Efficacy and safety of topical ciprofloxacin/dexamethasone versus neomycin/polymyxin B/hydrocortisone for otitis externa

OBJECTIVES: To compare the efficacy and safety of ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) otic suspension with that of neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1.0% (N/P/H) otic suspension in patients with acute otitis externa (AOE). STUDY DESIGN: Randomized, observer-masked, parallel-group, multicenter study. Patients were randomized to 7 days treatment with either CIP/DEX 3-4 drops twice daily or N/P/H 3-4 drops three times daily. POPULATION: Patients of either sex and older than 1 year, with a clinical diagnosis of mild, moderate, or severe AOE and intact tympanic membranes were recruited to participate. OUTCOMES MEASURED: Signs and symptoms of AOE, including ear inflammation, tenderness, edema and discharge (assessed on Days 3, 8 [End-of-Therapy] and 18 [Test-of-Cure]); microbiologic eradication (presumed or documented); and frequency of adverse events. RESULTS: Patients enrolled numbered 468. In culture-positive patients who met the inclusion criteria (N = 396), clinical cure rates at Day 18 were significantly higher with CIP/DEX than with N/P/H (90.9% vs. 83.9%; p = 0.0375), as were microbiologic eradication rates (94.7% vs. 86.0%; p = 0.0057). In addition, the clinical response was significantly better with CIP/DEX than with N/P/H at Days 3 and 18 (p = 0.0279 and p = 0.0321, respectively), as was the reduction in ear inflammation at Day 18 (p = 0.0268). Both preparations were well tolerated in pediatric and adult patients. CONCLUSIONS: 7 days treatment with CIP/DEX otic suspension administered twice daily is clinically and microbiologically superior to N/P/H otic suspension administered 3 times daily in the treatment of mild to severe AOE, and is equally well tolerated.     

Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times a day: a multicenter,randomized, evaluator-blinded trial to compare the efficacy,safety, and pain relief in pediatric patients with otitis externa

ABSTRACT

Introduction: Otitis externa (OE) is an infection of the external auditory canal affecting children and adults and is associated with symptoms of local pain and tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3% [Floxin otic solution]) for 10 days has been reported to be as effective and well tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension (Cortisporin otic suspension) administered four times daily for 10 days.

Objective: This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE.

Research design, patients, and methods: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7–10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7–9), and test of cure (7–10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity.

Main outcome measures: The overall clinical response was cure in the clinically evaluable patients, demonstrated by resolution of OE signs and symptoms at the test of cure visit. The overall clinical-microbiological response was cure in the microbiologically evaluable patients demonstrated by both clinical cure and microbiological eradication.

Results: For the clinically evaluable patients, equivalent cure rates were obtained between the once-daily ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the clinically and microbiologically evaluable patients, the overall cure rates were 96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. The eradication rates for the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. Decreases in pain severity were similar in both treatment groups. Statistical analyses were limited by the small numbers of patients in each treatment group.

Conclusion: In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.     

Dexamethasone phosphate in antibiotic ear drops for the treatment of acute bacterial otitis externa

ABSTRACT

Objectives: To compare the efficacy and safety of polymyxin sulfate 7500?IU/neomycin sulfate 3500?IU/dexamethasone phosphate 0.1% (PN?+?Dx) otic solution with polymyxin sulfate 7500?IU/neomycin sulfate 3500?IU (PN???Dx) in patients with acute bacterial otitis externa (AOE), in order to determine the possible benefit of the addition of dexamethasone.

Research design and methods: Active controlled, double-blind, randomized, parallel group, multi-center clinical trial in ear, nose, and throat (ENT) specialist practices with a planned interim analysis for sample size adaptation. In total, 338 patients aged 18–76 who had a previous episode of otitis externa within the last year were randomized to receive 10?±?2 days of treatment with two drops, three times daily, of either PN?+?Dx or PN???Dx.

