An article that appeared in Medscape, is attached.


Opposition Growing Against Azithromycin for Infections

Neil Canavan
February 18, 2014

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 NEW YORK CITY — Treatment guidelines increasingly recommend that certain
antibiotics, particularly the macrolide azithromycin, no longer be used to
treat many common infections. Inappropriate use has led to widespread
antibiotic resistance and is contributing to the emergence of super bugs.

At least one prominent emergency medicine expert suggests that the drug not
be used at all.

"If we don't stop, we're not going to have good antibiotics in the future,"
warned Joseph Lex, MD, from Temple University in Philadelphia, here at the
American Academy of Emergency Medicine (AAEM) 20th Annual Scientific
Assembly. "Every country that has recommended the use of narrow-spectrum
antibiotics instead has seen a fall in their resistance rates. We just have
to get to the point where we do the same thing."

Dr. Lex is hardly a lone voice in this call to move away from the abuse of
broad-spectrum antibiotics. Current guidelines present a chorus of similar
opinions.

Azithromycin was developed in 1980 and has been marketed in the United
States since 1991. As of 2011, it is the most commonly prescribed
antibiotic. The current indications for azithromycin are acute bacterial
exacerbations of chronic pulmonary disease, acute bacterial sinusitis,
community-acquired pneumonia, pharyngitis, tonsillitis, uncomplicated skin
and skin structure infection, urethritis and cervicitis, and genital ulcer
disease.

If we don't stop, we're not going to have good antibiotics in the future.


However, just last year, the Canadian Pediatric Society strongly
recommended that azithromycin not be used to treat acute pharyngitis,
otitis media, or community-acquired pneumonia ( *Paediatr Child Health*.
2013;18:311-313<http://www.cps.ca/documents/position/azithromycin-use-in-paediatrics>
).

That guidance did not recommend that clinicians consider not using it —
it's recommendation is "do not use," stressed Dr. Lex. The only exceptions
for azithromycin use area life-threatening beta-lactam allergy and
pneumonia caused by an atypical bacteria.

"The long half-life of azithromycin contributes to the development of
resistance," he explained. The way the drug is being used, "you're likely
to get a subinhibitory nasal pharyngeal concentration, so these kids
actually become carriers of azithromycin-resistant pneumococci."

*Alternatives*

The data show that macrolides have limited efficacy against 2 of the most
common bacterial pathogens associated with acute otitis media — *Haemophilus
influenzae* and *Streptococcus pneumoniae*.

Macrolide resistance is not a potential, it is a reality, and rates are
increasing. "There is a better drug than azithromycin for every one of the
indications," Dr. Lex pointed out.

The rhinosinusitis guidelines issued in 2012 by the Infectious Disease
Society of America (IDSA) recommend considering antibiotics if symptoms
persist beyond 10 days, are severe or worsening, or if there is high fever
and nasal discharge for at least 3 days ( *Clin Infect Dis*.
2012;54:1041-1045 <http://cid.oxfordjournals.org/content/54/8/1041.long>).
Macrolides are not recommended at all. "Roughly 30% of these cases will be
resistant to azithromycin," said Dr. Lex.

The acute bacterial sinusitis clinical practice guidelines from the
American Academy of Pediatrics recommend amoxicillin with or without
clavulanate for patients 1 to 18 years of age ( *Pediatrics*.
2013;132:e262-e280<http://pediatrics.aappublications.org/content/early/2013/06/19/peds.2013-1071>).
There is no recommendation for macrolides.

For group A streptococcal pharyngitis, the 2012 IDSA guidelines recommend
first-line treatment with penicillin, and macrolides only for patients
allergic to penicillin. "In the United States, 5% to 8% of pharyngeal
isolates of group A strep are resistant to a macrolide," Dr. Lex reported.

For children older than 2 years of age with bacterial pediatric pneumonia,
the 2011 IDSA clinical practice guidelines recommend first-line treatment
with amoxicillin with or without clavulanate ( *Clin Infect Dis*.
2011;53:e25-e76<http://cid.oxfordjournals.org/content/early/2011/08/30/cid.cir531.full>).
Second-line choices do not include macrolides. "We know that 80% of
pediatric pneumonia under the age of 2 is viral," said Dr. Lex, adding that
azithromycin has no activity against a virus.

In the 2007 consensus guidelines on the management of community-acquired
pneumonia in adults, macrolides in combination with doxycycline can be
considered in previously healthy adults who have not recently taken an
antibiotic ( *Clin Infect Dis*. 2007;44[Suppl
2]:S27-S72<http://cid.oxfordjournals.org/content/44/Supplement_2/S27.long>).
"This is before our concern about widespread macrolide overuse, and they're
still not recommending using a macrolide alone," Dr. Lex noted.

Recently, "there has been a spate of new treatment recommendations that
have demoted the use of azithromycin, especially in pediatrics," said Dr.
Lex.

"Unfortunately, physicians get into a groove — a habit of prescribing a
particular antibiotic for a particular condition. Right now, there's at
least a year or 2 of lag time before these recommendations are adopted."

*Patient Education*

"Part of the reason for the overuse of azithromycin is pressure from the
patients," Michael Epter, DO, emergency medicine physician in Las Vegas and
education chair for the AAEM, told *Medscape Medical News*. "Patients come
in with the symptomatology of a respiratory tract infection — which is
commonly due to virus — yet they will insist on receiving an antibiotic."

When this happens, azithromycin is usually the agent prescribed. "With the
once-a-day, 5-day regimen, patient compliance is high. Doctors like that."
Even newer-generation macrolides are not as easy to use.

This time of year, "patients come in with your basic winter cold. In the
majority of cases, it's a viral-related illness and antibiotics are only
effective for their placebo effect," said Dr. Epter.

Azithromycin is also overused in sinusitis, which has repeatedly been shown
to be the result of a viral infection. In fact, "94 of 100 patients will
show no change in their symptoms when treated with an antibiotic, yet the
use of azithromycin in sinusitis is rampant."

But no matter what the data say, it is a hard sell to convince patients to
settle for over-the-counter symptom relief. "I try to explain it to them,"
Dr. Epter lamented, "but it's an uphill battle."

He said he first tries to explain the consequences of antibacterial
resistance, and how treatment for a cold can complicate treatment for a
more serious subsequent problem, such as pneumonia. Unfortunately, he said,
more often than not, patients aren't happy until they get a prescription.

The easiest solution is point-of-care rapid testing to properly identify
and narrowly treat the offending bug. However, "that technology is not yet
being aggressively adopted in hospitals," said Dr. Epter. "We're still a
couple of years away from getting to that point."

*Dr. Lex and Dr. Epter have disclosed no relevant financial relationships.*

American Academy of Emergency Medicine (AAEM) 20th Annual Scientific
Assembly. February 14, 2014.

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