Chronic inflammatory diseases are caused due to prolonged inflammation at a specific site of the body. Among other inflammatory diseases, bacterial meningitis, chronic obstructive pulmonary disease (COPD), atherosclerosis and inflammatory bowel diseases (IBD) are primarily focused on because of their adverse effects and fatality rates around the globe in recent times. In order to come up with novel strategies to eradicate these diseases, a clear understanding of the mechanisms of the diseases is needed. Similarly, detailed insight into the mechanisms of commercially available drugs and potent lead compounds from natural sources are also important to establish efficient therapeutic effects. Zebrafish is widely accepted as a model to study drug toxicity and the pharmacokinetic effects of the drug. Moreover, researchers use various inducers to trigger inflammatory cascades and stimulate physiological changes in zebrafish. The effect of these inducers contrasts with the type of zebrafish used in the investigation. Hence, a thorough analysis is required to study the current advancements in the zebrafish model for chronic inflammatory disease suppression. This review presents the most common inflammatory diseases, commercially available drugs, novel therapeutics, and their mechanisms of action for disease suppression. The review also provides a detailed description of various zebrafish models for these diseases. Finally, the future prospects and challenges for the same are described, which can help the researchers understand the potency of the zebrafish model and its further exploration for disease attenuation.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited.
OBJECTIVE: To gain a better understanding about GAS meningitis.
METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized.
RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%.
CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

OBJECTIVE: Bacterial meningitis remains a global threat due to its high mortality. It is estimated that >1.2 million cases of bacterial meningitis are reported annually. Intracranial vasculopathy is an important, under-documented complication, easily detected by transcranial Doppler (TCD) ultrasonography. Following the PRISMA Guidelines, we reviewed the utility of TCD in bacterial meningitis.
METHODS: This is a systematic review of observational studies on the use of TCD in patients with CSF-proven bacterial meningitis. Characteristic changes in TCD parameters along the course of the disease, correlation of TCD findings with neuroimaging, and functional outcomes were evaluated.
RESULTS: Nine studies were included with a total of 492 participants (mean age of 42). The most common TCD finding was intracranial arterial stenosis of the MCA (50%-82%) and ischemia (33%) was the predominant neuroimaging finding. The presence of an abnormal TCD finding increased the risk of poor outcomes as high as 70%.
CONCLUSIONS: Patients diagnosed with bacterial meningitis who underwent TCD show alterations in cerebral blood flow, correlating with imaging findings and poor outcomes. It aids in the diagnosis of its sequelae and can predict the prognosis of its outcome. TCD is a cost-effective, reliable modality for diagnosing vasculopathy associated with bacterial meningitis. It may prove useful in our armamentarium of management. Large prospective studies with long-term follow-up data may help establish the use of TCD in bacterial meningitis.

The optimal duration of antibiotic treatment for the most common bacterial meningitis etiologies in the pediatric population, namely Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, is not well-established in the literature. Therefore, we aimed to perform an updated meta-analysis comparing shorter versus longer antibiotic treatment in children with meningitis. PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared shorter (up to 7 days) versus longer (10 days or double the days of the equivalent short course) duration of antibiotic treatment in children with meningitis and reported the outcomes of treatment failure, death, neurologic sequelae, non-neurologic complications, hearing impairment, nosocomial infection, and relapse. Heterogeneity was examined with I2 statistics. RevMan 5.4.1 was used for statistical analysis and RoB-2 (Cochrane) for risk of bias assessment. Of 684 search results, 6 RCTs were included, with a cohort of 1333 children ages 3 weeks to 15.5 years, of whom 49.51% underwent a short antibiotic course. All RCTs included monotherapy with ceftriaxone, except one, which added vancomycin as well. No differences were found comparing the short and long duration of therapy concerning treatment failure, relapse, mortality, and neurologic complications at discharge and at follow-up.  Conclusion: Because no statistically significant differences were found between groups for the analyzed outcomes, the results of this meta-analysis support shorter therapy. However, generalizing these results to complicated meningitis and infections caused by other pathogens should be made with caution. (PROSPERO identifier: CRD42022369843). What is Known: • Current recommendations on the duration of antibiotic therapy for bacterial meningitis are mostly based on clinical practice. • Defining an optimal duration of antibiotic therapy is essential for antimicrobial stewardship achievement, improving patient outcomes, and minimizing adverse effects. What is New: • There are no differences between shorter versus longer antibiotic treatment duration in regard to treatment failure, relapse, mortality, neurologic complications, and hearing impairment at discharge and at follow-up.

