Table 1.
Factors Associated With 1-Year All-Cause Mortality in Univariate Analysis Among the 117 Patients With Post-Solid Organ Transplantation Nocardiosis
| Characteristic |
Dead at 1 Year, n = 19 |
Alive at 1 Year, n = 98 |
P Value |
|---|---|---|---|
| Clinical characteristics | |||
| Age at diagnosis (y) (mean ± SD) | 61.4 (12.3) | 54.5 (13.5) | .07 |
| Male (n, %) | 14 (73.7) | 60 (61.2) | .44 |
| Charlson comorbidity indexa at diagnosis n = 112 (mean, SD) | 4.13 (1.7) | 3.71 (1.8) | .34 |
| History of tumorb n = 112 | 3 (18.8) | 5 (5.2) | .08 |
| Transplantation characteristics | |||
| History of previous transplant | 1 (5.2) | 17 (17.3) | .30 |
| Donor age (y) (mean ± SD) n = 110 | 54.5 (15.8) | 46.0 (16.8) | .044 |
| Deceased donor (vs living) | 18 (94.7) | 89 (90.8) | 1 |
| Nonthoracic (pancreas, liver, kidney) organ | 12 (63.2) | 66 (67.3) | .79 |
| Immunosuppressive regimen and rejection data | |||
| Cyclosporine A at diagnosis | 4 (21.1) | 17 (17.3) | .75 |
| Tacrolimus at diagnosis | 15 (78.9) | 78 (80.0) | 1 |
| High calcineurin inhibitor level in the month before Nocardia infection | 5 (26.3) | 46 (46.9) | .16 |
| Use of antiproliferative agents (azathioprine or mycophenolate mofetil) at diagnosis | 14 (73.7) | 81 (82.7) | .35 |
| Corticosteroids at diagnosis (mgc) (mean ± SD) n = 115 | 7.0 (4.0) | 9.1 (7.2) | .12 |
| Acute rejection episode in the year before diagnosis n = 116 | 2 (10.5) | 30 (30.6) | .09 |
| Acute rejection episode in the 6 months before diagnosis n = 116 | 1 (5.3) | 24 (24.5) | .07 |
| High-dose steroids in the 6 months before diagnosis n = 116 | 1 (5.3) | 19 (19.4) | .19 |
| Plasma exchange in the 6 months before diagnosis n = 116 | 0 (0) | 5 (5.1) | .59 |
| Depleting antibodiesd (antithymocyte globulin or rituximab) in the 6 months before diagnosis n = 116 | 0 (0) | 6 (6.1) | .59 |
| SXT prophylaxis at diagnosis | 2 (10.5) | 19 (19.4) | .52 |
| Associated infectious diseases | |||
| CMV infection in the 6 months before diagnosis | 3 (15.8) | 14 (14.3) | 1 |
| CMV disease in the 6 months before diagnosis | 2 (10.5) | 3 (3.1) | .19 |
| CMV serostatus | .67 | ||
| Low risk: D-R- | 5 (26.3) | 17 (17.3) | |
| Intermediate risk: D-R+ or D+R+ | 10 (52.6) | 50 (51.0) | |
| High risk: D+R- | 4 (21.1) | 27 (27.6) | |
| Bloodstream infection in the 6 months before diagnosis | 1 (5.3) | 5 (5.1) | 1 |
| Additional pathogene at diagnosis | 12 (63.2) | 28 (28.6) | <.01 |
| Fungal infectionf in the 6 months before diagnosis n = 112 | 6 (37.5) | 13 (13.5) | .029 |
| Biological characteristics | |||
| Glomerular filtration rateg (mL/min/1.73 m2) at diagnosis (mean, SD) n = 115 | 41.4 (24.3) | 50.1 (27.6) | .19 |
| White blood cell count at diagnosis (×1000/mm3) (mean, SD) n = 115 | 11.3 (5.8) | 11.5 (6.7) | .88 |
| Neutrophil count at diagnosis (×1000/mm3) (mean, SD) n = 105 | 9.5 (5.6) | 9.8 (6.7) | .98 |
| Lymphocyte count at diagnosis (×1000/mm3) (mean, SD) n = 105 | 0.6 (0.4) | 0.8 (0.6) | .35 |
