Antibiotics in Neurosurgery

Contents
1. 2. 3. 4. Introduction MRSA screening of surgical patients Contact details Prophylaxis in Neurosurgery Elective, clean non-implant Elective, non-shunt implants Emergency, non-shunt implants Clean/contaminated procedures Elective, shunt implant Emergency, shunt implant Implantation of Ommaya reservoir CSF leak Craniotomy Penetrating craniocerebral injury Empirical treatment guidelines CSF shunt infections Extra-ventricular device (EVD)-associated ventriculitis Post-operative meningitis (no EVD in-situ) Post-operative surgical site infection Brain abscess Subdural empyema Discitis Antibiotics administered intraventricularly Paediatric antimicrobial treatment doses Therapeutic drug monitoring Page 2 2 2 3 4 4 4 4 4 5 5 5 5 5 6 6 6 6 6 6 6 6 7 11 12

5.

6. 7. 8.

(For bloodstream infections, ventilator-associated pneumonia, etc, see Antibiotic Guidelines for Surgical Patients with Infection)

1. Introduction
These antibiotic guidelines are for the surgical prophylaxis and treatment of neurosurgical infections. They have been drafted according to best practice, e.g. the Scottish Intercollegiate Guideline Network (SIGN). As there is a dearth of clinical trials in this area, these guidelines will be updated as new information becomes available or at 3 yearly intervals. We are grateful to Dr E M Brown, Consultant Microbiologist, Frenchay Hospital, Bristol, for access to the North Bristol NHS Trust Antibiotic Guidelines. All patients with contaminated wounds (e.g. following trauma) should have their tetanus status assessed If the patient is allergic to one of the recommended agents, please contact the microbiologists for advice. Please refer to the paediatric BNF for advice on dosing of antimicrobials in paediatric patients.

2. MRSA screening of surgical patients who to screen

Patients known to be MRSA colonised and who are being re-admitted to hospital Patients admitted from another hospital or health-care facility (e.g. nursing home) Patients with non-intact skin, including wounds and ulcers Patients due to undergo elective high-risk surgery (e.g. spinal and shunt implants) If the patient has been in hospital or has a history of MRSA colonisation, please contact the microbiologists for advice, as the patients antibiotic prophylaxis or treatment will need adjustment.

3. Contact details
Medical enquiries Consultant Microbiologists Dr E Smyth Prof H Humphreys Dr F Fitzpatrick Phone Ext 2017 Ext 3312 Ext 2938 Ext 2667/3320/3321 Bleep 319/443 Consultant-on-call via switch Bleep 046 E mail edmondsmyth@beaumont.ie hilaryhumphreys@beaumont.ie fidelmafitzpatrick@beaumont.ie

Registrars office

Out of hours Pharmacy enquiries Antimicrobial Senior Pharmacist

Ms. Sarah Foley

sarahfoley2@beaumont.ie

4. Prophylaxis in neurosurgery
Antibiotic prophylaxis is the use of antimicrobial agents to prevent infection or to prevent the clinical manifestations of infection if incubating. There are a number of situations where prophylactic antibiotics may be indicated e.g. various types of surgery (see below) or the insertion of a medical device or prosthesis. The choice of agent is influenced by the procedure and the likely pathogens. 4.1 Surgical prophylaxis should be prescribed in the appropriate section of the drug Kardex. 4.2 The duration of antimicrobial surgical prophylaxis should be a SINGLE dose, except in in two circumstances. These are:

A. Blood loss fluid replacement

Serum antibiotic concentrations are reduced by blood loss and fluid replacement, especially during the first hour of surgery when antibiotic levels are high. In the event of major intra-operative blood loss (>1.5 litres) additional doses of prophylactic antibiotic should be considered after fluid replacement

B. Prolonged surgical procedures

Many antibiotics, such as cephalosporins like cefuroxime, are short acting and therefore an additional dose should be administered during the surgery if the procedure lasts longer than 3 hours.