Main outcome measures: Change in the clinical symptom score (consisting of the subscores redness, swelling, pain, and secretion) and of the visual analogue scale (VAS) rating for pain from Visit 1 (Day 1) to Visit 2 (Day 4?±?1), patient's assessment of efficacy at Visit 3 (Day 10?±?2), and the frequency and type of adverse events.

Results: There was a significantly greater reduction of swelling from Visit 1 to Visit 2 with PN?+?Dx, and more patients rated the efficacy of PN?+?Dx as ‘very good’ or ‘good’ at Visit 3 (p?=?0.03). There was also a significantly greater decrease in the clinical symptom score from Visit 1 to Visit 2 in the PN?+?Dx group in patients who had at least a moderately severe symptom score with more than seven points at Visit 1 (p?=?0.01) and in patients suffering from their current episode of otitis externa for more than 2 days (p?=?0.02). In total, 14 adverse events were reported during the study period with no related adverse drug reactions for PN?+?Dx.

Conclusions: The addition of dexamethasone phosphate to polymyxin B/neomycin significantly reduces swelling in patients with AOE and leads to significantly higher patient's ratings of treatment efficacy. It especially leads to an overall reduction of symptoms in cases of moderately or more severe otitis externa and cases lasting for more than 2 days.     

Comparative Efficacy of Two Anti-bacterial/Anti-inflammatory Formulations (Auricularum Otic Powder and Dex-Otict Drops) in the Medical Treatment of Otitis Externa

Summary

Background: Otitis externa (OE) is a common disorder which can cause severe pain and discomfort with discharge and hearing loss. The majority of topical preparations for OE treatment contain a combination of steroids and antibiotics and are administered as ear drops. Otic powder preparations are less common. We found no studies which compared the efficacy of the two dosage forms.

Objective: The purpose of the study was to compare the healing process of the external ear canal when treated locally either with otic powder (Auricularum), a preparation containing antibiotic, steroidal and antimycotic components, or with otic drops (Dex-Otic), a commercial ear drop preparation containing antibiotic and steroidal components.

Methods: The study was designed as an open, randomised, comparative clinical trial. Ambulatory patients suffering from OE were examined by an ear specialist and randomly divided into an otic powder (Auricularum) treatment group and an ear drop (Dex-Otic) treatment group. Each treatment group was treated in accordance with the daily doses recommended by the manufacturers. Patients were treated for a period of 14 days and examined on days 0,3, 7,10 and 14. Clinical signs and symptoms recorded were pain, erythema, swelling and discharge.

Results: A total of 67 patients entered the study. The probability of healing within 7 days was 74% in the otic powder group as opposed to 40% in the ear drops group (log rank test, p = 0.0013). The probability of total pain relief after 3 days of treatment was 60% in the otic powder group compared to 53% in the ear drops group (log rank test, p = 0.0001).

Conclusion: We conclude that treatment with an otic powder (Auricularum) may promote earlier healing and pain relief than does treatment with otic drops (Dex-Otic).     

Comparison of efficacy and safety of ciprofloxacin otic solution 0.2% versus polymyxin B-neomycin-hydrocortisone in the treatment of acute diffuse otitis externa

ABSTRACT

Objective: To compare the efficacy and safety of ciprofloxacin otic solution 0.2% to polymyxin B-neomycin-hydrocortisone (PNH) otic solution in the treatment of acute diffuse otitis externa in children, adolescents, and adults.

Methods: This was a randomized, parallel-group, evaluator-blind, active-controlled, multicenter, noninferiority study. The primary efficacy endpoint was clinical cure of otitis symptoms at the test-of-cure (TOC) visit. Clinical cure at the end-of-treatment (EOT) visit and percentages of patients with clinical improvement and resolution and/or improvement of otalgia at EOT and TOC visits were secondary efficacy endpoints.

