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From: (Jonathan R. Fox)
Subject: Re: Question re: antibiotic-resistant ear infection
Date: Wed, 03 Mar 1999 05:08:11 GMT

On Tue, 02 Mar 1999 20:02:50 GMT, tg <> wrote:

>My 20-month-old is experiencing a first-time, ongoing ear infection
>(started in January).  A 10-day trial of amoxycillin didn't work.  A
>subsequent trial of Zithromax helped signficantly but not completely,
>and a second trial of Zithromax helped some more; my daughter was
>essentially asymptomatic after that second trial, but the infection
>was still not quite gone.  The doctor took a wait-and-see approach at
>that point, which I appreciated, but the infection is rearing its ugly
>head again.  She has another doc's appt. tomorrow (Wed.), and her doctor
>and I will discuss further treatment.

If she was asymptomatic but you were told "the infection was still not
quite gone," to me that implies that the infection was in fact gone
but she still had a persistent middle ear effusion (fluid in the
middle ear) which is expected after an ear infection.  A middle ear
effusion can persist for up to 12 weeks after an ear infection.  The
wait-and-see approach is appropriate.  Too many physicians throw
unnecessary extra courses of antibiotics at asymptomatic effusions.

It is important to determine now, however, if whatever symptoms you
feel are signs that the infection is back really do represent a
recurrence of her ear infection or if they are unrelated to the
effusion she has.

>It's striking to me that this infection is so tough, given that it's
>her first.  I know we may ultimately be forced down the tubes-in-the-ears
>route, but I'm really hoping that this thing can be knocked out prior to
>that, especially since the coming change in weather should help improve
>things significantly.
>I've done some reading on Medline about resistant ear infections, but I'd
>like further input.  I don't like the idea of my daughter taking another
>strong antibiotic if it's not the best weapon against whatever particular
>type of bacteria she has.  My family as a whole has had little exposure to
>the stronger drugs, but even so, two of us have had bad reactions to two of them
>(Biaxin and Bactrim).  But having a culture taken from my daughter's ear
>doesn't sound particularly appealing, either--and I would assume it involves
>some risks.  Any comments or suggestions?

Ear infections resistant to treatment, if caused by
antibiotic-resistant bacteria, are typically caused by either
penicillin-resistant _Streptococcus pneumoniae_ or
beta-lactamase-producing _Haemophilus influenzae_.  Penicillin
resistance and beta-lactamase production both affect the usefulness of
amoxicillin, and frequently coexist with macrolide resistance, which
limits the usefulness of Zithromax.

If an ear infection does not respond to amoxicillin, an appropriate
next choice would ideally defeat both penicillin resistance and
beta-lactamase production.  Increasing the dose of amoxicillin to 80
mg/kg/day for 10 days (so-called "high dose" amoxicillin, compared to
the standard 40 mg/kg/day) can defeat intermediate
penicillin-resistance and is generally well tolerated.  This strategy
cannot be used with Zithromax, as increased doses of macrolides do not
overcome macrolide resistance.  Next, the addition of clavulanic acid
(as in Augmentin, which is amoxicillin plus clavulanic acid) can
overcome beta-latamase producers.

To give high dose amoxicillin with clavulanic acid, you cannot simply
raise the dose of Augmentin, since the child would get too much
clavulanic acid.  Since the new formulation of Augmentin containing a
higher amoxicillin-to-clavulanate ratio is not yet available to my
knowledge, we instead treat resistant infections with both amoxicillin
and Augmentin in equal amounts, to give 80 mg/kg/d total of
amoxicillin while avoiding the higher dose of clavulanic acid that
would result from giving all Augmentin at 80 mg/kd/d.

See the "Update on Drug-Resistant _Streptococcus pneumoniae_ and the
Management of Acute Otitis Media" in The Pediatric Infectious Disease
Journal, October 1998, Vol 17, No. 10, pp. 943-971 for more

Jonathan R. Fox, M.D.

From: (Jonathan R. Fox)
Subject: Re: Question re: antibiotic-resistant ear infection
Date: Thu, 04 Mar 1999 01:23:25 GMT

On Tue, 02 Mar 1999 23:06:41 -0500, Ed Mathes <>

>Since the pneumococcus is not a bet-lactam producing bug, augmentin has
>no role in treatment except for using it in high doses (the amoxicillin

Unless you're treating beta-lactamase-producing H. influenzae.