4.3 Give prophylaxis AT INDUCTION: The aim of prophylaxis is to have maximum tissue antibiotic levels at the time of first incision for this reason; prophylaxis is administered AT INDUCTION (30-60 MINUTES BEFORE SKIN INCISION). 4.4 MRSA Colonisation: If the patient has been in hospital or has a history of MRSA colonisation, please note that the patients antibiotic prophylaxis needs adjustment. 4.5 An agent that may be appropriate for surgical prophylaxis may not be the optimal agent for the treatment of an established infection. Therefore, the continuation of an agent that was initially used for prophylaxis may represent suboptimal therapy. If concerned, contact the microbiologists for advice.

PROCEDURE Elective clean, non-implant, e.g. odontoid screw Screen for MRSA beforehand (at least 5 days pre-op.) Elective, non-shunt implant, e.g. spinal rod Screen for MRSA beforehand (at least 5 days pre-op) Emergency, non-shunt implants and/or patient not screened for MRSA Clean/contaminated procedures e.g. sinuses or access via nasopharynx Elective shunt implant or revision. Screen for MRSA beforehand (at least 5 days pre-op)

PROPHYLACTIC REGIMEN

DURATION

MRSA negative CEFUROXIME 1.5g IV MRSA positive TEICOPLANIN 800mg IV

*1 dose at induction

TEICOPLANIN 800mg IV CEFUROXIME 1.5g IV plus METRONIDAZOLE 500mg IV MRSA negative CEFUROXIME 1.5g IV plus VANCOMYCIN 10mg intraventricularly plus GENTAMICIN 3mg intraventricularly MRSA positive eradicate MRSA. Then use TEICOPLANIN 800mg IV plus GENTAMICIN 3mg/kg IV plus VANCOMYCIN 10mg intraventricularly plus GENTAMICIN 3mg intraventricularly

*1 dose at induction *1 dose at induction

*1 dose at induction

*For prolonged operative procedures (>3 h) and/or major blood loss, additional intra-operative dose should be administered intravenously; 50% of original dose (every 3 hours) for cefuroxime or every 8 hours for metronidazole for the duration of the procedure. NO additional INTRAVENTRICULAR doses need to be given. NO additional doses of teicoplanin or gentamicin need to be given.

PROCEDURE Emergency shunt/implant or MRSA status unknown Implantation of Ommaya reserviour CSF leak (rhinorrhoea or otorrhoea) Craniotomy Screen for MRSA beforehand (at least 5 days pre-op) Penetrating craniocerebral injury

PROPHYLACTIC REGIMEN

DURATION

TEICOPLANIN 800mg IV plus GENTAMICIN 3mg/kg IV plus VANCOMYCIN 10mg intraventricularly plus GENTAMICIN 3mg intraventricularly

*1 dose at Induction

PROPHYLAXIS NOT REQUIRED

MRSA negative CEFUROXIME 1.5g IV MRSA positive TEICOPLANIN 800mg IV CEFUROXIME 1.5g IV plus METRONIDAZOLE 500mg IV 5 days *1 dose at Induction

*If procedure > 3 hours, and/or major blood loss, give an additional intra-operative dose intravenously; 50% of original every 3 hours for cefuroxime (i.e. cefuroxime 750mg IV) or every 8 hours for metronidazole for the duration of the procedure. NO additional INTRAVENTRICULAR doses need to be given. NO additional doses of teicoplanin or gentamicin need to be given.

5. Empirical Treatment Guidelines (before microbiology laboratory results available) for neurosurgical infections
INFECTION CSF shunt infections Extra-Ventricular Drain (EVD)-associated ventriculitis/meningitis Microbiology INVESTIGATIONS Shunt for culture REGIMEN Individualized after discussion with microbiology DURATION At least 2 weeks. Discuss with microbiology Individualized after discussion with microbiology. Monitor CSFs daily or as discussed with microbiology

Obtain 2nd CSF sample If initial sample suggestive (cells or Take blood cultures organisms seen on Gram stain)

Post-operative meningitis Blood cultures (no EVD in situ) Post-operative surgicalsite infection Brain abscess Blood cultures pus/swab for culture Pus/tissue for culture and TB

