sunitinib groups (p=0.9593). However, the mean Cmax for SU12662 for the groups: sunitinib + ciprofloxacin and sunitinib + levofloxacin were higher (p=0.0045 and 0.0672, respectively). ConclusionsThe study proved a significant effect of the coadministration of ciprofloxacin and levofloxacin on the pharmacokinetics of sunitinib in rabbits. The influence of moxifloxacin on the pharmacokinetics of sunitinib was insignificant. Therefore, this fluoroquinolone seems to be the most appropriate in combination with this tyrosine kinase inhibitor.

Prospective, Randomized, Study of Ampicillin-Sulbactam versus Moxifloxacin Monotherapy for the Treatment of Community-Acquired Complicated Intra-Abdominal Infections

The ideal antimicrobial treatment for intra-abdominal infections (IAIs) in the setting of fast-paced emergency departments (EDs) should be effective, convenient, and of limited resource utilization. Antibiotic monotherapy is a feasible option for this. We conducted a study in which we compared two regimens for antibiotic monotherapy recommended by published guidelines in ED patients with community-acquired, complicated IAIs (cIAIs). The study was a prospective, randomized, study of ampicillin-sulbactam versus moxifloxacin for cIAIs. After the diagnosis of cIAI was established, patients were assigned randomly to receive either moxifloxacin 400 mg intravenously (IV) qd followed by moxifloxacin 400 mg orally (PO) qd, or ampicillin-sulbactam 1.5 g IV qid followed by ampicillin-sulbactam 750 mg PO q12h. Source control procedures were used for all patients and all had complete follow-up. The primary efficacy variable for the study was the clinical response at the test-of-cure visit. A total of 116 patients were enrolled for prospective evaluation and randomized assignment to treatment with ampicillin-sulbactam (n=55) or moxifloxacin (n=61). At the test-of-cure evaluation, the overall clinical failure rate was 13.8%. The clinical failure rates in the ampicillin-sulbactam and moxifloxacin groups were 16.4% (9/55) and 11.5% (7/61), respectively (p=0.446). With regard to infection site, the clinical failure rate in cIAIs consisting of lower gastrointestinal (GI) tract infection was significantly lower in the moxifloxacin than in the ampicillin-sulbactam group (4.3% vs. 19.6%; p=0.024). According to multivariable analysis, independent risk factors for treatment failure were the time to ED presentation >24 h (odds ratio [OR] 6.8; 95% CI 1.3-36.2; p=0.024) and ampicillin-sulbactam therapy (OR 9.5; 95% CI 1.1-76.6; p=0.033). A significant difference existed in the clinical responses of the two groups. As compared with ampicillin-sulbactam, moxifloxacin was more effective for the treatment of community-acquired cIAIs of the lower GI tract. A higher risk of treatment failure for antibiotic therapy was found for patients presenting to the ED with symptoms of cIAIs lasting >24 h. Alternative antimicrobial agents should be considered for treating these patients.

The efficacy of moxifloxacin-based triple therapy in treatment of Helicobacter pylori infection: a systematic review and meta-analysis of randomized clinical trials

Recent evidence shows that moxifloxacin could exert an antimicrobial effect against Helicobacter pylori in both in vitro and in vivo models. To systematically evaluate whether moxifloxacin-containing triple therapy could improve eradication rates and reduce side effects in first-line or second-line anti-H. pylori treatment, eligible articles were identified by searches of electronic databases. We included all randomized trials comparing moxifloxacin-based triple therapy with standard triple or quadruple therapy during H. pylori eradication treatment. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/sensitivity analysis was also performed. We identified seven randomized trials (n=1263). Pooled H. pylori eradication rates were 79.03% (95%CI: 75.73-82.07) and 68.33% (95%CI: 64.44-72.04) for patients with moxifloxacin-based triple therapy or with standard triple or quadruple therapy, respectively (intention-to-treat analysis). The odds ratio (OR) was 1.82 (95%CI: 1.17-2.81), the occurrence of total side effects was 15.23% (95%CI: 12.58-18.20) and 27.17% (95%CI: 23.64-30.92) for groups with or without moxifloxacin, and the summary OR was 0.45 (95%CI: 0.26-0.77). In subgroup analyses, we noted that the second-line eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (73.33 vs 60.17%, OR: 1.78, 95%CI: 1.16-2.73, P<0.001). However, there was no difference in first-line eradication treatment. Findings from this meta-analysis suggest that moxifloxacin-based triple therapy is more effective and better tolerated than standard triple or quadruple therapy. Therefore, a moxifloxacin-based triple regimen should be used in the second-line treatment of H. pylori infection.

