Ten Years of KPC-Kp Bloodstream Infections Experience: Impact of Early Appropriate Empirical Therapy on Mortality

Background. In K. pneumoniae KPC (KPC-Kp) bloodstream infections (BSI), INCREMENT CPE score >7, Charlson Comorbidity Index (CCI) >= 3 and septic shock are recognized predictors of mortality, with a possible beneficial effect of combination therapy in seriously ill patients. Materials and Methods. We conducted a ten-year retrospective study including all KPC-Kp BSI in patients >= 18 years of age with the aim to evaluate the characteristics and impact of appropriate empirical therapy, either monotherapy or combination therapy, and targeted therapy on mortality. Appropriate therapy was defined as at least one active antimicrobial agent with in vitro activity against KPC-kp demonstrated by susceptibility testing, administered within 48 h from blood culture collection. Results. The median age of the 435 analyzed patients was 66.09 years (IQR 54.87-73.98). The median CCI was 4. KPC-Kp colonization was present in 324 patients (74.48%). The probable origin of the KPC-Kp BSI was not identified in 136 patients (31.26%), whereas in 120 (27.59%) patients, it was CVC-related, and in 118 (27.13%), it was respiratory. Source control was achieved in 87 patients (72.5%) with CVC-related KPC-Kp BSI. The twenty-eight-day survival was 70.45% for empirical monotherapy, 63.88% for empirical combination therapy and 57.05% for targeted therapy (p = 0.0399). A probable source of KPC-Kp BSI other than urinary, CVC or abdominal [aHR 1.64 (IC 1.15-2.34) p = 0.006] and deferred targeted therapy [HR 1.67 (IC 1.12-2.51), p= 0.013] emerged as predictors of mortality, whereas source control [HR 0.62 (IC 0.44-0.86), p = 0.005] and ceftazidime/avibactam administration in empirical therapy [aHR 0.37 (IC 0.20-0.68) p = 0.002] appeared as protective factors. Discussion. These data underline the importance of source control together with timing appropriateness in the early start of empirical therapy over the choice of monotherapy or combination therapy and the use of ceftazidime/avibactam against KPC-Kp BSI.