1. Dr. Richard Watts
Oxford University Press
2001 Evans Rd. Cary, NC 27513
Dear Editor,
Bacterial meningitis in adults without a history of trauma to the central nervous system is extremely
rare. Less than one in ten million adults in the United States are diagnosed with ​Escherichia coli
bacterial meningitis each year. This case highlights an extreme unique situation in which a 54 year old
man with no recent trauma acquired E.coli meningitis. Even more astonishingly, he was able to make a
full recovery. It is important to make providers and educators aware of extraordinary clinical cases such
as this because exceptions to the norm do exist.
Sincerely,
Eben Alexander, Liza Hashim, Delaney J. Hettithantrige, Jancarla M. Ocampo, Evan J. Rey
1

2.
Non­traumatic ​Escherichia coli​ Meningitis in an​ ​Otherwise
Healthy Adult Male
Eben Alexander 4​th1​
, Liza Hashim​1​
, Delaney J. Hettithantrige​1​
, Jancarla M. Ocampo​1​
, Evan J. Rey​1
1​
Edward Via College of Osteopathic Medicine, Blacksburg, Virginia 24060 United States
Correspondence: Eben Alexander 4th, ​ealexander@vcom.edu
2

3.
Abstract
Escherichia coli​ (​E.coli)​ is a Gram­negative rod of the enterobacteriaceae family, rarely known
to cause meningitis. Bacterial meningitis is found in neonates and adults with a route of infection such as
surgical procedures or trauma. A 54­year­old male was brought to the emergency department presenting
with a grand mal seizure. Symptoms consisted of uncontrolled muscle contractions and
unconsciousness. Over the next six days, he was further evaluated with labs and imaging and treated
with antibiotics, to no effect. On the second day, he was diagnosed with​ E. coli ​bacterial meningitis,
despite having no entry route. On the seventh day, the patient regained consciousness despite the
plateauing effects of the antibiotics and an estimated two percent chance of recovery. Of considerable
significance, this patient presented without pre­existing conditions, which demonstrates the rarity of this
case. This case study can be used to reference future unusual cases of ​E.coli​ meningitis.
Keywords​: Escherichia coli, non traumatic, meningitis, adults
3

4. Introduction
Bacterial meningitis is an inflammation of the meninges caused by bacteria invading the
subarachnoid space.​1​
The distinguishing factor of bacterial meningitis is the presence of bacteria within
the cerebrospinal fluid (CSF).​2​
The exact mechanism by which bacteria are able to get into the central
nervous system is still unknown; however, it is currently believed that bacterial pathogens will first
colonize the mucosal epithelium, and then invade the bloodstream. The bacteria must survive in the
bloodstream and cross the blood­brain barrier before multiplying in the CSF.​3​
Bacterial meningitis
reportedly occurs in​ 0.25 to 1 per 1000 live birth and occurs in 25% of neonates with bacteremia. ​E. Coli
accounts for 20% of that range.​4​
However, in adults it is even more rare; annual incidence is less than
one in 10 million in the United States.
A Gram­negative bacterial infection can result in meningitis in adults, but the pathogenic
organism requires a route of entry. It is often the result of cranial trauma accompanying fracture and
dural tear of the meninges with cerebrospinal fistula. Common post­traumatic bacterial meningitis
fracture sites include the frontal and ethmoid sinuses as well as the cribriform plate.​5​
There are fewer
reported cases of adult patients treated for non­traumatic, Gram­negative bacterial meningitis. In 1978, a
group of researchers conducted a review of several hundred adults treated for meningitis, eight of which
were diagnosed with spontaneous onset of Gram­negative bacterial meningitis, mainly ​E. coli​. The
relatively small population of patients with ​E. coli​ meningitis had several pre­hospital commonalities
including alcohol misuse and pre­existing comorbidities. In addition, on presenting to the hospital, these
patients were manifesting very similar symptoms: high­grade fever and confusion.​6
4

