Clinical And Laboratory Characteristics Of Hematogenous Disseminated Non-tuberculous Mycobacterial Disease In HIV Antibody Negative Patients

Background:In recent years,the incidence of Nontuberculous mycobacteria(NTM)disease has increased globally.It is getting more and more attention from clinicians and microbiologists.Among the NTM disease,the incidence of hematogenous disseminated NTM disease is very low.However,it is a critical condition with high mortality.Early diagnosis and treatment are essential to improve the prognosis.Previous studies were mainly focus on hematogenous disseminated NTM disease in Acquired Immune Deficiency Syndrome(AIDS)patients,but there was only little data of hematogenous disseminated NTM disease in Human Immunodeficiency Virus(HIV)antibody negative patients.This study aims to improve the understanding of hematogenous disseminated NTM disease in HIV antibody negative patients by analyzing its clinical,laboratory features and outcomes.Methods:Cases of hematogenous disseminated NTM disease in HIV antibody negative patients were retrospectively collected in Peking Union Medical College Hospital from January 2012 to October 2018.Clinical manifestations,laboratory examination data,treatment and prognosis were extracted from the hospital information system.Identification of existing NTM strains and detection of common drug resistance genes in frozen strains were accomplished.Statistical analysis was performed with SPSS 22.0.Results:Among the 23 HIV antibody negative patients with hematogenous disseminated NTM disease,21 cases had underlying diseases,with rheumatic disease(7 cases)as the most common one.The most common clinical manifestation was fever(23 cases),followed by weight loss(14 cases),cough(12 cases),superficial lymphadenopathy(9 cases).The most common species of NTM were Mycobacterium avium complex(10 cases).Laboratory examination showed anemia(hemoglobin 80(63-105)g/L),hypoalbuminemia[albumin 29(27-32)g/L],elevated erythrocyte sedimentation rate(ESR)[95(56-115)mm/h]and hypersensitive C-reactive protein(hsCRP)[103(52-161)mg/L],and decreased lymphocyte count[0.69(0.29-2.10)×109/L].Lymphocyte subset analysis indicated reduction of CD4+T cell counts[213(113-775)/ul],CD8+T cell counts[267(99-457)/ul],B cell counts[39(4-165)/ul],NK cell counts[88(32-279)/ul]and elevation of HLA-DR and CD38 expression in CD8+T cell[HLA-DR+CD8+%60(40-68)%and CD38+CD8+%81(65-90)%].The white blood cell counts,platelet counts,and high-sensitivity C-reactive protein in the dead patients were lower than surviving patients(The P values were 0.011,0.023,and 0.033,respectively).Total lymphocyte,CD8+T cell,B cell and NK cell counts were significantly lower in dead patients than surviving patients(The P value is 0.045,0.045,0.032 and 0.010,respectively).No mutation was detected at the 2058 and 2059 locus of 23S rRNA gene associated with macrolide resistance;1408,1409 locus of 16S rRNA gene related to amikacin resistance;460 locus of rp1C gene and 2270,2746,2810,2848 locus of 23S rRNA gene associated with linezolid resistance;codon 90,94,492 in resistance-determining region of gyrA/gyrB gene associated with fluoroquinolone resistance;513,516,526,531 codon of rpoB gene associated with rifamycin resistance..Conclusion:Hematogenous disseminated NTM disease in HIV antibody negative patients mainly manifested as fever,anemia,hypoalbuminemia,elevated inflammatory markers and proportion of activated CD8+ T cell and decreased CD4+ T cell,CD8+ T cell,B cell,NK cell counts.It was more common in patients with underlying disease.The most common species of NTM were Mycobacterium avium complex.No mutations in macrolides,amikacin,and linezolid-related resistance genes were detected in NTM strains isolated from blood samples from patients with hematogenous disseminated NTM disease.