Moxifloxacin Group Research Articles

Üç Farklı Kuşak Florokinolon Türevinin Ratlarda Eritrosit Frajilite ve Hematolojik Parametreler Üzerindeki Etkilerinin Araştırılması

Objektive: Fluoroquinolones (FQs) are synthetic broad-spectrum antimicrobial agents derived from nalidixic acid. They are used in the treatment of urinary tract infections, respiratory tract infections, skin infections, digestive system infections, genital infections and other bacterial infections. Although the relationship between FQs and oxidative stress has been demonstrated, their effects on erythrocyte fragility have not been adequately studied. In this study, the effects of three different FQ derivatives (ciprofloxacin (CIP), levofloxacin (LVX) and moxifloxacin (MXF)) on erythrocyte fragility and hematological parameters were investigated in rats at the end of the 1st, 7th and 14th day treatments.
 Material and Method: 72 Wistar albino male rats were divided into 4 groups with 18 rats in each group and sacrificed at three different time points (1st, 7th and 14th days).
 Results: A significant increase in 0.2% sodium chloride (NaCl) concentration erythrocyte fragility value was found in the MXF group on 1st day compared to the control group on 1st day. While the FQ derivatives used in the study did not cause a general change on the erythrocyte and leukocyte parameters, they caused various fluctuations on the platelet parameters such as PCT, PLCR, PDW, MPW and PLT.
 Conclusion: As a further study, it would be beneficial to reveal the reasons for these effects on platelet parameters with more detailed studies.

Nemonoxacin achieved a better symptomatic improvement and a prolonged interval to next exacerbation than moxifloxacin for outpatients with acute exacerbations of chronic obstructive pulmonary disease

Nemonoxacin is a novel non-fluorinated quinolone with strong antibacterial efficacy, but data of its effect on acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is rare. This study was conducted to compare the efficacy of oral nemonoxacin with moxifloxacin in AECOPD outpatients. In this retrospective observational study, a total of 101 AECOPD outpatients initially treated with nemonoxacin or moxifloxacin from July 2021 to March 2022 were enrolled. We collected COPD assessment test (CAT), Transition Dyspnea Indices (TDI) scores, and exacerbations information during 24 weeks follow-up from the electronic medical records. Kaplan–Meier curve was used to analyze the time to the next moderate/severe exacerbation. Compared to the moxifloxacin group, changes in CAT scores and TDI scores were significantly higher in the nemonoxacin group, and the nemonoxacin group also had a greater probability to reach the minimal clinically important difference of CAT (71.40% vs. 97.80%, p < 0.01) and TDI (40.50% vs. 60.00%, p < 0.05) at week 4. Despite no significant difference in the incidence of exacerbations between two groups, patients treated with nemonoxacin had a significantly prolonged time to next moderate/severe exacerbation than those with moxifloxacin (p < 0.05). Nemonoxacin achieved a better symptomatic improvement and a prolonged interval to next moderate/severe exacerbation for AECOPD outpatients.

Omadacycline in the treatment of community-acquired bacterial pneumonia in patients with comorbidities: a post-hoc analysis of the phase 3 OPTIC trial.

