Search Results (1,214)

Background: Cefazolin is being increasingly used to treat central nervous system infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) to mitigate the side effects of existing anti-Staphylococcal drugs. This study aims to develop a cerebrospinal pharmacokinetic (PK) model to predict the cefazolin concentration in cerebrospinal fluid (CSF) and to individualize the dosing regimen for MSSA meningitis. Methods: A cerebrospinal PK model was developed based on the existing literature and used to estimate the probability of attaining PK/ pharmacodynamic (PD) targets. These targets were set as 100% time above the minimum inhibitory concentration (T > MIC) in CSF. The cerebrospinal PK/PD breakpoint was defined as the highest MIC at which target attainment probability in CSF was ≥90%. The mean CSF/serum ratio estimated from the literature was 0.0525 after a dose of 1–3 g (sampling time: 1–9 h after dose) in adult patients with suspected meningitis. This ratio was incorporated into this PK model based on a hybrid approach. Results: For patients with creatinine clearance (CL_cr) = 90 mL/min, the cerebrospinal PK/PD breakpoint MICs of continuous infusion regimens (6–12 g/day) reached 0.5 µg/mL, which can inhibit the growth of 90% of the MSSA population (MIC₉₀). Furthermore, for patients with renal dysfunction (CL_cr = 30 mL/min), a dose reduction (4 g/day) may be required to avoid excessive drug exposure. Conclusions: High-dose continuous infusion of cefazolin may be appropriate for MSSA meningitis in patients with normal renal function, while dose adjustments are needed for those with renal impairment. Full article

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has emerged as a candidate for therapeutic repurposing due to its reported antifungal activity. We systematically reviewed in vitro, in vivo, and clinical evidence up to July 2025 (PubMed, Scopus, Web of Science). As a result, 322 records were screened and 63 studies were found to meet the inclusion criteria (PRISMA 2020). We close a critical gap by consolidating relevant evidence on Candida auris, including preclinical in vivo models, which have been under-represented in previous summaries. Outcomes included minimum inhibitory and fungicidal concentrations (MIC/MFC), biofilm inhibition, fungal burden, survival, and pharmacokinetic/pharmacodynamic parameters. Preclinical data indicate its activity against clinically relevant fungi—particularly Cryptococcus neoformans and Candida spp., including C. auris—as well as consistent anti-biofilm effects and synergy with amphotericin B, fluconazole, micafungin, or voriconazole. Mechanistic evidence implicates mitochondrial dysfunction, membrane perturbation, impaired protein synthesis, and calcium homeostasis disruption. However, its potential for clinical translation remains uncertain: in cryptococcal meningitis, small phase II studies suggested improved early fungicidal activity, whereas a phase III randomized trial did not demonstrate a benefit regarding survival. Pharmacokinetic constraints at conventional doses, the absence of an intravenous formulation, and safety considerations at higher doses further limit its immediate applicability. Overall, the available evidence supports sertraline as a promising adjuvant candidate, rather than a stand-alone antifungal. Future research should define PK/PD targets, optimize doses and formulations, and evaluate rational combinations through rigorously designed trials, particularly for multidrug-resistant and biofilm-associated infections. Full article

Pneumococcal meningoencephalitis is a severe infection associated with high morbidity and mortality. Although typically community-acquired, postoperative cases following elective ENT surgery are exceedingly rare. Antimicrobial resistance (AMR) among Streptococcus pneumoniae further complicates management, and missed opportunities for vaccination represent preventable risks. We report a case of a 41-year-old man with multiple comorbidities who developed fulminant S. pneumoniae meningitis 48 h after septoturbinoplasty. The clinical course was atypical, with altered consciousness but no classical meningeal signs, necessitating urgent intubation and intensive care admission. Cerebrospinal fluid cultures identified an MDR pneumococcal strain resistant to penicillin and macrolides but susceptible to vancomycin and meropenem. Empirical therapy with vancomycin and meropenem, combined with adjunctive corticosteroids and multidisciplinary ICU care, led to complete neurological recovery. This case highlights a rare but life-threatening postoperative complication and underscores two critical lessons. First, the growing challenge of multidrug-resistant pneumococcus requires timely recognition, aggressive empiric therapy, and access to effective agents. Second, the absence of pneumococcal vaccination in this high-risk surgical patient illustrates a preventable gap in care. Integrating vaccination screening into preoperative evaluations may reduce the risk of catastrophic postoperative CNS infections. Full article

