Moxifloxacin Group Research Articles

Efficacy of delafloxacin versus moxifloxacin against atypical bacterial respiratory pathogens in adults with community-acquired bacterial pneumonia (CABP): Data from the Delafloxacin Phase 3 CABP Trial

ObjectivesTo report atypical pathogens from clinical trial data comparing delafloxacin to moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP). MethodsMultiple diagnostic methods were employed to diagnose atypical infections including culture, serology, and urinary antigen. ResultsThe microbiological intent-to-treat (MITT) population included 520 patients; 30% had an atypical bacterial pathogen identified (156/520). Overall, 13.1% (68/520) had a monomicrobial atypical infection and 2.3% (12/520) had polymicrobial all-atypical infections. Among patients with polymicrobial infections, Streptococcus pneumoniae was the most frequently occurring co-infecting organism and Chlamydia pneumoniae was the most frequently occurring co-infecting atypical organism. For Mycoplasma pneumoniae and Legionella pneumophila, serology yielded the highest number of diagnoses. Delafloxacin and moxifloxacin had similar in vitro activity against M. pneumoniae and delafloxacin had greater activity against L. pneumophila. Two macrolide-resistant M. pneumoniae isolates were recovered. No fluoroquinolone-resistant M. pneumoniae were isolated. The rates of microbiological success (documented or presumed eradication) at test-of-cure were similar between the delafloxacin and moxifloxacin groups. There was no evidence of a correlation between minimum inhibitory concentration (MIC) and outcome; a high proportion of favorable outcomes was observed across all delafloxacin baseline MICs. ConclusionsDelafloxacin may be considered a treatment option as monotherapy for CABP in adults, where broad-spectrum coverage including atypical activity is desirable.

Evaluation of the Effect of Contezolid (MRX-I) on the Corrected QT Interval in a Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study in Healthy Chinese Volunteers.

Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1,600 mg) dose, placebo, and oral moxifloxacin at 400 mg in four separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (ΔΔQTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for ΔΔQTc was slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 h postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin, at 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 by having a lower confidence bound of ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and ΔQTcF interval with a slope of 0.227 ms per mg/liter (90% CI, 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

Comparative study of meibomian gland dysfunction and dry eye in post-cataract surgery patients treated with topical dexamethasone-moxifloxacin versus topical prednisolone-moxifloxacin combination eye drops

Postoperative dry eye and meibomian gland dysfunction (MGD) is common cause of morbidity. Its cause is still elusive and probably multifactorial. Various studies in the past have thrown some light on its mechanism but still we are not able to prevent its occurrence. Till date no study has analyzed the role of topical steroid as one of the factors influencing postoperative MGD and dry eye. The aim of this study was to compare the symptoms and signs of MGD and dry eye in post-cataract surgery patients treated with topical dexamethasone-moxifloxacin versus topical prednisolone-moxifloxacin combination eye drops. Seventy eyes of seventy patients of senile cataract who had no dry eye signs preoperatively, and had undergone uncomplicated phacoemulsification surgery were selected. The patients were divided randomly into two study groups – Group 1 patients were started on dexamethasone sodium phosphate -moxifloxacin hydrochloride and Group 2 patients were started on prednisolone acetate – moxifloxacin hydrochloride combination eye drops postoperatively in a tapering dose for 6 weeks. The data collected by scoring of clinical dry eye signs (corneal staining, TBUT, Schirmer test I and meibomian gland dysfunction assessed by meibum expressibility and meibum quality score) and symptoms scoring by SPEED II questionnaire. The study was done in both the groups preoperatively and at 1 week, 4 weeks and 8 weeks postoperatively. Both the groups were compared using independent paired t- test and Mann – Whitney test. The mean values of SPEED II, TBUT, corneal staining, meibomian gland expressibility, meibum quality were statistically significantly higher in all followup visits (at 1week, 4 weeks, and 8 weeks) in group 2 as compared to group 1.(p&amp;#60;.001). Post cataract surgery patients treated with dexamethasone – moxifloxacin eye drops had statistically significantly lesser symptoms and signs of dry eye and MGD as compared to patients treated with prednisolone-moxifloxacin combination eye drops.

A Phase 3 Study to Compare Delafloxacin With Moxifloxacin for the Treatment of Adults With Community-Acquired Bacterial Pneumonia (DEFINE-CABP).