The 2019 American Thoracic Society/Infectious Disease Society of America guidelines recommend respiratory fluoroquinolones to treat community-acquired bacterial pneumonia (CABP) in adults with comorbidities. Fluoroquinolones are effective against both typical and atypical pathogens. However, fluoroquinolone treatment has a risk of adverse effects, and the Food and Drug Administration has issued black box safety warnings for their use. Inpatient use of fluoroquinolones has reduced as a result; however, most antibiotic courses are completed as outpatients and discharge prescriptions account for the majority of fluoroquinolone use. As such, a new treatment option is needed to replace fluoroquinolones. Omadacycline is an aminomethylcycline antibiotic with a broad spectrum of activity and is available as a once-daily intravenous or bioequivalent oral formulation. This study assessed the safety and clinical efficacy of omadacycline compared with moxifloxacin for the treatment of adult CABP patients with Pneumonia Severity Index (PSI) risk class II/III and ≥1 comorbidity through a post-hoc analysis of the phase 3 OPTIC study (NCT02531438). In total, 239 omadacycline- and 222 moxifloxacin-treated patients were assessed. The median age was similar between groups (omadacycline: 57 years; moxifloxacin: 58 years), with 26.0% and 26.6%, respectively, ≥65 years of age. Early clinical response was 91.6% for patients with ≥1 comorbidity treated with omadacycline and 91.4% for those treated with moxifloxacin. Post-treatment evaluation results for overall response were 89.1% in the omadacycline group and 87.4% in the moxifloxacin group. Safety warnings have reduced inpatient use of fluoroquinolones; however, outpatient and discharge prescriptions account for the majority of fluoroquinolone use. Outpatients with comorbidities need an efficacious alternative to fluoroquinolones. Omadacycline maintains the similar efficacy and benefits of fluoroquinolones as a once-daily, monotherapy, bioequivalent oral option with potent in vitro activity against the most common CABP pathogens, including S. pneumoniae and atypical pathogens, but offers a materially different safety profile consistent with its tetracycline heritage. In conclusion, both omadacycline and moxifloxacin exhibited similar efficacy in patients with PSI risk class II/III and comorbidities. Omadacycline fulfills an unmet need as an oral monotherapy treatment option for adult patients with CABP, which will further reduce the use of fluoroquinolones. https://www.clinicaltrials.gov/study/NCT02531438, identifer: NCT02531438; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004071-13, identifier: EudraCT #2013-004071-13.

Comparison of Efficacy of Moxifloxacin and Ceftriaxone in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Objective: To compare the efficacy of Moxifloxacin and Ceftriaxone in acute exacerbation of chronic obstructive pulmonary disease. Methodology: This randomized trial was conducted in the Pulmonology Department, PIMS, Islamabad, between August 2018 and February 2019. Patients were screened from the OPD department, and before randomization, their sputum was collected over 24 hours in a solid, sterile plastic (60 mL) bottle at room temperature. They were randomized equally into two treatment groups using a lottery method. Group A received Moxifloxacin 400 mg orally once daily for five days, and group B received Ceftriaxone 1 g (IV infusion) once daily for five days. All the measurements (dyspnea grading, sputum volume, and character) were taken after five days of antibiotic therapy. Results: The mean age was 60.79 ± 13.34 years in Moxifloxacin and 59.86 ± 12.72 years in the Ceftriaxone group. In Moxifloxacin group, there were 49(68.06%) male and 23(31.94%) females and in the Ceftriaxone group, there were 49(68%) males and 23(31.94%) female cases. In Moxifloxacin, a total of 68(94.4%) cases recovered, while 4 (5.6%) cases did not achieve efficacy, whereas, in the Ceftriaxone group, 54 (75.0%) cases achieved efficacy and 18 (25.0%) were therapy failures. The efficacy of the oral Moxifloxacin group was significantly better than the oral Ceftriaxone group (p-value, &lt; 0.05). Conclusion: The efficacy of Moxifloxacin was better than Ceftriaxone in acute exacerbation of chronic obstructive pulmonary disease.

Safety study of moxifloxacin in children with severe refractory Mycoplasma pneumoniae pneumonia.

With the increase in macrolide-resistant M. pneumoniae infections, off-label use is difficult to avoid. This study assessed the safety of moxifloxacin in pediatric patients with severe refractory M. pneumoniae pneumonia (SRMPP). We retrospectively reviewed the medical records of children with SRMPP between January 2017 and November 2020 at Beijing Children's Hospital. They were divided into the moxifloxacin group and azithromycin group according to whether or not moxifloxacin was used. The clinical symptoms, radiographs of both knees, and cardiac ultrasounds of the children were collected after drug withdrawal for at least 1 year. A multidisciplinary team reviewed all adverse events and determined their relationship with moxifloxacin. A total of 52 children with SRMPP were included in this study (31 in the moxifloxacin group and 21 in the azithromycin group). In the moxifloxacin group, four patients had arthralgia, one had joint effusion, and seven had heart valve regurgitation. In the azithromycin group, three patients had arthralgia, one had claudication, and one had heart valve regurgitation; no obvious knee abnormalities were observed in the radiographs. No statistically significant differences in clinical symptoms or imaging findings were found between the groups. As for the adverse events, 11 patients in moxifloxacin group were deemed to be doubtfully related and one possibly related to moxifloxacin; in the azithromycin group, four patients were regarded to be doubtfully related to azithromycin and one not related. Moxifloxacin was well tolerated and safe for treating SRMPP in children.

