Let me see if I can provide some clarification. I think it's great that you're trying to understand your meds and I think that education can lead to better compliance because you understand why you do the meds that you do. So hat's off to you!
1. Bacteria need to have constant exposure to antibiotics, at adequate killing levels, until they are all dead in order to not induce resistance. PA is an extremely difficult bug to kill - hence CFers with PA being colonized. The theory with TOBI is that patients get flare ups often. Stress, colds, malnurishment, pick you poison. So TOBI is present to make sure that PA flare ups do not occure. If the PA moves from being dormant to being active, the TOBI is present to destroy the flare up. Of course, not all PA is killed. But it is killed to levels that reduce symptoms (and reduce white blood cell counts, inflammation, etc).
So let's say you're in the middle of your 28 day course. Day 14. Day 15 you catch a cold and your PA starts to flare up becuase your body is too busy fighting the cold virus to pay attention to your PA. So PA starts to grow. But no problem - you're on TOBI right now, so your TOBI starts to destroy the PA flare up. Cell, by cell, rod by rod, the PA levels are being reduced do to you inhaling TOBI twice a day. It may take a full 14 days of constant TOBI exposure to ensure that your PA goes down to dormant levels. But you got tired on Day 20 and decided not to do your TOBI that day. So the PA that hasn't yet been killed by the TOBI from days 15-20 now has a chance to grow for a day. These bacteria are "stronger" because they have survived the TOBI exposure for the past 5 days. But over the next 8 days that you're on TOBI, your levels of PA go down enough to where the flare up is under control.
A few months later you catch another cold. Or your stressed. Or whatever the reason. Your PA is flaring up again (as it inevitably always does). But this PA flare up is more virulent this time. Why? Because you skipped a treatment a few months ago and the bugs that were allowed to grow during the day you skipped the treatment multiplied. And now instead of your PA being made up of weaker and stronger parts, it's now mostly stronger parts. It's basically a Darwin's theory of evolution - only the strong survive. The bacteria that is stronger is called a mutation. Bacteria has become smarter to the antibiotic.
So back to your 2nd flare up. It's now harder and takes longer to treat your PA. Perhaps TOBI doesn't work for this flare up and you need IV meds.
Some bacteria take longer to mutate. But more virulent bacteria like PA can mutate more quickly.
Eventually, even if you're compliant with your TOBI every day, you will be resistant. But this will occure more slowly if you take it as prescribed.
2. Being off for a month doesn't lead to resistance. The aim is to reduce PA exposure to these antibiotics so that resistance doesn't occure as quickly. The ultimate goal is to hit the bacteria and hit is hard with an antibiotic for a month. Then, hopefully, the bacteria is at a dormant level. Constant exposure, even at a dormant level, can cause the bacteria to mutate. So taking 28 days off reduces antibiotic exposure and therefore reduces potential to resistance.
3. Inhaled antibiotics aren't any different to PO or IV or IM antibiotics in terms of developing resistance. IV antibiotics tend to develop resistance less frequently because ther is no room for patients to skip doses. Simple as that. I can send you an article from the CDC entitled "dead bugs don't mutate" alluding to the fact that hitting a bacteria hard with high doses of an antibiotic that KILLES (bacterialcidal) as opposed to antibiotics that are static is the way to go.
4. The reason why those who are resistant to Tobramycin are often sensitive to TOBI is because bacteria can be exposed to a higher level of Tobramycin when it's inhaled because there is little systemic exposure. In other words, you can only put so much tobramycin in the blood stream before you kill a patient. You can put much higher levels in the lungs because hardly any of the antibiotic reaches the blood stream.
Keep in mind that resistance is a relative term. If your doc tells you that your PA is resistant to TOBI, this simply means that the levels of Tobramycin that need to be achieved to kill PA can't be acheived because side effects would be too great. It doesn't mean that PA can't be killed by Tobra. It just can't in your body.
Hopefully this helps. If you need any clarification, please let me know.