Subdural empyema Discitis

Pus/tissue for culture and TB Pus/tissue for culture and TB

VANCOMYCIN (see table page 7) + GENTAMICIN intraventricularly (see table page 7) and contact microbiology for advice Individualised after discussion with At least 2 weeks but microbiology individualized after discussion with microbiology FLUCLOXACILLIN 2g IV qds 2 weeks but IV PO (VANCOMYCIN 1g IV bd if MRSA positive FLUCLOXACILLIN after 4872 hours as indicated. 2 or suspected) weeks IV if MRSA Frontal CEFOTAXIME 2g IV qds plus Treat for a minimum of 4-6 METRONIDAZOLE 500mg IV tds plus weeks with 2 weeks FLUCLOXACILLIN 2g IV qds parenteral administration Total duration and I/V to PO Temporal/parietal CEFTAZIDIME 2g IV switch after discussion with tds plus METRONIDAZOLE 500mg IV tds microbiology plus FLUCLOXACILLIN 2g IV qds CEFOTAXIME 2 g IV qds plus A minimum of 2 weeks but METRONIDAZOLE 500mg IV tds plus individualized after discussion FLUCLOXACILLIN 2g IV qds with microbiology Depends on clinical context. At least 6 weeks but Contact the microbiologists individualized after discussion with microbiology

# Requires regular therapeutic drug monitoring 6

6. Intraventricular antibiotic treatment regimens for patients with EVD-associated ventriculitis/meningitis

See page 8 for INTRATHECAL DRUG ADMINISTRATION OF ANTIBIOTICS VIA INTRAVENTRICULAR DEVICE

Antibiotic

Dosage according to CSF volume of distribution (baseline dosage) <normal normal moderately >normal markedly >normal

Frequency of baseline dosage (according to CSF drainage since previous dose) <50 ml over 3 days every third day 50-100 ml over 2 days alternate days 100-150 ml in 24 hours daily daily + 5mg for each 50ml, or part thereof, >150ml daily + 1mg for each 50ml, or part thereof, >150ml >150ml in 24 hours

VANCOMYCIN

5mg

10mg

15mg

20mg

GENTAMICIN

2mg

3mg

4mg

5mg

every third day

alternate days

daily

INTRATHECAL DRUG ADMINISTRATION OF ANTIBIOTICS VIA INTRAVENTRICULAR DEVICE

GENTAMICIN and VANCOMYCIN* are the only antibiotics recommended in this

policy for administration into the CSF. INTRAVENTRICULAR administration of antibiotics should only be used after consultation with the clinical microbiology team. A senior member of the team experienced in intraventricular administration should prescribe and administer the antimicrobials. It is good practice that a double check procedure is in place when preparing antimicrobials for intraventricular administration.
*Unlicensed route of administration

INTRODUCTION Currently there are two methods commonly used to administer antibiotics directly into the CSF: a) Intraventricular injection b) Lumbar intrathecal injection. This route is not recommended as it produces unreliable CSF concentrations 1) GENTAMICIN Only the preservative free Gentamicin Intrathecal 5mg/ml Solution for Injection should be used. (currently Aventis brand).1 This product can be given intrathecally or intraventricularly and does not need to be filtered for administration into the CSF. It is recommended to draw up the required dose with 2ml of Sodium Chloride 0.9% Injection Ph. Eur., to help with intraventricular administration. 2) VANCOMYCIN This product is not available as a ready to use intraventricular injection and needs to be prepared from the intravenous injection. The vancomycin intravenous injection solution needs to be diluted appropriately and sterilised before it enters the CSF.2,3 The following items are needed for preparation of the intraventricular vancomycin injection. a) 1 x vancomycin 500mg vial preservative and antioxidant free. Hospira brand is suitable.4 b) 1 x Water for Injection Ph. Eur. 10ml preservative free. B Braun brand is suitable.5 c) 1 x Sodium Chloride 0.9% w/v Intravenous Infusion BP 50ml sterile non-pyrogenic Baxter Viaflo bag is suitable.6