BackgroundThe clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin’s shape and charge profile uniquely impact its spectrum of activity and side effect profile. This phase 3 study compared the efficacy and safety of delafloxacin with moxifloxacin for the treatment of CABP.MethodsA randomized, double-blind, comparator-controlled, multicenter, global phase 3 study compared the efficacy and safety of delafloxacin 300 mg twice daily or moxifloxacin 400 mg once daily in adults with CABP. The primary end point was early clinical response (ECR), defined as improvement at 96 (±24) hours after the first dose of study drug. Clinical response at test of cure (TOC) and microbiologic response were also assessed.ResultsIn the intent-to-treat analysis population (ITT), ECR rates were 88.9% in the delafloxacin group and 89.0% in the moxifloxacin group. Noninferiority of delafloxacin compared with moxifloxacin was demonstrated. At TOC in the ITT population, the success rates were similar between groups. Treatment-emergent adverse events that were considered at least possibly related to the study drug occurred in 65 subjects (15.2%) in the delafloxacin group and 54 (12.6%) in the moxifloxacin group.ConclusionsIntravenous/oral delafloxacin monotherapy is effective and well tolerated in the treatment of adults with CABP, providing coverage for Gram-positive, Gram-negative, and atypical pathogens.ClinicalTrials.gov IdentifierNCT03534622.

2233. Efficacy and Symptom Resolution by Visit in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results

BackgroundEfficacy and safety of LEF were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the efficacy of LEF by visit based on a pooled analyses of LEAP 1/2 data.MethodsIn LEAP 1, PORT III–V patients (patients) received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400 mg q24h for 7 days. Criteria for defining the FDA primary endpoint of early clinical response (ECR) at 96 ± 24 hours after first dose were applied to each visit through late follow-up (LFU; days 27–34) in the intent-to-treat (ITT; all randomized patients) population. Investigator assessment of clinical response (IACR) was examined at end of treatment (EOT; within 2 days after last dose), test-of-cure (TOC; 5–10 days after last dose; EMA primary endpoint), and LFU in the modified ITT (mITT; received ≥1 dose of study drug) and clinically evaluable (CE; met predefined evaluability criteria) populations. Results are presented by visit for pooled LEAP 1/2 data.Results1289 ITT patients were randomized (LEF, n = 646; MOX, n = 643). Most patients in both groups achieved ECR at Day 3, with further increases through Day 7 and sustained efficacy through LFU (Fig 1). In mITT patients, IACR success rates at EOT/TOC/LFU were 87.1/85.0/83.2% with LEF and 88.1/87.1/86.1% with MOX; results were consistent in CE patients. The proportions of ITT patients with resolution of all baseline signs/symptoms of CABP increased similarly by visit in both treatment groups (Fig 2). Most patients did not achieve complete sign/symptom resolution until TOC, with fever generally being the first and cough the last to resolve. There was no apparent relationship between ECR and age, gender, renal status, SIRS, PORT, prior antibiotic use, baseline pathogens, typical/atypical pathogens, or mono/polymicrobial pathogens. The high percentage of patients at LFU with baseline symptom resolution suggests that symptom resolution was sustained.ConclusionIn this pooled analysis, efficacy results were similar by visit in the LEF and MOX groups, with high ECR rates maintained through LFU. LEF will provide a potential new effective systemic monotherapy alternative to fluoroquinolones for the empiric treatment of CABP. Disclosures All authors: No reported disclosures.

2245. Oral 5-Day Lefamulin for Outpatient Management of Pneumonia Outcomes Research Team (PORT) Risk Class III/IV Community-Acquired Bacterial Pneumonia (CABP): Post Hoc Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 2 Phase 3 Study

