Abstract

Background: Optimal management of intracranial infections relies on microbiological diagnosis and antimicrobial choice, but conventional culture-based testing is limited by pathogen viability and pre-sampling antimicrobial exposure. Broad-range 16S rRNA gene sequencing has been reported in the management of culture-negative infections but its utility in intracranial infection is not well-described. We studied the efficacy of 16S rRNA gene sequencing to inform microbiological diagnosis and antimicrobial choice in intracranial infections. Methods: This was a retrospective study of all intraoperative neurosurgical specimens sent for 16S rRNA gene sequencing over an 8-year period at a regional neurosurgical centre in the UK. Specimen selection was performed using multidisciplinary approach, combining neurosurgical and infection specialist discussion. Results: Twenty-five intraoperative specimens taken during neurosurgery from 24 patients were included in the study period. The most common reason for referral was pre-sampling antimicrobial exposure (68%). Bacterial rDNA was detected in 60% of specimens. 16S rRNA gene sequencing contributed to microbiological diagnosis in 15 patients and informed antimicrobial management in 10 of 24 patients with intracranial infection. These included targeted antibiotics after detection of a clinically-significant pathogen that had not been identified through other microbiological testing (3 cases), detection of commensal organisms in neurosurgical infection which justified continued broad cover (2 cases) and negative results from intracranial lesions with low clinical suspicion of bacterial infection which justified avoidance or cessation of antibiotics (5 cases). Conclusion: Overall, 16S rRNA gene sequencing represented an incremental improvement in diagnostic testing and was most appropriately used to complement, rather than replace, conventional culture-based testing for intracranial infection.

Highlights

  • Optimal management of intracranial infections relies on microbiological diagnosis and antimicrobial choice, but conventional culture-based testing is limited by pathogen viability and pre-sampling antimicrobial exposure

  • We studied the utility of a multi-disciplinary approach at our centre in selecting intraoperative specimens for 16S rRNA gene sequencing over an 8-year period

  • Specimens must be identified for 16S rRNA gene sequencing before they are discarded after prolonged culture

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Summary

Introduction

Optimal management of intracranial infections relies on microbiological diagnosis and antimicrobial choice, but conventional culture-based testing is limited by pathogen viability and pre-sampling antimicrobial exposure. The prognosis of brain abscess has improved substantially over the last 50 years, due to advances in imaging, minimally-invasive neurosurgical procedures and protocoled antimicrobial therapy.[1] microbiological diagnosis and antimicrobial rationalisation continues to rely on culture and susceptibility testing of intra-operative specimens These specimens are culture-negative in around a third of cases, often due to the use of pre-operative antibiotics or presence of fastidious organisms.[2] The dependence on prolonged, empirical antibiotic therapy in intracranial infections is well-recognised, as are the accompanying risks of antimicrobial resistance and drug toxicity.[3,4] there is a need to develop rapid and accurate diagnostic testing of intracranial specimens to inform antimicrobial choices and improve patient outcomes. The primary advantage of this technique is that it requires only genetic material for bacterial identification, compared to culture-based methods that require viable organisms

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