Interesting Article of the Week: Gonorrhea, Superbug.

The Emerging Threat of Untreatable Gonnococcal Infection.
Bolan GA, Sparling PF, Wasserheit JN
N Engl J Med 2012;366(6):485

This article was generated by the CDC and is about the increasing incidence of drug resistance of Neiseria gonorrhoeae, as well as the CDC’s newest recommendations for the treatment of gonorrhea.  Gonorrhea has slowly and inexorably conquered an impressive list of antibiotics, including penicillin, tetracycline and, most recently, flouroquinalones.  Currently, only two antibiotics remain for treatment of gonorrhea, and sure enough, signs of resistance to these two drugs are cropping up in Asia.

The good old days!

I am old enough to remember when gonorrhea was easily treatable with low dose (1.2 million units) of IM penicillin.  Then that wasn’t enough, and the dose increased to 2.4 million units.  Finally, even 4.8 million units plus probenecid wasn’t enough, and we switched to quinalones.  That worked for awhile, but in 2007, the CDC no longer recommended the use of quinalones because of increasing resistance.

Our final bulwark against this “wily” bug (an adjective used by the CDC in this paper!), is ceftriaxone (Rocephin) which is given as a single IM shot and high dose azithromycin.  Cefixime can theoretically also be used, but cefixime (Suprax) can be hard to find.  Your pharmacy might not carry it.   It also is less effective than ceftriaxone.

Like the early days of penicillin, the dose of ceftriaxone recommended by the CDC to treat gonorrhea is increasing.  It used to be 125mg but now the CDC recommends a dose of 250mg as a single IM injection.  In addition, the dose of ceftriaxone should be supplemented with 1 gram of azithromycin, which acts synergisticly with the ceftriaxone and hopefully, will delay the inevitable development of resistance.  And besides, we need to give the azithromycin anyway to treat the inevitable concomitant chlamydia infection!  This combination will cure 99% of gonococcal infections in the US.  (But not in Asia, where both cephalosporin and azithromycin resistance is being reported).

What if your patient reports a penicillin allergy?  Well, you can give 2 grams of azithromycin in a single dose and cause a horrific case of GI upset, but a better medical practice would be to give the ceftriaxone anyway.

According to the literature, the purported cross-reactivity of penicillins and cephalosporins is a myth, especially with 3rd and 4th generation cephalosporins like ceftriaxone.  First of all, of all patients who report a penicillin allergy, less than 10% actually do when tested.  Second, the crossreactivity theory was based on the fact that the molecular side chains of the first cephalosporins were similar to those of penicillin.  But this particular side chain is different in the 3rd and 4th generation cephalosporins, like ceftriaxone and not at all similar in structure to penicillin.   Even in a patient with a true IgE allergy to penicillin, you can still give ceftriaxone.  This recent evidence based review article, for example, states

“For penicillin-allergic patients, the use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy.”

Per the CDC, you can still give doxycycline 100mg po a day for 7 days instead of the single dose of azithromycin, though why you would want to do this, I don’t know.  Azithromycin therapy as a single dose is easier, more reliable, carries a lesser risk of failure, and is similarly cheap.

Since we should always know the cost of the medications we prescribe, here is the current cost of these therapies according to my source, the Idaho Average Actual Acquisition Cost for Generic Drugs:

ceftriaxone 250mg IM single dose            $1.05
Azithromycin 1000mg single dose            $3.16
doxycycline 100mg BID for seven days   $0.82

Summary:

1.  Neisseria gonorrhoeae is slowly but inexorably developing resistance to every single antibiotic used against it.  The day when an untreatable strain develops is within sight.

2.  The current recommendation of the CDC is to treat cases of gonorrhea with both ceftriaxone 250mg IM AND azithromycin 1000mg po as a single dose (which you should use anyway to treat chlamydia).

3.  You can still use ceftriaxone in penicillin allergic patients.

What do you use to treat gonorrhea infections in your facilities?  Please comment!

 

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