A Young Man With an Infection of the Arm: Antibiotic Therapy Decision-Making

A 24-year-old man presented for evaluation and treatment of a skin infection on his left arm. The infection had begun as an inflamed area on the dorsum of his left arm, roughly one-third of the way up from his wrist. The area was red, warm, and tender, but over the last 36 hours, the pain had worsened, and the area now had an exquisitely tender, shiny, red “pimple” at its center.

History and Physical Examination

He was otherwise very healthy, with no chronic medical diagnoses, and he was on no medications. He remembered having had a drug allergy as a boy but was not sure whether it was to penicillin. He enjoys athletics, and this infection had occurred during his participation in a summer recreational ice hockey league. The lesion had developed where the upper part of his hockey glove contacted his arm.

Physical examination revealed an otherwise healthy young man who was afebrile with normal vital signs. The only abnormal finding was a 5-cm, warm, red, exquisitely tender lesion on the dorsal aspect of his left forearm. At its center was a thinned, shiny area, measuring approximately 1 cm, which was fluctuant. There were no other lesions anywhere else on his skin. There was no lymphangitic streaking or axillary adenopathy.

Findings of a complete blood count included a white blood cell count of 12,900/µL, with a few band forms noted on the differential. An incision and drainage (I&D) resulted in the expression of several milliliters of purulent material and significant pain relief.

Which one of the following statements about this clinical vignette is most accurate?

A. Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred antibiotic for cellulitis, but clindamycin should be used when there is abcess formation.
B. Either clindamycin or TMP-SMX following I&D have equivalent eficacy and adverse effect profiles.
C. Clindamycin is the preferred therapy, with increased efficacy for cure, but it is associated with an increased toxicity profile.
D.  Adverse effects of antibiotics, such as diarrhea, can be expected to occur in only a small minority of patients.

Answer and discussion on next page.

Correct Answer: B

The patient presented here exemplifies the current situation of community-acquired skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) species. Variant MRSA species acquired in the hospital setting have been a serious nosocomial infection problem for decades. However, since the 1990s, community-acquired MRSA species, which have acquired antibiotic resistance yet have retained the intrinsic invasiveness and pathogenicity of community-acquired staphylococci, have become very common and a public health problem.^1-4

These organisms can be quite invasive, pathogenic, and communicable (as with contaminated surfaces and athletic equipment). They cause a wide array of skin infections, including cellulitis and abscesses; in a small percentage of cases, they cause more serious, deep infections such as osteomyelitis, leading to prolonged morbidity and a requirement for prolonged antibiotic therapy.^1,2

Choosing an effective yet safe initial antibiotic is important in outpatient cases of such skin infections. Happily, recent high-quality studies have yielded data providing guidance in managing this very common situation.

In one recent study, Miller and colleagues³ provided data regarding the currently accurate epidemiology/bacteriology of “uncomplicated” skin infections and reported the results of therapy using 2 relatively easy oral, outpatient antibiotic regimens. Their study of more than 500 cases in real-life situations demonstrated that cultures are obtained in approximately 56% of patients, with 40% of the cultures positive for S aureus, and 32% of those being MRSA. Stated another way, because approximately 50% of skin infections in which cultures are obtained prove to be MRSA, these organisms should be presumed to be causative, and empiric regimens should be directed at them.^2,3

Which Antibiotic Regimen is Better?

As to which regimen or regimens should be used, the authors randomly assigned patients to 1 of 2 arms: either 300 mg clindamycin 3 times daily, or 160 mg TMP and 800 mg SMX twice daily for 10 days. Of note, inclusion criteria comprised skin infections of significance, including abscess even greater than 5 cm, in addition to the presence of cellulitis alone. Of course, if there was abscess formation, appropriate I&D was included along with the antibiotics.

The results of Miller and colleagues’ study were very reassuring. Both of the antibiotic regimens demonstrated equivalent, excellent efficacy, with approximately a 90% cure rate documented at a visit at the completion of antibiotic regimen (approximately day 12-14), and an 83.9% cure rate for clindamycin versus a cure rate of 78.2% for TMP-SMX at the 1-month follow-up visit. There was no statistically significant difference between these regimens at either marker.

Additionally, the rate of adverse events also was essentially identical for clindamycin and TMP-SMX, including diarrhea (9.7% and 10.1%, respectively) and allergic manifestations of pruritus/rash (2.7% and 2.0%, respectively), despite clindamycin’s reputation for associated diarrhea and TMP-SMX’s reputation for associated allergy/rash. Of particular note, no case of Clostridium difficile-associated diarrhea was encountered. Therefore, one can conclude that good outcomes can be achieved in uncomplicated skin infections using a regimen of either clindamycin or TMP-SMX, and both regimens deliver their efficacy with a very satisfactory and acceptable incidence of adverse events (approximately 18%), essentially all of which are mild to moderate and resolve without sequelae.

The data presented makes Answer B the correct answer. Answer A is not correct, since abscess formation was not a discriminant determinant regarding efficacy of either antibiotic regimen. Answer C is not correct, since clindamycin is associated with neither enhanced efficacy nor an increased toxicity profile. Finally, although both regimens have equivalent diarrhea incidence, with prompt resolution without sequelae and essentially nil incidence of C difficile colitis, one can expect diarrhea in approximately 10% of cases. Answer D understates this (“a small minority”) and is not correct.

Outcome of the Case

Based on the vague history of having had some sort of drug allergy, the patient was started on clindamycin, 300 mg, 3 times a day. In addition, local wound care with packing, and local care of the abscess was arranged. He improved clinically over the next 2 weeks, and at 1 month he had experienced complete resolution of the lesion, with no recurrence after a week off antibiotics. He experienced a slight increase in bowel movements that was not problematic. To avoid potential reinfection with MRSA, he will be purchasing new equipment for the fall and winter hockey season.

Ronald Rubin, MD, is a professor of medicine at the Temple University School of Medicine and is chief of clinical hematology in the Department of Medicine at Temple University Hospital, both in Philadelphia, Pennsylvania.

References:

1. Hersh AL, Chambers HF, Maselli JH, Gonzales R. National trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections. Arch Intern Med. 2008;168(14):1585-1591.
2. Pallin DJ, Egan DJ, Pelletier AJ, Espinola JA, Hooper DC, Camargo CA Jr. Increased US emergency department visits for skin and soft tissue infections, and changes in antibiotic choices, during the emergence of community-associated methicillin-resistant Staphylococcus aureus. Ann Emerg Med. 2008;51(3):291-298.
3. Miller LG, Daum RS, Creech CB, et al; DMID 07-0051 Team. Clindamycin versus trimethoprim–sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372(12):1093-1103.
4. Wessels MR. Choosing an antibiotic for skin infections. N Engl J Med. 2015;372(12):1164-1165.