A Phase 2 study of the novel fluoroquinolone JNJ-Q2 in community-acquired bacterial pneumonia

A Phase 2 study of the novel fluoroquinolone JNJ-Q2 in community-acquired bacterial pneumonia

Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough ECG study

Vilazodone is a potent serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD) in adults. The effect of clinical and supratherapeutic doses of vilazodone on cardiac repolarization was determined in healthy volunteers. In this Phase 1, randomized, doubleblind, placebo- and active-controlled, 3-arm, parallel, single-center study, healthy subjects received placebo; moxifloxacin 400 mg; or vilazodone (sequentially escalated every 3 days) 10, 20, 40, 60, and 80 mg/day. The primary endpoint was the time-matched change from baseline in the QT interval corrected for heart rate (QTc) using an individual correction method (QTcI). Placebo-corrected time-matched analysis of the QTcI duration for the vilazodone treatment effect indicated that no vilazodone dose had an upper bound that approached or exceeded 10 ms, demonstrating no signal for a significant vilazodone effect on cardiac repolarization. Vilazodone had no significant effect on heart rate, PR, or QRS interval duration. The pharmacokinetic/pharmacodynamic model showed that the QTcI slope for vilazodone was not different from 0.0 and that the predicted increase from baseline in the QTc at Cmax for the highest therapeutic dose (156 ng/ml after 40 mg/day) was < 1 ms. The incidence of adverse events (AEs) was higher in the vilazodone group (57.6%) than in the moxifloxacin (37.0%) and placebo (35.6%) groups, though AEs were generally mild to moderate in severity and resulted in few discontinuations. Vilazodone had no significant effect on cardiac repolarization, heart rate, PR or QRS interval duration, or ECG morphology in healthy adult participants.

A Multiple‐Dose, Randomized, Double‐Blind, Placebo‐Controlled, Parallel‐Group QT/QTc Study to Evaluate the Electrophysiologic Effects of THC/CBD Spray

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray has proved efficacious in the treatment of spasticity in multiple sclerosis and chronic pain. A thorough QT/QTc study was performed to investigate the effects of THC/CBD spray on electrocardiogram (ECG) parameters in compliance with regulatory requirements, evaluating the effect of a recommended daily dose (8 sprays/day) and supratherapeutic doses (24 or 36 sprays/day) of THC/CBD spray on the QT/QTc interval in 258 healthy volunteers. The safety, tolerability, and pharmacokinetic profile of THC/CBD spray were also evaluated. Therapeutic and supratherapeutic doses of THC/CBD spray had no effect on cardiac repolarization with primary and secondary endpoints of QTcI and QTcF/QTcB, respectively, showing similar results. There was no indication of any effect on heart rate, atrioventricular conduction, or cardiac depolarization and no new clinically relevant morphological changes were observed. Overall, 19 subjects (25.0%) in the supratherapeutic (24/36 daily sprays of THC/CBD spray) dose group and one (1.6%) in the moxifloxacin group withdrew early due to intolerable AEs. Four psychiatric serious adverse events (AEs) in the highest dose group resulted in a reduction in the surpatherapeutic dose to 24 sprays/day. In conclusion, THC/CBD spray does not significantly affect ECG parameters. Additionally, THC/CBD spray is well tolerated at therapeutic doses with an AE profile similar to previous clinical studies.

