Drug Resistance and Pathogenic Spectrum of Patients Coinfected with Nontuberculous Mycobacteria and Human-Immunodeficiency Virus in Chengdu, China
Introduction
Nontuberculous mycobacteria (NTM) encompass a broad classification of mycobacterial species, excluding Mycobacterium tuberculosis complex and M. leprae. Approximately 186 unique mycobacterium species are recognized, with new species continually emerging. NTM infections are particularly prevalent in immunocompromised individuals, including those infected with human-immunodeficiency virus (HIV). These infections are significant causes of pulmonary and disseminated diseases, especially in the advanced stages of acquired immunodeficiency syndrome (AIDS). HIV is a major life-threatening virus spreading across China, with Chengdu in Sichuan Province having one of the highest incidences of HIV-infected patients. This study aims to analyze the clinical characteristics, drug resistance, and pathogen spectrum of patients coinfected with HIV and NTM in the Chengdu area, providing a scientific basis for the prevention, control, diagnosis, and treatment of these co-infections.
Methods
Ethical Approval
The study was approved by the Ethical Review Committee of the Public Health Clinical Center of Chengdu (No. 2017Y 025). As a retrospective study using routinely collected patient data, informed consent was waived.
Study Design and Population
This retrospective study enrolled 59 patients with confirmed consecutive culture-positive NTM and HIV, treated at the Public Health Clinical Center of Chengdu from January 2014 to December 2018. HIV diagnosis was based on the Chinese HIV and HIV Infection Diagnostic Criteria (WS293–2008), and clinical staging followed the 1993 Centers for Disease Control diagnostic criteria. The same NTM strain cultured multiple times in the same patient was not repeatedly counted. Medical records, including epidemiology, clinical features, imaging, and laboratory information, were recorded.
Culture and Identification of Bacterial Strains
The BACTEC MGIT960 system was used for Mycobacterium culture. Pulmonary samples were collected via expectoration, gastric aspiration, and sputum induction. Extrapulmonary samples (pleural fluid, spinal fluid, lymph nodes) were collected through lumbar puncture, pleural tap, fine needle aspiration, and lymph node biopsy. NTM isolates were grown on Löwenstein-Jensen (L-J) medium for up to 4 weeks. Identification used p-nitrobenzoic acid and 2-thiophenecarboxylic acid hydrazide. NTM strains were frozen in the hospital’s strain bank, with the control strain H37Rv monitored.
Identification of NTM and Drug Sensitivity
Tuberculous polymerase chain reaction (TB-PCR) was used for species/complex level identification. NTM identification employed gene chip or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry systems. NTM drug sensitivity testing (DST) used a kit from AUTOBIO diagnostics Co., Ltd., with critical concentrations for various drugs.
Laboratory Quality Control
External quality assessment was conducted at the National Tuberculosis Reference Laboratory of the Chinese Center for Disease Control and Prevention, including smear, culture, and DST. Blinded retesting of 10% of isolates was performed in a superior laboratory.
Diagnosis and Treatment
NTM-infected patients were categorized and diagnosed according to Chinese Pulmonary Tuberculosis Diagnostic Criteria (WS288–2017), 2012 Nontuberculous Mycosis Diagnosis and Treatment Expert Consensus, and updated World Health Organization guidelines.
Statistical Analysis
Data were analyzed using SPSS Statistics Client 19.0. Measurement data of normal distribution were expressed as mean ± standard deviation (SD), and non-normal distribution data as median (inter-quartile range [IQR]). Categorical variables were expressed as numbers and percentages. Chi-square (x2) analysis was used to analyze drug resistance rates of nine antituberculosis drugs (ATDs) over five years, with statistical significance set at P < 0.05.
Results
Patient Characteristics
From January 2014 to December 2018, 59 patients coinfected with HIV and NTM were randomly selected. Fifty-six (94.9%) patients had respiratory distress, two (3.4%) had cerebrospinal fluid-related complications, and one (1.7%) had ascites. Fifty patients were male, with a mean age of 45 years (range, 22–83 years). HIV acquisition routes included heterosexual contact (57.6%), homosexual contact (13.6%), injection drug use (8.5%), blood transfusion (1.7%), and unknown etiology (13.6%). Common clinical symptoms were cough and expectoration (79.7%), fever (61.0%), difficulty breathing (33.9%), weight loss (28.8%), diarrhea (16.9%), and weakness (15.3%).
Laboratory and Imaging Findings
The median CD4 count was 26 cells/mL (range, 1–179 cells/mL), with 84.7% having <50 cells/mL and 15.3% having <200 cells/mL. The median HIV RNA count was 5.3 log U/mL (4.2-5.8) log U/mL. Common laboratory findings included reduced white blood cell counts (67.8%), increased erythrocyte sedimentation rate (74.6%), C-reactive protein (88.1%), lactate dehydrogenase (61.0%), and alpha-hydroxybutyrate dehydrogenase (54.2%). Chest imaging showed patchy shadows (42.4%), nodules (32.2%), millet shadow (18.6%), cavity (11.9%), lymphadenectasis (16.9%), hydrothorax (16.9%), and hydropericardium (10.2%).
NTM Pathogenic Spectrum and Drug Resistance Situation
Seven NTM species/complex were identified, with Mycobacterium avium–intracellulare complex (MAC) (52.5%) and M. kansasii (27.1%) being predominant. Drug resistance rates were highest for isoniazid (100.0%), followed by rifampicin (94.9%), streptomycin (94.9%), ofloxacin (93.2%), amikacin (88.1%), capreomycin (81.4%), kanamycin (64.4%), ethambutol (52.5%), and clarithromycin (33.9%). No significant change in drug resistance rates was observed over five years.
Discussion
NTM infections are increasingly reported worldwide, particularly in immunocompromised individuals. In Chengdu, MAC and M. kansasii are the predominant NTM species in HIV-infected patients. Lower CD4 counts, especially <50 cells/mL, are significant risk factors for NTM infection. Patients coinfected with HIV and NTM often present with severe clinical symptoms and complications, including deep fungal infections, pneumocystis pneumonia, cytomegalovirus, and syphilis. The drug resistance of NTM strains in these patients is severe, with relatively low resistance to ethambutol and clarithromycin, making these drugs preferable when DST results are unavailable.
Conclusion
This study highlights the predominant NTM species, clinical characteristics, and drug resistance patterns in HIV-infected patients in Chengdu. The findings underscore the importance of timely and accurate DST to guide clinical treatment and improve patient outcomes. The low drug resistance rates of ethambutol and clarithromycin suggest their potential as first-line treatments in the absence of DST results.
doi.org/10.1097/CM9.0000000000000235
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