BACKGROUND: Bacterial meningitis is a central nervous system (CNS) infection disease of the meninges and brain parenchyma caused by the bacteria. Few cases of meningitis related to oral anaerobes have been reported in the literature. Here, we report a case of meningitis in a middle-aged woman, caused by oral anaerobes.
METHODS: A 58-year-old woman was admitted to hospital with fever, headache for 21 days and left limb weakness for 2 days. The blood cell counts (11.73 × 109/L), neutrophil counts (9.22 × 109/L) and high-sensitivity C-reactive protein levels (> 5.00 mg/L) were elevated. The brain computerized tomography (CT) scanning indicated the new right thalamus infarct. The brain cranial-enhanced magnetic resonance imaging (MRI) showed the right lateral paraventricular and right thalamic infarct, and abnormal signal in occipital horns of bilateral lateral ventricles were increased. In addition, the brain enhanced nuclear magnetic resonance (NMR) scanning suggested that meninges were thickened and enhanced at the base of the brain, with meningitis changes. The neck CT angiography (CTA) revealed arteriosclerotic changes. The metagenomic next-generation sequencing (mNGS) revealed Eubacterium brachy, Porphyromonas gingivalis, Fusobacterium nucleatum and Torque teno virus in her cerebrospinal fluid (CSF). The patient was diagnosed with purulent meningitis caused by infection of oral anaerobes, and treated with mannitol, ceftriaxone and vancomycin. Her symptoms alleviated. Subsequently, she was transferred to the infectious department and treated with ceftriaxone plus metronidazole (anti-anaerobes) and mannitol (reduce intracranial pressure). Her symptoms improved and currently received rehabilitation treatment.
CONCLUSIONS: We herein report a rare case involving meningitis caused by infection of oral anaerobes. The mNGS can accurately detect the pathogens of infectious diseases.

Most cases of gram-negative bacillary meningitis occur in neonates and infants. Meningitis in adults caused by Proteus mirabilis has been reported rarely. Evidence-based guidelines for the treatment of adult patients with gram-negative bacillus meningitis are scarce. The optimal duration of antibiotic therapy for these patients is an unanswered question in the medical literature. This article outlines a case of community-acquired meningitis caused by P. mirabilis in an adult patient who required an extended antimicrobial treatment, after failing to a three-week antibiotic regime. Our patient, a 66-year-old man with a history of neurogenic bladder, remote spinal cord trauma, and recurrent urinary tract infections presented to the emergency department reporting a two-day history of severe headache, fever, and confusion. Cerebrospinal fluid (CSF) revealed significant neutrophil-predominant pleocytosis, low glucose level, and elevated protein level. CSF culture grew few pan-susceptible P. mirabilis. The patient initially completed 21 days of ceftriaxone guided by susceptibility testing. Nine days after finishing antibiotic therapy, the patient was readmitted with recurrent headache, fever, and neck rigidity. A new CSF study again revealed pleocytosis, elevated polymorphonuclear cells, low glucose level, and elevated protein level, but with a negative CSF culture. The patient became afebrile, and his symptoms improved after two days of ceftriaxone. He completed an additional six-week regime of ceftriaxone. On the one-month follow-up visit, the patient remained afebrile, with no recurrent symptoms. Spontaneous community-acquired P. mirabilis meningitis is rare among adult patients. Experiences in the treatment of gram-negative bacillus meningitis in adults must be shared with the scientific community to build up a better understanding of this condition. In the context of this case, sterilization of the CSF, extended antibiotic therapy, and a close post-treatment follow-up are crucial for treating this life-threatening condition.

rRNA gene Sanger sequencing is being used for the identification of cultured pathogens. A new diagnostic approach is sequencing of uncultured samples by using the commercial DNA extraction and sequencing platform SepsiTest (ST). The goal was to analyze the clinical performance of ST with a focus on nongrowing pathogens and the impact on antibiotic therapy. A literature search used PubMed/Medline, Cochrane, Science Direct, and Google Scholar. Eligibility followed PRISMA-P criteria. Quality and risk of bias were assessed drawing on QUADAS-2 (quality assessment of diagnostic accuracy studies, revised) criteria. Meta-analyses were performed regarding accuracy metrics compared to standard references and the added value of ST in terms of extra found pathogens. We identified 25 studies on sepsis, infectious endocarditis, bacterial meningitis, joint infections, pyomyositis, and various diseases from routine diagnosis. Patients with suspected infections of purportedly sterile body sites originated from various hospital wards. The overall sensitivity (79%; 95% confidence interval [CI], 73 to 84%) and specificity (83%; 95% CI, 72 to 90%) were accompanied by large effect sizes. ST-related positivity was 32% (95% CI, 30 to 34%), which was significantly higher than the culture positivity (20%; 95% CI, 18 to 22%). The overall added value of ST was 14% (95% CI, 10 to 20%) for all samples. With 130 relevant taxa, ST uncovered high microbial richness. Four studies demonstrated changes of antibiotic treatment at 12% (95% CI, 9 to 15%) of all patients upon availability of ST results. ST appears to be an approach for the diagnosis of nongrowing pathogens. The potential clinical role of this agnostic molecular diagnostic tool is discussed regarding changes of antibiotic treatment in cases where culture stays negative.

