Randomized controlled trial of moxifloxacin compared with piperacillin-tazobactam and amoxicillin-clavulanate for the treatment of complicated intra-abdominal infections.

OBJECTIVE: 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). SUMMARY BACKGROUND DATA: cIAIs are commonly due to mixed aerobic and anaerobic bacteria and require both source control and broad-spectrum antibiotic therapy. METHODS: 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. RESULTS: : 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%). CONCLUSIONS: 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.

Eradication of common pathogens at days 2, 3 and 4 of moxifloxacin therapy in patients with acute bacterial sinusitis.

BACKGROUND: Acute bacterial sinusitis (ABS) is a common infection in clinical practice. Data on time to bacteriologic eradication after antimicrobial therapy are lacking for most agents, but are necessary in order to optimize therapy. This was a prospective, single-arm, open-label, multicenter study to determine the time to bacteriologic eradication in ABS patients (maxillary sinusitis) treated with moxifloxacin. METHODS: Adult patients with radiologically and clinically confirmed ABS received once-daily moxifloxacin 400 mg for 10 days. Middle meatus secretion sampling was performed using nasal endoscopy pre-therapy, and repeated on 3 consecutive days during treatment. Target enrollment was 30 bacteriologically evaluable patients (pre-therapy culture positive for Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and evaluable cultures for at least Day 2 and Day 3 during therapy visits), including at least 10 each with S. pneumoniae or H. influenzae. RESULTS: Of 192 patients enrolled, 42 were bacteriologically evaluable, with 48 pathogens isolated. Moxifloxacin was started on Day 1. Baseline bacteria were eradicated in 35/42 (83.3%) patients by day 2, 42/42 (100%) patients by day 3, and 41/42 (97.6%) patients by day 4. In terms of individual pathogens, 12/18 S. pneumoniae, 22/23 H. influenzae and 7/7 M. catarrhalis were eradicated by day 2 (total 41/48; 85.4%), and 18/18 S. pneumoniae and 23/23 H. influenzae were eradicated by day 3. On Day 4, S. pneumoniae was isolated from a patient who had negative cultures on Days 2 and 3. Thus, the Day 4 eradication rate was 47/48 (97.9%). Clinical success was achieved in 36/38 (94.7%) patients at the test of cure visit. CONCLUSION: In patients with ABS (maxillary sinusitis), moxifloxacin 400 mg once daily for 10 days resulted in eradication of baseline bacteria in 83.3% of patients by Day 2, 100% by Day 3 and 97.6% by Day 4.

Sequential intravenous/oral moxifloxacin versus intravenous piperacillin-tazobactam followed by oral amoxicillin-clavulanate for the treatment of complicated skin and skin structure infection.

In this prospective, double-blind, multicentre trial, adult patients with complicated skin and skin structure infection (cSSSI) randomly received sequential intravenous (i.v.)/oral (p.o.) moxifloxacin (400 mg once a day) or a control regimen of i.v. piperacillin-tazobactam (3.0/0.375 g every 6 h) followed by p.o. amoxicillin-clavulanate (800 mg every 12 h), each for 7-14 days. Clinical cure rates at the test-of-cure visit (10-42 days post therapy) for the efficacy-valid population were 79% (143/180) for the moxifloxacin-treated group and 82% (153/187) for the control group (95% confidence interval, -12.04, 3.29). Bacteriological eradication rates for Staphylococcus aureus, the most prevalent organism, were 78% and 80%, respectively. The incidence of drug-related adverse events was similar for both groups (31% moxifloxacin, 30% control). Sequential i.v./p.o. moxifloxacin was as effective and well tolerated as i.v. piperacillin-tazobactam followed by p.o. amoxicillin-clavulanate in treating patients with cSSSI.

Efficacy and tolerability of moxifloxacin in the treatment of acute bacterial sinusitis caused by penicillin-resistant Streptococcus pneumoniae: a pooled analysis.

BACKGROUND: Penicillin-resistant Streptococcus pneumoniae (PRSP) has become a relatively common pathogen in upper and lower respiratory tract infections, including acute bacterial sinusitis (ABS). OBJECTIVE: The goal of this analysis was to assess the efficacy and tolerability of moxifloxacin in the treatment of ABS caused by penicillin-sensitive S pneumoniae (PSSP) and PRSP METHODS: Two prospective, multicenter, open-label, noncomparative US trials of moxifloxacin were included in this pooled analysis. All patients received oral moxifloxacin 400 mg once daily for 7 to 10 days. Minimum inhibitory concentrations (MICs) of moxifloxacin and penicillin were determined using the E-test and standard broth-microdilution methods. The primary end point was clinical success at the test-of-cure visit (21-37 days after completion of therapy) in patients with a positive pretherapy sinus culture. Data are presented for patients with ABS caused by both PSSP and PRSP RESULTS: Of 806 patients enrolled in the 2 studies, 146 had microbiologically confirmed bacterial infection. Sixty-nine patients had ABS caused by S pneumoniae, including 15 confirmed cases of PRSP infection. The majority of the 69 clinically evaluable patients were white (n = 63) and female (n = 46), and the mean age of this population was 43 years. Investigators categorized the episode of ABS as severe in 26 (37.7%) of clinically evaluable patients and of moderate severity in the remainder (62.3% [43]); however, most patients (78.3% [54/69]) reported >/=1 severe symptom. The episode of ABS was classified as severe in 8 (53.3%) of the 15 patients with PRSP infection. Clinical and bacteriologic success at the test-of-cure visit was achieved in 93.3% (14/15) of patients with PRSP infection, compared with 88.4% (61/69) of all patients infected with S pneumoniae regardless of penicillin susceptibility. Moxifloxacin MICs against the 15 PRSP strains ranged from 0.06 to 0.25 microg/mL. Data from 805 patients were available for tolerability analysis. The most commonly occurring adverse events were nausea, headache, and diarrhea. Generally, adverse events were mild to moderate. None of the 6 serious adverse events reported were considered related to moxifloxacin therapy. CONCLUSION: In this small cohort of patients, moxifloxacin provided clinical and bacteriologic cures in the majority of patients with ABS caused by PRSP, including those with severe sinusitis.