The quinolones: past, present, and future.

The quinolone class of antimicrobial agents has generated considerable interest since its discovery >40 years ago. Substantial progress has been made in our understanding of the molecular mechanisms of the action of quinolones against pathogenic bacteria, the induction of resistance to quinolones in these organisms, and the potential of each quinolone compound to induce toxicity in treated patients. Here, these key discoveries are reviewed; the present indications approved by regulatory agencies are described in detail, with comments on adverse events caused by quinolones in treated patients; and speculation about the future of the quinolones is proffered, even though their future is difficult to predict, because many factors may affect their clinical usefulness. However, the emergence of bacterial resistance to the quinolones is a major factor that will determine the future clinical effectiveness of these agents, so that intense investigation of mechanisms to either prevent or curtail resistance to quinolones is of prime importance to their future.

Retrospective analysis of the safety profile of oral moxifloxacin in elderly patients enrolled in clinical trials.

BACKGROUND AND OBJECTIVE: As aging is associated with physiological changes, including renal and hepatic insufficiency, and a higher risk of drug interactions, special attention needs to be directed towards the safety of medications in the elderly. The objective of this analysis was to evaluate the safety of oral moxifloxacin in elderly patients who were enrolled in clinical trials and to compare these results to those of other commonly used antibacterials. METHODS: Safety data from 27 prospective, randomised, comparative phase II/III trials of oral moxifloxacin included in the Bayer clinical trial database were pooled and analysed by age group (<65 years of age, 65-74 years of age, > or = 75 years of age) and by treatment group (moxifloxacin vs comparator). The primary endpoints included rates of treatment-emergent adverse events (all adverse events regardless of causality), drug-related adverse events, drug-related serious adverse events, deaths and premature discontinuations because of a treatment-emergent adverse event. A treatment by age group interaction test was used to determine if the comparison between moxifloxacin and the comparator group in the incidence rates of any treatment-emergent or drug-related adverse events were affected by increasing age. RESULTS: Of the 12 231 patients who had valid safety data, 6270 had been treated with oral moxifloxacin and 5961 with a comparator antibacterial. The most frequently used comparators were cefuroxime and clarithromycin. Most patients (n = 9671) were <65 years of age (4939 moxifloxacin, 4732 comparator); 1636 patients were 65-74 years of age (842 moxifloxacin, 794 comparator); and 924 patients were > or = 75 years of age (489 moxifloxacin, 435 comparator). The treatment by age group interaction test revealed that the comparison of drug-related adverse event rates between the moxifloxacin and comparator group were not affected by increasing age (p = 0.43). Rates of premature termination between the moxifloxacin and comparator treatment groups also did not increase with age (p = 0.552). No arrhythmias related to corrected QT (QTc) interval prolongation were reported following oral moxifloxacin or comparator treatment in this large group of young and elderly patients. Overall, the number of deaths was similar between the treatment groups (17 moxifloxacin, 19 comparator). CONCLUSIONS: Drug-related adverse event rates associated with oral moxifloxacin or the comparator therapy used in these studies did not significantly increase with advancing age. This pooled analysis suggests that oral moxifloxacin can be safely used in elderly patients with characteristics consistent with those enrolled into the clinical trials.

Haemophilus influenzae in respiratory tract infections in community-based clinical practice: therapy with gatifloxacin.

In this community-based safety surveillance study, the advanced-generation fluoroquinolone gatifloxacin was administered empirically to 15625 adults with community-acquired respiratory tract infections (RTIs), including 1562 clinically evaluable patients with community-acquired pneumonia (CAP) and 2391 with acute exacerbations of chronic bronchitis (AECB). Haemophilus influenzae was the most common pathogen isolated in AECB (40.1%) and the second most common in CAP (36.8%). In vitro susceptibility to gatifloxacin and other fluoroquinolones, amoxicillin/clavulanate, ceftriaxone, cefuroxime axetil, tetracycline, and azithromycin ranged from 95.8% to 100%. In comparison, a significant percentage of the isolates were not susceptible to clarithromycin ( approximately 41%), ampicillin (22% to 28%), and trimethoprim/sulfamethoxazole (14% to 18%). The susceptibility pattern was generally independent of exposure to another antimicrobial in the previous 30 days. CAP and AECB patients infected with H. influenzae had signs and symptoms similar to those infected with Streptococcus pneumoniae. Among clinically evaluable patients with H. influenzae, gatifloxacin cured 159 of 166 (95.8%) with AECB and 112 of 118 (94.9%) with CAP. The cure rate was independent of the beta-lactamase status or serotype of the H. influenzae strain. H. influenzae is not a more benign pathogen in community-acquired RTIs but causes signs and symptoms that are indistinguishable from those caused by other pathogens, notably S. pneumoniae.

Antimicrobial activities of BMS-284756 compared with those of fluoroquinolones and beta-lactams against gram-positive clinical isolates.

The in vitro antibacterial activity of BMS-284756 was compared to those of ciprofloxacin, gatifloxacin, moxifloxacin, ceftriaxone, imipenem, piperacillin-tazobactam, and amoxicillin-clavulanic acid against 492 gram-positive clinical isolates. BMS-284756 was the most-active agent against Streptococcus pneumoniae, Streptococcus viridans, beta-hemolytic streptococci, methicillin-sensitive and -resistant Staphylococcus aureus, methicillin-sensitive and -resistant coagulase-negative staphylococci, and enterococci.