To Trick or Treat: Antimicrobial Prophylaxis for Prevention of Meningitis in
Traumatic Skull Fractures Associated with CSF Leak
Hannah J. Davis, Pharm.D.
PGY1 Pharmacy Resident
University Health System, San Antonio, Texas
Division of Pharmacotherapy, The University of Texas at Austin College of Pharmacy
Pharmacotherapy Education and Research Center
University of Texas Health Sciences Center at San Antonio
October 31, 2014
Learning Objectives:
1.
2.
3.
4.
Recall anatomy and physiology of skull bones and intracranial components
Describe pathophysiology of skull fractures with associated cerebrospinal fluid (CSF) leak
Evaluate role of antibiotic prophylaxis in the setting of CSF leak
Indicate appropriate use of antibiotic prophylaxis with CSF leak
Background
I) Why do we care?
A) CNS infections including meningitis can be associated with cerebrospinal fluid (CSF) leaks
B) Overall incidence is low
C) Associated with morbidity, mortality, and increased cost
D) Controversial role for antibiotic prophylaxis
Figure 1. Severity of Injuries
Traumatic
brain injury
(TBI)
Skull fractures
CSF fistula
Central
nervous
system (CNS)
infections
II) Traumatic skull fractures
A) Incidence
i) 1.7 million traumatic brain injuries (TBI) annually1
(a) 275,000 hospitalizations for nonfatal TBI2
(b) 52,000 TBI-related deaths
(c) 80,000-90,000 experience long-term disability
(d) Mechanism of injury1
(1) Fall – 28%
(2) Motor vehicle accident – 20%
(3) Blunt force – 19%
(4) Assault – 11%
(5) Blast injuries
(e) Severity of TBI based on Glasgow Coma Scale (GCS)
(1) Presence of skull fractures is a prognostic factor for worse outcome3
(i) Greater force of impact with trauma
ii) 30% of patients with TBI have associated skull fractures
(a) Incidence of fracture by type
(1) Basal skull fractures (BSF) 3.5-25%4,5
(i) Incidence lower in pediatric patients
1. Increased flexibility of skull base
2. Underdevelopment of ethmoid, frontal, and mastoid air cells
(2) Maxillofacial fractures 23%5
(3) Cranial vault fractures 1%5
Davis 2
B) Morbidity
i) Severe TBI with skull fractures is associated with a moderate or poor outcome6,7
(a) Intensive care unit admission, ventilator support during recovery, increased risk for
prolonged hospital length of stay8
ii) Permanent neurologic disorders6
(a) Epilepsy, blindness, deafness, diplopia, facial paralysis, other cranial nerve deficits 9,10
iii) Traumatic encephalocele
(a) Herniation of brain tissue
iv) Pneumocephalus4,11
(a) Entrapment of air under pressure in intracranial cavity
v) Cerebrospinal fluid leaks
(a) Escape of fluid that surrounds the brain and spinal cord
vi) Infectious complications12
(a) Meningitis, encephalitis, intracranial abscesses, subdural empyema
(b) Head trauma is the most common cause of recurrent bacterial meningitis
C) Mortality
i) Early mortality has substantially declined over time7
ii) 7% mortality in mild TBI with BSF13
iii) 22% mortality in patients with penetrating injury and CSF leak14
iv) 65% mortality in severe TBI with skull fractures3
(a) 30-54% mortality in severe TBI
D) Cost5
i) Average cost of hospital stay in TBI cohorts from 2005-2009
(a) Without meningitis: $32,319
(b) With meningitis: $42,808
ii) Independent risk factors for escalating cost of hospitalization
(a) Rhinorrhea OR 2.0 (CI 1.6-2.7) and otorrhea OR 2.3 (1.9-2.7)
(b) Posttraumatic meningitis OR 3.1 (CI 2.5-3.8)
(c) Surgical intervention
E) Fracture classifications1
i) Characteristics
(a) Linear
(b) Depressed
(c) Compound
(d) Open
(e) Closed
(f) Penetrating
Davis 3
ii) BSF
(a) Characteristics
(1) Thin and more vulnerable to trauma
(2) Air-filled sinuses and multiple foramen render skull base more vulnerable to trauma
(b) Anterior BSF
(1) Type I, cribriform
(2) Type II, frontoethmoidal
(3) Type III, lateral frontal
(4) Type IV, complex
(c) Middle BSF
(1) Longitudinal - parallel to petrous portion of temporal bone
