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Biomedical subjects

Roger Echols

Publications and source records attributed to Roger Echols.

8 recordsLinked to original sources
PubMed2006

Redefining penems.

The antimicrobial class of penems has the potential to address most of the relevant resistance issues associated with beta-lactam antibiotics because of their exceptionally broad spectrum of antibacterial activity and their intrinsic stability against hydrolytic attack by many beta-lactamases including ESBL and AmpC enzymes. The subclass of carbapenems covers the spectrum of hospital pathogens whereas the subclass of penems covers community pathogens. The only currently available penem, faropenem, has a low propensity for resistance development, beta-lactamase induction and selection of carbapenem-resistant Pseudomonas aeruginosa. This makes it attractive for the treatment of community-acquired infections and for step-down or sequential therapy following carbapenem treatment without jeopardizing the activity of carbapenems or the entire beta-lactam class in the hospital environment.

Anti-Bacterial Agents↗
PubMed2006

Randomized double-blind study comparing 7- and 10-day regimens of faropenem medoxomil with a 10-day cefuroxime axetil regimen for treatment of acute bacterial sinusitis.

OBJECTIVE: To compare the efficacy and safety of faropenem medoxomil, 300 mg twice daily for seven or ten days, with cefuroxime axetil 250 mg twice daily for ten days in adults with acute bacterial sinusitis (ABS). STUDY DESIGN AND SETTING: Prospective, double-blinded, phase III trial with entry criteria consistent with FDA/IDSA guidelines for diagnosis of ABS. Primary efficacy parameter was clinical response at 7 to 21 days posttherapy. RESULTS: One thousand ninety-nine subjects were randomized and treated; 861 were efficacy valid. Clinical cure rates were 80.3% for seven days of faropenem, 81.8% for ten days of faropenem, and 74.5% for 10 days of cefuroxime axetil. The incidence of adverse events and premature discontinuations were similar for the three treatment regimens. CONCLUSIONS: Seven- and ten-day faropenem medoxomil regimens were similar (noninferior) to a ten-day cefuroxime axetil regimen based on clinical response in patients with ABS. SIGNIFICANCE: A seven-day course of faropenem medoxomil 300 mg twice-daily regimen is a promising alternative for treatment of ABS.

Acute Disease↗
PubMed2005

Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure.

BACKGROUND: Because of concerns about arthrotoxicity, fluoroquinolones are restricted for use in children. This study describes the safety and efficacy of gatifloxacin when used for treatment of children with recurrent acute otitis media (ROM) or acute otitis media (AOM) treatment failure (AOMTF). METHODS: We performed an analysis of 867 children included in 4 clinical trials who had ROM and/or AOMTF and were treated with gatifloxacin (10 mg/kg once daily for 10 days). RESULTS: Gatifloxacin had adverse event rates that were similar overall to those of a comparator antibiotic (amoxicillin-clavulanate), except for increased diarrhea in children <2 years old receiving amoxicillin-clavulanate. There was no evidence of arthrotoxicity, hepatotoxicity, alteration of glucose homeostasis, or central nervous system toxicity acutely or during 1 year follow-up in any child. Regarding efficacy, in 2 noncomparative trials, the gatifloxacin cure rate of AOM was 89% (95% confidence interval [CI], 83%-95%) at the test of cure (TOC) visit, 3-10 days after completion of therapy. In 2 comparative trials of gatifloxacin versus amoxicillin-clavulanate, the efficacy of gatifloxacin was 88% (95% CI, 82%-94%). Gatifloxacin led to better clinical outcomes than amoxicillin-clavulanate for AOMTF (91% vs. 81%; P=.029), for AOMTF and age <2 years old (89% vs. 69%; P=.009), and for severe AOM in children <2 years old (90% vs. 75%; P=.012). Among children with AOMTF previously treated with amoxicillin-clavulanate or ceftriaxone injections, gatifloxacin cure rates were high (88% and 75%, respectively). CONCLUSIONS: Gatifloxacin appears to be safe for children, with no evidence of producing arthrotoxicity in 867 children exposed to the antibiotic when used as treatment for ROM and AOMTF.