Coccidioidal meningitis (CM) is a rare but life-threatening complication of disseminated coccidioidomycosis, occurring in ~16% of cases, particularly among children in endemic regions such as the southwestern US and northern Mexico. Without timely diagnosis and antifungal therapy, pediatric CM is almost universally fatal within the first year. Hydrocephalus develops in up to 50% of cases. In 2000, Galgiani et al. established fluconazole as first-line therapy for CM. Subsequent guidelines refined management but did not specifically address pediatric patients (>1 month–≤19 years). No studies in the fluconazole era have systematically evaluated risk factors for complications in this population. We therefore conducted a systematic review and proportional synthesis of pediatric CM cases, focusing on CNS complications and outcomes. PubMed/MEDLINE, Embase (Ovid), and Web of Science were systematically searched (2000–2025). PROSPERO registration ID (1130290). Inclusion criteria encompassed epidemiological studies, case series, and case reports that described at least one pediatric case of CM or CNS involvement, confirmed by diagnostic methods. Cases in adults, neonates (<1 month), congenital infections, teratogenicity studies, reviews, or incomplete reports were excluded. Only cases with complete individual data (n = 48) were included. Methodological rigor was ensured using JBI Critical Appraisal Tools. Of 1089 studies, 31 met the inclusion criteria, representing 3874 pediatric cases. CM/CNS involvement was confirmed in 165 cases (4.25%; 95% CI: 3.6–4.9%), with hydrocephalus in 62 (37.5%). Among 48 case reports with complete data, fluconazole was first-line therapy in 65%. Serum CF titers ≥ 1:16 were associated with hydrocephalus plus stroke (p = 0.027) and independently predicted adverse outcomes (relapse/death; OR = 4.5, p = 0.037), whereas lifelong azole therapy was associated with improved outcomes (overall survival mean, 82 vs. 32 months; p = 0.002). Pediatric CM remains highly lethal, with hydrocephalus a frequent and severe complication. High serum CF titers (≥1:16) predict poor outcomes, emphasizing the urgent need for standardized, pediatric-specific diagnosis and management guidelines. Full article

Glaesserella parasuis (G. parasuis), a common pathogenic bacterium in the porcine respiratory tract, can cause porcine polyserositis, arthritis, and meningitis. Alveolar macrophages are the first line of defense in the pulmonary innate immunity, and their abnormal apoptosis plays a critical role in the pathogenic process of G. parasuis. Long non-coding RNA maternally expressed gene 3 (MEG3) is associated with G. parasuis infection, but its mechanism remains incompletely unclear. This study aimed to investigate the role of MEG3 in G. parasuis-induced apoptosis of the porcine alveolar macrophage cell line 3D4/21 and its detailed molecular mechanism. Here, we found that MEG3 overexpression promoted G. parasuis-induced apoptosis and upregulated key extrinsic pathway proteins caspase-8 (CASP8) and caspase-3 (CASP3). Mechanistically, MEG3 functioned as a competing endogenous RNA by sponging ssc-miR-135, which directly targets and inhibits CASP8. Consequently, MEG3 overexpression alleviated ssc-miR-135-mediated repression of CASP8. Functional rescue experiments confirmed that either ssc-miR-135 mimic or CASP8 siRNA reversed the pro-apoptotic effect of MEG3. In conclusion, this study reveals that MEG3 relieves the inhibitory effect of ssc-miR-135 on CASP8 through competitively binding, thereby regulating G. parasuis-induced apoptosis of 3D4/21 cells. This study provides new insights into the pathogenic molecular mechanism of G. parasuis. Full article

We reviewed vancomycin-resistant Enterococcus (VRE) colonisation of inpatients of a spinal cord injury centre. The centre consists of one single occupancy en suite room and ten multi-occupancy rooms where two to six patients stay in a cubicle. These patients share bathroom and toilet facilities. Active screening for VRE is performed by taking rectal swabs on admission of patients to the spinal unit. The patients, who are colonised with VRE, are not isolated due to constraints in resources. During a twelve-month period (April 2024 to April 2025), 33 patients tested positive for VRE. In April 2025, 17 of 40 in-patients tested positive for VRE. During the last six 12-month periods from 2019, the number of patients testing positive for VRE has shown an upward trend from 18 during 2019–2020 to 33 during 2024–2025. No patient developed systemic infection with VRE (blood stream infection, endocarditis, meningitis, intra-abdominal sepsis, infection of a spinal implant or baclofen pump) during the study period. Twelve patients underwent implantation of a baclofen pump during 2024–2025. No patient developed VRE infection from the implant. We believe that non-isolation of patients colonised with VRE may be a pragmatic approach in a resource-poor healthcare facility. It is possible that non-isolation could have contributed to an increase in the number of patients who became colonised with VRE. Attention should be paid to infection prevention measures including hand washing and environmental cleaning to prevent the spread of VRE colonisation of inpatients and VRE infection of at-risk patients, e.g., immune-compromised individuals. Full article