| C-reactive protein at diagnosis (mg/L) (mean, SD) n = 109 | 91.8 (67.5) | 128.4 (90.9) | .13 |
| Nocardiosis characteristics and treatment | |||
| Time from transplantation to diagnosis (days) (mean, SD) | 1611.7 (1692.7) | 976.2 (1277.7) | .046 |
| Time from symptoms to diagnosis (days) (mean, SD) n = 114 | 19.4 (18.4) | 25.9 (24.1) | .21 |
| Disseminated infection | 9 (47.4) | 41 (41.8) | .85 |
| Lung or pleural involvement | 16 (84.2) | 85 (86.7) | .72 |
| Central nervous system involvement | 8 (42.1) | 22 (22.4) | .13 |
| Skin and soft-tissue involvement | 5 (26.3) | 32 (32.7) | .78 |
| Bloodstream infection | 2 (10.5) | 7 (7.1) | .64 |
| Nocardia species | .33 | ||
| N. farcinica | 8 (42.1) | 33 (33.7) | |
| N. non-farcinica | 11 (57.9) | 65 (66.3) | |
| Strain susceptible to SXT n = 113 | 14 (73.7) | 85 (86.7) | .44 |
| Appropriate antibioticsh during the first 2 weeks of treatment n = 111 | 15 (88.2) | 90 (95.7) | .23 |
| Administration of carbapenems, 3GC,i amikacin, or SXT during the first 2 weeks of treatment n = 113 | 15 (83.3) | 89 (93.7) | .15 |
| Bactericidal antibiotic (carbapenems, 3GC,i amikacin) during the first 2 weeks of treatment n = 109 | 10 (62.5) | 56 (60.2) | 1 |
| Association of 2 appropriate antibiotics during the first 2 weeks of treatment n = 111 | 7 (41.2) | 41 (43.6) | 1 |
| Antibiotic-related adverse effects n = 116 | 9 (47.4) | 45 (46.4) | 1 |
| Need for surgery | 4 (21.1) | 19 (19.4) | 1 |
Data are n (%) unless otherwise indicated. Diagnosis is the date of the diagnosis of nocardiosis, and n is the number of data analyzed (when <117).
Abbreviations: CMV, cytomegalovirus; D, donor; R, recipient; SD, standard deviation; SXT, trimethoprim–sulfamethoxazole.
aApart from “history of tumor,” none of the other individual variables of the Charlson comorbidity index were associated with 1-year mortality, with P values >.2.
bDefined as a nonmetastatic tumor (if active or initially treated in the 5 years before diagnosis of nocardiosis; n = 7) or metastatic solid tumor (n = 1).
cAll corticosteroid doses are expressed in milligrams of methylprednisolone equivalent per day.
dIn the 6 months before diagnosis of Nocardia infection, none of our patients received other types of lymphocyte-depleting or modulating antibodies.
eFifty-one additional microbial pathogens were identified at the time of nocardiosis among 40 patients, including 19 fungi, 11 CMV, 8 gram-negative bacteria, 4 gram-positive bacteria, 3 Clostridium difficile, 2 Legionella spp., 1 human herpesvirus 8, 2 other viruses, and 1 Toxoplasma gondii.
fNineteen patients experienced at least 1 invasive fungal infection (10 aspergillosis, 3 mucormycosis, 3 invasive candidiasis, 2 Alternaria spp., 1 Fusarium spp., 1 Scedosporium spp., 1 Pneumocystis).
gAs estimated by modification of diet in renal disease (MDRD) formula.
hAppropriate antibiotic is defined as a drug with demonstrated in vitro activity against the isolated Nocardia strain.
i3GC is the third-generation cephalosporin (restricted to ceftriaxone and cefotaxime).