Gut Colonization with Carbapenem Resistant Enterobacteriaceae(CRE) Leads to More Chemotherapy Inerruptions and Higher Mortality in Patients with Acute Leukemias Receiving Remission Induction Chemotherapy

Background: Neutropenic sepsisis a major cause of induction mortality in acute leukemia. The estimated incidence in various series ranges from 12% to 36% ^1-2. Carbapenem resistant enterobacteriaceae (CRE) colonization of the gut can increase the incidence of neutropenic sepsis to 50%^3-4. In the present study we report the prevalence of CRE gut colonization and its impact on outcomes of remission induction chemotherapy in patients with acute leukemias.

Primary Outcome: To compare induction mortality in patients with acute leukaemia who have CRE colonization of the gut at admission with a cohort of Non-CRE colonizer patients of acute leukemia receiving induction chemotherapy at our centre.

Secondary Outcomes: Compare the durations of febrile period, antibiotic use and chemotherapy interruptions in CRE colonizers vs. Non-CRE colonizers.

Methods: This is a prospective observational study. Institute ethics clearance was taken. Patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia(ALL) and mixed-phenotype acute leukemia(MPAL) who were admitted to our centre for remission induction chemotherapy from January 2017 to February 2018 were enrolled in our study. Perianal swab for diagnosing CRE colonization was taken at the time of admission. CRE were identified as per the Centre for Diseases Control (CDC) guidelines. On the basis of surveillance culture results patients were divided into cohorts of CRE-colonizers and Non-CRE-colonizers. These cohorts were followed up prospectively and parameters mentioned in primary and secondary outcome were recorded. Patients with probable and proven fungal infections as per EORTC criteria were excluded from our analysis. This was done in order to better dilineate the attributable cause of death to CRE infections.

Results:A total of 136 patients with acute leukemia were enrolled in our study. Almost half of the patients (67) had acute myeloid leukemia (49%), sixty four (47%) patients had acute lymphoblastic leukemia and four (3%) patients had mixed-phenotype acute leukmeia. 61% of patients had CRE colonization of the gut at the time of admission. There was no significant difference with regards to median age at presentation, sex and the underlying disease (AML, ALL, MPAL) between the CRE colonizers and non-CRE colonizers. Escherichia coli (E.coli) was the most prevalent bacteria among CRE colonizers and non-CRE colonizers (63% vs. 71%, P=0.42). More patients in the CRE colonizer cohort did not receive remission induction chemotherapy due to life threatening sepsis at the time of presentation (15% vs. 5%, P=0.07). Chemotherapy interruptions due to life threatening sepsis were seen in a significantly higher numebr of CRE colonizers compared to non-CRE colonizers (32% vs. 18%, P=0.02). Induction deaths in CRE colonizers were almost double that seen in non-CRE colonizers (40% vs. 21%, P=0.01). There was no significant difference in duration of fever, duration of antibiotic use and blood culture positivity between the two cohorts.

Conclusion:More than half of the patients with acute leukemia had CRE colonization of the gut at the time of presentation. Chemotherapy interruptions and deaths during induction were seen in a significantly higher number of patients colonized with CRE at the time of presentation. Patients with acute leukemia should be screened for CRE colonization of the gut prior to induction chemotherapy. This assumes importance is centres with high prevalence of CRE colonization as CRE colonisation of the gut is a predictor for induction mortality.

References:

1. J. de Naurois, I. Novitzky-Basso, M.J. Gill etal, Management of febrile neutropenia ESMO guidelines. Annals of Oncology, (2010) 21 (suppl_5): v252-v256

2. Collin BA, Leather HL, Wingard JR etal, Evolution, incidence, and suspecitibility of bacterial blood stream isolates from 519 bone marrow transplant patients. Clin Ifect Dis. 2001:33(7):947-53

3. Neil Gupta, Brandi M, Limbago et al, Carbapenem-Resistant Enterobacteriaceae: Epidemiology and Prevention, Healthcare Epidemiology, CID 2011:53 (1 July)

4. Mathews, V., Srivastava, A., George, B., Korula, A., Perumalla, S., Abubacker, F. N., N, N. P., Devasia, A., Abraham, A., Balaji, V., & Lakshmi, K. M. (2016).Multi-Drug Resistant Organisms Are Common in Fecal Surveillance Cultures and Do Not Predict Bacteremia but Correlate with Poorer Outcomes in Patients Undergoing Allogeneic Stem Cell Transplants. Blood, 128(22), 3406