L'antibioticoterapia topica è efficace nel trattamento della congiuntivite acuta nei bambini

Local antibiotic therapy is effective in acute infectious conjunctivitis Ten years after the last Cochrane review on the subject, this small randomized trial (88 participants aged 6 months to 7 years) aimed to test the efficacy of local antibiotic therapy (moxifloxacin) vs placebo in acute infectious conjunctivitis. To exclude the possible benefit related to the washout effect of placebo drops, a second control group with no treatment was included. Clinical healing time was significantly shorter in the moxifloxacin group than in the non-intervention group (3.8 vs. 5.7 days). An additional analysis was performed on the 2 control groups from which a shorter clinical healing time was found for placebo drops compared with no treatment; however, the difference was not statistically significant. The study was included in a meta-analysis with 3 previous studies comparing antibiotic therapy versus a control group with no antibiotic for the treatment of acute conjunctivitis in children aged 1 month to 18 years, with substantial confirmation of the already known results.

The efficacy of moxifloxacin-based triple-therapy in first-line treatment of Helicobacter pylori infection in Pakistan: randomized controlled trials

IntroductionThe challenge of eradicating &lt;i&gt;Helicobacter pylori&lt;/i&gt; through antibiotic treatment is still a significant concern due to the existence of antibiotic resistance. This study aimed to evaluate and compare the efficacy of sequential therapy based on levofloxacin versus triple therapy based on moxifloxacin in treating H. pylori infection in patients receiving first-line treatment.Material and methodsA total of 162 patients who were examined positive for &lt;i&gt;H. pylori&lt;/i&gt; were randomly assigned to either of 2 groups to receive the following: (a) levofloxacin 500mg BID, amoxicillin 1 g BID, and omeprazole 20 mg BID for the first 5 days, followed by levofloxacin 500 mg BID, tinidazole 500 mg BID, and omeprazole 20 mg BID (LAO-LTO group); or (b) moxifloxacin 400 mg OD, amoxicillin 1 g BID, and omeprazole 20 mg BID (MAO group) for 10 days.ResultsThe eradication rate of &lt;i&gt;H. pylori&lt;/i&gt; in the LAO-LTO group was 58.4% (45/77) and 76.3% (45/59), and in the MAO group it was 81.2% (69/85) and 92% (69/75), respectively, in ITT and PP analyses. Eradication rates of moxifloxacin-based triple therapies were significantly higher than those of levofloxacin-based regimens (p &lt; 0.001). The overall incidence of side effects and patient compliance was significantly lower in the moxifloxacin group (p &lt; 0.005) than in the levofloxacin group.ConclusionsMoxifloxacin-based triple therapy could be a significantly more effective first-line eradication treatment as compared to levofloxacin-based sequential therapy for &lt;i&gt;H. pylori&lt;/i&gt; infection in Pakistan.

Clinical and Microbiological Efficacy of Adjunctive Systemic Quinolones to Mechanical Therapy in Periodontitis: A Systematic Review of the Literature

Objectives To assess the clinical and microbiological efficacy of systemic quinolones adjunctive to mechanical therapy in periodontitis patients. Materials and Methods. A systematic review of the scientific literature was carried out. The search scheme comprised the Scopus, PubMed/MEDLINE, SCIELO (Scientific Electronic Library Online), and LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud) databases, together with the gray literature. MeSH terms and keywords were utilized to explore publications in all idioms. Only randomized clinical trials (RCTs) that met the selection criteria were included. Results A total of 4 RCTs were selected. These RCTs found superior clinical and microbiological efficacy of adjunctive systemic moxifloxacin (MOX) and levofloxacin (LV) compared to subgingival debridement plus placebo. Improvements in PD and CAL were 2.4 ± 0.8 mm and 2.7 ± 0.9 mm for LV, and 1.5 ± 0.5 mm and 1.8 ± 0.5 mm for MOX, respectively. After six months of follow-up, adjunctive MOX reduced the presence of Aggregatibacter actinomycetemcomitans to imperceptible levels, while LV markedly reduced this microorganism. Some adverse events were reported in the LV group and none in the MOX group. Conclusions Adjunctive MOX and LV improve probing depth and clinical attachment level compared with subgingival debridement alone in patients with periodontitis. The efficacy of these quinolones against A. actinomycetemcomitans was also superior.

Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials.

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (M. pneumoniae 71.2% [52/73]; L. pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

Postoperative endophthalmitis with and without intracameral moxifloxacin prophylaxis in a high volume surgery setting

ObjectiveThis study was conducted to understand the effects of intracameral moxifloxacin in decreasing the incidence of postoperative endophthalmitis after cataract surgery in an eye hospital with a high volume surgical...

Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis

BackgroundRifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis.MethodsIn an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months.ResultsAmong 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine–moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine–moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], −2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, −1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, −0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine–moxifloxacin group, and 14.3% in the rifapentine group.ConclusionsThe efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.)

Oral 5-Day Lefamulin for Outpatient Management of Community-Acquired Bacterial Pneumonia: Post-hoc Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 2 Trial.

Safe and effective oral antibiotics are needed for outpatient management of moderate to severe community-acquired bacterial pneumonia (CABP). We describe a post-hoc analysis of adults with CABP managed as outpatients from the Lefamulin Evaluation Against Pneumonia (LEAP) 2 double-blind, noninferiority, phase 3 clinical trial. LEAP 2 compared the efficacy and safety of oral lefamulin 600mg every 12h (5days) vs. oral moxifloxacin 400mg every 24h (7days) in adults (inpatients and outpatients) with Pneumonia Outcomes Research Team (PORT) risk classes II‒IV. Overall, 41% (151 of 368) of patients receiving lefamulin and 43% (159 of 368) of patients receiving moxifloxacin started treatment as outpatients-44% and 40%, respectively, were PORT risk class III/IV, and 21% in both groups had CURB-65 scores of 2‒3. Early clinical response (at 96±24h) and investigator assessment of clinical response success rates at test of cure (5‒10days after last study drug dose) were high and similar in both groups among all (lefamulin, 91% vs. moxifloxacin, 89‒90%), PORT risk class III/IV (89‒91% vs. 88‒91%), and CURB-65 score 2‒3 (87‒90% vs. 82‒88%) outpatients. Few outpatients (lefamulin, 2.6%; moxifloxacin, 2.5%) discontinued the study drug because of treatment-emergent adverse events (TEAEs). No outpatient in the lefamulin group was hospitalized for a TEAE, compared with 5 patients (3%), including two deaths, in the moxifloxacin group. These data suggest that 5days of oral lefamulin can be given in lieu of fluoroquinolones for outpatient treatment of adults with CABP and PORT risk class III/IV or CURB-65 scores of 2‒3.

A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia

Objectives To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). Patients and methods This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7–10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). Results A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. Conclusion Sitafloxacin 100 mg qd or 100 mg bid for 7–10 days is not inferior to moxifloxacin 400 mg qd for 7–10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

Treatment of Community-Acquired Pneumonia: A Focus on Lefamulin.

ObjectiveThe goal of this article is to review the clinical pharmacology, pharmacokinetics, efficacy, and safety of lemafulin. Data SourcesWe performed a systematic literature review using the search terms of lefamulin and BC-3781 in the PubMed and EMBASE databases. We also cross-referenced the pertinent articles and searched ClinicalTrials.gov to identify ongoing and nonpublished studies.Study Selection and Data ExtractionPublished data from 2005 to 2019 evaluating the clinical pharmacology, efficacy, and safety studies of lefamulin were analyzed. Data SynthesisIn phase 3 clinical trials, two multicenter, randomized double-blinded studies—Lefamulin Evaluation Against Pneumonia 1 and 2 (LEAP 1 and 2)—compared the efficacy and safety of lemafulin with moxifloxacin in patients diagnosed with community-acquired bacterial pneumonia (CABP). Lemafulin given in doses of 600 mg orally or 150 mg intravenously were reported to have comparable efficacy to those of moxifloxacin with or without linezolid in patients with CABP. After the trial, the lefamulin group had an early clinical response (ECR) of 87.3% and the moxifloxacin group had an ECR of 90.2%. The difference of − 2.9% in the ECR was non-significant (CI − 8.5, 2.8).Relevance to patients and clinical practiceLemafulin exhibits a unique binding property; therefore, it possess a potentially lower predisposition for the development of bacterial resistance and cross-resistance to other antimicrobial classes. Lefamulin is active against gram-positive including methicillin-resistant strains and atypical organisms which are often implicated in CABP.Lefamulin may be a safe alternative for adult patients with CABP who may not be candidates for respiratory fluoroquinolones.Lefamulin demonstrates both bactericidal and bacteriostatic activity against gram-positive, fastidious gram-negatives, atypical pathogens, and some gram-negative anaerobes. It is bactericidal in vitro against Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae (including macrolide-resistant strains) at concentrations of 0.06, 0.5, and 0.008 µg/ml respectively, and bacteriostatic against Staphylococcus aureus and Streptococcus pyogenes. The agent also demonstrates both time- and concentration-dependent killing against the pathogens S. pneumoniae and S. aureus.In vitro susceptibility testing demonstrated an MIC50/90 of 0.06/0.12 µg/ml against S. pneumoniae and S. aureus. The SENTRY Antimicrobial Surveillance Program found that at a concentration ≤ 1 µg/ml, lefamulin inhibited 100% S. pneumoniae isolates, 99.8% of S. aureus isolates, and 99.6% of methicillin-resistant S. aureus isolates. It was not affected by resistance to various antibiotic classes such as beta-lactams, fluoroquinolones, or macrolides.