Results: A total of 630 patients were randomized to ciprofloxacin twice daily (n = 318) or PNH 3 times daily (n = 312) for 7 days. Ciprofloxacin was shown to be noninferior to PNH. The percentage of patients with clinical cure at the TOC visit was 86.6% with ciprofloxacin and 81.1% with PNH; the treatment difference was 5.6% in favor of ciprofloxacin (95% CI: ?0.9 to 12.1). At the EOT visit, clinical cure was achieved in 70.0% and 60.5% of patients, respectively, with a treatment difference in favor of ciprofloxacin (9.5%, 95 CI: 1.2 to 17.9). In all secondary efficacy variables, ciprofloxacin and PNH showed similar results, including pain duration and resolution. The clinical cure rate for patients with baseline cultures showing P. aeruginosa was 87.5% in the ciprofloxacin group and 78.6% in the PNH group, a treatment difference of 8.9% in favor of ciprofloxacin (95% CI: 0.6 to 17.3); for patients with baseline cultures showing S. aureus, the clinical cure rate was 72.7% for the ciprofloxacin group and 75.9% for the PNH group (treatment difference of 3.1% in favor of PNH, 95% CI: ?21.1% to 27.4%). Most adverse events were mild and unrelated to study medication in both treatment groups. A limitation of this study is the assessment of signs and symptoms at baseline and after treatment, which does not provide data to evaluate the interim response.

Conclusions: Ciprofloxacin otic solution 0.2% was found to be noninferior to PNH. This efficacy, good tolerability, and ease of administration make ciprofloxacin otic solution 0.2% without a topical steroid an attractive option for the treatment of acute otitis externa.     

Phase III efficacy and safety study of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis

ABSTRACT

Objective: To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of vehicle in the treatment of bacterial conjunctivitis.

Research design and methods: This was a randomized, multicenter, double-masked, vehicle-controlled study. A total of 957 patients aged 1 year and older with bacterial conjunctivitis were randomized to treatment with besifloxacin ophthalmic suspension 0.6% or vehicle applied topically three times daily for 5 days.

Main outcome measures: Primary endpoints were clinical resolution and microbial eradication of baseline bacterial infection at Visit 2 (Day 5?±?1). Secondary endpoints included clinical resolution and microbial eradication at Visit 3 (Day 8 or 9), individual clinical outcomes at follow-up visits, and safety.

Clinical trial registration: NCT number, NCT00347932.

Results: Three hundred and ninety patients had culture-confirmed bacterial conjunctivitis. Clinical resolution and microbial eradication were significantly greater with besifloxacin ophthalmic suspension than with vehicle at Visit 2 (45.2% vs. 33.0%, p?=?0.0084; and 91.5% vs. 59.7%, p?<?0.0001, respectively) and Visit 3 (84.4% vs. 69.1%, p?=?0.0011; and 88.4% vs. 71.7%, p?<?0.0001, respectively). Results for secondary endpoints of individual clinical outcomes were consistent with primary endpoints. Fewer eyes receiving besifloxacin ophthalmic suspension experienced adverse events than those receiving vehicle (9.2% vs. 13.9%; p?=?0.0047).

Conclusions: Besifloxacin ophthalmic suspension produces clinical resolution and microbial eradication rates significantly better than vehicle and is safe for the treatment of bacterial conjunctivitis.

Limitations: A limitation of this study is the lack of a non-treatment control group.     

Systematic review and meta-analysis of budesonide/formoterol in a single inhaler

ABSTRACT

Objective: To compare the effectiveness of budesonide/formoterol using fixed dosing (BUD/FORM) with inhaled corticosteroid (ICS) alone or alternative ICS and long-acting β₂-agonist (LABA) regimens for adults with moderate/severe asthma.

Methods: BIOSIS, CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in July 2006. No restriction was placed on language. Meta-analysis of randomised controlled trials (RCTs) using a fixed effects model. RCTs were included if the comparator with BUD/FORM had an equivalent daily dose of ICS at the start of the trial. The primary outcome measure was, ‘treatment failure’, defined as: asthma-related serious adverse event, oral glucocorticosteroid treatment, A&E visit and/or admission to hospital, withdrawal due to a need for additional asthma therapy.

