Preliminary Study on Drug Susceptibility Profile and Resistance Mechanisms to Macrolides of Clinical Isolates of Non-tuberculous Mycobacteria from China

Objective Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria（NTM） isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. Methods Four macrolides, including clarithromycin（CLAR）, azithromycin（AZM）, roxithromycin（ROX）, and erythromycin（ERY）, were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23 S r RNA and erm, were analyzed with nucleotide sequence analysis. Results Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191 A and T2221 C on rrl were specific for the M. abscessus complex（MABC）. Seven sites, G2140 A, G2210 C, C2217 G, T2238 C, T2322 C, T2404 C, and A2406 G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192 G, T2358 G, and A2636 G, were observed only in M. fortuitum and one site G2152 A was specific for M. gordonae. The genes erm（39） and erm（41） were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. Conclusion The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23 S r RNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.

Distribution Characteristics of Drug Susceptibility Test Results of Tuberculosis and Non-Tuberculous Bacilli in Patients with Opportunistic Infections of AIDS

Objective: To understand the distribution of drug susceptibility test results of opportunistic infections of tuberculosis and non-tuberculous bacilli in AIDS patients. Methods: The AIDS patients who were hospitalized in our hospital from January 2016 to June 2019 were collected as the research objects, and patients with opportunistic tuberculosis and non-tuberculous bacilli from AIDS patients were screened for drug susceptibility tests, and the distribution characteristics of drug susceptibility were analyzed. Results: 179 strains of tuberculosis and non-tuberculous mycobacteria were isolated from the specimens of AIDS patients, including 135 cases of tuberculosis mycobacteria and 44 cases of non-tuberculous mycobacteria. In the results of the drug susceptibility test, most strains of Mycobacterium tuberculosis showed sensitivity to commonly used drugs, and a few strains showed resistance;most strains of non-tuberculous mycobacteria showed resistance, and a few strains showed sensitivity. Conclusion: AIDS opportunistic infection of Mycobacterium tuberculosis and non-tuberculous mycobacteria have significant differences in drug sensitivity test results. Timely detection and analysis are of great significance to the diagnosis and treatment of the disease.

Lack of correlation between surface water area and infection with Pseudomonas aeruginosa and the non-tuberculous mycobacteria (NTMs) in patients with cystic fibrosis (CF)

Background People with cystic fibrosis(CF)may develop clinically significant chronic respiratory infections with Pseudomonas aeruginosa(PA)and non-tuberculous mycobacteria(NTM).Open water has been suggested to be an important source for continuous or intermittent exposure to these pathogens.To date,there has been a paucity of studies examining the relationship between chronic PA and NTM infection in CF patients and surfaces waters,including blue spaces.The aim of this study was therefore to examine the relationship between chronic pulmonary infection with PA and NTMs in children and adults with CF in European countries and area of surface waters,including blue spaces.Methods European CF registry data detailing incidence of chronic PA and NTM infection in adults and children with CF in Europe(n=41,486 in 24 European countries)was correlated with surface water area data from the same countries(approx.678,278 km2)employing Spearman coefficients.Results Correlation of chronic PA infection in children and adults and surface water area were not significant(p=0.0680 and p=0.8448,respectively),as was NTM infection(p=0.7371 and p=0.0712,respectively).Conclusions Acquistion of PA and its avoidance in people with CF is a complicated dynamic,not solely driven by close association with surface water,but through the integration of several other factors,including mitigations by people with CF to avoid high risk scenarios with surface water.This study was unable to demonstrate a correlation between PA and NTM infection in people with cystic fibrosis and surface water area at a national level.CF patients should continue to be vigilant about potential infection risks posed by water and take evidence-based decisions regarding their behaviour around water to protect them for acquiring these organisms from these sources.

Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections

Background:It is difficult to quickly distinguish non-tuberculous mycobacterial(NTM)infection from tuberculosis(TB)infection in human immunodeficiency virus(HIV)-infected patients because of many similarities between these diseases.A simple and effective way to determine the differences using routine blood tests is necessary in developing countries.Methods:A retrospective cohort study was conducted to recruit HIV-infected patients with either NTM infection or TB infection diagnosed for the first time according to mycobacterial culture and microscopic identification from May 2010 to March 2016.These data included the analysis of blood cells,liver function,renal function,C-reactive protein(CRP),and erythrocyte sedimentation rate(ESR),and were compared between the HIV/TB and HIV/NTM groups.Results:A total of 240 patients were enrolled.The number of HIV/TB and HIV/NTM patients was 113 and 127,respectively.There were no significant differences in the CD4 T-cell count,age,sex,percentage of patients initiating antiretroviral therapy(ART)before the explicit diagnosis of TB or NTM infection.NTM infection was more likely to be restricted in the pulmonary while TB infection also involves extra-pulmonary sites.Both the leukocyte count(5.60×109/L)and the proportion of neutrophils in the leukocyte count(76.70%)in the HIV/TB group were significantly higher than those in the HIV/NTM group(4.40×10^(9)/L[P=0.0014]and 69.30%[P<0.001].The analysis of liver function markers indicated that the concentration of albumin but not ALT and AST was significantly lower in the HIV/TB group than in the HIV/NTM group(P<0.001).The creatinine and urea levels were not significantly different between the two groups.The ESR(84.00 mm/h)and the concentration of CRP(59.60 mg/L)were significantly higher in the HIV/TB group than in the HIV/NTM group(52.00 mm/h and 19.60 mg/L,respectively)(P<0.001).To distinguish TB infection from NTM infection,the best cut-off value was 69.5 mm/h for ESR,with a positive predictive value(PPV)of 0.740 and negative predictive value(NPV)of 0.721,and 48.8 mg/L for CRP,with a PPV of 0.676 and NPV of 0.697.Conclusion:The dissemination character as well as stronger immune response characterized by higher inflammation markers(e.g.WBC,ESR,CRP)can help distinguish TB from NTM infection in HIV-infected patients who need empirical therapy or diagnostic therapy immediately in low-income areas.

Thoracoscopic management for bronchiectasis with non-tuberculous mycobacterial infection

Background Non-tuberculous mycobacteria （NTM） have emerged as important opportunistic pathogens of the human being in recent years. Patients with pre-existing bronchiectasis are susceptible to NTM. However, information about its occurrence among bronchiectatic patients in Shenzhen, China is lacking and its impact on the course of bronchiectasis following surgical intervention is unknown. This preliminary study aimed to investigate the prevalence of NTM in bronchiectasis that required surgery in our center, evaluate the role of intraoperative routine screening for NTM, and summarize our initial experience in thoracoscopic management for bronchiectatic patients with NTM. Methods A retrospective analysis of clinical, microbiological data of our bronchiectatic patients with NTM over 5 years was made and 40 patients with bronchiectasis were studied to determine the role of intraoperative routine screening for NTM. Results The prevalence of NTM in this population of patients with bronchiectasis in our center was 6.7% （7/105）. The diagnostic yield of the 40 intraoperative specimens was 7.5% （3/40）. Of the 7 patients with bronchiectasis and NTM, 3 patients developed postoperative wound infections. All were cured with chemotherapy for 8-12 months along with vigorous surgical debridement. Another patient had a slow growth of mycobacteria involving double lungs and the right thoracic cavity and recovered after chemotherapy for nearly 14 months and tube drainage. The affected tissue was completely resected in the remaining 3 patients with no operative mortality and postoperative morbidity, and routine intraoperative screening for NTM was initiated in these patients. Conclusions NTM is not uncommon in bronchiectatic patients which deserves surgeons＇ utmost attention. Routine intraoperative screening for NTM identified otherwise unsuspected patients has shown favorable outcomes. Thoracoscopic management for bronchiectasis with NTM is technically feasible although its role remains to be defined.

Misdiagnosis of tuberculosis and the clinical relevance of nontuberculous mycobacteria in Zambia

Objective:To determine the accuracy of TB diagnosis of TB in Zambia in the era of increasing HIV prevalence.Methods:Sputum of the clinically diagnosed TB cases was additionally subjected to liquid culture and molecular identification.This study distinguished between TB cases confirmed by positive Mycobacterium tuberculosis(M.tuberculosis) cultures and mycobacterial disease caused by non-tuberculous mycobacteria(NTM).Results:Only 49% of the 173 presumptively diagnosed TB cases was M.tuberculosis cultured,while in 13% (22) cases,a combination of M.tuberculosis and NTM was found.In 18% of the patients only NTM were cultured.In 28% ,no mycobacteria was cultivable.HIV positive status was correlated with the isolation of NTM(P【0.05).Conclusions:The diagnosis of tuberculosis based on symptoms, sputum smear and/or chest X-ray leads to significant numbers of false-positive TB cases in Zambia,most likely due to the increased prevalence of HIV.The role of NTM in tuberculosislike disease also seems relevant to the false diagnosis of TB in Zambia.

Pulmonary cavitary disease due to Mycobacterium xenopi

Non-tuberculous mycobacteria are a significant cause of pulmonary infections worldwide and can be clinically challenging.Mycobacterium xenopi(M.xenopi)has a low pathogenicity and usually requires immunosuppression or lung diseases.We describe herein a scarce case of pulmonary cavitary disease attributed to M.xenopi in a 57-year-old Caucasian patient with underlying structural lung disease successfully treated with rifampicin,ethambutol,clarithromycin,and amikacin.