Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study.

OBJECTIVE: The aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs). METHODS: Data of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems. Patients were randomized to receive either intravenous/oral moxifloxacin (MXF, N = 110) 400 mg q.d. or intravenous piperacillin/tazobactam 4.0/0.5 g t.d.s. followed by oral amoxicillin/clavulanate 875/125 mg b.d. (PIP/TAZ-AMC, N = 96), for 7-21 days until the end of treatment (EOT). The primary endpoint was clinical cure rates in the per-protocol (PP) population at the test-of-cure visit (TOC, 14-28 days after EOT). RESULTS: There were no significant differences between the demographic characteristics of PP patients in either treatment group. At TOC, MXF and PIP/TAZ-AMC had similar efficacy in both the PP and intent-to-treat (ITT) populations: MXF: 76.4 % versus PIP/TAZ-AMC: 78.1 %; 95 % confidence interval (CI) -14.5 %, 9.0 % in the PP population; MXF: 69.9 % versus PIP/TAZ-AMC: 69.1 %; 95 % CI -12.4 %, 12.1 % in the ITT population. The overall bacteriological success rates were similar in both treatment groups (MXF: 71.7 % versus PIP/TAZ-AMC: 71.8 %; 95 % CI -16.9 %, 10.7 %). A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30.9 % versus PIP/TAZ-AMC: 31.8 %, respectively). Death occurred in three MXF-treated patients and one PIP/TAZ-AMC-treated patient; these were unrelated to the study drugs. CONCLUSION: Moxifloxacin has shown favorable safety and efficacy profiles in DFI patients and could be an alternative antibiotic therapy in the management of DFI. CLINICAL TRIAL: NCT00402727.

Moxifloxacin for the treatment of patients with complicated intra-abdominal infections (the AIDA Study).

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.

Moxifloxacin vs ampicillin/sulbactam in aspiration pneumonia and primary lung abscess.

BACKGROUND: Aspiration pneumonia (AP) and primary lung abscess (PLA), are diseases following aspiration of infectious material from the oropharynx or stomach. An antibiotic therapy, also covering anaerobic pathogens, is the treatment of choice. In this study we compared moxifloxacin (MXF) and ampicillin/sulbactam (AMP/SUL) concerning efficacy and safety in the treatment of AP and PLA. METHODS: Patients with pulmonary infections following aspiration were included in a prospective, open-label, randomized, multicenter trial. Sequential antibiotic therapy with MXF or AMP/SUL was administered until complete radiologic and clinical resolution. RESULTS: A total of 139 patients with AP and PLA were included, 96 were evaluable for efficacy (EE, 48 patients in each treatment group). The overall clinical response rates in both groups were numerically identical (66.7%). MXF and AMP/SUL were both well tolerated, even after long-term administration [median duration of treatment (range) in days MXF versus AMP/SUL: AP 11 (4-45) vs 9 (3-25), PLA 30.5 (7-158) vs 35 (6-90)]. CONCLUSION: In the treatment of aspiration-associated pulmonary infections moxifloxacin appears to be clinically as effective and as safe as ampicillin/sulbactam; but, however, having the additional benefit of a more convenient (400 mg qd) treatment.

A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis.

The aim of this study was to compare the efficacy and safety of once daily dosing with moxifloxacin (BAY 12-8039) with that of coamoxiclav given three times daily for the treatment of acute exacerbation of chronic bronchitis (AECB). Moxifloxacin (one 400 mg tablet daily) was administered orally for 5 days and co-amoxiclav (three 625 mg tablets daily) was given orally for 7 days. The study was randomized, non-blinded, multinational (12 countries) and multicentre (68 centres). A total of 575 patients, all with clear signs of AECB, were treated, 292 with moxifloxacin and 283 with co-amoxiclav. Of these, 512 patients were evaluable for efficacy (261 in the moxifloxacin group and 251 in the co-amoxiclav group). The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and rhonchi. The success rate for moxifloxacin in the evaluable patients was 96.2% and that for co-amoxiclav was 91.6%. The 95% confidence intervals for this difference (0.4%; 8.7%) indicate equivalence in the treatments. Sputum samples were taken from patients and 140 of these contained a pathogen, Haemophilus influenzae being the most frequently isolated. Moraxella catarrhalis and Streptococcus pneumoniae were also commonly isolated pathogens. The eradication rate at 14 days in the evaluable patients was 87.7% in the moxifloxacin group and 89.6% in the coamoxiclav group. Both drugs were well tolerated with no significant differences in the numbers of drug-related adverse events or the numbers of patients withdrawing because of an adverse event. These results and the broad spectrum of antibacterial activity make moxifloxacin a promising and safe alternative to conventional therapy for the empirical treatment of AECB.

Treatment of hypertensive emergency. Comparison of a new dosage form of the calcium antagonist nitrendipine with nifedipine capsules.

OBJECTIVE: To present the efficacy and tolerability of a new oral dosage form of the calcium antagonist nitrendipine compared to nifedipine capsules in patients with hypertensive emergency. DESIGN: Multicenter randomized double blind clinical study. SETTING: 23 study centres (hospitals) in Germany. PATIENTS: 161 patients between 20 and 70 years with acutely elevated blood pressure (systolic 200-250 mmHg, diastolic between 110-140 mmHg) with and without concomitant clinical symptoms. INTERVENTIONS: Double blind treatment with 10 mg nifedipine or 5 mg nitrendipine. Nifedipine was administered as capsules, nitrendipine was given from a small plastic tube (vial), containing 1 ml alcoholic solution. Every patient received in addition to the test medication a placebo corresponding to the other product. Patients with insufficient treatment after 45 min were given either an additional capsule of 10 mg nifedipine or a further vial containing 5 mg nitrendipine according to their group and maintaining the double dummy procedure. MEASUREMENTS AND RESULTS: Blood pressure and heart rate were measured repeatedly during 4 h, before and 90 min after beginning of the treatment a 12 channel resting ECG was recorded. At 45 min after administration the blood pressure had fallen significantly from 216.0/117.4 mmHg to 170.0/93.3 mmHg under nifedipine and from 216.9/117.3 mmHg to 177.4/94.4 mmHg under nitrendipine. 61.6% of the nifedipine patients and 58.8% of the nitrendipine patients had already reached blood pressure values < 180/100 mmHg after 45 min and in both groups 83% of these patients were still in this limit at the end of the observation period after 4 h. Tolerability was very good in both groups. CONCLUSION: The new dosage form of nitrendipine (vial with 1 ml of alcoholic solution) represents an alternative in the treatment of hypertensive emergency.