A Simple Bundle to Control an Outbreak of Carbapenem-Resistant Enterobacteriacae in an Onco-Hematological Inpatient Unit: Report from a Single Center

INTRODUCTION: Carbapenem-Resistant Enterobacteriaceae (CRE) are an emerging global healthcare problem given their rising incidence and the elevated morbidity and mortality associated with bloodstream infections (BSI) due to these pathogens. Patients with hematological malignancies are at higher risk of complications, as they frequently require prolonged hospitalization and develop severe neutropenia and mucositis, becoming severely immunocompromised. Therefore, mortality rates of CRE bacteremia in these patients are as high as 60%. Despite their severity and growing incidence, few strategies have been described to effectively control the spread of CREs, particularly in the high-risk and endemic settings. Here we describe an effective and feasible intervention to control an outbreak of CREs in an onco-hematological inpatient unit.

METHODS: Our onco-hematological inpatient unit is set in a hospital with 350 beds in southeast Brazil. It has 9 beds in double-occupancy rooms with a volume of about 180 patients a year, mainly with acute leukemia and other hematological malignancies. Prior to the outbreak, interventions for the control of CRE spread consisted of: 1) contact precautions in single-bed rooms for CRE carriers and 2) strict room and hand-hygiene measures. Interventions for the CRE outbreak consisted of: 1) use of single-bed rooms for patients with acute leukemia or other hematological diseases with severe and prolonged neutropenia, irrespective of their CRE status; 2) weekly rectal swabs for CRE carrier status assessment; 3) reinforcement of strict room and hand hygiene practices; 4) nursing staff cohorting according to CRE status and for patients with and without acute leukemia; 5) selective digestive tract decontamination (SDD) with gentamycin 60 mg qid and antimicrobial prophylaxis with amoxicillin 500 mg tid.

RESULTS: The first case of CRE colonization in our unit was diagnosed in 2013. CRE spread had a stable incidence from 2013 to 2016, with 4.0-5.0 new CRE-carriers (either colonization or BSI)/1000 patients-day. Between September, 1^st, 2016 and December, 31^st, 2016, this incidence increased to 11.4, peaking in the first trimester of 2017, with 20.8 new CRE-positive/1000 patients-day, despite the control measures already in place (Figure 1). Altogether, from September 1st, 2016 to March 31st, 2017, a total of 29 patients became CRE carriers, 11 (38%) of them developed bacteremia, with a mortality rate of 54.5%. The most frequent underlying malignancies in CRE-positive patients were acute leukemia (16/29, 55.2%) and non-Hodgkin lymphomas (6/29, 20.7%). The underlying malignancy had no impact in mortality rates associated with CRE bacteremia. Table 1 summarizes the characteristics of CRE-positive patients.

In the three-month period following the intervention, the incidence of new CRE carriers fell sharply: only 2 patients became CRE-positive in this period, resulting in an incidence of 2.8/1000 patients-day, with no new bacteremia episodes. In total 5 patients (3 colonized prior and 2 after the intervention) received SDD, of which 2/5 (40%) developed bacteremia while receiving gentamycin. We also observed a reduction in the acute leukemia mortality rate in the comparison between the first and second trimester of 2017 (before and after the intervention): 36.4% vs.14.3% (p= 0.6 by Fisher's Exact Test).

CONCLUSIONS: We report the successful use of an inexpensive and simple bundle of interventions to control an outbreak of CRE in an onco-hematological inpatient unit, which positively impacted on mortality, with a substantial 2.5-fold reduction in the mortality of acute leukemia patients. Although many of these interventions have already been described in this setting, the cohorting of severely neutropenic patients in single-bed rooms, irrespective of CRE status, as an effective measure has never been reported. Given the rapid and persistent decrease in the incidence of new CRE-positive patients, we believe that this component was crucial for the success of this bundle. A longer follow-up is needed to assess whether SDD for CRE carriers is effective in preventing bacteremia. The increasing number of reports of CRE outbreaks in onco-hematological patients from different parts of the world highlight the importance of these findings.

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