Table 1.
Clinical Characteristics of 14 Patients with TMP-SMX–associated Respiratory Failure
| Characteristic | Value |
|---|---|
| Median age (range), yr | 16.5 (10–37) |
| Sex, F, n (%) | 9 (64) |
| Race, n (%) | |
| White | 11 (79) |
| Mixed race | 1 (7) |
| Asian | 2 (14) |
| Geographical region, n (%) | |
| Midwest | 6 (43) |
| West | 2 (14) |
| Northeast | 2 (14) |
| Southeast | 4 (29) |
| TMP-SMX exposure | |
| Median duration (range), d | 21 (7–28) |
| Indication for TMP-SMX, n (%) | |
| Acne | 8 (57) |
| Skin or soft tissue infection | 5 (36) |
| Urinary tract infection | 1 (7) |
| Symptoms at hospital admission, n (%) | |
| Any respiratory symptoms | 14 (100) |
| Shortness of breath | 14 (100) |
| Chest pain | 8 (57) |
| Cough | 9 (64) |
| Hypoxemia | 13 (93) |
| Any constitutional symptoms | 11 (79) |
| Fever | 8 (57) |
| Pharyngitis | 4 (29) |
| Malaise | 4 (29) |
| Vital signs at hospital admission, n (%) | |
| Temperature ≥38°C | 8 (57) |
| Heart rate >100 beats/min | 13 (93) |
| Respiratory rate >20 breaths/min | 13 (93) |
| Oxygen saturation on room air | |
| ≥90% | 6 (43) |
| 80–89% | 4 (29) |
| ≤79% | 4 (29) |
| Laboratory results at hospital admission, n (%) | |
| White blood cell count >11,000 × 103/μl | 0 (0) |
| White blood cell count <4,500 × 103/μl | 1 (7) |
| White blood cell count >80% neutrophils | 6 (43) |
| Absolute eosinophil count >500/μl | 0 (0) |
| Creatinine mg/dl >2 × upper limit of normal | 0 (0) |
| Alanine aminotransferase U/L >2 × upper limit of normal | 1 (7) |
| Absolute eosinophil count >500/μl during hospitalization, n/total n (%) | 9/10 (90) |
| Air leak syndrome prior to intubation, n (%) | |
| Pneumomediastinum | 8 (57) |
| Pneumothorax | 5 (36) |
| Median hospital length of stay (range), d | 102 (16–459) |
| Median duration of advanced airway (range), d | 122 (12–455) |
| Tracheostomy, n (%) | 13/14 (93) |
| ECMO, n/total n (%) | 12/14 (86) |
| VV, n/total n (%) | 7/12 (58) |
| VA, n/total n (%) | 1/12 (8) |
| VA to VV or VV to VA, n/total n (%) | 4/12 (33) |
| Median ECMO duration (range), d | 71 (9–193) |
| Ambulating on ECMO, n/total n (%) | 6/12 (50) |
| Treatment, n (%) | |
| Broad-spectrum antimicrobials | 14 (100) |
| Systemic glucocorticoids | 14 (100) |
| Intravenous immunoglobulin | 4 (29) |
| Plasmapheresis | 4 (29) |
| Hydroxychloroquine | 1 (7) |
| Azathioprine | 1 (7) |
| Mycophenolate | 1 (7) |
| Rituximab | 1 (7) |
| Lung pathology, n/total n (%) | 9/14 (64) |
| Biopsy or autopsy consistent with DAIDE | 7/9 (78)* |
| Organ transplant, n/total n (%) | 3/14 (21) |
| Lung | 2/3 (67) |
| Heart/lung | 1/3 (33) |
| Death, n (%) | 5 (36) |
Definition of abbreviations: DAIDE = diffuse alveolar injury with delayed epithelialization; ECMO = extracorporeal membrane oxygenation; TMP-SMX = trimethoprim–sulfamethoxazole; VA = venoarterial; VV = venovenous.
In two specimens in which DAIDE morphology was not observed, one biopsy was on Day 18 of hospitalization; the sample was a small fragment of peripheral lung demonstrating alveolar hemorrhage consistent with the clinical history of hemothorax. The second was explanted lung tissue from a 16-year-old female who received a bilateral lung transplant on Day 98 of hospitalization; this showed advanced-stage fibrosis, lung architecture remodeling, and bronchiolarization consistent with a history of DAIDE but not diagnostic (6).