amoxicillin-potassium-clavulanate-combination and Intestinal-Perforation

This prospective, randomized, open, international, multicenter study of adults with complicated intra-abdominal infections (cIAI) compared the efficacy and safety of sequential intravenous (i.v.) to oral (p.o.) moxifloxacin 400 mg once daily, with that of i.v. ceftriaxone 2 g once daily, plus metronidazole 500 mg three times daily, followed by p.o. amoxicillin/clavulanate 625 mg three times daily. The primary efficacy variable was clinical cure at test of cure (TOC) (day 28-42 after study entry) in the per protocol (PP) population. Of 595 patients in the study, 511 patients were valid for PP analysis (246 moxifloxacin, 265 ceftriaxone/metronidazole). Sequential moxifloxacin was noninferior to the comparator regimen--clinical cure rates at TOC were 80.9% versus 82.3% (moxifloxacin versus ceftriaxone/metronidazole; 95% CI -8.9, 4.2%). The incidence of adverse events was comparable between the two treatment groups. Therefore, sequential moxifloxacin monotherapy is as effective and safe as combination therapy with i.v. ceftriaxone plus i.v. metronidazole followed by oral amoxicillin/clavulanate for the treatment of cIAI.

Topics: Abdominal Abscess; Administration, Oral; Adult; Aged; Amoxicillin-Potassium Clavulanate Combination; Anti-Infective Agents; Appendicitis; Aza Compounds; Bacterial Infections; Ceftriaxone; Drug Therapy, Combination; Female; Fluoroquinolones; Gastrointestinal Diseases; Humans; Infusions, Intravenous; Intestinal Perforation; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Moxifloxacin; Peritonitis; Prospective Studies; Quinolines

To compare the safety and efficacy of sequential intravenous (IV) to oral (PO) moxifloxacin treatment against a standard antimicrobial regimen of IV piperacillin-tazobactam followed by PO amoxicillin-clavulanate for the treatment of adults with complicated intra-abdominal infection (cIAI).. cIAIs are commonly due to mixed aerobic and anaerobic bacteria and require both source control and broad-spectrum antibiotic therapy.. A prospective, double-blind, randomized, phase III comparative trial. Patients with cIAI were stratified by disease severity (APACHE II score) and randomized to either IV/PO moxifloxacin (400 mg q24 hours) or comparator (IV piperacillin-tazobactam [3.0/0.375 g q6 hours] +/- PO amoxicillin-clavulanate [800 mg/114 mg q12 hours]), each for 5 to 14 days. The primary efficacy variable was clinical cure rate at the test-of-cure visit (days 25-50). Bacteriologic outcomes were also determined.. : Of 656 intent-to-treat patients, 379 (58%) were valid to assess efficacy (183 moxifloxacin, 196 comparator). Demographic and baseline medical characteristics were similar between the 2 groups. Clinical cure rates at test-of-cure were 80% (146 of 183) for moxifloxacin versus 78% (153 of 196) for comparator (95% confidence interval, -7.4%, 9.3%). The clinical cure rate at test-of-cure for hospital-acquired cIAI was higher with moxifloxacin (82%, 22 of 27) versus comparator (55%, 17 of 31; P = 0.05); rates were similar for community-acquired infections (80% [124 of 156] versus 82% [136 of 165], respectively). Bacterial eradication rates were 78% (117 of 150) with moxifloxacin versus 77% (126 of 163) in the comparator group (95% confidence interval, -9.9%, 8.7%).. Once daily IV/PO moxifloxacin monotherapy was as least as effective as standard IV piperacillin-tazobactam/PO amoxicillin-clavulanate dosed multiple times daily for the treatment of cIAIs.

Topics: Abdominal Abscess; Administration, Oral; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Appendicitis; Aza Compounds; Bacterial Infections; Cross Infection; Double-Blind Method; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Injections, Intravenous; Intestinal Perforation; Male; Middle Aged; Moxifloxacin; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Quinolines; Safety; Stomach Rupture; Treatment Outcome