BackgroundSite-of-care decisions (e.g., admission vs. outpatient) in CABP management can be challenging for healthcare providers. Here we describe a post hoc analysis of adults with CABP managed as outpatients in the LEAP 2 double-blind, noninferiority, Phase 3 trial.MethodsLEAP 2 compared the efficacy and safety of oral lefamulin (LEF) 600 mg every 12 hours for 5 days vs. oral moxifloxacin (MOX) 400 mg every 24 hours for 7 days in adults with PORT Risk Class II-IV. Descriptive statistics were generated to characterize demographics, baseline characteristics, efficacy, and safety outcomes in the subpopulation of outpatients in LEAP 2.ResultsOverall, 42% (310/736) of patients started treatment as outpatients (41% [151/368] LEF and 43% [159/368] MOX). Age, gender, and BMI were generally similar in both treatment groups. 44% (66/151) LEF and 40% (64/159) MOX outpatients had PORT Risk Class III or IV, and 21% in both groups (31/151 LEF and 34/159 MOX) had CURB-65 score 2 or 3. Comorbidities included smoking history (43% LEF vs. 34% MOX), hypertension (26% vs. 30%), COPD/asthma (14% vs. 18%), and diabetes mellitus (7% vs. 11%). Early clinical response (ECR) responder rates and investigator’s assessment of clinical response (IACR) success rates at the test of cure (TOC) visit were high and similar in both groups among all, PORT Risk Class III/IV, and CURB-65 score 2 or 3 outpatients (Table 1). In the PORT Risk Class III/IV subset, 86% LEF vs. 80% MOX patients were both an ECR responder and IACR success at TOC. In the CURB-65 score 2 or 3 subset, 87% LEF vs. 74% MOX patients were both an ECR responder and IACR success at TOC. Treatment-emergent adverse event (TEAE) rates were similar in both groups (Table 2). Consistent with overall study results, the difference between groups in related TEAEs was driven by gastrointestinal disorders (20% LEF vs. 5% MOX), specifically diarrhea (15% vs. 1%). Rates of TEAEs leading to discontinuation were low and similar in both groups. No LEF outpatient had an SAE or was admitted during the study, compared with 5 (3%) SAEs, including 2 deaths, in the MOX group.ConclusionThese study data suggest that PORT Risk Class III or IV patients can be effectively managed as outpatients with 5 days of oral LEF as an alternative to fluoroquinolones for the treatment of CABP. Disclosures All authors: No reported disclosures.

Moxifloxacin and Sitafloxacin Treatment Failure in Mycoplasma genitalium Infection: Association with parC Mutation G248T (S83I) and Concurrent gyrA Mutations.

The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

EFFICACY AND SAFETY OF LEFAMULIN VS MOXIFLOXACIN FOR ATYPICAL RESPIRATORY PATHOGENS IN ADULTS WITH COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA: POOLED RESULTS FROM THE LEFAMULIN EVALUATION AGAINST PNEUMONIA (LEAP) 1 AND LEAP 2 DOUBLE-BLIND NONINFERIORITY PHASE-3 CLINICAL TRIALS

SESSION TITLE: Tuesday Electronic Posters 1 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: Efficacy/safety of lefamulin (LEF), a first-in-class systemic pleuromutilin developed for IV/oral treatment of community-acquired bacterial pneumonia (CABP), was shown in 2 noninferiority phase 3 trials (LEAP 1, LEAP 2). We report LEF efficacy/safety in patients (pts) with atypical respiratory pathogens in pooled LEAP 1/LEAP 2 analyses. METHODS: In LEAP 1, adults with CABP (PORT III–V) received LEF 150mg IV q12h for 5–7d or moxifloxacin (MOX) 400mg IV q24h for 7d, with an optional oral switch (600mg LEF q12h or 400mg MOX q24h). In LEAP 2, adults with CABP (PORT II–IV) received oral LEF for 5d or oral MOX for 7d. Primary endpoints were early clinical response (ECR) at 96±24h after first dose in the intent-to-treat population (ITT, all randomized pts) for the US Food and Drug Administration and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10d after last dose) in the modified ITT (mITT) (received ≥1 dose) and clinically evaluable (met predefined criteria) populations for the European Medicines Agency. Mycoplasma pneumoniae [MP], Legionella pneumophila [LP], and Chlamydophila pneumoniae [CP] were identified at baseline (BL) from pt samples by culture, serology, urinary antigen testing, and real-time PCR. MP and LP isolates were tested for LEF susceptibility by broth microdilution. Analyses herein were done in the microbiologic ITT population (microITT, pts with BL CABP-causing pathogen who received ≥1 dose). RESULTS: In the pooled microITT population (N=709), atypical pathogens were identified in 25.0% (91/364) of LEF-treated pts (PORT II n=26 [28.6%], III n=49 [53.8%], IV n=16 [17.6%]) and 25.2% (87/345) of MOX-treated pts (PORT II n=21 [24.1%], III n=44 [50.6%], IV n=22 [25.3%]). PORT in this subgroup was similar to the overall ITT population (PORT I/II n=376 [29.2%], III n=675 [52.4%], IV/V n=238 [18.5%]). Of pts with MP, LP, and CP, most (71.2% [52/73], 96.9% [63/65], and 79.3% [46/58], respectively) were identified by ≥1 standard diagnostic modality. All 17 cultured MP isolates were susceptible to LEF (MIC50/90=≤0.001/≤0.001μg/mL); the 2 LP isolates were inhibited by 0.5–1μg/mL LEF. In the microITT population, ECR (LEF 85.3%–92.6%, MOX 90.3%–96.8%) and IACR at TOC (LEF 74.1%–89.7%, MOX 74.2%–97.1%) rates in pts with atypical pathogens were high, similar between arms, and consistent with overall pooled results (ECR: LEF 89.3%, MOX 93.0%; IACR: LEF 83.2%; MOX 86.7%). Rates of pts with atypical pathogens with ≥1 treatment-emergent adverse event were 53.8% (49/91) and 66.7% (58/87) in the LEF and MOX groups, respectively. CONCLUSIONS: Short-course LEF therapy (5–7d) for BL atypical pathogens resulted in high ECR responder and IACR success rates in the microITT population and was generally well tolerated. CLINICAL IMPLICATIONS: If approved, LEF may provide a new IV and oral monotherapy alternative to fluoroquinolones and macrolides in pts infected with atypical pathogens. DISCLOSURES: Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/15/2019 by Elizabeth Alexander, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $20001 - $100000 Added 03/15/2019 by Elizabeth Alexander, source=Web Response, value=stock options Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Steven Gelone, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Steven Gelone, source=Web Response, value=Ownership interest Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Lisa Goldberg, source=Web Response, value=Stock Removed 03/14/2019 by Lisa Goldberg, source=Web Response Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/14/2019 by Lisa Goldberg, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $20001 - $100000 Added 03/14/2019 by Lisa Goldberg, source=Web Response, value=Stock Grant relationship with Contrafect Please note: $20001 - $100000 Added 03/14/2019 by Gregory Moran, source=Web Response, value=Grant/Research Support Consultant relationship with Allergan Please note: $5001 - $20000 Added 03/14/2019 by Gregory Moran, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Nabriva Please note: $1001 - $5000 Added 03/14/2019 by Gregory Moran, source=Web Response, value=Honoraria Employee relationship with Nabriva Therapeutics Please note: $5001 - $20000 Added 03/15/2019 by Susanne Paukner, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: $5001 - $20000 Added 03/15/2019 by Susanne Paukner, source=Web Response, value=Stocks and stock options Speaker/Speaker's Bureau relationship with Allergan Please note: $20001 - $100000 Added 03/14/2019 by Christian Sandrock, source=Web Response, value=Honoraria Advisory Committee Member relationship with Nabriva Please note: $1001 - $5000 Added 03/14/2019 by Christian Sandrock, source=Web Response, value=Honoraria Employee relationship with UC Davis Please note: >$100000 Added 03/14/2019 by Christian Sandrock, source=Web Response, value=Salary Employee relationship with Nabriva Therapeutics Please note: >$100000 Added 03/07/2019 by Jennifer Schranz, source=Web Response, value=Salary Consultant relationship with Nabriva Please note: $5001 - $20000 Added 03/15/2019 by Andrew Shorr, source=Web Response, value=Consulting fee

Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia

New antibacterials are needed to treat community-acquired bacterial pneumonia (CABP) because of growing antibacterial resistance and safety concerns with standard care. To evaluate the efficacy and adverse events of a 5-day oral lefamulin regimen in patients with CABP. A phase 3, noninferiority randomized clinical trial conducted at 99 sites in 19 countries that included adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 or more CABP symptoms; and 2 or more vital sign abnormalities. The first patient visit was on August 30, 2016, and patients were followed up for 30 days; the final follow-up visit was on January 2, 2018. Patients were randomized 1:1 to receive oral lefamulin (600 mg every 12 hours for 5 days; n = 370) or moxifloxacin (400 mg every 24 hours for 7 days; n = 368). The US Food and Drug Administration (FDA) primary end point was early clinical response at 96 hours (within a 24-hour window) after the first dose of either study drug in the intent-to-treat (ITT) population (all randomized patients). Responders were defined as alive, showing improvement in 2 or more of the 4 CABP symptoms, having no worsening of any CABP symptoms, and not receiving any nonstudy antibacterial drug for current CABP episode. The European Medicines Agency coprimary end points (FDA secondary end points) were investigator assessment of clinical response at test of cure (5-10 days after last dose) in the modified ITT population and in the clinically evaluable population. The noninferiority margin was 10% for early clinical response and investigator assessment of clinical response. Among 738 randomized patients (mean age, 57.5 years; 351 women [47.6%]; 360 had a PORT risk class of III or IV [48.8%]), 707 (95.8%) completed the trial. Early clinical response rates were 90.8% with lefamulin and 90.8% with moxifloxacin (difference, 0.1% [1-sided 97.5% CI, -4.4% to ∞]). Rates of investigator assessment of clinical response success were 87.5% with lefamulin and 89.1% with moxifloxacin in the modified ITT population (difference, -1.6% [1-sided 97.5% CI, -6.3% to ∞]) and 89.7% and 93.6%, respectively, in the clinically evaluable population (difference, -3.9% [1-sided 97.5% CI, -8.2% to ∞]) at test of cure. The most frequently reported treatment-emergent adverse events were gastrointestinal (diarrhea: 45/368 [12.2%] in lefamulin group and 4/368 [1.1%] in moxifloxacin group; nausea: 19/368 [5.2%] in lefamulin group and 7/368 [1.9%] in moxifloxacin group). Among patients with CABP, 5-day oral lefamulin was noninferior to 7-day oral moxifloxacin with respect to early clinical response at 96 hours after first dose. ClinicalTrials.gov Identifier: NCT02813694; European Clinical Trials Identifier: 2015-004782-92.

