For PID patients, as well as for the general population, antibiotic resistance has become a serious problem for the risk of a significant failure of treatment necessary to control the infections that represent the most important morbidity and mortality factor in PID. Since no previous study has investigated the spectrum of antibiotic resistance among patients with PID, we propose to investigate: 1) bacterial colonization of the proximal airways; 2) the antibiotic sensitivity of microorganisms in PID patients treated for a long period of time with antibiotic prophylaxis 3) monocyte and neutrophils functions when exposed to isolated colonizing microorganisms, 4) immunoglobulins effect on the killing activity of patients' PMN/monocyte when exposed to sensitive or multidrug-resistant bacteria isolated from their throat. Nasopharyngeal swabs will be obtained from PIDs patients. The rate of sensitive and multi drug resistant S. pneumoniae and H. influenzae will be investigated. Moreover, since additional risk factor for infections in PIDs are the alterations of the innate immune system, which involve a set of cells and mechanisms involved in the host defence by a nonspecific and fast response and since many pathogens have evolved efficient strategies to evade chemotaxis, phagocytosis, and killing, we plan to evaluate PMN and monocyte activity after stimulation with sensitive and multi-drug resistant H. influenzae and S. pneumoniae isolated from PIDs. We will take advantage of the recently settled randomized, double arm study to evaluate the efficacy and safety of azithromycin for the long term prophylactic treatment of primary antibody deficiency coordinated by our group. Beside the possible beneficial effect of antibiotic prophylaxis we should verify if the prolonged use of these drugs might be associated with emergence of clinically significant bacterial resistance or immunosuppression.
Resistance to current antibiotics is rapidly increasing. PID patients are highly predisposed to recurrent, severe and unusual infections especially in gastrointestinal and respiratory tracts. Organisms responsible in gastrointestinal and respiratory tract infections are among the most antibiotic resistant organisms. Unlike immunocompetent individuals, infections in PID patients require the use of broad-spectrum antibiotics with long durations of administration. It is not clear if patients with PID are more likely to develop infections with antibiotic resistant microorganisms or not. It is well known that prolonged administration of antibiotics can result in antibiotic resistance which in turn causes failure of treatment, development of otherwise preventable irreversible complications as a sequel of poorly managed infections, increased mortality and unnecessary expenditure of financial resources due to the need for using more potent antibiotics or even designing new antibiotics. Despite the inevitable need for effective antibiotic therapy in PID patients, currently there is no evidence-based standard protocol for antibiotic administration specified for PID and the few available guidelines are based on expert opinions as well as the results of few observational studies on limited number of PID patients. In order to prove the efficacy of antibiotic prophylaxis and to eventually include it in the guidelines for PID patients, our group coordinated a recently settled three years, phase II, randomized, double arm, multi-center study to evaluate the efficacy and safety of azithromycin for the long term prophylactic treatment of primary antibody deficiency patients suffering from repeated acute exacerbations, a project founded by AIFA. Moreover, some possible benefits might be due to the fact that that some antibiotics such as azithomycin, beside the antibacterial role modulate host defense through effects on host innate immunity, in particular by altering inflammation and autophagy. However, since antibiotic prophylaxis may result in antibiotic resistance to the administered agent we plan to study in the large cohort of PID patients attending the Reference Centre for Primary Immunodeficiency at Sapienza the rate of colonizing bacteria, the rate of antibiotic resistant strains, the function of patients¿ innate immune cells in fighting sensitive and multidrug resistant colonizing bacteria and finally to understand if polyvalent immunoglobulins regularly administered to our patients might have a role in potentiating the effector mechanisms of innate immune cells against multi-resistant bacteria. To the best of our knowledge, the current study is the first to investigate the bacterial colonization and the antibiotic susceptibility profiles among PID patients and to link data on isolated microorganisms to the immune response that PID patients mount to respond to infection.