NAsal MEthicillin-resistant Staphylococcus (NAMES): a Prospective Study to Assess the Impact of Antibiotic Therapy on Nasal Colonization with Methicillin-resistant Staphylococcus Aureus (MRSA) Inhospitalized Children

Antimicrobial resistance (AMR) is recognized as one of the major threats to global health [1], causing up to 25.000 deaths in the European Union every year, longer hospitalizations and increased healthcare costs. It is well known that antimicrobial use is the main driving force towards AMR and up to 50% of antimicrobial prescriptions are either inappropriate or unnecessary [2]. It is then important to understand how to optimize antimicrobial usage not only in adults but also in infants, as they show different resistance patterns and have peculiar characteristics that may lead to incorrect administration and alteration of the pharmacokinetic and pharmacodynamic properties of the drug [3]. Antimicrobials are the most prescribed drugs in children [4][5] and this excessive usage has been recorded not only in developed countries, but also in low-income and middle-income ones [6]. In Europe, Italy reported one of the highest prescriptions rates, four times higher than the UK and six times higher than the Netherlands [7][8]. 84% of Italian infants in the community have already received at least one course of antibiotics at 2 years of age [9]. A point-prevalence survey (PPS) showed that 38.9% of hospitalized Italian infants received at least one antibiotic prescription both for treatment and prophylaxis; in children, the most commonly used antibiotic classes were third generation cephalosporins and penicillins plus enzyme inhibitors, with a high prescription rates of carbapenems and quinolones as well, often off-label [10]. In order to limit misuse and overuse of antibiotics in children, the joint SHEA-IDSA-PIDS position paper states the importance of introducing antimicrobial stewardship programs (ASPs) in all healthcare institutions [11].

Antimicrobial stewardship has been defined as "the optimal selection, dosage, and duration of antimicrobial therapy that results in the best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance" [12]. So far, little progress has been made with developing pediatric ASPs, especially outside the United States healthcare system.

One of the most important studies conducted in Europe in this field, the ARPEC project, was designed as a PPS: this type of strategy is very useful if repeated regularly, as it allows to monitor prescription trends over time and to identify the problem of inappropriate antibiotic usage [13]. However, it has been shown that PPSs are not sufficient by themselves to change the clinical practice if not combined with other methods [14], such as pre-prescription authorization, prospective audit and feedback, educational and training programmes or technological means of support. In USA, methicillin-resistant Staphylococcus aureus (MRSA) in children mainly causes skin and soft tissue infections but invasive diseases were increasingly reported in 1995-2010 [15]. Studies on MRSA carriage in healthy children showed great geographic variation (from less than 1% in Belgium to 15% in Taiwan) that depend on many local differences [16]. Nevertheless, very few studies have been performed on the influence of antibiotic prescription in the acquisition of resistant microorganism such MRSA in pediatric population.

The aim of this study is to estimate the incidence of MRSA nasal colonization and invasive disease and to investigate the impact of antibiotic treatment during hospitalization on the acquisition of MRSA nasal colonization in children.