Moxifloxacin suppresses airway inflammation and modulates expression of caveolin-1 and flotillin-1 in airway smooth muscle cells of asthmatic rats.

Moxifloxacin (MXF) possesses anti-inflammatory properties on asthmatic airway smooth muscle cells (ASMCs) beyond their antimicrobial effects, but the mechanisms are still unknown. This study was to investigate effects of MXF on expression of caveolin-1 (Cav-1) and flotillin-1 (FLOT1) in ASMCs in asthmatic rats. ASMCs were collected from the airway and cultured in vitro. Cells from normal rats were treated with normal saline (Group N); cells from asthmatic rats were incubated with normal saline (Group A) or MXF (20 mg/L) (Group M); Cav-1 expression was up-regulated by transferring Cav-1 expressing lentivirus (Group L) and FLOT1 expression down-regulated by using siRNA in cells from asthmatic rats (Group S). The expressions of Cav-1, FLOT1 and p65 NF-κB were measured by Western blotting and quantificational real-time polymerase chain reaction (qRT-PCR), and interleukin-8 (IL-8) and eotaxin contents were measured by enzyme-linked immunosorbent assay (ELISA). Compared with normal control, Cav-1 expression significantly decreased in asthmatic groups (P<0.01); MXF up-regulated Cav-1 expression in asthmatic groups (P<0.01). However, compared with normal control, the expression of FLOT1 and p65 NF-κB dramatically increased in asthmatic groups (P<0.01); MXF down-regulated the expression of FLOT1 and p65 NF-κB in asthmatic groups (P<0.01); meanwhile, the expressions of FLOT1 and p65 NF-κB decreased after up-regulation of Cav-1 expression in asthmatic groups (P=0.01). Compared with asthmatic groups, the IL-8 and eotaxin contents significantly decreased in MXF Groups, Cav-1 up-regulation asthmatic groups and FLOT1 down-regulation asthmatic groups (P<0.01). MXF can modulate the airway inflammation, upregulate Cav-1 expression, downregulate the expression of FLOT1 and p65 NF-κB in asthmatic rat ASMCs, which may be related to the anti-inflammatory effects of MXF in asthmatic ASMCs.

Study on the drug–drug interaction of antituberculosis drugs — PA-824 and moxifloxacin based on pharmacokinetics in rats by LC–MS/MS

A simple, rapid, and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous quantitation of PA-824 and moxifloxacin in rat plasma using carbamazepine as an internal standard (IS). The sample preparation involved a one-step protein precipitation method with methanol. The separation was performed on Inertsil® ODS3 C18 column (150 mm × 4.6 mm, 5 μm) and maintained at 30 °C. The mobile phase consisted of 0.1% formic acid in acetonitrile–water (90:10 v/v) with fast isocratic elution at a flow rate of 0.6 mL/min and a run time of 10 min. A mass spectrometer was run in the positive ion electrospray ionization (ESI) mode using multiple reaction monitoring (MRM) to monitor the mass transitions. The MRM transitions were chosen to be m/z 360.1 → m/z 175.0 for PA-824, m/z 402.0 → m/z 383.9 for moxifloxacin, and m/z 237.1 → m/z 194.0 for IS. The method was fully validated in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery, and stability, respectively. The method was successfully applied to drug–drug interaction (DDI) study of PA-824 and moxifloxacin in rats. The results show that the main pharmacokinetic parameters of PA-824, namely, Tmax, t1/2, and AUC(0–t), increased more in the PA-824 and moxifloxacin group than in the PA-824 group. However, there were little changes in the main pharmacokinetic parameters of moxifloxacin from single and combined groups.

