Central Nervous System Infection Research Articles

Nogo-A exacerbates sepsis-associated encephalopathy by modulating microglial SHP-2/NLRP3 balance and inducing ROS and M1 polarization.

Sepsis, a systemic inflammatory response caused by infection, can lead to sepsis-associated encephalopathy (SAE), characterized by brain dysfunction without direct central nervous system infection. The pathogenesis of SAE involves blood-brain barrier disruption, neuroinflammation and neuronal death, with neuroinflammation being the core process. Nogo-A, a neurite growth-inhibitory protein in the central nervous system, is not well understood in sepsis. This study explores Nogo-A's mechanisms in sepsis, focusing on SAE. Using in vivo and in vitro methods, healthy SPF C57BL/6J male mice were divided into Sham, Nogo-A-NC-Model, and Nogo-A-KD-Model groups, with sepsis induced by abdominal ligation and puncture. Morris water maze tests assessed learning and memory, and brain tissues underwent hematoxylin-eosin (HE) staining, Nissl staining, and Western blot analysis. In vitro, Nogo-A gene knockdown models were constructed using BV-2 microglia cells to study inflammation and oxidative stress. Results showed Nogo-A expression affected learning and memory in septic mice, with knockdown reducing neuronal damage. Bioinformatics analysis suggested Nogo-A may activate reactive oxygen species (ROS) to inhibit p-SHP2, activating mitochondrial autophagy and promoting neuronal apoptosis. Western blot results confirmed that Nogo-A affects mitochondrial autophagy and neuronal survival by inhibiting SHP2 and activating ROS. Nogo-A's role in neuroinflammation and neuroprotection was emphasized, revealing its impact on endoplasmic reticulum (ER) stress, mitochondrial autophagy, and NLRP3 inflammasome activation. This study provides a theoretical basis for SAE treatment, suggesting further multi-gene and multi-pathway analyses and validation in clinical samples. Developing gene therapy and drug interventions targeting Nogo-A pathways will offer more effective treatment strategies.

Frequency of a Positive Cerebrospinal Fluid Study in Patients Presenting With Febrile Seizures

Background: Febrile seizures are a common neurological condition in pediatric practice, affecting 2-5% of children globally. These seizures occur in the context of fever without evidence of central nervous system infection or metabolic disturbance. While often benign, febrile seizures are associated with significant morbidity and can cause considerable distress for both patients and caregivers. The role of cerebrospinal fluid (CSF) abnormalities in the pathogenesis of febrile seizures is not well understood, but identifying these factors may help predict the risk of seizure occurrence. Objective: To determine the frequency of positive cerebrospinal fluid abnormalities in pediatric patients with febrile seizures and to assess the impact of these abnormalities on the risk of febrile seizures. Methods: This prospective cohort study was conducted from January 2022 to December 2023 at the Department of Paediatrics, Combined Military Hospital, Rawalpindi. A total of 117 pediatric patients aged 1 to 12 years with a history of febrile seizures presenting with a febrile illness were included. Patients with prior febrile seizures, metabolic/electrolyte disorders, or signs of meningeal infection were excluded. Comprehensive data collection included demographic information, clinical history, and CSF analysis for cell count, total protein, glucose, lactate, and electrolyte levels. Patients were monitored for febrile seizure occurrence during hospitalization. Data were analyzed using SPSS version 25, with continuous variables expressed as medians and interquartile ranges (IQR) and categorical variables as frequencies and percentages. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between CSF abnormalities and febrile seizures. Results: The median age of the patients was 3.0 years (IQR: 2.0), with 57.3% (n=67) being male. Febrile seizures occurred in 22.2% (n=26) of patients during hospitalization. Elevated CSF total protein (>60 mg/dL) was observed in 28.2% of patients, CSF glucose (>42 mg/dL) in 12.0%, CSF lactate (>2.0 mmol/L) in 13.7%, and CSF calcium (>1.25 mmol/L) in 10.3%. These abnormalities were significantly associated with an increased risk of febrile seizures: CSF total protein (OR: 3.55, 95% CI: 1.42–8.86, p=0.005), CSF glucose (OR: 13.59, 95% CI: 3.79–48.71, p<0.001), CSF lactate (OR: 4.61, 95% CI: 1.53–13.92, p=0.004), and CSF calcium (OR: 15.52, 95% CI: 3.81–63.36, p<0.001). Conclusion: This study identified significant associations between elevated CSF total protein, glucose, lactate, and calcium levels and an increased risk of febrile seizures in pediatric patients. CSF analysis could be a valuable tool in identifying children at higher risk for febrile seizures, potentially guiding preventive strategies and clinical management.

