The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae

Abstract

The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.

Keywords: 16S rRNA; CRKP; carbapenem; colonization resistance; intestinal microbiota.

Fig 1

The bacterial count and shedding duration. Panel A, the study process comprising the collection of feces prior to administration with carbapenems on day −2, injection of carbapenems into the tail vein on day −1, collection of feces and then inoculation with CRKP strain on day 0, and subsequent collection of feces. Panel B, a chart showing the trend of bacterial shedding (n = 10, mean ± SEM). Panel C, the change in body weight along with the time. Panel D, bacterial on day 1 after inoculation with bacterial strain. Panel E, duration of bacterial shedding in each group. Each dot represents a mouse. Statistical analyses were performed using the Kruskal–Wallis test. Abbreviations: CON, included two groups without administration of a carbapenem nor saline (n = 5) and saline (n = 5); ETP, etapenem; IPM, imipenem/cilastatin; MEM, meropenem; Error bar, 95% confidence interval (CI). Ns for not significant and P > 0.05, * for P ≤ 0.05, ** for P ≤ 0.01, *** for P ≤ 0.001, **** for P ≤ 0.0001.

Fig 2

The diversity and richness of murine gut microbiota before and after administration of a carbapenem. Panels A and B, the boxplots of Shannon index and ACE index after administration of a carbapenem (n = 8), respectively. Panel C, diversity between murine microbiomes (β diversity) was assessed by principal coordinated analyses (PCoA) (Bray-Crutis matrix) of ASVs and every clustering of before (T1) and after (T2) administration of a carbapenem (n = 8), every ellipse represents the 95% CI of a group. Panels D and E, histograms of the top 10 taxa species abundance at the phylum level and at the genus level, respectively. CON, included two groups without administration of a carbapenem nor saline (n = 4) and saline (n = 4); ETP, etapenem; IPM, imipenem/cilastatin; MEM, meropenem; N, without administration with a carbapenem nor saline; NS, saline. T1, T2, and T3 are the time points on the day before carbapenem administration (as shown in Fig. 1A day −2), after carbapenem administration on the same day (day −1), and after inoculation of the bacterial strain on the same day (day 1). Ns for not significant and P > 0.05, * for P ≤ 0.05, ** for P ≤ 0.01, *** for P ≤ 0.001, **** for P ≤ 0.0001.

Fig 3

LEfSe for analysis of murine gut microbiota ASVs composition between a carbapenem group and the saline control group after antibiotic or saline treatment (LDA > 4). The length of the bar chart represents the contribution of different species. ETP, etapenem; IPM, imipenem/cilastatin; MEM, meropenem; NS, saline. T2 is the time point on the day after carbapnem administration (as shown in Fig. 1A day −1), and detailed taxonomic labels can be found in Table S2.