In this study, we tried to use FMT to treat the CRKP infection in a renal transplant patient. FMT was first reported to be utilized for the treatment of described severe diarrhea in 4th century China, and now has been used worldwide to successfully treat patients with recurrent C. difficile infection (CDI) that is unresponsive to antibiotic treatment . Currently, clinical trials have also been performed to detect the efficacy of FMT for the treatment of other diseases such as ulcerative colitis (UC)[3, 4], irritable bowel syndrome (IBS), constipation, and metabolic syndrome[7, 8]. However, up till now, the effect of FMT on CRKP infection has not been reported. To date, FMT has not yet been investigated with respect to its effect on the CRKP infection.
The CRKP we isolated from the patient was resistant against most antibiotics except tigecycline and polymyxin. According to data from European Centre for Disease Prevention and Control, more than a third of the Klebsiella pneumoniae isolates were resistant to at least one antimicrobial agent. Few available treatment options are left for patients infected with multidrug-resistant CRKP, and combination therapy or colistin is the common treatment methods. In the present study, combination treatment of tigecycline, meropenem and phosphonomycin was evaluated in the CRKP infection. Since the effect of the combined therapy was of limited therapeutic benefit, FMT was performed for treatment. One week after FMT, the patient’s urine and anal swab cultures returned negative for CRKP, and 17 days after FMT, the incision showed complete healing. Moreover, the patient had no symptoms of infection two months after FMT.
Our results obtained from microbiome analysis showed that before FMT, Bacteroides and Klebsiella were predominant in the patient’s fecal sample, and the relative abundance of Klebsiella was even up to 38.9%. Klebsiella pneumoniae are ubiquitously distributed and considered as opportunistic pathogens inhabiting mucosal surfaces of intestines in healthy adults without inducing pathology. However, on some occasions, Klebsiella could disseminate from mucosae to other parts of the host causing infections including pneumonia, urinary tract infections, bloodstream infections and sepsis. Clinical evidence and basic experiment suggest that liver abscess could also be induced when Klebsiella translocate across the intestinal epithelium[11, 12]. To prevent rejection, the patient was placed on tacrolimus, mycophenolate mofetil, and prednisone after kidney transplantation. Among these drugs, tacrolimus is shown to have the effect of increasing intestinal permeability. Under this condition, it may be easier for CRKP to translocate across the intestinal epithelium to other places and induce infection. Thus, we speculate that the Klebsiella in the gut was very likely to be the source of the CRKP in the patient’s incision secretion, urine and blood cultures.
Obvious shift in microbial composition could be observed before and after FMT. The microbial composition of the patient post FMT resembled the donor composition. It should be noted that relative abundance of genera such as Phascolarctobacterium and Lachnoclostridium increased after FMT, while the relative abundance of Klebsiella significantly decreased. Presumably, the removal of gut Klebsiella by FMT could be an important contributor to reduce the number of the CRKP in the patient’s incision and urine. Similar to previous studies, we also found that the gut microbiota richness and diversity of the patient increased rapidly following FMT. The increased diversity of gut microbiota may have a positive effect on maintaining the stability of the colonic epithelial barrier and preventing Klebsiella pneumoniae from translocating, since Klebsiella pneumoniae was observed to barrier function and increase colonic permeability to luminal toxins, whereas other species such as Lactobacillus brevis could improve the tightness of the barrier. Moreover, relative abundance of Ruminococcus, Coprocpccus, and Clostridium were negatively correlated with that of Klebsiella, indicating that these genera may have distinct function from Klebsiella, and could partially limit the growth of Klebsiella.
Our research has several limitations. Firstly, since this study is a case report, more clinical studies and basic experiments are needed to confirm the therapeutic effect of FMT on CRKP infection and explore its mechanisms. Secondly, though no recurrent infection was observed in the patient, 2 months after FMT, the follow-up time was not long enough to investigate the sustained effect of FMT on CRKP infection. However, despite these limitations, this study demonstrated the therapeutic effect of FMT on CRKP infection, and may shine some light on the treatment of the infections caused by multidrug-resistant CRKP for the patients after transplantation.