cefpodoxime-proxetil and Pneumonia--Pneumococcal

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.. 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.. 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.. 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.. The results of this study suggest that cefditoren may have a role in the treatment of CAP in ambulatory patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefpodoxime Proxetil; Ceftizoxime; Cephalosporins; Child; Community-Acquired Infections; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Pneumococcal; Prospective Studies; South Africa; Streptococcus pneumoniae; Treatment Outcome; United States

We evaluated in vitro and in vivo activities of cefpodoxime proxetil (CPDX-PR) in comparison with other oral beta-lactams, cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), and faropenem (FRPM), against penicillin-susceptible and -resistant Streptococcus pneumoniae. In vitro activities (MICs) of CPDX, CFDN, CDTR, and FRPM against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of penicillin G, < or = 0.063 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of penicillin G, 0.125-1 microgram/ml), and penicillin-resistant S. pneumoniae (PRSP: MIC of penicillin G, > or = 2 micrograms/ml), were tested by an agar dilution method. The MIC80s of CPDX against 27 PSSP strains, 23 PISP strains, and 23 PRSP strains were 0.032, 1, and 8 micrograms/ml, respectively, which were superior to or equal to those of CFDN (0.063, 4, and 8 micrograms/ml) and were inferior to those of CDTR (0.016, 0.5, and 1 microgram/ml) and FRPM (< or = 0.008, 0.25, and 1 microgram/ml). Infection was induced in mice by inoculating with a PRSP clinical isolate, 9605 or 9601 (serotype 6), or 10692 (serotype 19), through the nares of male ddY mice into the lungs. The mice were treated with drugs with doses of 2-50 mg/kg at 18, 26, 42, and 50 hours after the infection. Viable cell numbers in the lungs and blood were assayed at 66 hours after the infection. The efficacy of each drug was dose-dependent. CPDX-PR showed the most potent in vivo efficacy among the drugs tested against the infections caused by the PRSP strains. MICs of the drugs against PRSP 9605, 9601, and 10692 were as follows: CPDX, 4, 4 and 2 micrograms/ml; CFDN, 16, 16, and 4 micrograms/ml; CDTR, 1, 1, and 0.5 microgram/ml; and FRPM, 1, 0.5, and 0.5 microgram/ml, respectively. Thus, CPDX-PR showed a stronger in vivo activity than that expected from the MICs of CPDX. This was probably caused by the pharmacokinetic advantage of CPDX over the other drugs used in this study.

Topics: Animals; Anti-Bacterial Agents; beta-Lactams; Cefdinir; Cefpodoxime Proxetil; Ceftizoxime; Cephalosporins; Lactams; Male; Mice; Microbial Sensitivity Tests; Penicillin Resistance; Pneumonia, Pneumococcal; Prodrugs; Streptococcus pneumoniae