High Rate of Imipenem Non-Susceptibility among Clinical Nocardia spp. Isolated from Lung Transplant Recipients

Abstract

Listen

Translate article

Nocardia spp. cause serious disease in lung transplant recipients, with mortality rates as high as 40%. Dual antibiotic therapy with amikacin and either imipenem or trimethoprim-sulfamethoxazole (TMP-SMX) is commonly recommended as empiric treatment. Imipenem therapy may avoid TMP-SMX and amikacin adverse effects. We evaluated the real-world activity of common antibiotics against Nocardia spp. isolated from lung transplant recipients with clinical nocardiosis. This IRB-approved, retrospective chart review included adults who underwent lung transplant after January 1, 2012 and were diagnosed with nocardiosis posttransplant. Antibiotic susceptibilities were assessed at a national reference lab. Of the 600 patients who underwent lung transplant during the study period, 13 developed nocardiosis, and 11 (85%) had susceptibility data. Of the 13 patients with nocardiosis, interstitial lung disease was the most common transplant indication, and most received basiliximab induction. The most common immunosuppressive regimen at the time of Nocardia spp. isolation was mycophenolate mofetil, tacrolimus, and prednisone. Six patients (46%) had augmented immunosuppression within 6 months before diagnosis with rituximab, anti-thymocyte globulin, or steroid pulse. Nocardiosis occurred a median of 13 months after transplant (range, 6-55); 6 patients had disseminated disease. Eight of the 13 patients (62%) survived 6 months post-diagnosis. Imipenem was active against only 4 isolates (36% susceptibility). Of the 7 non-susceptible isolates to imipenem, only 1 patient had received a carbapenem posttransplant. The most active antibiotics were TMP-SMX (100%), linezolid (100%), and amikacin (91%). The most active β-lactam was ceftriaxone (45%), followed by amoxicillin/clavulanate (40%). Five of the 13 patients (38%) received TMP-SMX for pneumocystis prophylaxis immediately preceding nocardiosis diagnosis. Despite high historical in vitro activity, imipenem was poorly active against these clinical Nocardia spp. Local epidemiologic data are needed to guide empiric therapy. Despite potential toxicities and prior prophylactic use, TMP-SMX should be the backbone of combination therapy, with the second agent selected based on the likelihood of central nervous system disease, susceptibilities, and toxicities.