Research Article: Colonization with multidrug resistant organisms determines the clinical course of patients with acute myeloid leukemia undergoing intensive induction chemotherapy

Date Published: January 23, 2019

Publisher: Public Library of Science

Author(s): Olivier Ballo, Ikram Tarazzit, Jan Stratmann, Claudia Reinheimer, Michael Hogardt, Thomas A. Wichelhaus, Volkhard Kempf, Hubert Serve, Fabian Finkelmeier, Christian Brandts, Senthilnathan Palaniyandi.


The global spread of multidrug-resistant organisms (MDRO) complicates treatment and isolation measures in hospitals and has shown to increase mortality. Patients with disease- or therapy-related immunodeficiency are especially at risk for fatal infections caused by MDRO. The impact of MDRO colonization on the clinical course of AML patients undergoing intensive induction chemotherapy—a potentially curative but highly toxic treatment option—has not been systematically studied.

312 AML patients undergoing intensive induction chemotherapy between 2007 and 2015 were examined for MDRO colonization. Patients with evidence for MDRO before or during the hospital stay of induction chemotherapy were defined as colonized, patients who never had a positive swab for MDRO were defined as noncolonized.

Of 312 AML patients 90 were colonized and 130 were noncolonized. Colonized patients suffered from significantly more days with fever, spent more days on the intensive care unit and had a higher median C-reactive protein value during the hospital stay. These findings did not result in a prolonged length of hospital stay or an increased mortality rate for colonized patients. However, in a subgroup analysis, patients colonized with carbapenem-resistant enterobacteriaceae (CRE) had a significantly reduced 60- and 90-day, as well as 1- and 2-year survival rates when compared to noncolonized patients.

Our analysis highlights the importance of intensive MDRO screening especially in patients with febrile neutropenia since persisting fever can be a sign of MDRO-colonization. CRE-colonized patients require special surveillance, since they seem to be at risk for death.

Partial Text

Acute myeloid leukemia (AML) is a hematological malignancy of the myeloid blood lineage. Due to the fatal course of this aggressive disease a curative therapy approach can only be achieved by intensive induction chemotherapy, usually consisting of cytarabine in combination with an anthracycline [1]. Due to its high toxicity this treatment protocol is reserved for younger patients with limited comorbidities [2]. Standard induction chemotherapy for these patients—excluding the unique treatment for acute promyelocytic leukemia subtype—contains cytarabine combined with an anthracycline such as daunorubicin [3]. Treatment related mortality (TRM) is seen in about 4.5% of these patients [4]. Bacterial infections are the most common cause for TRM in these patients and in patients with chemotherapy-induced neutropenia in general [5].

Several studies have analyzed the clinical impact of MDRO in patients with hematologic malignancies (HM). These studies differ in the MDRO that were analyzed, in the underlying disease of the study population and in the treatment of these patients [6, 18–31]. Most of these studies analyzed the impact of MDRO infections rather than the effect of MDRO colonization only. To our knowledge the present study is the first to investigate the role of MDRO colonization in AML patients receiving standard intensive induction chemotherapy. This is of particular interest given the increasing spread of MDRO colonization worldwide.




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