Randomized, double-blind, multicenter comparison of oral cefditoren 200 or 400 mg BID with either cefuroxime 250 mg BID or cefadroxil 500 mg BID for the treatment of uncomplicated skin and skin-structure infections.

BACKGROUND: Uncomplicated skin and skin-structure infections are commonly observed in medical practice. Because these infections typically are confined to the superficial layers and seldom lead to the destruction of skin structures and resultant systemic dissemination, in general they can be treated with an oral antibiotic with potent microbiologic activity against gram-positive pathogens. OBJECTIVE: This paper compares the efficacy and tolerability of 3 beta-lactam antibiotics in patients with uncomplicated skin and skin-structure infections. METHODS: Two double-blind, multicenter, parallel-group studies were conducted, in which patients aged > or = 12 years with uncomplicated skin and skin-structure infections were randomized to receive cefditoren 200 or 400 mg, cefuroxime 250 mg, or cefadroxil 500 mg, each BID for 10 days. Study 1 compared cefditoren with cefuroxime; Study 2 compared cefditoren with cefadroxil. Clinical and microbiologic responses were assessed at a posttreatment visit (within 48 hours of treatment completion) and test-of-cure visit (7-14 days after treatment completion). Patients were monitored closely throughout the study with the use of physical examinations, clinical laboratory tests, and assessment of adverse events. RESULTS: A total of 1,685 patients (855 males, 830 females; mean age, 41.1 years [range, 12-95 years]) were enrolled. Within both studies, the 3 treatment groups were similar at baseline based on demographic characteristics and types of infection. Cellulitis (26%), wound infection (25%), and simple abscess (15%) were the most common infections. Clinical cure rates at the test-of-cure visit were 85% (443/523) for cefditoren 200 mg, 83% (427/516) for cefditoren 400 mg, 88% (234/265) for cefuroxime, and 85% (211/248) for cefadroxil. At the test-of-cure visit, cefditoren 200 mg had eradicated significantly fewer of the causative pathogens isolated before treatment in microbiologically evaluable patients than did cefuroxime in Study 1 (P = 0.043) but significantly more of the pathogens than did cefadroxil in Study 2 (P = 0.018). Eradication rates for the most commonly isolated pathogens were generally similar in the 3 treatment groups in both studies, with the only significant difference favoring cefditoren 200 and 400 mg over cefadroxil for Peptostreptococcus species in Study 2 (P = 0.016 and P = 0.003, respectively). A minority of patients (< or = 5% in any treatment group) discontinued study-drug treatment prematurely due to a treatment-related adverse event, with statistically higher rates for cefditoren 400 mg than for cefditoren 200 mg and the comparator cephalosporins (each P < 0.05). All 3 cephalosporins were generally well tolerated. Most adverse events (>93%) were categorized as mild to moderate, with the most common being diarrhea, nausea, and headache. CONCLUSION: In this population of patients with uncomplicated skin and skin-structure infections, including those due to Staphylococcus aureus or Streptococcus pyogenes, the clinical cure rate and tolerability of cefditoren were comparable to those of cefuroxime and cefadroxil.

A comparison of cefditoren pivoxil and amoxicillin/ clavulanate in the treatment of community-acquired pneumonia: a multicenter, prospective, randomized, investigator-blinded, parallel-group study.

BACKGROUND: Cefditoren pivoxil is a broad-spectrum cephalosporin that is approved for the treatment of pharyngitis, acute exacerbations of chronic bronchitis, and skin and skin-structure infections. OBJECTIVE: This study was conducted to examine the efficacy and tolerability of cefditoren in the treatment of community-acquired pneumonia (CAP). Amoxicillin/clavulanate was chosen as a comparator because of its established efficacy and general acceptance as a standard of care in CAP. METHODS: This multicenter, prospective, randomized, investigator-blinded, parallel-group trial compared oral cefditoren 200 and 400 mg BID with oral amoxicillin/clavulanate 875/125 mg BID for 14 days in adult outpatients with CAP. RESULTS: Eight hundred two patients (404 men, 398 women; mean age, 50 years; age range, 12-93 years) with CAP were enrolled. Comparable clinical cure rates were observed among evaluable patients in all treatment groups at both the posttreatment and follow-up visits: 88.0% (125/142) for cefditoren 200 mg, 89.9% (143/159) for cefditoren 400 mg, and 90.3% (130/144) for amoxicillin/clavulanate at the posttreatment visit, and 86.5% (128/148), 86.8% (138/159), and 87.8% (129/147) for the respective groups at the follow-up visit. Of 82 Streptococcus pneumoniae strains isolated before treatment, 22 (26.8%) had reduced susceptibility to penicillin, 12 (14.6%) of them penicillin resistant. Overall eradication rates at the posttreatment visit for pathogens isolated from microbiologically evaluable patients were 84.0%, 88.6%, and 82.6% for cefditoren 200 mg, cefditoren 400 mg, and amoxicillin/clavulanate, respectively. In the respective treatment groups, 80.6%, 88.6%, and 88.0% of Haemophilus influenzae strains and 95.0%, 96.2%, and 89.5% of S pneumoniae strains were eradicated. The rates of resolution of or improvement in clinical signs and symptoms were comparable between treatment groups. The treatment regimens were well tolerated, with 4.9%, 3.0%, and 5.2% of patients in the respective treatment groups requiring discontinuation of study drug due to an adverse event. CONCLUSIONS: In this study in adult outpatients with CAP, both doses of cefditoren demonstrated equivalence to amoxicillin/clavulanate based on rates of clinical and microbiologic cure. All 3 regimens were effective in resolving or improving the clinical signs and symptoms of CAP. Both cefditoren and amoxicillin/ clavulanate were well tolerated.

