Epidemiology, clinical characteristics, and outcomes of patients having central nervous system infections in Almaza fever military hospital: A retrospective study

*Corresponding author: Mohammad Emam Mohammad Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Epidemiology, clinical characteristics, and outcomes of patients having central nervous system infections in Almaza fever military hospital: A retrospective study Mohammad Emam Mohammad 1, *, Abou Bakr Farrag 2, Aisha Abo EL Fotoh 3 and Mohamed Abdel Salam Elgohary 1 1 Department of tropical medicine and infectious disease, Military Medical Academy, Cairo, Egypt. 2 Department of preventive, social and occupational medicine, Military Medical Academy, Cairo, Egypt. 3 Department of public health, community medicine, environmental and occupational Medicine, Faculty of medicine, Ain Shams University, Cairo, Egypt. GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 Publication history: Received on 31 August 2025; revised on 07 October 2025; accepted on 10 October 2025 Article DOI: https://doi.org/10.30574/gscbps.2025.33.1.0385 Abstract Objective: This study aimed to describe the epidemiology, clinical characteristics, management, and treatment outcomes of patients diagnosed with central nervous system (CNS) infections at a tertiary care hospital in Egypt. Methods: A retrospective analysis was conducted on 104 patients admitted with suspected CNS infections between July 2021 and October 2023. Data extracted from hospital records included patient demographics, clinical features, laboratory and neuroimaging results, treatment regimens, and final outcomes. Results: The median patient age was 50 years, with a male predominance (71.2%). The most common diagnoses were encephalitis (45.2%) and meningitis (41.3%). A causative pathogen was identified in only 42.3% of cases, with Streptococcus pneumoniae being the most frequent (13.5%). No etiology was found in 57.7% of cases. Diabetes was the most frequent comorbidity (27.9%). The universal clinical feature was disturbed consciousness, followed by fever and headache. The most used empirical treatment was a combination of ceftriaxone, vancomycin, and acyclovir (57.6%). The overall cure rate was 80.7%, and the mortality rate was 5.7%. All cases of cryptococcal meningitis and 10% of cerebral malaria cases were fatal. Conclusion: In this cohort, CNS infections primarily affected older adults, with a high rate of unknown etiology. The use of empirical broad-spectrum therapy was associated with a favorable overall outcome. However, the findings highlight an urgent need for enhanced diagnostic methods to identify pathogens, especially in fatal fungal and parasitic infections, to guide targeted treatment and potentially improve survival. Keywords: Central nervous system infections; Meningitis; Encephalitis; Epidemiology; Treatment outcomes; Egypt 1. Introduction Central nervous system (CNS) infections represent a critical challenge in medicine due to their severe consequences and the imperative for prompt recognition, diagnosis, and treatment to save lives. These infections encompass distinct clinical syndromes like acute bacterial meningitis, viral meningitis, and encephalitis, alongside focal infections such as brain abscesses, subdural empyema, and infectious thrombophlebitis. Often, these conditions initially present with nonspecific prodromal symptoms like fever and headache. Crucial to early management is the urgent differentiation between these conditions, identification of the causative pathogen, and initiation of appropriate antimicrobial therapy. GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 99 Global and Regional Burden of CNS Infections Globally, meningitis remains a formidable disease, causing an estimated 250,000 deaths in 2019 and leaving one in five affected individuals with severe long-term sequelae. Vaccination programs, such as Egypt's expanded national vaccination program against Neisseria meningitidis and the introduction of influenza, measles, mumps, and rubella vaccines, are expected to significantly reduce local incidence rates of these infections. Viral meningitis is more prevalent than bacterial meningitis, though typically less severe. A significant proportion (up to 70%) of encephalitis cases have unknown etiologies, and non-infectious processes can also cause the condition. CNS infections are clinically characterized by symptoms such