antibiotics for skin abscesses?

NEJM just published a study looking at trimethoprim-sulfamethoxazole (TMP/SMX) vs placebo in patients with uncomplicated skin abscesses (see skin abscesses tmp smx nejm2016 in dropbox, or N Engl J Med 2016;374:823). details:

--study done in 5 US ERs, assessing TMP/SMX at highish dose of 320mg/1600mg (ie, two DS tablets) twice daily (n=630) for 7 days vs placebo (n=617). Inclusion criteria included having the abscess a minimum of 1 week and that it was at least 2.0cm in size, as measured from the borders of induration.

diameter (as measured from the borders of 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 1.5cm deep; erythema 7.0x5.0cm; 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

--results:

    --of those who took at least 1 dose of med, 64.7% were 100% adherent, 17.2% took 76-99%.

    ​--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/SMX vs 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 -5.2 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 followup 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 raised 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 (as in the above study as well), so there needs to be a pretty large study to show efficacy of antibiotics in the remaining patients. there is some concern in the literature that in the era of MRSA, there might need to be more use of antibiotics. we do not have enough granular data from this study to know if the 85.7% who were cured with I&D and placebo included a large % of those with MRSA.

--of course, TMP/SMX is not benign: it can be associated with c. diff infections, renal/electrolyte problems, hepatotoxicity, drug interactions, and life-threatening reactions (eg Stevens-Johnson syndrome in about 3/100K people, also erythema multiforme). the low baseline rate of adverse effects (around 5%) is also much higher in those with HIV, esp if severely immunocompromised. and there is also the development of resistant organisms, and microbiome changes (though, interestingly, a VA study did not find significant increases in antibiotic resistance in the post MRSA period, when 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, eg NEJM 2014; 370: 1039)​, though the above study was extra cautious and used twice that amount.

--so, how should this affect practice? of course, at the time of presentation, we do not know the borganism causing the infection, though the above study reinforces the large role of MRSA. and, as per many prior blogs, i am very concerned about longterm effects of frequent antibiotic use on resistance (the study just mentioned is somewhat reassuring) and the microbiome. i would certainly use antibiotics in those who might be immunocompromised (eg diabetics, etc), and those with extensive infections (not sure really what the cutoff is here), but my bent, after this study, would be to offer them more often to healthy people as well.  the 7.2% difference in cure is clinically significant, as is the pretty large differences in patients who need to come back for subsequent surgical drainage and skin infections at new sites. so, i think it makes sense to discuss the potential pros and cons with the patient...