Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent antibiotic resistance threat.¹ The Centers for Disease Control and Prevention (CDC) recommends contact isolation precautions for CRE colonized or infected patients to limit healthcare-associated transmission.² Most U.S. inpatient facilities, however, do not perform routine screening to detect CRE. Our objective was to measure the prevalence of CRE perirectal colonization upon hospital unit admission (results unknown to clinical staff) and to evaluate whether CRE carriers were already on contact precautions for other indications at the time of unit entry.

There were 3,784 unit admissions during the study period: 2,034 (54%) in the MICU and 1,750 (46%) in the Transplant Unit. Of these encounters, 3,249 (86%), representing 2,424 unique patients, had stored perirectal admission screening swabs.

Overall, 126 of 3249 admission swabs (3.9%), from 117 unique patients, tested positive for one or more CRE (95% CI: 3.2 – 4.6%). The CRE prevalence was higher among MICU admissions compared to Transplant Unit admissions (4.7% vs. 2.8%, p=0.01). Of the 126 CRE-positive swabs, 26 (21%) were positive for carbapenemase production (from 24 unique patients), yielding a CP-CRE admission prevalence of 0.8% (95% CI: 0.5 – 1.2%). The prevalence of CP-CRE was similar in both units (0.8% in the MICU vs. 0.9% in the Transplant Unit, p=0.74). The majority of CP-CRE were Klebsiella pneumoniae (46%), followed by Enterobacter cloacae (35%), Citrobacter amalonaticus (11%), and Escherichia coli (8%).

During the study period, 817 (25%) patients were on contact precautions at unit admission. The majority of patients with perirectal CRE and CP-CRE colonization (72 [57%] and 13 [50%], respectively) were not on contact precautions at unit entry. Relative to non-carriers, however, CRE and CP-CRE carriers were still more likely to be on contact precautions (ORs, respectively: 2.18 [95% CI: 1.50 – 3.15] and 2.93 [95% CI: 1.28 – 6.72]). The most common infection control flag indication(s) among CRE carriers were a history of VRE (46%), MRSA (39%), or MDRGN organisms (39%) (Figure). Patients with an MDRGN history were nearly 3.5 times more likely to test CRE-positive (OR 3.42, 95% CI: 1.83 – 6.36) (Table). Three CRE carriers (all CP-CRE-negative MICU patients) had documented recent international hospitalization: one patient was not on contact precautions at unit admission, and two patients were already isolated for history of MDRGNs.

Two of 26 patients who had CP-CRE isolated on admission perirectal surveillance were already on contact precautions with a CRE ‘flag,’ because of a prior CRE-positive culture (unrelated to study screening). In sixteen additional encounters, patients were isolated based upon an institutional CRE flag, but they tested CP-CRE-negative. The sensitivity and specificity of a CRE flag for predicting CP-CRE colonization at unit admission was 7.7% and 99.5%, respectively.

Identifying CRE-colonized patients at hospital unit admission can facilitate timely infection control interventions, such as placing colonized patients on contact precautions, in order to limit healthcare-associated transmission. The CDC recommends CRE colonization screening in limited instances (e.g., patients with recent international hospitalization),² but most U.S. hospitals do not perform routine CRE colonization screening. Evaluating patients admitted to a medical intensive care unit and a solid organ transplant unit, we found that CRE colonization unit-admission prevalence was infrequent (3.9%), and only 21% of CREs were carbapenemase-producers. These findings are similar to the proportions of CRE (3.1%) and CP-CRE (32% of CRE) among clinical isolates reported to the National Healthcare Safety Network in 2015 and 2017, respectively.⁶

The majority of CRE and CP-CRE colonized patients were not on contact precautions at unit admission. Of particular concern, only one CP-CRE carrier (two encounters) had a known history of CRE, which may reflect a true lack of prior positive cultures, or incomplete data from institutions outside the Johns Hopkins Health System. Moreover, no CP-CRE colonized patients were recently hospitalized internationally. Our findings suggest that many CP-CRE carriers — and the potential they pose for onward transmission — are missed for infection control interventions under existing institutional protocols.

Although most CRE-colonized patients were not on contact precautions at unit admission, CRE and CP-CRE-colonized patients were still two-to-three times more likely than non-carriers to be on contact precautions. The most common indications were histories of VRE, MRSA, and/or MDRGNs. These findings are consistent with the overlap in risk factors (e.g., antibiotic use, exposure to high-risk healthcare facilities) between CRE and other drug-resistant organisms.^7–9 Moreover, an MDRGN history was associated with colonization with CRE, but not CP-CRE, which may reflect differing acquisition pathways between CRE types.¹⁰ Identifying additional risk factors for CRE colonization, particularly among patients who lack MDRGN histories, could enhance targeted screening efforts.

This was a single-center study with some missing swabs, and our results should be validated in other cohorts. In addition, contact precautions policies vary between hospitals, which could impact generalizability of these findings. We only ascertained contact precaution status at unit admission, and patient status may have changed during unit stay. Screening method may also affect organism recovery, although CDC guidance endorses peri-rectal swabs for CRE surveillance².

In summary, the majority of CRE-colonized patients in this study were not on contact precautions at unit admission. Given low colonization prevalence, further research on CRE colonization risk factors among U.S. inpatients is necessary in order to develop algorithms for identifying and screening patients at greatest risk of harboring CRE.