Sa1922 Superiority of Acid Suppression for Esomeprazole-Based Helicobacter pylori Eradication Therapy in Japanese CYP2C19 Rapid Metabolizers

Background/Aims: The increasing trend of antibiotic resistance requires effective secondline Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori that would determine the effect of the eradication therapy in long-term follow up period after second-line treatment. Methods: During 2003-2011, 898 patients who had failed previous H. pylori eradication on standard triple therapy were treated with either of two regimens: 1, esomeprazole (20 mg b.i.d), tripotassum dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (40 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, follow-up H. pylori tests were performed with 13C urea breath test or invasive tests (Giemsa histology, CLO test, and culture). In patients who were maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. Results: Mean follow-up periods were 34.1 months and 35.6 months in the quadruple therapy group (n = 65) and moxifloxacin group (n = 177), respectively. H. pylori reappeared in 9 (13.8%) of EBMT and in 31 (17.5%) of MEA, resulting in the annual reinfection rate of 4.88% and 3.13% per year, respectively (P = 0.496). In addition, recrudescence rate of EBMT and MEA group was found to be 1.52% and 3.28% (MEA), respectively (P = 0.679). Multivariate analysis showed that there was no association with any clinical risk factor for H. pylori reinfection. Conclusion: This long-term reinfection rate of H. pylori stayed rather low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy, thus reinfection cannot affect the choice of second-line treatment.

Baseline Correction in Parallel Thorough QT Studies

In parallel thorough QT (TQT) studies, it has been speculated that either baseline correction should be omitted, under the assumption that it only adds noise to the data, or a time-averaged baseline instead of a time-matched baseline correction should be considered in order to reduce the study variability. This study characterized the assumptions and implications of different baseline correction approaches in parallel TQT studies submitted for regulatory review. 57 parallel TQT studies conducted between 2002 and 2009 in 5591 healthy volunteers were evaluated. Only moxifloxacin and placebo arms, including their baselines, were considered. The options of using no baseline correction, time-averaged baseline correction, and time-matched baseline correction were examined and compared. QTc values exhibited a diurnal pattern, with longer QTc intervals during sleep preserved when correcting for a time-averaged baseline. Post-dose and baseline QTc values were highly correlated (mean ρ = 0.80, range 0.56-0.98 and mean ρ = 0.79, range 0.50-0.96 in the placebo and moxifloxacin groups, respectively). The variability of raw QTc values was substantially larger than that of baseline-adjusted QTc values. The difference in the point estimate of QTc differences between moxifloxacin and placebo differed by up to ± 4 ms between the time-averaged and the time-matched baseline corrections. Statistical tests indicate that assumptions of time-averaged baseline and no baseline correction are not appropriate. Baseline correction in parallel TQT studies leads to more precise QTc estimates. Because of possible inaccuracy introduced by time-averaged baseline correction, the time-matched baseline correction appears to be preferable for a parallel TQT study to both reduce the intrinsic variability due to circadian patterns and obtain more accurate point estimates.

Comparative roles of moxifloxacin and levofloxacin in the treatment of pulmonary multidrug-resistant tuberculosis: a retrospective study

