LITERATURE UPDATE


one of the leading factors encouraging the development of new therapeutic strategies. The increased resistance to antibiotics can be atributed to several factors, such as early and unnecessary administration, incorrect dosing, or incomplete antibiotic treatment. One of the diseases that calls for improved understanding of this problem is meningitis, which – if ineffectively treated – may result in severe neurological complications and death. This study provides an overview of


the current antibiotic strategies for bacterial meningitis along with the therapeutic challenges associated with standard treatment options. In addition, it also presents the current progress in bacteriophage research, highlighting both their potential to replace some common antibiotic therapies in the treatment of meningitis and the significant lack of clinical studies regarding most of them. The research on phage therapy


targeting meningitis-associated pathogens is limited, and, where it exists, it is predominantly focused on mouse models. There, its efficiency seems mostly promising. Nevertheless, comprehensive clinical trials are needed to properly determine the efficacy and safety of phage therapy in humans before it becomes a significant alternative to antibiotics.


Sex differences in bacterial meningitis and associations with socioeconomic indicators: a systematic review and meta- analysis with metaregression Liechti FD, van Etekoven CN, Brouwer MC, Bijlsma M, van de Beek D. BMJ Glob Health. 2025 Apr 30; 10 (4): e016802. doi: 10.1136/bmjgh-2024-016802.


In this study, the authors aimed to describe global sex-specific proportions and case fatality ratios of bacterial meningitis and to explore their associations with the Human Development Index (HDI) and Gender Inequality Index (GII). Google Scholar and MEDLINE (via


PubMed.gov) were searched in January 2022 using the terms “bacterial meningitis” and “mortality”. Studies with a mean observation period after the year 1940 and reporting ≥10 patients with community-acquired bacterial meningitis and their survival status were included, irrespective of the participants’ age. Studies that selected participants by specific risk factors, reported specific pathogens only, or had >10% missing outcomes were disregarded. Data were extracted by one researcher and validated by a second researcher. The main outcomes, sex-specific proportions, and case fatality ratios were analysed using


random-effects models. Associations with HDI and GII were explored using metaregression. In this meta-analysis with


metaregression, from 371 studies with 157,656 meningitis episodes, 217 (58%) reported the patients’ sex and 41 (11%) reported sex-specific outcomes. Proportion of males was 58% (95% confidence interval [CI] 57–59%, prediction interval [PI] 45–71%). Case fatality ratios were slightly higher in females (male-to-female fatality ratio 0.89, 95% CI 0.78–1.01, PI 0.53–1.49). The size of the male proportion was strongly associated with HDI (per index point –0.64, 95% CI –0.88 to –0.40; R2 16%; P<0.001) and GII (per index point 0.61, 95% CI 0.39–0.83; R2 19%; P<0.001). Sex-specific case fatality ratios were weakly associated with HDI (per index point 0.53, 95% CI –0.19 to 1.25; R2 2%; P=0.15) and GII (per index point –0.58, 95% CI –1.55 to 0.39; R2 7%; P=0.24). Based on worldwide reporting from the last 80 years, the authors show that indicators of human development and gender inequality are associated with sex- based disparities and case fatality ratios in bacterial meningitis.


Neuronal Autoantibodies in Adults After Community-Acquired Bacterial Meningitis Staal SL, Ter Horst L, Brenner J, van de Beek D, Titulaer MJ, Brouwer MC. Neurol Neuroimmunol Neuroinflamm. 2025 Sep; 12 (5): e200454. doi: 10.1212/NXI.0000000000200454.


Long-term cognitive impairment is observed in 14–32% of patients surviving community-acquired bacterial meningitis. The authors hypothesised that the impairment might be linked to secondary immune activation due to the development of neuronal autoantibodies, similar to post-infectious autoimmune encephalitis after viral encephalitis. In this cross-sectional observational


study, the authors included adult patients from a prospective, nationwide cohort study of community-acquired bacterial meningitis in the Netherlands, the MeninGene study. The presence of neuronal autoantibodies was evaluated in follow-up serum samples at seven days, at three months, or over a year. Immunohistochemistry on complete rat brain slices was performed for the initial screening. If positive or ambiguous, immunocytochemistry using live primary rat hippocampal neurons and cell-based assays expressing extracellular targets were performed; immunoblots were used for intracellular targets. In total, 118 patients were included, of whom 24 of 100 (24%) had cognitive impairment and 14 of 109 (13%) had


52 WWW.PATHOLOGYINPRACTICE.COM April 2026


focal neurologic deficits at discharge. Causative pathogens were Streptococcus pneumoniae in 98 patients (83%), Neisseria meningitidis in four (3%), and other pathogens in six (5%); in 10 patients (9%), no causative pathogen was identified. Two of 118 patients (2%) had neuronal autoantibodies in follow-up serum: one had leucine-rich glioma inactivated 1 antibodies, and one had unspecified antibodies. None of the patients was positive for NMDA receptor antibodies. There was no clear evidence of post-


infectious autoimmune encephalitis after bacterial meningitis. Therefore, acute brain damage caused by the infection itself seems to be the most plausible explanation for long-term cognitive impairment and neurologic disabilities.


Heparin-binding protein levels as an emerging key biomarker for accurate diagnosis of bacterial meningitis: A promising yet preliminary evaluation Shi M, Wei Y, Huang H, Guo R, Luo F. Microb Pathog. 2025 May; 202: 107417. doi: 10.1016/j.micpath.2025.107417.


This systematic review aims to consolidate evidence on the potential of heparin-binding protein (HBP) as an emerging and promising biomarker for diagnosing bacterial meningitis (BM). The authors conducted a comprehensive search across PubMed, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases, with no restrictions on publication date or language. Sixteen studies, encompassing a total


of 2,032 participants, were included in the analysis. The results consistently demonstrated that HBP expression levels both in cerebrospinal fluid (CSF) and blood are markedly elevated in cases of BM compared to patients with non- central nervous system (CNS) infections or other types of meningitis, such as viral meningitis. The pooled sensitivity estimate for HBP


measured in CSF was 0.94 (95% confidence interval [CI] 0.88–0.97), and the specificity was 0.96 (95%CI 0.90–0.98). The diagnostic odds ratio (DOR) was calculated as 327 (95%CI 96–1,110). According to Fagan’s nomogram, an initial probability of 20% for a positive test result increased to 85% following a positive HBP test, while a negative test reduced the probability to just 2%.


The diagnostic performance of CSF


HBP surpassed that of procalcitonin in detecting BM. Furthermore, in cases where symptoms of CNS infection are present, HBP levels in blood also demonstrate notable diagnostic accuracy. These findings suggest that HBP holds significant potential as a biomarker for BM. However,


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