as fever, headache, vomiting, seizures, loss of consciousness, altered sensorium, focal neurological deficits, and blurred vision, with variations depending on the etiology and brain involvement [1]. Lowand middle-income countries (LMICs) disproportionately bear the burden of CNS infections. These infections can result from a wide range of viruses, leading to varied neurological manifestations. Common viral etiologies include enteroviruses, herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human immunodeficiency virus (HIV). Cryptococcus is the most common cause of fungal CNS infections, particularly in sub-Saharan Africa, where it is a leading cause of meningitis [1]. The global burden of disease reported a 21% reduction in deaths from CNS infections between 1990 and 2016, but an increase in incidence from 2.50 to 2.82 million cases during the same period. While viral meningitis is more common, bacterial meningitis is more serious if left untreated. Viral CNS infections range from 0.26 to 17 cases per 100,000 people, with incidence varying by age and other factors. In the U.S., viral meningitis incidence is approximately 0.7 cases per 100,000 people per year, and viral encephalitis is 1.7 cases per 100,000 people per year. Resource-limited settings face a particularly high burden of viral CNS infections, associated with high morbidity and mortality rates. For instance, acute encephalitis syndrome in sub-Saharan Africa has an estimated annual incidence of 4.3 cases per 100,000 people and a case-fatality rate of up to 45% in some regions [1]. Fungal CNS infections contribute significantly to morbidity and mortality globally, especially in immunocompromised individuals. Cryptococcosis, the most common fungal infection affecting the CNS, accounts for an estimated 223,100 cases and 181,100 deaths annually worldwide. Among people living with HIV, approximately 152,000 cases of cryptococcal meningitis occur each year, with 112,000 deaths, predominantly in sub-Saharan Africa. Other fungal pathogens like Aspergillus and Candida species also cause significant morbidity and mortality, particularly in immunocompromised patients. Mycobacterial infections, especially CNS tuberculosis, are common in Southeast Asia, accounting for 1% of all TB cases and being the most frequent form of CNS TB [1]. Immune Responses in CNS Infection: The CNS has an "immune privilege" status due to local tissue barriers and immunosuppressive microenvironments, restricting the flow of cells, infections, or macromolecules. Key physical barriers include the blood-brain barrier (BBB), blood-cerebrospinal fluid (CSF) barrier, and arachnoid barrier. Under pathological conditions, peripheral immune cells can cross the BBB. CSF transport through skull channels and into marrow cavities suggests a mechanism for pathogens to induce immune cell release in response to inflammation [2]. T-cell-mediated immune regulation involves resident microglia and perivascular macrophages inhibiting foreign bodies. T cells are crucial for eradicating viral and intracellular bacterial infections, often clearing viral infections noncytolytically. Activated T cells can move from blood vessels to the subarachnoid space via the choroid plexus stroma. Both CD4+ and CD8+ T lymphocytes are found in meninges, choroid plexus, parenchyma, and naïve brain. Myeloid cells as antigen-presenting cells (APCs) activate and recruit antiviral T cells [2]. Immune responses in the CNS are divided into innate and adaptive. The initial strong innate response throughout the CNS provides antimicrobial defense, followed by adaptive immune responses if infection persists. Microglia, astrocytes, and other APCs express Major Histocompatibility Complex (MHC) class II and co-stimulatory molecules, activating Tcell subtypes and stimulating humoral immune responses (antibody production by B cells). B lymphocytes reside primarily in the meninges, particularly the dura mater layer, and gut-sensitized B cells may contribute to CNS humoral immunity when pathogens breach the blood-brain barrier [2]. Neurotropism is the ability of microorganisms to invade and reside in neural tissue. Neurotropic viruses vary in their neurovirulence and neuroinvasiveness; for example, herpes simplex viruses are highly neuroinvasive but weakly neurovirulent toward the peripheral nervous system. Viral genomic makeup, biological location, host immunological state, and