(2) Transverse - perpendicular to petrous portion of temporal bone
(3) Sella turcica fractures
(d) Posterior BSF
(1) Clivus
(i) Transverse, oblique, longitudinal
(2) Occipital
(i) Ring fracture- encircles foramen magnum at skull base
(ii) Occipital condyle- type I – IV
iii) Facial fractures15
(a) Le Fort I
(1) Horizontal maxillary fracture, separating the teeth from upper face, fracture line
passes through alveolar ridge, lateral nose and inferior wall of maxillary sinus
(b) Le Fort II
(1) Pyramidal fracture, passes through posterior alveolar ridge, lateral walls of maxillary
sinuses, inferior orbital rim and nasal bones
(c) Le Fort III
(1) Craniofacial disjunction, fracture line passes through nasofrontal suture, maxillofrontal suture, orbital wall and zygomatic arch
Figure 2. Le Fort Fracture Classifications
Le Fort I
Le Fort II
Le Fort III
www.hakeem-sy.com/main/node/26408
Davis 4
III) CSF
A) Function16
i) Provide physical support and buoyancy for brain/spinal elements
ii) Remove by-products of metabolism from neural tissues and regulates chemical
environment of brain
B) Production and circulation16,17
i) Produced by choroid plexus in the lateral, third, and fourth ventricles at a rate of 20-30
mL/h
(a) Approximately 90-150 mL total volume
ii) Flows from: lateral ventricles to third ventricle to fourth ventricle through subarachnoid
space and circulates through meninges before being reabsorbed via arachnoid granulations
IV) CSF leaks
A) CSF fistula5
i) A fracture involving skull or facial structures may produce a breach in dura
ii) Abnormal passageway allowing escape of CSF from subarachnoid space
iii) Can be associated with CSF leak
B) Types of CSF leaks
i) Rhinorrhea18,19
(a) 72% of CSF leaks
(b) CSF leak through nares
(c) Origins of leak19,20
(1) Fistula of anterior cranial fossa
(2) Fistula of temporal bone
(3) Fistula of middle cranial fossa through sphenoid sinus
(d) Presentation19,20
(1) Fluid initially may appear sanguineous
(2) Unilateral or bilateral clear fluid
(3) Discharge amount varies from drops to stream-like flow
(4) Reserviour sign
(i) Rush of fluid when patient brought from supine to upright with neck flexed
(ii) Useful for collection of diagnostic samples
(5) Anosmia19
(i) Inability to perceive odor
(ii) Present in 80% of cases or rhinorrhea and only 5% in TBIs
(6) Target sign or halo effect19,21
(i) CSF will migrate further when CSF/blood applied to filter paper
1. Apparent on pillowcase or sheets
(ii) Bull’s eye stain appearance
(7) Battles sign
(i) Periorbital ecchymosis
Davis 5
ii) Otorrhea
(a) 28% of CSF leaks18
(b) CSF leak through ear
(1) Typmpanic membrane may be intact or ruptured22
(i) Healing of tympanic membrane occurs within 1 week in ~80%23
(c) Origins of leak
(1) BSF involving temporal bone22
(d) Presentation21,23
(1) Clear fluid draining from ear
(2) Conductive hearing loss
(i) 20% still present 7 years post trauma
(3) Sensation of fluid or bubbles in ear
(4) Hemotympanum
(i) Presence of blood in tympanic cavity of middle ear
(5) Battles sign
(i) Retroauricular ecchymosis
C) Diagnosis of CSF leaks
i) High clinical suspicion of CSF leak in patients with skull fractures24
(a) Prompt recognition is key for instituting treatment and preventative measures9,21
(b) Potential to be overlooked due to nature of concomitant issues
ii) Diagnostic markers can confirm presence of CSF leak25
(a) Produced in CSF and when present in sample indicate presence of CSF
(1) Beta-2 transferrrin
(2) Beta-trace protein
iii) Confirm presence of concomitant fractures with imaging
(a) Computed tomography (CT) scan
(b) Formerly, X-ray
D) Incidence of CSF leak
i) 1-3% of all TBIs5,16,22
ii) 9 - 11% of penetrating head injuries4,20
iii) 10-30% of BSF6,25
iv) 36% of Le Fort fractures20
E) Time to presentation of CSF leak25
i) Acute
(a) Within 2 days following injury – 50%
ii) Delayed
(a) Within 1 week – 70%
