Infections

A woman newly meeting diagnostic criteria for nodular MAC pulmonary disease, with mild but new symptoms and radiographic progression. The disagreement is not about the diagnosis — it is about how much force a conditional, very-low-certainty recommendation to treat should carry in a patient who sits outside the smear-positive, cavitary disease that recommendation is explicitly weighted toward.

A man with confirmed macrolide-resistant MAC lung disease and stage 3b chronic kidney disease. The disagreement is whether an inhaled aminoglycoside whose pivotal trial included — but underperformed in — macrolide-resistant patients is enough on its own, or whether his infection needs the systemic drug levels his renal function makes harder to give safely.

A woman newly diagnosed with M. abscessus pulmonary disease, whose isolate's erm(41) genotype suggests a truncated, non-functional gene — the pattern associated with true macrolide susceptibility. The disagreement is whether that genotype result is enough to build the regimen around an actively working macrolide, or whether real-world outcomes in this organism argue for treating it as inert regardless.

A frequent-exacerbator with chronic Pseudomonas colonization, whose two candidate suppressive therapies are backed by directly conflicting trial results from the same research program. The disagreement is whether PROMIS-I's positive result still stands once its prematurely-terminated twin's null result is taken seriously — and what to do about NTM-resistance stewardship before starting either option.

An older woman with declining lung function and thick, difficult-to-clear sputum despite standard airway clearance technique. The disagreement is not whether to escalate pharmacologic clearance therapy — it's which agent, once a CF-proven option is raised aloud and has to be corrected against the one trial that tested it directly in her population.

A man with cystic fibrosis, newly diagnosed with MAC pulmonary disease, on elexacaftor/tezacaftor/ivacaftor that has transformed his lung function over three years. The disagreement is what to do about the rifamycin his NTM regimen would ordinarily include, since the guideline that specifies it was never written with his drug regimen — or his diagnosis — in mind.

A frail man with post-stroke dysphagia and a witnessed aspiration event, developing fever and a new infiltrate within hours. The disagreement is whether to treat at all — and, once the day count is taken seriously, whether the familiar community-pneumonia regimen everyone reaches for is even the right drug.