A Practical Approach to Antimicrobial Stewardship for Central Nervous System Infections.

A Practical Approach to Antimicrobial Stewardship for Central Nervous System Infections.

Human Herpesvirus 6-A Rare Aetiologic Agent for CNS Infections in Immunocompetent Individuals or an Underestimation?

Background: Human herpesvirus 6 (HHV-6) is considered a ubiquitous virus, with many countries reporting a seroprevalence of more than 80-90% among the general population. However, this virus is unique among herpesviruses in its ability to integrate into the genetic material of the host's cells. Thus, there are three ways by which HHV-6 can cause an active infection-primary infection, reactivation of a latent acquired infection, or activation of iciHHV-6 (inherited chromosomally integrated HHV-6). Whole blood quantitative polymerase chain reaction (qPCR) is very useful in distinguishing between iciHHV-6 and primary infection/reactivation. Our aim is to assess the role of HHV-6 in the aetiology of central nervous system (CNS) infections in adults and children, to describe all HHV-6-positive cases in an attempt to determine the susceptible population and to identify potential risk factors that can be linked to HHV-6 meningoencephalitis. Methods: We performed a retrospective study involving patients that were admitted to Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania, with a diagnosis of meningitis or encephalitis. We only selected the clinical records of patients that had a multiplex PCR Biofire® FilmArray® meningitis/encephalitis panel. Results: We report a 5% HHV-6 positivity in the cerebrospinal fluid (CSF) of patients with CNS infections tested with a commercial multiplex PCR M/E (meningitis/encephalitis) panel. Additionally, 2% to 4% of the total study population (n = 100) had active HHV-6 infections, which denotes 40 to 80% of the HHV-6-positive samples. We did not observe any statistically significant correlation between HHV-6 positivity in the CSF and variables such as age, sex, or comorbidities, including obesity, diabetes, hypertension, immunosuppression, or oncologic disease. Therefore, no risk factors could be linked with HHV-6 positivity in the CSF. Conclusions: although multiplex qualitative PCR is highly useful for providing rapid results and identifying nearly every pathogen that can cause meningitis/encephalitis, we have to be aware of this type of test's limitations. All patients with HHV-6 detectable in their CSF via a multiplex PCR test should also undergo qPCR testing from both CSF and blood to prevent over-diagnosing HHV-6 CNS infections, to avoid unnecessary antiviral treatments, and ensure the accurate identification of the true diagnosis.

Diagnostic prediction models for bacterial meningitis in children with a suspected central nervous system infection: a systematic review and prospective validation study

ObjectivesDiagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population...

Changes in optic nerve sheath diameter and its correlation with degree of consciousness, pupil diameter, and light reflex in children with central nervous system infection after osmotherapy.

