A new porcine reproductive and respiratory syndrome (PRRS) was first recognized in 1987; however, the causative virus (PRRSV) was first isolated in the Netherlands in 1991 and soon thereafter in the USA (1,2). Since the discovery of this virus, much has been learned about it and its related diseases. A modified-live vaccine became available for pigs and has been widely used in all pig-producing areas. The widespread and appropriate use of vaccines has reduced the morbidity and mortality of pigs (3,4). However, PRRS is still one of the most prevalent swine diseases, together with porcine influenza, and has a huge economic impact worldwide. The virus and the syndrome continue to evolve with clinical variations of the disease (3), making it difficult to find an effective vaccine-based prevention strategy. Several aspects of PRRSV evolution and its interaction with the host are still poorly understood and are largely based on knowledge learned fromin vitroorin vivoexperimental infections (5). However, it is known that PRRSV has a tropism for macrophages of lymphoid tissues and lungs in which it mainly replicates (6–8). Infection by PRRSV is not the only cause of death in nursery pigs; the secondary infections can often also be the cause of death; PRRSVs are frequently coinfecting with the other viruses or bacteria, which are most commonly found on pig farms (9–12). In fact, some published papers argue that an antibiotic-free production strategy could be risky in a PRRSV-endemic setting, especially if other bacterial coinfections are involved since pigs are exposed to severe clinical disease (13). Obviously, the judicious use of ABs can improve animal health (13). Furthermore, there are some ABs that may have antiviral effects. For instance, it seems that several quinolone-containing ABs inhibit the replication of PRRSV (14,15). Unfortunately, the increased and inappropriate use of some ABs to control bacterial infections in veterinary clinics have increased the risk of occurrence and diffusion of multidrug-resistant bacteria (12). Antibiotic resistance is one of the top health issues of major international health organizations. Among the various uses of ABs, low-dose, prolonged courses of ABs in food-producing animals or their use in nonbacterial diseases create ideal selective conditions for the propagation of resistant strains (16). Although antimicrobials are necessary for human and animal health, two thirds of future worldwide growth of the use of antimicrobials is predicted to be in animal production, particularly for the pig chain. According to the European Medicines Agency (EMA) Report, from 2010 to 2018, the estimated weight at AB treatment of livestock and slaughtered animals decreased more than 10% in Italy, unlike other countries in which it remained relatively stable or increased. Nevertheless, Italy is one of the countries in Europe in which the sales of veterinary antimicrobial agents for food-producing animals is the highest. Moreover, it is most commonly used in premixed or oral solutions while the use of injectable, intramammary, or intrauterine preparations is very low (17). For these reasons, greater monitoring AB use is needed, highlighting risk factors in the various production phases and assessing whether the implemented control strategies are working or not. It should be noted that, in Italy, the pig supply chain is very fragmented; therefore, it is not easy to collect data regarding the use of medicine at different production stages. The aim of this study was to investigate how the serological status (seropositive or seronegative) related to PRRS affected production performances and AB use in Italian weaning and fattening units. The authors' hypothesis was that a PRRS seronegative status positively influenced production performance, with animals being more productive and resistant to environmental bacterial infection, which allowed lower AB consumption.