Introduction
Cerebrospinal fluid (CSF) leaks carry a risk of ascending bacterial meningitis of up to 19 per cent.Reference Daudia, Biswas and Jones1 Cerebrospinal fluid leaks from the anterior skull base are increasingly being managed by rhinologists rather than neurosurgeons. Patients with a CSF leak are commonly referred to rhinologists specialising in anterior skull base surgery for endoscopic repair, which may not take place for several weeks after diagnosis.
There are currently no UK guidelines for the use of antibiotics and/or immunisations in patients with an active anterior skull base CSF leak. We aimed to define current UK practice in this area with a view to producing appropriate guidelines for use by all ENT surgeons in the UK.
Materials and methods
A web-based survey of all members of the British Rhinological Society was undertaken, distributed via the ENT-UK British Rhinological Society e-mail list with a hyperlink to the survey website.
Those contacted were asked to fill in the survey only once. The internet protocol (‘IP’) address of the referring computer was logged, but no personal information was retained. Entries from duplicate internet protocol addresses were rejected. The survey results were collected over a period of 30 days in June and July 2013.
The questions asked in the survey can be seen in Table I. The literature regarding antibiotic prophylaxis and the use of immunisations in patients with known CSF leaks was reviewed.
Survey questions
CSF = cerebrospinal fluid; pre-med = pre-medication; post-op = post-operative
Results
A total of 260 British Rhinological Society members were e-mailed. Fifty-two members completed the survey, giving a response rate of 20 per cent. Of those, 43 (82.7 per cent) reported being involved in the management of patients with CSF rhinorrhoea, and it was those individuals' responses that were reviewed thereafter in order to obtain an accurate picture of current UK practice in this subspecialist area.
Six (14 per cent) of the rhinologists who responded routinely prescribe prophylactic antibiotics prior to definitive repair of a CSF leak, in addition to any that may be given in the peri-operative period (Figure 1).
Pie chart showing responses to question 2: ‘Do you routinely prescribe prophylactic antibiotics?’
Fifteen of the 43 responders (34.9 per cent) routinely ask patients with a CSF leak to seek immunisation against one or more organisms. One surgeon only does so if the primary repair fails. Of those 15 surgeons, 86.7 per cent advise immunisation against Streptococcus pneumoniae (pneumococcus), 60 per cent against Neisseria meningitides (meningococcus) and 46.7 per cent against Haemophilus influenzae (type b) (Figure 2). Only 46.7 per cent recommend immunisation against all 3 organisms, which equates to just 16.3 per cent of the 43 rhinologists whose responses were analysed. No responders recommended vaccination against any other pathogen.
Bar chart showing responses to question 3: ‘Do you routinely advise immunisation?’
One responder commented that they sometimes obtained functional antibody results before recommending vaccination against pneumococcus alone.
Discussion
Cerebrospinal fluid leaks from the anterior skull base may be congenital, spontaneous, traumatic, inflammatory or neoplastic in origin. Congenital leaks often relate to a meningocele or meningoencephalocele. These dural sacs may also be seen in some ‘spontaneous’ cases which perhaps represent a longstanding defect in the anterior skull base through which a meningocele develops, for example in response to weight gain. Traumatic CSF leaks may follow a head injury or be iatrogenic in origin. Certain inflammatory conditions, such as fungal rhinosinusitis, may cause erosion of the skull base, as can tumours of the nose and paranasal sinuses. Many anterior skull base leaks can be repaired endoscopically, with reported success rates of 75–100 per cent, and therefore the rhinologist is now frequently the person to whom such patients are referred.Reference Bernal-Sprekelsen, Alobid, Mullol, Trobat and Tomas-Barberan2, Reference Lund, Stammberger, Nicolai, Castelnuovo, Beal and Beham3
The diagnosis may be evident, for example in a patient with unilateral clear rhinorrhoea after a head injury with an obvious anterior skull base fracture on imaging. However, it can be less clear cut and require more time-consuming investigations, including measurement of beta-2 transferrin in the rhinorrhoea, computed tomography (CT) and magnetic resonance imaging scans, and in some cases a CT cisternogram.Reference Psaltis, Schlosser, Banks, Yawn and Soler4 Whilst these investigations are taking place, and prior to planning of definitive surgical repair, patients with a CSF leak remain at risk of ascending bacterial meningitis.
The incidence of meningitis in patients with an active CSF leak has been reported as being up to 10 per cent per year, year on year.Reference Eljamel and Foy5 It therefore seems reasonable to consider giving these patients some form of prophylaxis against meningitis. We were unable to find any published UK guidelines on the use of antibiotics and/or immunisations for this purpose. There are no published guidelines from the British Rhinological Society, the Society of British Neurological Surgeons, or the National Institute for Health and Care Excellence regarding the use of antibiotics and/or immunisations in patients with CSF leak, traumatic or otherwise.
A systematic review into the use of prophylactic antibiotics for iatrogenic CSF leaks concluded that there was no evidence either way.Reference Moralee6 However, in view of the potential for causing bacterial resistance or even a change in nasopharyngeal flora to more invasive organisms, the author felt that it was justifiable to withhold antibiotics in the absence of any clinical suspicion of meningitis.