On Wed, 03 Mar 1999 21:37:19 GMT, (Anna) wrote:

>I just wanted to ask you wether it is hard to take a sample from
>earinfections? Do you normally not do that in USA? And dont you either
>(in a case like this when it doesn't totally heal out even after 3
>courses with antibiotics) make a resistance test in the lab? I belive
>that in Sweden it is pracsis not to give antibiotica if not totally
>needed and if this would happen, one would culture and check for
>resistance. To know exactly wich bugger one is dealing with as well as
>exactly wich antibiotic to use, and even in wich consentration.

It is true that in Sweden, physicians there have adopted a much more
conservative approach to treating ear infections (otitis media) with
antibiotics.  This is believed to be a factor in the low incidence of
penicillin-resistance among pneumococci there.

While it is not a well known fact, most ear infections will resolve on
their own without antibiotics.  However, in the United States,
treating all ear infection with antibiotics has remained the standard
of care for two reasons, in my opinion:  First, the duration of pain
and fever are significantly shortened by antibiotics, and one would
agree that American medical "consumers" demand relief from symptoms
without concern for long-term consequences.  Second, suppurative
complications of untreated otitis such as mastoiditis or meningitis,
although rare, can have devastating consequences.  The physician in
the U.S., given our legal system, takes a substantial risk in not
treating an ear infection, compared to a physician in Sweden, where a
patient does not necessarily hit the jackpot by having an adverse
outcome from failure to treat.

These reasons are not necessarily bad things.  I side with the parents
in prefering to relieve an infant's suffering by treating with
antibiotics.  And the benefit of the measurable decrease in
suppurative complications of otitis media seen since the advent of
antimicrobial therapy may indeed outweigh the risks of and problems
created by antibiotic-resistance.  Time will tell.

Finally, on your question regarding culture of middle ear fluid by a
technique known as tympanocentesis:  This procedure is not done as
frequently as in the past, and has become a lost art among
pediatricians.  The procedure is now largely in the hands of the ENT
specialist, and, naturally, not all children with ear infections can
be nor should they be referred to a specialist.  Empiric therapy
without culture has proven effective for most children.  Infants with
recurrent or troublesome infections often do undergo typanocentesis,
but it is otherwise not a routine procedure.

Jonathan R. Fox, M.D.

From: B. Harris)
Subject: Re: Question re: antibiotic-resistant ear infection
Date: 4 Mar 1999 08:06:40 GMT

In <36dda347.8863222@wingate> (Anna) writes:

>On Tue, 02 Mar 1999 23:06:41 -0500, Ed Mathes <>

>>The best antibiotic is still.....amoxicillin. In doses higher than we
>>did prescribe. The recommendation is 80mg/kg/day divided doses for 10
>>days. This seems to eradicate 93% of resistant pneumococcus. Zithromax
>>is around 80%, right there with the lower dose amoxicillin. Cefzil also
>>has good coverage (and tastes good). Final choice is a sulfa-drug.
>>Tympanocenesis (removing the fluid behind the ear with a needle passed
>>thru the ear drum) is usually therapeutic in and of itself...but most
>>doctors also prescribe a course of antibiotics.
>>I hope this information helps.
>>Edward J. Mathes, RPA-C
>>Internal Medicine

>I just wanted to ask you wether it is hard to take a sample from
>earinfections? Do you normally not do that in USA? And dont you either
>(in a case like this when it doesn't totally heal out even after 3
>courses with antibiotics) make a resistance test in the lab? I belive
>that in Sweden it is pracsis not to give antibiotica if not totally
>needed and if this would happen, one would culture and check for
>resistance. To know exactly wich bugger one is dealing with as well as
>exactly wich antibiotic to use, and even in wich consentration.
>Would really like to know, it is strange how diffrent we seem to treat
>a lot of diseases in our countries. If anyone else has any clue ...  I
>would really appreciate it too  :))

   Well, basically there's a terrible entrenched sentiment in the US to
treat kids with acute pain from an earache, with antibiotics.  But that
pain generally subsides in 24 hours no matter what you do, and because
we humans are post hoc ergo propter hoc organisms ("after this,
therefore because of this") the antibiotic gets the credit.  There is
pretty good evidence that otitis media in kids is best treated with
narcotics alone unless it lasts for an unusual length of time.  Because
whether or not you treat the condition with antibiotics or not makes
not a whit of difference in most acute cases (if you want references
for this, I can certainly provide them).  And you can tell which ones
are eventually going to need treatment, by simply waiting.  That goes
against the grain in DO SOMETHING American medicine.  Swedes seem to
tolerate anything the government says is good for them. Unfortunately,
the "market system" of the US, which has the worst features of both
socialism and capitalism (rather like fascism) will not allow us to
treat otitis media in children rationally.  And that's all there is to
it.   It MIGHT, if parents had to pay the cost of the antibiotic,
including the hidden costs of developing the next generation of
antibiotics against resistant bugs.  But we do not allow that.

