Mycobacterium abscessus (MAB) is a rapidly growing species of Non-Tuberculous Mycobacteria (NTM) that causes chronic infection in humans. Commonly found in soil and water, MAB poses a serious threat to individuals with compromised immune systems or underlying lung conditions. The most common disease form is a persistent lung infection, especially in patients with Cystic Fibrosis or severe COPD, but MAB also causes serious skin and soft tissue infections. The prolonged and intense treatment regimen required highlights the challenge of achieving a definitive cure.
Current Standard Treatment Protocols
The current approach to treating Mycobacterium abscessus infection involves a rigorous, multi-drug regimen delivered in two distinct phases over an extended period. The initial phase is an intensive course of antibiotics designed to quickly reduce the bacterial load, typically lasting between two and four months.
During this intensive phase, patients receive a daily oral macrolide, such as azithromycin, combined with at least two intravenous (IV) antibiotics. Commonly used IV drugs include amikacin, tigecycline, cefoxitin, or imipenem, selected based on the isolate’s susceptibility profile. This phase aims to achieve culture conversion, which is the elimination of bacteria from the patient’s respiratory secretions.
Following the intensive treatment, patients transition to a continuation phase lasting 12 to 18 months after cultures become negative. This phase typically relies on a macrolide, sometimes combined with inhaled amikacin and one or two other oral agents like linezolid or clofazimine. The lengthy duration is intended to suppress any remaining mycobacteria and prevent relapse, though the entire process is often limited by drug toxicity.
Why Mycobacterium Abscessus is So Difficult to Eradicate
The difficulty in eradicating MAB stems from physiological and genetic factors that render it intrinsically resistant to many common antibiotics. One significant factor is the erm(41) gene, which confers inducible resistance to macrolides like clarithromycin. This gene is initially silent, but drug exposure activates it, causing the bacterium to quickly become resistant by modifying its ribosomal target.
The mycobacterium also possesses a thick, waxy cell wall rich in mycolic acids, which acts as a physical barrier. This structure impedes the penetration of many antibiotic molecules into the bacterial cell. Furthermore, MAB is notorious for its ability to form biofilms, which are protective communities of bacteria encased in an extracellular matrix.
Within these biofilms, bacteria are shielded from high concentrations of antibiotics and the host’s immune cells. The matrix makes the bacteria significantly more tolerant to treatment than their free-floating counterparts, allowing them to persist within the host despite aggressive multi-drug therapy.
Defining Treatment Success and Recurrence
For MAB infection, “cure” centers on sustained microbiological and clinical success following treatment. Treatment success is defined as achieving sustained clinical improvement in symptoms alongside culture conversion. Culture conversion requires three consecutive negative sputum or tissue cultures, with the treatment period extending for a minimum of 12 months after the first negative culture.
Even with this intensive, prolonged treatment, overall success rates remain low, typically ranging from 40% to 50% across all patients. Outcomes differ significantly between MAB subspecies. Patients infected with the massiliense subspecies, which lacks a functional erm(41) gene and is more susceptible to macrolides, often see success rates of 80% to 90%.
In contrast, patients infected with the abscessus subspecies, which harbors the functional resistance gene, experience much lower success rates, sometimes as low as 25% to 50%. The high rate of recurrence, particularly in patients with severe underlying lung damage, means long-term management and suppressive therapy may be necessary rather than outright eradication.
Developing New Strategies for Cure
Given the unsatisfactory cure rates, research is focused on developing novel strategies to overcome MAB’s intrinsic defenses. One promising avenue is bacteriophage therapy, which utilizes naturally occurring viruses that specifically target and destroy bacterial cells. Phages can penetrate the protective biofilm structure and kill multidrug-resistant MAB strains, offering a highly targeted treatment alternative.
Investigators are also exploring new drug combinations to circumvent the organism’s resistance mechanisms. For instance, combining existing drugs, such as rifaximin with clarithromycin, has shown potential in restoring macrolide effectiveness against resistant strains. This approach aims to find synergistic combinations that can overcome the erm(41) gene’s induced resistance.
Finally, researchers are actively repurposing existing drugs approved for other conditions to use against MAB. This includes testing new tetracycline-class antibiotics like omadacycline and eravacycline, which have shown good activity against MAB in laboratory studies. Additionally, inhibiting the mycolic acid pathway, which builds the mycobacterial cell wall, represents a targeted strategy to break down the organism’s exterior defenses.