Neisseria lactamica meningitis as the initial presentation of a rhino–cerebrospinal fluid fistula in an adult with remote cranial trauma

Abstract

Background

Neisseria lactamica is a commensal of the upper respiratory tract in children and is rarely isolated in adults. Its genome shares approximately 60% homology with Neisseria meningitidis but lacks the virulence genomic islands essential for blood–brain barrier invasion. Meningitis due to Neisseria lactamica is exceptionally rare and few cases are reported in literature, mainly among pediatric patients. To date, only one case of Neisseria lactamica meningitis in an adult, associated with head trauma, has been reported in the literature (1991).

Case presentation

We report the case of a 58-year-old woman with a remote history of cranial trauma who presented with acute-onset headache, nausea, vomiting, and photophobia. Cerebrospinal fluid (CSF) analysis was consistent with acute bacterial meningitis. Despite negative multiplex PCR testing for common neurotropic pathogens, Neisseria lactamica was isolated from both CSF and blood cultures. Imaging revealed a skull base defect of the sphenoid sinus with an associated rhino-CSF fistula. Antimicrobial therapy was de-escalated to ceftriaxone monotherapy based on susceptibility testing, followed by successful endoscopic surgical repair of the CSF leak. The patient made a full recovery.

Conclusion

This case represents the only adult case of Neisseria lactamica meningitis reported since 1991, emphasizing the need to recognize this organism as a potential cause of meningitis in patients with anatomical defects, to differentiate it microbiologically from Neisseria meningitidis, and to search for anatomical defects when it is isolated.

Background

Bacterial meningitis is a life-threatening infection of the central nervous system with causative organisms varying by age and risk factors. In adults, Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae are the most common pathogens [1].

Neisseria lactamica is a Gram-negative diplococcus that commonly colonizes the upper respiratory tract, particularly in infants and young children, and is only rarely isolated in adults [2]. It is generally regarded as a non-pathogenic commensal species. In contrast, Neisseria meningitidis is a well-recognized human pathogen and a leading cause of invasive bacterial meningitis and septicemia worldwide [1].

Although N. lactamica and N. meningitidis are closely related and share approximately 60% genomic homology, important differences in virulence-associated structures and genetic determinants account for their markedly distinct clinical behavior [3], [4]. A key distinguishing feature is the absence of a polysaccharide capsule in N. lactamica, whereas the capsule represents the principal virulence factor of N. meningitidis, enabling resistance to complement-mediated killing and facilitating bloodstream invasion. Furthermore, N. lactamica lacks several meningococcal virulence factors involved in adhesion, immune evasion, and traversal of the blood–brain barrier, including specific outer membrane proteins and genomic regions associated with invasiveness. [Table 1] [5].

Table 1.

N. lactamica vs N. meningitidis.

Features	Neisseria lactamica	Neisseria meningitidis s	References
Usual role	Commensal	Major invasive pathogen	Dorey RB et al [12]. Rausch-Phung EA et al [13].
Age distribution	Infants and toddlers	All ages	Bennett JS et al [3].
Capsulate	Absent	Present	Kim JJ et al [5].
Virulence genomic islands	Absent	Present	Kim JJ et al [5].
Reported meningitis cases	Very rare	Common	Lauer BA et al [9]. ; Greenberg LW et al [10]. ; Hansman D et al [11]. ; Denning DW et ak [8].

These biological differences largely explain the commensal nature of N. lactamica and the rarity of invasive disease. In addition, colonization with N. lactamica has been associated with reduced acquisition of N. meningitidis in human challenge studies, likely through immune cross-reactivity and ecological competition within the nasopharyngeal niche [6], [7].

Reported cases of N. lactamica meningitis have occurred almost exclusively in pediatric patients who appeared to be immunocompetent, although immune status was not consistently investigated or explicitly reported. Invasive disease in adults remains exceptionally rare. To date, only one adult case of N. lactamica meningitis has been described in the literature; this case, reported in 1991, was associated with prior head trauma [8]. Here, we present an additional adult case in which N. lactamica meningitis represented the initial manifestation of a previously undiagnosed skull base defect with a rhino-CSF fistula.

Case description

A 58-year-old woman presented to the Emergency Department of Policlinico Umberto I in Rome with acute-onset pulsatile headache, nausea, vomiting, photophobia, and positional cerebrospinal fluid (CSF) rhinorrhea. On examination, she was alert and oriented but demonstrated signs of meningeal irritation, including neck stiffness. Additional findings included arterial hypertension, and bradycardia. Laboratory investigations demonstrated neutrophilic leukocytosis (white blood cell count 16,0 ×10⁹/L, neutrophils 13,8 ×10⁹/L) and elevated inflammatory markers (C-reactive protein 17.19 mg/dL). Cerebrospinal fluid analysis revealed cloudy fluid with marked neutrophilic pleocytosis (422 cells/µL), hypoglycorrhachia (42 mg/dL), and elevated protein concentration (74 mg/dL), consistent with acute bacterial meningitis.

