Observational Study
Copyright ©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
Table 1 Spectrum of nosocomial fever of unknown origin (n = 80)
Etiologies
n (%)
Infectious disorders34 (42.5)
Pneumonia21 (26.2)
Ventilator-associated pneumonia117
Hospital-acquired pneumonia24
Bloodstream infections9 (11.2)
Bacteraemia with unknown primary site36
Catheter-related blood stream infection43
Intra-abdominal Infections3 (3.75)
Clostridioides difficile diarrhea1
Peritonitis1
Gall bladder perforation with peritonitis and intra-abdominal collections1
Catheter-associated urinary tract infection51 (1.3)
Multi-site infections2 (2.5)
Ventilator-associated pneumonia and pressure ulcer61
Ventilator-associated pneumonia7 and catheter-related blood stream infection81
Non-infectious disorders31 (38.7)
Central fever6 (7.5)
Thrombophlebitis6 (7.5)
Pneumonitis without infection4 (5)
Acute pancreatitis3 (3.8)
Rhabdomyolysis3 (3.8)
Venous thromboembolism2 (2.5)
Drug fever2 (2.5)
Alcohol withdrawal syndrome1 (1.3)
Central pontine demyelination1 (1.3)
Transfusion reaction1 (1.3)
Acute hemolysis1 (1.3)
Atelectasis1 (1.3)
Undiagnosed15 (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 ± SD42.9 ± 16.539.2 ± 17.445.8 ± 14.10.098
Male gender64 (80)26 (76.5)26 (83.9)0.456
Pre-existing comorbidities
Any48 (60)21 (61.8)20 (64.5)0.818
Diabetes19 (23.8)7 (20.6)8 (25.8)0.618
Hypertension14 (17.5)7 (20.6)4 (12.9)0.409
Chronic kidney disease8 (10)2 (5.9)4 (12.9)0.413
Epilepsy8 (10)5 (14.7)3 (9.7)0.711
Coronary artery disease or heart failure7 (8.8)3 (8.8)4 (12.9)0.701
Miscellaneous111 (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 disorders220 (25)5 (14.7)9 (29)0.161
Medical emergencies
Neurological disorders332 (40)14 (41.2)16 (51.6)0.399
Toxicological disorders419 (23.7)6 (17.6)9 (29)0.277
Gastro-intestinal disorders57 (8.75)3 (8.8)1 (3.2)0.615
Renal disorders66 (7.5)2 (5.9)2 (6.5)1.000
Miscellaneous716 (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 ± SD101.6 ± 0.7101.7 ± 0.8101.5 ± 0.70.714
Pulse rate (per minute), mean ± SD104.2 ± 20.6109.0 ± 23.4100.0 ± 16.00.079
Tachycardia, n (%)36 (45)18 (52.9)12 (38.7)0.250
Systolic blood pressure (mmHg), mean ± SD127.9 ± 21.9128.8 ± 23.6126.3 ± 21.20.655
Diastolic blood pressure (mmHg), mean ± SD76.8 ± 12.979.5 ± 14.574.4 ± 11.20.118
Mean arterial pressure (mmHg), mean ± SD93.8 ± 14.695.9 ± 16.391.67 ± 13.70.262
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 catheters72 (90)31 (91.2)29 (93.5)1.000
Endotracheal tubes64 (80)28 (82.4)24 (77.4)0.619
Nasogastric tubes64 (80)29 (85.3)24 (77.4)0.414
Central lines25 (31.3)9 (26.5)5 (16.1)0.311
Non-tunnelled dialysis catheters7 (8.8)4 (11.8)0 (0)0.115
Percutaneous catheters6 (7.5)3 (8.8)1 (3.2)0.614
Laboratory investigations
Hemoglobin (g/L), mean ± SD110.7 ± 27.4109.0 ± 28.2109.6 ± 28.10.933
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 ± SD82.7 ± 7.082.2 ± 6.484.3 ± 6.20.199
Lymphocytes (%), mean ± SD8.2 ± 4.48.2 ± 4.17.8 ± 4.40.610
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 ± SD141.0 ± 8.2140.2 ± 7.2142.0 ± 8.70.368
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 ± SD63.9 ± 10.362.2 ± 9.764.4 ± 11.50.418
Albumin (g/L), mean ± SD31.6 ± 5.831.2 ± 5.731.4 ± 5.60.863
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
Sensitivity77% (58-90)77% (58-90)72% (51-88)76% (56-90)
Specificity48% (28-69)24% (9-45)44% (22-69)48% (28-69)
False negative rate23% (10-42)23% (10-42)28% (12-49)24% (10-44)
False positive rate52% (31-72)76% (55-91)56% (31-78)52% (31-72)
Positive likelihood ratio1.47 (0.96-2.26)1.01 (0.75-1.36)1.30 (0.80-2.09)1.46 (0.95-2.24)
Negative likelihood ratio0.49 (0.23-1.05)0.97 (0.38-2.52)0.63 (0.28-1.42)0.50 (0.23-1.08)
Diagnostic odds ratio3.03 (0.96-9.62)1.04 (0.30-3.69)2.06 (0.57-7.36)2.90 (0.91-9.23)
Youden’s index0.25 (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)