Antibiotic Tolerability in <i>Nocardia</i> Infection Among Kidney Transplant Recipients: A Multicenter Cohort Study

ABSTRACT Background Nocardia infection is a rare but severe complication in kidney transplant (KT) recipients, with high morbidity and mortality. Data on antibiotic tolerability in this population are scarce. Methods We conducted a retrospective, multicentric study across six Spanish transplant units to analyze clinical characteristics, treatment strategies, and antibiotic tolerability in KT patients diagnosed with Nocardia infection. Results Twenty‐six cases of Nocardia infection were identified, predominantly in elderly male patients with significant comorbidities and a high immunosuppressive burden. Pulmonary involvement was the most common presentation, although extrapulmonary manifestations also occurred. Only 36% of infections occurred within the first posttransplant year. Most patients received initial combination therapy, followed by prolonged treatment—primarily with trimethoprim–sulfamethoxazole (TMP‐SMX) or linezolid. However, antibiotic tolerability was poor: TMP‐SMX was discontinued in 80% of cases due to adverse effects, mainly hyperkalemia, metabolic acidosis, and acute kidney injury. Linezolid was withdrawn in 90% of patients because of myelotoxicity. Tedizolid, used in 38.4% of cases, showed better tolerability, with only 20% of treatment discontinuation and no relapses reported during follow‐up. Overall, mortality during treatment reached 30.8%, mainly due to infectious causes. Conclusions This is the largest series of Nocardia infection in KT recipients in Spain and the first to specifically evaluate antibiotic tolerability. TMP‐SMX and linezolid were poorly tolerated, reinforcing the need for alternative strategies. Tedizolid showed a favorable safety profile and may be considered a promising first‐line option in high‐risk patients. Further prospective studies are needed to confirm these findings and support guideline development.