Impact of Two Antibiotic Therapies on Clinical Outcome and Gut Microbiota Profile in Liver Transplant Paediatric Candidates Colonized by Carbapenem-Resistant Klebsiella pneumoniae CR-KP

Abstract

Colonization by multidrug-resistant (MDR) organisms in liver transplant (LT) candidates significantly affects the LT outcome. To date, consensus about patient management is lacking, including microbiological screening indications. This pilot study aimed to evaluate the impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization in LT paediatric candidates to enable optimal prevention and therapeutic strategies that exploit both clinical and microbiological approaches. Seven paediatric patients colonized by CR-KP were evaluated before and until one-year post LT. At the time of the transplant, patients were stratified based on antibiotic (ATB) prophylaxis into two groups: ‘standard ATB’ (standard ATB prophylaxis), and ‘targeted ATB’ (MDR antibiogram-based ATB prophylaxis). Twenty-eight faecal samples were collected during follow-up and used for MDR screening and gut microbiota 16S rRNA-based profiling. Post-transplant hospitalization duration was comparable for both groups. With the exception of one patient, no serious infections and/or complications, nor deaths were recorded. A progressive MDR decontamination was registered. In the ‘standard ATB’ group, overall bacterial richness increased. Moreover, 6 months after LT, Lactobacillus and Bulleidia were increased and Enterobacteriaceae and Klebsiella spp. were reduced. In the ‘targeted ATB’ group Klebsiella spp., Ruminococcus gnavus, Erysipelotrichaceae, and Bifidobacterium spp. were increased 12 months after LT. In conclusion, both antibiotics prophylaxis do not affect nor LT outcomes or the risk of intestinal bacterial translocation. However, in the ‘standard ATB’ group, gut microbiota richness after LT was increased, with an increase of beneficial lactic acid- and short-chain fatty acids (SCFA)-producing bacteria and the reduction of harmful Enterobacteriaceae and Klebsiella spp. It could therefore be appropriate to administer standard prophylaxis, reserving the use of ATB-based molecules only in case of complications.

In Silico Docking, Resistance Modulation and Biofilm Gene Expression in Multidrug-Resistant Acinetobacter baumannii via Cinnamic and Gallic Acids

“…Antimicrobial resistance is reflected in longer hospitalization periods, elevated health care financial burdens, more severe complications and higher mortality rates [ 4 , 5 ]. It also casts a shadow over medical advancements such as chemotherapy, organ transplantation and other surgeries due to the risk of sepsis with difficult management [ 6 ]. Moreover, the problem of antimicrobial resistance is aggravated in resource-limited countries as well as in high-risk groups, including neonates [ 7 ].…”

Surgical Site Infections After Pediatric Liver Transplantation—Impact of a Change in Perioperative Prophylactic Antibiotic Protocol

“…The synthesis of these findings suggests that MDR carriers might benefit from individually tailored antibiotic regimens, as discussed in the literature [11,37] and already practiced in some European liver transplant centers [19]. However, a study tempering enthusiasm for this approach was published by Cardile et al on adult LTX recipients who were carriers of carbapenem-resistant Klebsiella pneumoniae [38]: In the standard antibiotic treatment group, microbiota richness after liver transplant patients was increased and harmful Enterobacteriaceae and Klebsiella spp. reduced compared with the group receiving targeted MDR antibiogram-based antibiotic treatment.…”

“…However, a study tempering enthusiasm for this approach was published by Cardile et al. on adult LTX recipients who were carriers of carbapenem‐resistant Klebsiella pneumoniae [38]: In the standard antibiotic treatment group, microbiota richness after liver transplant patients was increased and harmful Enterobacteriaceae and Klebsiella spp. reduced compared with the group receiving targeted MDR antibiogram‐based antibiotic treatment.…”

Antimicrobial Resistance in Organ Transplant Recipients

“…However, in another study including different SOT, mainly LT, with a previous CRE colonization, T-PAP was more common in the group of patients who developed a CRE infection after SOT (10). In addition, a small single-center experience evaluating T-PAP vs. standard PAP in 7 LT pediatric recipients colonized with CRE observed a progressive restoration of gut microbiota in the standard group, meanwhile in the T-PAP (consisting in both intravenously and orally colistin based regimens) group persistent dysbiosis was recorded even after 12 months of follow-up (43).…”