Epidemiological Characteristics of Carbapenem-Resistant Enterobacterales in Japan: A Nationwide Analysis of Data from a Clinical Laboratory Center (2016-2022)

Abstract

In Japan, nationwide epidemiological surveys on carbapenem-resistant Enterobacterales (CREs), including comprehensive information, are scarce, with most data available only through public reports. This study analyzed data on the Enterobacterales family collected from nationwide testing centers between January 2016 and December 2022, focusing on isolates that met the criteria for CRE in Japan based on drug susceptibility. We investigated 5,323,875 Enterobacterales isolates of 12 different species; among 4696 (0.09%) CRE strains, the proportion of major CRE isolates was as follows: Escherichia coli, 31.3%; Klebsiella pneumoniae, 28.0%; Enterobacter cloacae, 18.5%; and Klebsiella aerogenes, 6.7%. Moreover, over a 7-year period, Providencia rettgeri, E. cloacae, K. aerogenes, and K. pneumoniae demonstrated relatively high CRE percentages of 0.6% (156/26,185), 0.47% (869/184,221), 0.28% (313/110,371), and 0.17% (1314/780,958), respectively. The number of CRE strains isolated from different samples was as follows: urine, 2390; respiratory specimens, 1254; stool, 425; blood, 252; others, 375. In the broader context, including colonization, the predominant isolates of CREs collected at nationwide testing centers are E. coli and K. pneumoniae. Furthermore, recently, attention has been directed toward less common CRE species, such as Klebsiella oxytoca and Providencia rettgeri, and thus, it might be necessary to continue monitoring these less common species.

Keywords: carbapenem-resistant Enterobacterales; carbapenemase producing; infection surveillance; multidrug-resistant organisms.

Figure 1

Annual frequency of representative CRE species from 2016 to 2022. In 2019 and 2021, K. pneumoniae was the most prevalent, but in other years, E. coli was the most common. The combined total of carbapenem-resistant E. coli and K. pneumoniae accounted for over 50% annually. “Others” includes the following bacterial species: S. marcescens, K. oxytoca, P. stuartii, P. rettgeri, C. koseri, C. freundii, M. morganii, and P. mirabilis.

Figure 2

Temporal trends of four representative CRE species. The bar graph represents the number of CRE isolates, while the line graph illustrates the percentage of CRE isolates, The dashed line represents the regression analysis of isolated CRE counts (A–D). In 2017, both E. coli and K. pneumoniae shown a decreasing trend, as indicated in the regression analysis. E. cloacae and K. aerogenes showed significance was obtained in ANOVA. E. cloacae exhibited a significantly higher CRE percentage than C. freundii, E. coli, M. morganii, K. oxytoca, S. marcescens, P. stuartii, C. koseri, and K. pneumoniae for seven years. The CRE percentage of K. aerogenes was significantly higher than that of P. mirabilis.

Figure 3

The proportion of submitted samples containing representative CRE isolates. E. coli, the most common CRE isolate, was found in approximately 65% of urinary samples. Unlike E. coli, K. pneumoniae, E. cloacae, and K. aerogenes showed a higher frequencies in upper respiratory and sputum samples.