Effect of combination antibiotic therapy on clinical failure rate for skin and soft tissue infections

Background

Despite guideline recommendations for skin and soft tissue infection (SSTI) consisting of empirical single antibiotic therapy, multiple studies have evaluated the use of a first-generation cephalosporin and sulfamethoxazole-trimethoprim or clindamycin to optimize coverage for staphylococcal and streptococcal species. No studies have evaluated a tetracycline with a cephalosporin for this indication.

Objective

This study evaluated combination therapy with doxycycline plus cephalexin compared with cephalexin or doxycycline alone in SSTI.

Methods

This retrospective, single-center cohort study, conducted at an academic medical center, included consecutive adults who visited the emergency department (ED) with an SSTI, identified with ICD-10 codes, and received a prescription for cephalexin, doxycycline, or both. Admitted patients or those with antibiotics in the previous 30 days or wound care for chronic infections were excluded. The primary outcome was clinical failure defined as documented worsening of infection or incision and drainage (I&D) on follow-up, change in antibiotic, or subsequent hospitalization. Chi-square test was used for the primary outcome.

Results

Patients (N = 419) were predominately white, Hispanic, males with a mean age of 46 ± 16 years, and consistent between groups. History of intravenous drug use was present in 23% of patients, most often in the doxycycline (30%) or combination groups (30%). Clinical failure occurred in 49 patients (12%). There was no difference in clinical failure between cephalexin and combination therapy (17 vs. 13, P = 0.45) or doxycycline versus combination therapy (19 vs. 13, P = 0.27). The predominant reason for clinical failure was worsening of infection (31), followed by change in antibiotic (18) and hospitalization (16). I&D predominately occurred in the doxycycline (44%) and combination groups (30%), with methicillin-resistant Staphylococcus aureus being the most commonly identified organism (15).

Conclusion

In ED patients with SSTI, single antibiotic therapy did not result in increased incidence of clinical failure compared with combination therapy with a first-generation cephalosporin and tetracycline.