Re: Gentamicin Side Effects - Ototoxicity

January 30, 2004

This is no big authoritative answer; I was always told that both drugs are

oto (ear)-toxic and reno (kidney)-toxic, but that Gentamicin is more likely

to affect the ears; I am still told this and have one brother who is deaf as

he was treated (nocf) with Gentamicin for meningitis; well, he is still here!

That is why they do those peaks and troughs on those meds. I do not re-

member whether Garamycin was the same thing as Gentamicin--

So cheery, Love, n

Re: Great Article ...

Hi,

since I saw no reply to Rosemary's post, I want to point out why it

is a great article. For many years now CF-researchers are exploring

methods, how they can make cells of PWCF to produce functioning CFTR

again.

And for those patients with stop mutations (that's all the mutations

ending with an X) they've come one (big?) step closer to a solution.

Gentamicin, a drug that is commonly used as an antibiotic, is able to

restore the function of the CFTR in stop mutations.

I've copied an article below about one young woman, who took part in

the study.

Peace

Torsten

18-year-old Amy Crews tries to live a normal life.

Amy Crews

" I don't want people to feel sorry for me. I don't want to be pitied. "

Kerry Lambert

Amy's Stepfather

" We don't focus on the fact that she's got a disease. We focus on the

life that she's living. "

Amy was diagnosed with cystic fibrosis when she was two months old.

She's had a number of surgeries including having one lung removed.

Recently, she decided to be part of research.

Amy Crews

Has Cystic Fibrosis

" I hope that the research goes as they hope that it goes and that

they can use this new medicine to help other people and help me. "

Scientist Bedwell says the research involves repairing a gene.

All genes start and stop creating a full length protein. In 10% of CF

patients, there is a premature stop and the protein is not made

properly.

Bedwell, Ph.D.

Molecular Biologist

University of Alabama at Birmingham

Birmingham, AL

" What we're doing is we're tricking the machinery into bypassing that

first stop, the premature stop, and reading all the way to the end so

that you make a full-length, functional protein. "

Research shows the antibiotic, gentimicin, can correct the problem.

Bedwell, Ph.D.

" This is one of the first times we've actually altered the cellular

machinery to do something we wanted it to do. "

Amy's gene was changed while on the medication.

The downside, according to her pediatrician J.P. Clancy, is that

Gentimicin has severe side effects, and can't be used long-term.

J.P. Clancy, M.D.

Amy's Pediatrician

" It isn't a permanent fix. It can only work for the period of time

that the medication is used. "

But researchers say this discovery is a step in the right direction.

The treatment can be repeated, but side effects of the drug may

include kidney failure and hearing loss. Animal studies are underway

to find a way to deliver this drug without causing the side effects.

Tests on other similar drugs are also underway. Researchers say it

will take time to see if the disease progression is slowed in

patients.

----------------------------------------------------------------------

----------

HEALTHY FOR LIFE EXTRA

BACKGROUND: Cystic Fibrosis is a genetic disease that affects

approximately 30,000 children and adults in the United States. It is

a chronic disease. It causes the body to produce an abnormally thick,

sticky mucus, due to the faulty transport of salt within the cells

that line organs such as the lungs and pancreas, to their outer

surfaces. The thick mucus obstructs the pancreas, preventing enzymes

from reaching the intestines to help break down and digest food. For

many years, CF was considered a disease of children and teens because

lung infections and respiratory complications often led to early

death. Now, doctors say patients with CF are living into their 30s

and 40s. In fact, more than 38 percent of the people with CF in the

United States are now 18 years or older. Advances in care are

increasing the survival age. In 1989, scientists also discovered the

gene defect that leads to CF. This was a huge step, say researchers,

but genetic research has taken time because there are hundreds of

different types of problems in the gene that can cause different

types of CF.

NEW RESEARCH: In 10 percent of CF patients, there is a premature

mutation that causes a stop in the formation of a protein. Scientists

say a gene is like a sentence that begins with a capital letter and

ends with a period. When the gene is properly formed, a full length,

functional protein is formed. In patients with an x mutation, there

is a premature stop in the middle of the sentence, and the protein is

not properly formed. Researchers from the University of Alabama at

Birmingham say they have found a way to trick the gene into passing

the premature stop and continuing to the end. They say the commonly

used antibiotic gentamicin is effective at tricking the gene.

Research done in the United States and in Israel shows patients who

were on the drug had a change in their gene.

THE PROBLEM: While this discovery is very promising, the problem is

that it is not permanent. Gentamicin is a toxic drug and can cause

severe side effects if the patient is on it too long. The side

effects can include kidney failure and hearing loss. Right now, a

multi-center study is underway looking at other ways to administer

this drug to patients to reduce the risk of these side effects.