High intracranial pressure (ICP) is one of the most common complications of central nervous system (CNS) infection. Failure to control high intracranial pressure results in brain herniation and death. One of the treatments for high ICP involves the administration of osmotherapy in the form of 3% NaCl or 20% mannitol with observation during administration. Observation of ICP during administration of osmotherapy is possible through measurement of optic nerve sheath diameter (ONSD), which could be correlated with degree of consciousness, pupil diameter, and light reflex. Previous studies have not correlated ONSD with degree of consciousness, pupil diameter, and light reflex during the administration of osmotherapy. To provide insights of incorporating ONSD measurement as a form of non-invasive bedside method for ICP monitoring by correlating it with degree of consciousness, pupil diameter, and light reflex at several time points. This study is a prospective cohort study, performed at Dr. Hasan Sadikin General Central Hospital Bandung, Cibabat General Regional Hospital, and General Regional Hospital Bandung Kiwari on children aged 2-18 years with decreased consciousness and CNS infection, from June 2023. Inter-rater reliability was performed with a correlation coefficient of 0.90. Measurement of ONSD, degree of consciousness, pupil diameter, and light reflex simultaneously up to 48 h after initiation of osmotherapy to 30 patients. Correlational analyses were performed using Spearman's rank. Observation for 48 h after administration of osmotherapy showed changes in ONSD. A significant positive correlation was found between ONSD and degree of consciousness (r = 0.621 for the right eye and r = 0.602 for the left eye, p < 0.001). A significant positive correlation was found between ONSD and light reflex (r = 0.801 for the right eye and r = 0.812 for the left eye, p < 0.001). No significant correlation was found with changes of pupil diameter (r = -0.136 for the right eye and r = -0.141 for the left eye, p > 0.05). A significant correlation was found between ONSD and degree of consciousness and light reflex in children aged 2-18 years with CNS infection during administration of osmotherapy.

Validation of the encephalitis criteria in adults with a suspected central nervous system infection: An updated score

ObjectivesWe aimed to validate and refine the encephalitis criteria proposed by the International Encephalitis Consortium in a cohort of adults initially suspected of a central nervous system (CNS) infection. MethodsWe included patients from two prospective cohort studies consisting of adults suspected of a CNS infection whom underwent a diagnostic lumbar puncture. We evaluated the test characteristics of the criteria for both possible and probable encephalitis. The reference standard was a final clinical diagnosis of encephalitis. Recalibration of the criteria was done by adjusting the weight of each criterion based on their respective odds. ResultsIn total 1446 episodes were evaluated, of whom 162 (11%) had a clinical diagnosis of encephalitis. Possible encephalitis had a sensitivity of 41% (95% CI 33-49) and a specificity of 88% (95% CI 86-90). Probable encephalitis had a sensitivity and specificity of respectively 27% (95% CI 20-34) and 95% (95% CI 94-96). Through odds-based weighting we recalibrated the weight of each individual criterion, resulting in a model consisting of an altered mental status (weight of 2), seizures (weight of 3), elevated CSF leukocyte count (weight of 5) and abnormalities on neuroimaging (weight of 9). We proposed a cut-off at 5 for possible encephalitis, (sensitivity 93% [95% CI 88-96]; specificity 51% [95% 49-54]), and at 8 for probable encephalitis (sensitivity 51% [95% CI 44-59]; specificity 91% [95% CI 89-92]). ConclusionsWe validated and refined the existing diagnostic criteria for encephalitis, leading to a substantially enhanced sensitivity. These updated criteria hold promise to facilitate the accurate identification of encephalitis.

LC-MS metabolomics and lipidomics in cerebrospinal fluid from viral and bacterial CNS infections: a review.

There is compelling evidence that a dysregulated immune inflammatory response in neuroinfectious diseases results in modifications in metabolic processes and altered metabolites, directly or indirectly influencing lipid metabolism within the central nervous system (CNS). The challenges in differential diagnosis and the provision of effective treatment in many neuroinfectious diseases are, in part, due to limited understanding of the pathophysiology underlying the disease. Although there are numerous metabolomics studies, there remains a deficit in neurolipidomics research to provide a comprehensive understanding of the connection between altered metabolites and changes in lipid metabolism. The brain is an inherently high-lipid organ; hence, understanding neurolipidomics is the key to future breakthroughs. This review aims to provide an integrative summary of altered cerebrospinal fluid (CSF) metabolites associated with neurolipid metabolism in bacterial and viral CNS infections, with a particular focus on studies that used liquid chromatography-mass spectrometry (LC-MS). Lipid components (phospholipids) and metabolites (carnitine and tryptophan) appear to be the most significant indicators in both bacterial and viral infections. On the basis of our analysis of the literature, we recommend employing neurolipidomics in conjunction with existing neurometabolomics data as a prospective method to enhance our understanding of the cross link between dysregulated metabolites and lipid metabolism in neuroinfectious diseases.

Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection.

Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections. Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality. All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin. After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.

Childhood Health and Educational outcomes afteR perinatal Brain injury (CHERuB): protocol for a population-matched cohort study

IntroductionOver 3000 infants suffer a brain injury around the time of birth every year in England. Although these injuries can have important implications for children and their families, our understanding...

Central Nervous System Infection with Hypervirulent Klebsiella pneumoniae

Hypervirulent Klebsiella pneumoniae (hvKp) infections are being increasingly reported globally, and cause severe central nervous system (CNS) and multiorgan infections even in immunocompetent individuals. The recent emergence of hvKp antibiotic resistance has generated escalating concern about effective infection control for this potentially neuroinvasive pathogen. Herein, we report two cases of Klebsiella pneumoniae-related CNS infection, including one patient with antimicrobial-resistant hvKp, confirmed by string test that demonstrated a hypermucoviscous phenotype.

Utilidad del PCR múltiplex de hemocultivo para el diagnóstico microbiológico de infecciones nosocomiales del sistema nervioso central en pacientes críticos

Background and objectiveTo determine the usefulness of a molecular biology technique for nucleic acid amplification using real-time polymerase chain reaction (PCR) originally designed for microbiological diagnosis in blood cultures, when applied to cerebrospinal fluid (CSF) samples. Materials and methodsRetrospective, observational, single-center study, carried out between January 2017 and February 2024 in a 28-bed multipurpose critical care unit. All patients with suspected postneurosurgical infection and CSF cytochemical alterations were included. In addition to the microbiological study of the CSF by traditional methods, the BioFire® Blood Culture Identification2 (BCID) panel was applied directly to CSF samples. Traditional culture methods were considered as the reference standard for microbiological identification. The main variable of interest was the percentage of concordance of microbial identification between traditional cultures and BCID. Results29 patients were included. The diagnosis of central nervous system infection was confirmed in 14 cases (48.2%), 7 post-neurosurgical meningitis, 6 infections associated with ventriculostomy and 1subdural empyema. The most frequently found microorganisms were Acinetobacter baumannii and Klebsiella pneumoniae. No discordances were found between PCR and cultures, so both the positive (14/14) and negative identification concordance (15/15) were 100% between both methods. ConclusionsIn patients with suspected post-neurosurgical infection and compatible CSF alterations, multiplex PCR blood cultures applied directly to CSF samples could be considered a useful and accurate tool for rapid microbiological diagnosis in infections of the central nervous system.

Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice

Since prion diseases result from infection and neurodegeneration of the central nervous system (CNS), experimental characterizations of prion strain properties customarily rely on the outcomes of intracerebral challenges. However, natural transmission of certain prions, including those causing chronic wasting disease (CWD) in elk and deer, depends on propagation in peripheral host compartments prior to CNS infection. Using gene-targeted GtE and GtQ mice, which accurately control cellular elk or deer PrP expression, we assessed the impact that peripheral or intracerebral exposures play on CWD prion strain propagation and resulting CNS abnormalities. Whereas oral and intraperitoneal transmissions produced identical neuropathological outcomes in GtE and GtQ mice and preserved the naturally convergent conformations of elk and deer CWD prions, intracerebral transmissions generated CNS prion strains with divergent biochemical properties in GtE and GtQ mice that were changed compared to their native counterparts. While CWD replication kinetics remained constant during iterative peripheral transmissions and brain titers reflected those found in native hosts, serial intracerebral transmissions produced 10-fold higher prion titers and accelerated incubation times. Our demonstration that peripherally and intracerebrally challenged Gt mice develop dissimilar CNS diseases which result from the propagation of distinct CWD prion strains points to the involvement of tissue-specific cofactors during strain selection in different host compartments. Since peripheral transmissions preserved the natural features of elk and deer prions, whereas intracerebral propagation produced divergent strains, our findings illustrate the importance of experimental characterizations using hosts that not only abrogate species barriers but also accurately recapitulate natural transmission routes of native strains.