(b) Within 3 months – 99%
iii) Sources of delayed presentation19,20
(a) Edema, inflammation, hematoma obstructing flow
(b) May appear in times of increased intracranial pressure (ICP)
Davis 6
F) Duration of CSF leak
i) Temporary
(a) Less than 24 hours
ii) Persistent
(a) Present greater than 7 days
(b) Characteristics of injury which prevent arachnoid mesh from sealing to dura21,26,27
(1) Fracture site mobility
(2) Disrupted blood supply
(3) Infections
iii) Intermittent
(a) Soft tissue or brain can obstruct flow
G) Treatment of CSF leak with skull fractures
i) Reduction and fixation of facial fractures as appropriate20
(a) Stabilize fracture and prevents disruption of dura by reducing movement of facial
skeleton
(b) Facilitate body’s natural repair of anterior fossa CSF leak
ii) Conservative treatment16,20
(a) Facilitate spontaneous resolution of CSF leak
(1) Adhesion formation and granulation from local inflamed meninges
(2) Mucosal swelling, local fibrosis, regenerated nasal mucosa
(3) Dura mater dose not regenerate
(b) Strict CSF precautions20,25
(i) Bed rest
(ii) Avoid: nose blowing, Valsalva maneuvers, straws, incentive spirometer
1. To prevent increase intracranial pressure
(2) Head elevation16,25
(i) At least 15º
(ii) To prevent negative gradient allowing ascending path for bacteria between
intracranial and paranasal sinus cavities
(c) Duration of treatment is controversial
(1) Typically pursued for 1 week
(d) Spontaneous resolution outcomes
(1) Within 3 days in 40% of all cases22
(2) Within 1 week in 70% of rhinorrhea16,22,28
(3) Within 10 days in 85% of rhinorrhea16
(4) Ultimately in 98% of rhinorrhea
(5) Otorrhea ceases spontaneously in nearly all cases
(6) Spontaneous closure higher with temporal bone fractures than BSF
Davis 7
iii) CSF diversion
(a) If conservative treatment fails25
(i) Typically after 1 week29
(b) Treatment options
(1) Temporary CSF drainage device placed
(i) Lumbar drain
(ii) External ventricular drain (EVD)
(iii) Duration less than 7 days due to increased infection risk
iv) Surgical management4,16
(a) Employed for definitive closure of CSF leak
(1) Failure of conservative management and CSF diversion
(b) Approaches
(1) Advances in neurosurgical approaches from open craniotomies to endoscopic
procedures
(2) Surgical approach and graft type used to repair leak depends on individual clinical
scenario
(i) Based on force of impact, location of fistula, temporal relationship between the
leak and traumatic event
(ii) Endoscopic endonasal approach preferred
(iii) Transcranial approach, extracranial approach, suprasinus transfrontal approach
also available
(c) Outcomes25
(1) 75-100% success rate
V) CNS Infections4,20,22,30
A) CSF fistulas allow direct access of nasophyaryngeal and middle ear flora to the subarachnoid
space
B) Pathogens30,31
i) Most common: Streptococcus pneumoniae, Haemophilus influenzae
ii) Less common: gram-negative, more resistant pathogens
C) Can appear within hours or up to years after injury4,19,24
i) Median onset 5-13 day
D) Risk factors for meningitis
i) CSF leaks
(a) Not associated with severity of leak or size of dural tear19,20
(b) Rhinorrhea increases risk 23-fold5
(c) Otorrhea increases risk 9-fold
(d) Persistent leaks increase risk 9-fold16,24,28,32,33
(1) Improper healing or traumatic encephaloceal
ii) Pneumocephalus increase risk up to 4-fold11,16
Davis 8
iii) Fracture types
(a) Penetrating fractures14
(1) Compound fractures with skull depressed deeper than thickness of cranium12
(2) Incidence of infection ~ 10%34
(b) Frontobasilar fractures proximal to midline33
(c) Fracture displacement > 1 cm
iv) GCS < 829
(a) Associated with severity of injury and increased utilization of invasive interventions
v) Surgical interventions are associated with a 5-fold increase risk retrospectively5
(a) Craniotomies12
(1) Incidence 0.8-1.5%
(i) Risk associated with concomitant infection at site of incision and duration of
