Alternating Mupirocin/Gentamicin is Associated with Increased Risk of Fungal Peritonitis as Compared with Gentamicin Alone - Results of a Randomized Open-Label Controlled Trial.

UNLABELLED: ♦ BACKGROUND AND OBJECTIVES: Catheter-related infection, namely exit-site infection (ESI) and peritonitis, is a major infectious complication and remains a main cause of technique failure for patients receiving peritoneal dialysis (PD). Topical application of antibiotic cream might reduce catheter-related infection but emergence of resistant or opportunistic organisms could be a concern. Optimal topical agents and regimens remain to be determined. We did a study to examine the effect of an alternating topical antibiotic regimen in preventing catheter-related infection. ♦ METHOD: We performed a single-center, randomized, open-label study to compare daily topical application of gentamicin cream with a gentamicin/mupirocin alternate regimen to the exit site. Patients randomized to alternating regimen were asked to have daily application of gentamicin cream in odd months and mupirocin cream in even months. Primary outcomes were ESI and peritonitis. Secondary outcomes were catheter removal or death caused by catheter-related infection. A total of 146 patients (71, gentamicin group; 75, alternating regimen group) were enrolled with a total follow-up duration of 174 and 181 patient-years for gentamicin and alternating groups, respectively. All patients were followed up until catheter removal, death, transfer to another unit, transplantation or the end of the study on March 31, 2014. There were no significant differences in the age, sex, dialysis vintage, and rate of diabetes, helper-assisted dialysis and methicillin-resistant Staphylococcus aureus (MRSA) carriage state. ♦ RESULTS: No difference was seen in the time to first ESI or peritonitis. However, the time to first gram-negative peritonitis seemed longer for the gentamicin group (p = 0.055). The 2 groups showed a similar rate of ESI (0.17/yr vs 0.19/yr, p = 0.93) but P. aeruginosa ESI was less common in the gentamicin group (0.06/yr vs 0.11/yr, p < 0.001). There was no difference in the incidence of ESI due to non-tuberculous mycobacteria. Peritonitis rate was significantly lower in the gentamicin group (0.22/yr vs 0.32/yr, p < 0.001), with a striking decrease in gram-negative peritonitis (0.08/yr vs 0.14/yr, p < 0.001), and fungal peritonitis (0.006/yr vs 0.03/yr, p < 0.001), which was all antibiotics-related episodes with antecedent use of systemic antibiotics for the treatment of catheter-related infections. There was no significant difference in the catheter loss or death related to catheter-related infection. ♦ CONCLUSION: Alternating gentamicin/mupirocin cream application appeared as effective as gentamicin alone in preventing ESI except for P. aeruginosa. However, it was inferior to gentamicin in the prevention of peritonitis episodes, especially for those caused by gram-negative organisms. It was also not useful in reducing catheter-related infection due to opportunistic organisms but instead associated with a higher incidence of antibiotic-related fungal peritonitis.