Using clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) after incision and drainage of a simple abscess results in a higher cure rate than incision and drainage alone for infections with Staphylococcus aureus, according to a double-blind, randomized, controlled trial published online June 28 in the New England Journal of Medicine.
Clindamycin resulted in nearly half as many recurrences compared with TMP-SMX or placebo, though clindamycin also had about twice as many adverse events.
“Our findings show a clinical benefit of antibiotic therapy in addition to incision and drainage that seems limited to patients with S aureus infection,” report Robert S. Daum, MD, from the University of Chicago Medical Center, in Illinois, and his colleagues.
“The cumulative data from our investigation and that of Talan et al. call into question the perception — largely based on expert opinion or smaller, underpowered, and lower-quality non-inferiority trials — that cure rates do not improve with the addition of systemic antibiotic treatment after incision and drainage,” they write.
Thirteen of the participants had clindamycin-resistant S. aureus. “These data underscore the potential clinical relevance of in vitro resistance to clindamycin,” the authors write. “Participants infected with a clindamycin-resistant S. aureus isolate who were treated with clindamycin had cure rates similar to those who were given placebo.”
The researchers recruited 786 participants from six academic medical centers in the United States: the University of Chicago Medical Center, Illinois; San Francisco General Hospital, California; Harbor–University of California Los Angeles Medical Center in Torrance; Vanderbilt University Medical Center in Nashville, Tennessee; Washington University in St. Louis, Missouri; and Morehouse School of Medicine–Emory University in Atlanta, Georgia.
Of the 786 participants in the trial, 64.2% were adults and 35.8% were children, divided into three age groups (<1 year, 1-8 years, 9-17 years). All participants had a skin abscess 5 cm or smaller in diameter, with a mean depth of 1.64 cm and a mean area of 3.89 cm2. The abscess was 2 cm or smaller in diameter in 44.6% of participants.
All patients received the standard treatment of incision and drainage. Then the researchers randomly divided the participants into three groups for 10 days of treatment: 266 participants received clindamycin (300 mg three times daily), 263 received TMP-SMX (trade name Bactrim; 80 mg of trimethoprim
and 400 mg of sulfamethoxazole twice daily), and 257 received placebo. Randomization was also stratified “according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of non-purulent cellulitis.”
Two thirds (67%) of the participants’ abscesses had presence of S. aureus, and nearly half (49.4%) had methicillin-resistant S. aureus (MRSA). Among the other participants, 13.2% had coagulase-negative staphylococci, 6.9% had streptococcus species, and 15% had other organisms.
Ten days after treatment ended, 83.1% of participants receiving clindamycin and 81.7% of those receiving TMP-SMX had been cured in an intent-to-treat analysis compared with 68.9% of those in the placebo group (P < .001 for comparison between each antibiotic group and the placebo group).
In a per-protocol analysis, the cure rates were 92.9% in the clindamycin group, 92.7% in the TMP-SMX group, and 80.5% in the placebo group. Cure rates were significantly higher in children who received clindamycin than in children receiving TMP-SMX or placebo.
Among patients with MRSA infections, there was no significant difference between the antibiotics, with cure rates of 81.7% for clindamycin and 84.6% for TMP-SMX (P = .63). Both were higher than that seen with placebo (62.9%; P ≤ .001).
Clindamycin’s advantage was primarily seen in methicillin-sensitive S aureus infections, where it led to an 89.1% cure rate, compared with a 79.6% cure rate with TMP-SMX and 65.9% with placebo. Thirteen individuals had S. aureus that was resistant to clindamycin. Meanwhile, cure rates did not differ among any of the groups for patients who did not have an S. aureus infection.
Findings Contradict Current Recommendations
Although these findings appear to contradict current recommendations for standard of care, they were not surprising to Jesse Keller, MD, an assistant professor of dermatology at Oregon Health & Science University in Portland.
“Although we were taught and trained you don’t need antibiotics, what I commonly see happening around medicine, everyone just feels a little bit safer giving antibiotics, and that goes for patients as well,” Dr Keller told Medscape Medical News. “I don’t think this is different than what is actually being done. Now we have something to back us up.”