Results: Of the 330 papers identified in the literature search, 15 met the inclusion criteria. The following alternative treatments were found: ICS alone (BUD), BUD/FORM adjustable maintenance dose (BUD/FORM-AMD), and salmeterol/fluticasone in a single inhaler (SALM/FP). Meta-analysis of treatment failure demonstrated a 50% increase with BUD versus BUD/FORM (Relative Risk [RR] 1.50, 95% confidence interval [95% CI]: 1.12–2.02, p = 0.007; 2 RCTs); a trend in favour of a reduction with BUD/FORM-AMD versus BUD/FORM (RR 0.88, 95% CI: 0.77–1.02, p = 0.09; 11 RCTs); and no evidence of a difference with SALM/FP versus BUD/FORM (RR 0.99, 95% CI: 0.83–1.16, p = 0.86; 3 RCTs). Significant heterogeneity was not detected in the primary analyses. Secondary analyses demonstrated the following significant differences: hospitalisations/A&E visits (49% increased risk with SALM/FP vs. BUD/FORM, RR 1.49, 95% CI: 1.07–2.08, p = 0.02, and 28% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.72, 95% CI: 0.52–0.99, p = 0.04); and use of oral steroids (51% increase in risk with BUD vs. BUD/FORM, RR 1.51, 95% CI: 1.10–2.09, p = 0.01, and 19% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.81, 95% CI: 0.70–0.95, p = 0.01).

Conclusions: Fixed-dose BUD/FORM is an effective treatment option for adult patients with moderate/severe asthma when compared to BUD and SALM/FP, with adjustable maintenance dosing demonstrating important advantages over fixed dosing in relation to exacerbation prevention and reduced treatment load.     

Efficacy and tolerability of twice-daily pregabalin for treating pain and related sleep interference in postherpetic neuralgia: a 13‐week,randomized trial

ABSTRACT

Objective: This trial evaluated the efficacy and safety of pregabalin dosed twice daily (BID) for relief of neuro-pathic pain associated with postherpetic neuralgia (PHN).

Research design and methods: The 13‐week, double-blind, placebo-controlled study randomized 370 patients with PHN to pregabalin (150, 300, or 600?mg/day BID) or placebo.

Main outcome measures: Primary efficacy measure was endpoint mean pain score from daily pain diaries. Secondary efficacy measures included endpoint mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). Safety evaluations included adverse events (AEs), physical and neurologic examinations, 12-lead ECG, vital signs, and laboratory testing.

Results: Pregabalin provided significant, dose-proportional pain relief at endpoint: difference from placebo in mean pain score, 150?mg/day, –0.88, p = 0.0077; 300?mg/day, –1.07, p = 0.0016; 600?mg/day, –1.79, p = 0.0003. Weekly mean pain scores significantly improved as early as week 1. Sleep interference in all pregabalin groups was also significantly improved at endpoint, compared with placebo (?p < 0.001), beginning at week 1 (?p < 0.01). At study termination, patients in the 150 (p = 0.02) and 600?mg/day (p = 0.003) groups were more likely to report global improvement than were those in the placebo group.

Most AEs were mild or moderate. Among pregabalin-treated patients, 13.5% withdrew due to AEs, most commonly for dizziness (16 patients, 5.8%), somnolence (8, 2.9%), or ataxia (7, 2.5%).

Conclusions: Pregabalin, dosed BID, reduced neuropathic pain associated with PHN and was well tolerated. It also reduced the extent to which pain interfered with sleep. Pregabalin's effects were seen as early as week 1 and were sustained throughout the 13‐week study.     

Effects and mechanisms of pirfenidone,prednisone and acetylcysteine on pulmonary fibrosis in rat idiopathic pulmonary fibrosis models

Context: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown.

Objective: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF.

Materials and methods: Rat IPF model was established by endotracheal injection of 5?mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100?mg/kg once daily), prednisone (H, 5?mg/kg once daily) and acetylcysteine (N, 4?mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay.

Results: After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p?p?p?r?=??0.506, p?r?=?-0.676, p?r?=??0.590, p?r?=??0.530, p?r?=??0.553, p?Discussion and conclusion: Pirfenidone, prednisone and acetylcysteine can inhibit airsacculitis and pulmonary fibrosis in rat IPF models, which may be related with enhanced caveolin-1, reduced TNF-α, TGF-β1, PDGF.     

Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy

ABSTRACT

Objective: To examine the efficacy and safety of tramadol/acetaminophen (APAP) for the management of painful diabetic peripheral neuropathy (DPN).

Methods: Adults with painful DPN involving the lower extremities received 37.5?mg tramadol/325?mg APAP or placebo, up to 1–2 tablets four times daily, for 66 days. Subjects rated average daily pain and sleep interference from 0 (‘none’) to 10 (‘pain as bad as you can imagine’ or ‘complete interference’) every night. Baseline values were recorded for 7 days before starting study medication. The primary endpoint was change in mean of average daily pain scores from baseline to final week. Secondary efficacy outcomes included pain intensity, sleep interference, quality of life, mood, and global impression of change. Potential study limitations included permission to use serotonin reuptake inhibitors concomitantly (except venlafaxine or duloxetine) and the lack of a tramadol-alone or APAP-alone control group.

Results: A total of 160 subjects received tramadol/APAP and 153 received placebo. Tramadol/APAP reduced average daily pain significantly compared to placebo from baseline to the final week (–2.71 vs. –1.83, p = 0.001). Tramadol/APAP was associated with significantly greater improvement than placebo (?p ≤ 0.05) for all measures of pain intensity, sleep interference, and global impression, as well as several measures of quality of life and mood. The only adverse event reported by > 10% of subjects in either the tramadol/APAP or placebo group was nausea (11.9% and 3.3%, respectively). Adverse events resulted in early study discontinuation for 8.1% and 6.5% of subjects in the tramadol/APAP and placebo groups, respectively.

Conclusion: Tramadol/APAP was more effective than placebo and was well tolerated in the management of painful DPN.     

A comparison of the safety and intraocular pressure lowering of bimatoprost/timolol fixed combination versus latanoprost/timolol fixed combination in patients with open-angle glaucoma*

ABSTRACT

Purpose: To compare the efficacy and tolerability of a once daily evening dose of the latanoprost/timolol fixed combination (LTFC) with that of a once-daily evening dose of the bimatoprost/timolol fixed combination (BTFC) in patients with open-angle glaucoma with elevated intrao­cular pressure (IOP) insufficiently responsive to mono­therapy with prostaglandin analogues/prostamides.

Design: Prospective, randomized, evaluator masked, single-center study.

Participants: 36 patients with a diagnosis of open-angle glaucoma, with or without pseudoexfoliation, and inadequate control of IOP, insufficiently responsive to monotherapy with prostaglandin analogues/prostamides.

Main outcome measure: The primary end-points were the change in IOP at 9:00?am from baseline to week 4, and the difference between treatment groups in the mean diurnal IOP reduction from baseline to week 4.

Results: BTFC provided significantly greater mean diurnal IOP reduction [mean (standard deviation)] 2.8 (0.9)?mmHg, compared with LTFC 2.1 (0.6)?mmHg, p = 0.0214. Both treatments significantly reduced the IOP from baseline at each IOP time-point measured, p < 0.0001, and for the mean diurnal IOP; p = 0.0049 for the LTFC, and p < 0.0001 for the BTFC. There were no significant differences in average hyperemia scores among groups, 1.25 (0.5) vs. 1.62 (0.69), p = 0.3835, for the LTFC and the BTFC, respectively.

Conclusions: The results of this study showed a significantly higher IOP-lowering effect of a once-daily evening dose of the BTFC compared to that of a once-daily evening administration of the LTFC.     

Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized,investigator-blinded study

ABSTRACT

Objective: To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/clavulanate in patients diagnosed with acute bacterial sinusitis.

Research design and methods: In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12?years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000?mg once daily or amoxicillin/clavulanate 875?mg/125?mg twice daily for 14?days.

Main outcome measures: Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10?days following the completion of treatment. Radiological response was assessed at a follow-up visit.