Cefditoren pivoxil versus cefpodoxime proxetil for community-acquired pneumonia: results of a multicenter, prospective, randomized, double-blind study.

BACKGROUND: According to recently issued treatment guidelines, appropriate empiric choices for ambulatory patients with community-acquired pneumonia (CAP) are a macrolide, doxycycline (for patients aged > or = 8 years), or an oral beta-lactam agent with good activity against pneumococci. OBJECTIVE: This study was designed to compare cefditoren pivoxil, a new beta-lactam, with cefpodoxime proxetil, a beta-lactam with an established role in the treatment of CAP. METHODS: This was a multicenter, prospective, randomized, double-blind study conducted in the United States and South Africa. Ambulatory patients with a diagnosis of CAP were randomized to 14 days of treatment with cefditoren 200 or 400 mg BID or cefpodoxime 200 mg BID. Assessments of clinical cure and pathogen eradication were conducted at 2 visits during treatment, 1 posttreatment visit (s48 hours after completion of treatment), and 1 follow-up visit (7-14 days after completion of treatment). The development of resistant pathogens was assessed at the follow-up visit but not thereafter. The relative cost of treatment was not assessed. RESULTS: The study enrolled 851 patients. Comparable clinical cure rates were observed among evaluable patients in the 3 treatment groups at both the posttreatment and followup visits: at the posttreatment visit, cure rates were 90.5% (162/179) for cefditoren 200 mg, 89.7% (148/165) for cefditoren 400 mg, and 92.2% (153/166) for cefpodoxime 200 mg; at the follow-up visit, they were a respective 88.4% (160/181), 87.2% (143/164), and 90.4% (151/167). Of the 171 strains of Streptococcus pneumoniae isolated before treatment, 22 (12.9%) had reduced susceptibility to penicillin, 5 (2.9%) of them penicillin resistant (minimum inhibitory concentration > or = 2 microg/mL). At the posttreatment visit, the overall eradication rates of pathogens isolated from microbiologically evaluable patients were 88.7% (134/151), 89.9% (134/149), and 95.7% (134/140) in the respective treatment groups (P = 0.031, cefditoren 200 mg vs cefpodoxime). Eradication rates of S pneumoniae were 93.8% (45/48), 95.7% (45/47), and 95.6% (43/ 45) in the respective treatment groups; those of Haemophilus influenzae were 90.2% (46/51), 97.7% (43/44), and 97.4% (37/38). The rates of resolution and/or improvement in clinical signs and symptoms were comparable between groups. The study drugs were well tolerated, with 1.7%, 2.5%, and 1.4% of patients in the respective groups discontinuing study drug prematurely due to a treatment-related adverse event, the majority of these associated with the digestive system. CONCLUSION: The results of this study suggest that cefditoren may have a role in the treatment of CAP in ambulatory patients.

ClinRefLink: implementation of infobutton-like functionality in a commercial clinical information system incorporating concepts from textual documents.

Clinical information systems offer an opportunity to provide clinicians with medical reference materials during clinical encounters when the information is most beneficial. Implementation of this "Infobutton" concept has been described by a number of institutions with locally developed clinical information systems and electronic medical records. This article describes the development of an infobutton-like application called ClinRefLink embedded within a commercial clinical information system. ClinRefLink is somewhat unique in that it offers clinicians the option to perform reference searches based on clinical entities identified within narrative documents. In the first 30 days after implementation, 1018 reference searches were performed. The characteristics of the clinicians and the clinical context of the search terms are described. These data support the value of clinical term extraction from narrative documents as a component of an infobutton system.