OBJECTIVES : This systematic review assessed the disease and economic burden of MRGN in Japan.

METHODS : Pubmed, Embase, and ICHUSHI databases were systematically searched to identify English and Japanese language literature from 2014 to 2019 that assessed healthcare resource utilization, QoL, incidence, and prevalence for MRGN.

RESULTS : 16 studies for disease burden and three studies for economic burden met the inclusion criteria. For disease burden, one study stated cefotaxime-non-susceptible Enterobacteriaceae (CTXNS-En) bacteremia to be associated with inappropriate empirical therapy, and the frequent occurrence of a delay in appropriate therapy likely contributes to inferior clinical responses (n=26 out of 37 cases). Another study concluded that, metallo-beta-lactamase (MBL) producing Enterobacteriaceae bloodstream infection was fatal, although rare, in patients with severe diseases and long-term hospitalization which highlights the higher chance of MRGN infections in Japanese hospital and nursing setting. MRGN also affects Japanese pediatric population, with one-fourth of gram-negative bacilli (GNB) bloodstream infection (BSI) cases were multi-drug resistance (MDR) (n=154 out 629), posing a serious threat to vulnerable infants and toddlers with underlying diseases. For economic burden, one study found that Imipenemase (IMP) carbapenem producing Enterobacteriaceae (CPE, IMP-CPE) were associated with prolonged ICU hospital stays and had different clinical and microbiological characteristics than non-CPE (10 vs 25 days of hospital admission). Patients with history of prior hospitalization and antibiotic use within 90 days had a higher cost burden of acquiring carbapenem-resistant Enterobacteriaceae (CRE) compared to those who did not acquire CRE (Mean cost of 220,710 JPY vs 69,904 JPY).

CONCLUSIONS : With rising antibiotic use, growing resistance, and narrowing treatment options, it is evident that disease and economic burden is high in Japan as well. However, this study found very limited studies which quantify this burden and further investigation into the topic, particularly the economic burden of MRGN, is needed in Japan.