ADMINISTRATION OF SYSTEMIC PROPOLIS VERSUS MOXIFLOXACIN AS ADJUNCTIVE TREATMENT OF SEVERE GENERALIZED PERIODONTITIS

To-date, emerging bacterial resistance to the commonly prescribed antibiotics in the management of periodontitis has become a challenging problem making scientists continually seek for new agents. In the present study, propolis (PRO) (natural bee glue) and moxifloxacin (MXF) (new quinolone antibiotic) were evaluated in the treatment of severe generalized periodontitis (gP) as adjuncts to scaling and root planing (SRP). Fifty four subjects with severe gP were randomly assigned into three groups (3 subjects did not complete the study after participation). Group I in which SRP alone was performed to gP patients (SRP group; n=17); group II in which SRP was done to gP patients combined with orally administered propolis 400 mg once daily for 7 days (PRO group; n=16); and group III in which SRP was performed to gP patients combined with oral moxifloxacin 400 mg once daily for 7 days (MXF group; n=18). Pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), plaque (PI) and gingival (GI) indices were recorded at baseline, after 6 and 12 weeks of SRP. Salivary interleukin-1 beta (IL-1β) was evaluated at the same time points for all groups. All three procedures led to significant reductions in PD, CAL, BOP, PI and GI after 6 and 12 weeks. PD reduction and CAL gain were significantly greater in the PRO and MXF groups compared to SRP group at 6 and 12 weeks after therapy (p 0.05). Likewise, in PRO and MXF groups, the salivary inflammatory marker (IL-1β) was significantly reduced in comparison to SRP group (p < 0.01). In all groups, salivary IL-1β levels were decreased at 6 and 12 weeks compared to baseline values. It was concluded that the adjunctive use of PRO and MXF to SRP had significantly improved the treatment outcomes in subjects with severe gP comparable to SRP alone. Thus, PRO and MXF showed promising results in the treatment of periodontal disease. KEYWORDS Propolis, Moxifloxacin, Adjunctive treatment, Periodontitis.

A Moxifloxacin-based Regimen for the Treatment of Recurrent, Drug-sensitive Pulmonary Tuberculosis: An Open-label, Randomized, Controlled Trial.

The substitution of moxifloxacin for ethambutol produced promising results for improved tuberculosis treatment outcomes. We conducted an open-label, randomized trial to test whether a moxifloxacin-containing treatment regimen was superior to the standard regimen for the treatment of recurrent tuberculosis. The primary and secondary outcomes were the sputum culture conversion rate at the end of 8 weeks and the proportion of participants with a favorable outcome, respectively. We enrolled 196 participants; 69.9% were male and 70.4% were co-infected with human immunodeficiency virus (HIV). There was no significant difference between the study groups in the proportion of patients achieving culture conversion at the end of 8 weeks (83.0% [moxifloxacin] vs 78.5% [control]; P = .463); however, the median time to culture conversion was significantly shorter (6.0 weeks, interquartile range [IQR] 4.0-8.3) in the moxifloxacin group than the control group (7.9 weeks, IQR 4.0- 11.4; P = .018). A favorable end-of-treatment outcome was reported in 86 participants (87.8%) in the moxifloxacin group and 93 participants (94.9%) in the control group, for an adjusted absolute risk difference of -5.5 (95% confidence interval -13.8 to 2.8; P = .193) percentage points. There were significantly higher proportions of participants with Grade 3 or 4 adverse events (43.9% [43/98] vs 25.5% [25/98]; P = .01) and serious adverse events (27.6% [27/98] vs 12.2% [12/98]; P = .012) in the moxifloxacin group. The replacement of ethambutol with moxifloxacin did not significantly improve either culture conversion rates at the end of 8 weeks or treatment success, and was associated with a higher incidence of adverse events. NCT02114684.

Omadacycline for Community-Acquired Bacterial Pneumonia

BackgroundOmadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia.MethodsIn a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used.ResultsThe intention-to-treat population included 386 patients in the omadacycline group and 388 patients in the moxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, −1.6 percentage points; 95% confidence interval [CI], −7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, −2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial.ConclusionsOmadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438.)

Safety and efficacy of intracameral moxifloxacin for prevention of post-cataract endophthalmitis: Randomized controlled clinical trial

