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In vitro amikacin resistance linked to kanamycin cross-resistance but not streptomycin in M. avium-intracellulare complexLost to Amikacin? Streptomycin Might Still Work

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Key Takeaway
Consider streptomycin as a potential alternative for amikacin-resistant M. avium-intracellulare complex, noting unclear cross-resistance patterns.

This single-center retrospective study examined cross-resistance patterns among aminoglycosides in 20 patients with M. avium-intracellulare complex pulmonary disease who harbored rrs mutations and had developed amikacin resistance. The analysis involved paired comparisons of streptomycin and kanamycin minimum inhibitory concentration (MIC) values before and after the acquisition of amikacin resistance, alongside in vitro generation of resistant strains.

results showed that kanamycin MIC values uniformly increased to greater than 256 g/mL following the development of amikacin resistance. In contrast, streptomycin MIC values did not exhibit a significant increase. Genetic analysis revealed that amikacin- and kanamycin-resistant isolates shared mutations at position 1408 in the rrs gene. Conversely, streptomycin-resistant isolates exhibited distinct mutations at position 20 in the same gene. Clinical efficacy was observed in two cases where streptomycin remained effective after amikacin resistance developed.

No adverse events, serious adverse events, discontinuations, or tolerability issues were reported in this study. A key limitation is the requirement for future studies correlating streptomycin MIC values with clinical outcomes. The study suggests streptomycin may be a potential therapeutic alternative for amikacin-resistant M. avium-intracellulare complex pulmonary disease. However, the association between amikacin and kanamycin cross-resistance is noted, while the occurrence of cross-resistance among aminoglycosides remains unclear.

The Hidden Option for Tough Lung Infections

Many people with severe lung infections feel hopeless when standard drugs stop working. This is especially true for a rare but dangerous germ called Mycobacterium avium-intracellulare complex, or MAC.

Doctors often turn to amikacin to fight these stubborn bacteria. But sometimes, the bacteria learn to resist this powerful medicine. When that happens, patients face a scary choice: stop treatment or find a new drug that might not exist.

MAC infections are hard to treat because they grow very slowly. They often require years of taking multiple antibiotics. If one drug fails, the whole treatment plan can collapse.

This is frustrating for patients who want to breathe easier. It is also difficult for doctors who need effective options. Currently, there are very few backup drugs for when amikacin stops working.

The Surprising Twist

For years, scientists thought amikacin and streptomycin were safe bets to use together. They believed that if a germ resisted amikacin, it would still fear streptomycin.

But here is the twist. New research shows this might not be true for MAC. The study reveals a clear divide between two common backup drugs. One fails completely, while the other might still save the day.

Think of bacteria like a lock and a key. The drug is the key, and the bacteria have a lock on their surface. If the lock changes shape, the key no longer fits.

Amikacin and kanamycin are like two identical keys. If the bacteria change their lock to stop amikacin, the identical kanamycin key also gets stuck. They both fail.

Streptomycin, however, is a different key. It fits a slightly different part of the lock. Even if the bacteria change their lock to stop amikacin, the streptomycin key might still turn.

Researchers looked at 20 patients who had already developed resistance to amikacin. They tested how well streptomycin and kanamycin worked against the bacteria in these patients.

They also grew the bacteria in a lab to see exactly how the bacteria changed. They used advanced gene sequencing to find the specific changes in the bacteria's DNA.

The results were very clear. When patients became resistant to amikacin, the bacteria also became resistant to kanamycin. The drug stopped working in every single case.

However, streptomycin told a different story. The bacteria did not automatically become resistant to streptomycin just because they resisted amikacin. In fact, two patients in the study responded well to streptomycin after failing amikacin.

This means streptomycin could be a real lifeline for patients who have lost other options. It offers a new path when the old roads are blocked.

But There Is a Catch

This doesn't mean this treatment is available yet.

The study is important, but it is still in the early stages. We need more data to know if this works for everyone. The study only looked at 20 patients. That is a small group for such a serious disease.

Also, the study was done in a single hospital. We need to see if these results hold true in other places with different patients.

If you or a loved one has a MAC infection, talk to your doctor about all available options. Do not assume that if one drug fails, all drugs will fail.

Ask your doctor if streptomycin is an option if amikacin stops working. Be honest about side effects, as streptomycin can cause hearing issues in some people.

The goal is to find a way to clear the infection without harming your health. Every patient is different, and the right plan depends on your specific situation.

Scientists will need to run larger studies to confirm these findings. They must link drug test results to how patients actually feel and recover.

If streptomycin proves safe and effective, it could become a standard backup drug. This would give doctors a vital tool to fight tough infections.

Until then, research continues. The medical community is working hard to find better ways to treat these difficult lung diseases.

Would you discuss trying a different drug if your current one stopped working?

Early symptoms of MAC infection How antibiotics fight bacteria Questions to ask your doctor about lung health

Study Details

Study typeCohort
Sample sizen = 20
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
Aminoglycoside drugs, amikacin, streptomycin, and amikacin liposome inhalation suspension are crucial for treating refractory Mycobacterium avium-intracellulare complex pulmonary disease. In Mycobacterium tuberculosis, cross-resistance occurs between amikacin and kanamycin, but not between amikacin and streptomycin in genetic drug susceptibility testing. However, the occurrence of cross-resistance among aminoglycosides remains unclear in M. avium-intracellulare complex. We aimed to evaluate cross-resistance among aminoglycosides to determine whether streptomycin or kanamycin remains effective after the development of amikacin resistance. This single-center retrospective study included 20 patients with amikacin-resistant M. avium-intracellulare complex harboring rrs mutations. Paired analyses of streptomycin and kanamycin minimum inhibitory concentration values before and after amikacin resistance development were performed. In addition, streptomycin- and kanamycin-resistant strains were generated in vitro and resistance-associated mutations were identified using whole-genome sequencing. No significant increase was observed in streptomycin minimum inhibitory concentration values following amikacin resistance. In contrast, kanamycin values uniformly increased to >256 g/mL after the acquisition of amikacin resistance. Furthermore, amikacin- and kanamycin-resistant isolates shared mutations at position 1408 in the rrs gene, whereas streptomycin-resistant isolates exhibited mutations at position 20 in the rrs gene. These results suggest that amikacin and kanamycin exhibit cross-resistance in M. avium-intracellulare complex, whereas amikacin and streptomycin may not. Two cases in our cohort in which streptomycin treatment was effective after the acquisition of amikacin resistance further support these findings. In conclusion, streptomycin may be a potential therapeutic alternative for amikacin-resistant M. avium-intracellulare complex pulmonary disease. Future studies correlating streptomycin minimum inhibitory concentration values with clinical outcomes are required.
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