A Cochrane review of the evidence for antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures was published in 2011.Reference Ratilal, Costa, Sampaio and Pappamikail7 The review comprises a meta-analysis of 5 randomised, controlled trials (RCTs) and 17 non-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention in patients with a skull base fracture (although not necessarily an active CSF leak). The results do not support the use of prophylactic antibiotics in patients with a skull base fracture, with or without a CSF leak.
Despite such evidence, or lack thereof, 14 per cent of the rhinologists who responded to our survey routinely prescribe antibiotic prophylaxis for patients with a CSF leak.
There are vaccinations available for the three most common organisms responsible for bacterial meningitis, namely S pneumoniae, N meningitides and H influenzae (type b).Reference Brodie8 All three are now routinely given as part of the UK childhood immunisation programme.Reference Cameron and Pebody9 However, there are no UK guidelines regarding their use in patients with CSF leaks.
There are different types of pneumococcal vaccine: the older 23-valent polysaccharide vaccine, and the newer 7-, 10- and 13-valent conjugate vaccines.10–12 Some European countries, including Ireland, Denmark, Finland, Sweden, Norway, Germany and Switzerland, recommend that patients with a known CSF leak are given the 23-valent polysaccharide vaccine.Reference Pebody, Leino, Nohynek, Hellenbrand, Salmaso and Ruutu11 In the UK, this vaccine is recommended for cochlear implant users (as the implants carry a risk of CSF leak), but not for those with a known CSF leak. Some countries in Europe (including Ireland, France, Italy, Denmark, Finland and Switzerland) recommend the use of the 7-valent conjugate vaccines in patients with a CSF leak, instead of or as well as the 23-valent polysaccharide vaccine.Reference Pebody, Leino, Nohynek, Hellenbrand, Salmaso and Ruutu11 The June 2014 online edition of the British National Formulary recommends pneumococcal vaccination; specifically, a single dose of the 23-valent polysaccharide vaccine, for individuals at increased risk of pneumococcal infection including ‘conditions where leakage of cerebrospinal fluid may occur’.12 There is no mention of CSF leak in the meningococcal or haemophilus vaccine sections.
The British National Formulary states that ‘most individuals can safely receive the majority of vaccines’.12 Whilst side effects are not common, they can include local reactions such as pain and inflammation, gastrointestinal disturbances, fever, headache, irritability, loss of appetite, fatigue, myalgia, and malaise. Other side effects include influenza-like symptoms, dizziness, paraesthesia, drowsiness, arthralgia, rash and lymphadenopathy. Hypersensitivity reactions, such as bronchospasm, angio-oedema, urticaria and anaphylaxis, are very rare.12
Only 35 per cent of those responders who manage patients with CSF leaks recommend vaccination against one or more of the organisms known to cause meningitis. Within this group, the majority advise immunisation against pneumococcus, which agrees with recommendations across Europe and within the British National Formulary. However, the rates fall to 60 per cent for meningococcus and to less than 50 per cent for haemophilus, with less than half of rhinologists suggesting that all three vaccinations are administered. Given the potentially serious, if not fatal, outcomes of bacterial meningitis, and the widely accepted safe use of these vaccines as part of the UK childhood immunisation schedule, it would seem prudent to advise patients with a CSF leak to be vaccinated against all three organisms.
• There are no UK guidelines on antibiotic and/or immunisation use for active anterior skull base cerebrospinal fluid (CSF) leaks
• The incidence of meningitis in patients with an active CSF leak has been reported as up to 10 per cent per year
• Many European countries recommend routine immunisation against pneumococcus in patients with a known CSF leak
• There is no evidence to support the use of prophylactic antibiotics in patients with an anterior skull base CSF leak
• Of the UK rhinologists surveyed in this study, 14 per cent prescribe prophylactic antibiotics prior to repair of CSF leak, and 34.9 per cent recommend immunisation
• We propose that all patients with an anterior skull base CSF leak are immunised against pneumococcus, meningococcus and haemophilus
We believe that patients should be advised to seek immunisation immediately if there is a proven CSF leak or a high clinical suspicion of one. The primary antibody response to immunisation takes 5 to 10 days; the secondary response occurs after approximately 21 days.Reference Siegrist, Plotkin, Orenstein and Offit13 Only a single dose of each vaccine is required to provide lifelong immunity against the bacteria. Patients will therefore remain protected in the event of a failure of the repair. The cost, according to the current edition of the British National Formulary, is £8.32 for the pneumococcal vaccine and £37.76 for a combined meningococcus and haemophilus vaccine; this is clearly a small amount when compared with the potential costs of a hospital admission with meningitis.12
Conclusion
There is no evidence to support the use of prophylactic antibiotics in the management of patients with anterior skull base CSF leaks, but we suggest that all patients with a proven (or strongly suspected) CSF leak should be immunised against pneumococcus, meningococcus and haemophilus prior to undergoing endoscopic repair.
Acknowledgements
We would like to thank the members of the British Rhinological Society who completed the online survey.
