Predictors and Outcomes of Healthcare-Associated Infections Caused by Carbapenem-Nonsusceptible Enterobacterales: A Parallel Matched Case-Control Study.

Objectives: The increasing incidence of carbapenem-nonsusceptible Enterobacterales as major pathogens in healthcare associated infections (HAIs) is of paramount concern. To implement effective prevention strategies against carbapenem-nonsusceptible Enterobacterales (CnSE) HAIs, it is crucial to identify modifiable factors associated with these infections. We identified risk factors for CnSE-HAIs, and compared clinical outcomes of CnSE-HAI and carbapenem-sensitive Enterobacterales (CSE)-HAI patients. Methods: We conducted a multi-centre parallel matched case-control study in two 1700-bedded Singapore acute-care hospitals from 2014-2016. Patients with CnSE-HAIs and CSE-HAIs were compared to a common control group without HAIs (1:1:3 ratio), matched by time-at-risk and patient ward. Carbapenem nonsusceptible was defined as non-susceptibility to either meropenem or imipenem. Presence of healthcare associated infections were defined by the criteria provided by the European Centre for Disease Prevention and Control. Outcomes of CnSE-HAI and CSE-HAI patients were compared using multivariable logistic and cox regression; the models were adjusted for infection and treatment characteristics. Results: Eighty CnSE-HAI and 80 CSE-HAI patients were matched to 240 patients without HAIs. All CRE-HAIs patients had prior antibiotic exposure, with 44 (55.0%) with prior carbapenem exposure. The most common CnSE-HAIs were intra-abdominal infections (28.8%) and pneumonia (23.8%). The most common CnSE species was Klebsiella spp. (63.8%). In the risk factor analysis, presence of drainage devices [adjusted odds ratio (aOR), 2.19; 95% CI, 1.29 - 3.70] and prior carbapenem exposure (aOR,17.09; 95% CI, 3.06 - 95.43) independently predicted CnSE-HAIs. In the crude outcomes analysis, CnSE-HAI patients had higher all-cause in-hospital mortality and longer time to discharge compared to CSE-HAI patients. After adjusting for differences in receipt of antibiotics with reported susceptibility to the Enterobacterales, there was no significant difference in all-cause in-hospital mortality between the two groups (aOR, 1.76; 95% CI, 0.86-3.58). Time to discharge remained significantly longer in patients with CnSE-HAI (adjusted hazard ratio, 0.71; 95% CI, 0.51 - 0.98) after adjusting for disease severity, receipt of antibiotics with reported susceptibility and receipt of appropriate source control. Conclusion: Appropriate management of deep-seated Enterobacterales infections and reducing exposure to carbapenems may reduce risk of CnSE-HAIs in Singapore. Efforts to improve antimicrobial therapy in CnSE-HAI patients may improve patient outcomes.

Estimating the economic cost of carbapenem resistant Enterobacterales healthcare associated infections in Singapore acute-care hospitals.

Quantifying the costs of hospital associated infections (HAIs) caused by carbapenem-resistant Enterobacterales (CRE) can aid hospital decision makers in infection prevention and control decisions. We estimate the costs of a CRE HAI by infection type and the annual costs of CRE HAIs to acute-care hospitals in Singapore. We used tree diagrams to estimate the costs (in Singapore dollar) of different CRE HAI types from the health service perspective and compared them to the costs of carbapenem-susceptible HAIs. We used two approaches to estimate costs-direct costs of consumables for infection prevention and treatment; and costs associated with lost bed days. Cost of a HAI were extrapolated to annual CRE HAI incidence in Singapore acute-care hospitals to estimate the annual cost to the hospitals. We found that the cost of a CRE HAI based on direct cost and lost bed days are SGD$9,913 (95% CI, SGD$9,431-10,395) and SGD$10,044 (95% CI, SGD$9,789-10,300) respectively. CRE HAIs are markedly higher than the carbapenem-susceptible HAIs for all infection types. In both approaches, CRE pneumonia was the costliest infection. Based on a CRE HAI incidence of 233 per 100,000 inpatient admissions, CRE HAIs costed SGD$12.16M (95% CI, SGD$11.84-12.48M) annually based on direct costs, and SGD$12.33M (95% CI, SGD$12.01-12.64M) annually based on lost bed days. In conclusion, we described the cost of CRE HAIs in Singapore hospitals and identified infections with the highest costs. The findings may be useful in informing future economic evaluations of competing CRE HAI prevention and treatment programmes.