Neurosurgical infections (adult only) Antibiotic Guidelines Classification: Clinical Guideline Lead Author: Antibiotic Steering Committee Additional author(s): as above Authors Division: DCSS & Tertiary Medicine Unique ID: 144TD(C)25(E2) Issue number: 4 Expiry Date: January 2021 Contents Who should read this document? 2 Key practice points 2 Background/ Scope/ Definitions 2 What is new in this version? 3 Guideline Microbiology and Antimicrobial rationale Neurosurgical Infections Guideline Tables Implantable electronic stimulator device infection 4 4 5 10 Standards Explanation of terms and definitions 11 11 References and Supporting Documents 11 Roles and Responsibilities 12 Document control information (Published as separate document) Document Control 13 Policy Implementation Plan Monitoring and Review Endorsement Equality analysis Page 1 of 14
Who should read this document? This policy applies to all clinical staff involved the prescribing of antimicrobials. Key Practice Points This policy recommends empirical therapy regimens for neurosurgical infections in adults: Brain abscess Subdural empyema Intracranial epidural abscess Septic intracranial thrombophlebitis CSF shunt infections Postoperative / Post neurosurgical meningitis EVD (External ventricular drain) related ventriculitis Post neurosurgical wound infection including osteomyelitis Implantable electronic stimulator device infection Background/ Scope/ Definitions Antimicrobial agents are among the most commonly prescribed drugs and account for 20% of the hospital pharmacy budget. Unfortunately, the benefits of antibiotics to individual patients are compromised by the development of bacterial drug resistance. Resistance is a natural and inevitable result of exposing bacteria to antimicrobials. Good antimicrobial prescribing will help to reduce the rate at which antibiotic resistance emerges and spreads. It will also minimise the many side effects associated with antibiotic prescribing, such as Clostridium difficile infection. It should be borne in mind that antibiotics are not needed for simple coughs and colds. In some clinical situations, where infection is one of several possibilities and the patient is not showing signs of systemic sepsis, a wait and see approach to antibiotic prescribing is often justified while relevant cultures are performed. This document provides treatment guidelines for the most common situations in which is required. The products and regimens listed here have been selected by the Trust's Medicines Management Group on the basis of published evidence. Doses assume a weight of 60-80kg with normal renal and hepatic function. Adjustments may be needed for the treatment of some patients. This document provides treatment guidelines for the appropriate use of antibiotics. The recommendations that follow are for empirical therapy and do not cover all clinical circumstances. Alternative antimicrobial therapy may be Page 2 of 14
needed in up to 20% of cases. Alternative recommendations will be made by the microbiologist in consultation with the clinical team. This document refers to the treatment of adult patients (unless otherwise stated). Please refer to up to date BNF/SPC for a full list of cautions, contra-indications, interactions and adverse effects of individual drugs. In the case where an antibiotic prescription is necessary, probiotic therapy should be considered in order to reduce the risk of C. difficile infection. What is new in this version? For neurosurgical infections covered in this policy; use oral metronidazole in preference of IV if enteral route available. Advice on appropriate trough serum Vancomycin level to aim for when treating neurosurgical infections (15-20 mg/l if mg/l if continuous infusion). Once daily dosing of Ceftriaxone IV advised for intra-cranial epidural abscess (provided no evidence of dural infection or meningitis). For CSF shunt infections; post-operative/ post neurosurgical meningitis; and EVD related ventriculitis, duration of IV antibiotics changed to 10-14 days (from last positive CSF culture) and IT antibiotics to 5 days. Advice on use of rifampicin in neurosurgical infections removed. Empirical antibiotic regime for post neurosurgical wound infections involving the bone flap, changed to and Ceftriaxone 2g IV once daily; with caveat for the use of Meropenem IV. Page 3 of 14