surgery greater than 4 hours
(b) EVDs
(1) Incidence 4-17%
(i) Increased risk associated with colonization of catheter at time of surgery
Figure 3. Incidence of Meningitis Associated with CSF Leaks in Literature10,17,22,24, 26,27,3043,46,49,50
2010
2009
2004
2004
2004
1996
1995
1995
1993
1992
1991
1988
1986
1983
1978
1976
1976
1975
1973
1966
1966
1954
1942
4.3% (2 / 47)
0% (0 / 9)
18.5% (15 / 81)
0% (0 / 34)
0% (0 / 12)
10.3% (10 / 97)
6.8% (6 / 88)
4% (2 / 50)
9.8% (21 / 215)
3.6% (1 / 28)
4% (2 / 50)
1.4% (2 / 138)
8.3% (3 / 36)
6.1 % (2 / 33)
0% (0 / 7)
3.4% (2 / 58)
1.9% (1 / 52)
4.7% (2 / 43)
8.7% (13 / 149)
22.2% (12 / 54)
3% (1 / 33)
19% (16 / 84)
52.4% (11 / 21)
0%
10%
20%
30%
40%
50%
60%
70%
Davis 9
E) Incidence
i) 0.2- 17.8% of TBI 5,11
ii) When CSF leak is present5,25
(a) Range: 0-52%
(b) Median: 4.24%,
(c) Rhinorrhea: 7-38%
(d) Otorrhea: 2.6%
iii) Penetrating injury with CSF leak: 36%22
(a) 1.7% without CSF leak
iv) 12- 50% of cases are associated with recurrence35
F) Mortality6,20
i) Early studies found morbidity and mortality rates of 50% and 25% respectively for
intracranial infections following CSF rhinorrhea
ii) Recent literature suggests posttraumatic meningitis is associated with ~10% mortality rate
VI) Role of antibiotic prophylaxis24
A) Early publications emphasized importance of antibiotic use as a means of reducing meningitis
i) Advocated for patients who presented with CSF leak or pneumocephalus
ii) Recommended duration of prophylaxis 5-7 days after cessation of CSF leak
iii) Recommendation was based on perceived or theoretical risk of infection and experience of
authors
B) Proposed mechanism of benefit48,49
i) Antibiotics maintain sterility of CSF until defect in dura closes spontaneously or is
surgically corrected
ii) Antibiotics may eradicate bacterial colonization in nasopharynx, nasal sinuses, and aural
canal
Literature Review
C) 24 studies evaluating incidence of meningitis in patients with CSF leak
i) 19 evaluate the role of antibiotic prophylaxis
ii) Literature dating back to 1942
Figure 4. Role of Antibiotics
Position on Antibiotic Prophylaxis in Literature
16%
Supportive
53%
31%
Neutral stance
Does not support
Davis 10
D) Conflicting meta-analysis published18,49
i) Brodie et al. 1997
(a) Objective: determine efficacy of antibiotic prophylaxis in CSF leaks
(b) Population: 6 studies involving 324 patients
(1) Included all articles with case series and sufficient data to allow evaluation
(2) Findings
(i) 237 patients received prophylactic antibiotics and 87 did not
(ii) Overall incidence of meningitis: 15/234 (6.4%)
1. Antibiotic prophylaxis: 6/237 (2.5%)
2. Inadequate/no antibiotic prophylaxis: 9/87 (10%)
3. Associated with p value=0.006
(3) Conclusion: meningitis rate was significantly lower in patients who received
antibiotic prophylaxis
ii) Villalobos et al. 1998
(a) Objective: determine efficacy of antibiotic prophylaxis in patients with BSF
(1) Evaluated CSF leaks as a secondary endpoint
(b) Population: 12 studies involving 1241 patients
(1) CSF leak: 9 studies involving 547 patients
(c) Findings in patients with CSF leaks
(1) 297 received prophylactic antibiotics and 250 did not
(i) 6 studies with 179 patients with either rhinorrhea or otorrhea were evaluated
(ii) Overall incidence of meningitis 63/547 (11.5%)
1. Antibiotic prophylaxis: 29/297 (9.7%)
2. Inadequate/no antibiotics: 34/250 (13.6%)
3. Common OR 1.34 (CI 0.75-2.41)
(d) Concluded antibiotic prophylaxis after BSF does not appear to decrease risk of
meningitis
VII) Primary Literature
Leech PJ et al. The Lancet. 1973;1:1013-1016
24
Objective
Investigate incidence of meningitis, morbidity and mortality with adequate and inadequate
antibiotic prophylaxis
Trial design
Retrospective, single center review at teaching hospital in Glasgow
Patients
Inclusion: skull fracture with associated CSF leak from 1943-1972