Anti-Infective Agents↗
PubMed2005

Randomized, investigator-blinded, multicenter, comparative study of gatifloxacin versus amoxicillin/clavulanate in recurrent otitis media and acute otitis media treatment failure in children.

BACKGROUND: Recurrent otitis media and acute otitis media treatment failure are commonly encountered in the pediatric population. OBJECTIVE: To compare the clinical efficacy of gatifloxacin with amoxicillin/clavulanate for the treatment of acute otitis media treatment failure and recurrent otitis media. METHODS: Three hundred fifty-four children 6 months-7 years with recurrent otitis media and/or acute otitis media failure were stratified according to age (younger than 2 years versus 2 years or older) and then randomly assigned to 10 days of treatment with gatifloxacin 10 mg/kg once daily or amoxicillin/clavulanate 90 mg/6.4 mg in 2 divided doses. Tympanocentesis was performed in 116 children with acute otitis media treatment failure and 52 with recurrent otitis media at study entry to validate the clinical diagnosis and provide microbiologic data. The primary outcome measure was clinical resolution of infection at the test-of-cure visit 3-10 days after completing treatment. RESULTS: Clinical resolution of acute otitis media was observed in 79.0% (49 of 62) of clinically evaluable children younger than 2 years and 90.3% (56 of 62) of those 2 years or older who were treated with gatifloxacin as compared with 77.6% (45 of 58) of children younger than 2 years and 79.7% (47 of 59) of children 2 years or older treated with amoxicillin/clavulanate. In patients with acute otitis media treatment failure, clinical response rates for children younger than 2 years and those 2 years or older were 87.5% (21 of 24) and 97.0% (32 of 33) with gatifloxacin versus 63.6% (14 of 22) and 83.9% (26 of 31) with amoxicillin/clavulanate. The corresponding clinical response rates in patients with recurrent otitis media were 79.2% (19 of 24) and 85.7% (18 of 21) with gatifloxacin and 90.5% (19 of 21) and 76.0% (19 of 25) with amoxicillin/clavulanate. Clinical success in those subjects having pretreatment middle ear fluid pathogens was similar for the 2 regimens [80.0% (24 of 30) gatifloxacin, 77.1% (27 of 35) amoxicillin/clavulanate]. Emergence of fluoroquinolone-resistant strains was not observed. Both drugs were generally well-tolerated. Diarrhea was the most common drug-related adverse event (10% gatifloxacin, 18% amoxicillin/clavulanate). No evidence of abnormal joint or gait findings was found during a 12-month follow-up. CONCLUSIONS: Gatifloxacin once daily is at least as effective and well-tolerated as amoxicillin/clavulanate twice daily in children with acute otitis media treatment failure or recurrent otitis media. There was no evidence of arthrotoxicity or emergence of fluoroquinolone-resistant bacteria in gatifloxacin-treated children.

Acute Disease↗
PubMed2005

Randomized, investigator-blinded, multicenter study of gatifloxacin versus amoxicillin/clavulanate treatment of recurrent and nonresponsive otitis media in children.

