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Single irrigation of the peri-implant space with a cefazolin-based triple antibiotic solution is a routine antibiotic prophylaxis measure during implant-based breast augmentation and reconstruction. Cefazolin, however, is less efficacious against resistant Staphylococcus species, which are the predominant bacterial species isolated from the peri-implant space. Vancomycin is effective against resistant Staphylococcus species and may be a more appropriate prophylactic agent. The availability of single-injection long-acting anesthetic agents allows the novel use of the elastomeric infusion pump for continuous irrigation of antibiotic solution into the peri-implant space. The efficacy of continuous irrigation with a vancomycin-based solution is evaluated here.Study patients (N = 163; group 1) who underwent immediate, direct-to-implant breast reconstruction received continuous infusion of a vancomycin-based triple antibiotic solution. Patients also received a single injection of liposomal bupivacaine in the pectoralis major/minor muscles for pain control. A historic control group (N = 113; group II) received ropivacaine local anesthetic via the infusion pump and a single intraoperative irrigation of the peri-implant space with the vancomycin-based triple antibiotic solution. Incidence of postsurgical infection during the 6 weeks after surgery was compared between the groups.Group I patients had a statistically significant lower incidence of infections (1.9%) than group II patients (6.4%) (P = 0.007). There were no vancomycin-related adverse effects.Continuous breast irrigation with a vancomycin-based triple antibiotic solution is a safe and effective accompaniment for immediate implant reconstruction. Use of intramuscular anesthetic injection for postoperative pain control allows the elastomeric infusion pump to be available for local tissue antibiotic irrigation.