title: False negative β-2 transferrin in the diagnosis of cerebrospinal fluid leak in the presence of Streptococcus pneumoniae.
abstract: OBJECTIVE
  The objectives of this study were to examine the presence of β-2 transferrin (β2TRNSF) in cerebrospinal fluid (CSF) contaminated in vitro by various bacteria and explore the mechanism (passive or active) responsible for β2TRNSF elimination. Early diagnosis of CSF leakage may change treatment decisions and minimize the risk of meningitis and encephalitis. β2TRNSF is a protein present exclusively in CSF. Its detection is highly useful in cases of CSF leakage, although it has never been examined in the presence of central nervous system infection.
  
  
  METHODS
  Prospective patient analysis.
  
  
  METHODS
  Sterile CSF drawn from patients was contaminated in vitro with several microorganisms chosen for their ability to cause neurosurgical-related infections: Streptococcus pneumoniae, methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. β2TRNSF was examined at two time points: following immediate inoculation (t0) and following an overnight incubation (t18) over various bacterial concentrations. Samples of CSF inoculated with S pneumoniae were also examined in the presence of ciprofloxacin. For β2TRNSF analysis we used immunoblotting electrophoresis and enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  CSF samples collected from nine patients were analyzed. β2TRNSF was not detected following S pneumoniae inoculation at both time points when immunoblotting electrophoresis was used. Quantitative analysis using ELISA demonstrated significant β2TRNSF concentration decrease. The addition of ciprofloxacin led to the same results.
  
  
  CONCLUSIONS
  CSF leak detection using β2TRNSF may be deceiving in the presence of a S pneumoniae cerebral nervous system infection. A passive process is suggested, as β2TRNSF disappeared either immediately or following incubation with inactive bacteria.
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Hebrew University School of Medicine-Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Korem
authors.forename: Haim
authors.initials: H
authors.lastname: Ovadia
authors.forename: Iddo
authors.initials: I
authors.lastname: Paldor
authors.forename: Allon E
authors.initials: AE
authors.lastname: Moses
authors.forename: Colin
authors.initials: C
authors.lastname: Block
authors.forename: Ron
authors.initials: R
authors.lastname: Eliashar
authors.forename: Nir
authors.initials: N
authors.lastname: Hirshoren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002494:Central Nervous System Infections / Q000150:complications* / Q000382:microbiology / Q000401:mortality; D065634:Cerebrospinal Fluid Leak / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000209:etiology; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005188:False Negative Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000134:cerebrospinal fluid / Q000150:complications* / Q000382:microbiology; D011446:Prospective Studies; D013296:Streptococcus pneumoniae / Q000302:isolation & purification*; D014168:Transferrin / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D014168:Transferrin
keywords: Streptococcus pneumoniae; cerebrospinal fluid leakage; electrophoresis; enzyme-linked immunosorbent assay; β-2 transferrin