A 47-year-old woman presented with a two-year history of progressive visual symptoms and headaches. Lumbar puncture revealed lymphocytic pleocytosis, elevated protein, low glucose, and a CSF CrAg titer of 1:256. She was treated empirically for cryptococcal meningitis with amphotericin B, flucytosine, and fluconazole for 15 months. Her symptoms persisted, and repeated CSF and serum CrAg, fungal cultures, and an extensive infectious workup were negative. CSF flow cytometry eventually demonstrated a monoclonal B-cell population suggestive of a lymphoproliferative process. Imaging, including MRI and PET scans, did not reveal systemic disease. A ventriculoperitoneal (VP) shunt was placed for symptom management. This case emphasizes the limitations of CrAg testing and the potential for false positives. It underscores the need for integrating clinical, laboratory, and imaging data when evaluating chronic meningitis. Full article

Background: Acinetobacter baumannii is a highly concerning pathogen in hospital settings, responsible for severe infections such as ventilator-associated pneumonia, urinary tract infections, and meningitis. Its remarkable genetic plasticity facilitates the rapid acquisition of antibiotic resistance, significantly complicating treatment and increasing mortality rates. As multidrug-resistant (MDR) infections continue to rise, phage therapy emerges as a viable alternative. Methods: This study reports the isolation and characterization of Acinetobacter phage vB_AbaM_A72 from stagnant water in Jalisco, Mexico. Results: Transmission electron microscopy revealed a myovirus-like morphology with an icosahedral head (91.32 ± 0.12 nm) and a contractile tail (123.77 ± 0.19 nm). The phage exhibited high environmental resilience, tolerating temperatures up to 60 °C and pH ranging from 5 to 11. Notably, A72 demonstrated a narrow host range but effectively inhibited the growth of an MDR A. baumannii strain for at least 12 h across different multiplicities of infection. Whole-genome sequencing confirmed the absence of virulence, antibiotic resistance, or lysogeny-associated genes. Comparative genomic analysis identified A72 as the first member of a newly described Obolenskvirus species, sharing only 76.4% similarity with its closest relatives. Conclusions: These findings underscore the importance of fully characterizing novel bacteriophages to expand therapeutic libraries and reinforce the feasibility of phage therapy as a promising approach against MDR A. baumannii infections. Full article

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis and is associated with high morbidity and mortality, especially in resource-limited settings. In Mozambique, where both tuberculosis and HIV are highly prevalent, TBM poses significant diagnostic and therapeutic challenges. This study aimed to describe the clinical characteristics and to identify predictors of TBM mortality among persons living with HIV (PLWH) in a rural hospital in Mozambique. Methods: We conducted a retrospective cohort study at Carmelo Hospital of Chokwe (CHC) between 2015 and 2020. We included 372 PLWH diagnosed with TBM (PTBM); data on demographics, clinical presentation, and laboratory findings were extracted from patient records. TBM diagnosis was considered for confirmed cases based on a hospital-adapted algorithm incorporating clinical features, cerebrospinal fluid (CSF) analysis, TB-LAM, and Xpert MTB/RIF testing. Cox proportional hazard models were used to identify independent predictors of mortality, and Kaplan–Meier survival curves with log-rank tests were used to assess survival differences across clinical subgroups. Significance was considered at a p value ≤ 0.05 with an adjusted hazard ratio (AHR) 95% CI in the multivariate analysis. Results: Overall, 372 PTBM contributed to a total of 3720 person-months (PM) of treatment follow-up, corresponding to a mortality incidence of 3.76 deaths per 100 person-months. Factors independently associated with increased mortality included male sex (adjusted hazard ratio [aHR]: 1.80; 95% CI: 1.21–2.68; p = 0.004), BMI < 18.5 kg/m² (aHR: 2.84; 95% CI: 1.46–5.55; p = 0.002), Immunovirological failure to ART (aHR: 2.86; 95% CI: 1.56–5.23; p = 0.001), CSF opening pressure >40 cmH₂O (aHR: 2.67; 95% CI: 1.46–4.86; p = 0.001), and TBM severity grading III (aHR: 4.59; 95% CI: 1.79–11.76; p = 0.001). TBM involving other organs also significantly worsened survival (aHR: 2.03; 95% CI: 1.27–3.25; p = 0.003). Conclusions: TBM mortality in PLWH was driven by ART failure, high CSF pressure, and malnutrition. Male sex and severe neurology also increased risk. Urgent interventions are proposed: optimize ART, manage intracranial pressure, provide nutritional support, and use corticosteroids. An integrated care approach is essential to improving survival in resource-limited settings. Full article