Doctors are also testing other similar drugs to see if they will be

as effective as gentamicin in correcting this problem in the gene.

The hope is that, if a drug can correct the problem in the gene, the

progression of the disease will be stopped in the patient. At this

point, the drug has not been tested in anyone long enough to see if

the progression of CF is stopped. However, it has been tested long

enough to see the change in the gene.

FOR MORE INFORMATION

Eubanks

Research Coordinator

University of Alabama at Birmingham

620 ACC

16000 7th Avenue South

Birmingham, AL 35233

vaeubanks@...

January 30, 2004

Hi n,

I'm sorry your teen is having hearing problems, and I hope you can

determine the cause. I'm a cause-and-effect type person, so it would

drive me nuts not to know the reason for hearing loss. Since the

cause of your teen's hearing loss is undetermined, are the doctors

suggesting that tobramycin and gentamicin be avoided in the future?

I've read medical abstracts suggesting that aminoglycoside

antibiotics (such as gentamicin and tobramycin):

1) Cause ototoxicity and vestibular (balance) damage when the body is

deficient in magnesium. Ironically, it's well-known that both of

these meds deplete magnesium. It's my belief that since inhaled

antibiotics (such as TOBI) get into the bloodstream, that over time

even inhaled TOBI contributes to magnesium-deficiency just like IV

and oral antibiotics.

2) Studies suggest that ototoxic damage can be lessened to a degree

if magnesium is supplemented as soon as possible (within eight days,

I think) of first symptoms.

3) People are at greater risk of ototoxicity and vestibular damage

when taking iron or supplements containing iron while using

aminoglycoside antibiotics.

So maybe it's a wise idea to keep iron-free multivitamin/mineral

tablets on hand and switch to those whenever you have to take IV or

inhaled aminoglycoside antibiotics. I would never want to discontinue

daily multivitamin/mineral tablets during antibiotic therapy since

the body is under such stress at that time and because the meds

deplete the body of nutrients. You just have to be careful to time

the doses of your multi so it doesn't compete with the antibiotics.

Kim

Going through old mails found reference to Gentamicin and side

effects.

My CWCFaged 16 has experienced hearing difficulties in one ear -

following MRI scan and meetings with consultants have been advised

that loss of hearing may be hereditary / due to virus / or due to

Side effects of Toby or Gentamicin. We have had iv's twice yearly

for approx 8 years using Toby but only once using Gentamicin.

Are there any stats for occurances of side effects both of Toby and

Gentamicin - we have been told that we will have access to

alternative to Toby - is there any information on these and their

effectiveness ( and side effects). At this stage have not been

advised what they are.

n

February 1, 2004

Hello-

I just joined this group hoping to find information about this

topic. My daughter is 18; she was just diagnosed with bilateral

vestibular damage after using gentamicin for the first time.

Needless to say, we are devastated.

Lyn's hearing is fine, but she cannot safely drive, snowboard, walk

some days (never in darkness), drive her motorcycle, dance.... All

of the things that made her life bearable have been taken away.

Does anyone have any experience with this? I have questions such

as : Could more gentamicin take away her hearing as well? Is there

therapy available? How often should she have had her levels checked?

Could just this one course have done this, or is it a cumulative

effect after years of tobra (with no problems)?

The ironic thing is that she has not been this healthy (cough-wise)

in a long time; gentamicin is what she needed to clear up her lung

infection.

We live in a remote area of Michigan. There is no one else with cf

within 100 miles or more, so we often feel quite alone. I have been

strong through the past 18 years, handling liver disease and

diabetes, but this is just too much. Every time I see her motorcycle

(her 18th birthday gift) sitting in the garage, I think of her huge

smile as she would climb on, headed for happiness and the feeling of

freedom.... My heart hurts.

February 1, 2004

Welcome aboard; this is just plain tragic; I am so sorry--n Rojas, wcf,

mom of 3 adults, the youngest of whom also has cf--and we both rode motor

cycles for years----AND I am from Michigan!!!!!!

From: jamaca

To: cfparents

Sent: Sunday, February 01, 2004 6:04 AM

Subject: Re: Gentamicin Side Effects - Ototoxicity

Hello-

I just joined this group hoping to find information about this

topic. My daughter is 18; she was just diagnosed with bilateral

vestibular damage after using gentamicin for the first time.

Needless to say, we are devastated.

Lyn's hearing is fine, but she cannot safely drive, snowboard, walk

some days (never in darkness), drive her motorcycle, dance.... All

of the things that made her life bearable have been taken away.

Does anyone have any experience with this? I have questions such

as : Could more gentamicin take away her hearing as well? Is there

therapy available? How often should she have had her levels checked?

