Specificities of Meningitis and Meningo-Encephalitis After Kidney Transplantation: A French Retrospective Cohort Study

Abstract

Kidney transplant recipients develop atypical infections in their epidemiology, presentation and outcome. Among these, meningitis and meningoencephalitis require urgent and adapted anti-infectious therapy, but published data is scarce in KTRs. The aim of this study was to describe their epidemiology, presentation and outcome, in order to improve their diagnostic and management. We performed a retrospective, multicentric cohort study in 15 French hospitals that included all 199 cases of M/ME in KTRs between 2007 and 2018 (0.9 case per 1,000 KTRs annually). Epidemiology was different from that in the general population: 20% were due to Cryptococcus neoformans, 13.5% to varicella-zoster virus, 5.5% to Mycobacterium tuberculosis, and 4.5% to Enterobacteria (half of which produced extended spectrum beta-lactamases), and 5% were Post Transplant Lymphoproliferative Disorders. Microorganisms causing M/ME in the general population were infrequent (2%, for Streptococcus pneumoniae) or absent (Neisseria meningitidis). M/ME caused by Enterobacteria, Staphylococci or filamentous fungi were associated with high and early mortality (50%-70% at 1 year). Graft survival was not associated with the etiology of M/ME, nor was impacted by immunosuppression reduction. Based on these results, we suggest international studies to adapt guidelines in order to improve the diagnosis and the probabilistic treatment of M/ME in SOTRs.

Keywords: Cryptococcus neoformans; encephalitis; enterobacteriales; immunosuppression; kidney transplantation; meningitis; opportunistic infections; transplant infectious diseases.

FIGURE 1

Flow Chart. ICD, international classification of diseases; CNS, central nervous system; CSF, cerebrospinal fluid; M/ME, meningitis/meningo-encephalitis.

FIGURE 2

Causes of meningitis and meningoencephalitis in kidney transplant recipients. Cases of M/ME are represented according to type of etiology (A), main microorganism or cause (B), type of Fungi (C), virus (D), or bacteria (E). (F) All Enterobacteriales; (G) proportion of extended spectrum beta-lactamase producing Enterobacteriales. VZV, varicella-zoster virus; MUC, meningitis of unknown cause; VZV, varicella-zoster virus; PTLD, post-transplant lymphoproliferative disorder; HSV, herpes simplex virus; CMV, cytomegalovirus; EBV, Epstein-Barr virus; HEV, hepatitis E virus; HIV, human immunodeficiency virus; ESBL, extended-spectrum betalactamase.

FIGURE 3

Distribution of M/ME over time after KT according to the etiology. (A) Cytomegalovirus cases, (B) Gram-negative rod cases, (C) Filamentous fungi, (D) Post-transplant lymphoproliferative disorders.

FIGURE 4

Biological characteristics in the different groups of microorganisms or causes. (A) Last CD4⁺ count before M/ME onset, (B) C-reactive protein at admission for M/ME, (C) CSF cellularity, (D) CSF protein level, (E) glucose CSF/blood ratio and (F) ROC Curve of the glucose CSF/blood ratio to discriminate bacterial and fungal M/ME from the other M/ME. Elts, elements; F, fungi; B, bacteria; V, viruses; P, parasites; O, other.

FIGURE 5

Patient and graft survival. (A) Patient survival in the global population presented according to the group of causative microorganism or cause. (B) Survival of patients suffering fungal M/ME. (C) Survival of patients presenting with bacterial M/ME. (D) Graft survival according to reduction of immunosuppression of M/ME. F, fungi; B, bacteria; V, viruses; P, parasites; O, others; CN, Cryptococcus neoformans; FF, filamentous fungi; GNR, Gram-negative rods.