Admission screening and cohort care decrease carbapenem resistant enterobacteriaceae in Vietnamese pediatric ICU’s

To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay, mortality, and costs in three Intensive Care Units (ICU’s) at the Vietnamese National Children’s Hospital. CRE screening using rectal swabs and ChromIDCarbas elective culture at admission and if CRE negative, once weekly. Patients were treated in cohorts based on CRE colonization status. CRE colonization at baseline point-prevalence screening was 76.9% (103/134). Of 941 CRE screened at admission, 337 (35.8%) were CREpos. 694 patients met inclusion criteria. The 244 patients CRE negative at admission and screened > 2 times were stratified in 8 similar size groups (periods), based on time of admission. CRE acquisition decreased significant (OR − 3.2, p < 0.005) from 90% in period 2 (highest) to 48% in period 8 (last period). Patients with CRE acquisition compared to no CRE acquisition had a significantly higher rate of culture confirmed HAI, n = 20 (14%) vs. n = 2 (2%), longer hospital stays, 3.26 vs. 2.37 weeks, and higher total treatment costs, 2852 vs. 2295 USD. Admission CRE screening and cohort care in pediatric ICU’s significantly decreased CRE acquisition, cases of HAI and duration of hospital-stay.


Design
This was a prospective intervention cohort study with a quasi-experimental design at the Vietnamese National Children's Hospital (VNCH) ICU's It was performed to assess the effectiveness of CRE admission screening and cohort care on CRE acquisition and colonization, HAI, treatment outcome and costs. Implemented from 2018-03-20 to 2018-06-20 ( Fig. 1). Conventional Infection Prevention and Control (IPC) measures were already in place in the ICU's, including instructions for hand hygiene, availability of alcoholic hand rub, personal protective equipment, gloves and shoe protection, and an active antibiotic stewardship group. The project promoted and strengthened these IPC measures. According to CRE colonization status in the baseline PPS in the ICU's, patients were moved to CRE positive (CREpos) or CRE negative (CREneg) cohorts. Following the PPS, all new admissions were CRE screened and cohorted in a separate area for newly admitted patients with unknown colonization status. The fecal screening samples were transported to the microbiology lab and cultured. According to screening result, patients were moved to either the CREpos or CREneg cohort. The cohort care intervention started at the same time as the admission screening as it was considered unethical to not cohort patient once their CRE-status was known. Patients

Economic outcomes
Data on the cost of hospital stay was obtained from the hospital economic division after patient discharge. The total cost was assessed in relation to CRE colonization and HAI. CRE screening cost was estimated at 3 USD per patient / two screenings.

Sample size
The sample size was based on admission CRE colonization rate of ~ 30% and at discharge ~ 80% [7,

Statistics
The primary outcome,Secondary outcomes,Microsoft Corp) was used for preliminary data input. The IBM SPSS Statistics software (version 22 IBM, CA,Free Statistics and Forecasting Software [17] and Social Science Statistics [18]. p-value of < 0.05 was considered significant. Acinetobacter baumannii

Baseline CRE point prevalence survey
Pseudomonas aeruginosa in the acquisition assessment cohort. 144 (37.1%) of the CREneg patients were admitted < 7 days and not rescreened (Fig. 2). There was a significant correlation between CRE colonization and HAI (p < 0.005) as well as HAI related mortality (p < 0.05) when compared to CREneg patients. CREpos patients had a significantly higher number of hospitals days and healthcare cost compared to CREneg patients, 23.4 days and 2568 USD vs. 8.1 days and 1351 USD, respectively (Table 2). For patients with a mortal outcome, the average duration of hospital stay was significantly longer for CREpos patients (27.6 days) vs. CREneg (8.8 days).

CRE acquisition
244 patients CREneg at admission were rescreened. An average 2.35 screenings were performed per patient, with 147 (60%) CREpos in rescreening (acquisition). Patients with CRE acquisition vs. no acquisition were screened on average 2.5 and 2.1 times, respectively. The cohort of 244 CREneg patients were stratified according to ICU: NICU (109), PICU (60) and SICU (75). In each ICU, all patients were split in 8 similar size groups, (periods), based on time of admission, roughly corresponding to weeks. A significant negative correlation between CRE acquisition and periods was seen (p < 0.0005), corresponding to a significant decrease in acquisition in univariate-and multivariate analysis (OR − 3.2, p < 0.005). A significant decrease of CRE acquisition was seen from the 2nd to the 8th period in the PICU (p < 0.05) and SICU (p < 0.005), however not in the NICU (p < 0.2). When assessing CRE acquisition in NICU from the 2nd up to the 6th period (n = 68), a significant (p < 0.05) decrease of CRE acquisition was seen (Fig. 3).
CRE acquisition was significantly correlated with culture confirmed HAI (p < 0.005), weeks of hospital stay (p < 0.0005) and total treatment cost (p < 0.05), but not with mortality and bacterial infections based on CD10 codes (Table 3). In multivariate analysis, a significant correlation between CRE acquisition and weeks of hospital stay was seen (p < 0.001), however not with healthcare cost, the latter likely due to highly significant (p < 0.00001) co-variation between healthcare cost and weeks of hospital stay. A significant correlation (p < 0.001) was seen between periods and decreased healthcare cost (cost decreased with time), but no significant correlation with HAI or weeks of hospital stay.

