Introduction
TMP (mg/kg/day) | SMX (mg/kg/day) | Standard dose used in the study | |
---|---|---|---|
High dose | 15–20 | 75–100 | Not used |
Intermediate dose | 10–15 | 50–75 | 2400 mg b.i.d. |
Low dose | 4–6 | 20–30 | 960 mg b.i.d. |
Methods
Setting and study population
Treatment conditions
Data collection and analyses
Results
Study cohort
Clinical characteristics at presentation
Step-down group (n = 24) | Intermediate-dose group (n = 80) | Risk ratioa (95 % CI) |
p value#
| |
---|---|---|---|---|
Clinical parameters at admission | ||||
Gender M/F ratio | 16/8 | 46/34 | 1.36 (0.64–2.87) | 0.42 |
Age (years) | 61 (47–71) | 60 (49–64) | 0.43 | |
Age > 50 years | 17 (71) | 59 (74) | 0.89 (0.46–1.93) | 0.78 |
Age > 65 years | 9 (38) | 21 (44) | 1.55 (0.77–3.14) | 0.23 |
Duration of respiratory symptoms at diagnosis | 7 (3–19) | 10 (3–14) | 0.87 | |
Temperature (°C) | 37.8 (37.3–38.8) | 37.7 (37.0–38.3) | 0.27 | |
Respiratory rate (breaths per min) | 24 (20–30) | 23 (16–30) | 0.33 | |
Underlying condition | ||||
HIV infection | 5 (21) | 12 (15) | 1.35 (0.58–3.11) | 0.50 |
Solid organ transplantation | 6 (25) | 27 (34) | 0.72 (0.31–1.64) | 0.42 |
Haematology malignancy | 7 (29)b
| 25 (31) | 0.93 (0.43–2.01) | 0.85 |
Other | 7 (29) | 16 (20) | 1.44 (0.68–3.07) | 0.34 |
Laboratory results | ||||
Leukocyte count (×109/l) | 7.2 (3.6–10.9) | 7.2 (4.8–11.3) | 0.91 | |
Leukocyte count elevated (>ULN) | 8 (33) | 26 (33) | 1.00 (0.48–2.13) | 0.97 |
C-reactive protein (mg/l) | 74 (36–153) | 92 (48–194) | 0.43 | |
C-reactive protein >100 mg/l | 10/21 (48) | 28/61 (46) | 1.05 (0.50–2.20) | 0.89 |
Creatinine (µmol/l) | 86 (74–134) | 88 (64–147) | 0.52 | |
Creatinine elevated (>1.5 ULN) | 5 (21) | 20 (25) | 0.82 (0.34–1.97) | 0.65 |
Lactate dehydrogenase elevated (>1.5 ULN) | 7/23 (30) | 42/78 (54) | 0.46 (0.21–1.03) |
0.048
|
PaO2 (kPa) | 7.9 (6.5–9.2) | 7.9 (6.9–8.8) | 0.84 | |
Indication for steroid treatment [PaO2 (kPa) < 9.0] | 11/16 (69) | 48/61 (79) | 0.67 (0.27–1.68) | 0.40 |
Start steroid schedule at diagnosis | 21/23 (91) | 55/65 (85) | 1.67 (0.44–6.17) | 0.42 |
Outcome of diagnostic methods on BAL | ||||
PCR positive | 24 (100)c
| 76 (100)d
| – | – |
Microscopy positive | 14/20 (70) | 41/72 (57) | 1.49 (0.66–3.72) | 0.29 |
C
t value | 33.7 (30.4–34.6) | 34.1 (30.7–37.1) | 0.74 |
Mortality and relapse
Step-down group (n = 24) | Intermediate-dose group (n = 80) | Risk ratioa (95 % CI) |
p value#
| |
---|---|---|---|---|
ICU admission and hospital stay | ||||
ICU admission | 4 (17) | 26 (33) | 0.49 (0.18–1.32) | 0.13 |
Length of hospitalization (days) | 15 (9–24) | 15 (8–33) | 0.91 | |
Toxicity | ||||
(Pre-switch) in file reported TMP–SMX toxicity | 5 (21) | 4 (5) | 2.78 (1.37–5.65) |
0.02
|
Outcome | ||||
30-day relapse rate | 1 (4) | 0 | – | 0.06 |
30-day mortality | 1 (4) | 13 (16) | 0.28 (0.04–1.91) | 0.13 |
100-day mortality | 2 (8) | 20 (25) | 0.34 (0.09–1.33) | 0.08 |
Patient | Age | Sex | Underlying condition | Duration of symptoms (days) | PaO2 (kPa) | Respiratory rate (bpm) | ICU admission (duration in days) | TMP–SMX regimen | Treatment duration at death (days) | Cause of death |
---|---|---|---|---|---|---|---|---|---|---|
1 | 36 | V | Kidney transplantation | NA | 6.6 | NA | Yes (11) | ID | 14 | Respiratory failure |
2 | 73 | M | Pulmonary fibrosis | 15 | 6.4 | NA | Yes (16) | ID | 18 | Respiratory failure |
3 | 86 | M | Rheumatoid arthritis | 14 | 6.6 | 24 | Yes (7) | ID | 8 | Respiratory failure, renal failure |
4 | 75 | M | Kidney transplantation | 14 | 7.8 | 24 | Yes (6) | ID | 13 | Abdominal sepsis |
5 | 63 | M | Waldenstrom macroglobulinemia | 14 | 8.2 | 24 | Yes (4) | ID | 5 | Sepsis, respiratory failure, renal failure |
6 | 53 | V | Autoimmune hepatitis, RA | NA | 8.4 | 40 | Yes (14) | ID | 14 | Multi-organ failure, upper gastrointestinal bleeding |
7 | 47 | M | Metastasized rectal carcinoma | 1 | 6.1 | NA | No | ID | 8 | Respiratory failure |
8 | 64 | M | Interstitial lung disease | 2 | NA | 30 | Yes (12) | ID | 14 + 6a
| Respiratory failure |
9 | 68 | M | HIV | 7 | 7.4 | 20 | Yes (17) | ID | 20 | Respiratory failure |
10 | 57 | V | Autoimmune hepatitis | NA | NA | 18 | Yes (3) | ID | 18 | Hypovolemic shock due to abdominal bleeding |
11 | 51 | M | ALL, allogenic HCT | 3 | NA | 20 | No | SD | 4 | Respiratory failure |
12 | 60 | M | Pulmonary fibrosis, Crohn disease | 2 | 5.1 | 30 | Yes (16) | ID | 14 + 3a
| Respiratory failure |
13 | 61 | V | Lung carcinoma, Cushing | NA | 8.7 | NA | Yes (12) | ID | 14 | Abdominal sepsis, respiratory failure |
14 | 83 | M | CLL, hypogammaglobulinemia | 2 | 5.7 | 22 | No | ID | 12 | Unknown |