To evaluate the safety and efficacy of intracameral (IC)0.5% moxifloxacin in the prevention of post-cataract endophthalmitis. University of Campinas, São Paulo, Brazil. Prospective randomized partially masked single-site clinical trial. Patients who had phacoemulsification were randomized into two groups in block sizes of 4. Group A (moxifloxacin group) consisted of patients who received an IC injection of0.03mL (150μg) of undiluted 0.5% moxifloxacin at the end of surgery. Group B (control group) consisted of patients who received no IC medication. The postoperative prescription for both groups consisted of 0.5% moxifloxacin and 0.1% dexamethasone. Patients were monitored for 6weeks after surgery. The primary outcome was the incidence of acute endophthalmitis in each group. Secondary outcomes were corrected distance visual acuity (CDVA), endothelial cell density (ECD), intraocular pressure (IOP), and central corneal thickness (CCT). The study comprised 3640 eyes from 3640 patients. There were 1818 patients in Group A and 1822 patients in Group B. The incidence of endophthalmitis within 6weeks of follow-up was 1 (0.05%) of 1818 eyes in the moxifloxacin group and 7 (0.38%) of 1822 eyes in the control group (P=.035). There was no significant difference in CDVA (P=.202), ECD (P=.482), IOP (P=.105), or CCT (P=.558). No ocular or systemic study-related adverse events were observed. The IC injection of undiluted 0.5% moxifloxacin can be safely applied as the last step of phacoemulsification. It was found to be effective in reducing the risk for endophthalmitis. This study represents the first controlled randomized clinical trial to evaluate the safety and efficacy of IC moxifloxacin in the prevention of post-cataract endophthalmitis.

Effects of topical azithromycin, moxifloxacin, and povidone iodine on conjunctival bacterial flora in patients undergoing intravitreal injection.

To compare effects of 5% topical povidone iodine with prophylactic topical azithromycin and moxifloxacin on bacterial flora in patients undergoing intravitreal injection. A total of 132 patients were randomly assigned to receive treatment with azithromycin or moxifloxacin, or no treatment (control group). In total, 528 specimens were obtained at the time of admission, 4 days before intravitreal injection, 4 days after intravitreal injection, and 8 days after intravitreal injection. Samples were immediately sent to the microbiology laboratory for incubation. The microorganism observed most frequently was coagulasenegative Staphylococcus (23.8%). When the results of samples obtained on Day 4 before injection were assessed, growth of coagulase-negative Staphylococcus was significantly lower in the moxifloxacin group, compared with controls (p=0.049). Acinetobacter baumannii continued to grow after administration of azithromycin (p=0.033). When the results of four days after intravitreal injection were evaluated, growth of coagulase-ne gative Staphylococcus was higher in controls, compared with patients who received azithromycin or moxifloxacin (p=0.004). Eradication rate was significantly higher in the moxifloxacin group than in the control group (p=0.001). Samples obtained on Day 8 after intravitreal injection showed similar levels of bacterial growth in all groups (p=0.217). Moxifloxacin was more effective than 5% povidone iodine in controlling the growth of conjunctival bacterial flora. Use of moxifloxacin in combination with 5% povidone iodine resulted in a synergistic effect.

Comparative study of efficacy and safety of garenoxacin and moxifloxacin in acute exacerbation of chronic bronchitis in COPD patients

Background: Acute exacerbation of chronic bronchitis in COPD (AECB) is the major cause of morbidity, mortality and marked reduction in quality of life and imposes significant burden on both patients and healthcare systems. Bacterial infections causing AECB frequently require antibacterial treatment, so more evidences are needed to guide better antibiotic choice. Objective of the study was planned to compare efficacy and safety of Garenoxacin, a new fluoroquinolone versus moxifloxacin for treatment of Acute exacerbation of Chronic bronchitis in COPD patient.Methods: This was a prospective open label comparative study done in department of pharmacology and T.B &amp; Chest of Government Medical College attached Dr Shusila Tiwari Hospital, Haldwani. 60 subjects with clinical symptoms suggestive of Anthonisen type II AECOPD (any two of following criteria: Increased dyspnea, cough, sputum purulence) were enrolled and randomized to receive either Moxifloxacin 400 mg once daily for 7 days or Garenoxacin 400mg once daily for 7 days. The primary outcome measure was clinical success rate at day 7 visit. Secondary outcome measures were changes in clinical global impression (CGI) scales and incidence of adverse events.Results: The mean age of patient was 60.98±9.9 years and 57.9±9.3 years in the Moxifloxacin and Garenoxacin groups. The clinical success rates were comparable with 86.2% in moxifloxacin group 84.6% and in garenoxacin group. Adverse effects were mild and self limiting. We observed two adverse effects in garenoxacin and three in moxifloxacin group.Conclusions: The result of study showed that garenoxacin is comparable to moxifloxacin in terms of efficacy and safety.

Moxifloxacin versus levofloxacin for antibacterial prophylaxis in acute leukemia patients.

