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©The Author(s) 2025.
World J Crit Care Med. Sep 9, 2025; 14(3): 106496
Published online Sep 9, 2025. doi: 10.5492/wjccm.v14.i3.106496
Published online Sep 9, 2025. doi: 10.5492/wjccm.v14.i3.106496
Table 1 Spectrum of nosocomial fever of unknown origin (n = 80)
Etiologies | n (%) |
Infectious disorders | 34 (42.5) |
Pneumonia | 21 (26.2) |
Ventilator-associated pneumonia1 | 17 |
Hospital-acquired pneumonia2 | 4 |
Bloodstream infections | 9 (11.2) |
Bacteraemia with unknown primary site3 | 6 |
Catheter-related blood stream infection4 | 3 |
Intra-abdominal Infections | 3 (3.75) |
Clostridioides difficile diarrhea | 1 |
Peritonitis | 1 |
Gall bladder perforation with peritonitis and intra-abdominal collections | 1 |
Catheter-associated urinary tract infection5 | 1 (1.3) |
Multi-site infections | 2 (2.5) |
Ventilator-associated pneumonia and pressure ulcer6 | 1 |
Ventilator-associated pneumonia7 and catheter-related blood stream infection8 | 1 |
Non-infectious disorders | 31 (38.7) |
Central fever | 6 (7.5) |
Thrombophlebitis | 6 (7.5) |
Pneumonitis without infection | 4 (5) |
Acute pancreatitis | 3 (3.8) |
Rhabdomyolysis | 3 (3.8) |
Venous thromboembolism | 2 (2.5) |
Drug fever | 2 (2.5) |
Alcohol withdrawal syndrome | 1 (1.3) |
Central pontine demyelination | 1 (1.3) |
Transfusion reaction | 1 (1.3) |
Acute hemolysis | 1 (1.3) |
Atelectasis | 1 (1.3) |
Undiagnosed | 15 (18.8) |
Table 2 Sociodemographic profile, pre-existing conditions, and acute medical disorders, n (%)
Parameter | Total (n = 80) | Infectious (n = 34) | Non-infectious (n = 31) | P value |
Age (years), mean ± SD | 42.9 ± 16.5 | 39.2 ± 17.4 | 45.8 ± 14.1 | 0.098 |
Male gender | 64 (80) | 26 (76.5) | 26 (83.9) | 0.456 |
Pre-existing comorbidities | ||||
Any | 48 (60) | 21 (61.8) | 20 (64.5) | 0.818 |
Diabetes | 19 (23.8) | 7 (20.6) | 8 (25.8) | 0.618 |
Hypertension | 14 (17.5) | 7 (20.6) | 4 (12.9) | 0.409 |
Chronic kidney disease | 8 (10) | 2 (5.9) | 4 (12.9) | 0.413 |
Epilepsy | 8 (10) | 5 (14.7) | 3 (9.7) | 0.711 |
Coronary artery disease or heart failure | 7 (8.8) | 3 (8.8) | 4 (12.9) | 0.701 |
Miscellaneous1 | 11 (13.8) | 5 (14.7) | 5 (16.1) | - |
Charlson comorbidity index, median (IQR) | 0 (0-2) | 0 (0-1.25) | 0 (0-2) | 0.719 |
Age-adjusted Charlson comorbidity index, median (IQR) | 0 (0-2) | 0 (0-2) | 1 (0-2) | 0.389 |
Substance use disorders2 | 20 (25) | 5 (14.7) | 9 (29) | 0.161 |
Medical emergencies | ||||
Neurological disorders3 | 32 (40) | 14 (41.2) | 16 (51.6) | 0.399 |
Toxicological disorders4 | 19 (23.7) | 6 (17.6) | 9 (29) | 0.277 |
Gastro-intestinal disorders5 | 7 (8.75) | 3 (8.8) | 1 (3.2) | 0.615 |
