Non-tuberculosis mycobacterial infections, or NTM, can be a challenge to treat and are increasing in incidence worldwide,” Christina G. Rivera, PharmD, BCPS, AAHIV-M, notes. “Drug resistance and/or intolerance to first-line agents leads clinicians
to consider second-line agents and emerging strategies. NTM management can involve monitoring for adverse events, specialized dosing, and therapeutic drug monitoring.” 

For a study published in Infectious Diseases and Therapy, Dr. Rivera and colleagues examined NTM pharmacotherapy, including treatment models, favored regimens according to NTM species and infection location, and strategies for difficult-to-treat species.

“Our team set out to provide key NTM treatment tenets and bring forward the most recent trends in a reasonably usable format for busy clinicians,” Dr. Rivera explains. “With a narrative review, we had the flexibility to provide the information we found to be most relevant based on our active practice in NTM clinics.”

Use Agents With MicrobiologicActivity for Specific Species

Pharmacotherapy for NTM disease often involves antimycobacterials in combination with bronchial hygiene/clearance regimens and/or surgical resection to reduce bacterial burden, according to the study authors. They wrote that the development of safe and effective pharmacotherapy regimens for NTM disease “is complex, in part because of treatment regimen variability based on different NTM species, infection sites, and disease severities.”

Patient characteristics may increase this complexity, the researchers continued, due to advanced age, body weight, and comorbidities. The treatment is also time-intensive, with multiple drugs and lab tests required. Dr. Rivera and colleagues noted,
however, that a general framework for the management of NTM disease is useful and should incorporate the following guidance:

At least two drugs with activity against the isolated NTM species should be used, as certain drug combinations can have a synergistic effect. Disease severity and infection location should direct the number of drugs used initially. As many as four drugs are often used for severe disease; two drugs may be used for uncomplicated NTM skin and soft tissue infections.

For infections caused by certain species, including Mycobacterium abscessus complex, treatment may occur in two stages: an initial phase of 1-3 months, followed by an extended maintenance phase. The initial phase usually employs more drugs and IV therapy, while the maintenance phase preferably uses only oral agents and as few as two drugs. Duration is guided by response and tolerability.

Mycobacterium species identification and susceptibility testing guide drug selection. An association between in vivo outcomes and in vitro susceptibility results are absent for many infections, with several exceptions. However, susceptibility testing is normally advised. Empiric treatment based on susceptibility patterns is typically started for severe and/or disseminated disease while microbiology results are processing. Macrolides, except in the presence of resistance, are a “backbone” of most NTM regimens.

“A bedrock for creating an effective NTM pharmacotherapy regimen is incorporating agents with microbiologic activity for the specific NTM species,” Dr. Rivera says (Table). “Further tailoring and considerations are needed for individualizing patient care, but this is an essential ingredient.”

‘Promising’ Areas for Future Research

The researchers “hope that physicians find this a practically useful resource for management of NTM, and/or use it as a tool to broaden under-standing and interest,” according to Dr. Rivera. Areas for future research “are deep and promising in NTM,” she continues. Examples include the establishment of best practices for phage therapy, which the researchers described as an “evolving
technology,” and exploration of omadacycline as a potential first-line oral treatment for Mycobacterium abscessus pulmonary disease.

“Other areas that personally intrigue me are the impact of a multidisciplinary team for NTM management, the utility of pharmacogenomics, and phage-drug interactions,” Dr. Rivera says.