Critical Care Medicine-Infections and Immunologic Disease>>>>>CNS Infections
Question 2#

A 66-year-old woman is brought to the ED after being found down in her home by her maid; no family member is reachable. On arrival, she has:

Her mental status is altered with a Glasgow Coma Scale (GCS) of 8, but her physical examination is otherwise normal including a nonfocal neurological examination. Soon after presentation, she has multiple emetic episodes and is intubated for airway protection. A head CT shows no signs of an acute intracranial process. A urine toxicology screen is negative. Empiric antimicrobial therapy with vancomycin and ceftriaxone is initiated after blood cultures are obtained, and she is transferred to the ICU for further care. Contact is finally established with her husband who reports that she had been having severe headaches, body aches, and fever for the past few days. He also reports that she has a history of osteoarthritis and well-controlled diabetes and was in a motor vehicle accident several years ago requiring emergent splenectomy. Her vaccination status is not known. An LP is performed approximately 13 hours after initial antibiotics administration, which shows:

CSF gram stain is negative, and cultures have no growth at 48 hours. Multiplex polymerase chain reaction (PCR) on CSF is positive for Neisseria meningitidis.

Which of the following interpretations of the CSF findings is MOST correct?

A. Prior antibiotics do not affect CSF glucose or CSF protein and do not alter the yield of CSF cultures
B. Prior antibiotics do not affect CSF glucose or CSF protein but do alter the yield of CSF cultures
C. Prior antibiotics decrease both CSF glucose and CSF protein and decrease the yield of CSF cultures within a few hours of initiation
D. Prior antibiotics alter both CSF glucose and protein and decrease the yield of CSF cultures within a few hours of initiation

Correct Answer is D


Correct Answer: D

In suspected bacterial meningitis, LP should ideally precede empiric antibiotic therapy. However, multiple factors including overreliance on CT imaging before LP have increasingly led to delay in LP until after initiation of antimicrobials. Antimicrobials can affect measurements of CSF glucose, protein, and potentially other indices as well, and decrease the yield of CSF cultures making accurate diagnosis more challenging. The data on postantimicrobial CSF analysis is very limited, is largely retrospective, and mostly extrapolated to the adult population from pediatric literature. CSF culture has a reported sensitivity of 88% for microbiological diagnosis, which decreases to 70% with any prior antibiotic use and sensitivity declines further as the duration of time receiving antibiotics increases. As duration of antimicrobial therapy increases, CSF glucose levels increase and CSF protein levels decrease as compared with preantimicrobial measurements, which is likely a reflection of pathogen clearance from the CSF. Complete clearance of meningococcus from the CSF occurs within 2 hours of antimicrobial therapy initiation, and pneumococcus clearance begins around 4 hours into therapy. Other pathogens seem to be more persistent. However, it is important to note that CSF pleocytosis and neutrophilic count are not as readily affected by antibiotics, and the counts are relatively preserved even after 24 hours of antimicrobial therapy. The following parameters predict bacterial infection with high accuracy and should therefore inform differential diagnosis even in the absence of microbiological data and regardless of administration of antimicrobial therapy:


  1. Kanegaye JT, Soliemanzadeh P, Bradley JS, Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics. 2001;108:1169-1174.
  2. Nigrovic LE, Malley R, Macias CG, et al. Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis. Pediatrics. 2008;122:726-730.
  3. Venkatesh B, Scott P, Ziegenfuss M. Cerebrospinal fluid in critical illness. Crit Care Resusc. 2000;2:42-54.