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

Abstract

The increasing incidence of infections by carbapenemresistant enterobacteria (CRE), in particular carbapenemresistant Klebsiella pneumoniae (CRKp), is a significant public health challenge worldwide.1 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. 1-3The Gruppo Italiano Trapianto Midollo Osseo (GITMO) recently performed a retrospective study (2010)(2011)(2012)(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.4 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 b...

Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group

“…Empiric treatment with noncarbapenem β-lactams, or even carbapenems [2 be inappropriate in centers with high resistance rates to these antibiotics an to increased mortality [2,13]. In our study, approximately 40% of commun for empiric therapy are tricky because of significant geographical variations Practical decisions on empiric therapy must be based on continuously upda concerning local resistance patterns and bacteremia rates [26].…”

“…All P values are 2 side the analyses were performed using the statistical software SAS version 9.4 ( Sixty-five HSCT centers from 25 countries reported data on 655 GNR episod 591 patients (1.1 episodes [range, [1][2][3][4] Abbreviations: allo, allogeneic; auto, autologous; βL/βLI, β-lactam/β-lactamase inhibitor; GVHD, g host disease; HSCT, hematopoietic stem cell transplant; ICU, intensive care unit.…”

Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis

“…should be considered on a case-by-case basis for patients who come from areas with high endemicity, in an outbreak setting and in patients who have had previous infections with MDR pathogens. 68 …”

“…76 In patients with CRK, combination therapy with colistin/polymyxin B, tigecycline and gentamicin with the addition of meropenem is recommended. 68 In summary, keys to successful management of MDR pathogens are correct identification of bacteria, early initiation of effective therapy and stringent infection control measures to prevent transmission to other patients. 68 Antimicrobial lock therapy Intraluminal colonization and biofilm formation allow pathogens to evade immune clearance and attenuate antimicrobial efficacy.…”

Italian consensus conference for the outpatient autologous stem cell transplantation management in multiple myeloma

“…Colonization by carbapenemresistant and Gram-negative MDR pathogens is a contraindication to outpatient ASCT given the crucial role played by timely MDRtargeted empiric antibiotic therapy in carriers of MDR bacterial infections. 51,52 Colonization by extended spectrum betalactamases producing Enterobacteriaceae do not represent an absolute contraindication, but should be taken into account if empiric antibacterial therapy is required during NF (see below).…”