Dalla conoscenza degli antibiotici alla valutazione del ruolo dei vaccini nella lotta all’antibiotico resistenza: uno studio di coorte nella provincia di Messina

Antibiotic resistance (AMR) is, today, a problem of global importance in social and economic terms, given the growing spread of bacteria resistant to the different classes of antibiotics. In the US, the Centers for Disease Prevention and Control (CDC) estimates that over two million people acquire antibiotic-resistant infections each year, and of these, 23,000 die. An equivalent data is found in Europe with about 25,000 deaths every year. In Italy, the Istituto Superiore di Sanità, through the data relating to the five-year period 2012-2016, highlights that, for all pathogens under surveillance, resistance to antibiotics remains high, generally above the European average. The situation is more critical for Gram-negative bacteria given the reduced availability of effective antibiotics. At the same time, the last 25 years have been marked by the increasing development, in the pharmaceutical field, of increasingly effective vaccines, such as those directed against pneumococci, Haemophilus influenzae type b (Hib), Rotavirus and, recently, ACWY meningococcus and B, as well as the most innovative flu vaccines. Immunization may have the potential to reduce antibiotic use in several ways: 1. Primary direct effect: vaccines against bacterial diseases reduce the incidence of the disease and consequently the use of antibiotics. Examples of such vaccine interventions currently licensed include Hib and Pneumococcal conjugate vaccines while future vaccines under development in this category include Group B Streptococcal and Staphylococcal vaccines. 2. Secondary direct effect: vaccines can limit the use of antibiotics for secondary diseases by reducing the incidence of the primary disease. 3. Indirect effect: reduction of inappropriate antibiotic prescription through vaccination for viral and / or parasitic diseases in which fever or diarrhea are the primary manifestations. To these three modalities is added the effect of the herd immunity with subsequent reduction in both the circulation of the pathogen in the general population and in antibiotic resistance. However, these effects may be limited by the presence of microbial strains not included in vaccines or by their gene variation. Given the demonstration of a clear link between an increase in the use of antibiotics and increased resistance to antibiotics, the use of vaccinations can have substantial repercussions in the fight against antibiotic resistance. The use of vaccines is essential not only in children and the elderly, but also in subjects with particular morbid conditions such as cardiovascular, respiratory, metabolic diseases, primary and / or secondary immunosuppression, etc., which expose them to an increased risk of contracting invasive infectious diseases and developing serious complications in this case. The prevention of infectious diseases through vaccinations therefore represents a priority in the field of Public Health even more for these subjects who would benefit from targeted vaccination interventions and which should be the subject of specific programs. The DPCM on the new LEA guarantees free admission of the vaccinations foreseen by the PNPV 2017-2021 for these subjects at risk of all ages. The aim of the research is to evaluate the impact of vaccinations in the fight against antibiotic resistance by reducing, at the same time, the use of antibiotics both through the direct effect of vaccination on the decrease of the related pathology and through the indirect effect on the prescription. inappropriate antibacterial drugs for viral diseases. Main results Increase in vaccination coverage and reduction in the use of antibiotics through proper counseling Additional results 1. Reduction of antibiotic resistance of vaccine target bacteria. 2. Reduction of all infectious episodes (eg fever, respiratory disease, diarrhea), including those in patients with pre -existing medical conditions 3. Reduction in the need for hospitalization and lost working days due to infection. 4. Reduction of mortality from all related causes The research project was carried out at the UOSD of Hospital Hygiene of the AOU “ G.Martino ” of Messina from 1st October 2020 to 31st June 2022 in three phases. In the first phase, the vaccines as per the WHO list were administered at the vaccination center belonging to the UOSD of Hospital Hygiene to which patients, healthcare workers and students of the health care area belonging to the university polyclinic are addressed. Ad hoc vaccination paths have been created for the following categories of "fragile" patients: a) Patients with HIV b) Patients with IBD c) Patients with splenectomy or to undergo splenectomy d) Patients with HPV infection. National immunization prevention plan indicates, in fact, specific vaccinations for patients suffering from certain pathological conditions of risk, such as cardiovascular, respiratory, metabolic, immunosuppressive diseases, which expose them to an increased risk of contracting invasive infectious diseases and develop, in this case, serious complications. The second phase, which began at the same time as the first and lasted a total of two years, involved the analysis of the consumption of the main classes of antibiotics in the health districts relating to the ASP 5 of Messina. The following systems were used: a) Pharmanalysis b) TS system. The last phase of the study involved the assessment of knowledge, attitudes and perception towards antibiotics in the cohort of patients enrolled through an ad hoc questionnaire. The primary objective of the research project was to increase vaccination coverage (VC) in the Messina health district both for the general population and for the categories of frail patients identified in the study design. Vaccination coverage represents, in fact, the indicator par excellence of vaccination strategies as they provide information on their actual implementation on the territory and on the efficiency of the vaccination system. We can, therefore, affirm that in the Messina district the vaccination coverage values remain stable and, at times, touch or exceed the national and regional ones. It was not possible in the study to analyze in its entirety the VC data of all cohorts due to the non-updating of the OnVac system that collects data since the year 2000. This therefore represents a limitation for the study as well as the lack of data integration relative vaccination coverage with data on the consumption of antibiotics ad personam. A first result of the research project is the observation of a general increase in vaccination coverage in the Messina health district and a simultaneous reduction in the prescription of antibiotics and their consumption in the study population. A potential bias in the research is represented by the spread of the SARS-CoV-2 pandemic following the design and start of the research and which, due to the containment measures adopted by the various world health authorities, has led to a reduction in the circulation of pathogens in the environment. The strengths of this study were the advantage of being able to access a vaccination center located in the same hospital where patients were followed, leading to greater privacy, a better knowledge of infections by healthcare personnel, the most frequent opportunities to start vaccination and recall (occasion of the first visit, follow-up visits), the protected environment, the possibility of checking the antibody titre, the application of personalized vaccination programs through, where possible, the integration between clinical and laboratory. In the study sample, an increase in vaccination coverage was observed for all vaccines, as previously described. The greatest increase was observed for HPV vaccination and this has assumed great importance due to the increased risk of contracting other sexually transmitted diseases compared to the general population in the categories identified; in this perspective, primary prevention is of crucial importance, given the limited prevention offered by condoms for some sexually transmitted diseases such as HPV, HSV-2 and syphilis. In the third phase, the knowledge, attitudes and perception of antibiotics and antibiotic resistance were assessed since in Italy the resistance to antibiotics remains among the highest in Europe and is, in most cases, above the average. European, so much so that every year 7 to 10 percent of patients undergo a multi-resistant bacterial infection. In the sample under study, an adequate level of knowledge was generally highlighted, although some evident gaps were found, as noted by other authors previously. In our study, knowledge was considered satisfactory if ≥80% of participants answered correctly to each of the statements described regarding antibiotic knowledge and antibiotic resistance. The limitations of this study are the lack of an integrated system with the electronic health record for comparing the consumption rate of antibiotics and the ad personam vaccination coverage, the small sample size, due to the COVID-19 pandemic and, the absence of vaccination coverage data for cohorts below the year 2000. However, in the present study, the application of an ad hoc protocol together with the possibility of accessing the service in a comfortable environment suitable for protecting privacy led to an increase in coverage vaccines in the sample enrolled, also leading to a better approach with antibiotics and their limited consumption. The correct application of the guidelines, the role of public health and prevention are the cornerstones of the health system of each country. Their importance should also be highlighted in consideration of the recent pandemic that has hit the world, remembering that health does not only depend on the physical well-being of an individual but also on his psycho-social well-being.