Results: The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [–2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [–12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [–4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2?days–5?days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure (?p = 0.027) and improvement/resolution rate of nasal congestion (?p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was ≥ 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER (?p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group (?p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events.

Conclusion: In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.     

Levofloxacin for the treatment of pneumonia caused by Streptococcus pneumoniae including multidrug-resistant strains: pooled analysis

ABSTRACT

Objective: To determine the clinical and microbiologic efficacy of levofloxacin for the treatment of subjects with pneumonia caused by multidrug-resistant (MDR) Streptococcus pneumoniae (MDRSP) and non-MDRSP strains.

Research design and methods: A pooled analysis was conducted using data from ten clinical studies in pneumonia: five comparative studies and five noncomparative studies conducted from 1992 to 2002. This analysis included data from levofloxacin-treated subjects with S.?pneumoniae isolated at study entry. Susceptibility of S.?pneumoniae isolated from subjects at study entry was determined against representative agents from five antimicrobial classes: tetracyclines, sulfonamides, second-generation cephalosporins, penicillins, and macrolides. Isolates were classified as MDRSP (based on resistance to two or more antimicrobial classes) or non-MDRSP (intermediate resistance or susceptible to all classes or resistant to 1 antimicrobial class). Clinical and microbiologic efficacy of levofloxacin (i.v., p.o., or i.v./p.o. for 5 to 14 days) in the microbiologically evaluable population was determined at post-therapy; a test for homogeneity of the odds ratio of the difference in clinical success for comparative versus noncomparative studies was performed.

Main outcome measures and results: The main outcome measures were clinical success rates and microbiologic eradication rates of 419 microbiologically evaluable levofloxacin-treated subjects with MDRSP or non-MDRSP. Clinical success rates were 96.3% (52/54) and 95.1% (347/365), respectively (difference ?1.2; 95% confidence interval [CI]: ?6.7, 4.3). Similarly, per pathogen microbiologic eradication rates for MDRSP and non-MDRSP were 96.3% (52/54) and 95.6% (350/366), respectively (difference ?0.7; 95%?CI: ?6.1, 4.8). Study limitations include the use of data from comparative and noncomparative studies. A test for homogeneity of the odds ratios for clinical success in comparative versus noncomparative studies showed no significant difference (p?=?0.27).

Conclusions: These data support the use of levofloxacin for patients with community-acquired pneumonia caused by S.?pneumoniae, including MDR strains.     

Once-daily ofloxacin otic solution versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times a day: a multicenter, randomized, evaluator-blinded trial to compare the efficacy, safety, and pain relief in pediatric patients with otitis externa

INTRODUCTION: Otitis externa (OE) is an infection of the external auditory canal affecting children and adults and is associated with symptoms of local pain and tenderness. Twice-daily topical treatment with ofloxacin otic solution (0.3% [Floxin otic solution]) for 10 days has been reported to be as effective and well tolerated as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension (Cortisporin otic suspension) administered four times daily for 10 days. OBJECTIVE: This study compared the efficacy, safety, and ear-pain resolution of once-daily ofloxacin otic solution (0.3%) versus neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension administered four times daily, in children with OE. RESEARCH DESIGN, PATIENTS, AND METHODS: This multicenter, randomized, parallel-group, evaluator-blinded study was conducted at 34 centers in 278 pediatric OE patients aged 6 months to 12 years. Patients received five drops of ofloxacin otic solution (0.3%) in the affected ears once daily or three drops of neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension four times daily, for 7-10 days. Patient evaluations were performed at pretherapy (day 1), end of therapy (days 7-9), and test of cure (7-10 days post-treatment) visits. Data for 208 patients were clinically evaluable and those for 90 patients were microbiologically evaluable. Scores were obtained for patient assessments of pain severity. MAIN OUTCOME MEASURES: The overall clinical response was cure in the clinically evaluable patients, demonstrated by resolution of OE signs and symptoms at the test of cure visit. The overall clinical-microbiological response was cure in the microbiologically evaluable patients demonstrated by both clinical cure and microbiological eradication. RESULTS: For the clinically evaluable patients, equivalent cure rates were obtained between the once-daily ofloxacin-treated and four-times-daily neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients (93.8% and 94.7%, respectively). For the clinically and microbiologically evaluable patients, the overall cure rates were 96.4% versus 97.1% for the ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. The eradication rates for the prevalent pathogen, Pseudomonas aeruginosa, were 98% versus 100% for ofloxacin-treated and neomycin sulfate/polymyxin B sulfate/hydrocortisone-treated patients, respectively. Decreases in pain severity were similar in both treatment groups. Statistical analyses were limited by the small numbers of patients in each treatment group. CONCLUSION: In the treatment of OE in children, once-daily ofloxacin otic solution was as effective and safe as neomycin sulfate/polymyxin B sulfate/hydrocortisone otic suspension given four times daily. The two treatments provide rapid and comparable pain relief; however, ofloxacin otic solution does not have the risk of ototoxicity associated with neomycin and provides effective pain relief without adjunctive steroids.     