Laboratory confirmation of invasive meningococcal disease (IMD) relies on detection of Neisseria meningitidis in a biological specimen. Clinical management guidelines for patients presenting with signs and/or symptoms of meningitis and encephalitis emphasize the need for appropriate specimen collection for laboratory testing. To explore the potential for IMD under-diagnosis, we reviewed medical records of patients admitted with signs and/or symptoms of meningitis or encephalitis at five hospitals in Louisville, Kentucky, in 2014 to 2023. Among 675 patients admitted with meningitis and/or encephalitis with cerebrospinal fluid (CSF) cultures who received antibiotics, 300 (44.4%) received antibiotics before CSF collection. Among 431 with blood cultures who received antibiotics, 133 (30.9%) received antibiotics before blood collection. Among 751 patients with CSF collected, 651 (86.7%) CSF specimens were tested using polymerase chain reaction (PCR) for N. meningitidis detection. No blood specimens were PCR-tested. These findings indicated that current standard-of-care practices may lead to IMD under-diagnosis. Since public health surveillance relies on IMD laboratory diagnosis, these findings highlight the potential for under-ascertained IMD by surveillance. Full article

Healthcare professionals (HCPs) working in paediatric settings are routinely exposed to respiratory pathogens, increasing their risk of asymptomatic colonisation by meningitis-associated bacteria. This study is the first to assess oropharyngeal and nasopharyngeal carriage of major bacterial meningitis pathogens among paediatric HCPs in Benin, and to identify associated risk factors. A cross-sectional analytical study was conducted in nine hospitals between 1 September 2023 and 30 September 2024. Data collection involved a structured questionnaire and paired oropharyngeal and nasopharyngeal swabs. Culture-based identification and antimicrobial susceptibility testing were performed according to CA-SFM guidelines. By culture method, Streptococcus pneumoniae was the most frequently isolated pathogen, mainly from oropharyngeal samples (47.5%). Most of these strains exhibited multidrug resistance. In nasopharyngeal samples analysed by real-time PCR, detection rates for S. pneumoniae were markedly higher (24.4%) compared to culture (5.0%), highlighting the limited sensitivity of conventional methods in detecting asymptomatic carriage. Pneumococcal colonisation was significantly associated with recent respiratory tract infections, and residence in high-risk areas (p < 0.05). These findings underscore the need for enhanced molecular surveillance, along with strengthened infection control measures and targeted vaccination strategies, to mitigate the risk of horizontal transmission in paediatric wards. Full article

Bacterial meningitis is one of the most serious infections. Salmonella meningitis is associated with a high prevalence of long-term adverse outcomes, often linked to acute complications and a broad range of potential neurological sequelae following the infection. Acute complications such as brain abscesses and chronic complications such as hearing loss and developmental delay. In this report, we present a case of a 2-month-old male patient with seizures, hypoactivity and respiratory symptoms, who was found to have Salmonella bacteremia complicated by Salmonella and Human Herpes Virus-6 (HHV-6) meningitis, as well as rhinovirus bronchiolitis, along with follow-up findings. The patient’s data, including demographics, presenting symptoms, physical examination findings, and whole exome sequence results, as well as investigations such as complete blood count (CBC), cerebrospinal fluid (CSF) analysis, liver enzyme levels, and imaging findings, were collected from the electronic medical record system using a case report form. In addition, immunological workups were performed, as serious Salmonella infections were more common in immunocompromised patients. In the literature, there was no clear correlation between Salmonella and HHV-6 meningitis, rhinovirus bronchiolitis, and the complications that developed in this infant. This case report provides valuable insights into the clinical spectrum and long-term outcomes of patients with Salmonella meningitis. Full article