5. Case report
A 54 year­old man without recent head or spine trauma was experiencing severe back pain and
headache for five hours prior to having a grand mal seizure. Shortly after the onset of the seizure, he was
admitted to the emergency room where blood was drawn, 15 milligrams of intravenous Diazepam was
administered, and a lumbar puncture was performed. Differential diagnosis included alcohol withdrawal,
hallucinogenic street drugs, traumatic head injury, encephalitis, meningitis, injury due to a previous lack
of oxygen, stroke, blood vessel malformation within the brain, tumor, drug withdrawal, low blood
glucose, sodium, calcium, or magnesium.
When the lumbar puncture was taken, fluid gushed out revealing an opaque liquid. Readings in
the manometer revealed viscous white and slightly green pus. More sedatives were administered after
the lumbar puncture led to increased convulsing. CSF testing revealed Gram­negative bacteria. Soon
after, a CT was taken which displayed diffuse blurring of the gray­white junction. After one hour in the
Emergency Room (ER), he became completely unresponsive. The patient was then intubated and sent
to the Medical Intensive Care Unit (MICU) for further care.
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6. Figure 1. CT Scans of patient three days after onset of symptoms
In the MICU, he was continued on intravenous antibiotics (Cefotaxime, Tobramycin,
Imipenem) that were started before departing the ER. The specific antibiotics were occasionally
changed during the week, and one used beyond maximum recommended dose in a desperate
effort to control the infection. Within 24 hours the Gram­negative bacteria in the CSF was
confirmed as ​Escherichia coli.​ There was minimal change in the blood counts (as depicted in
Table 1) over the course of the next five days. Additionally, his Glasgow Coma Scale ranged
from 4 to 8 (alert and oriented is 15) during the week; his APACHE II score was 18 (range: 0­71;
the higher the score, the more indicative of disease and risk of death) in the ER.
6

7.
Table 1. Results​7
After six days in coma, the patient began showing voluntary muscle response to verbal stimuli.
By seven days after onset of symptoms he became alert enough to try to pull the endotracheal tube out
and was quickly weaned off of ventilation. The patient remained in the MICU for another two days and
a subsequent seven days in hospital, followed by outpatient therapy before making a full recovery over
eight weeks. Considering the unwavering WBC and glucose levels for the first five days, after­action
review with the participating physicians was inconclusive as to the mechanism of recovery.
Discussion
Escherichia coli​ meningitis is a rare disease in adults. It is more common after trauma and
extremely rare without trauma. Previous studies have demonstrated that patients with spontaneous ​E.coli
meningitis had pre­existing conditions such as diabetes and chronic alcoholism.​8​
However, prior to onset
of his symptoms, this patient was in his normal state of health, without comorbidity; furthermore, there
was no reasonable portal of entry for ​E. coli, ​as the patient did not recall any recent central nervous
system trauma. For this patient, the chances of full recovery of cognitive function were exceedingly low.
7

8. Previous studies have shown that spontaneous ​E.coli ​meningitis results in a higher incidence of death
when compared to non­spontaneous bacterial meningitis.​8
Despite the rarity of this case, the patient presented similarly to other cases previously reported
in literature. In the Berk and McCabe study, 18 of the 30 patients had a CSF white cell count between
1000 and 4999 leukocytes/mm​3​
. Further, eight of the patients had a glucose count below 9 mg/dL. This
patient had similar ranges, with a CSF white cell count of >4300 leukocytes/mm​3​
and a CSF glucose of
1 mg/dL.​8
Conclusion
After being admitted to the hospital, the patient spent six days in coma on general spectrum
antibiotics before coming out of coma and progressing toward a full recovery. Despite no known portal
of entry, no noticeable effect on the patient’s immune system by the antibiotics, the patient was able to
regain consciousness from his comatose state and make a full recovery. This case study shows an
extremely unique incidence of non­traumatic adult ​E. coli​ meningitis in the patient. Although there are
not many documented cases of non­traumatic Gram­negative bacterial meningitis in adults, better
understanding the disease in neonates can help demonstrate the pathophysiology of the disease in adults
as well.
Acknowledgements
We would like to thank the patient for allowing us to have access to his medical history.
8

