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.