Tuberculous meningitis (TBM) is a severe illness that is predominantly observed in countries with a high burden of tuberculosis. It is primarily found in infants and human immunodeficiency virus (HIV)-infected adults, and, if left untreated, causes irreversible damage to the host’s nerve and brain tissue, often leading to mortality. Current methods of TBM detection relies on cerebrospinal fluid (CSF) culture, which may only yield results in up to 6 weeks, is not very sensitive, and requires a biological safety level III laboratory to conduct. Other detection methods are equally not very sensitive and laborious. This research investigates the detection of interferon-gamma (IFN-γ) protein biomarker using fluoroimmunoassay with an optical biosensor and a custom-manufactured chip. The glass-surface of the chip was treated with 3-aminopropyltriethoxysilane (APTES) and incubated with glutaraldehyde to prepare for immobilization, after which a sandwich ELISA format was used to perform a dilution series by immobilizing the capture antibody, IFN-γ protein, and fluorescein isothiocyanate (FITC)-stained detection antibody onto the chip. The optical biosensor excited the FITC-stained antibodies to capture the emission light at multiple exposures, which were then merged to create a high dynamic range (HDR) image for image processing. The results from the optical biosensor were verified with a Zeiss LSM780 confocal microscope (Carl Zeiss (Pty) Limited, Cape Town, South Africa). The system demonstrated the capability to rapidly identify the biomarker, detect the binding sites, and quantify IFN-γ in blood serum. This fluorescent optical sensor proposes a possible approach for the development of a point-of-care system for TBM, providing a quicker and simpler method for the early detection of TBM. Full article

Background/Objectives: Streptococcus agalactiae (Group B Streptococci, GBS) is Gram-positive, beta-hemolytic coccus known to be transmitted by vertical transmission in neonates during birth with neonatal sepsis, pneumonia, and meningitis. In adults, particularly the elderly and those with diabetes mellitus, GBS can also cause pneumonia and sepsis. Penicillin is the drug of choice, and GBS is generally susceptible to this antibiotic. This study investigates trends in GBS isolation rates and penicillin non-susceptibility over time at a university hospital. Methods: We retrospectively analyzed 24 years (2000–2023) of microbiological data from Ilsan Paik Hospital to investigate trends in GBS isolation and penicillin susceptibility. Isolates were identified and tested using the Vitek 2 system, following CLSI guidelines. WHONET 2023 was used for data aggregation and analysis. Trends were analyzed by dividing the study period into three intervals: Period 1 (2000–2009), Period 2 (2010–2019), and Period 3 (2020–2023). Antimicrobial susceptibility rates for total GBS and PCN-NS GBS (penicillin non-susceptible group B Streptococcus) were compared using chi-square tests. Results: Among 257,884 total isolates, 3003 (1.16%) were GBS, and 29 (0.97%) were PCN-NS. GBS and PCN-NS isolation rates increased significantly across the three periods (p = 0.0001 and p = 0.009, respectively). PCN-NS GBS showed reduced susceptibility to all tested antimicrobials, with no drug showing higher susceptibility compared to total GBS. Conclusions: This study demonstrates a statistically significant rise in both GBS isolation rate and penicillin non-susceptibility over time. Given the emergence of multidrug-resistant GBS strains, susceptibility testing and interdisciplinary collaboration between microbiologists and clinicians are critical to guiding effective antimicrobial therapy and preventing neonatal and adult GBS infections. Full article

Background: Invasive meningococcal disease (IMD) is an uncommon but potentially life-threatening condition, resulting in life-long sequelae or death in up to 20% of cases. Most IMD cases are caused by Neisseria meningitidis serogroups (Men) A, B, C, W, X, and Y. The highest IMD incidence is among children < 5 years of age (YOA). We reviewed IMD epidemiology data and existing national immunization programs (NIP) in the Americas and identify unmet needs to decrease IMD burden in young children. Methods: Using national surveillance data and published literature from 2006 to 2024, we evaluated the IMD burden and national vaccination strategies for children < 5 YOA in the Americas, focusing on Canada, the United States, Brazil, Chile, Argentina. Results: The highest IMD incidence was among infants, followed by children 1–4 YOA, with MenB infections predominating in both age groups. Chile has both MenACWY (2014) and MenB (2023) infant vaccination in its NIP. Argentina and Brazil’s NIPs include MenACWY (2017) and MenC (2010) vaccinations for infants, respectively. In Canada, MenC (2002) vaccination is recommended at 1 YOA (replaced by MenACWY in 2024 in Manitoba); MenB vaccination is selectively recommended. In each country, the incidence of IMD caused by vaccine-preventable serogroups decreased following the introduction of the respective meningococcal vaccination in the NIP. Conclusions: Comprehensive meningococcal vaccination programs in the Americas have the potential to reduce the IMD burden in children < 5 YOA. National recommendations and NIPs could reduce IMD burden by offering equitable access to protection against IMD, aligning with the WHO roadmap to defeat meningitis by 2030. Full article