Meningitis Infections Research Articles

Streamlining marker-less allelic replacement in Streptococcus pneumoniae through a single transformation step strategy: easyJanus.

We introduce a new strategy aimed at streamlining the process for marker-less allelic replacement in Streptococcus pneumoniae, a Gram-positive bacterium and leading cause of pneumonia, meningitis, and ear infections. Our approach involves a modified genetic arrangement of the Janus cassette to facilitate self-excision during the segregation step. Since this new method reduces the amount of exogenous DNA required, it is highly amendable to the use of synthetic DNA for construction of the mutagenic construct. Our streamlined strategy, called easyJanus, offers significant time and cost savings while concurrently enhancing the efficiency of obtaining marker-less allelic replacement in S. pneumoniae.

Development and evaluation of a real-time multienzyme isothermal rapid amplification assay for rapid detection of Streptococcus pneumoniae

Streptococcus pneumoniae is a significant pathogen causing infectious diseases, including pneumonia, otitis media, septicemia, and meningitis. The introduction of multivalent vaccines has coincided with a remarkable decrease in the number of pneumococcal-related deaths. Despite this, pneumococcal infection remains a significant cause of death among children under 5 years old and adults aged 65 or older at a global level. Therefore, early detection of S. pneumoniae infection is crucial for prognosis of pneumococcal infection patients. In this study, we evaluated the utility of a real-time multienzyme isothermal rapid amplification (MIRA) assay for detecting S. pneumoniae and other non-S. pneumoniae bacterial species. A primer–probe set targeting the S. pneumoniae lytA gene was designed, followed by optimization of parameters for the MIRA assay. At the same time, we validated the real-time MIRA assay for detecting S. pneumoniae using 79 clinical isolates identified by VITEK MS. The results showed a detection sensitivity and specificity of 100%. These results demonstrate that the designed real-time MIRA assay is a promising, rapid, simple, and reliable method for detecting S. pneumoniae infection in resource-limited areas. It has great potential for application in detecting not only S. pneumoniae but also other non-S. pneumoniae bacterial species.

Infective Endocarditis by Campylobacter Species-A Narrative Review.

Infective endocarditis (IE) is a disease that may cause significant morbidity and mortality. IE is classically caused by Gram-positive microorganisms; however, Gram-negative bacteria may seldom also be the cause. Campylobacter species cause zoonosis and may also infect humans, mainly causing gastrointestinal infection by C. jejuni or invasive disease by C. fetus, such as bacteremia, sepsis, meningitis, or vascular infection. Campylobacter species IE has rarely been described, and most reports are cases and/or case series. Thus, the characteristics of this disease, including its epidemiology, clinical presentation, treatment, and outcome, remain largely unknown. This study aimed to review all published Campylobacter IE cases and describe their characteristics. A thorough search of PubMed, the Cochrane Library, and Scopus for published studies providing information on epidemiology, clinical findings, treatment, and outcome of Campylobacter IE cases was performed for the present narrative review. A total of 22 studies containing data from 26 patients were located and included. Among all patients, 73.1% were male; the median age was 65 years. Among all patients, 36.4% had a history of a prosthetic valve. The most commonly affected valve was the aortic, followed by the mitral. Fever, heart failure, and sepsis were the most frequent clinical findings. The most commonly isolated pathogen was C. fetus, with only one patient having C. jejuni IE. Antimicrobial resistance was low for all antimicrobials, with tetracycline having the highest resistance. Aminoglycosides and beta-lactams were the most commonly used antimicrobials. Surgery was performed in 48% of patients. The mortality rate was 26.9%. Patients who died were more likely to have sepsis, shock, and heart failure and were less likely to have been treated with aminopenicillins; however, no factor was identified in a multivariate logistic regression model as an independent factor for overall mortality.

Rheumatoid meningitis in the absence of rheumatoid arthritis: 2 cases

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis (RA) that has been increasingly recognized by neurologists. However, the diversity of its clinical manifestations makes its diagnosis difficult. RM does not have a unified diagnostic standard, and its link with RA needs to be studied further. Here we report two cases of RM without a history of RA. The first patient, an 80-year-old woman, presented with sudden unilateral limb weakness, with brain MR showing abnormal signals in the leptomeningeal of the right frontal parietal. Subarachnoid hemorrhage was excluded after imaging examination, and infectious meningitis was ruled out after cerebrospinal fluid (CSF) examination. The patient was diagnosed as having RM, she had increased levels of CCP and AKA, the markers of RA, but no history of the disease or other clinical manifestations of it. Another case, a 65-year-old man, was hospitalized with Bell’s palsy. We found that he had intracranial imaging changes highly consistent with those characteristic of RM during his routine examination. Except for the left peripheral facial palsy, the patient had no other neurological signs or symptoms and no RA history. After a careful physical examination, we found no joint or other manifestations or serological abnormalities consistent with RA (RF, CCP, AKA, etc.). However, after excluding infection meningitis and considering the patient’s unique imaging results, we diagnosed him as having RM. We report these two cases as references for clinical diagnosis and treatment of RM, providing a discussion of our rationale.