SAFETY OF AMISELIMOD IN HEALTHY SUBJECTS: RESULTS FROM A PHASE 1 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Abstract Objective To evaluate the safety profile of amiselimod, a selective sphingosine 1-phosphate receptor modulator which has been shown to regulate lymphocyte trafficking and is in development for the treatment of inflammatory bowel disease. Methods A randomized, double-blind, multiple-dose, placebo-controlled, parallel study with a nested crossover design evaluated the safety and tolerability profile of amiselimod. Healthy adults were randomized in a 2:1:1 ratio during a 28-day treatment period accordingly: a single dose of placebo followed by oral amiselimod (upwardly titrated in doses ranging from 0.4 to 1.6 mg to achieve 0.4 mg and 0.8 mg steady-state exposure; a single dose of oral moxifloxacin 400 mg followed by placebo; or placebo followed by a single dose of moxifloxacin 400 mg. The safety population included all subjects who received at least one dose of treatment. Adverse events (AE) and serious AEs were collected. Treatment-emergent AEs were defined as an AE that was starting or worsening at the time of or after study drug administration. Changes in clinical laboratory parameters (including lymphocyte counts), physical examinations, vital signs, and electrocardiogram parameters (including heart rate, PR, QRS, and QT intervals) were recorded. Subjects were permitted to withdraw if lymphocyte counts were ≤ 0.2 x 109/L. Results The safety population included 190 subjects of which 95 received amiselimod and 95 were in the combined moxifloxacin group. Subjects were 40% female, 83% white, and the mean (standard deviation) age was 39.0 (8.8) years. The discontinuation rate was 8% (n=8) in the amiselimod group and 4% (n=4) in the moxifloxacin group. Three subjects who received amiselimod discontinued because they met the stopping criteria for low lymphocyte counts. One subject experienced an amiselimod-related serious AE of atrial fibrillation on day 26 (after receiving amiselimod 1.6 mg for 3 of the preceding 4 days) that required hospitalization, cardioversion, and led to discontinuation. No deaths were reported. All other AEs were mild to moderate in severity. Decreased white blood counts were the most commonly reported TEAE, followed by headache and constipation (Table). Reductions in white blood counts returned to normal range after study discontinuation without sequelae. Decreased neutrophils, lymphocytes and hemoglobin, and increased creatine kinase, alanine aminotransferase, and aspartate aminotransferase were reported, all of which resolved without sequelae. The mean absolute lymphocyte count for amiselimod exhibited a gradual decrease from predose (1.681 thou/uL) to a nadir of 0.424 thou/uL on day 27 (Figure). Changes to vital signs, physical examinations, and ECG parameters were within normal limits. Conclusions Upwardly titrated doses of amiselimod ranging from 0.4 to 1.6 mg were generally well tolerated in healthy subjects.