Renal disorders6 | 6 (7.5) | 2 (5.9) | 2 (6.5) | 1.000 |
Miscellaneous7 | 16 (20) | 9 (26.5) | 3 (9.7) | - |
Table 3 Clinical and laboratory characteristics at fever onset
Parameter | Total (n = 80) | Infectious (n = 34) | Non-infectious (n = 31) | P value |
Time to fever onset post-hospitalization (days), median (IQR) | 5 (3-8) | 5 (3.75-9) | 5 (3-7) | 0.229 |
Temperature (F), mean ± SD | 101.6 ± 0.7 | 101.7 ± 0.8 | 101.5 ± 0.7 | 0.714 |
Pulse rate (per minute), mean ± SD | 104.2 ± 20.6 | 109.0 ± 23.4 | 100.0 ± 16.0 | 0.079 |
Tachycardia, n (%) | 36 (45) | 18 (52.9) | 12 (38.7) | 0.250 |
Systolic blood pressure (mmHg), mean ± SD | 127.9 ± 21.9 | 128.8 ± 23.6 | 126.3 ± 21.2 | 0.655 |
Diastolic blood pressure (mmHg), mean ± SD | 76.8 ± 12.9 | 79.5 ± 14.5 | 74.4 ± 11.2 | 0.118 |
Mean arterial pressure (mmHg), mean ± SD | 93.8 ± 14.6 | 95.9 ± 16.3 | 91.67 ± 13.7 | 0.262 |
Glasgow coma scale, median (IQR) | 10 (8-11) | 10 (8-14.3) | 9 (7.0-11.0) | 0.185 |
Intensive organ support requirement | ||||
Mechanical ventilation, n (%) | 64 (80) | 28 (82.4) | 24 (77.4) | 0.619 |
Vasopressor therapy, n (%) | 11 (13.8) | 5 (14.7) | 4 (12.9) | 1.000 |
Hemodialysis, n (%) | 8 (10) | 5 (14.7) | 0 (0) | 0.054 |
In-situ catheters or tubes, n (%) | ||||
Urinary catheters | 72 (90) | 31 (91.2) | 29 (93.5) | 1.000 |
Endotracheal tubes | 64 (80) | 28 (82.4) | 24 (77.4) | 0.619 |
Nasogastric tubes | 64 (80) | 29 (85.3) | 24 (77.4) | 0.414 |
Central lines | 25 (31.3) | 9 (26.5) | 5 (16.1) | 0.311 |
Non-tunnelled dialysis catheters | 7 (8.8) | 4 (11.8) | 0 (0) | 0.115 |
Percutaneous catheters | 6 (7.5) | 3 (8.8) | 1 (3.2) | 0.614 |
Laboratory investigations | ||||
Hemoglobin (g/L), mean ± SD | 110.7 ± 27.4 | 109.0 ± 28.2 | 109.6 ± 28.1 | 0.933 |
Platelet count (per μL), median (IQR) | 165500 (109250-230250) | 168000 (125500-237250) | 198000 (110000-254000) | 0.590 |
Total leucocyte count (per μL), median (IQR) | 12640 (10005-18842) | 12490 (9500-19165) | 14420 (1.280-23400) | 0.123 |
Leukocytosis, n (%) | 54 (67.5) | 22 (64.7) | 23 (74.2) | 0.408 |
Neutrophils (%), mean ± SD | 82.7 ± 7.0 | 82.2 ± 6.4 | 84.3 ± 6.2 | 0.199 |
Lymphocytes (%), mean ± SD | 8.2 ± 4.4 | 8.2 ± 4.1 | 7.8 ± 4.4 | 0.610 |
Neutrophil to lymphocyte ratio, median (IQR) | 10.6 (7.2-20.7) | 10.5 (6.5-18.7) | 12.0 (7.4-23.7) | 0.470 |
Sodium (mmol/L), mean ± SD | 141.0 ± 8.2 | 140.2 ± 7.2 | 142.0 ± 8.7 | 0.368 |
Blood urea (mmol/L), median (IQR) | 8.7 (5.1-15.4) | 6.8 (4.4-11.2) | 9.2 (5.0-16.3) | 0.164 |
Creatinine (mol/L), median (IQR) | 91.1 (61.9-209.7) | 97.2 (57.5-296.1) | 92.9 (61.9-210.4) | 0.478 |
Bilirubin (mol/L), median (IQR) | 13.5 (6.8-23.6) | 12.6 (8.6-27.4) | 13.5 (6.7-20.0) | 0.454 |