Epidemiology of cryptococcal meningitis and fluconazole heteroresistance in Cryptococcus neoformans isolates from a teaching hospital in southwestern China.

Cryptococcal meningitis (CM), a common and serious opportunistic infection mostly caused by Cryptococcus neoformans, is primarily treated with fluconazole. Nevertheless, Cryptococcus neoformans strains that undergo repeated exposure to azoles can gradually acquire heteroresistance to fluconazole. The management of this specific CM infection poses a substantial challenge. Determining a globally accepted definition for fluconazole heteroresistance and developing effective and prompt methods for identifying heteroresistance is of utmost importance. We collected data on the clinical and epidemiological characteristics of patients diagnosed with CM. All the available Cryptococcus neoformans strains isolated from these patients were collected and subjected to antifungal susceptibility testing and evaluation of fluconazole heteroresistance. AIDS was present in 40.5% of the patients, whereas 24.1% did not have any underlying diseases. Patients with chronic diseases or impaired immune systems are susceptible to infection by Cryptococcus neoformans, a fungus that frequently (39.6%, 19/48) shows heteroresistance to fluconazole, as confirmed by population analysis profile (PAP).IMPORTANCEFluconazole heteroresistance poses a significant threat to the efficacy of fluconazole in treating cryptococcal meningitis (CM). Unfortunately, the standard broth microdilution method often misses the subtle percentages of subpopulations exhibiting heteroresistance. While the population analysis profile (PAP) method is esteemed as the gold standard, its time-consuming and labor-intensive nature makes it impractical for routine clinical use. In contrast, the Kirby-Bauer (KB) disk diffusion method offers a simple and effective screening solution. Our study highlights the value of KB over PAP and minimum inhibitory concentration (MIC) by demonstrating that when adjusting the inoculum concentration to 1.0 McFarland and subjecting samples to a 72-hour incubation period at 35°C, the KB method closely mirrors the outcomes of the PAP approach in detecting fluconazole heteroresistance. This optimization of the KB method not only enhances assay efficiency but also provides a blueprint for developing a timely and effective strategy for identifying heteroresistance.

The postulated role of brain pulsations and arachnoid membranes in cerebrospinal fluid circulation, ventriculomegaly and related CSF disorders

Hydrocephalus can be obstructive or communicating. In cases of communicating hydrocephalus, patients will typically have enlarged brain ventricles. It has long been thought that the reason for this is obstruction to the outflow of cerebrospinal fluid from the subarachnoid space, which also results in raised intracranial pressure (ICP). However, there are several clinical and anatomic observations that are not well explained by this idea. These are for example, the conditions of Normal pressure hydrocephalus (NPH) which has normal ICP but ventriculomegaly, and idiopathic intracranial hypertension (IIH) which has raised ICP but normal sized ventricles. This hypothesis states that the mechanism for raised ICP and large ventricles seen in communicating hydrocephalus (ventriculomegaly) are different and seeks to explain the cause of ventriculomegaly using illustrative examples. It also suggests explanations for why ventriculomegaly occurs in NPH, infectious or carcinomatous meningitis, but is absent in IIH, or dural venous sinus thrombosis. Based on operative neurosurgical observations it states that the arachnoid membranes in the basal cisterns serve as part of a directional CSF flow mechanism consisting of fluid diodes, or “Tesla valves” of arachnoid membrane, containing CSF that is propelled by brain pulsations from the point of exit from the 4th ventricle to its points of absorption. This hypothesis suggests explanations for the physiologic appearance of a near uniform subarachnoid space, as well as the occurrence of the syndrome of the trephined and external hydrocephalus seen following a decompressive craniectomy. Also suggested are avenues of further research testing with MRI phase contrast CSF flow studies, classification of anatomic and peri-operative observations and rationale for creation of novel experiments to test the hypothesis, and aid diagnosis and treatment of a number of cranial CSF disorders.

Integrating DNA/RNA microbe detection and host response for accurate diagnosis, treatment and prognosis of childhood infectious meningitis and encephalitis

BackgroundInfectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy.MethodsHere we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL).ResultsOur pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM.ConclusionsThis study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.

Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease: a randomised strategy trial.

