Clinical Analysis And Drug Sensitivity Of Nontuberculous Mycobacterial Disease

Nontuberculous mycobacteria(NTM)generally refers to mycobacteria other than Mycobacterium tuberculosis(MTB)and Mycobacterium leprae.According to its growth rate,it is divided into rapidly growing mycobacteria(RGM)and slowly growing mycobacteria(SGM).NTM is a kind of opportunistic pathogenic bacteria,which is distributed in the environment of domestic water,natural water,soil and aerosol.Clinically,infections such as M.abscessus and M.fortuitum in RGM,M.avium complex,M.kansasii,and M.marinum among SGM are the most common.In recent years,the incidence of nontuberculous mycobacteria disease has been increasing globally,and the isolation rate of NTM in China has also increased from 4.9% in 1990 to 22.9% in 2010,which has become an important public health threat to human health.Patients with nontuberculous mycobacteria disease are clinically more common in the lung and cause chronic lung diseases,followed by lymphadenitis,skin diseases,and transmissible diseases.Nontuberculous mycobacteria lung disease and tuberculosis are very similar in clinical symptoms,imaging characteristics,histopathology,and etiology.Many patients with nontuberculous mycobacteria lung disease are often misdiagnosed as tuberculosis and given anti-tuberculosis treatment,but NTM is naturally resistant to most anti-tuberculosis drugs,and the treatment effect is often poor.At present,the methods for distinguishing between NTM and tuberculosis mainly include PNB selective culture,nucleic acid amplification,MPT64 antigen detection method.However,there are problems such as the long time required for PNB culture and the natural deletion of PCR amplified sequences.Therefore,it is important to find a fast and accurate diagnostic method that is easy to be used in the clinic for an effective anti-nontuberculous mycobacteria drug treatment program.Based on the clinical database of 573 patients with nontuberculous mycobacteria pulmonary disease and 593 patients with pulmonary tuberculosis diagnosed in Shanghai Pulmonary Hospital from 2009 to 2019,we compared the basic physiological and clinical characteristics of nontuberculous mycobacteria pulmonary disease and tuberculosis,and discussed the related risk factors of nontuberculous mycobacteria pulmonary disease patients;The clinical characteristics of rapidly growing mycobacteria and slowly growing mycobacteria in NTM patients were compared;The differences in drug resistance between rapidly growing mycobacteria and slowly growing mycobacteria were compared;The difference of clinical indexes between the patients with nontuberculous mycobacteria pulmonary disease and tuberculosis and with positive results in T-spot test was analyzed;and the indexes with potential differential diagnostic value were screened and evaluated.The results indicated that there were statistically significant differences in age、cough、hemoptysis、fever、bronchiectasis and pulmonary cavity between patients with untreated NTM pulmonary disease and tuberculosis(P<0.05).The probability of nontuberculous mycobacteria lung disease was higher in patients over 60 years old with high higher incidence of bronchiectasis.In addition,NTM strains from the patients showed differential resistance to isoniazid、rifampicin、ethambutol、streptomycin、amikacin、chloramphenicol、ofloxacin and other anti-tuberculosis drugs.Resistance to rifampicin and ethambutol between rapidly growing mycobacteria and slowly growing mycobacteria were statistically significantly different.In the clinical indices of the two groups patients,HGB、Lym%、EO%、HCT、MCV、PDW、P-LCR、HDL、AT3、RBP in NTM group were significantly higher than those in tuberculosis group(P<0.05);while WBC、Neu%、PLT、PCT、C3、TT、CRP、D-Dimer、T-spot、MDSIL-2R、ESR in the tuberculosis group were higher than those in the NTM group(P<0.05).ROC curve analysis was performed,and the areas under the T-spot and CRP curves were 0.755、0.732 with tuberculosis patients as control.The diagnostic threshold of T-spot counts was 17.5,with the sensitivity of 80.5%,and the specificity of 62.2%.The cutoff value of CRP was 9.5 mg/L,with the sensitivity of 67.5%,and the specificity of70.1%;Counts of T-spot combined with MCH and MDSIL-2R showed the highest specificity of 95.8% in differentiation of NTM and TB both with positive T-spot TB results,with sensitivity of 56.9%,and AUC area of 0.801;In addition,the specificities of PLT combined with AT-3,T-spot with MCV,T-spot with RBP and PCT was 88.9%,85.4% and84.0% with the sensitivity of 51.3%,58.5% and 68.4%,respectively and AUC between0.7-0.9.In the second part of the project,24 clinical antibiotics from five major categories were tested for in vitro drug sensitivity studies on different NTM strains.It was found that when the single drug was used,moxalactam showed better inhibitory effect on M.scrofulaceum.Similarly,doxycycline showed good antibacterial activity on M.marinum and M.kansasii;Faropenem and vancomycin both showed good inhibitory effects on M.scrofulaceum and M.marinum;Clindamycin showed better inhibitory effect on M.scrofulaceum and M.kansasii.clarithromycin and linezolid in combination showed synergistic inhibitory effect on M.avium and M.kansasii;doxycycline and clarithromycin have a synergistic inhibitory effect on M.avium.In summary,this paper analyzes the differences in clinical manifestation and characteristics between patients with NTM pulmonary disease and patients with tuberculosis.Wefind that T-spot combined with MCH,MDSIL-2R,and RBP,PCT;PLT with AT-3,T-spot and MCV can improve differential diagnosis of patients with NTM lung disease and tuberculosis with positive results in T-spot TB tests.In addition,for the first time,our study indicate that antibiotics such as moxalactam、faropenem、doxycycline、vancomycin、clindamycin showed inhibitory effects on in vitro growth of different nontuberculous mycobacteria,which laid a foundation for evaluation for their further clinical application.