9. References
1. Yikilmaz, A., & Taylor, G. A. (2008). Sonographic findings in bacterial meningitis in neonates
and young infants. ​Pediatric Radiology​, ​38​(2), 129–137. doi:10.1007/s00247­007­0538­6
2. Tunkel, A. R., & Scheld, W. M. (1993). Pathogenesis and pathophysiology of bacterial
meningitis. ​Clinical Microbiology Reviews​, ​6​(2), 118–136.
3. Kim, K. S. (2003). Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury.
Nature Reviews Neuroscience​, ​4​(5), 376­385.
4. Khalessi, N., & Afsharkhas, L. (2014). Neonatal Meningitis: Risk Factors, Causes, and
Neurologic Complications. ​Iranian Journal of Child Neurology​,​8​(4), 46–50.
5. Hand, W. L., & Sanford, J. P. (1970). Posttraumatic Bacterial Meningitis. ​Annals Of Internal
Medicine​, ​72​(6), 869­874.
6. Crane, L. R., & Lerner, A. M. (1978). Non­traumatic gram­negative bacillary meningitis in the
Detroit Medical Center, 1964­1974 (with special mention of cases due to Escherichia coli).
Medicine​, ​57​(3), 197­210.
7. Alexander, Eben III MD. ​Proof of Heaven​. New York: Simon & Schuster, 2012. Print.
8. Berk, S. L., & Mccabe, W. R. (1980). Meningitis caused by gram­negative bacilli. ​Annals of
internal medicine​, ​93​(2), 253­260.
9

10. Justification
Abstract
We wrote this abstract to make our case report comprehensible to readers before they read the case
report. We chose to follow the case report instructions from the Oxford Journal, which limited the
abstract word count to 150. Our first four sentences describe the bacteria relevant to this case, as well as
the course the bacteria can take through the human body. The rest of the abstract is pertinent to the case
itself and presents the subject, as well as the significance of the case.
​Introduction
We provided background information and literature review for bacterial meningitis to give a general
introduction to this topic. We emphasized the rarity of the disease in adults with no history of trauma to
emphasize the uniqueness of this case study. We researched the occurrence of bacterial meningitis in
neonates to be able to compare to the occurrence in adults with and without trauma to the CNS.
​Case Report
We chose to report on this case because this is the only documented case where an adult contracted ​E.
coli​ meningitis since 1978.
Materials and Methods
The Oxford Medical Case Reports manuscript instructions did not call for a materials and methods
section therefore, we did not include this section in our report.
10

11. Discussion
We wanted to reiterate how rare the disease is, and moreover, how it is exceedingly rare when it occurs
in adults, without cranial or neurosurgical trauma. Furthermore, it was important to note that despite his
comatose state, the patient had a full recovery, with only one of outpatient therapy after discharge from
the hospital.
Conclusion
We summarized the main point of this case study by emphasizing the rarity of this case. It is important
for us to note that this case can be applied for future research involving neonates.
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12. CME Questions
1. Which of the following bacteria is considered a gram negative rod?
a. Bacillus anthracis
b. Clostridium difficile
c. Escherichia coli*
d. Staphylococcal aureus
e. Streptococcus pyogenes
2. What is the distinguishing factor in the diagnosis of bacterial meningitis?
a. Headache
b. Bacteria within the cerebrospinal fluid (CSF)*
c. Bacteria within the urine
d. Nausea
e. Disorientation
3. Which of the following patient presentations is most likely to be diagnosed with bacterial
meningitis?
a. A patient who was recently involved in a motor vehicle accident that resulted in severe
trauma to the ethmoid sinus*
b. A relief worker who recently traveled to an area where bacterial meningitis is common
c. A child with a history of ear infections
d. A construction worker who has had recent shortness of breath
e. A patient who was recently diagnosed with diabetes
4. Which procedure can be performed to diagnose bacterial meningitis?
a. Chest x­ray
b. Lumbar puncture*
c. Urinalysis
d. Glucose curve
e. Ultrasound
5. Which of the following routes of colonization would a bacteria take to cause bacterial
meningitis?
a. Mucosal epithelium → blood → CSF*
b. Nasal cavity → esophagus → respiratory tract
c. Cornea → anterior chamber of eye → canal of Schlemm
d. Blood → mucosal epithelium → CSF
e. Mucosal epithelium → blood → urine
12