Could just this one course have done this, or is it a cumulative

effect after years of tobra (with no problems)?

The ironic thing is that she has not been this healthy (cough-wise)

in a long time; gentamicin is what she needed to clear up her lung

infection.

We live in a remote area of Michigan. There is no one else with cf

within 100 miles or more, so we often feel quite alone. I have been

strong through the past 18 years, handling liver disease and

diabetes, but this is just too much. Every time I see her motorcycle

(her 18th birthday gift) sitting in the garage, I think of her huge

smile as she would climb on, headed for happiness and the feeling of

freedom.... My heart hurts.

-------------------------------------------

The opinions and information exchanged on this list should IN NO WAY

be construed as medical advice.

PLEASE CONSULT YOUR PHYSICIAN BEFORE CHANGING ANY MEDICATIONS OR TREATMENTS.

------------------------------------

------------------------------------------------------------------------------

February 1, 2004

Hi There! Welcome to the best place on cyberspace! Sorry to hear

about Lyn's problem. Question: Is she taking Magnesium? If she is

not, she should...All those antibiotics, bronchodilators, deplete

Magnesium in our bodies. If you have time scan through some of the

posts and look for Kim Payne's posts, they are very informative and

well worth reading... She is our Magnesium Queen and we are very

honor to have her on board. There was one not too long ago that was

excellent. I will try to repost it. I believe Lyn will benefit from

chelated Magnesium.

Again welcome,

mom of LUisa 10 wcf, Venanzio 7 nocf and Pepe 4 nocf

> Hello-

>

> I just joined this group hoping to find information about this

> topic. My daughter is 18; she was just diagnosed with bilateral

> vestibular damage after using gentamicin for the first time.

> Needless to say, we are devastated.

>

> Lyn's hearing is fine, but she cannot safely drive, snowboard, walk

> some days (never in darkness), drive her motorcycle, dance.... All

> of the things that made her life bearable have been taken away.

>

> Does anyone have any experience with this? I have questions such

> as : Could more gentamicin take away her hearing as well? Is

there

> therapy available? How often should she have had her levels

checked?

> Could just this one course have done this, or is it a cumulative

> effect after years of tobra (with no problems)?

>

> The ironic thing is that she has not been this healthy (cough-wise)

> in a long time; gentamicin is what she needed to clear up her lung

> infection.

>

> We live in a remote area of Michigan. There is no one else with cf

> within 100 miles or more, so we often feel quite alone. I have

been

> strong through the past 18 years, handling liver disease and

> diabetes, but this is just too much. Every time I see her

motorcycle

> (her 18th birthday gift) sitting in the garage, I think of her huge

> smile as she would climb on, headed for happiness and the feeling

of

> freedom.... My heart hurts.

February 2, 2004

Hi,

I'm so sorry for your daughter's vestibular damage. I can imagine how

heartbreaking this is for her and for you. You're right, it's not

enough that the CF causes respiratory problems and you've also

battled with her diabetes and liver problems, it's not fair that

balance should beforever affected by a medicine that was prescribed

in good faith.

Yes, more gentamicin can worsen her problem, and yes, could effect

her hearing as well. Yes, there are some new types of therapy

available to help attenuate the effects of vestibular damage. In

fact, someone is currently enrolling people in a study right now, and

will pay transportation costs. This was posted on the Cystic-L just a

couple days ago. I may not still have that post but if you're not a

member of Cystic-L, I'll put out the request for you to get the

information again. The woman who posted it has vestibular damage from

aminoglycoside antibiotcs too, and battled her insurance company to

pay for innovative therapies.

Was your daughter in the hospital the entire time she was on

gentamicin? Sometimes they only check peak and trough levels until

they get the dosage consistent, then they only check maybe once a

day. I've heard stories from people who go home to finish out IVs,

but NO ONE tells them that they should continue getting peak and

trough checked. My son has only had IVs twice (knock wood), but both

times, after dismissed to finish IVs at home, his doctor wrote orders

to have peak and trough checked every 72 hours. If he ever has to

have IVs in the future, I want them to check more frequently than

every 72 hours because my son has a history of metabolizing meds

quickly.

And yes, the one-time use of gentamicin could have caused the damage,

or yes, it could have been a cummulative effect from using

tobramycin. Both are aminoglycosides and notarious for their ototoxic

effects. Please don't be lulled into thinking that inhaled TOBI is

any safer than IV. TOBI does get into the bloodstream, though of

course it's not as much as the IV version.

By your subject line, I'm guessing you already saw the post I wrote a

few days ago. But if not, I've cut and pasted below.

Kim

Mom of (24 with CF) and (21 without)

<snip>I've read medical abstracts suggesting that aminoglycoside