Les (azithromycin, clarithromycin and ciprofloxacin) are mainly prescribed for airway infections

Les (azithromycin, clarithromycin and ciprofloxacin) are mainly prescribed for airway infections (i.e., bronchitis and pneumonia) and infections affecting the throat, nose and ears (pharyngitis, sinusitis, earache). Table 4. Minimum/Mean/Maximum ratio (in ) of antibiotics originating from hospitals found Lausanne wastewater, calculated from 5 years of monthly consumption data.Substance Azithromycin Clarithromycin Clindamycin Ciprofloxacin Metronidazole Norfloxacin Ofloxacin Sulf/trimR 0.02 0.27 0.35 0.17 0.17 0.58 0.03 0.01 Substance Azithromycin Clarithromycin Clindamycin Ciprofloxacin Metronidazol Norfloxacin Ofloxacin Sulf/trimRatio ( ) Minimum 0 7.7 0 28.6 18.3 0 0 16.2 Mean 6.5 15.2 40.7 35.1 34.5 2.7 0.6 30.5 Maximum 33.2 41.9 66.3 44.9 46.6 10.0 2.2 51.R is the correlation coefficient. Consumption in hospitals and ambulatory do not correlate. doi:10.1371/journal.pone.0053592.tdoi:10.1371/journal.pone.0053592.tAntibiotics Origin in WastewaterFigure 6. Computed monthly PEC at WTP inlet (one box per month). Each box was obtained from five monthly total sales data (total of 5 y of data available, giving 5 sets of each month). The red line locates 25331948 the median of the five months considered. Upper and lower box limits correspond to the 75th and 25th percentiles, respectively. Upper and lower whiskers correspond to the last datum being within 1.5IQR of the higher and lower quartile, respectively. IQR is the interquartile range, i.e., the difference between the upper and lower quartiles. doi:10.1371/journal.pone.0053592.gThe seasonality of the pathologies these substances treat explains the observed seasonality in ambulatory sales data. The other substances, for which there is no Title Loaded From File seasonal pattern in ambulatory sales, have more diverse pathologies. In many cases, they are used for non-seasonal diseases, typically infections of skin, bones, joints, urinary-genital tract, stomach and peritonitis.Hospital Title Loaded From File ConsumptionPrevious studies that evaluated the proportion of hospitalsourced pharmaceuticals to the total WTP load typically used a fixed figure [34?7]. This figure was often obtained from comparison of measurements of hospital effluent and WTP influent. Recently, Le Corre et al. [27] suggested calculating this ratio from sales data, but the study is limited by the fact that authors could only provide annual data. Yet, figure 5 shows that monthly variability of this ratio can be significant. Our data set do not reveal seasonal periodicity in the ratio of antibiotics originating from hospitals. This is explained by the seemingly random (i.e., aperiodic) behaviour of hospital antibiotic consumption, which dominates over any periodic seasonal consumption (Table 3). For some substances (e.g., ofloxacin and norfloxacin), the monthly ratio remains constantly low, with little fluctuation. On the other hand, it is difficult to draw any conclusion on the monthly variation of the hospital ratio for other substances. A specific case that can be identified is ciprofloxacin, which has a high mean annual ratio of hospital use (35 ), but low monthly fluctuation (see Table 4 and Figure 5). In general, these results suggest that hospital antibiotic use is largely disconnected from non-hospital use, perhaps due to different protocols used forhospital and non-hospital patients. Another possibility is that drugs are used to treat different diseases in hospitals than in the community. Verlicchi et al. [38] summarized existing literature estimates of ratios of ho.Les (azithromycin, clarithromycin and ciprofloxacin) are mainly prescribed for airway infections (i.e., bronchitis and pneumonia) and infections affecting the throat, nose and ears (pharyngitis, sinusitis, earache). Table 4. Minimum/Mean/Maximum ratio (in ) of antibiotics originating from hospitals found Lausanne wastewater, calculated from 5 years of monthly consumption data.Substance Azithromycin Clarithromycin Clindamycin Ciprofloxacin Metronidazole Norfloxacin Ofloxacin Sulf/trimR 0.02 0.27 0.35 0.17 0.17 0.58 0.03 0.01 Substance Azithromycin Clarithromycin Clindamycin Ciprofloxacin Metronidazol Norfloxacin Ofloxacin Sulf/trimRatio ( ) Minimum 0 7.7 0 28.6 18.3 0 0 16.2 Mean 6.5 15.2 40.7 35.1 34.5 2.7 0.6 30.5 Maximum 33.2 41.9 66.3 44.9 46.6 10.0 2.2 51.R is the correlation coefficient. Consumption in hospitals and ambulatory do not correlate. doi:10.1371/journal.pone.0053592.tdoi:10.1371/journal.pone.0053592.tAntibiotics Origin in WastewaterFigure 6. Computed monthly PEC at WTP inlet (one box per month). Each box was obtained from five monthly total sales data (total of 5 y of data available, giving 5 sets of each month). The red line locates 25331948 the median of the five months considered. Upper and lower box limits correspond to the 75th and 25th percentiles, respectively. Upper and lower whiskers correspond to the last datum being within 1.5IQR of the higher and lower quartile, respectively. IQR is the interquartile range, i.e., the difference between the upper and lower quartiles. doi:10.1371/journal.pone.0053592.gThe seasonality of the pathologies these substances treat explains the observed seasonality in ambulatory sales data. The other substances, for which there is no seasonal pattern in ambulatory sales, have more diverse pathologies. In many cases, they are used for non-seasonal diseases, typically infections of skin, bones, joints, urinary-genital tract, stomach and peritonitis.Hospital ConsumptionPrevious studies that evaluated the proportion of hospitalsourced pharmaceuticals to the total WTP load typically used a fixed figure [34?7]. This figure was often obtained from comparison of measurements of hospital effluent and WTP influent. Recently, Le Corre et al. [27] suggested calculating this ratio from sales data, but the study is limited by the fact that authors could only provide annual data. Yet, figure 5 shows that monthly variability of this ratio can be significant. Our data set do not reveal seasonal periodicity in the ratio of antibiotics originating from hospitals. This is explained by the seemingly random (i.e., aperiodic) behaviour of hospital antibiotic consumption, which dominates over any periodic seasonal consumption (Table 3). For some substances (e.g., ofloxacin and norfloxacin), the monthly ratio remains constantly low, with little fluctuation. On the other hand, it is difficult to draw any conclusion on the monthly variation of the hospital ratio for other substances. A specific case that can be identified is ciprofloxacin, which has a high mean annual ratio of hospital use (35 ), but low monthly fluctuation (see Table 4 and Figure 5). In general, these results suggest that hospital antibiotic use is largely disconnected from non-hospital use, perhaps due to different protocols used forhospital and non-hospital patients. Another possibility is that drugs are used to treat different diseases in hospitals than in the community. Verlicchi et al. [38] summarized existing literature estimates of ratios of ho.