PMC8131010_01
Treatment timeline for CRKP infection.
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Multi-locus sequence typing (MLST) of seven sets of DNA fragments derived from housekeeping genes was performed to examine the genetic diversity of CRKP strains isolated from the incision, urine, and fecal samples of the patient, and the results revealed that all the three strains were exclusively grouped into ST11 (Table S1 and Figure S1). Table S2 and Figure S3), indicating its hypermucoviscous and hypervirulent phenotype. Since the CRKP isolated from the patient was resistant against most antibiotics except tigecycline, fosfomycin and polymyxin (Table S3), the combination treatment of with tigecycline (50 mg/12 hours), fosfomycin (4 g/8 hours) and meropenem (1~2 g/8 hours) and was utilized for treating the infection. The detailed treatment timeline for the CRKP infection is shown in Figure 1.
Surgical incision and renal function indexes in the patient post-FMT. (A) Surgical incision for kidney transplantation in the patient. (B) Serum creatinine and blood urea nitrogen (BUN) levels.
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The patient's incision began to heal three days after FMT, and showed complete healing 17 days after FMT (Figure 2A). Moreover, there was no obvious increase in serum creatinine and blood urea nitrogen (BUN) after FMT (Figure 2B), suggesting FMT did not have adverse effect on the patient's renal function.
Alpha and beta diversity of the gut microbiota of the donor and the patient pre- and post-FMT. Histograms compared Chao1 index (A) and Shannon index (B) of the fecal microbiome in the donor and the patient pre- and post-FMT. PCoA plots showed the microbial community variation of the donor and the patient pre- and post-FMT based on weighted UniFrac distance (C) and unweighted UniFrac distance (D). FMT 1W, FMT 3W and FMT 2M represented 1 week, 3 weeks and 2 months after FMT.
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Table S2 and Figure S3), indicating its hypermucoviscous and hypervirulent phenotype. Since the CRKP isolated from the patient was resistant against most antibiotics except tigecycline, fosfomycin and polymyxin (Table S3), the combination treatment of with tigecycline (50 mg/12 hours), fosfomycin (4 g/8 hours) and meropenem (1~2 g/8 hours) and was utilized for treating the infection. The detailed treatment timeline for the CRKP infection is shown in Figure 1. Alpha diversity analyses showed that before FMT, the patient was associated with obviously lower species richness (Chao1 index, Figure 3A) and diversity (Shannon index, Figure 3B) than the donor, which significantly increased at one week, three weeks and two months after FMT (Figure 3A and B), indicating that FMT could lead to an increase in the richness and diversity of the patient fecal microbiota. Both the weighted (Figure 3C) and unweighted (Figure 3D) UniFrac methods revealed significant divergence of the microbial communities between the donor and the patient before FMT. It should be noted that though the patient microbial community post-FMT still differed from the donor one, their distances visibly decreased, especially at one week and three weeks after FMT (Figure 3C and D).
Gut microbial compositions of the donor and the patient pre- and post-FMT. (A) Cumulative histograms representing average distributions of major taxa at genus level. FMT 1W, FMT 3W and FMT 2M represented 1 week, 3 weeks and 2 months after FMT. (B) Pie chart representing the relative abundance of Klebsiella (red). (C) Network diagrams showing the relationship between Klebsiella and other genera. Red indicated positive correlation and blue indicated negative correlation.
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Furthermore, we analyzed the microbial compositions in detail, and the results were visualized as cumulative histograms (Figure 4A). Results of the cluster analysis showed that the fecal microbial composition of the patient following FMT was more similar to the donor microbial composition than that of the patient collected prior to FMT (Figure 4A). It should be noted that the relative abundance of Klebsiella significantly decreased at one week after FMT (61.15% vs 1.5%), and remained low at three weeks (1.4%) and two months (6.0%) after FMT (Figure 4B). Moreover, the relative abundances of Ruminococcus, Coprococcus, and Clostridium were negatively correlated with that of Klebsiella, indicating that these genera may competitively interact with Klebsiella (Figure 4C).