Worsening of the lung function due to tobramycin inhalation

Question

Dear expert team,
I have been diagnosed (23, CF) with Pseudomonas aeruginosa lately for the first time. We decided to eradicate with 3x750mg ciprofloxacin p.o. over 3 weeks and inhalation with 2x300mg tobramycin with a 28-days-change with 2x2 Mio. I.U. Colistin over 6 months altogether. My general condition is not really well already for months - even before the finding of Pseudomonas - but also not really bad, either.
Even after only 3 days of ciprofloxacin, I felt an improvement. I started on the 4th day additionally with the inhalation of tobramycin for the first time, whereupon the improvement disappeared nearly immediately and for the moment the same indifferent state as before appeared. During the whole time of inhalation with tobramycin I had nearly every day blood in the sputum, if only miminal amounts. According to the package insert possible side effects of tobramycin are a reduction of FEV1 as well as coughing blood. I maintained the therapy however like this and after there was no change at all for one week, finally again an improvement appeared. In the meantime I feel as good as I did not for years and the PA could not be detected in the last sputum.
During the inhalation with Colistin I did not have any problems at all, shortly the second cycle of inhalation with tobramycin should begin. I am now worried, that because of the tobramycin my lung function decreases again to a fair to bad condition, as this time the respective antagonist in the form of ciprofloxacin is missing, which compensated the seemingly caused worsening of the lung function via tobramycin.
Now I am thinking about it, how I should react, in case I realize that via the inhalation of Tobramycin my lung function gets indeed worse again. Should I stop the therapy and try to keep the good condition as long as possible, but risk however that the PA recolonizes in the short runs? Or should I continue the therapy for the 6 months even if I feel worse, then, but have higher chances that the PA does not recolonize for now?
Many thanks for your advice in advance,
Yours sincerely,

Answer

Dear questioner,
many thanks for the interesting and again and again discussed question concerning Tobi and worsening of the lung function and coughing blood. Especially the question about coughing blood is discussed controversially.
But first to the easier question about worsening of breathing. Indeed it comes in a not small part of patients to an "asthma-like" reaction with obstruction after Tobi, this can last in part also for a longer time. Therefore it is also important that you inhale with a so-called beta2-mimetic (salbutamol, formoterol or salmeterol) before the inhalation of Tobi (about 15-30 min before) in order to avoid such an obstruction. In case you do this already, and it comes still to a documented worsening of the lung function, I would indeed recommend not to inhale Tobi anymore but only the Colistin (without interruption for total 6 months, whereby this eradication scheme is not really investigated).
In an actual big international study it could naemly be shown that also in adults the PA can be eradicated in about 60% of cases with one month of Tobi inhalation and that two months Tobi have not been better (ELITE-study). Independent of that, I think, that you should discuss this with your CF doctors in charge.
Now to your second question, which is more controversial concerning coughing blood and Tobi: It is right that in the package insert the side effect of coughing blood is mentioned, however there is an acutal assortment of a Mr. Flume from Chapel Hill, and he was able to show with the help of the American CF-registry that Tobi is not a risk for coughing blood and not only he, but also the adult CF-clinic of the Royal Brompton in London recommends, even in case of coughing blood not to stop the Tobi (also the DNAse). We in Zurich do it like this, that we stop the Tobi only in case of increased irritation of the throat.
In summary I recommend to you: As you seem to really react to Tobi with an asthma, I would leave it out and at best only for the total of half a year inhale with Colistin (as said is our special scheme in Zurich and not investigated, and probably the month Tobi is sufficient, which you already did). In case of a re-occurence of Pseudomonas I would try Tobi again, however inhale this in the hospital before and control the lung function after 1-2 hours. Of course you should inhale a beta2-mimetic as mentioned above.
According to your description, that you feel as good as you did not for years, I assume, that you reduce the Pseudomonas in your bronchial system clearly at the moment and probably could even eradicate it.
Best regards,
Dr.med. Markus Hofer

09.02.2011