Forty nine subjects with acute bacterial exacerbations of
chronic bronchitis (ABECB) treated with
grepafloxacin were evaluated for parameters predictive of clinical outcome. Signs and symptoms associated with ABECB were serially collected and evaluated for changes.
Coughs per day, sputum volume and the percentage of sputum neutrophils were associated with clinical outcome. A by groups analysis, based on clinical success was performed using Cox regression analysis to determine factors associated with time to clinical success and time to reduction in sputum volume,
coughs per day and sputum neutrophil percent. Factors evaluated included AUIC (AUC/MIC), isolate species, years and type of underlying
lung disease, alcohol use, smoking history and number of ABECB within the previous 12 months. AUIC<276 (mg h/l)/mg/l (P<0.03) and or the presence of mild
bronchiectasis (P<0.01) were associated with longer time to clinical success. In addition a relationship was found between AUIC>212 (mg h/l)/mg/l (P<0.01) and AUIC>576 (mg h/l)/mg/l (P<0.02) and decreasing days to sputum volume reduction and
coughs per day, respectively. A diagnosis of mild
bronchiectasis prolonged the time to reduce
coughs per day (P<0.03) and neutrophil percentage (P<0.01). Patients with mild
bronchiectasis were found to have an increase in the time to clinical success,
coughs per day improvement and sputum neutrophil percent improvement. AUIC is an important PK/PD parameter predictive of successful outcome in ABECB, even in subjects with mild
bronchiectasis. Grepafloxicin has been withdrawn from sale since these studies were carried out. This work is published to illustrate the relationship between pharmacodynamics and clinical efficacy and the use of AUIC as a valuable predictive parameter for
fluoroquinolones.