Macrolide-Resistant MAC: Salvage Therapy With Reduced Renal Function
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.
Walter T., a 71-year-old man, has spent most of his retirement rebuilding a 1962 fishing boat in his driveway, a project his neighbors have taken to calling “the ten-year restoration” since he shows no sign of finishing it. He was diagnosed with nodular/bronchiectatic MAC lung disease three years ago and started on the standard thrice-weekly azithromycin-ethambutol-rifampin regimen, but went through an eight-month stretch two years back, after his wife died, when he missed most of his follow-up visits and, by his own admission now, took his azithromycin far more consistently than the other two drugs — functionally, for a stretch he can’t precisely date, macrolide monotherapy. His most recent sputum culture grew MAC again, and susceptibility testing this time confirmed acquired macrolide resistance, a clarithromycin MIC well above the resistant breakpoint, consistent with the 23S rRNA point mutation that kind of intermittent macrolide-only exposure is known to select for. He also carries stage 3b chronic kidney disease, attributed to two decades of hypertension, with a baseline eGFR that has held fairly steady in the high 30s to low 40s for the past several years.
Today’s eGFR of 38 sits at the bottom of his own established range rather than below it — a reading that matters less as a sign of acute injury than as a real, if not severe, ceiling on how freely the team can dose a systemic aminoglycoside without careful monitoring. His amikacin MIC of 16 µg/mL matters for a narrower reason: CONVERT excluded isolates above 64 µg/mL before randomization, so on the one susceptibility that governs the drug being proposed, he is inside the trial’s population rather than outside it. On the other, he is inside its weaker half. CONVERT reported culture conversion in 29.0% of patients at six months against 8.9% on guideline-based therapy alone, and roughly a fifth of that cohort carried clarithromycin-resistant isolates like his — they were studied, not excluded, but they converted less often than macrolide-susceptible patients, and clarithromycin resistance has since been repeatedly flagged as a predictor of persistent culture positivity. What the trial establishes for Walter, then, is that ALIS is a reasonable move and not that 29.0% is his number.
ID/pulmonary joint clinic, reviewing the resistant culture
Add ALIS to a rebuilt backbone — ethambutol, clofazimine, and inhaled amikacin — and drop the macrolide entirely, since it isn’t doing anything for him anymore. In the CONVERT trial, adding ALIS to guideline-based therapy in refractory MAC disease produced culture conversion in 29.0% of patients at six months, against 8.9% on guideline-based therapy alone.
The inhaled route matters specifically for Walter — it limits systemic amikacin exposure at a time when his kidneys make systemic exposure a real concern, not a hypothetical one.
I’d go systemic.
You’re quoting 29.0% as though it’s Walter’s number. It isn’t. CONVERT did enroll macrolide-resistant patients — about a fifth of the reported cohort — so I won’t claim he’s outside the trial. He’s inside its worst-performing slice. Those patients converted less often than the macrolide-susceptible majority carrying that headline figure, and clarithromycin resistance has kept turning up since as a predictor of staying culture-positive on ALIS-containing regimens. Adding an inhaled aminoglycoside to a regimen that has already lost its most important drug is the version of this intervention that worked least well.
IV amikacin, dose-adjusted for his renal function with real trough monitoring, gets systemic drug levels to a genuinely higher-burden infection in a way inhaled therapy alone doesn’t.
You’re right that his subgroup is the one that underperformed, and I won’t pretend 29.0% is what we’re offering him.
But underperforming is not the same as not working, and his amikacin MIC of 16 is the number that decides whether ALIS is worth trying at all — CONVERT excluded isolates above 64 before randomization, and above that threshold conversion essentially stopped. He is well inside it. Renal impairment doesn’t take systemic amikacin off the table either — it means dosing it properly; extended-interval dosing with trough monitoring can be done safely at an eGFR of 38, and this isn’t end-stage disease. Start ALIS now, since it’s the lower-risk first move and is specifically approved for this scenario, and keep dose-adjusted systemic amikacin in reserve if six-month cultures haven’t converted.
Agreed: start ALIS with the rebuilt ethambutol-clofazimine backbone now, hold systemic amikacin in reserve with a renal dosing plan already specified, and repeat cultures at six months per CONVERT’s own primary endpoint window.
Not agreed: how long to wait before escalating to systemic amikacin if cultures remain positive. The pulmonologist wants to hold to the full six-month window CONVERT itself used before calling the inhaled approach inadequate. The infectious disease physician wants an earlier interim culture check at three months, given Walter’s prior adherence gap and a stated worry about missing an early signal that this regimen isn’t working in someone whose follow-up history is already uneven.