environmental factors determine CNS viral infections. Flavivirus infections affect specific brain regions like anterior horn neurons, substantia nigra, thalamus, and neocortex. Flavivirus neuroinvasion is influenced by envelope protein glycosylation, which enhances axonal and transepithelial transport, and entry into host cells is facilitated by various cellular attachment factors. Flaviviruses also increase BBB permeability by disrupting tight junctions. CD8+ T GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 100 cells are vital for clearing West Nile virus-infected cells from the CNS. SARS-CoV-2 can enter the CNS via axonal transport through cranial nerves or by crossing the BBB/blood-CSF barrier after viremia. Future SARS-CoV-2 variants could exacerbate CNS issues, and immunization may affect CNS complications [2]. Immunosuppressive Effects of Pathogens: Some pathogens cause immunosuppression by impeding hemopoiesis or antigen presentation. Measles virus infection leads to temporary immunosuppression, depleting lymphocytes during acute infection. However, increased adaptive immune responses eventually eliminate the virus. HIV primarily targets helper T cells, leading to their depletion and Acquired Immunodeficiency Syndrome (AIDS), and can cause APC abnormalities. CMV infection suppresses hemopoiesis, affecting bone marrow stromal cells or directly infecting progenitor cells. Measles, HIV, and CMV cause systemic immunosuppression through various mechanisms: altering cytokine equilibrium, impairing macrophage and dendritic cell activities, inhibiting hemopoiesis, and generating immunosuppressive proteins. Aspergillus fumigatus, an airborne fungus, causes high mortality in immunodeficient persons and produces gliotoxin, which hinders neutrophil function and innate immunity by reducing LTB4 formation, interfering with neutrophil phagocytic activities [2]. Infection-Induced Autoimmune Responses: Infections can trigger autoimmune responses when the immune system reacts to self-antigens, often due to inherent deficiencies in peripheral self-tolerance, genetic defects, or other factors. Multiple sclerosis (MS) is a prevalent CNS autoimmune illness. Viruses or bacterial infections are often the root causes of autoimmune diseases, with viruses potentially initiating autoimmune reactions by influencing immune cells for selfdefense. Molecular mimicry is a basic mechanism by which normal immune responses can shift to autoimmune responses following an infection [2]. Diagnosis of CNS Infections: Diagnosis typically involves clinical presentation, blood tests, blood culture and is confirmed by cerebrospinal fluid (CSF) analysis and neuroimaging. Lumbar puncture for CSF analysis is almost always performed when CNS infection is highly suspected. However, diagnostic methods lack consistent results globally, and variations in studies exist. Challenges in diagnosing meningitis/encephalitis include varied clinical presentations with overlapping symptoms such as fever, headache, neck stiffness, altered consciousness, seizures, and focal neurological findings, which can be associated with diverse infectious agents [3]. Furthermore, an etiology is not always identified due to a lack of targeted testing, the vast number of potential infectious causes, and the fact that about 10% of suspected cases are eventually found to have non-infectious origins. Routine CSF parameters can suggest the type of infection (bacterial, viral, or fungal) but are not specific. Bacterial meningitis cultures, while useful, take 2–5 days and can yield false negatives due to fastidious organisms, prior antibiotic treatment, or improper specimen handling. For nonbacterial ME, clinical suspicion is necessary to order the correct viral agent testing. Delays in diagnosis and treatment can occur when laboratories, especially in smaller or rural areas, rely on reference laboratories for CSF testing. In Egypt, bacterial septic meningitis (73.0%) is predominantly caused by Streptococcus pneumoniae (43.0%), with viral septic meningitis (22.0%) primarily attributed to HSV (32.8%) and enteroviruses (24.5%) [3]. Clinical Presentation and Diagnosis: Patients with CNS infections can present with a range of symptoms, including headache, fever, focal neurological deficits, seizures, acute confusion, lethargy, neck pain, photophobia, back pain, nausea, vomiting, syncope, coma, and dermatological manifestations. Constitutional