Aspartate transaminase (U/L), median (IQR) | 45.7 (25.9-87.8) | 44.5 (28.3-85.9) | 49.5 (23.0-102.0) | 0.984 |
Alanine transaminase (U/L), median (IQR) | 32.1 (17.5-69.3) | 35.1 (19.8-57.0) | 29.2 (16.2-74.0) | 0.778 |
Alkaline phosphatase (U/L), median (IQR) | 101 (75.3-132.8) | 92.5 (71-123.3) | 103 (75.5-133.5) | 0.711 |
Total protein (g/L), mean ± SD | 63.9 ± 10.3 | 62.2 ± 9.7 | 64.4 ± 11.5 | 0.418 |
Albumin (g/L), mean ± SD | 31.6 ± 5.8 | 31.2 ± 5.7 | 31.4 ± 5.6 | 0.863 |
Table 4 Sepsis screening tools and biomarkers at fever onset
Parameter | Total (n = 80) | Infectious (n = 34) | Non-infectious (n = 31) | P value |
Sepsis screening tools | ||||
SIRS, median (IQR) | 3 (3-4) | 3 (3-4) | 3 (3-4) | 0.949 |
SIRS ≥ 2, n (%) | 78 (97.5) | 33 (97.1) | 31 (100) | 1.000 |
qSOFA, median (IQR) | 2 (1-2) | 2 (1-2) | 2 (1-2) | 0.957 |
qSOFA ≥ 2, n (%) | 57 (71.3) | 25 (73.5) | 21 (67.7) | 0.608 |
SOFA, median (IQR) | 6 (4-8) | 6.5 (4-8.3) | 6 (3-8) | 0.736 |
NEWS, median (IQR) | 12 (9-14) | 12.5 (9.5-8.3) | 12 (8-14) | 0.726 |
NEWS ≥ 7, n (%) | 67 (83.8) | 28 (82.4) | 27 (87.1) | 0.736 |
qNEWS, median (IQR) | 6 (3-6) | 5 (3-6) | 6 (3-6) | 0.496 |
MEWS, median (IQR) | 6 (4.25-8) | 7 (5-8) | 6 (5-8) | 0.863 |
Sepsis biomarkers | ||||
Procalcitonin (μg/L), median (IQR) | 1.9 (0.5-12.1) | 2.8 (0.8-25.9) | 1.0 (0.5-4.6) | 0.156 |
C- reactive protein (mg/L), median (IQR) | 123.0 (55.9-225.6) | 107.2 (50.5-209.0) | 136.5 (51.9-245.3) | 0.566 |
Table 5 Diagnostic performance of serum procalcitonin and combined sepsis screening tools and procalcitonin
Parameters | PCT 0.85 μg/L | PCT 0.50 μg/L | qSOFA 2 + PCT 0.85 μg/L | SIRS 2 + PCT 0.85 μg/L |
Sensitivity | 77% (58-90) | 77% (58-90) | 72% (51-88) | 76% (56-90) |
Specificity | 48% (28-69) | 24% (9-45) | 44% (22-69) | 48% (28-69) |
False negative rate | 23% (10-42) | 23% (10-42) | 28% (12-49) | 24% (10-44) |
False positive rate | 52% (31-72) | 76% (55-91) | 56% (31-78) | 52% (31-72) |
Positive likelihood ratio | 1.47 (0.96-2.26) | 1.01 (0.75-1.36) | 1.30 (0.80-2.09) | 1.46 (0.95-2.24) |
Negative likelihood ratio | 0.49 (0.23-1.05) | 0.97 (0.38-2.52) | 0.63 (0.28-1.42) | 0.50 (0.23-1.08) |
Diagnostic odds ratio | 3.03 (0.96-9.62) | 1.04 (0.30-3.69) | 2.06 (0.57-7.36) | 2.90 (0.91-9.23) |
Youden’s index | 0.25 (0.00-0.49) | 0.01 (-0.22 to 0.23) | 0.16 (-0.12 to 0.45) | 0.24 (-0.01 to 0.49) |
- Citation: Saini S, Pahil S, Mohindra R, Sachdeva N, Sharma N, Pannu AK. Diagnostic utility of sepsis screening tools, procalcitonin, and C-reactive protein in nosocomial fever of unknown origin. World J Crit Care Med 2025; 14(3): 106496
- URL: https://www.wjgnet.com/2220-3141/full/v14/i3/106496.htm
- DOI: https://dx.doi.org/10.5492/wjccm.v14.i3.106496