Phages in the fight against antimicrobial resistance : An innovative decolonization strategy for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae in the endemic Brazilian context

As antimicrobial resistance is rising, new strategies are urgently needed to prevent the dissemination of multidrug resistant (MDR) bacteria. Phage therapy (PT) has increasingly been used on a case-by-case basis, mainly in MDR bacterial infections. This research project aims to analyze the use of PT in a high prevalence context of antimicrobial resistance, at the University Hospital of the Federal University of São Paulo (UNIFESP). The project will focus on phages active against one of the most prevalent MDR bacteria at the UNIFESP, the Klebsiella pneumoniae harboring the Klebsiella pneumoniae carbapenemase (KPC-KP), in a specific clinical situation: the decolonization of hematological patients colonized with KPC-KP. The objectives are to assess safety and efficacy through clinical and microbiological criteria and better understand phage-pharmacokinetics. Hematological patients colonized with a KPC-KP susceptible to at least one of the available phages will receive the phage or a combination of active phages, previously assembled by the Hospital Pharmacist as a magistral preparation, orally and intra-rectally for 14 days. Patients presenting no phage-susceptible isolate will serve as controls. They will be followed up on day 7, day 14 and at 6 months to assess for safety and KPC-KP carriage. The quantitative measure of KPC-KP will be determined by qPCR using the SYBR-green method as well as by a culture-based method. The isolates will be molecularly characterized and tested for phage resistance. Blood and urine samples will be collected to look for the presence of phages and of neutralizing antibodies through a neutralizing antibody assay. We expect to enroll 30 patients. We hypothesize that there will be no major safety issues and that PT will at least show a relative reduction in the KPC-KP concentration, if not eradication. This project aims to analyze PT in the decolonization of KPC-KP in a high risk population, which, so far, has only been reported once in a case report. Taking place in a high endemicity setting, it will enable the enrollment of a high number of patients within a short period. This study will serve as a preliminary analysis for developing a larger randomized controlled trial. Investigating possible pathways of decolonizing carriers of MDR bacteria with the use of PT constitutes not only a lifesaving option for patients but also a major public health advance in the fight against antimicrobial resistance.