symptoms like lymphadenopathy, arthralgias, and myalgias may also occur. Meningitis: Acute meningitis, an infection of the meninges, is the most common infectious disease of the CNS. The classic triad includes fever, neck stiffness, and altered mental status, with 99–100% of meningitis patients presenting with at least one component. S. pneumoniae meningitis can lead to rapid clinical decline and death, although pneumococcal vaccines have reduced mortality. Listeria monocytogenes should be suspected in infants and elderly patients, and Neisseria meningitidis is concerning due to its epidemic potential [3]. Encephalitis: Patients with encephalitis can exhibit symptoms ranging from subtle deficits to unresponsiveness, including neurological manifestations seen in meningitis and seizures. A hallmark is acute onset of febrile illness (fever above 38°C within 72 hours). Meningeal symptoms may be absent. Altered mentation can range from confusion to obtundation. The presentation often reflects the causative agent's predilection for certain CNS cells; for example, herpes simplex virus infections affecting the temporal lobe can lead to aphasia, anosmia, temporal lobe seizures, and focal neural deficits [3]. In conclusion, CNS infections are a diverse and critical group of medical conditions requiring swift and accurate diagnosis and treatment. Their varied etiologies, complex immune interactions, and diverse clinical presentations underscore the ongoing challenges in management and prevention worldwide. GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 101 2. Materials and methods • Aim of the work: Improve clinical management and treatment outcome by identifying epidemiologic features and factors affecting treatment and outcomes. 2.1. Objectives of the Study • To determine the most common causes of central nervous system infections. • To find out the factors affecting clinical management and treatment outcome. • To determine the impact of HIV on central nervous system infection. • To know the impact of travelling history on central nervous system infection. • To know the effect of the new method of diagnosis of central nervous system infection on clinical outcomes. Study Design: A descriptive retrospective study. Study Settings: Almaza fever military hospital. Study Population: All patients admitted to Almaza Fever Military Hospital intensive care unit with clinical presentation suggesting of a central nervous system infection. Inclusion criteria: Patients with case definitions of central nervous system infections involving infection of the brain (cerebrum and cerebellum), spinal cord, optic nerves, and their covering membranes. It includes: • Meningitis: An illness with sudden onset of fever (>38.5°C rectal or >38.0°C axillary) and one or more of the following: neck stiffness, altered consciousness, other meningeal irritation signs or petechial or purpureal rash. • Meningoencephalitis: is an inflammation of the brain parenchyma with or without involvement of the meningeal structures. • Encephalitis: is defined as inflammation of the brain parenchyma associated with neurologic dysfunction • Parasitic infection of the brain. • Patients who included were admitted to Almaza Fever Military Hospital from July 2021 to October 2023 and were included in the study. • Suspected or clinically diagnosed cases in all age groups would be included. 2.2. Exclusion criteria • All those patients whose diagnosis was uncertain and inconclusive were excluded from the study. • Patients would be excluded from the study, like pregnant women and post-traumatic. • Patients had contraindications to CSF lumbar puncture. • Patients had incomplete data records. 2.3. Sample selection All patients admitted to the intensive care unit at Almaza Military Fever Hospital who met the criteria for central nervous system infection in the period from July 2021 to October 2023. 2.4. Methods Registered data in hospital databases and the procedures had been done for all cases included. Registration data for all the patients included in the study will be retrieved from hospital records and collected in a pre-prepared sheet. 