This study compared the efficacy of moxifloxacin and levofloxacin in the treatment of multidrug-resistant tuberculosis (MDR-TB) in Shanghai, China. A retrospective analysis of 158 patients with MDR-TB receiving either moxifloxacin- or levofloxacin-containing regimens was performed. Clinical data from patients were subjected to univariate analysis, stratification and multiple logistic regression to compare the roles of moxifloxacin and levofloxacin in multidrug regimens. In total, 72 patients received 400mg of moxifloxacin once daily and 86 patients received 509.9±79.4mg (mean±standard deviation) of levofloxacin once daily together with similar active agents for similar durations. The times to sputum culture conversion were similar. Adverse reactions occurred at comparable rates. The combined treatment success rate was 60.1%, being higher among ofloxacin-susceptible than ofloxacin-resistant cases (67.5% vs. 52.0%; P<0.05). The success rates for the moxifloxacin group were 65.3% (overall), 77.1% (ofloxacin-susceptible cases) and 54.1% (ofloxacin-resistant cases) in comparison with 55.8%, 60.4% and 50.0%, respectively, for the levofloxacin group. No demographic, clinical, bacteriological or treatment characteristics were independent predictors of favourable outcome. Fourteen patients from the moxifloxacin group and twelve patients from the levofloxacin group had bacteriological relapse after treatment cessation. In conclusion, compared with levofloxacin, moxifloxacin did not show superior efficacy when incorporated into multidrug regimens used for the treatment of MDR-TB.

Differences in efficacy of piperacillin sulbactam sodium and moxifloxacin in community-acquired pneumonia

Objective To investigate the differences of piperacillin sulbactam sodium and moxifloxacin in community-acquired pneumonia (CAP).Methods A analysis of 140 cases of CAP patients,were randomly divided into two groups,of which 70 cases piperacillin sulbactam sodium; remaining 70 cases moxifloxacin comparative clinical efficacy.Results The moxifloxacin group therapy effective rate of 88.57％ greater than 68.57％ of the piperacillin,the differences were statistically significant(P＜0.05).Conclusions Moxifloxacin in the treatment of CAP more effective than piperacillin sulbactam sodium,and the appropriate cost worth in clinical practice,patients Adaptation and contraindications. Key words: piperacillin sulbactam sodium; moxifloxacin; CAP

Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropneia in patients with hematological malignancies

Recent studies have shown the prophylactic efficacy of fluoroquinolones against infections in patients with chemotherapy-induced neutropenia. However, little is known about the differences between fluoroquinolones, and there are some concerns about the emergence of resistant bacteria. In this retrospective study, we compared the prophylactic efficacy of moxifloxacin (MFLX) and tosufloxacin (TFLX) for chemotherapy-induced febrile neutropenia. The cumulative incidences of febrile neutropenia were 74.7% (59 of 79) in the MFLX group and 81.1% (219 of 270) in the TFLX group (log-rank test p = 0.044). Subgroup analysis revealed a more prominent prophylactic advantage of MFLX in patients with acute myeloid leukemia (AML) or long duration of neutropenia (p = 0.013 and 0.008, respectively). There were no significant differences in the incidences of adverse events and fluoroquinolone resistant bacteria in both groups. This study indicates that prophylaxis with MFLX is more beneficial to reduce febrile neutropenia episodes than TFLX, especially in patients with high-risk disease.

Safety of besifloxacin ophthalmic suspension 0.6% in refractive surgery: a retrospective chart review of post-LASIK patients

BackgroundTo evaluate the safety of besifloxacin ophthalmic suspension 0.6% when used in laser-assisted in situ keratomileusis (LASIK) prophylactic antibiotic regimens.MethodsRetrospective surveillance of LASIK surgery cases where besifloxacin ophthalmic suspension 0.6% or moxifloxacin ophthalmic solution 0.5% were prescribed as prophylactic medications. Surgeons from nine US surgical centers provided retrospective case information on surgical outcomes from consecutive cases and reported any adverse events related to the antibacterial used. The primary endpoint was the incidence of adverse drug reactions.ResultsA total of 801 case reports (801 eyes; 534 besifloxacin, 267 moxifloxacin) were obtained. The mean (standard deviation [SD]) age at time of surgery was 36.1 (10.6) years. The mean (SD) duration of antibiotic treatment was 8.6 (2.2) days in the besifloxacin group and 8.0 (2.3) in the moxifloxacin group; daily dosing frequency was higher in the moxifloxacin group preoperatively, on the day of surgery, and postoperatively. There were no reports of adverse drug reactions for the 801 eyes in this surveillance. There were no differences between the besifloxacin and moxifloxacin treatment groups in rates of unexpected corneal findings (2.1% vs 1.5%, P = 0.949). The distribution of final visual acuity for the besifloxacin and moxifloxacin groups were similar (P = 0.793). Most cases had a final visual acuity of 20/20 or better.ConclusionIn this retrospective surveillance study, the prophylactic use of besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in patients undergoing LASIK surgery was not associated with any adverse drug reactions.