Rare Central nervous system infection by Chryseobacterium indologenes diagnosed using metagenomic next-generation sequencing.

Rare Central nervous system infection by Chryseobacterium indologenes diagnosed using metagenomic next-generation sequencing.

Candida parapsilosis intracerebral abscess and intralesional amphotericin B: a novel treatment approach to a rare infection. Illustrative case.

Candida parapsilosis has been implicated in central nervous system (CNS) infections (i.e., meningitis or ventriculitis) but has not been previously reported to cause intracerebral abscesses. CNS infections secondary to C. parapsilosis are notoriously difficult to treat due to the poor CNS penetration of amphotericin B. Historically, intraventricular amphotericin B has been used to treat C. parapsilosis ventriculitis. A 15-year-old female with no comorbidities presented with nonresolving headaches, photophobia, fevers, and meningism. Computed tomography (CT) of the brain revealed a right frontal abscess. After multiple drainage surgeries, subsequent CT scans showed reaccumulation of her abscess. C. parapsilosis was cultured, and the patient was then taken to the operating room where an external ventricular drain catheter was successfully placed within the abscess cavity. Pus was repeatedly aspirated, followed by the instillation of intralesional amphotericin B twice a day for 2 weeks. The patient's clinical condition improved substantially with complete resolution of symptoms, improvement of infective markers, and resolution of radiological features of the abscess. Follow-up of the patient revealed the absence of symptoms and image characteristics of abscess on CT 3 months posttreatment. Intralesional amphotericin B is a novel but effective treatment of C. parapsilosis intracerebral abscess, an organism not previously described as a cause of intracerebral abscesses. https://thejns.org/doi/10.3171/CASE2484.

Subdural Empyema as a Rare Complication Caused by Neisseria meningitidis B

Subdural empyema (SDE) is an intracranial collection of purulent material located between the dura and the arachnoid mater. It is a serious central nervous system infection which can cause neurological sequelae and high mortality. We report one of the rare cases of SDE secondary to Neisseria meningitidis to underline the interest of evoking this diagnosis especially in patients not responding to standard antimicrobial therapy.

Clinical application and evaluation of metagenomic next-generation sequencing in pathogen detection for suspected central nervous system infections

Central nervous system Infections (CNSIs) is a disease characterized by complex pathogens, rapid disease progression, high mortality rate and high disability rate. Here, we evaluated the clinical value of metagenomic next generation sequencing (mNGS) in the diagnosis of central nervous system infections and explored the factors affecting the results of mNGS. We conducted a retrospective study to compare mNGS with conventional methods including culture, smear and etc. 111 suspected CNS infectious patients were enrolled in this study, and clinical data were recorded. Chi-square test were used to evaluate independent binomial variables, taking p < 0.05 as statistically significant threshold. Of the 111 enrolled cases, 57.7% (64/111) were diagnosed with central nervous system infections. From these cases, mNGS identified 39.6% (44/111) true-positive cases, 7.2% (8/111) false-positive case, 35.1% (39/111) true-negative cases, and 18.0% (20/111) false-negative cases. The sensitivity and specificity of mNGS were 68.7% (44/64) and 82.9% (39/47), respectively. Compared with culture, mNGS provided a higher pathogen detection rate in CNSIs patients (68.7% (44/64) vs. 26.5% (17/64), p < 0.0001). Compared to conventional methods, positive percent agreement and negative percent agreement was 84.60% (44/52) and 66.1% (39/59) separately. At a species-specific read number (SSRN) ≥ 2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] 0.758, 95% confidence interval [CI] 0.663–0.854). In bacterial CNSIs patients with significant CSF abnormalities (CSF WBC > 300*106/L), the positive rate of CSF mNGS is higher. To sum up, conventional microbiologic testing is insufficient to detect all neuroinvasive pathogens, and mNGS exhibited satisfactory diagnostic performance in CNSIs and with an overall detection rate higher than culture (p < 0.0001).