2.5. Statistical Analysis The collected data will be coded, revised, and entered into the Statistical Package for Social Science (IBM SPSS) version 20. The data were presented as numbers and percentages for the qualitative data, mean, standard deviations, and ranges for the quantitative data with parametric distribution and median with inter quartile range (IQR) for the quantitative data with non-parametric distribution. GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 102 3. Results Table 1 Demographic data among studied patient No % Gender Male 74 71.2% Female 30 28.8% Residence Rural 39 62.5% Urban 65 37.5% Age Mean ±SD 44.14 20.08 Range 4 82 Median 50 0-18 years old 11 10.5% 18-50 years old 40 38.46% Over 50 years old 53 50.9% Most of the studied patients (n =74) were male. The median age of the studied patients ranged from 4 to 82 years old with median 50 years old; 50.9% (n =53) of all the studied patients were over 50 years old. and 10.5% (n =11) of the studied patients were under 18 years old. Table 2 Medical history among studied patients (n = 104) No % Diabetes 29 27.9% Hypertension 18 17.3% Travel history to endemic area 10 9.6% Urinary tract infection 8 7.7% Upper respiratory tract infection 5 4.8% Ischemic heart disease 4 3.8% HIV 2 1.9% Postsurgical intervention 2 1.9% Meningitis 2 1.9% Benign breast tumor excised 1 1.0% Parotitis 1 1.0% Polio 1 1.0% Right benign brain tumour 1 1.0% Hospital stay Mean ±SD 11.77 5.32 Range 2 22 Median 11 GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 103 The hospital stay duration of the studied patients ranged from 2 to 22, with median 11. From the various comorbidities measured. 27.88% of patients (n=29) were diabetic, 17.3% (n=18) of patients were hypertensive, 3.6% (n=4) of patients had ischemic heart disease, and 1.9% (n=3) of patients had HIV infections. Table 3 Suspected diagnosis among studied patients (n = 104) No % Final diagnosis Encephalitis 47 45.2% Meningitis 43 41.3% Cerebral malaria 10 9.6% Focal brain lesion 4 3.9% From the final diagnosis, encephalitis was the most common final diagnosis that was found in 47 patients (45.2%), followed by meningitis, which was found in 43 patients (41.3%). Table 4 Culture results among studied patients or CSF BioFire (n = 104) No % Culture No growth 60 57.7% Streptococcus pneumonia (S pneumonia) 14 13.5% Herps simplex virus (HSV) 10 9.6% Positive blood film for malaria 10 9.6% Neisseria meningitis (N. meningitidis) 2 1.9% Klebsiella pneumoniae (K. pneumoniae) 2 1.9% Escherichia coli (E. coli) 2 1.9% Staphylococcus aureus (S. aureus) 2 1.9% Cryptococcus neoformans (C. neoformans) 2 1.9% The results were as follow: 57.7% (No=60) of studied patients had undetected etiology. Streptococcus pneumoniae was the most commonly detected, found in 14 patients (13.5%), followed by a positive blood film for malaria, which was found in 10 patients (9.6%), and the same herpes simplex virus was found in 10 patients. Table 5 Main presenting symptoms & signs among studied patients (n = 104) No % Disturbed conscious level Yes 104 100% Fever Yes 94 90.4% No 10 9.6% Headache Yes 65 62.5% No 39 37.5% Convulsion Yes 32 30.7% No 72 69.2% neck rigidity Yes 27 26% GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 104 No 77 74% Vomiting Yes 19 18.2% No 85 81.7% Fever Headache convulsion Vomiting Neck rigidity C. neoformans (2)100% (2)100% (2)100% (2)100% (2)100% E. coli (2)100% (2)100% (2)100% HSV (8)80% (6)60% (2)20% K. pneumoniae (2)100% N. meningitidis (2)100% (2)100% S. pneumonia (14)100% (12)85.7% (10)71.4% (2)14.3% (8)57.1% S. aureus (2)100% Cerebral malaria 100%(10) 70%(7) 30%(3) 10%(1) %(0) Undetected (52)86.7% (35)65% (15)25% (12)20% (15)25% X2 103.99 56.027 180.211 126.805 144.595 P value 0.001 0.001 0.001 0.001 0.001 Disturbed conscious level was the main symptom that was found in 104 patients (100%), followed by fever that was found in 94 patients (90.4%), followed by headache that was found in 65 patients (62.5%), followed by convulsion that was found in 32 patients (30.7%). Two (100%) patients with cryptococcal meningitis had fever, headache, convulsion, vomiting, and neck rigidity. Patients with HSV infections: 14 patients (100%) had fever, 12 patients (85.7%) had headache, 10 patients (71.3%) had convulsion, 2 patients (14.3%) had vomiting, and 8 patients (57.4%) had neck rigidity. Table 6 Glasgow Coma Scale among studied patients (n = 104) GCS Mean SD Minimum Maximum Median 10.69 2.19 5 14 11 No % Above 11 49 47.12% Below 11 55 52.88% Below 11 11 and over 11 Meningitis 18 25 41.8% 58.2% Encephalitis 15 32 40% 60% Focal brain lesion 2 2 50% 50% Cerebral malaria 6 4 60% 40% Below 11 11 & over 11 GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 105 C. neoformans (2)100% E. coli (2)100% HSV (3)30% (7)70% K. pneumoniae (1)50% (10)50% N. meningitidis (2)100% S. pneumonia (5)35.6% (9)64.4% S. aureus (2)100% Undetected (24)40% (36)60% X2 103.99 56.027 P value 0.001 0.001 The median GCS of the studied patients ranged from 5 to 14, with a mean of 10.69 and a median was 11. 