Antimicrobial prophylaxis has been a part of medical practice for decades, initially as a perioperative safeguard against surgical infections. In the era following the onslaught of the HIV pandemic, antimicrobial prophylaxis became common in the setting of secondary immunodeficiencies. In recent years, it was proposed that patients with inborn errors of immunity (IEI) could also benefit from such interventions. With the nature of myriad IEI elucidated, it became possible to anticipate which pathogens pose the greatest threat for such patients by exploiting the proverbial chinks in the (immunological) armor. Here, we review current IEI antimicrobial prophylaxis practices and guidelines as well as their scientific justification. We will focus on prophylaxis of Pneumocystis jirovecii, Toxoplasma gondii, encapsulated bacteria, bronchiectasis exacerbations, Mycobacteria, Candida and other fungi, and viruses (especially Herpesviridae) in particular. We will strive to elucidate the challenges related to the cost, logistics, and risks associated with such antimicrobial prophylaxis in IEI.