   I can tell from long experience in outpatient clinics, urgent care
centers, and ERs, however, that when second and third generation
pediatric cephalosporins are involved, and also liquid Augmentin, that
those self-pay patients who are informed that 3 days of waiting to give
antibiotic will make no difference in their child's health, and that if
he or she is clearly getting better in that time, they can save
themselves a lot of money by just giving ibuprofen and codeine (elixer,
or even crush appropriate fraction of a Tylenol #3), will elect to
forgo the expensive antibiotic.  So long as they have the prescription
in hand, and know they can get it at a 24 hour pharmacy any time, if
they think they really need it.   It would be much the same for high
dose amoxicillin, if they really had to pay the cost of future
penicillin resistent pneumococcus.  Which they don't.

   Interestingly, if you must give high dose amoxicillin, or the
equivalent, the clearly superior way to do it is to give
bacampacillin/Spectrobid, which allows huge doses to be given of
ampicillin (an equivalent drug, bacterially speaking) without the GI
effects you get from unabsorbed antibiotic.  But Spectrobid in not made
in a pediatric elixer, and even as a pill is almost impossible to find,
due to its patent having expired long before the charms of an oral
antibiotic which is capable of giving IV levels, were economically
appreciated.  So it goes.  We have people here bemoaning patents and
price gouging--- but we need to understand what happens when do not let
people people profit long term from the long-delayed and unexpected
benefits of inventions.  Basically, what happens is that you're left in
a state with no inventions when you need them.  That's the price you
DON'T see for "information socialism."  Have you (or any readers) even
heard of Spectrobid?  No?  Well, there's a reason for that.  And the
reason is POLITICAL, not scientific.  So YOU give 80 mg/kg/day
amoxicillin to an 18 month old, and YOU change the diapers.  BUT, I
would like you to think about Marx all the time you're doing it.

                                         Steve Harris, M.D.

From: B. Harris)
Subject: Re: Question re: antibiotic-resistant ear infection
Date: 5 Mar 1999 11:38:48 GMT

In <> Ed Mathes <>

>I think even the Swedes would have treated this one. Unfortunately,
>tympanocentesis...needle drainage of the middle a technique
>long-since forgotten by pediatricians. Oftentimes it is
> draing an abscess.

   Sure.  But the rupture that happens in a tympanum spontaneously is
likely to be less trumatic than one you make with a needle.  This has
actually been proven.  After all, YOU don't know where exactly the
thing is least strong, nor do you know for certain how big the rent
needs to be at minimum.  Nature neatly minimizes all that in a sort of
principle of least action, and does it in such a way that when the
pressure is off, the tissue flaps neatly superpose again (I am reminded
here of the controversy surrounding episiotomy in childbirth, where
some of the issues and answers are the same, provided the stress toward
rupture is applied "naturally").  The only thing a tympanocentesis
saves is a couple of hours of pain.  And not without risk and cost.  A
narcotic/NSAID combo, for a tympanum about to blow, might well serve
better.  And one that isn't, doesn't usually hurt that much anyway, or
at least not for long.  The only time your hand is forced is for that
chronic effusion that stays and stays and stays.  But these are
relatively rare.

From: (Jonathan R. Fox)
Subject: Re: Erybid vs amoxicillin?
Date: Sat, 10 Apr 1999 02:43:09 GMT

On Fri, 02 Apr 1999 16:43:02 -0500, Ed Mathes <>

>H.flu here runs about 30% resistant to -cillin.  Based on the
>recommendations of the cdc for treating resistant otitis media, we have
>been applying that to URIs in general.  Double the dose of amox to increase
>MIC if patinet not better after 3 days on standard dose amox.  If
>beta-lactamase suspected, change to a beta-lactam antibiotic (augmentin).
>One local ID guy commented that "we are losing zithromax" because it is
>being prescribed for just about everything and has lousy H.flu and

Macrolide resistance tends to run with penicillin resistance, and,
unlike penicillin resistance, cannot be overcome with increased dose.
I just saw a kid today whose eardrum perforated, now draining thick
goo, on day 5 of Zithromax.  I do not understand why people still use
Zithromax for otitis media.  Maybe it's the cute little baby books
with the Zithromax zebras looking in each other's ears.  Still works
great on atypical pneumonia, but not for otitis.

Jonathan R. Fox, M.D.

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