In this study, we compare the sensibility and specificity of FAGIP vs standard tests in a population of KTR with diarrhea.We performed a double-blind, observational, prospective cohort study in KTR from a single university hospital. The study was approved by the Institutional Review Board (IRB) CERC-MIT.KTR hospitalized for acute diarrhea (< 7 days), or developed diarrhea during their hospital stay from April 2022 to February 2024 (with an interruption from May 2023 to October 2023 for the replacement of expired FAGIP kits and the relocation of the PCR device) were included in the study. Inclusion criteria were adults transplanted with a functional kidney having expressed their nonopposition. Exclusion criteria were having a non-functional kidney transplant, resolution of diarrhea before samples could be achieved, patient already included in the study for a diarrhea episode, and patient with a known positive CMV-PCR in blood tests during the 7 days preceding the study, as the diagnosis of CMV-related diarrhea doesn't rely on stool tests. Patients were included prospectively at their hospital admission and followed during their entire hospital stay.Standard tests were prescribed by the attddending physician following the procedures of each local laboratory: (i) bacteriological cultures for classical digestive pathogens (Salmonella spp., Shigella spp., Campylobacter spp., Yersinia spp.), enzyme immunoassay for shiga-toxin in case of bloody stools, (ii) tests for toxinogenic C. difficile, (iii) tests for enteropathogenic parasites (cryptosporidium, microsporidium) in the parasitology department (3 stool samples within 5 days), and (iv) tests for enteric viruses (adenovirus, enterovirus, sapovirus, norovirus) in the virology department.FAGIP was performed on a stool sample by an independent clinical study technician, blinded from the patient, the circumstances of diarrhea and the results of standard analyses. Investigators and clinicians were blinded from the FAGIP results in order not to interfere with the management of the patients.Clinical and biological data were prospectively collected from electronic medical files.Thirty-four patients were included in the study. Clinical and microbiological characteristics are summarized in table 1. The median age was 51 years. Immunosuppression included corticosteroid (100%), mycophenolate mofetil (97.1%), or tacrolimus (97.1%). The median delay time between from transplantation and diarrhea was 6.1 months. Twenty-three (67.6%) patients had AKI and 55.9% had intravenous hydration. The median serum creatinine was 2.79 mg/dL. Amongst 34 patients, 30 (88.2%) had a stool culture, 31 (91.1%) a parasitological stool test, but only 9 (26.5%) a virological test. FAGIP was performed in all patients. Antimicrobial treatment for diarrhea was initiated in 4/34 (11.8%) patients, with a delay of 5 days.Six (17.6%) patients had a diagnosis of infectious diarrhea (Table 1). In two of them, the diagnosis was made in spite of negative stool tests: one patient had a blood culture positive for Klebsiella pneumoniae and E.coli with a negative stool culture, and the second patient was diagnosed with CMV disease. FAGIP was negative in these 2 patients.In the 4 patients with a positive standard test, FAGIP was also positive and identified the same pathogen. In 3 cases, FAGIP detected a second pathogen (Table 1). In the 30 patients with negative standard tests, FAGIP was positive in 9 patients. Altogether, FAGIP was positive in 13 out of 34 patients (38.2%).To investigate the significance of a positive FAGIP with negative standard tests, we studied clinical and demographic features: systolic arterial blood pressure (BP) was lower in patients with a positive FAGIP (median 121 vs 138 mmHg, p=0.049). Other features including temperature, kidney function, and length of stay were not significantly different.1/ In our cohort of 34 patients, standard methods had limited yield since it could identify pathogens in only 4/34 (11.7%) patients (3 parasites and 1 bacteria). The virological test could be performed in only 26.5% of patients, underscoring the difficulty of performing repeated stool sampling in real-life settings.2/ FAGIP was concordant with standard methods in the 4 patients with a positive standard test.3/ FAGIP was positive in 9/34 patients with negative standard tests (26.5%). In these 9 patients, FAGIP positivity with negative standard tests could have warranted a specific treatment or modification of immunosuppressive regimen. However, it is not possible at this stage to distinguish asymptomatic carriage from authentic active infection (as suggested by the slightly lower BP). Eventually, all these patients evolved well without a specific treatment. Therefore, it is also possible that FAGIP results were falsely positive, by detecting DNA or RNA of pathogens that can persist a while in stool after healing an infection, or colonizing non-pathogenic agents.An interventional study is thus needed to assess the effect of treating patients based on FAGIP results. Resolution of diarrhea, but also health costs and antibiotic resistance are relevant outcomes since the integration of highly sensitive multiplex PCR tests generally leads toward more antibiotics, anti-viral and anti-parasitic drugs use.In conclusion, FAGIP is an easy to implement and sensitive method for the identification of diarrhea-associated pathogens in KTR. Its increasing use in place of the standard microbiology tests raises concerns about overdiagnosis and overtreatment that will need further prospective evaluation.
Ferrié et al. (Tue,) studied this question.