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.

Highlights

  • Pandemics are unique public health emergencies that can result in a large sudden increase in the use of a restricted set of pharmaceuticals within a short time period

  • As penicillins were not monitored in this study, we argue that the November 2011 data might serve as an adequate proxy for ‘background’ antibiotics prescribed during the study period

  • 4782,LOQ 57258 27846 3234 69475 9677 4257 56136 8956 3548 a Predicted amount of drug excreted from the daily doses (ADQ) of antibiotic consumed during 24-h sampling from Benson and Oxford wastewater treatment plant (WWTP) influent as per: b Primary Care Trust (PCT) and c National (NHS BSA) statistics for antibiotic use. d Measured environmental load (MEL) from 24-hourly wastewater inlet samples

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Summary

Introduction

Pandemics are unique public health emergencies that can result in a large sudden increase in the use of a restricted set of pharmaceuticals within a short time period. Depending on the severity of the pandemic, antibiotics have the potential to significantly exceed inter-pandemic usage for the treatment of secondary bacterial respiratory infections [2]. The large load and high concentration of bioactive pharmaceuticals entering the wastewater and receiving rivers from widespread human consumption and excretion during a pandemic can potentially disrupt (micro)organisms through non-target effects [6,7,8,9,10,11,12] and cause the failure of wastewater treatment plants (WWTPs) to treat effluent to the required standard [13,14], hasten the generation of antiviral resistance in wildfowl and other influenza-susceptible organisms [15,16,17,18], and accelerate the generation and spread of (novel) antibiotic resistance in the environment [2,19,20]

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