Meningitis is a potential complication of elective intracranial surgery (EIS). The prevalence of meningitis after EIS varies greatly in the literature. The objective of this study was to estimate the overall pooled prevalence of meningitis following EIS. Four databases (PubMed, Scopus, Web of Science, and Embase) were searched to identify relevant studies. Meta-analyses of proportions were used to combine data. Cochran\'s Q and I2 statistics were used to assess and quantify heterogeneity. Additionally, several subgroup analyses were conducted to investigate the source of heterogeneity and examine differences in the prevalence based on variables such as geographical regions, income level, and meningitis type. The meta-analysis included 83 studies (30 959 patients) from 26 countries. The overall pooled prevalence of meningitis after EIS was 1.6% (95% CI 1.1-2.1), with high heterogeneity present (I2 = 88%). The pooled prevalence in low- to middle-income countries and high-income countries was 2.7% (95% CI 1.6-4.1) and 1.2% (95% CI 0.8-1.7), respectively. Studies that reported only aseptic meningitis had a pooled prevalence of 3.2% (95% CI 1.3-5.8). The pooled prevalence was 2.8% (95% CI 1.5-4.5) in studies that reported only bacterial meningitis. Similar prevalence rates of meningitis were observed in the subgroups of tumor resection, microvascular decompression, and aneurysm clipping. Meningitis is a rare but not exceptional complication following EIS, with an estimated prevalence of 1.6%.

The genus Nocardia consists of a group of gram-positive environmental bacteria. They typically cause lung and brain infections in immunocompromised patients, even though one out of three infected patients have a normally functioning immune system. Being a ubiquitous microorganism, in some cases Nocardia has been associated with nosocomial acquired infections and surgical procedures. A review of the literature in this field follows the case report. A 47-year-old woman underwent an endoscopic third ventriculostomy and a left retro-sigmoid craniotomy for a schwannoma removal. Meningeal symptoms began a week later, in association with C reactive protein rise and leukocytosis. Cerebrospinal fluid (CSF) examination was clear with hypoglycorrhachia, hyperprotidorrachia and polymorphonuclear cells. Cultural exam was negative. At the brain magnetic resonance imaging (MRI) purulent material was described in the occipital ventricular horns. Empirical broad spectrum antibiotic therapy was given for 31 days until the brain MRI showed a resolution of the infection. Ten days later, the patient was admitted to the hospital because of new meningeal symptoms. Cerebrospinal fluid culture and Polymerase-chain reaction (PCR) Multiplex for the most important meningitis viruses and bacteria tested negative. A broad-spectrum antibiotic therapy was started with no benefit; thus, a broad-spectrum antifungal therapy was added with little success on clinical status. Meanwhile, a 16s and 18s rRNA PCR was executed on a previous Cerebrospinal fluid with negative results, excluding bacterial and fungal infections. For this reason, all the therapies were stopped. After a few days, high fever and meningeal signs reappeared. The brain MRI showed a meningoventriculitis. An Ommaya catheter with reservoir was inserted and the drawn CSF resulted in the growth of Nocardia farcinica. Antibiogram-based antibiotic therapy was started with intravenous imipenem and trimethoprim-sulfamethoxazole, showing clinical benefit. The patient was sent home with oral linezolid and amoxicillin/clavulanate for a total of 12 months of therapy. Nocardia rarely causes post-neurosurgical complication in a nosocomial setting. This case shows the difficulty in detecting Nocardia and the importance of the correct microbiological sample and antibiogram-based antibiotic therapy to achieve successful treatment.

UNASSIGNED: Abiotrophia defectiva is an uncommon and potentially severe cause of bacterial meningitis that can be seen in the setting of neurosurgical procedures. We describe here a case of A. defectiva meningitis in a patient with VP shunt revision.
UNASSIGNED: The patient is a 59-year-old female with VP shunt placed several years prior in the setting of normal pressure hydrocephalus. She underwent successful shunt repair following worsening gait abnormalities. On post-operative day 8 she was brought to the emergency room with fevers, photophobia and altered mentation. CSF cultures returned positive for A. defectiva and she was treated with intravenous vancomycin. Due to the presence of retained hardware she was discharged on chronic suppressive therapy with oral amoxicillin.
UNASSIGNED: This case illustrates A. defectiva as a cause of bacterial meningitis following neurosurgical intervention. It is important to consider this fastidious organism and tailor antimicrobial therapy appropriately to prevent significant morbidity and mortality. As was the case with our patient, suppressive therapy may be warranted in setting of retained hardware.