52.88% (No=55) of studied patients were below 11. 2 patients (100%) with cryptococcal infection showed GSC below 11; 3 (30%) patients with HSV infection showed GSC below 11; 1 (50%) patient with Klebsiella infection showed GSC below 11; 10 (50%) patients with malaria infection showed GSC below 11; 5 (35.6%) patients with streptococcal infection showed GSC below 11; and 24 (40%) patients with unknown infection showed GSC below 11. Table 7 The results of laboratory investigations among studied patients (n = 104) White blood cells (WBC)/ Complete blood count (CBC) Mean SD Minimum Maximum Median 14.15 9.08 3 56 12 No % Above 12 45 43.26% Below 12 59 56.74% White blood cells/CSF Mean SD Minimum Maximum Median 815.74 1685.28 4 10000 135 No % Above 135 51 49.03% Below 135 53 50.97% No % COVID swab No 104 100.0% WBC in CBC WBC in CSF Below 12 12 and over 12 Below 135 Above 135 Meningitis 17 26 10 34 39.5% 60.5% 23.2% 67.85 Encephalitis 26 21 31 16 55.3% 44.7% 70% 30% Focal brain lesion 4 4 100% 100% Cerebral malaria 7 3 10 0 GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 106 70% 30% 100% C. neoformans 0 2 0 2 0 100% 0 100% E. coli 2 0 0 2 100% 0 0 100% HSV 8 2 8 2 80% 20% 80% 20% N. meningitidis 0 2 0 2 0 100% 0 100% K. pneumoniae 0 2 0 2 0 100% 0 100% S. pneumoniae 2 12 0 14 14.3% 85.7% 0 100% S. aureus 2 0 2 0 100% 0 100% 0 Undetected aetiology 29 31 32 28 48.33 51.66% 53.33% 46.66% Chi Square test X2 35.693 12.968 P value 0.003 0.113 WBC/CBC of the studied patients ranged from 3 to 56, with a mean of 14.15 and a median was 12. 43.26% (No=45) of studied patients were above 12. WBC/CSF of the studied patients ranged from 4 to 10000, and 49.03% (N = 51) were over 135. 67.7% of patients with meningitis had white blood cells in CSF above 135, while in encephalitis 70% were below 135. 2 (100%) patients with cryptococcal infections had elevated WBC above 12000 in CBC, 2 (20%) patients with HSV had elevated WBC above 12000 in CBC, 12 (85.7%) patients with streptococcal infections had elevated WBC above 12000 in CBC, and 31 (51.6%) patients with unknown infections had elevated WBC above 12000 in CBC. 2 (20%) patients with HSV had elevated WBC above 135 in CSF, 14 (100%) patients with streptococcal infections had elevated WBC above 135 in CSF, and 28 (46.66%) patients with unknown infections had elevated WBC above 135 in CSF. Table 8 CT lung and brain among studied patients (n = 104) CT lung No % Free 83 79.8% Consolidation 11 10.5% Consolidation+ ground glass opacity 6 5.7% Ground glass opacity 4 3.9% CT/ MRI brain among studied patients No % GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 113 Viral pathogens were 9.6% and fungal pathogens were 1.9% in our study, which was not comparable with a study conducted in Australia [7], which stated that viral pathogens were 41.2%, bacterial 24.1%, and fungal 4.8%. Undetected etiologies in our study highlight the need for expanded diagnostics (e.g., multiplex PCR) to identify viral/atypical pathogens. 4.5. Treatment and Outcomes: Our study used ceftriaxone + vancomycin + acyclovir in 57.6% of cases, likely covering both bacterial and viral etiologies. Sabry's study used various ceftriaxone-based regimens, with corticosteroids like dexamethasone reducing complications. Outcomes in our study show an 80.7% cure rate and 5.7% mortality, while Sabry's study [4] reports higher mortality (28.7% for septic meningitis), possibly due to more severe bacterial cases. The empirical use of antivirals (acyclovir) and antimalarials reflected diverse etiologies (encephalitis, malaria) in our study, while Sabry stated corticosteroid use underscores bacterial meningitis management guidelines. Lower mortality in our study might indicate milder cases or effective empirical treatment. Empirical therapy: Ceftriaxone + vancomycin + acyclovir (57.6%) was the most used regimen, reflecting adherence to guidelines for bacterial and viral coverage, which was comparable with a study in Nepal that stated that ceftriaxone + vancomycin and anti-tuberculous treatment in all TB cases and another study conducted in Laos [12] that suggested ceftriaxone and doxycycline for broader coverage, possibly due to increased rickettsial infection incidence. High complete cure rate (80.7%), but mortality (5.7%) occurred predominantly in cryptococcal (100% fatality) and cerebral malaria (10%) cases, highlighting the need for early pathogen-specific interventions. 