Exclusion: not specified
Outcomes
Incidence of meningitis, morbidity and mortality
Methods
Adequate prophylaxis: penicillin 500 mg PO QID and sulfadimidine 500 mg PO Q6H from time
of injury until 1 week after CSF leak cessation
Inadequate prophylaxis: those not meeting above criteria
Diagnostic criteria: not specified for skull fractures, CSF leak, or meningitis
Follow up: clinic visits, postal query, reviewing cases of meningitis at hospital; for up to ten years
Davis 11
Statistics
Not specified





n=155
Referred for neurosurgical care: 141/155
CSF leak associated with fracture: 108/155
Surgical repair of rhinorrhea: 65/118
Le Fort fractures: all received antibiotic prophylaxis, incidence not specified
Rhinorrhea
Results
Otorrhea
Mortality
Morbidity
Pathogens
Adequate
Prophylaxis
n=95
No Adequate
Prophylaxis
n=54
Number
76
42
Meningitis
leak < 1 week
0 (0%)
7 (17%)*
Number
19
12
Meningitis
1 (5%)
5 (41.7%) *
Overall
2/155 (3%)
Attributable
0/15 (0%)
Anosmia
Majority
Recurrent rhinorrhea
4/124
Streptococcus pneumonia n=5, coliforms n=1, no growth n= 5
* p ≤0.05
Increased incidence of meningitis associated with otorrhea if fracture was associated with
middle fossa (p=0.01)
 All patients with meningitis recovered satisfactorily
 The inference is clear: all cases of CSF otorrhea should receive adequate antibiotic
prophylaxis from time of injury until 1 week after the leak has ceased.
 The benefit of adequate chemotherapy in protecting patients from meningitis in patients with
rhinorrhea has been demonstrated.
Strengths
 Large patient population
 Majority of fractures associated with middle or anterior fossa
 Morbidity and mortality were examined as endpoints
Limitations
 Temporal bias: variations in surgical procedures, CSF precautions, antibiotic selection,
prevalence of resistant organisms
 Included pre-existing cases of meningitis
 High incidence of meningitis with otorrhea
 Unknown exposure to antibiotics in patients receiving inadequate prophylaxis
 Incidence of meningitis in rhinorrhea arm no longer associated with adequate or inadequate
prophylaxis following first week
 Extensive referral from outside hospitals
 Unknown baseline characteristics
 Statistical analysis used not specified
 Lack of specification of diagnostic techniques for fractures, CSF leak, meningitis
 Results favored use of antibiotic prophylaxis
 Questionable validity
 Broad spectrum of antibiotics and extended duration of treatment

Authors’
conclusions
Critique
Take home
points
Davis 12
50
Ignelzi RJ et al. J Neurosurg. 1975;43:721-726
Objective
Primary: determine efficacy of antibiotic prophylaxis in treatment of BSF
Post hoc: determine effect of prophylactic antibiotics on nasopharyngeal flora
Trial design
Combined retrospective and observational prospective at Denver General Hospital
Retrospective arm: patients admitted with BSF, initiated on antibiotic prophylaxis (ampicillin,
cephalothin, or other)
Prospective arm: withheld antibiotic prophylaxis for BSF; antibiotic treatment was indicated if
fever, neck stiffness, clinical deterioration
Patients
Retrospective arm: Adult patients with traumatic BSF who survived > 10 days
Prospective arm: Adult patients with BSF admitted for 10 day observation, excluded patients who
received antibiotics for other indications
Outcomes
Rates of CNS and other other infections, nasopharyngeal cultures on admission, day 5 and 10
Methods
First year: Antibiotic prophylaxis (ampicillin or cephalothin 1 g Q6H IV x 3 days or until 2 days
after cessation of CSF leak then IM or PO antibiotics for duration of hospitalization
Posterior nasopharynx cultures: Post hoc endpoint, randomized to receive either no antibiotic,
ampicillin or cephalothin; obtained at hospital admission, day 5 and day 10
Follow up: method unspecified
Statistics
Results
 ANOVA
 Fisher’s exact test
 Chi-square
 n=129 with 136 BSF
