Crossing the Blood Brain Barrier; The Identification and Introduction to Treatment of Meningitis

MENINGITIS: DEFINITION
DEFINITION OF MENINGITIS (DISTINGUISHED FROM ENCEPHALITIS):
THIS IS INFLAMMATION OF THE MENINGES CAUSED BY VIRAL OR BACTERIAL INFECTION AND IS MARKED BY AN INTENSE PROGRESSIVE HEADACHE WITH FEVER, ALTERED MENTATION FROM DROWSINESS TO AGITATION OR EVEN COMA, PHOTOPHOBIA, OPISTHOSTONUS (MUSCULAR RIGIDITY NOT UNLIKE THAT SEEN IN TETANUS).  MENINGITIS CAN LEAD IN SEVERE CASES TO SEIZURES, ALTERED MENTATION (USUALLY DESCRIBED AS DELIRIUM IF THE PATIENT IS STILL AROUSEABLE) AND, ULTIMATELY, DEATH. Encephalitis is an infection of the brain matter and includes many causes, most are viral.  A key most important form is Herpes Encephalitis because it requires immediate antirvial treatment (empiric) just as bacterial meningitis.   A cold sore, altered mentation especially combativeness, low grade fever may all be present but the most important clue is the cold sore (fever blister) and it may represent either herpes type I or type II (herpes gentalia) since the sexual behavior of humans now has caused the virus to be at any site (this has always been true).  They are treated the same and the more dangerous of the two is herpes on the face for the patient and herpes in the vaginal canal for the newborn.  The mother is monitor for vaginal viral particles prior to delivery and otherwise is delivered by c-section to prevent neonatal herpes encephalitis.  Treatment of the mother with antiviral prior to vaginal delivery must be a decision between mother and physician or to have a c-section.   Most of the US population test positive for exposure to this virus.  FYI: don’t ever scrub a cold sore or touch your eye if you have a cold sore; get the antiviral treatment and not an OTC med.  You can spread it to your eye and have a lifelong of ocular complications and by scrubbing it you can spread it all over your face such that each outbreak will be all over your face! [tell your patients!!!]
Meningitis is caused by many bacterial pathogens but a key finding is a purple skin rash that may be petechial or look like purpura.
BACTERIAL PATHOGENS BY AGE GROUP:
Newborns:  Ecoli, group B strep
Age: 3 months to 3 years: add Listeria moncytogenes to the list which now also includes Pneumococcus and Hemophilus type B and Meningococcus despite the vaccines.
Age ≥3years: Pneumococcus and Meningococcus
Any patient with MRSA infection, fever, muscle rigidity, altered mentation: consider Staph aureus including MRSA (methicillin-resistant S. aureus).
Alcoholics: add Listeria monocytogenes to Pneumococcus and Meningococcus as most common agents. (ampicillin is needed for Listeria infections).
MENINGITIS: CLINICAL PRESENTATION:
This finding with fever and irritability in an infant is a presumed case of meningococcal meningitis but there are other conditions that can mimic this.  However, since this is a “rapid killer” even when treated early and empirically, such patients should be treated intravenously without any delay!  In medicine we say for heart attacks, “time is muscle”…for meningitis and encephalitis, time is brain!  REMEMBER ACLS: antibiotic, then CT, then lumbar puncture if Ct does not show evidence of imminent herniation or brain edema, and the “S” is for administer a steroid (9 mg) of dexamethasone IV to prevent healing loss.  It may also reduce brain edema and allow the patient enough improvement if they have a mass (tumor in their brain such as GBH) to wake up and speak!.  Cancer patients are at risk for CNS infection and infection everywhere.  That is why no patient who is receiving chemotherapy near the nadir of their WBC count has a true contraindication for any rectal examination for anything but a lifesaving reason.  I can’t think of any that would be typical in this situation but physicians often omit rectal exams when they should not and this is the one time they should not do i because it can it can seed the blood with bacteria from the rectum (a combination of anaerobes…such an infection would likely lead to a  fatal outcomel).