Guideline Microbiology of Neurosurgical Infections Typical organisms commonly associated with community acquired intracranial abscesses are Streptococcus milleri and anaerobes. Typical organisms associated with neurosurgical infections following trauma and neurosurgery are Staphylococcus aureus and Gram negative bacilli like Klebsiella spp, Enterobacter spp, E. coli etc. Typical organisms associated with shunts, drains (EVD) and implants (e.g. titanium cranioplasty) are coagulase negative staphylococci, diptheroids, Propionibacterium spp, S. aureus, etc. Rationale for route, dose, choice and duration of antimicrobial therapy Antibiotics need to cross the blood brain barrier for effective management of neurosurgical infections. Hence intravenous route (parenteral route), maximum dose of the antibiotics and prolonged therapy (typical course length of up to 6 weeks) is recommended for optimal management of neurosurgical infections. There are limited numbers of antibiotics (i.e. metronidazole, rifampicin) which have high bioavailability and are effective in crossing the blood brain barrier even when given orally. Page 4 of 14
Clinical diagnosis Initial antibiotic therapy Typical Comments Brain abscess in a patient admitted from the community (infective source paranasal sinuses, otogenic, dental or unknown source) Brain abscess secondary to open or penetrating trauma Brain abscess Postoperative following any neurosurgical operation / intervention / procedure Subdural empyema (secondary to contiguous source infection, haematogenous spread or following trauma) Subdural empyema for patients who have recently had neurosurgical operation / procedure /regimen Ceftriaxone 2g IV twice daily Metronidazole 400mg po every 8 hours (IV Metronidazole 500mg can be used if no enteral route) Ceftriaxone 2g IV twice daily Metronidazole 400 mg po every 8 hours (IV Metronidazole 500mg can be used if no enteral route) Meropenem IV 2g every 8 hours Ceftriaxone 2g IV twice daily Metronidazole 400 mg po every 8 hours (IV Metronidazole 500mg can be used if no enteral route) Meropenem IV 2g every 8 hours duration Page 5 of 14
Clinical diagnosis Initial antibiotic therapy Typical Comments Intracranial epidural abscess /regimen Ceftriaxone 2g IV twice daily (some patient may be able to step down to 2g once daily based on weight/progress/size of collection and providing there is no evidence of dural infection or meningitis) duration Suppurative / septic intracranial thrombophlebitis Metronidazole 400 mg po every 8 hours (IV Metronidazole 500mg can be used if no enteral route) Ceftriaxone 2g IV twice daily Metronidazole 400 mg po every 8 hours (IV Metronidazole 500mg can be used if no enteral route) Page 6 of 14
Clinical diagnosis Initial antibiotic therapy Typical Comments CSF shunt infections: Shunt needs to be removed and EVD (external ventricular drain) needs to be inserted /regimen duration 10-14 days Please review microbiology culture. Meropenem IV 2g every 8 hours Discuss positive CSF microscopy/culture results with the duty microbiologist as additional/alternative agents may be indicated e.g: For Gram positives: Duration of treatment depends on clinical and microbiological response before reshunting. If repeated positive CSF cultures while on appropriate antibiotics, then extend treatment to10-14 days after last positive culture. Intrathecal (IT) vancomycin 20mg daily 5 days For Gram negatives: Intrathecal (IT) gentamicin 5mg daily 5 days See EVD policy for administration information Page 7 of 14
Clinical diagnosis Initial antibiotic therapy Typical Comments Post-operative / Post neurosurgical meningitis /regimen Meropenem IV 2g every 8 hours duration 10-14 days May be bacterial or aseptic. Review Microbiology culture results to determine if aseptic or infective. Please modify. *ASEPTIC MENINGITIS Occurs more frequently after surgery involving the posterior fossa, and it may occur as a result of a local inflammatory reaction to blood breakdown products or to tumor antigens. CSF samples remain culture negative or sterile. Antibiotic therapy can be stopped after 3 7 days if CSF samples are culture negative / sterile and the diagnosis of Aseptic meningitis is confirmed following clinical assessment of the patient and review of microbiology results. Page 8 of 14
Clinical diagnosis Initial antibiotic therapy Typical Comments External ventricular drain (EVD) related ventriculitis Diagnosis is confirmed if bacteria are seen or isolated from two consecutive samples of CSF (Gram stain and / or culture) /regimen Meropenem IV 2g every 8 hours duration 10-14 days Please review. Discuss positive CSF microscopy/culture results with the duty microbiologist as additional/alternative agents may be indicated e.g: For Gram positives: Intrathecal (IT) vancomycin 20mg daily For Gram negatives: Intrathecal (IT) gentamicin 5mg daily 5 days 5 days Remove and replace infected EVDs if repeat CSF samples continue to be culture positive despite appropriate intrathecal and / or systemic antibiotic therapy. If repeated positive CSF cultures while on appropriate antibiotics, then extend treatment to10-14 days after last positive culture. See EVD policy for administration information Page 9 of 14
