TObi

Question

Hello,
I am a parent of a child with CF.
I’ve got a question about the treatment with the nebuliser solution Tobi-300. I know that it’s strictly individual, but I am interested what are the criteria for treatment.
If a patient has Pseudomonas aeruginosa in the lungs and has started treatment with Tobi, then can you tell me:
1. What is the minimal prolongation of treatment?
2. What is the maximum prolongation of treatment?
3. What tests must be run during the treatment with Tobi-300 and at what intervals of time?
4. If the patient feels good and Pseudomonas aeruginosa is not isolated in sputum at the moment, shall he stop taking Tobi?
5. Is there any other test to find out Pseudomonas aeruginosa in the lungs that must be run upon a small child who cannot give sputum samples? A blood test? If there is something, please, write me.

Best regards,
S. A.

Answer

Hello,
Thank you for your queries about Tobi-300 and I apologise for the delay in answering this question. I will now try to address each of your questions separately. With regard to questions 1 and 2 there is no recommended minimum of maximum prolongation period. The recommended dose of Tobi-300 for children is one ampule twice daily for 28 days. You then should have a break from Tobi-300 for 28 days before starting another 28-day treatment course again. Treatment with Tobi should be continued on this cyclic basis for as long as the physician considers that the patient is gaining clinical benefit from the inclusion of TOBI in their treatment regime. As long as there is no side effects (see below) then there is no recommended minimum of maximum prolongation period.
With regard to question 3 various tests should be done with patients who are commenced on TOBi-300. These include lung function, renal function and auditory assessment.
• Lung function: The first dose of TOBI should be given under supervision, and patients should be given a bronchodilator if this is part of the current regimen for the patient. FEV1 should be measured before and after nebulisation of the antibiotic. In children too young to perform FEV1 then clinical examination is normally used. If there is evidence of TOBI-induced bronchospasm in a patient not receiving a bronchodilator the test should be repeated, on a separate occasion, using a bronchodilator. Evidence of bronchospasm in the presence of bronchodilator therapy may indicate an allergic response. If an allergic response is suspected TOBI should be discontinued.
• Baseline renal function should be assessed. Renal function should be reassessed after every 6 complete cycles of TOBI therapy. If there is evidence of toxicity, all tobramycin therapy should be discontinued until blood levels of TOBI reach safe levels. Treatment may then be resumed at the physician's discretion. Patients receiving other antibitics like TOBI (aminoglycoside therapy) should be monitored as clinically appropriate taking into account the risk of cumulative toxicity.
• Auditory toxicity or hearing loss did not occur with TOBI therapy during controlled clinical studies. However in patients with a predisposing risk due to previous prolonged, systemic aminoglycoside therapy it may be necessary to consider audiological assessment before initiating TOBI therapy. Patients should also be asked to reports any tinnitus or hearing loss during treatment and if this occurs the physician should consider referring them for audiological assessment.

In answer to your 4th question there is no uniform published guidance on how long a course of Tobi-300 should last however pragmatically this probably depends on whether the aim is eradication or managment of chronic pseudomonas infection. For eradication there is no clear consensus on the length of the course and indeed the length of treatment varies accross Europe but usually lasts been 6- 12 months i.e. 3 -6 cycles. If after this length treatment is completed the patient feels good and the patient has three successive negative sputum samples the CF doctor may decide to stop Tobi-300. For patients with chronic pseudomonas the approach is different in that the patient may remain on Tobi-300 indefinately. The use of Tobi-300 in patients with chronic pseudomonas should be monitored reguarly (see above) and e.g. renal function should be checked yearly.
In answer to your last question there are a number of alternatives when a child cannot give sputum sample. These are outlined in European Guidelines and include cough swabs, nasopharygeal aspirate or deep throat swabs. Some centres may also perform a test called a Bronchoalveolar lavage in which a scope is passed into the lungs and then fluid is squirted in and then recollected for examination. You should discuss these options with your CF doctor.
Some laboratories offer antibody tests but there are some uncertainties about intrepretation of results. Your Cf centre will probably have a policy of them.
There are some guidelines that have been used to answer your questions
Standards of Care - Standards for the Clinical Care of Children and Adults with Cystic Fibrosis in the UK 2001. May 2001.
Flume et al Cystic Fibrosis Pulmonary Guidelines Chronic Medications for Maintenance of Lung Health Am J Respir Crit Care Med. 2007 Nov 15;176(10):957-69.
Doring et al. Therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus. Eur Respir J 2000; 16: 749-767.
Döring et al . Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. Journal of Cystic Fibrosis, Volume 3, Issue 2, Pages 67-91.

Yours sincerely,
Dr. J. Bradley

28.04.2009

The answer is edited by: Prof Judy Bradley