Model [26]: PEC M|fexcreta V ??Clarithromycin Clindamycin Metronidazole NorfloxacinJ01FA09 J01FF01 P01AB01 J01MA25 10?0 40 30OfloxacinJ01MA01/ S01AX70Sulfamethoxazole J01EE50 10?0TrimethoprimJ01EEWhen different values were found, the highest (worst case) was selected. Data from the Compendium SuisseH can be found at http://www.kompendium.ch (site last accessed in June 2012). doi:10.1371/journal.pone.0053592.twhere PEC is the model output (monthly basis), i.e., the concentration at the entrance of the WTP, V is the monthly volume of wastewater reaching the WTP, M is the monthly massAntibiotics Origin in WastewaterFigure 4. Seasonal fluctuations of antibiotic sales are shown in the left column. ambulatory (dark grey, left axis) and hospitals (light grey, right axis). The data are normalized to the annual mean. On the right side of the figure, two columns of plots show periodograms for ambulatory sales and hospital usage (left to right, respectively). The peak in the ambulatory-sales periodogram occurs at 0.08 month21, i.e., a period of 12 Calcitonin (salmon) months for these sales, indicated by the dashes.Antibiotics Origin in WastewaterFigure 5. Ratio of hospital use to total use for the Lausanne WTP basin. Results are presented for clindamycin (green), trimethoprim (red) and ciprofloxacin (blue). This ratio shows considerable volatility, depending on the month and substance considered. doi:10.1371/journal.pone.0053592.gof antibiotic prescribed (sum of ambulatory and hospital prescriptions), and fexcreta is the excretion ratio of the substance. Excretion ratios for the list of substances investigated are presented in Table 2. In this study, we used the PEC model and monthly sales data to Dimethylenastron cost investigate fluctuations of antibiotic concentrations in the WTP influent. Monthly dry weather water volumes to the WTP were used so that predicted concentrations were not distorted by any dilution effects.Results and Discussion Periodicity in Consumption CycleFluctuations in ambulatory antibiotic consumption are compared with consumption of antibiotics in hospitals for the selected substances. Figure 4 shows the monthly fluctuation of sales normalized to the annual mean for both ambulatory and hospital uses. Three groups of substances emerge in Figure 4. The first group is comprised of azithromycin, clarithromycin and ciprofloxacin. These substances present clear seasonality of their ambulatory Table 3. Correlation coefficient of ambulatory and hospitals sales.sales data. The visual evidence of this seasonality is supported by the periodogram of the ambulatory sales signal, with a dominant frequency found at 0.083 month21, which corresponds to a 12months period. For azithromycin and clarithromycin, the highest ambulatory sales in winter are around three times greater than the minimum consumption observed during summer. Ciprofloxacin ambulatory sales vary somewhat, between +20 of the annual mean. Some seasonality was also observed for norfloxacin ambulatory sales. This periodicity is absent for the hospitals uses. The second group of substances is composed of ofloxacin, clindamycin and sulf/trim. No seasonal fluctuation was found for these antibiotics, either in the ambulatory sales data or in hospital use. Finally, metronidazole was found to have a clear six months period in its ambulatory sales. Differences in seasonal cycles for antibiotics sales data can be explained by considering their different therapeutic uses. The substances with high seasonality in ambulatory sa.Model [26]: PEC M|fexcreta V ??Clarithromycin Clindamycin Metronidazole NorfloxacinJ01FA09 J01FF01 P01AB01 J01MA25 10?0 40 30OfloxacinJ01MA01/ S01AX70Sulfamethoxazole J01EE50 10?0TrimethoprimJ01EEWhen different values were found, the highest (worst case) was selected. Data from the Compendium SuisseH can be found at http://www.kompendium.ch (site last accessed in June 2012). doi:10.1371/journal.pone.0053592.twhere PEC is the model output (monthly basis), i.e., the concentration at the entrance of the WTP, V is the monthly volume of wastewater reaching the WTP, M is the monthly massAntibiotics Origin in WastewaterFigure 4. Seasonal fluctuations of antibiotic sales are shown in the left column. ambulatory (dark grey, left axis) and hospitals (light grey, right axis). The data are normalized to the annual mean. On the right side of the figure, two columns of plots show periodograms for ambulatory sales and hospital usage (left to right, respectively). The peak in the ambulatory-sales periodogram occurs at 0.08 month21, i.e., a period of 12 months for these sales, indicated by the dashes.Antibiotics Origin in WastewaterFigure 5. Ratio of hospital use to total use for the Lausanne WTP basin. Results are presented for clindamycin (green), trimethoprim (red) and ciprofloxacin (blue). This ratio shows considerable volatility, depending on the month and substance considered. doi:10.1371/journal.pone.0053592.gof antibiotic prescribed (sum of ambulatory and hospital prescriptions), and fexcreta is the excretion ratio of the substance. Excretion ratios for the list of substances investigated are presented in Table 2. In this study, we used the PEC model and monthly sales data to investigate fluctuations of antibiotic concentrations in the WTP influent. Monthly dry weather water volumes to the WTP were used so that predicted concentrations were not distorted by any dilution effects.Results and Discussion Periodicity in Consumption CycleFluctuations in ambulatory antibiotic consumption are compared with consumption of antibiotics in hospitals for the selected substances. Figure 4 shows the monthly fluctuation of sales normalized to the annual mean for both ambulatory and hospital uses. Three groups of substances emerge in Figure 4. The first group is comprised of azithromycin, clarithromycin and ciprofloxacin. These substances present clear seasonality of their ambulatory Table 3. Correlation coefficient of ambulatory and hospitals sales.sales data. The visual evidence of this seasonality is supported by the periodogram of the ambulatory sales signal, with a dominant frequency found at 0.083 month21, which corresponds to a 12months period. For azithromycin and clarithromycin, the highest ambulatory sales in winter are around three times greater than the minimum consumption observed during summer. Ciprofloxacin ambulatory sales vary somewhat, between +20 of the annual mean. Some seasonality was also observed for norfloxacin ambulatory sales. This periodicity is absent for the hospitals uses. The second group of substances is composed of ofloxacin, clindamycin and sulf/trim. No seasonal fluctuation was found for these antibiotics, either in the ambulatory sales data or in hospital use. Finally, metronidazole was found to have a clear six months period in its ambulatory sales. Differences in seasonal cycles for antibiotics sales data can be explained by considering their different therapeutic uses. The substances with high seasonality in ambulatory sa.