Empirical intravenous antimicrobial therapy was promptly initiated with ceftriaxone, vancomycin, and ampicillin. Multiplex PCR testing of the CSF for common neurotropic pathogens (E. coli K1; H. influenzae; L. monocytogenes; N. meningitidis; S. agalactiae; S. pneumoniae; S. pyogenes; M. pneumoniae; HSV1,2,6; Enterovirus; Parechovirus umano; VZV; C. gatti/C. neoformans) was negative. Conventional microbiological evaluation of CSF and blood culture isolates revealed Gram-negative diplococci, oxidase-positive colonies growing on chocolate and blood agar in 5% CO₂ atmosphere, consistent with Neisseria spp. The organism was subsequently identified as Neisseria lactamica by MALDI-TOF mass spectrometry (Bruker) with a species-level identification score of 2.05. Antimicrobial therapy was therefore de-escalated to ceftriaxone monotherapy based on susceptibility testing (penicillin minimum inhibitory concentration: 0.38 µg/mL). Neuroimaging identified a large bony defect of the right sphenoid wall with communication between the sphenoid sinus and the middle cranial fossa, consistent with a rhino-CSF fistula. Only subsequently did it emerge that the patient had sustained severe cranial trauma following a motor vehicle accident 10 years earlier.

After 24 days of targeted antimicrobial therapy, the patient underwent successful endoscopic surgical repair of the CSF leak through a multidisciplinary neurosurgical and otorhinolaryngological approach. The clinical course was favorable, with complete resolution of symptoms and no evidence of relapse at one-month follow-up.

Discussion

To date, only four cases of Neisseria lactamica meningitis have been reported in the literature, three of which occurred in children younger than seven years. The first case involved a 7-month-old infant with acute purulent meningitis in whom N. lactamica was isolated from both blood and cerebrospinal fluid (CSF) [9]. The second described a 6-month-old infant who initially presented with bilateral otitis media and subsequently developed meningitis, with N. lactamica isolated from blood, CSF, and a throat swab [10]. The third pediatric case occurred in a 6-year-old child with microbiologically confirmed N. lactamica meningitis [11]. In these reports, the authors primarily focus on the isolation and identification of Neisseria lactamica from the cerebrospinal fluid of children with meningitis. However, they do not report or discuss any underlying immunodeficiency or preceding head trauma in the patients.

Only one adult case of N. lactamica meningitis has been previously reported. This involved a 46-year-old woman with a history of severe craniofacial trauma due to a motor vehicle accident, complicated by sinus involvement and a persistent CSF leak. Similar to our patient, she presented with headache, nausea, vomiting, fever, photophobia, and neck stiffness, and CSF analysis revealed neutrophilic pleocytosis, hypoglycorrhachia, and elevated protein concentrations. In both cases, meningitis occurred in the context of a CSF fistula secondary to prior cranial trauma, highlighting the critical role of structural defects of the skull base as predisposing factors for invasive infection by organisms traditionally considered of low pathogenicity [8].

Consistent with this observation, reviews of nonpathogenic Neisseria species emphasize that N. lactamica, while commonly regarded as a benign commensal and potentially protective against meningococcal colonization, may rarely cause invasive disease in the presence of specific anatomical abnormalities or host-related risk factors [12].

Our patient shared many clinical and laboratory features with the previously reported adult case. Both presented with nuchal rigidity but without altered mental status, and fever was absent at presentation in our patient. This is consistent with evidence indicating that the classic triad of fever, altered mental status, and nuchal rigidity is present in only approximately 44% of cases of bacterial meningitis [13]. In both instances, prompt initiation of empirical antimicrobial therapy, followed by pathogen-directed treatment and definitive surgical repair of the underlying anatomical defect, resulted in complete clinical recovery.

Notably, both reported adult cases of N. lactamica meningitis had favorable outcomes, in contrast to meningitis caused by Neisseria meningitidis, which is associated with rapid disease progression and higher mortality if not treated promptly. Although the clinical presentations of meningitis caused by these two species may overlap, their pathogenic potential differs substantially. Experimental studies suggest that these differences are related to distinct patterns of modulin expression and host–pathogen interactions [14]. Previous in vitro research has demonstrated that meningeal cells remain viable after prolonged exposure to N. lactamica, whereas N. meningitidis induces extensive necrotic cell death [14]. These findings support the concept that N. meningitidis is a highly invasive pathogen, whereas N. lactamica lacks the capacity for sustained tissue invasion.

Conclusion

This case represents an exceptionally rare instance of Neisseria lactamica meningitis in an adult and underscores the importance of considering underlying anatomical abnormalities, such as rhino–cerebrospinal fluid fistulas, in patients with a history of cranial trauma presenting with bacterial meningitis. Although N. lactamica is generally regarded as a harmless commensal and is rarely detected in adults, it may exceptionally cause invasive central nervous system infection when structural defects permit direct communication between the upper respiratory tract and intracranial spaces. In this context, the pathogenesis is more consistent with local invasion through a skull base discontinuity rather than hematogenous spread, in keeping with the organism’s limited virulence potential and lack of a polysaccharide capsule and meningococcal genomic islands. Accurate microbiological identification is therefore essential, as differentiation from Neisseria meningitidis has important diagnostic, prognostic, therapeutic and public health implications. To our knowledge, this represents the only adult case of N. lactamica meningitis reported since 1991, highlighting the need to recognize this organism as a potential cause of meningitis in patients with anatomical defects and to actively investigate for structural abnormalities when it is isolated.

CRediT authorship contribution statement

Corbo Irene: Writing – original draft. Comi Michela: Writing – original draft. Ficco Riccardo: Supervision. Defendini Carolina: Supervision. Mastroianni Claudio M.: Validation, Supervision. Figliomeni Sara: Writing – review & editing, Writing – original draft. Osimiri Claret: Writing – original draft. Ashurova Rabiyya: Writing – original draft. Oliva Alessandra: Supervision. Aronica Raissa: Supervision. Marincola Federica: Supervision.

Declaration of Competing Interest

The authors declare that they have no conflicts of interest regarding the publication of this paper.