At follow-up 1 month later, 78.6% in the clindamycin group, 73% in the TMP-SMX group, and 62.6% in the placebo group remained cured in the intent-to-treat analysis. The recurrence rate among those initially cured was 6.8% in the clindamycin group, compared with 13.5% in the TMP-SMX group (P = .03) and 12.4% in the placebo group (P = .06).
Saul Hymes, MD, the medical director of Pediatric Antimicrobial Stewardship at Stony Brook Children’s Hospital in New York, said that the results may make him change his treatment approach. “This does make me possibly more likely to use antibiotics, though, based on local resistance patterns, for me, I would be more inclined to use Bactrim [TMP-SMX],” Dr Hymes told Medscape Medical News.
Dr Keller similarly noted that “local variation in what bugs are resistant to” may influence which antibiotics clinicians might choose. At his and Dr Hymes’ hospitals, the bacteria have considerably greater susceptibility to TMP-SMX than to clindamycin.
Despite the advantage seen with the antibiotics, Dr Hymes remains cautious in how best to interpret these findings in light of the need for antibiotic stewardship.”But this, to me, doesn’t mean to start giving everybody clindamycin and Bactrim willy nilly either,” Dr Hymes said, adding that he may hold off if he has concerns about patient adherence. “And if it’s a patient with a high risk of side effects from antibiotics, such as a history of C diff., then maybe those are the kids that you do aggressive drainage and you watch them more closely.”
The authors noted a similar caution. The group receiving clindamycin experienced twice as many adverse events (21.9%) than the TMP-SMX group (11.1%) or the placebo group (12.5%). Diarrhea and nausea were the most common adverse events, and all resolved without sequelae. No cases of Clostridium difficile occurred.
“Antibiotic-related side effects, particularly if frequent or serious, should be taken into account when deciding whether to treat a drained abscess with an antibiotic,” the researchers wrote. “Our findings suggest that there is a trade-off between more adverse effects and a lower likelihood of infection recurrence when one uses clindamycin rather than TMP-SMX.”
Dr Hymes would recommend taking stewardship into consideration as well, stating that studies focusing on cost-effectiveness and downstream consequences would be needed before any recommendations in care changed.
“If we weren’t living in a world with the dangers of antimicrobial resistance and a very active increasing need to perform antimicrobial stewardship, then sure, treat everybody,” Dr Hymes said. But if they develop a resistant organism, the fact that it’s a skin infection means it’s easily transmissible to someone else.
“Yes, they might get better. Yes, it might reduce recurrent infections. But this study didn’t look at the cost-benefit analysis or consider potential downstream effects from C diff., or with a quality of life or economic standpoint,” he pointed out.
Dr Hymes also said it would be important to assess whether to give antibiotics on a case-by-case basis, taking into account whether the patient has a history of MRSA or of abscesses in general. He would also be interested in finding out how the results may differ, if at all, in subpopulations at greater risk for infections, such as athletes or residents of long-term-care facilities. But without cost-benefit and quality-of-life assessments, he reserves judgment on what findings like these may mean in the big picture.
“I think especially in the era of antibiotic resistance, when you’re talking about infections that are less severe, even when antibiotics may help, there may be benefits of not using them,” he said.
The research was funded by the National Institutes of Health. Dr Daum reported advisory board fees from Pfizer and Dynavax and grant funding from Theravance and Merck. Drs Miller, Creech, and Chambers reported a variety of financial disclosures, including grant funding or consulting or advisory board fees involving Abbott, Achaogen, Allergan, AstraZeneca, Cempra, Cepheid, Genentech, GlaxoSmithKline, Gilead Sciences, Merck, Pfizer, Theravance, and/or Tetraphase. Dr Chambers previously held stock in Merck. Dr Keller and Dr Hymes have disclosed no relevant financial relationships.
N Engl J Med. Published online June 28, 2017. Abstract
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