Risk factors and prophylaxis for nocardiosis in solid organ transplant recipients: A nested case‐control study

Abstract

Background: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis. Methods: We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients.Results: One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35).Conclusions: Multiple measures of immunosuppression and lack of trimethoprimsulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients.Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

Outcomes of transplant recipients with pretransplant Nocardia colonization or infection

“…33 There is mixed evidence regarding the effectiveness of primary prophylaxis, although studies where TMP-SMX prophylaxis was dosed more frequently have tended to show a greater effect. [8][9][10]12 In this study, prophylaxis was almost universally dosed at least daily, which may have impacted outcomes. Additionally, Nocardia may be related to specific activities and exposures, most notably outdoor activities such as gardening.…”

“…These patients all received TMP-SMX prophylaxis, and its role in reducing risk of posttransplant nocardiosis warrants further study. Due to the overlap in risk factors between Nocardia and Pneumocystis, [9][10][11] TMP-SMX should be preferentially used rather than alternative Pneumocystis prophylaxis agents among patients with a history of nocardiosis and heightened immunosuppression. In addition, based on these patients and existing literature suggesting higher or more frequently dosed TMP-SMX prophylaxis may be effective in preventing nocardiosis, 10,33 we would suggest TMP-SMX prophylaxis be dosed as 80-400 mg daily or 160-800 mg thrice-weekly for the typically recommended duration for posttransplant Pneumocystis prophylaxis.…”

“…[3][4][5][6][7][8] Several studies have examined risk factors for nocardiosis among transplant recipients, largely noting different measures of immunocompromise or posttransplant complications being associated with greater risk of Nocardia infection. [8][9][10][11] Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis has shown mixed results in SOT and HSCT populations. 3,5,[8][9][10][11][12] Importantly, nocardiosis has been associated with increased mortality among transplant recipients, with several factors such as underlying comorbidities increasing this risk.…”

“…[8][9][10][11] Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis has shown mixed results in SOT and HSCT populations. 3,5,[8][9][10][11][12] Importantly, nocardiosis has been associated with increased mortality among transplant recipients, with several factors such as underlying comorbidities increasing this risk. 10,11,[13][14][15] As an intracellular pathogen with the capability to evade host immune response that relies on cellular immunity, Nocardia recurrence has been described in approximately 5% of SOT recipients.…”

“…3,5,[8][9][10][11][12] Importantly, nocardiosis has been associated with increased mortality among transplant recipients, with several factors such as underlying comorbidities increasing this risk. 10,11,[13][14][15] As an intracellular pathogen with the capability to evade host immune response that relies on cellular immunity, Nocardia recurrence has been described in approximately 5% of SOT recipients. 14,16,17 However, little data exist regarding any impact of pretransplant Nocardia infection or colonization on posttransplant outcomes.…”