 n=40 with CSF leak
 Follow up: 3-24 months
Baseline characteristics
 Treated group had increased incidence facial fractures and one compound depressed fracture
 No antibiotic prophylaxis group had more patients unconscious for > 24 hours, CNS
operations, prior medical illness
 Prophylaxis: ampicillin: n=41 cephalothin: n=9 other: n=4
Prophylaxis
No Prophylaxis
(Retrospective)
(Prospective)
CSF leak n=17
CSF leak n=26
CNS infections
2 (12%)
0 (0%)
Pathogens isolated
Resistant E. coli n=1,
no growth n=1
N/A
Attributable mortality
1 (50%)
N/A
Attributable morbidity
Mortality, overall
1 (50%)
7.2%
N/A
7.4%
Davis 13
Nasopharyngeal Cultures Results
Antibiotic Exposure
Day 0
Day 5
Day 10
None (n=5)
Normal
Unchanged
Unchanged
Cephalothin (n=3)
Normal
Gram-negative (n=2)
Increased normal (n=1)
Gram-negative (n=2)
Increased normal (n=1)
Ampicillin (n=2)
Normal
Gram-negative
Gram-negative
Normal- Streptococcus and Staphylococcus sp.
Gram negative- resistant to antibiotic therapy
Outcomes Associated with Antibiotic Administration
Antibiotic administered
Nasopharyngeal flora not sterilized
Alteration of flora to resistant bacteria
Alteration of potential pathogen
Authors’
conclusions



Antibiotics are ineffective in preventing CNS infections and in some cases, harmful.
Antibiotics associated with more resistant, invasive and potentially pathogenic organisms in
nasopharynx.
Recommend close observation for early signs of meningitis and if present, start appropriate
antibiotics.
Strengths
Critiques
Take home
points
 Included observational prospective arm
 Post hoc investigation of antibiotic impact on nasopharyngeal flora
Limitations
 Not specific to those with CSF leak, x-ray confirmation of fracture was present in 14/129
patients
 Not adequately powered to determine no difference exists or more harm associated with
antibiotics, limited number of patients with CSF leak in 2 year time frame
 Unknown demographic information; epidemiologic, fracture specific, time to onset/duration
of CSF, role of CSF precautions, duration of leak, duration of antibiotics or length of
hospitalization
 More selective criteria for the prospective portion



No benefit demonstrated with antibiotic prophylaxis
Nasopharyngeal cultures demonstrated no sterilization of site
Change from usual nasopharyngeal flora to gram-negative/resistant bacteria
Davis 14
Eljamel MS. Br J Neurosurg. 1993;7:501-505
35
Objective
Evaluate efficacy of antibiotic prophylaxis in patients with CSF leak prior to surgical dural repair
Trial design
Retrospective analysis of patients with CSF leaks who received adequate or inadequate antibiotic
prophylaxis prior to surgical dural repair at Mersey Regional
Patients
Inclusion: adult patients with CSF fistula
Exclusion: patients who received antibiotics for reasons other than CSF leak, from time of surgical
dural repair forward
Outcomes
Meningitis, mortality, and pathogens isolated
Methods
Similar age, CSF leak type, duration of leak, presence/absence of skull fractures
Adequate antibiotic prophylaxis: if started within 3 days of onset of CSF leak; penicillin 500 mg
Q6H and sulponamide 500 mg Q6H and continued for at least one week after CSF leak cessation
Meningitis diagnosis: based on clinical signs and symptoms, confirmed by isolating pathogen or
cytology of CSF
CSF leak: confirmed surgically or post-mortem
Follow-up: until surgical dural repair, death or 1990
Statistics




Chi-square test with Yate’s correction
Two-tailed p values
Log rank
Kaplan-Meier


Results
n= 253
Excluded= 38 patients for receiving antibiotics for other indications (pneumonia, facial
fixation) or were receiving antibiotics other than penicillin and sulponamide
Baseline characteristics
 Mean age 35 years old, majority male, with rhinorrhea and skull fractures
 More patients in the prophylaxis arm had facial fractures and pneumocephalus
