Management of carbapenem resistant Klebsiella pneumoniae infections in stem cell transplant recipients: an Italian multidisciplinary consensus statement.

The increasing incidence of infections by carbapenemresistant enterobacteria (CRE), in particular carbapenemresistant Klebsiella pneumoniae (CRKp), is a significant public health challenge worldwide. The interim results of the last European survey on CRE (EuSCAPE project 2013) indicate that CRKp is endemic in Italy, and that this endemicity is mostly contributed to by strains producing KPC-type carbapenemases. CRKp infections are associated with high morbidity and mortality rates, particularly among Intensive Care Units (ICU) patients, recipients of solid organ transplants (SOT) and patients with hematological malignancies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) recently performed a retrospective study (2010-2013) which involved 52 stem cell transplant (SCT) centers to assess the epidemiology and the prognostic factors of CRKp infections in autologous and allogeneic SCT. Cases of CRKp infection were reported in 53.4% of the centers and were documented in 0.4% of autologous and 2% of allogeneic SCTs. A CRKp colonization was followed by an infection in about 30% of cases. The infection-related mortality rate was 16% in autologous and 64.4% in allogeneic SCT. A pre-transplant CRKp infection and inadequate first-line treatment were independent factors associated with an increase in mortality in allogeneic SCT patients who developed a CRKp infection. Indeed, despite the administration of a first-line CRKp-targeted antibiotic therapy (CTAT) (see below), 55% of patients who received a CTAT still died. These data underscored the challenge regarding CRKp infections, particularly in the allogeneic-SCT setting, in terms of outcome and management of post-transplant complications, and also raised an issue about the eligibility for transplant among patients who got colonized or had developed a CRKp infection before transplant. Based on these original data and on the recent literature, a multidisciplinary group of experts from GITMO, the Italian Association of Clinical Microbiologists (Associazione Microbiologi Clinici Italiani; AMCLI), the Italian Society of Infectious and Tropical Diseases (Società Italiana Malattie Infettive e Tropicali; SIMIT), and the Italian National Transplant Center (Centro Nazionale Trapianti; CNT) was convened with the aim of providing consensus recommendations for the management of CRKp infection/colonization in autologous and allogeneic-SCT recipients. The Expert Panel (EP) included 17 specialists in hematology, infectious diseases, clinical microbiology and nursing, who were selected by virtue of their expertise in research and clinical practice of infections in SCT. The areas of major concern were defined by generating clinical key issues using the criterion of clinical relevance, i.e. impact on patient management and risk of inappropriateness, and recommendations were obtained according to a nominal group technique. The EP focused its discussion on four key-issues considered relevant for the present recommendations that are shown in Table 1. Detection of CRKp carriers before and after SCT. Colonization by CRKp represents a condition predictive of a subsequent infection in immunocompromised patients. The EP agreed that the detection of CRKp carriers seems to be the crucial means for infection control and appropriate therapy, but well-defined colonization survey strategies (i.e. timing and frequency of tests) have not been standardized. Considering that the primary colonization site of enterobacteria is the intestinal tract, screenings are focused on the detection of intestinal carriage of CRKp, usually by analysis of rectal swabs. Three levels of isolation may be considered in the infection control strategy: known to be colonized, known to be not colonized and results pending. Infection control strategies and management of CRKp carriers in the SCT setting. Infection control of CRE should be planned in every department, throughout the entire hospital, and at regional, national or multinational level. The differences in morbidity and mortality of infections due to CRE in populations of patients with various underlying diseases and comorbidity profiles should be considered