ACLS is not just for cardiac life support…it is my mnemonic to remember the sequence of treatment or approach to meningitis and encephalitis.  With herpes I//II encephalitis it is the same sequence, but the antibiotic is replaced with an antiviral such as acyclovir or norvir intravenously.  No delay as this can lead to death in the ED!  Any patient with a fever blister (which can by type I/II herpes infection on the face, can travel retrograde (cephalic) to the brain and usually this is a teenager with agitation, low grade fever and fever blister.  Treatment must be empiric and the final Dx may even have to await a brain biopsy since MRI may not be absolutely diagnostic.  YOU MIGHT THINK..why is he writing about this.  IT MATTERS FOR THE ONE CASE YOU WILL SEE IN YOUR CAREER.  Many of the questions on board exams are items you may see only a few times in a 40 year span of healthcare.  BUT these are the items that if you don’t know them in enough detail you may have failure of recognition or failure of treatment and the outcome is devastating for the patient.
THIS IS WHY THERE IS A MINIMUM CORE CONTENT OF MATERIAL YOU MU COMMIT TO MEMORY AND IT IS NOW AND HAS BEEN 2500 PAGES BY 500+ AUTHORS (AND IS ALL CONTAINED IN JUDITH TINTINALLI’S, STUDY GUIDE OF EMERGENCY MEDICINE).  YOU NEED THIS AND ROSENS’ THREE VOLUME SERIES OF TEXTS TO READ FOR YOUR LIFETIME. I HAVE NOW BEEN THROUGH 8 EDITIONS OF TINTINALLI IN MY TEACHING.  IT IS MASSIVE AND IT IS A DAILY READING ISSUE.  THIS DOESN’T INCLUDE MY CME AND LLSA (ABEM REQUIRED) ANNUAL READINGS AND TESTS.  EMERGENCY PHYSICIANS ARE GREAT IF THEY MASTER THIS MATERIAL AND KEEP A LIFELONG APPROACH TO RELEARNING IT.  THIS IS NECESSARY REINFORCEMENT.  THIS IS WHY I SPEND TIME ON TEST-TAKING, MASTERY OF YOUR MIND AND OTHER SUCH TOPICS.
Remember that any young child especially those under 1 year of age may not demonstrate any nuchal rigidity on examination.  If the parents are concerned about a change in behavior with loss of activity or responsiveness or irritability even if sporadic, treat the patient!  FEVER may or may not be present for a variety of reasons.
MENINGITIS ANTIBIOTICS 2017

Dwight Collman MD
1.  Ampicllin
2.  Cefotaxime
3.  The combination Ampicllin and Cefotaxime in pediatric patients age 3 months to 3 years
4.  Ceftriaxone: may be used as a singe agent in otherwise healthy adults and chlidren ≥3 years of age.
CAVEATS:
The combination of Ceftriaxone and Vancomycin when MRSA or staph infection is suspected
Gentamicin (an antibiotic that would not be used alone but increases efficacy of third generation cephalosporins (Ceftriaxone, Cefotaxime) if gram negative organisms are suspected clinically
Penicillin G.  The oldest drug in the list but very effective against organisms that originate in the mouth (this is the location of one of the most “dangerous” combination of organisms that are anaerobic and lethal because they help each other in the progression of an infection…i.e., they are synergistic.  For this reason.  Usually a combination of antibiotics are administered.  In some cases (not including just meningitis, in which it may actually be appropriate to start with triple synergistic coverage: gram positives, gram negatives, anaerobes are the three categories that are the offending organisms in this situation
Rifampin. Also an old antibiotic but used primarily for prophylactic treatment of anyone (including health care providers) exposed to an active case of meningococcal meningitis.  Administering mouth to mouth resuscitation would be an obvious reason for such treatment if this infection is suspected in the patient.  Sadly, even today, many providers will not provide such basic life support for fear of dying of this infection or others.  Get your vaccinations and take the prophylaxis or don’t go into medicine.   There will come a day when there is no ambulance bag.  You took an oath to save lives.
Vancomycin.  This drug is not used alone in meningitis but it is one of the key antibiotics on our list all of us should know!!! (this means by age group, history, the board WILL ask TIs about these agents.  They don’t ask about antibiotic diseases.  Dosages are only asked if it is an APLS or ACLS drug.  So relax.  Just know the list of antibiotics to use by circumstance and by age group.
Examples: Alcoholics:  they are prone to many complications (aspiration pneumonia, staph infections after a viral illness), and depressed immunity.  They are also at higher risk for Listeria infections so ampicillin is added for this reason.
Children between the age of 3 Mos to 3 years: Ampicillin plus Cefotaxime to provide standard coverage plus coverage for listeria (this age group is prone to listeria infection also).