A multicentre,randomized, controlled trial of oseltamivir in the treatment of influenza in a high-risk Chinese population

ABSTRACT

Objective:?To evaluate the efficacy and safety of oseltamivir treatment in a population at high risk for influenza.

Research design and methods:?This was a randomized, open-label, controlled trial involving Chinese patients with chronic respiratory diseases (chronic bronchitis, obstructive emphysema, bronchial asthma or bronchiectasis) or chronic cardiac disease. Patients showing symptoms of influenza were randomly assigned to receive oral oseltamivir 75?mg twice daily for 5 days (oseltamivir group), or symptomatic treatment (control group) within 48?h after symptom onset.

Main outcome measures:?The main outcome measures were duration and severity of illness in influenza-infected patients. Other outcome measures included incidence of complications, antibiotic use, hospitalization and total medical cost.

Results:?Of the 118 recruited patients, 56 were identified as influenza-infected through laboratory tests (oseltamivir, N = 27; control, N = 29). Relative to symptomatic treatment, oseltamivir significantly reduced the duration of influenza symptoms by 36.8% (?p = 0.0479), and the severity by 43.1% (?p = 0.0002). In addition, oseltamivir significantly reduced the duration of fever by 45.2% (?p = 0.0051), and the time to return to baseline health status by 5 days (?p = 0.0011). The incidence of complications (11% vs. 45%, p = 0.0053) and antibiotic use (37% vs. 69%, p = 0.0167) were also significantly lower in the oseltamivir group compared with the control group. The cost of treating influenza and its complications was comparable between the two groups (?p = 0.2462).

Conclusions:?Oseltamivir is effective and well tolerated in high-risk patients with chronic respiratory or cardiac diseases. It can reduce the duration and severity of influenza symptoms and decrease the incidence of secondary complications and antibiotic use, without increasing the total medical cost.     

Efficacy and safety of extended-release fluvastatin in Turkish patients with hypercholesterol­aemia: TULiPS (Turkish Lipid Study)

ABSTRACT

Objective: The efficacy and safety of extended-release fluvastatin (fluvastatin XL), 80?mg once daily, was assessed in Turkish patients with primary hypercholesterolaemia (low-density lipoprotein cholesterol (LDL?C) 3.37–5.70?mmol/l and triglyceride (TG) <?4.52?mmol/l).

Research design: in this open-label, prospective, multi-centre study, 154 patients were given fluvastatin XL 80?mg once daily and lipid levels were assessed after 2 and 12 weeks.

Results: Fluvastatin XL 80?mg once daily significantly reduced LDL?C levels by 38.8 and 38.1% at weeks 2 (n = 140) and 12 (n = 116), respectively (?p < 0.001 vs. baseline). Treatment with fluvastatin XL for 2 and 12 weeks significantly reduced total cholesterol levels by 30.2 and 27.4%, respectively (?p < 0.001 vs. baseline) and reduced TG levels by 14.9 and 7.5%, respectively (?p < 0.001 vs. baseline). Following stratification by risk factors for coronary heart disease (CHD) according to the National Cholesterol Education Program Adult Treatment Panel iii guidelines, 87.3% of patients with ≥?2 risk factors, and 67.4% of patients with existing CHD or CHD risk equivalents achieved target LDL?C levels (<?3.37?mmol/l and <?2.59?mmol/l, respectively) with fluvastatin XL. Fluvastatin XL reduced high-density lipoprotein cholesterol by 8.9 and 4.7% at weeks 2 and 12 weeks, respectively. fluvastatin XL 80?mg once daily was generally well-tolerated.