4.6. Mortality and Comorbidities: The mortality rate (5.7%) was lower than in similar studies (10–15% van de Beek [9] & 27% India study [8]), possibly due to prompt ICU care and empirical treatment efficacy. The mortality rate (5.7%) was comparable with a study conducted in Australia [7], which stated that the mortality rate was 4.4% due to adherence to guidelines. Mortality rate: 5.7%, linked to cryptococcal infections (100% mortality), which highlighted challenges in managing fungal CNS infections and cerebral malaria. Mortality rates in a study conducted in Laos [12] reported 26.3%, and a study conducted in India [8] reported 21%, which was not comparable with our study's 5.7%. The lower mortality in our study could be due to better treatment protocols, earlier diagnosis, early empirical treatment (e.g., ceftriaxone + vancomycin in 57.6% of cases), exclusion of severe comorbidities (e.g., only 1.9% HIV co-infection vs. 24.8% in Laos [12]), or differences in pathogen virulence. However, our study had a smaller sample size, which might affect reliability. All studies emphasize early intervention to reduce complications. 5. Conclusion This descriptive study provides a comprehensive overview of CNS infections managed at a tertiary military hospital in Egypt. The findings reveal a distinct epidemiological profile characterized by an older patient population and a high burden of encephalitis, contrasting with studies from other regions where bacterial meningitis dominates younger cohorts. The high rate of undetected etiologies (57.7%) highlights a significant diagnostic challenge, likely attributable to limitations in available microbiological testing and possibly prior antibiotic use. Despite this diagnostic gap, the empirical treatment strategy primarily employing a combination of ceftriaxone, vancomycin, and acyclovir was associated with a high cure rate (80.7%) and a relatively low overall mortality (5.7%). However, the 100% mortality observed in cryptococcal meningitis cases signals an area for urgent improvement in the early recognition and management of fungal pathogens. GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 098-115 114 The study underscores several key points for clinical practice and future research: • Enhanced Diagnostics: There is a pressing need to implement advanced diagnostic techniques, such as multiplex PCR and CSF antigen testing, to reduce the number of cases with unknown etiology and allow for pathogen-directed therapy. • Vigilance for Specific Pathogens: Clinicians should maintain a high index of suspicion for herpes simplex virus encephalitis and cryptococcal meningitis in immunocompromised patients, ensuring timely and appropriate treatment. • Age-Specific Considerations: The predominance of older adults with comorbidities like diabetes suggests that management protocols should be tailored to address the complexities of this demographic. In conclusion, while empirical broad-spectrum therapy appears effective in this setting, optimizing outcomes for CNS infections in Egypt hinges on closing the diagnostic gap. Future efforts should focus on strengthening laboratory capacity and conducting prospective studies to better understand the evolving epidemiology and optimal management of these serious infections. Compliance with ethical standards Acknowledgments Authors wish to thank Major General Med. Tarek El Nagdy, manager of the medical military academy, and Major General Med. Ashraf Zaki, leader of Almaza Military Fever Hospital, as well as all staff of Almaza Military Fever Hospital. Disclosure of conflict of interest Authors declare no conflict of interest of any sort Statement of ethical approval Ethical approval was obtained from the Ethical Committee of medical military academy. Statement of informed consent Consent to extract data from hospital records obtained from the Almaza Military Fever Hospital administration. This data will not be used for any purpose other than this research study. References [1] Faizi, N., Hassan, J. (2023). 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