A Randomized, Double‐Blind, Placebo‐ and Positive‐Controlled, Three‐Way Crossover Study in Healthy Participants to Investigate the Effect of Savolitinib on the QTc Interval

Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, bioavailable, selective MET-tyrosine kinase inhibitor. This randomized, double-blind, 3-way, crossover phase 1 study of savolitinib versus moxifloxacin (positive control) and placebo-evaluated effects on the QT interval after a single savolitinib dose. Healthy non-Japanese men were randomized to 1 of 6 treatment sequences, receiving single doses of savolitinib 600 mg, moxifloxacin 400 mg, and placebo. The primary end point was time-matched, placebo-adjusted change from baseline in the QT interval corrected for the time between corresponding points on 2 consecutive R waves on electrocardiogram (RR) by the Fridericia formula (ΔΔQTcF). Secondary end points included 12-lead electrocardiogram (ECG) variables, pharmacokinetics, and safety. All 3 treatment periods were completed by 44 of 45 participants (98%). Baseline demographics were balanced across treatment groups. After a single savolitinib 600-mg dose, the highest least-squares mean ΔΔQTcF of 12 milliseconds was observed 5 hours postdose. Upper limits of the 2-sided 90% confidence interval for ΔΔQTcF exceeded 10 milliseconds (the prespecified International Council for Harmonisation limit) 3-6 hours postsavolitinib but otherwise remained less than the threshold. Savolitinib showed no additional effect on PR, QRS, QT, or RR intervals. A positive ΔΔQTcF signal from the moxifloxacin group confirmed study validity. Savolitinib was well tolerated, with a low incidence of adverse events. In this thorough QT/QTc study, QTcF prolongation was observed with a single savolitinib 600-mg dose. ECG monitoring will be implemented in ongoing and future studies of savolitinib to assess the clinical relevance of the observed QT changes from this study.

A New Treatment Experience in Pseudomonas Keratitis: Topical Meropenem and Cefepime.

To compare the efficacy of topical meropenem and cefepime treatments with respect to moxifloxacin as new treatment options in an experimental Pseudomonas keratitis model. Twenty-four rabbits in which keratitis are induced using Pseudomonas aeruginosa were divided into four groups according to treatment options. A solution of 50 mg/mL meropenem was prepared and topically applied to the first group, 50 mg/mL cefepime solution to the second group, topical 0.5% moxifloxacin drop to the third group, and topical isotonic (0.9% saline) solution to the fourth (control) group. The eyes were examined before and after treatment to score the clinical severity. After the subjects were sacrificed, their corneas were excised. To determine the efficacy of treatments, clinical score, bacterial load, and histopathological and immunohistochemical findings were evaluated. When the three treatment groups were compared, there was a significant difference in the colony-forming unit (CFU) value, polymorph-nuclear leukocyte (PMNL) infiltration, and matrix metalloproteinase (MMP)-9 immunoreactivity (P=0.022, P=0.038, and P=0.037, respectively). The CFU values, PMNL infiltration scores and MMP-9 immunoreactivity were significantly lower in the meropenem and moxifloxacin groups compared with the cefepime group (P<0.05 for all). There was no significant difference between the meropenem and moxifloxacin groups in respect of the CFU values, PMNL infiltration, and MMP-9 immunoreactivity (P=0.842, P=0.784, and P=0.699, respectively). The results of our study indicate that topical meropenem is at least as effective as topical moxifloxacin in the treatment of Pseudomonas keratitis. The meropenem and moxifloxacin are safer and suitable in the limited corneal invasion than cefepime. Thus, topical meropenem may be an alternative drug in the treatment of this condition. Clinical studies are needed to be conducted to assess this possibility more accurately.

A comparative randomized study to evaluate the effect of azithromycin 1.5% eyedrops versus moxifloxacin 0.5% eyedrops on bacterial conjunctivitis

Objective To evaluate the effect of azithromycin 1.5% eyedrops versus moxifloxacin 0.5% eyedrops on bacterial conjunctivitis. Background Purulent bacterial conjunctivitis affects all ages, with high frequency in newborns and children. This study evaluates the effect of azithromycin 1.5% eyedrops with moxifloxacin 0.5% eyedrops in treatment of bacterial conjunctivitis. Patients and methods A prospective comparative randomized controlled clinical trial was conducted that included 100 participants with purulent bacterial conjunctivitis at Menoufia outpatient clinic. Patients received either azithromycin 1.5% eyedrops twice daily for 7 days or moxifloxacin 0.5% eyedrops three times per day for 7 days. The primary variable was clinical cure at days 3 and 7 on the worst eye. The cure was defined as absence of purulent discharge and bulbar conjunctivitis. Results Overall, 88% of patients in the azithromycin group and 90% in the moxifloxacin group were clinically cured at D7. Clinical cure with azithromycin was not inferior to moxifloxacin at day 7, and discharge was absent in 92% of patients treated with azithromycin and 94% with moxifloxacin. Azithromycin and moxifloxacin were well tolerated. Conclusion Azithromycin 1.5% for 7 days was as effective as moxifloxacin for 7 days. Furthermore, patients on azithromycin presented clinical cure on day 3 as patients on moxifloxacin.

