[An emerging problem: heteroresistance in Mycobacterium tuberculosis]

Area of Science:

• Infectious Diseases
• Genomics
• Microbiology

Context:

• Mixed infections involving Mycobacterium tuberculosis (Mtb) present complex challenges in clinical management.
• Heteroresistance (HTR) describes the coexistence of drug-susceptible and drug-resistant Mtb variants within a single patient.
• HIV/AIDS patients with adherence issues are particularly vulnerable to the development of complex Mtb infections.

Purpose:

• To investigate the occurrence and characteristics of Mtb heteroresistance in HIV/AIDS patients with treatment adherence problems.
• To utilize complete genomic sequencing for the precise diagnosis of monoclonal HTR.
• To highlight the clinical implications of coexisting sensitive and resistant Mtb variants.

Summary:

• Three cases of HIV/AIDS patients with a history of treatment non-adherence were diagnosed with monoclonal Mtb heteroresistance (HTR).
• Complete genomic sequencing identified the coexistence of two distinct Mtb variants from the same strain, each with different drug resistance profiles, in lung and lymph node samples.
• Monoclonal HTR was confirmed by the presence of two variants of the same Mtb strain exhibiting varied resistance patterns.

Impact:

• Highlights the critical importance of considering Mtb heteroresistance, especially in patients with prior treatment failures and high bacterial loads.
• Genomic sequencing is crucial for accurate diagnosis of HTR, enabling tailored therapeutic strategies.
• The presence of both sensitive and resistant Mtb variants can compromise treatment efficacy and patient outcomes in advanced HIV/AIDS.