Intra- and inter-pandemic variations of antiviral, antibiotics and decongestants in wastewater treatment plants and receiving rivers

Abstract

The concentration of eleven antibiotics (trimethoprim, oxytetracycline, ciprofloxacin, azithromycin, cefotaxime, doxycycline, sulfamethoxazole, erythromycin, clarithromycin, ofloxacin, norfloxacin), three decongestants (naphazoline, oxymetazoline, xylometazoline) and the antiviral drug oseltamivir's active metabolite, oseltamivir carboxylate (OC), were measured weekly at 21 locations within the River Thames catchment in England during the month of November 2009, the autumnal peak of the influenza A[H1N1]pdm09 pandemic. The aim was to quantify the pharmaceutical response to the pandemic and compare this to drug use during the late pandemic (March 2010) and the inter-pandemic periods (May 2011). A large and small wastewater treatment plant (WWTP) were sampled in November 2009 to understand the differential fate of the analytes in the two WWTPs prior to their entry in the receiving river and to estimate drug users using a wastewater epidemiology approach. Mean hourly OC concentrations in the small and large WWTP's influent were 208 and 350 ng/L (max, 2070 and 550 ng/L, respectively). Erythromycin was the most concentrated antibiotic measured in Benson and Oxford WWTPs influent (max=6,870 and 2,930 ng/L, respectively). Napthazoline and oxymetazoline were the most frequently detected and concentrated decongestant in the Benson WWTP influent (1650 and 67 ng/L) and effluent (696 and 307 ng/L), respectively, but were below detection in the Oxford WWTP. OC was found in 73% of November 2009's weekly river samples (max=193 ng/L), but only in 5% and 0% of the late- and inter-pandemic river samples, respectively. The mean river concentration of each antibiotic during the pandemic largely fell between 17-74 ng/L, with clarithromycin (max=292 ng/L) and erythromycin (max=448 ng/L) yielding the highest single measure. In general, the concentration and frequency of detecting antibiotics in the river increased during the pandemic. OC was uniquely well-suited for the wastewater epidemiology approach owing to its nature as a prodrug, recalcitrance and temporally- and spatially-resolved prescription statistics.

Figure 1. The 21 river sampling locations within the River Thames Catchment (TC) in southern England and the location of the Oxford and Benson WWTPs.

Figure 2. Correlation between population upstream and daily load of OC in river (mg OC/d) for each of the four sampling points: November 3 (diamond), November 10 (square), November 16 (triangle) and November 24 (‘x’), 2009.

Figure 3. Mean (diamond; with standard deviation (upper and lower error bar)) and maximum (asterisk) concentration (ng/L) of pharmaceuticals across the 21 River Thames locations during (A) the four sampling occasions in November 2009 (intra-pandemic, n = 84); (B) 15 March, 2010 (late-pandemic. n = 21); and (C) 11 May, 2011 (inter-pandemic, n = 21).

‘Maximum’ data label is above asterisk, while ‘mean’ data label is to the right of the diamond. Decongestants were omitted as none were found >LOQ.

Figure 4. Mean load of oseltamivir (OC) per capita per day (µg/cap/d) across all river sampling locations throughout November 2009 (intra-pandemic period).

Triangles indicate the population upstream at that location.

Figure 5. Comparison of pharmaceutical (A) abundance (% of samples above the limit of quantification (LOQ)) and (B) the maximum river concentration (ng/L) during the pandemic period (November, 2009), late pandemic period (March 2010) and the inter-pandemic period (May 2011).