title: Diagnostic value of sepsis biomarkers in hematopoietic stem cell transplant recipients in a condition of high prevalence of gram-negative pathogens.
abstract: OBJECTIVE
  A decision about the need for antimicrobial therapy in a patient with febrile neutropenia after hematopoietic stem cell transplantation (HSCT) is often complicated because of the low frequency of culture isolation and reduced clinical manifestation of infection. Usefulness and choice of sepsis biomarkers to distinguish bloodstream infection (BSI) from other causes of febrile episode is still argued in HSCT recipients in modern epidemiological situations characterized by the emergence of highly resistant gram-negative microorganisms. In this study a comparative analysis of diagnostic values of presepsin, procalcitonin (PCT), and C-reactive protein (CRP) was performed as sepsis biomarkers in adult patients after HSCT in a condition of high prevalence of gram-negative pathogens.
  
  
  METHODS
  A prospective observational clinical study was performed at the Center of Hematology and Bone Marrow Transplantation in Minsk, Republic of Belarus. The biomarkers (presepsin, PCT, and CRP) were assessed in a 4-hour period after the onset of febrile neutropenia episode in adult patients after HSCT. Microbiologically-confirmed BSI caused by a gram-negative pathogen was set as a primary outcome.
  
  
  RESULTS
  Clinical and laboratory data were analyzed in 52 neutropenic patients after HSCT aged 18-79years. Out of the biomarkers assessed, the best diagnostic value was shown in presepsin (area under the curve [AUC]: 0.889, 95% confidence interval [CI]: 0.644-0.987, p<.0001) with 75% sensitivity and 100% specificity, then in PCT (AUC: 0.741, 95% CI: 0.573-0.869, p=.0037) with 62% sensitivity and 88% specificity. The optimal cut-off value for CRP was set as 165mg/L, while it had an average diagnostic value (AUC: 0.707, 95% CI: 0.564-0.825, p=.0049) with low sensitivity (40%) and should not be routinely recommended as a biomarker in adult patients with suspected BSI after HSCT.
  
  
  CONCLUSIONS
  Presepsin may be recommended in adult patients with suspected gram-negative BSI after HSCT as a possible additional supplementary test with a cut-off value of 218pg/mL. PCT is inferior to presepsin in terms of sensitivity and specificity, but still shows a good quality of diagnostic value with an optimal cut-off value of 1.5ng/mL. CRP showed an average diagnostic value with low sensitivity (40%) and should not be routinely recommended as a biomarker in adult patients with suspected BSI after HSCT in a condition of high prevalence of gram-negative pathogens.
authors: Department of Infectious Diseases, Belarusian State Medical University, Minsk, Belarus. Electronic address: igor.stoma@gmail.com.
authors: Igor
authors: I
authors: Stoma
authors: Department of Infectious Diseases, Belarusian State Medical University, Minsk, Belarus.
authors: Igor
authors: I
authors: Karpov
authors: City Clinical Hospital No. 9, Minsk, Belarus.
authors: Anatoly
authors: A
authors: Uss
authors: City Clinical Hospital No. 9, Minsk, Belarus.
authors: Oleg
authors: O
authors: Rummo
authors: City Clinical Hospital No. 9, Minsk, Belarus.
authors: Natalia
authors: N
authors: Milanovich
authors: City Clinical Hospital No. 9, Minsk, Belarus.
authors: Igor
authors: I
authors: Iskrov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000032:analysis; D064147:Febrile Neutropenia / Q000209:etiology; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000382:microbiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000628:therapy; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D015995:Prevalence; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; C000594167:presepsin protein, human; D002116:Calcitonin; D002097:C-Reactive Protein
keywords: Bloodstream infections; C-reactive protein; Hematopoietic stem cell transplantation; Presepsin; Procalcitonin