Antibiotic Prophylaxis May Lower SSIs in Skin Cancer Surgery

Nancy A. Melville

June 09, 2023

Delivering microdose incision-site injections of clindamycin significantly reduced the rate of surgical site infections (SSIs) in skin cancer surgery.

However, prophylaxis with flucloxacillin did not significantly lower SSI rates compared with not using incision site antibiotics.

The rate of postoperative SSIs was 2.1% in the clindamycin arm, vs 5.7% in the control arm and 5.3% in the flucloxacillin arm.

"Based on these results, we recommend the routine adoption of incisional microdosed clindamycin for patients undergoing skin cancer surgery," the study authors conclude. "This strategy appears suitable for widespread implementation because of the magnitude of the effect observed and the absence of adverse events."

The study was published online late last month in JAMA Surgery.

Skin cancer surgery carries a high risk of SSIs, which represent costly yet largely preventable complications of surgery.

Despite the risk, there's a lack of evidence from randomized clinical trials of the role of antibiotic prophylaxis in reducing rates of SSIs among patients undergoing skin cancer surgery. Previous studies have investigated incisional antibiotic prophylaxis to reduce SSIs with Mohs micrographic surgery, but these surgeries represent a relatively small proportion of overall skin cancer surgeries.

To understand whether this benefit extends to more general skin cancer surgeries, investigators recruited patients from a high-volume skin cancer center in New Zealand who were treated from February to July 2019. In the double-blind, prospective PICASSo trial, patients were randomly assigned to receive an incision site injection of buffered local anesthetic alone (control group), buffered local anesthetic with microdoses of flucloxacillin (500 μg/mL), or buffered local anesthetic with microdoses of clindamycin (500 μg/mL). The most common surgery type was excision and direct closure (approximately 80% in all arms), and the mean volume injected per length of direct closure was 1.5 mL/cm.

The primary endpoint was the rate of postoperative SSIs, defined as a postoperative wound infection score of 5 or more. The SSI rate was calculated as the number of lesions with SSIs per total number of lesions in the group.

Overall, 681 patients with 1133 total lesions were included in the study. Compared with the control arm, the rate of postoperative SSIs was nearly threefold lower among patients who received clindamycin — 2.1% (9 of 422) vs 5.7% (22 of 388) in the control arm (P = .01 for clindamycin vs control).

However, flucloxacillin did not demonstrate the same effectiveness. The flucloxacillin arm and the control arm demonstrated similar postoperative SSI rates — 5.3% (17 of 323) vs 5.7%.

The results were similar after adjusting for baseline differences and lesion ulceration.

The researchers also found that the proportion of lesions that required postoperative systemic antibiotics was four times higher among the control arm in comparison with the clindamycin arm (8% vs 2.1%; P < .001). It was two times higher than in the flucloxacillin arm (8% vs 4%; P = .03).

Treatment with microdoses of incisional flucloxacillin and clindamycin was safe and well tolerated.

The researchers speculated that clindamycin's greater effectiveness may come down to its slightly broader coverage of commonly cultured bacteria in skin and soft tissue infections, including community-associated methicillin-resistant Staphylococcus aureus. Clindamycin is known to have more efficacy against anaerobic bacteria that may be lurking in chronically ulcerated skin lesions and is associated with less local tissue inflammation compared with flucloxacillin.

Overall, "clindamycin was significantly more effective at preventing SSI than flucloxacillin in our study," the authors conclude. They note that the use of clindamycin as a first-line prophylaxis agent against SSIs for patients undergoing skin cancer surgery is a practical option.

"These results establish evidence-based guidelines for antibiotic prophylaxis in one of the most common surgical interventions performed worldwide, where they have been previously absent," the researchers say.

The authors of an editorial published with the study underscore other advantages of incisional microdosing with antibiotics.

"One advantage of cutaneous antibiotic administration is improved drug delivery to poorly perfused tissue, which would have limited reach by the systemic circulation," wrote Amanda R. Sergesketter, MD, of Duke University, Durham, North Carolina, and Scott T. Hollenbeck, MD, of the University of Virginia, Charlottesville.

"While not evaluated in this study, local antibiotic delivery may be especially relevant to larger and more complex wounds," the editorialists say. They note that the next step for future studies should be to evaluate prophylaxis in more complex situations.

"Such studies should be considered enthusiastically, given the clearly favorable impact on surgical site infections demonstrated in the PICASSo trial," Sergesketter and Hollenbeck say.

The study was supported by a grant from the New Zealand Health Research Council. Hollenbeck reported educational grants to Duke University from Allergan, Acelity, Synovis, Integra, Smith & Nephew, Stryker, Cook, KLs Martin, Bard, VOptix, Scanlan, True Digital Surgery, Nautilus, Mitaka, Checkpoint Surgical, and Omniguide, and he is a founder and equity holder for InSoma Bio, a premarket company focused on tissue regeneration.

JAMA Surg. Published May 24, 2023. Abstract, Editorial

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