By Dr. Geoffrey Modest
NEJM just a published a study looking at trimethoprim-sulfamethoxazole (TMP/SMX) vs placebo in patients with uncomplicated skin abscesses (see N Engl J Med 2016;374:823).
- Study done in 5 US ERs, assessing TMP/SMX at dose of 320mg/1600mg (i.e., two DS tablets) twice daily (n=630) for 7 days vs placebo (n=617). Patients had to have the abscess for at least 1 week, and it had to be at least 2cm in diameter, including the induration.
- Mean age 35; 58% male; 4.0 days of symptoms; 18% with fever; 11% diabetic; 4% with chronic skin conditions; site: 13% head/neck, 21% trunk/abdomen/back, 21% groin/buttocks, 23% arms/hands, 21% legs/feet; mean abscess size 2.5 cm x 2.0 cm x 5cm deep; erythema 7.0×5.0cm; wound culture: 45% MRSA, 16% methicillin-sensitive S. aureus, 12% coagulase-negative staph, 5% strep)
- Main outcome was clinical cure 7-14 days after the end of the treatment period
- Of those who took at least 1 dose of med, 64.7% were 100% adherent, and an additional 17.2% took 76-99% of the meds.
- Modified intention-to-treat population (took at least one dose of med): clinical cure in 80.5% on TMP/SMX vs 73.6% on placebo (difference 6.9 percentage points (2.1-11.7, p=0.005)
- Per-protocol population (took at least 75% of doses during first 5 days and had in-person test-of-cure): clinical cure in 92.9% on TMP/SMXvs 85.7% on placebo (difference 7.2 percentage points (3.2-11.2, p<0.001)
- 7-14 days after treatment period, TMP/SMX also associated with lower rates of:
- Subsequent surgical drainage (3.4% vs 8.6%, difference of -5.2 percentage points (-8.2 to -2.2)
- Skin infections at new sites (3.1% vs 10.3%, difference of -7.2 percentage points (-10.4 to -4.1)
- Infections in household members (1.7% vs 4.1%, difference of -2.4 percentage points (-4.6 to -0.2)
- No difference in invasive infections (0.4% in each group)
- Extended follow-up at 42-56 days: an invasive infection occurred in 1 patient in the TMP/SMX arm, “unrelated to the original abscess”
- Adverse events: overall similar rates, most considered mild. Most common were GI (42.7% vs 36.1%); no cases of c. diff-diarrhea.
So, this study raises a few issues:
- Historically, the primary treatment for cutaneous abscesses had been incision and drainage (I&D). Smaller studies have shown no benefit of antibiotics. The concern here is that >80% of abscesses are cured with I&D alone (as in the current study), so there needs to be a pretty large study to show efficacy of antibiotics in the remaining patients. Also, there is some question in the literature as to whether the situation now is different in the era of MRSA, that antibiotics may play a greater role in treatment of abscesses. To show this, there would need to be an even larger study to see if MRSA needs different treatment. But, from a primary care perspective, we do not know the organism at the time of presentation and need to treat empirically anyway, and this study is therefore applicable/useful.
- Of course, TMP/SMX is not benign: it can be associated with c. diff infections, renal/electrolyte problems, hepatotoxicity, drug interactions, and other life-threatening reactions (g. Stevens-Johnson syndrome in about 3/100K people, or erythema multiforme). Overall, adverse reactions are on the order of 5%, though higher in those with HIV, esp if more severely immunocompromised. And there is the development of resistant organisms and microbiome changes (though, interestingly, a VA study did not find significant increases in antibiotic resistance in the post- vs pre- MRSA period, after which much more TMP/SMX has been prescribed — see Antimicrob Agents Chemother. 2012; 56 (11): 5655)
- Still not so clear what the correct dose should be: there are data that a single DS pill bid achieves adequate serum levels for MRSA, and that is what I have been prescribing (the guidelines I’ve seen recommend 1-2 tabs bid, g. NEJM 2014; 370: 1039), though the current study was extra cautious and used the 2 tablet bid regimen
- So, this study does raise the issue of routinely using TMP/SMX for abscesses in people with uncomplicated skin infections. As with many clinical issues, the right path for an individual patient is not so clear. The positives of treating are the higher cure rate by 7%, but also the pretty significant 5% decrease in need for subsequent surgical drainage and the 7% decrease in skin infections in new sites. The negatives are the immediate adverse effects of TMP/SMX, about 5% but including some rare fatal reactions, the potential for drug resistance (though not so much in above cited study) and perhaps longish term microbiomeMy bias is that I would lean more strongly to using antibiotics in a few instances: in immunocompromised person (including diabetes), in some sites more than others (e.g., face/neck and groin area — anecdotally, I did have a patient many years ago with a groin abscess, and put on anti-staph antibiotics, but developed a fatal case of necrotizing fasciitis, so I do treat groin infections much more aggressively/broadly, covering anaerobes as well), and in a really mean looking, large (?not sure how to quantitate) abscess, especially if large surrounding area of cellulitis/induration or systemic symptoms (fevers, etc.). I think the conclusion is that there needs to be a discussion with the patient and a collaborative decision, reviewing risks/benefits.
For prior blog on using bleach baths for recurrent infections, see http://blogs.bmj.com/bmjebmspotlight/2014/04/02/primary-care-corner-with-geoffrey-modest-md-bleach-baths-to-decrease-recurrent-skin-infections/
the recommendations are for 1/4 cup of bleach in 1/4 bathtub (13 gallons of water), though will add the caveat, per Dr. Richard Bird, that it is not uncommon for people to add a lot more bleach or into only small amounts of water, and that they can get an associated cough or precipitate asthma (toxic reaction to the bleach/chlorine). Also can get rashes.