by Dr Geoffrey Modest
A recent article found that either clindamycin or trimethoprim/sulfamethoxazole (TMP/SMX) are superior to placebo for uncomplicated skin abscesses (see Daum RS. N Engl J Med 2017;376:2545-55 ).
Details:
— multicenter, prospective, double-blind trial of 786 outpatient adults and children who had a skin abscess <5 cm in diameter (or <3 cm if 6-11 months old, <4 cm if 1-8 yo), and two of: erythema, swelling/induration, local warmth, purulent drainage, tenderness.
— patients randomized to clindamycin 150 mg TID vs TMP/SMX 80/400 mg BID vs placebo, for 10 days
— 57% male, mean age 25.5 (64% > 18yo/13% 9-17yo/21% 1-18yo/2% <1yo), 62% African-American/31% white, temperature 37°C, area of wound 4 cm², surrounding erythema 27 cm²
— all had incision and drainage of their abscess
— Exclusion criteria: infection in a body site requiring specialized management (perirectal, genital, hand infection), human or animal bites, oral temperature higher than 38.5°C (38.0°C in children 6-11 months of age), systemic inflammatory response syndrome, immunosuppressive therapy, immunocompromising conditions (e.g. diabetes, renal failure), BMI >40
Results:
— S. aureus was isolated from 527 (67%); MRSA was isolated from 388 (49%)
— intention-to-treat analysis 10 days after therapy: cure rate in clindamycin group was 83%, TMP/SMX group 82% (no statistical difference), but in the placebo group was 69%, significantly lower (p<0.001)
— For those who could be evaluated (those that completed the required study visits): 93% of clindamycin group, 93% of TMP/SMX group, and 81% of placebo were cured.
— children did slightly better than adults overall, especially in the clindamycin group
— For those without S. aureus, 90.5% on clindamycin, 90.8% on TMP/SMX , and 90.8% on placebo were cured (i.e. no benefit in non-S. aureus infections by antibiotics)
— for those with S. aureus (similar numbers for MRSA and MSSA), around 95% on clindamycin, 92% on TMP/SMX , and 70% on placebo were cured
— treatment failure was mostly because of a lesion at a different body site, or use of a rescue medication (done largely in the placebo group), but rarely due to worsening of the original lesion.
— at the one month follow-up visit:
–79% of the clindamycin group, 73% on TMP/SMX , and 63% on placebo remained cured.
–new infections at one month were less common in the clindamycin group (7%), than in the TMP/SMX group (14%), p=0.03, or the placebo group (13%), p=0.06
— adverse events were more common with clindamycin (22%) than with TMP/SMX (11%) or placebo (13%). All adverse events were without sequelae. One participant on TMP/SMX had a hypersensitivity reaction (fever, rash, thrombocytopenia, and hepatitis). Most common adverse events were diarrhea (16% clindamycin, 5% TMP/SMX, 7% placebo) and nausea (2%, 4%, 2%). No C difficile infections
Commentary:
— Skin abscesses are quite common, affecting 4% of people in the United States annually. Often these are treated as outpatients with clindamycin or TMP/SMX, given the large percent of community MRSA
— In this study TMP/SMX was effective at a lower dose than often prescribed, though a 10-day course was given (vs 7 days). It is possible that the cure rates might have been higher with higher doses of TMP/SMX
— 13 patients had resistance to clindamycin and did not fare as well (54% cure vs 85% in clindamycin-susceptible infections). There were no cases of TMP/SMX resistance
— this study suggests that antibiotics help, though held-wisdom previously was that there was not much additional benefit after incision and drainage alone.
— there were minimal severe adverse reactions. Prior studies have found about 5% on TMP/SMX have severe reactions (and 1 person did above), and these can be fatal.
— for clindamycin, there was a meta-analysis (see Brown KA. Antimicrobial Agents and Chemotherapy 2013; 57: 2326) that found that, as compared to no antibiotic exposure, the Odds Ratio of C difficile infection for clindamycin was 16.80, fluoroquinolones 5.50, cephalosporins 5.68, macrolides 2.65, TMP/SMX 1.81
— it was mentioned in the supplementary materials of the current study that 33 in the placebo group (13%) used “rescue meds”, whereas 12 in clindamycin (5%) and 15 in TMP/SMX (6%) did. There is no comment on what meds were used or what the outcomes were for those who continued with their assigned meds/placebo and did not require rescue meds
so:
–it seems quite likely from this study that antibiotics help, as also noted in a prior blog , a study comparing TMP/SMX at 4-fold higher doses (320/1600 mg bid) finding benefit from the antibiotic but noting that >80% responded just to I&D. And, 80+% of people seem to get better without antibiotics (in several other studies), and even in this study, 81% of those completing the study were cured. (70% of those with documented S aureus infections).
— there are really bad/occasionally lethal short-term potential adverse events from these antibiotics, especially severe systemic reactions to TMP/SMX and severe C difficile infections with clindamycin
–and there are potential long-term bad effects on the microbiome. As an example, this blog reviews a large prospective observational study finding antibiotic usage was associated with later development of colonic adenomas, including high-risk ones
–it was also notable in this study that there were not many cases of the abscess area getting worse in the placebo group with “treatment failure”
–so, in lower risk patients (nondiabetics, immunocompromise, etc), it might be reasonable just to watch the patient, holding the antibiotics but prescribing them if they were not getting better in a few days. I would be inclined to use antibiotics even in this lower-risk group if there were uncertainty about being able to have close followup (returning to clinic or phone followup), to assess the progress.