Main findings
In all ICU's combined, CRE acquisition decreased significantly from 90% in period 2 to 48% in period 8 during the intervention. The decrease was most pronounced in the PICU and SICU: from 100 and 78% period 2, to 43% and 22% period 8, respectively. In the NICU, a significant decrease of CRE acquisition was detected from period 2

HAI
Patients with CRE colonization and acquisition had significantly higher rates of culture confirmed HAI with Enterobacteriaceae,2). Correlation between colonization and HAI was shown in our previous study [7] and has been established in other studies also [27,25,28].

Treatment outcome
The mortality rate in CRE colonized patients with culture confirmed HAI was significantly higher (24%) compared to non-colonized patients with HAI (7%). Similar results was seen in our previous 2017 study [7,7]. Other studies have also shown high mortality rates in patients with infections caused by CRE [12,20,Enterobacteriaceae,,

Costs
, 9,23,29-31, The hospital cost in Vietnam is to a high extent covered by the health insurance, provided for free to children up to 6 years of age. At the time of the intervention, the costs for CRE screening were not reimbursed, despite potentially being able to save large resources for the health insurance. Patients with HAI occupy an ICU place for a longer time and blocks new admissions that require more investigations, hence pose an economic burden for the hospitals, in addition to increased patient mortality and morbidity.
The intervention was performed at a low cost, about 3 USD per agar plate, which can be used for two cultures. Costs for laboratory and ICU labor was however not accounted for. The aim of this intervention was to perform it at a cost level, which would allow a continuous CRE screening and cohort care.

Strengths and limitations
One major limitation in this study is that it was an interventional study with no control group. Further, the intervention, for ethical reasons, started immediately after a patients CRE status was revealed. As this was no randomized controlled trial of CRE screening and cohort care, the results of this study can only be interpreted as indicative. The intervention was performed in pre-existing facilities and without extra staff, beside the research team. The cohorts could in most situations not be completely physically separated and it was not always possible to have designated staff. The high CRE colonization rate at admission made it challenging to isolate patients. Of 604 patients screened CREneg at admission, only 244 (40.4%) were re-screened. Reasons for this include that many patients were admitted for < 48 h, patients were moved with short notice when discharged from ICU, lack of staff and reluctance to rectal swab patients after death. Despite these limitations, which in LMIC are a realistic actual setting, our study showed that admission CRE screening and cohort care intervention significantly can reduce the rates of CRE acquisition and HAI as well as shorten hospital stays and decrease costs.
Higher levels of HAI, higher treatment costs and a higher level of HAI-related mortality was seen in CREpos patients when compared to CREneg. One possible confounder is whether CREpos patients represents a group of patients with higher levels of co-morbidities (more ill patients) and therefore more prone to get colonized, have longer treatment periods in the hospital and be more likely to get nosocomial infections (HAI's) and suffer a mortal outcome from these. The intervention design without a control group does not allow for determining whether associations of CRE colonization (initial) and acquisition with HAI, costs, and mortality (later), are causal. The group of patients treated in a separate cohort while awaiting their admission CRE screening results contained both CREneg and CREpos patients. Although it was the ambition to distance the patients in the group, possibly exposure could not be excluded, providing a risk of patients initially screening CREneg becoming colonized while awaiting their screening results. Some patients were likely colonized during this waiting period, which was deemed nonpreventable in this intervention. In ideal conditions, complete isolation of patients from one another would be preferred but was not possible within the VNCH ICU's. The 7-day follow-up screening on all admitted patients was used, to limit the transmission of CRE in the CREneg cohort.

Conclusion
The admission CRE screening and cohort care intervention showed that CRE acquisition can be reduced with limited resources and be cost-effective by reducing CRE colonization, HAI and duration of hospital stay. As large proportions of patients were CRE colonized at admission, indicating a significant CRE spread in non-tertiary level hospitals, CRE screening should be implemented in all healthcare levels in the endemic Vietnamese system, however likely not applicable to other countries with lower levels of CRE. To enable permanent CRE admission screening and cohort care implementation, economic incentives for the health care sector to use CRE screening as a tool (such as reimbursement for screening costs from the health insurance system) should be warranted. The significant reduction in CRE acquisition found in this study is indicative, as there was no control group and further since the intervention, for ethical reasons, started as soon as patients CRE status were known. To create evidence, a randomized controlled trial in a larger patient material assessing the effects of CRE screening and cohort care would be recommended.