The primary endpoint of this study was to determine the incidence of febrile neutropenia among patients receiving either moxifloxacin or levofloxacin for antibacterial prophylaxis. Secondary endpoints were number of documented infections and in-hospital mortality in patients who develop febrile neutropenia. A single-center retrospective cohort analysis at a large tertiary care academic medical center was conducted. This study included adult acute leukemia patients (age ≥18 years old) who received inpatient antibacterial prophylaxis (moxifloxacin or levofloxacin) from 1 July 2012 to 1 October 2014. Patients were excluded from the study if they were treated with antimicrobial therapy in the preceding five days or admitted to the hospital with neutropenic fever. Fisher's exact test was used for categorical data and Mann-Whitney test for continuous data. Logistic regression analysis was used to determine risk factors for febrile neutropenia. Eighty-five patients were included in the final analysis with 40 patients who received moxifloxacin and 45 patients who received levofloxacin. Baseline characteristics were similar between the two groups. Twenty-two patients experienced febrile neutropenia requiring intravenous antibiotics in the moxifloxacin group and 30 patients in the levofloxacin group (P = 0.190). Age and duration of neutropenia appeared to predict for febrile neutropenia; however, after multivariate analysis, longer duration of neutropenia was shown to be the best predictor for febrile neutropenia with an odds ratio of 4.69 (95% CI, 1.697-12.968). Both groups had similar rates of documented infections and in-hospital morality. Moxifloxacin and levofloxacin showed similar rates of febrile neutropenia when used for neutropenic antibacterial prophylaxis in acute leukemia patients.

Effect of moxifloxacin on oxidative stress, paraoxonase-1 (PON1) activity and efficacy of treatment in patients with multiple drug-resistant tuberculosis

Purpose: To investigate the effect of moxifloxacin on paraoxonase-1 (PON1) activity, and serum oxidative stress in patients with multiple drug-resistant tuberculosis (MDR-TB).Methods: A total ofof 130 MDR-TB patients who were treated with moxifloxacin from October 2014 to October 2010 in Eastern Medical District of Linyi People's Hospital of Shandong Province, China were randomly divided into an observation group (65 cases, moxifloxacin group) and control group (65 cases, non-moxifloxacin group). Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), PON1 levels and treatment efficacy for groups were determined.Results: Compared with pre-treatment levels, TOS (23.3 ± 4.7 vs 13.9 ± 3.3 umol H2O2 Eq/L, t = 13.20, p = 0.00) and OSI (17.4 ± 4.8 vs 5.7 ± 1.4 U, t = 18.87, p = 0.00) of the observation group significantly decreased, while TAS (1.4 ± 0.5 vs 3.5 ± 0.7 umol Trolox Eq/L, t = 19.68, p = 0.00) and PON1 (15.5 ± 6.9 vs 31.1 ± 8.3 U/L, t = 11.65, p = 0.00) significantly increased. TOS (23.3 ± 4.7 vs 13.9 ± 3.3 umol H2O2 Eq/L, t = 7.73, p &lt; 0.05) and OSI (16.9 ± 5.5 vs 7.4 ± 3.2U, t = 12.04, p = 0.05) reduced significantly in the control group. Moxifloxacin correlated positively with △TAS (r = 0.697, p = 0. 04) and △PON1 (r = 0.785, p = 0.01), but correlation with △TOS (r = -0.625, p = 0.01) was negative. Efficacy was significantly higher in the observation group than that in the control group (81.54 % vs 56.92 %, p =0.00).Conclusion: Oxidative stress injury in MDR-TB patients may be effectively managed by combination of moxifloxacin with anti-TB treatmentKeywords: Multiple drug-resistant TB, Moxifloxacin, Paraoxonase, Oxidative stress

Systemic Moxifloxacin in Streptococcus viridans Endophthalmitis

ABSTRACTPurpose: To evaluate the effectiveness of prophylactic systemic moxifloxacin in a rabbit model of Streptococcus viridans (S. viridans) endophthalmitis.Methods: Animals (n=60) were divided into three groups. Intravenous moxifloxacin, vancomycin, normal saline was administered to 20 animals in each group and two hours later, 104 colony-forming units (CFU) of S. salivarius were intravitreally injected into the left eye. Intravenous antibiotics injection was repeated on days 1, 2, and 3 after inoculation. The clinical features, bacterial culture from vitreous aspirates of 10 eyes from each group were evaluated on days 1, 3, 5, and 7. On day 7, eyes for clinical feature examination were enucleated for histopathologic examination.Results: Clinical scores and log10CFU/ml values were lower in moxifloxacin group on all examination days. Histopathologic examination showed less inflammation and relatively well-preserved retina in the moxifloxacin group.Conclusions: Systemic moxifloxacin may have a prophyactic effect for S. viridans endophthalmitis after intraocular procedure.