By Dean L. Winslow, MD, FACP, FIDSA

Dr. Winslow is Chairman, Department of Medicine, Santa Clara Valley Medical Center, Clinical Professor of Medicine and Pediatrics (Affiliated), Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine.

Dr. Winslow reports no financial relationships relevant to this field of study. SYNOPSIS: Five hundred twenty-four children and adults with either cellulitis or abscesses larger than 5 cm (smaller for children) were enrolled in a multisite prospective study of clindamycin vs. trimethoprim-sulfamethoxazole dosed for 10 days. Cure rates did not differ between the treatments, and rates of adverse events were similar in the two groups.

SOURCE: Miller LG, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med 2015;372:1093-1103.

Five hundred twenty-four patients (including 155 children) were enrolled in a prospective, double-blinded, randomized trial of clindamycin vs. trimethoprim-sulfamethoxazole in uncomplicated skin infections. Fifty-three percent had cellulitis, 31% had abscesses, and 16% had mixed cellulitis/abscess. Staphylococcus aureus was isolated from 41% of patients, and 77% of these were methicillin-resistant S. aureus (MRSA). Overall cure rates were 80% in the clindamycin group and 78% in the trimethoprim-sulfamethoxazole group. Cure rates did not differ significantly between the two antibiotics in the subgroups of children, adults, and abscess vs. cellulitis. Rates of adverse events were similar in the two groups.

COMMENTARY

While this study is a bit difficult to interpret due to a mix of cellulitis (non-suppurative) and abscess (suppurative), the data are important since it is a large study and addresses a real-world question of which of two reasonable choices of antibiotics works best in uncomplicated skin infections commonly encountered in the primary care and emergency department (ED) setting.

It could be argued that inclusion of a placebo arm would have been helpful since previous studies suggest that incision and drainage alone is appropriate treatment for small abscesses and antibiotics are not necessary. However, an earlier study performed in children demonstrated that abscesses larger than 5 cm were often associated with treatment failure unless adjunctive antibiotics were administered.1 As expected, cultures were not obtainable in patients with cellulitis without abscess (and presumably were almost always due to beta-hemolytic streptococci). The surprisingly high response rate of cellulitis to trimethoprim-sulfamethoxazole suggests that the historical concern about poor activity of trimethoprim-sulfamethoxazole against streptococci may be unfounded. Interestingly, a recent study showed that S. pyogenes are generally trimethoprim-sulfamethoxazole susceptible if low-concentration thymidine agar is used for susceptibility testing.2

The rates of S. aureus resistance to clindamycin and trimethoprim-sulfamethoxazole were 5.2% and 0.2%, respectively, and although a slightly lower cure rate was seen with clindamycin in those rare clindamycin-resistant strains of Staph (73% with clindamycin vs. 92% with trimethoprim-sulfamethoxazole), this should not necessarily preclude the empiric use of clindamycin in uncomplicated skin infections where close follow up can be assured. Interestingly, no cases of C. difficile infection were seen in either arm of the study, suggesting that this is not a serious concern in this relatively young and healthy population when only a 10-day course of therapy is prescribed.

The results of this study did reinforce a couple of things I teach the residents and fellows.1 Clindamycin is a great antibiotic for skin (and bone) infections as long as one knows that the Staph. aureus is susceptible in vitro. Clindamycin is just as effective and as well tolerated as linezolid — and much less expensive.2 It adds further evidence to support my dislike of the common ED practice of prescribing both cephalexin and trimethoprim-sulfamethoxazole to patients with skin infections. (My fear is that when a patient treated with this combination develops a rash, then they are often labeled for life as being “allergic to beta-lactam antibiotics and sulfonamides.”) This should reassure the practitioner that despite our previous concerns, trimethoprim-sulfamethoxazole probably treats uncomplicated streptococcal skin infections adequately.

REFERENCES

  1. Lee MC, et al. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatr Infect Dis J 2004;23:123-127.
  2. Bowen AC, et al. Is Streptococcus pyogenes resistant or susceptible to trimethoprim-sulfamethoxazole? J Clin Microbiol 2012;50:4067-4072.