Introduction:
Antibiotics use in Italy is among the highest in Europe. This overuse can lead to anti-microbial resistance and harm humans, animals, and plants. Their accumulation in surface waters, and its consequent toxicity for animals and plants, is an emerging problem. This study aimed to estimate antibiotics environmental impact on the Italian surface waters.

Method:
We integrated drug utilisation and eco-toxicological data to assess antibiotics burden on the Italian surface waters. We extracted the predicted no-effect concentrations (PNEC) from the European Medicines Agency (EMA) and the Swedish Medicines Agency (FASS) environmental risk assessment reports. We then estimated the Italian predicted environmental concentrations (PEC). We used Italian drug utilisation data for 2020, the total number of inhabitants on January 1st, 2020, and the default values proposed by the European Chemical Agency for wastewater production and disposal. We calculated the environmental risk as PEC/PNEC ratio and classified it as high (>10), moderate (>1), low (>0.1), and insignificant (≤0.1).

Results:
We obtained the environmental risk for 56 antibiotics for which Italian consumption data were available. We found a high environmental risk for one glycopeptide (vancomycin: PEC/PNEC=71.002), two penicillins (ampicillin: 43.376; amoxicillin: 41.346), one cephalosporin (cefazolin: 26.201), and one macrolide (azithromycin, 10.263). The risk was moderate for two fluoroquinolones (levofloxacin: 8.333; ciprofloxacin: 3.371), three cephalosporins (ceftriaxone: 5.823; cefepime: 2.147; cefixime: 1.867), two penicillins (piperacillin: 3.194; flucloxacillin: 1.377), and one macrolide (clarithromycin: 2.917). Vancomycin, azithromycin, ciprofloxacin, levofloxacin, ceftriaxone, cefixime, piperacillin, and clarithromycin are also on the Watch group of the AWaRe classification.

Conclusions:
Multiple antibiotics have a high/moderate environmental impact on Italian surface waters, most of which have a relatively high risk of selecting bacterial resistance (those in the Watch group). Appropriate prescription and adherence practices of these antibiotics may reduce the negative impact on the environment and improve purification procedures and green drug development.