We conducted a retrospective, multicenter study of patients with invasive nocardiosis admitted to 22 intensive care units (ICUs) from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique (Grrr-OH) during 2004–2023 in France and Belgium. We established inclusion criteria as unplanned ICU medical admission, age >18 years, and a documented invasive nocardiosis diagnosis (before or during ICU stay). We excluded cases of suspected nocardiosis without microbiological documentation or those with a lack of medical chart data.

Documented nocardiosis was determined by a positive culture for Nocardia species or a Nocardia PCR-based assay coupled with organ involvement. Disseminated nocardiosis was characterized by the infection affecting >2 noncontiguous sites; bacteremia constituted dissemination if 1 organ was involved. Organ failures were identified based on the Sepsis-related Organ Failure Assessment score.

We performed a comparison between patients admitted to the ICU for Nocardia infection and patients enrolled in the HIGH multicenter clinical trial (9), which included immunocompromised patients admitted to the ICU for acute respiratory failure and compared the effect of high-flow nasal oxygen versus standard oxygen on 28-day mortality. We excluded diagnoses of Pneumocystis infection, acute pulmonary edema, and specific lung lesions, which we assumed could be easily distinguished from nocardiosis.

We present continuous data as median (interquartile range) and categorical data as numbers and percentages. We compared characteristics between our cohort and data from the HIGH clinical trial by using a Wilcoxon rank-sum test (continuous variables) or Fisher exact test (categorical variables). We used only variables that were statistically significant (p<0.05) in univariate analysis in multivariate analysis and conducted an assessment of collinearity. We performed 2-sided statistical analyses by using R statistical software version 2023.03.0+386 (The R Foundation for Statistical Computing, https://www.r-project.org).

In total, we studied 50 patients with invasive nocardiosis who were admitted to the ICU. The median age was 59 (47–67) years; 39 (78%) were men, and 11 (22%) were women. We took into account such details as patient demographics, concurrent diseases, and immunosuppressive therapies (Table 1). Almost all patients (46 [92%]) were immunocompromised; the primary causes were solid organ transplantation (18 [36%]), systemic autoimmune diseases (12 [24%]), and hematologic malignancies (10 [20%]). Steroid therapy was administered to most patients (34 [68%]). Low-dose trimethoprim/sulfamethoxazole prophylaxis was given to 12 (24%) patients.

We noted disseminated infection in almost half of the patients (48%); the most frequently involved organs were lungs (98%), central nervous system (47%), and skin (20%) (Table 2). At admission to intensive care, 33 (66%) patients had acute respiratory distress and 19 (38%) experienced coma (defined by a Glasgow Coma Scale score ≤8) or septic shock. Overall, 45 (90%) patients exhibited >1 organ failure; the most common were respiratory failure (33 [66%]) and multiorgan dysfunction (25 [50%]). Computed tomography scans revealed alveolar consolidations in 43 (86%) patients and cavitated nodules in 26 (52%) patients. Magnetic resonance imaging of the brain in 23 (46%) patients revealed multiple lesions in 14 (61%) patients and brain herniation in 6 (26%) patients.

Most (62%) patients received dual therapy or triple therapy, including aminoglycosides (10 [20%]), most commonly trimethoprim/sulfamethoxazole (80%) and carbapenem (51%) (Appendix Table 1). Upon admission to the intensive care unit, 32 patients (63%) required oxygen support, and 19 (38%) required mechanical ventilation. The ICU mortality rate was 22%, and the all-cause mortality rate at 1 year was 44%. In multivariable analysis, factors significantly associated with 1-year mortality included vasopressor use, fungal coinfection, and neurologic involvement (Appendix Table 2).

Figure

Figure. Comparison between nocardiosis and other immunocompromised pneumonia in a study of patients admitted to intensive care units in France and Belgium during 2004–2023. Other immunocompromised pneumonia data extracted from the...

We compared cases of Nocardia infection against cases of other immunocompromised pneumonia in patients admitted to the ICU (2,11) (Figure; Appendix Table 3). Patients with Nocardia infection were younger and had a higher prevalence of autoimmune diseases and solid organ transplants. Lung consolidation (86% vs. 27%; p = 0.001) and cavitated nodules (52% vs. 1%; p = 0.001) were significantly more frequent. Upon admission to the ICU, patients with nocardiosis were rated as more severe on the Sepsis-related Organ Failure Assessment and Glasgow Coma Scale compared with patients with other immunocompromised pneumonia, but there was no significant difference in ICU mortality (22% vs. 32%; p = 0.184).

Based on the findings for our study population, critically ill patients with nocardiosis exhibit frequent and severe pulmonary and neurologic involvement; 44% of patients die (22 of 50) and 14% (7 of 50) experience disability at the 1-year mark. Several cohorts have documented Nocardia infections within diverse immunocompromised populations, reporting mortality rates of 16%–40% (3,4). In our analysis, we conducted a comparative assessment with other pneumonia cases in immunocompromised patients (9) to elucidate situations warranting consideration of Nocardia infection. Cellular immunosuppression appears to be necessary for the development of a severe Nocardia infection, which is consistent with previous studies (4,6,10), particularly among organ transplant recipients, patients with systemic autoimmune diseases, and those with hematologic malignancies. Co-infections, particularly fungal ones, were reported as an independent prognostic factor for mortality in this population (11) and could partially explain this initial severity. Such findings highlight the burden of immunosuppression and the need for vigilance in assessing concurrent infections in this population. Two recent studies suggest that trimethoprim/sulfamethoxazole could be protective against Nocardia infections (11,12). Because invasive Nocardia infections are rare, results of our study may lack statistical power, and significant prognostic or distinctive factors might have gone unnoticed. However, we believe the inclusion of patients from 22 ICUs, with few cases missing data, provides a relevant overview of nocardiosis in critically ill patients.

In summary, in this study of critically ill patients with nocardiosis, we observed high mortality rates, posing a diagnostic challenge for critical care practitioners. Our findings emphasize the need for a heightened level of vigilance in monitoring patients for Nocardia infection in the intensive care setting, especially among immunocompromised patients who exhibit pulmonary nodules and neurologic involvement.