Metagenomic next-generation sequencing of cerebrospinal fluid reveals etiological and microbiological features in patients with various central nervous system infections.

The application of metagenomic next-generation sequencing (mNGS) in pathogens detection of cerebrospinal fluid (CSF) is limited because clinical, microbiological, and biological information are not well connected. We analyzed the 428 enrolled patients' clinical features, pathogens diagnostic efficiency of mNGS in CSF, microbial community structure and composition in CSF, and correlation of microbial and clinical biomarkers in CSF. General characteristics were unspecific but helpful in formulating a differential diagnosis. CSF mNGS has a higher detection rate (34.6%) compared to traditional methods (5.4%). mNGS detection rate was higher when the time from onset to CSF collection was ≤20 days, the CSF leukocytes count was >200 × 106/L, the CSF protein concentration was >1.3 g/L, or CSF glucose concentration was ≤2.5 mmol/L in non-postoperative bacterial CNS infections (CNSi). CSF was not strictly a sterile environment, and the potential pathogens may contribute to the dysbiosis of CSF microbiome. Furthermore, clinical biomarkers were significantly relevant to CNS pathogens. Clinical data are helpful in choosing a proper opportunity to obtain an accurate result of mNGS, and can speculate whether the mNGS results are correct or not. Our study is a pioneering study exploring the CSF microbiome in different CNSIs.

Electrochemically synthesized nanostructured gold-bismuth as novel sensor for efficient determination of cefotaxime in aqueous media

Antibiotics are crucial due to their widespread use in human and veterinary medicine. Cefotaxime, a third-generation cephalosporin, prevents bacterial production and treats central nervous system infections like meningitis and septicemia. This study developed a novel electrochemical sensor for detecting Cefotaxime (CFTX) by electrodepositing gold-bismuth nanoparticles (Au-Bi NPs) on a carbon paste electrode (CPE). The electrochemical parameters were optimized for the successful deposition of Au-BiNPs. Morphological and X-ray diffraction (XRD) analyses revealed nanoparticle clusters of cubic Au and stacked monoclinic BiNPs on the CPE surface, with crystallite sizes of 7.5 and 6.3 nm, respectively. Cyclic voltammetry (CV) showed that the sensor had superior electrochemical activity for CFTX oxidation compared to bare CPE, BiNPs/CPE, and AuNPs/CPE, mainly due to the synergetic effect of Au-Bi nanoparticles. Electrochemical impedance spectroscopy (EIS) indicated minimal resistance to electron transfer at Au-BiNPs/CPE. Voltammetric investigations revealed a diffusion-controlled electrooxidation process involving two protons and two electrons, influenced by solution pH and scan rate. The sensor displayed excellent analytical parameters for CFTX detection, including a wide linear range (0.5 μM to 20 μM), high sensitivity (4.55 μAμM−1 cm−2), and a low detection limit (0.094 μM). Density Functional Theory (DFT) calculations provided theoretical insights into the sensor’s performance. The sensor also showed excellent reproducibility, repeatability (RSD values of 3.74 % and 1.71 %, respectively), and long-term stability of about one month, offering a new method for accurate and sensitive CFTX detection.

Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer.

Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53-0.93], p=.014), pneumonia (adjusted SHR 0.76 [0.59-0.99], p=.040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39-0.79], p=.001), but not urinary tract infection (adjusted SHR 0.91 [0.62-1.35], p=.643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess.