Integrated safety summary of phase II and III studies comparing oral nemonoxacin and levofloxacin in community-acquired pneumonia.

BACKGROUND: Nemonoxacin, a novel nonfluorinated quinolone, has broad-spectrum antibacterial activity, including activity against antibiotic-resistant strains, and was developed for treating community-acquired pneumonia (CAP). This report provides an integrated safety summary of oral nemonoxacin from two phase II and one phase III clinical studies. METHODS: Patients with mild CAP were randomized for treatment with nemonoxacin 500 mg (NEMO-500MG), nemonoxacin 750 mg (NEMO-750MG), or levofloxacin 500 mg (LEVO), orally, once daily, for 7-10 days. Hematological, gastrointestinal, and hepatic disorders; electrocardiography abnormalities; and reported quinolone-associated clinical concerns were included in this analysis. RESULTS: A total of 520, 155, and 320 subjects were assigned to receive NEMO-500MG, NEMO-750MG, and LEVO, respectively. The incidence of adverse events (AEs) was the highest (54.8%) in the NEMO-750MG group (NEMO-500MG, 36.9%; NEMO-750MG, 54.8%; LEVO, 39.7%) and that of drug-related AEs was comparable between the three groups (NEMO-500MG, 22.9%; NEMO-750MG, 31.0%; LEVO, 22.5%). The majority (>80%) of the patients showed mild drug-related AEs and the distribution based on severity was similar between the groups. The most commonly reported drug-related AEs included neutropenia (NEMO-500MG, 2.5%; NEMO-750MG, 8.4%; LEVO, 4.4%), nausea (NEMO-500MG, 2.5%; NEMO-750MG, 7.1%; LEVO, 2.5%), leukopenia (NEMO-500MG, 2.3%; NEMO-750MG, 4.5%; LEVO, 3.1%), and increased alanine aminotransferase level (NEMO-500MG, 4.4%; NEMO-750MG, 0%; LEVO, 2.5%). CONCLUSION: Nemonoxacin was well tolerated and no clinically significant safety concerns were identified, suggesting that it possesses a desirable safety and tolerability profile similar to that of levofloxacin, and may be a suitable alternative to fluoroquinolones for treating patients with CAP.

Previous antibiotic exposure and evolution of antibiotic resistance in mechanically ventilated patients with nosocomial infections.

PURPOSE: This study aimed to evaluate the impact of previous antibiotic exposure and the influence of time interval since exposure on the evolution of antibiotic-resistant infections. METHODS: We retrospectively analyzed 167 mechanically ventilated patients with nosocomial infections over a 3-year period, with focus on infections in the bloodstream, urinary tract, lower respiratory tract, and surgical sites. RESULTS: Of 167 patients, 62% were confirmed as antibiotic resistant. The most common isolated pathogen was extended-spectrum ß-lactamase Enterobacteriaceae (43.9%), followed by methicillin-resistant Staphylococcus aureus (22.8%), and carbapenem-resistant Acinetobacter baumannii (17.5%). Multivariate analysis revealed that the association between resistance and the time interval increased within 10 days (odds ratio [OR], 2.45; P=.133) and peaked at 11 to 20 days (OR, 7.17; P=.012). The data were categorized into 2 groups: when the time interval was more than 20 days, there was a 23.9% reduction in resistance rate compared with when the time interval was 20 days or less (OR, 0.36; P=.002). CONCLUSIONS: Although antibiotic exposure increased resistance rate in nosocomial infections, this association decreased as time interval increased. Antibiotic stewardship should consider the significance of time interval while investigating the evolution of subsequent antibiotic-resistant infections.

Efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia.

Nemonoxacin, a novel nonfluorinated quinolone, exhibits potent in vitro and in vivo activities against community-acquired pneumonia (CAP) pathogens, including multidrug-resistant Streptococcus pneumoniae. Patients with mild to moderate CAP (n = 265) were randomized to receive oral nemonoxacin (750 mg or 500 mg) or levofloxacin (500 mg) once daily for 7 days. Clinical responses were determined at the test-of-cure visit in intent-to-treat (ITT), clinical per protocol (PPc), evaluable-ITT, and evaluable-PPc populations. The clinical cure rates for 750 mg nemonoxacin, 500 mg nemonoxacin, and levofloxacin were 89.9%, 87.0%, and 91.1%, respectively, in the evaluable-ITT population; 91.7%, 87.7%, and 90.3%, respectively, in the evaluable-PPc population; 82.6%, 75.3%, and 80.0%, respectively, in the ITT population; and 83.5%, 78.0%, and 82.3%, respectively, in the PPc population. Noninferiority to levofloxacin was demonstrated in both the 750-mg and 500-mg nemonoxacin groups for the evaluable-ITT and evaluable-PPc populations, and also in the 750 mg nemonoxacin group for the ITT and PPc populations. Overall bacteriological success rates were high for all treatment groups in the evaluable-bacteriological ITT population (90.2% in the 750 mg nemonoxacin group, 84.8% in the 500 mg nemonoxacin group, and 92.0% in the levofloxacin group). All three treatments were well tolerated, and no drug-related serious adverse events were observed. Overall, oral nemonoxacin (both 750 mg and 500 mg) administered for 7 days resulted in high clinical and bacteriological success rates in CAP patients. Further, good tolerability and excellent activity against common causative pathogens were demonstrated. Nemonoxacin (750 mg and 500 mg) once daily is as effective and safe as levofloxacin (500 mg) once daily for the treatment of CAP.

Mortality and readmission among ventilator-dependent patients after successful weaned discharge from a respiratory care ward.

BACKGROUND/PURPOSE: Patients on prolonged mechanical ventilation in Taiwan are stepped down to a respiratory care ward (RCW) for further respiratory care. Only a few patients in the RCW can ultimately be weaned and discharged. In this study, we tried to determine factors that predict mortality and readmission of these patients in the post-discharge period. METHODS: Between May 1, 2004 and October 31, 2006, clinical data were retrospectively analyzed for eligible patients in a RCW. Patients who were successfully weaned from mechanical ventilation were enrolled in this study. RESULTS: A total of 243 patients were eligible for evaluation, and 67 patients were successfully weaned and discharged. By Kaplan-Meier curve, 36 (67.1%) patients were readmitted within 3 months after discharge, and among these, 23 (63.9%) had mechanical ventilation reinstituted at the time of first readmission. The most common cause of readmission was airway infection (80.5%). Overall mortality and readmission rates at 1 year after weaned discharge were 32.9% and 88.2%, respectively. By multivariate analysis, patients with neurologic causes of ventilator dependency were less likely to be readmitted (hazard ratio = 0.36; p =0.034), and neoplastic diseases (hazard ratio = 4.66; p =0.031) were independently associated with mortality. CONCLUSION: Underlying comorbidities and causes of ventilator dependency are important predictors of mortality and readmission among patients after weaned discharge from a RCW.