BACKGROUND: Decreased susceptibility of pathogens to currently used agents for recurrent otitis media has provided the impetus for identifying new antimicrobial options. OBJECTIVE: To compare gatifloxacin with amoxicillin/clavulanate in children with recurrent or nonresponsive acute otitis media (AOM). METHODS: Included in this multicenter randomized trial were 413 patients, ranging in age from 6 months to 7 years, who had recurrent AOM (at least 3 episodes in the previous 6 months or 4 episodes in the previous 12 months) and/or had failed antibiotic therapy for AOM within 14 days of enrollment. Diagnosis required evidence of acute inflammation and otoscopic findings of middle ear effusion; baseline tympanocentesis was optional and encouraged. Children were randomly assigned (2:1) to 10 days of oral therapy with gatifloxacin suspension (10 mg/kg of body weight once daily) or amoxicillin/clavulanate suspension (45/6.4 mg/kg/d in 2 divided doses). RESULTS: : Clinical cure was obtained in 90.2% (222 of 246) of patients in the gatifloxacin group and 84.3% (102 of 121) of those in the amoxicillin/clavulanate group (95% confidence interval, -1.9-12.9) 3-10 days after treatment ended. Gatifloxacin was associated with higher clinical cure rates than was amoxicillin/clavulanate in children younger than 2 years of age (92.0% versus 80.0%, respectively). Cure rates by pretreatment pathogen in the gatifloxacin and amoxicillin/clavulanate groups were 92.1% (35 of 38) versus 88.9% (16 of 18) for Streptococcus pneumoniae infections and 88.2% (30 of 34) versus 92.3% (12 of 13) for Haemophilus influenzae infections, respectively. Sustained clinical cures 3-4 weeks after treatment ended were obtained in 74.4% (183 of 246) of patients treated with gatifloxacin and 72.7% (88 of 121) of those treated with amoxicillin/clavulanate. Adverse events considered drug-related occurred with similar frequency in the 2 groups. Six patients (2.2%) in the gatifloxacin group and 2 patients (1.5%) in the amoxicillin/clavulanate group developed transient symptoms of mild or moderate arthralgia. CONCLUSIONS: In this comparative evaluation of fluoroquinolone therapy in children with AOM, gatifloxacin was similar in clinical efficacy to amoxicillin/clavulanate 45/6.4 mg/kg/d for treatment of recurrent/nonresponsive infections.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2004

Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with community-acquired respiratory tract infections.

Garenoxacin (T-3811ME, BMS-284756) is a novel, broad-spectrum des-F(6) quinolone currently under study for the treatment of community-acquired respiratory tract infections. This analysis assessed garenoxacin population pharmacokinetics and exposure-response relationships for safety (adverse effects [AE]) and antimicrobial activity (clinical cure and bacteriologic eradication of Streptococcus pneumoniae and the grouping of Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis). Data were obtained from three phase II clinical trials of garenoxacin administered orally as 400 mg once daily for 5 to 10 days for the treatment of community-acquired pneumonia, acute exacerbation of chronic bronchitis, and sinusitis. Samples were taken from each patient before drug administration, 2 h following administration of the first dose, and on the day 3 to 5 visit. Individual Bayesian estimates of the fu (fraction unbound), the Cmax, and the fu for the area under the concentration-time curve from 0 to 24 h (fu AUC(0-24)) were calculated as measurements of drug exposure by using an ex vivo assessment of average protein binding. Regression analysis was performed to examine the following relationships: treatment-emergent AE incidence and AUC(0-24), Cmax, or patient factors; clinical response or bacterial eradication and drug exposure (fu Cmax/MIC, fu AUC(0-24)/MIC, and other exposure covariates); or disease and patient factors. Garenoxacin pharmacokinetics were described by a one-compartment model with first-order absorption and elimination. Clearance was dependent on creatinine clearance, ideal body weight, age, obesity, and concomitant use of pseudoephedrine. The volume of distribution was dependent on weight and gender. Patients with mild or moderate renal dysfunction had, on average, approximately a 16 or 26% decrease in clearance, respectively, compared to patients of the same gender and obesity classification with normal renal function. AE occurrence was not related to garenoxacin exposure. Overall, clinical cure and bacterial eradication rates were 91 and 90%, respectively, for S. pneumoniae and 93 and 92%, respectively, for the grouping of H. influenzae, H. parainfluenzae, and M. catarrhalis. The fu AUC(0-24)/MIC ratios were high (>90% were >200), and none of the pharmacokinetic-pharmacodynamic exposure measurements indexed to the MIC or other factors were significant predictors of clinical or bacteriologic response. Garenoxacin clearance was primarily related to creatinine clearance and ideal body weight. Although garenoxacin exposure was approximately 25% higher for patients with moderate renal dysfunction, this increase does not appear to be clinically significant as exposures in this patient population were not significant predictors of AE occurrence. Garenoxacin exposures were at the upper end of the exposure-response curves for measurements of antimicrobial activity, suggesting that 400 mg of garenoxacin once daily is a safe and adequate dose for the treatment of the specified community-acquired respiratory tract infections.

Adolescent↗