Clinical diagnosis Initial antibiotic therapy Typical Comments Post neurosurgical wound infection not involving the skull bone / bone flap Post neurosurgical wound infection involving the bone flap (infected cranioplasty), skull bone osteomyelitis /regimen IV / oral Flucloxacillin 1g every 6 hours If penicillin allergic, Clindamycin IV 900mg every 8 hours OR oral 450mg every 6 hours (depending on clinical severity / assessment) duration 7 14 days Check MRSA status and consider IV vancomycin if known to be colonised with MRSA. Please review.. Ceftriaxone 2g IV once daily* Consider Meropenem 1g IV every 8 hours if patient has recently had broad spectrum antibiotics or is known to be colonised with multi-resistant Gram negatives e.g. ESBL or AMPc producers. Page 10 of 14
Clinical diagnosis Early postimplantation inflammation (localised erythema affecting the incision site within 30 days of implantation, including simple stitch abscess) Implantable electronic stimulator device infection Initial antibiotic therapy /regimen Oral / IV Flucloxacillin 1g every 6 hours If penicillin allergic, oral Clindamycin 450mg every 6 hours OR IV 900mg every 8 hours (depending on clinical severity / assessment) Typical Comments duration 7 10 days Discuss with microbiology if known to be colonised with MRSA. Review culture results and modify antibiotic treatment following discussion. Generator pocket / lead infection (spreading cellulitis affecting the site OR purulent exudate OR wound dehiscence OR erosion through skin OR fluctuance (abscess) ) Daptomycin IV 6mg/kg once daily (round up to nearest dose: 350mg, 500mg, 700mg or 850mg) Check CK weekly and at baseline. Discontinue statins during treatment. 6 weeks if device remains insitu 14 days if device removed Please review. Generator pocket / lead infection and severe sepsis (hypotension or signs of organ dysfunction) Piperacillin-tazobactam IV 4.5g every 8 hours (if allergic to penicillin use Meropenem 1g every 8 hours unless history of anaphylaxis, angioedema, urticaria or other severe reaction to a penicillin) 14 days following device removal Urgent device removal indicated Please review Page 11 of 14
Clinical evidence of infection involving the central nervous system (e.g. brain abscess, epidural abscess) Meropenem IV 2g every 8 hours 6 weeks Urgent device removal indicated Please review Page 12 of 14
Standards Document the Indication/rationale for antimicrobial therapy, including clinical criteria relevant to this. Review and document the patient s allergy status Ensure the choice of antibiotic complies with the antibiotic guidelines and you have documented any clinical criteria relevant to the choice of agent. Document a management plan including a stop or review date. Where relevant, consider drainage of pus or surgical debridement/removal of foreign material. Explanation of terms & Definitions NA References and Supporting Documents 1. Report by the Infection in Neurosurgery working party of the British Society for Antimicrobial chemotherapy. The rational use of antibiotics in the treatment of brain abscess: Br J Neurosurgery 2000; 14: 525-530 2. Working party on the use of antibiotics in Neurosurgery of the British Society for Antimicrobial chemotherapy. Treatment of infections associated with shunting for hydrocephalus. Br J Hospital Medicine 1995; 53: 368 373 3. Infection in Neurosurgery working party of the British Society for Antimicrobial chemotherapy. The management of neurosurgical patients with postoperative bacterial or aseptic meningitis or external ventricular drain associated ventriculitis. Br J Neurosurgery 2000; 14: 7 12 4. Beek D, Drake JM, Tunkel AR. Nosocomial bacterial meningitis. N Eng J Med 2010; 362:146 154 5. Bjerknes S, Skogseid IM, Saehle T, Dietrichs E, Toft M. Surgical Site Infections after Deep Brain Stimulation Surgery: Frequency, Characteristics and Management in a 10-Year Period. PLoS ONE 9(8): e105288 doi: 10.1371/journal.pone.0105288 Page 13 of 14
6. Tunkel, A et al. 2017 Infectious Diseases Society of America s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clinical Infectious Diseases 2017 Roles and responsibilities All clinical staff involved in the prescribing of antimicrobials to adhere to this policy including full documentation on EPMAR as detailed. Page 14 of 14