Effects on clinical outcomes of adjunctive moxifloxacin versus amoxicillin plus metronidazole in periodontitis patients harboring Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia: exploratory analyses from a clinical trial.

<p>Objective: Considering the etiopathogenesis of periodontitis, it is relevant to evaluate the efficacy of the adjunctive use of systemic antimicrobials based on microbial occurrence. This report explores whether patients harboring Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), or Tannerella forsythia (Tf) at baseline could receive greater clinical benefits from adjunctive moxifloxacin (MXF) and amoxicillin plus metronidazole (AM+MT) in comparison to patients without the presence of these microorganisms before therapy for generalized periodontitis. A control group was established that received subgingival debridement (SD) alone.<br /> Method and materials: Thirty-six patients younger than 30 years of age were randomly allocated to one of three treatment groups: SD plus placebo, systemic MXF with SD, or AM+MT combined with SD. Subgingival samples were studied. The effects of the therapies on probing depth and clinical attachment level, including interactions with Aa, Pg, or Tf at baseline, were explored using regression models.<br /> Results: At 6 months, all treatment groups showed improved clinical outcomes in patients harboring Aa, Pg, or Tf at baseline compared to the patients who did not harbor these microorganisms at baseline. Indeed, in the presence of Aa, Pg, or Tf at baseline, the patients receiving antimicrobial protocols showed the most significant gains compared to the control group. Furthermore, the percentage of sites ≥ 6 mm was reduced in the test groups, compared to the control group; these periodontopathogens were not present in sites with probing depth ≥ 6 mm in the MXF group. The interactions of Aa, Pg, and Tf with the test groups significantly improved clinical parameters at 6 months (P &lt; .001). Interestingly, the R2 value in the models that explored clinical attachment gain produced a high degree of correlation (&gt; 0.75), indicating that a high percentage (&gt; 75%) of the total variation in clinical attachment level gain can be explained by the independent variables.<br /> Conclusions: Although all patients benefited from the treatments, patients harboring Aa, Pg, or Tf at baseline showed improved clinical benefits at 6 months, suggesting that Aa, Pg, or Tf at baseline may change the effects of systemic MXF and AM+MT in generalized periodontitis. After 6 months, Aa, Pg, and Tf were not present in sites with probing depth ≥ 6 mm in the MXF group.</p>.

A comparative study of effect of fluoroquinolones on blood glucose levels in rats

Background: Fluoroquinolones (FQ) are frequently prescribed because of their broad-spectrum applicability in treatment of community acquired pneumonia and urinary tract infections. Increased use has raised some concerns regarding side effects like dysglycaemia, tendon rupture and QT interval prolongation. Gatifloxacin was banned in India in 2011 for causing fatal hypoglycemia. This study compares the effect of different fluoroquinolones on blood glucose levels in rats.Methods: 24 rats were divided into four study groups. Each group was administered one fluoroquinolone namely levofloxacin 9 mg, moxifloxacin 7.2 mg, ciprofloxacin 18 mg and ofloxacin 14.4 mg respectively for five days. The changes in blood glucose levels were observed for 10 days.Results: The mean blood glucose levels in all the four groups dropped below the baseline by day five. A statistically significant reduction in mean glucose levels was found in the moxifloxacin, ciprofloxacin and levofloxacin group. Among the rats that were given ofloxacin, the reduction in the mean blood glucose levels was not statistically significant. After stopping the drugs, the blood glucose levels in all the four groups returned near to the baseline within five days.Conclusions: The use of fluoroquinolones causes hypoglycemia in rats. The blood glucose level reduction associated with moxifloxacin was maximum, whereas ofloxacin appeared to have the minimum effect on blood glucose levels. These effects do not appear to be permanent and the dysglycaemia subsided after the drugs were stopped.