treatment of skin infections in era of MRSA

A study done in 4 centers (Univ of Chicago, San Francisco General Hosp, Harbor-UCLA , and Vanderbilt Univ Med Ctr) looked at the efficacy of clindamycin vs trimethoprim-sulfamethoxazole (TMP-SMX) for uncomplicated skin infections (see skin infections tmpsmx vs clinda nejm 2015 in dropbox, or N Engl J Med 2015;372:1093-103​). the question was: which medication is preferred in the current era of community-acquired methicillin-resistant Staph aureus (MRSA), which seems to be extremely common around the country? details:

--524 patients, including 155 children. 30.5% with abscess (>5cm, in adults), 53.4% with cellulitis, 15.6% with both; the patients were 52.3% male, 53.2% black, 40.3% white, 28.6% hispanic. mean age 27.1. 29.6% children.

--patients were randomized to clindamycin (adults at 300mg tid) or TMP-SMX (on double-strength tablet bid), all for 10 days. Pediatric doses adjusted by body weight

-- of those with positive cultures (n=277), 217 had s. aureus [167 with MRSA, 77.0% of the staph infections, with 21 (12.4%) resistant to clinda and 1 resistant to TMP-SMX; 52 were methicillin sensitive]; 32 were strep of different varieties; 10 were proteus, 38 coagulase-negative staph, 15 diphteroids, and a smattering of others. Note: all of the cultures were from those with abscesses, not cellulitis (cellulitis being 53.4% of the skin infections)

--no difference in outcomes between these medications: 80.3% were cured with clindamycin, 77.7% with TMP-SMX in intention-to-treat analysis, but in the 466 evaluable patients, it was 89.5% with clindamycin and 88.2% with TMP-SMX.

--no difference in children vs adults, in those with abscesses vs cellulitis. also no difference in subgroups infected with s. aureus, MRSA, or MSSA. of the 15 patients with clindamycin-resistant staph, 11 were cured (73.3%) vs 91.7% of those sensitive to clinda

--adverse events: similar: 18.9% with TMP-SMX​  and 18.6% with clindamycin, with both antibiotics associated with diarrhea in about 10%, nausea 2.5%, pruritus in 1.5%, rash in 1%. no cases of clindamycin-associated c. diff infections.

so, a few points:

--it is pretty remarkable how well TMP-SMX did, since a reasonable percentage of the patients had strep which is felt not to be sensitive to TMP-SMX. and, it is generally held that cellulitis is much more likely than abscesses to be caused by strep (though we cannot really culture cellulitis), yet the cure rate with TMP-SMX was the same for cellulitis and abscesses. there is some literature suggesting that the way sensitivity testing is done may underestimate TMP-SMX sensitivity. [as a general point, agar-plate antibiotic resistance is not always an accurate reflection of what happens in the body. for example, many organisms causing urinary tract infections seemingly resistant to antibiotics may in fact respond, perhaps related to the high concentration of antibiotics in the urine]

--several studies have found that antibiotics do not add much to the primary treatment of abscesses (which is: incision and drainage, I&D), so the high cure rate with any antibiotic may not be surprising. so, for example, 73.3% of those with clindamycin-resistant staph in the above study "responded" to antibiotics, but these bacterial isolates were from abscesses and may not have needed antibiotics. but i should add that the literature on this is really all over the place. some studies suggest that abscesses> 5cm (as in the above study) do better with antibiotics in addition to I&D. some find that MRSA infections in particular respond better when antibiotics are added. but there are studies to the contrary.

--there have been studies finding that cephalosporins or other b-lactam antibiotics with anti-strep activity work somewhat better than TMP-SMX for skin infections, though given the very high prevalence of MRSA that we find at our health center, we have been mostly using TMP-SMX as the primary agent and with good results​ (again, we only culture those with abscesses). i had a patient with morbid obesity and diabetes a few years ago who had a very large inner thigh abscess and surrounding cellulitis from documented MRSA, sent home from the hospital on linezolid, but i was unable to get the required prior approval and switched him to TMP-SMX​, and he had a great result... In general, we do usually add antibiotics for skin infections because of the articles suggesting benefit in MRSA, and there was even an article suggesting less likely recurrences if use TMP-SMX​. 

note: i have several other articles in the BMJ on-line blogs on MRSA, including the use of bleach baths ( http://gmodestmedblogs.blogspot.com/2014/03/use-of-bleach-baths-to-decrease.html ), the new Infectious Disease Society guidelines on treatment of skin infections (http://gmodestmedblogs.blogspot.com/2014/07/soft-tissue-infection-guidelines.html ) and skin abscess treatment (http://gmodestmedblogs.blogspot.com/2014/03/skin-abscesses-treatment.html )