 Majority of patients received antibiotic prophylaxis within 24 hours of injury
 Mean follow-up 2.5 years
Adequate Prophylaxis
Inadequate Prophylaxis
n=106
n=109
52
26
Facial fractures
76
75
Skull fractures
99
97
Rhinorrhea
17 days
20 days
Duration CSF leak, mean
31 (29%)
12 (11%)*
Pneumocephalus
7 (6%)
10 (9%)
Meningitis, first week
8 (8%)
13 (12%)
Meningitis, per year
20 (19%)
36 (33%)
Meningitis, total
6
22
Streptococcus pneumoniae
3
0*
Gram-negative
11
14
No pathogen isolated
86 (81%)
84 (77%)*
Survival free from meningitis,
1 month
20 (19%)
25 (22%)
Mortality
*p value <0.05
Davis 15
Strengths
Critiques
 Large population
 Specific to CSF leaks
 Fracture type specified
 Primary endpoint examining efficacy of antimicrobial prophylaxis
 Excluded patients receiving antibiotics for other indications
Limitations
 More pneumocephalus and facial fractures in antibiotic prophylaxis arm
 Mean duration of CSF leak 17-20 days
 Broad antibiotic coverage and extended duration of prophylaxis
 Unknown demographic information, mode of injury, incidence of penetrating or other fracture
characteristics, number of patients receiving CSF diversion
Authors’
conclusions


These data do not support routine use of antibiotic prophylaxis in patients with CSF leak
It is ethically justifiable to withhold antibiotic prophylaxis in patients with CSF fistula until a
prospective controlled double-blind trial has settled the question
Take home
points

No statistically significant in incidence of meningitis in a well-designed retrospective review
VIII) Limitations in literature
A) Lack of power of individual studies
i) Infrequent incidence of CSF leaks
ii) Even lower incidence of post-traumatic meningitis
B) Confounding factors in studies
i) Retrospective
ii) Lack of randomization
C) Temporal bias
i) Treatment of CSF leak
(a) CSF precautions
(b) CSF diversions and surgical management
ii) Antibiotic availability
iii) Alteration in pathogens
IX) Conclusions
A) Overall the data supporting the use of antibiotic prophylaxis to prevent meningitis in post
traumatic CSF leaks is of poor quality
B) Convincing evidence to support antibiotic prophylaxis is lacking
C) Randomized, prospective, multicenter trials are needed to provide further evidence
D) Harm has been demonstrated with administration of prophylactic antibiotics
Davis 16
X) Recommendation
i) Antibiotic prophylaxis in skull fractures with CSF leak not recommended to prevent
meningitis
(a) Closed fractures of basilar skull or skull vault
ii) Concomitant conditions may benefit from antibiotic prophylaxis
(a) Le Fort facial fractures, open/penetrating fractures, compound/depressed skull fractures
(b) Potential benefit in high-risk subsets of patients with multiple risk factors cannot be fully
excluded based on current level of evidence
(1) Lack of randomization
(2) High risk patients typically received antibiotic prophylaxis
(c) Antibiotic prophylaxis when selected should cover pathogens most likely to colonize
patient’s nasopharynx
(d) Duration should be one week after CSF leak resolution
iii) Regardless of presence of antibiotic prophylaxis, patients should be monitored for signs
and symptoms associated with meningitis
(a) If suspected, empiric treatment of meningitis should be promptly initiated
(1) Obtain cultures
(2) Vancomycin + cefepime
Davis 17
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
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Davis 19
Appendix A
Score
1
2
Glasgow Coma Scale (GCS)
Eye opening
Verbal response
Motor response
None
Incomprehensible sounds
No movements
Extends to pain
3
4
5
None
Open to painful
stimulation
Open to voice
Open spontaneously
-
Inappropriate words
Confused, disoriented
Oriented, converses
6
-
-
Abnormal flexion to pain
Withdrawals to pain
Localizes to painful
stimulus
Obeys commands
Severity of TBI based on GCS
Severity
GCS Score
13-15
Mild
9-12
Moderate
<8
Severe
Davis 20