Discussion

Antibiotic resistant pathogens present a significant threat in modern medicine, making current antibiotics less effective.^{Reference Naghavi, Murray, Ikuta, Mestrovic, Swetschinski and Sartorius2} As such, antibiotic stewardship is essential as global resistance continues to rise.

At present, there is limited evidence based data available evaluating antibiotic usage in patients undergoing anterior skull base surgery involving closure of a CSF leak. Indeed, there is a significant variation in practice for the use of peri-operative and post-operative antibiotics in anterior skull base surgery as documented in a survey of the North American Skull Base Society.^{Reference Fang, Hawn, Agarwal, Moskowitz, Kshettry and McKean3}

A met-analysis study, published in 2023, regarding antibiotic prophylaxis for endoscopic endonasal skull base tumour surgery demonstrated similar conclusions regarding antibiotic usage. Regimes varied from two doses of a single agent to more commonly prolonged post-operative courses up to 5 days with the use of more than one agent.^{Reference Kwon, Shin, Yoon, Kim and Byun4}

The endoscopic endonasal approach, through the paranasal sinuses, provides a direct corridor to the central component of the anterior skull base. It is classed as clean contaminated surgery. Unfortunately, the honeycomb nature of the sinuses attached to the undersurface of the skull base presents a significant issue for antiseptic preparation. In contrast to traditional surgery, where by the surgical field undergoes antiseptic preparation before the skin is incised, this is really impossible to achieve within the nasal cavity. As the endonasal instruments pass in and out of the nostrils all the sterile surgical instruments eventually become contaminated. These instruments continually pass through the non-sterile endonasal corridor and beyond the dura during the operation. When repairing the anterior skull base defect, graft material will also pass through this non-sterile corridor before being placed beyond the dura to effect a CSF repair.

It is therefore not surprising that meningitis can occur following such procedures and that surgeons prescribe prophylactic antibiotics in order to reduce the risk of this serious complication. In searching the literature, it is easy to find the overall post-operative meningitis rate for endoscopic endonasal anterior skull base surgery, but this overall figure can be misleading. In one meta analysis, published in 2020, of 2275 cases a post-operative meningitis rate of 1.6 per cent was recorded.^{Reference Abiri, Abiri, Goshtasbi, Lehrich, Sahyouni and Hsu5} However, such data combine cases where intra-operative CSF was evident, with surgery where no CSF was encountered and the vast majority of the patients are in the latter group. One would assume that the risk of meningitis would be significantly increased in the presence of active CSF leak into the nasal cavity at the time of the operation. In one systematic review, the post-operative meningitis rate following anterior skull base surgery involving CSF was however 13 per cent.^{Reference Lai, Trooboff, Morgan and Harvey6} In this current series, all repairs were caried out by one surgeon affording some uniformity to surgical technique and post-operative care.

At present, no consensus exists on the type of repair that should occur in anterior skull base surgery whether CSF is observed intraoperatively or not. This was highlighted in a recent national prospective observational study in the UK.^{Reference Khan, Bandyopadhyay, Patel, Schroeder, Cabrilo and Choi7}

None of the cases in the current study underwent any formal peri-operative decontamination of the nasal cavity before the start of surgery. All patients had a single dose, single agent peri-operative antibiotic. This is in contrast to most reported studies utilising multiple doses in the post-operative period. Augmentin was chosen as the peri-operative antibiotic of choice as it probably has the best cover for nasal and sinus bacteria.^{Reference Shibao, Toda, Tomita, Ogawa and Yoshida8} If the patient has a penicillin allergy, then Teicoplanin has been used.

In addition at the end of the surgical procedure all patients have had a small dissolvable nasal pack placed over the repair site, specifically to hold any onlay pedicle grafts in place. Lumbar drains at the time of the repair were not used even if the CSF defect was deemed to be high flow.

The exact type or repair depended upon the defect size and if the CSF flow was deemed to be high or low flow. In general, spontaneous low flow leaks have been repaired by a fat plug technique with an onlay free mucosal graft.^{Reference Wormald and McDonogh9} Defects involving high flow CSF leaks involved an inlay graft with underlay support or a gasket type seal if an inlay graft was not possible followed by an onlay pedicled nasoseptal flap.^{Reference Nix, Tyagi and Phillips10}

Post-operatively, patients were advised to use saline nasal rinses twice daily for one month.

In identifying cases of post-operative meningitis, the patients electronic records and microbiology results were searched for a minimum of 60 days post-procedure. In addition, all letters pertaining to the procedure were also reviewed to the limit of the electronic record in order to capture any patient that may have developed meningitis and had been admitted to another hospital. Meningitis was defined as having positive culture results or being treated for suspected meningitis. Adopting this wide definition of meningitis without having to have positive culture results may have resulted in overestimation of the rate of post-operative meningitis in this current series.

Overall, 10 of the 285 patients were treated for suspected meningitis in the post-operative period (3.5%). Of the six patients with positive culture results, this equates to a 2 per cent post-operative bacterial meningitis rate following the repair of a CSF leak in the anterior skull base, utilising a single dose of an antibiotic in the peri-operative period. The small number of positive cultures grew diverse organisms allowing no inferences to be made about this.

This rate of post-operative meningitis compares favourably with the reported literature, especially in the context of a single agent single dose antibiotic. Kong et al. report a 17.4 per cent post-operative meningitis rate in 46 patients following repair of a skull base defect with patients receiving a 5 day post-operative course of antibiotics.^{Reference Kong, Kim, Kim, Min, Nam and Park11} Ivan et al. report a 13 per cent meningitis rate cased upon 75 cases.^{Reference Ivan, Iorgulescu, El-Sayed, McDermott, Parsa and Pletcher12} Conger et al. report a 2.1 per cent post-operative bacterial meningitis rate in 284 patients receiving a 24 hour to 5 day post-operative antibiotic course.^{Reference Conger, Zhao, Wang, Eisenberg, Griffiths and Esposito13}

Of the 10 patients in this series, only 6 had CSF cultures drawn from a lumbar puncture that grew organisms. Three patients had no growth following CSF cultures, and one patient did not have a CSF sample taken for culture. Of the three patients with no growth, two of the patients had resection of a craniopharyngioma and may have developed a chemical meningitis, due to dispersion of the craniopharyngioma contents during resection.

It is noteworthy that 9 of the 10 patients that developed a post-operative meningitis had undergone resections of skull base tumours, meningiomas, craniopharyngioma and chordomas and had developed a post-operative CSF leak. This reached significance with a Fishers exact test. As such, developing a CSF leak following a repair of the anterior skull base endoscopically is the most significant risk factor for post-operative meningitis, an observation previously documented.^{Reference Kono, Prevedello, Snyderman, Gardner, Kassam and Carrau14} In contrast no cases of post-operative meningitis were observed following repair of a spontaneous or traumatic anterior skull base CSF leak.