title: Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias.
abstract: Carbapenem-resistant Klebsiella pneumoniae (CRKP) spread and infections in patients with haematological malignancies are a serious concern especially in endemic areas. Treatment failures and delay in appropriate therapy for CRKP infections are frequent and the mortality rate associated with CRKP bacteremia in neutropenic haematological patients is reported about 60%.
  
  
  
  Haematological patients harboring CRKP hospitalized between February 2012 and May 2013 in an Italian Teaching hospital were examined. Conditions favouring CRKP spread in a haematological unit, risk factors for bacteremia in CRKP-carriers and for CRKP bacteremia-related death were evaluated in this observational retrospective study.
  
  
  
  CRKP was isolated in 22 patients, 14 (64%) had bacteremia. Control measures implementation, particularly the weekly rectal screening for CRKP performed in all hospitalized patients and contact precautions for CRKP-carriers and newly admitted patients until proved CRKP-negative, reduced significantly the CRKP spread (14 new carriers identified of 131 screened patients vs 5 of 242 after the intervention, p = 0.001). Fifty-eight percent of carriers developed CRKP bacteremia, and acute myeloid leukemia (AML) resulted independently associated with the bacteremia occurrence (p = 0.02). CRKP bacteremias developed mainly during neutropenia (86%) and in CRKP-carriers (79%). CRKP bacteremias were breakthrough in 10 cases (71%). Ten of 14 patient with CRKP bacteremias died (71%) and all had AML. The 70% of fatal bacteremias occurred in patients not yet recognized as CRKP-carriers and 80% were breakthrough. Initial adequate antibiotic therapy resulted the only independent factor able to protect against death (p = 0.02).
  
  
  
  The identification of CRKP-carriers is confirmed critical to prevent CRKP spread. AML patients colonized by CRKP resulted at high risk of CRKP-bacteremia and poor outcome and the adequacy of the initial antibiotic therapy may be effective to improve survival. To limit the increase of resistance, the extensive use of antibiotics active against CRKP should be avoided, but in the setting of high CRKP pressure and high-risk CRKP-colonized haematological patients, timely empiric antibiotic combinations active against CRKP could be suggested as treatment of febrile neutropenia.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Via Benevento 6, 00161, Rome, Italy. micozzi@bce.uniroma1.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Micozzi
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Via Benevento 6, 00161, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gentile
authors.affiliation: Azienda Policlinico Umberto I, Rome, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Minotti
authors.affiliation: Azienda Policlinico Umberto I, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cartoni
authors.affiliation: Azienda Policlinico Umberto I, Rome, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Capria
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Via Benevento 6, 00161, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Ballarò
authors.affiliation: Azienda Policlinico Umberto I, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Santilli
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Via Benevento 6, 00161, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Pacetti
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Via Benevento 6, 00161, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Grammatico
authors.affiliation: Ospedale S. Maria della Misericordia, Perugia, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bucaneve
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza Università di Roma, Via Benevento 6, 00161, Rome, Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology* / Q000401:mortality; D015780:Carbapenems / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D024881:Drug Resistance, Bacterial; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D006784:Hospitals, Teaching; D006801:Humans; D017053:Infection Control / Q000379:methods; D007558:Italy / Q000453:epidemiology; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
keywords: Bacteremia; Carbapenem-resistant Klebsiella pneumoniae; Haematological malignancies; Neutropenia; Spread