<span class="paragraphSection"><div class="boxTitle">Objectives</div>Invasive infections caused by KPC-producing <span style="font-style:italic;">Klebsiella pneumoniae</span> (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients.<div class="boxTitle">Methods</div>Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days. Cox regression analysis including a propensity score was used to investigate the impact of the use of two intestinal decolonization regimens with oral aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of KPCKP infections and microbiological success. The study was registered with ClinicalTrials.gov (NCT02604849).<div class="boxTitle">Results</div>The study sample comprised 77 colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up, decolonization was associated with a lower risk of mortality in multivariate analyses (HR 0.18; 95% CI 0.06–0.55) and a lower risk of KPCKP infections (HR 0.14; 95% CI 0.02–0.83) and increased microbiological success (HR 4.06; 95% CI 1.06–15.6). Specifically, gentamicin oral therapy was associated with a lower risk of crude mortality (HR 0.15; 95% CI 0.04–0.54), a lower risk of KPCKP infections (HR 0.86; 95% CI 0.008–0.94) and increased microbiological response at 180 days of follow-up (HR 5.67; 95% CI 1.33–24.1). Neomycin/streptomycin therapy was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06–0.9).<div class="boxTitle">Conclusions</div>Intestinal decolonization with aminoglycosides is associated with a reduction in crude mortality and KPCKP infections at 180 days after initiating treatment.</span>
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