d) 1 x 0.22micron sterilising filter Millipore Millex GP Sterilising Sterile Filter is suitable.7 Preparation of VANCOMYCIN 10mg/ml solution USE ASEPTIC TECHNIQUE 1) Reconstitute 500mg vial of vancomycin with 9.7ml of water for injection (this allows for displacement volume8). This gives a final concentration of 500mg/10ml. 2) Withdraw 19ml from a Sodium Chloride 0.9% w/v 50ml infusion bag and discard is a 9ml overfill in the 50ml infusion bag). 3) Add the 10ml of reconstituted vancomycin solution (500mg/10ml above) to the infusion bag and mix well. The bag will now contain VANCOMYCIN 500mg/50ml = 10mg/ml Administration of VANCOMYCIN intraventricularly USE ASEPTIC TECHNIQUE 1) Withdraw an appropriate amount of vancomycin 10mg/ml solution from infusion bag using a sterile syringe. 2) Remove the cover from the package that contains the sterilising filter unit. 3) Attach the syringe to the sterilising filter unit and remove from package. 4) Hold the syringe vertically with the filter unit pointing upwards and expel air by gently pushing the syringe plunger until the solution exits the unit. 5) Adjust volume to required amount. (See table below). Note solutions may only be filtered in one direction to avoid damage to filter membrane. 6) Inject solution into patients CSF via intraventricular access device; ensure sterilising unit is securely attached to both the syringe and access device. 7) Flush the catheter with 2ml Sodium Chloride 0.9% w/v Injection Ph. Eur.
6

(there

VANCOMYCIN dose required 5mg 10mg 15mg 20mg

Volume of 10mg/ml solution to be used 0.5ml 1ml 1.5ml 2ml

References 1) Electronic Medicines Compendium (eMC) accessed July 2009 http://emc.medicines.org.uk/medicine/14425/SPC/Gentamicin Intrathecal 5mg/ml Solution for Injection (sanofi-aventis)/ 2) Luer MS & Hatton J: Vancomycin administration into the cerebrospinal fluid: a review. Ann Pharmacother. 1993; 27:912-21. 3) Aalfs RL & Connelly JF: Comment: dilution of Vancomycin for intrathecal or intraventricular administration. Ann Pharmacother. 1996; 30:415 4) Personal email from Medical Information Officer, Mayne Pharma Plc, UK. Date March 1st 2007(On file). 5) Package insert for Water for Injections Ph. Eur. B Braun Medical Ltd, Ireland. July 2009 6) Viaflo Technical Support Brochure for Sodium Chloride 0.9% Intravenous Infusion BP, Baxter Healthcare Ltd., Ireland. May 2007. 7) Millipore website accessed July 2009. http://www.millipore.com/techpublications/tech1/pf0627en00 8) Personal email from Medical Information Administrator, Hospira UK Ltd, UK. Date 7th August 2009.

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7. Paediatric antimicrobial treatment doses. BNF for children 2008 chapter 5 NB 1. When calculating the dose for a child dose according to weight. BUT remember the adult dose should not be exceeded. 2. Where renal or hepatic impairment exists, consult more detailed references or contact pharmacy.
Antimicrobial CEFOTAXIME
Child 1month 18 years

50mg/kg IV every 8 12hours, increase to every 6 hours in very severe infections & meningitis (max. 12g daily) 25mg/kg IV every 8 hours; dose doubled in severe infection, febrile CEFTAZIDIME neutropenia & meningitis (max. 6g daily) FLUCLOXACILLIN 12.5mg 25mg/kg IV every 6 hours (max. 1g every 6 hours), may be doubled in severe infection. 50mg/kg IV (max. 2g) every 6 hours for CNS METRONIDAZOLE 7.5mg/kg IV (max. 500mg) every 8 hours VANCOMYCIN

15mg/kg IV every 8 hours (max. daily dose 2g)

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8. Therapeutic drug monitoring (TDM) for intravenous VANCOMYCIN & GENTAMICIN

VANCOMYCIN

Serum level pre 3rd dose, then Check pre dose levels every 2 3 days Serum level 18-24 hours after 1st dose, then Check trough levels every 2 3 days Impaired renal function check pre dose levels daily

Pre-dose: 10 15mg/L

GENTAMICIN once daily

Pre-dose: <1mg/L

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