The Þrst evidence of Pa in respiratory secretion (sputum) cultures is a landmark for disease progression in cystic Þbrosis (CF). Virtually all CF patients acquire Pa during their lifetime. Until recently the bacterium was rarely eradicated once established. Although the course of pulmonary infection is not yet fully understood, it has been hypothesized that an increase in the prevalence of Pa may be associated with an increased use of prophylactic antibiotics targetting Staphylococcus aureus (Sa). To examine this hypothesis, bacteriological records of CF patients diagnosed at The Hospital for Sick Children (HSC) between 1970 and 1989 were reviewed, since during this period the approach to prophylactic antibiotic treatment underwent considerable change. Patients were followed for at least nine years, until their most recent culture. The Þrst detection of Pa in the sputum cultures of each patient was considered to be the time of onset of Pa. Kaplan Meier survival curves and the log-rank statistic were computed to compare the age of onset for patients diagnosed during 1970-79 and 1980-89. Since males and females have been reported to have different risks of Pa infection, and since age at diagnosis clearly affects the age of documented colonization, Cox proportional hazard regression was used to assess the joint effects of these variables along with the calendar year of CF diagnosis. Of the 463 patients who fulÞlled the study criteria, 391 (84%) have had at least one culture positive for Pa. Median age of onset of Pa was signiÞcantly earlier in the 1970-79 cohort than in the 1980-89 cohort, 3.4 years vs. 5.9 years (p=0.0002). This difference between the 70Õs and 80Õs was seen in those diagnosed under 2 years of age (1.8 vs. 3.3 years) and those diagnosed older than 2 years (9.6 vs. 12.8 years). Cox regression models demonstrated that the effects of age at diagnosis and decade of diagnosis were independent and there was no interaction between these factors. Age of onset was not different for males and females. Moreover, there was no difference in nutritional status of the patients in the study cohorts. Changes in antibiotic prescribing pattern at HSC during the study period coincided with the change in age of onset of Pa. During the seventies, anti-Sa antibiotics were routinely prescribed for newly diagnosed patients even in the absence of Sa in their sputum cultures. During the early eighties, this regimen was gradually modiÞed. When date of diagnosis was stratiÞed into shorter periods, the change in age of onset was seen to correspond closely to the change in antibiotic prescribing pattern. These Þndings provide strong support for the hypothesized link between prophylactic antibiotic use and the world-wide increase in prevalence of Pa over the last few decades. As CF survival increases it will be ever more important to consider the potential long term effects of antibiotic and other therapeutic regimens. (Supported by CCFF) 427