Hydrophilic Acrylic Intraocular Lens as a Drug Delivery System: Influence of the Presoaking Time and Comparison to Intracameral Injection

To evaluate the influence of different intraocular lens (IOL) presoaking times in an antibiotic solution and to compare the results with intracameral antibiotic injection alone. Part A: 45 IOLs were soaked in gatifloxacin, moxifloxacin, or prednisolone acetate for 10 min, 24 h, and 1 week and then placed in a vial with a balanced salt solution. The solutions were sampled 12 and 24 h later. Part B: 90 eyes of 45 rabbits were divided into three groups. Group A received intracameral injection of moxifloxacin after lens removal and nonpresoaked IOL implantation. Groups B and C were implanted with IOLs that were presoaked for 15 min in moxifloxacin (group B) or gatifloxacin (group C), after lens removal with no intracameral antibiotic injections. Aqueous humor samples were taken 2, 4, 6, 8, and 10 h after surgery for high-performance liquid chromatography. Part A: In comparison with the 24-h group, the 10-min group showed release of about 30% of the antibiotics amount; the 1-week group showed a longer release time of the antibiotics and an increase of 27% for gatifloxacin and 43% for moxifloxacin. No prednisolone acetate was found. Part B: The moxifloxacin concentrations in the intracameral injection group were higher after surgery, but with faster antibiotic decrease in comparison with both presoaked IOL groups. Intracameral antibiotic injection showed a high antibiotic concentration for a short time. Presoaked IOLs showed slower decrease rates of the antibiotic level.

A Single-Blinded Randomized Clinical Trial Comparing Polymyxin B-Trimethoprim and Moxifloxacin for Treatment of Acute Conjunctivitis in Children

To perform a randomized controlled trial comparing moxifloxacin hydrochloride with polymyxin B-trimethoprim for the treatment of acute conjunctivitis. Patients ages 1-18 years old with acute conjunctivitis had cultures performed and were randomized to receive either moxifloxacin hydrochloride or polymyxin B-trimethoprim ophthalmic solution for 7 days. Response to treatment was determined by phone query on day 4-6 and by examination with post-treatment conjunctival culture on day 7-10. One hundred and twenty-four patients were enrolled. Eighty patients (65%) had recognized pathogens (55 Haemophilus influenzae, 22 Streptococcus pneumoniae, 4 Moraxella catarrhalis) isolated from their conjunctiva. One hundred fourteen (56/62 moxifloxacin and 58/62 polymyxin B-trimethoprim) completed the 4-6 day evaluation, with 43/56 (77%) of the moxifloxacin group and 42/58 (72%) of the polymyxin B-trimethoprim group clinically cured according to parents (noninferiority test P=.04). Eighty-nine (39/56 moxifloxacin and 50/58 polymyxin B-trimethoprim) patients completed the 7-10 day evaluation. Clinical cure was observed in 37/39 (95%) of the moxifloxacin and 49/51 (96%) of the polymyxin B-trimethoprim treated groups (noninferiority test P≤.01). Clinical cure rates for culture positive and negative conjunctivitis were not different. There was no statistically significant difference in bacteriologic cure rates between the 2 groups. Polymyxin B-trimethoprim continues to be an effective treatment for acute conjunctivitis with a clinical response rate that does not differ from moxifloxacin. Use of polymyxin B-trimethoprim for the treatment of conjunctivitis would result in significant cost savings compared with fluoroquinolones.

