mycophenolic-acid and Escherichia-coli-Infections

Transplant recipients are treated with immunosuppressive (IS) therapies, which impact host-microbial interactions. We examined the impact of IS drugs on gut microbiota and on the expression of ileal antimicrobial peptides.. Mice were treated for 14 days with prednisolone, mycophenolate mofetil, tacrolimus, a combination of these 3 drugs, everolimus, or water. Feces were collected before and after treatment initiation. Ileal samples were collected after sacrifice. Fecal and ileal microbiota were analyzed by pyrosequencing of 16S rRNA genes and enumeration of selected bacteria by culture, and C-type lectins were assessed in ileal tissues by reverse transcriptase-quantitative polymerase chain reaction.. Prednisolone disrupted fecal microbiota community structure, decreased Bacteroidetes, and increased Firmicutes in the feces. Prednisolone, tacrolimus, and mycophenolate mofetil modified fecal microbiota at the family level in each experimental replicate, but changes were not consistent between the replicates. In ileal samples, the genus Clostridium sensu stricto was dramatically reduced in the prednisolone and combined IS drug groups. These modifications corresponded to an altered ileal expression of C-type lectins Reg3γ and Reg3β, and of interleukin 22. Interestingly, the combined IS treatment enabled a commensal Escherichia coli to flourish, and dramatically increased colonization by uropathogenic E. coli strain 536.. IS treatment alters innate antimicrobial defenses and disrupts the gut microbiota, which leads to overgrowth of indigenous E. coli and facilitates colonization by opportunistic pathogens.

Topics: Animals; Antimicrobial Cationic Peptides; Drug Therapy, Combination; Escherichia coli Infections; Feces; Gastrointestinal Microbiome; Host-Pathogen Interactions; Ileum; Immunocompromised Host; Immunosuppressive Agents; Lectins, C-Type; Mice, Inbred C57BL; Models, Animal; Mycophenolic Acid; Opportunistic Infections; Prednisolone; Reverse Transcriptase Polymerase Chain Reaction; Ribotyping; Tacrolimus; Time Factors; Urinary Tract Infections; Uropathogenic Escherichia coli

Urinary tract infection (UTI) is the most frequent infectious complication among renal transplant recipients and a frequent cause of bacteremia, sepsis and acute graft failure. To evaluate the incidence, risk factors, type of pathogens and long-term effect of UTIs on graft and patient survivals in our center, we performed a retrospective cohort study reviewing the medical records of patients who received a renal transplant at our center from June 1986 to December 2009, excluding patients who lost their grafts in the first month due to arterial or veins thrombosis and acute antibody-mediated rejection. We studied 393 kidney-transplanted recipients; at least one UTI occurred in 221 (53.69%) patients during the follow-up period. The most frequent pathogens isolated in urine culture were Escherichia coli (n = 39, 18.4%) and Klebsiella pneumonia (n = 31, 14.6%). When patients with UTIs were compared with those without UTIs, female gender and use of mycophenolate mofetil or azathioprine seemed to be risk factors for UTIs on univariate analysis. However, female gender was the only independent risk factor on multivariate analysis RR = 1.964 (1.202-3.207), P = 0.007. This study confirmed that UTIs remain a major problem in renal transplant recipients, and female gender was the only independent risk factor.

Topics: Adult; Azathioprine; Chi-Square Distribution; Escherichia coli; Escherichia coli Infections; Female; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Klebsiella Infections; Klebsiella pneumoniae; Logistic Models; Male; Multivariate Analysis; Mycophenolic Acid; Retrospective Studies; Risk Assessment; Risk Factors; Tunisia; Urinary Tract Infections; Young Adult