Conclusions: This open-label study indicates fluvastatin XL 80?mg once daily is an effective and well-tolerated lipid-lowering therapy for the reduction of CHD risk in Turkish patients.     

Hospitalization rates among patients with community-acquired pneumonia treated with telithromycin vs clarithromycin: results from two randomized,double-blind,clinical trials

SUMMARY

Aims: To compare hospitalization rates among patients with community-acquired pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on pooled data from two randomized, double-blind, multinational clinical trials.

Patients and methods: Adult patients with CAP eligible for oral therapy (Study 1, n = 448; Study 2, n = 575) received telithromycin 800?mg once daily for 10 (Study 1, 2-arms), 5 or 7 (Study 2, 3-arms) days, or clarithromycin 500?mg twice daily for 10?days. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use, as well as CAP-related length of hospital stay and hospitalization costs, were compared by treatment group (intent to treat populations) up until the late post-therapy visit (Days 31–36). Study investigators blinded to treatment regimen assessed whether hospital admissions were CAP related.

Results: Despite equivalent clinical efficacy for telithromycin vs clarithromycin in the clinically evaluable per-protocol populations (n = 784) (88.8% [428/482] vs 90.1% [272/302] – difference: –1.3%; 95% CI: –6.0, 3.4), telithromycin treatment for 5, 7, or 10?days was associated with significantly fewer CAP-related hospitalizations (?p = 0.023) and CAP-related hospital days (?p = 0.025) vs clarithromycin (reduction of 2.3 hospitalizations and 23.4 hospital days per 100 patients). Accordingly, estimated CAP-related hospitalization costs were significantly lower (?p = 0.025) for telithromycin recipients (US$30?231 less per 100 patients). CAP-related hospitalizations, duration of hospital stay, and hospitalization costs for 7- to 10-day telithromycin – the approved dosing regimen for CAP – were significantly lower (?p = 0.023, 0.025, and 0.025, respectively) than for clarithromycin.

Conclusions: Data from this study indicate that telithromycin 800?mg once daily for 5, 7, or 10?days provides an effective therapy for patients with CAP, and may be associated with fewer CAP-related hospitalizations and hospital days than clarithromycin 500?mg twice daily for 10?days. Treatment with telithromycin could, therefore, potentially translate into cost savings in the management of CAP.     

Is rheumatoid arthritis associated with reduced immunogenicity of the influenza vaccination? A systematic review and meta-analysis

Objective: To determine whether immunogenicity and safety of the influenza vaccination in rheumatoid arthritis (RA) patients are significantly different from those in a healthy population.

Methods: PubMed, MEDLINE, Embase, Cochrane Library and Web of Science were searched on 31 August 2016. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality and outcomes. The primary outcome was seroprotection (SP) rate after immunization.

Results: Thirteen studies were included. The SP rates did not significantly differ between the RA patients and healthy controls for the H3N2 (RR?=?0.96, 95% CI, 0.82 to 1.13, p?=?.64) and B strain (RR?=?0.95, 95% CI 0.84 to 1. 08, p?=?.44). Nevertheless, RA was associated with a significant decrease in SP rate for the H1N1 strain (RR?=?0.72, 95% CI 0.60 to 0.86, p?p?=?.04).

Conclusions: Immunogenicity was significantly different between RA patients and healthy controls for the H1N1 strain, but not for the H3N2 or B strains. Adverse event rates were higher in RA patients. Adjuvant and special kinds of immunosuppressive biologics may play an important role in immunogenicity of inactivated influenza vaccines for RA patients.