The Comparison of Fluoroquinolones to Nonfluoroquinolone Antibacterial Agents for the Prevention of Endophthalmitis in a Rabbit Model

Topical antibacterial agents, used as an off-label indication, are frequently administered pre- and postoperatively to prevent endophthalmitis. We compared topical treatment with fluoroquinolone (FQ) anti-infectives to non-FQ antibacterial agents to prevent Staphylococcus aureus endophthalmitis. We hypothesize that FQ anti-infectives are more effective than non-FQ antibacterial agents for preventing endophthalmitis. Moxifloxacin 0.5%, ofloxacin 0.3%, gentamicin 0.3%, chloramphenicol 0.5%, polymyxin B/trimethoprim (10,000 units/mL/0.1%), povidone-iodine 5%, and saline were tested for topical treatment to prevent endophthalmitis. Topical treatment was applied every 15 min for 1 h (5 drops) to the left eye of 14 rabbits for each antibacterial agent and saline. After appropriate anesthesia, the anterior chambers were injected with 1×10(5) colony-forming units of a clinical endophthalmitis isolate of a S. aureus that was susceptible to all tested antibacterials. One drop was administered immediately and another 4 drops of topical treatment were applied over 24 h after injection. At 24 h postinjection, the eyes were graded for clinical signs of endophthalmitis (ocular discharge, conjunctivitis/scleral injection, limbal injection, hypopyon*, iritis*, anterior chamber cells*, anterior chamber flare*, corneal infiltration, and fibrin production*) using a severity scale (0-3). The indication of clinical endophthalmitis was a total score of >3.0 for the presentations marked with an asterisk. The data were analyzed using Fisher's Exact Randomization or Mann-Whitney nonparametric testing. Topical ofloxacin (14/14, 100% without endophthalmitis) and moxifloxacin (13/14, 93%) prevented the clinical presentation of endophthalmitis significantly more frequently (P=0.03, Fisher's Exact Test (FE)) than topical gentamicin (7/14, 50%), povidone iodine (4/14, 29%), chloramphenicol (0/14, 0%), polymyxin B/trimethoprim (0/14, 0%), and saline (0/14, 0%). The median total clinical scores for the ofloxacin (0.5) and moxifloxacin (0.8) groups were significantly (P=0.008, Mann-Whitney Test (MW)) lower than gentamicin (5.7), chloramphenicol (17.5), polymyxin B/trimethoprim (21.2), povidone-iodine (15.5), and saline (18.7). The FQs, ofloxacin and moxifloxacin, were more effective in preventing endophthalmitis than the non-FQ antibacterial agents in a rabbit S. aureus endophthalmitis model. The observed results are consistent with the hypothesis that FQs penetrate into the anterior chamber at more effective levels than many of the common non-FQ antibacterial agents.

Efficacy and safety profile of moxifloxacin in treatment of urogenital system infections: A meta-analysis of randomized controlled trials

higher than conventional therapy [RR = 1.08, 95%CI (1.02, 1.14), P = 0.008; RR = 1.09, 95%CI (1.04, 1.14), P = 0.0005; RR = 1.04, 95%CI (0.99, 1.09), P = 0.08]; the incidences of adverse drug reactions between moxifloxacin and control group were not statistically significant [RR = 0.88, 95%CI (0.72, 1.06), P = 0.17]. In three large studies of pelvic inflammatory disease (PID) patients, no statistically significant difference was found between moxifloxacin monotherapy group and control group about clinical cure rates, microbiological success rates and the incidences of adverse drug reactions [RR = 0.98, 95%CI (0.95, 1.02), P = 0.33; RR = 1.06, 95%CI (0.96, 1.16), P = 0.25; RR = 0.85, 95%CI (0.68, 1.05), P = 0.13]. Moxifloxacin can be suggested as the regimen of choice for treatment of urogenital system infections.