Carbapenem-Resistant Enterobacteriaceae (CRE) and Their Impact on Stem Cell Transplantation: A Single Center Experience

The increasing incidence of CRE is one of the most important issue since they are an important threat to public health. CRE cause a variety of diseases, ranging from pneumonia to urinary tract infections, to serious bloodstream or wound infections. CRE infection typically occurs in ill patients and patients with exposure to acute and long-term care settings. The symptoms vary depending on the underlying disease. CRE, particularly Klebsiella Pneumoniae (KPC), have high levels of resistance to antibiotics and occasionally are resistant to all available antibiotics. Patients with hematological malignancies are therefore the most vulnerable to CRE. We analyzed the incidence and prevalence and the impact of CRE-KPC colonization and infection in our center focusing on patients submitted to SCT in our division of Hematology from 2010 to 2013. Surveillance was adopted sistematically in 2010, when the first case of KPC was discovered, using peri-rectal swab at admission and weekly thereafter on all patients admitted to the division of Hematology. Epidemiology control was reinforced on stem cell transplant recipients either autologous or allogeneic according to our local policies and included contact precautions and preemptive contact precautions, patients cohorting, chlorhexidine bathing and empirically oriented antibiotics on the base of the results of susceptibility antibiotics testing for febrile severely neutropenic patients colonized with KPC. One hundred-seventy consecutive patients submitted to autoSCT and 91 submitted to alloSCT were analyzed. Colonization prior to autoSCT (at least six months prior to the procedure) was not observed until 2012 when 2 patients presented KPC colonization. No patients had KPC infection prior to auto SCT. Twelve patients after autoSCT presented KPC colonization and 6 of them developed microbiologically documented KPC infection at time of transplantation during the phase of neutropenia and included one sepsis, 4 urinary tract infections and one pneumonia. All of them received CRE-oriented empiric antibiotics followed by rapid de-escalation at resolution of fever, symptoms and neutropenia. Colonization with CRE-KPC after auto-SCT was 7.% No deaths were observed. 91 alloHSCT procedures were performed in 88 patients (47 MUD, 41 sibling, 3 cord blood). KPc colonization/infection prior to HSCT ((at least six months prior to the procedure) had occurred in 14 cases (15.4%). Sixteen patients developed microbiologically documented KPC infection during different phases after transplantation (incidence 17.6%). Infections included 10 sepsis, 2 urinary tract infections and 2 pneumonia. Eight cases occurred within 100^th day from transplant and were defined as “early” infections. Remaining cases were classified as “late” (4 cases, occurred <6^th month) and “very late” (4 cases, >6^th month), All colonized patients received KPc-oriented empiric antibiotics in case of fever. Eleven deaths were registered among cases (11/16, 69%). Of them, 2 deaths were considered due to KPc only (2/16, 12.5%), while 6 pts died with KPc infection. Remaining 3 deaths were due to other causes. Notably the majority of KPc related deaths occurred late mainly in the setting of concurrent post-transplantation complications ie GVHD. Incidence of CRE-KPC infection after autoSCT was 3.52% and 15.4% after alloSCT in a center in which profound prevention strategies were implemented during the last 4 years. Mortality related to CRE-KPC was substantial after alloSCT although lower than expected, particularly in the early phase post HSCT. Systematic surveillance and prompt combined antibiotic therapy may be a possible explanation. The incidence of colonization is still rising and all possible efforts should made in order to reduce diffusion of CRE-KPC. CR-KPC colonizations was significantly different between allogeneic and autologous recipients reflecting differences in underlying disorders, previous chemotherapy and previous hospitalizations.