Mortality associated with HIV-associated cryptococcal meningitis remains high even in the context of clinical trials (24-45% at 10 weeks); mortality at 12-months is up to 78% in resource limited settings. Co-prevalent tuberculosis (TB) is common and preventable, and likely contributes to poor patient outcomes. Innovative strategies to increase TB preventative therapy (TPT) provision and uptake within this high-risk group are needed. The IMPROVE trial (Integrated management of cryptococcal meningitis and concurrent opportunistic infections to improve outcomes in advanced HIV disease) is a nested open label, two arm, randomised controlled strategy trial to evaluate the safety (adverse events) and feasibility (adherence and tolerability) of two ultra-short course TPT strategies, in the context of recent diagnosis and treatment for cryptococcal meningitis. We will enrol 205 adults with HIV-associated cryptococcal meningitis from three hospitals in Uganda. Participants will be randomised to either inpatient initiation (early) or outpatient initiation (standard, week 6) of 1HP (one month of isoniazid and rifapentine). Participant follow-up is to include TB screening, 1HP pill counts and tolerability reviews on alternate weeks until week-18. The trial primary endpoint is TB-disease free 1HP treatment completion at 18-weeks, secondary endpoints: 1HP treatment completion, 1HP discontinuation, grade ≥3 adverse events and serious adverse events, drug-induced liver injury, incident active TB, 18-week survival; rifapentine, fluconazole and dolutegravir concentrations will be measured with intensive sampling in a pharmacokinetic sub-study of 15 eligible participants. The IMPROVE trial will provide preliminary safety and feasibility data to inform 1HP TPT strategies for adults with advanced HIV disease and cryptococcal meningitis. The potential impact of demonstrating that inpatient initiation of 1HP TPT is safe and feasible amongst this high-risk subpopulation with advanced HIV disease, would be to expand the range of clinical encounters in which clinicians can feasibly provide 1HP, and therefore increase the reach of TPT as a preventative intervention. ISRCTN18437550 (05/11/2021).

Potential diagnostic and distinguishing roles of microneedle‐based biosensors in bacterial and aseptic meningitis

AbstractMeningitis, which is defined by inflammation of the meninges, is a major cause of death and morbidity worldwide. Traditional diagnostic approaches, such as imaging procedures and the study of cerebrospinal fluid, are intrusive, time consuming and sometimes non‐specific. The suggested approach entails creating a biosensor based on microneedles that can detect in real time without the requirement for labels. The biosensor uses highly sensitive detection techniques to detect changes in ionic current and modulation of impedance in response to biomolecules that are of interest, such as proteins and nucleic acids, which are linked to meningitis infections. Initial studies have shown that the microneedle‐based biosensor for meningitis diagnosis is both feasible and effective. When it comes to identifying bacterial and aseptic meningitis biomarkers from blood and cerebrospinal fluid (CSF) samples, the biosensor showed excellent sensitivity and specificity. This novel technique has the potential to enhance patient outcomes by facilitating prompt intervention and tailored therapy by offering a quick, safe and accurate way to distinguish between bacterial and aseptic meningitis. To maximise the biosensor's performance and confirm its therapeutic usefulness in various contexts, more investigations and advancements are necessary.

Meningites infecciosas: aspectos epidemiológicos da doença no estado de Mato Grosso do Sul

Introduction: Meningitis is a global medical emergency that requires immediate diagnosis and treatment due to its high mortality and morbidity rates. Objective: To depict the epidemiology of infectious meningitis in the state of Mato Grosso do Sul from 2010 to 2022. Method: For this research, a cross-sectional, descriptive, retrospective, and quantitative study was conducted using the state of Mato Grosso do Sul as the unit of analysis. The sample was delimited to the period from 2010 to 2022, and the information was coded and collected from the Notifiable Diseases Information System (SINAN), considering the year and month of notification, notification municipality, age, sex, race/color, education, etiology, serogroup, confirmation criteria, and case evolution. Results: During the analyzed period, 2,826 cases of meningitis were reported, with 71.3% confirmed. The most affected individuals were males of mixed race/color and children aged 0 to 9 years. The prevalence in the state was 7.7 cases per 10,000 inhabitants. The majority of meningitis cases (39.7%) were classified as unspecified meningitis and 23.1% as aseptic meningitis. The lethality rate during the study period was 11.3%, with a concentration of deaths at the extremes of age. Conclusions: Although meningitis is a well-known disease, its lethality rate remains high. It is suggested to intensify control and prevention actions in municipalities, combined with demonstrating the importance of notifying the disease to epidemiological surveillance, which will help in organizing more targeted and specific action strategies to combat cases.

Investigating the Diagnostic Significance of Neutrophil Percentage to Albumin Ratio (NPAR) in Patients with Infectious Meningitis

Background: Meningitis, characterized by inflammation of the meninges, typically presents with fever, headache, and neck rigidity. Despite the availability of numerous diagnostic techniques, determining the etiology of infectious meningitis remains challenging, often leading to diagnostic delays and increased mortality. The neutrophil percentage-to-albumin ratio (NPAR) is a novel biomarker for systemic infection and inflammation. Objective: To assess the neutrophil-to-albumin ratio in cases of infectious meningitis. Methods: Following REC approval (05/01/REC-206-2020), this cross-sectional study included 78 patients with clinical findings consistent with meningitis. Data on age, gender, fever, headache, neck rigidity, and Glasgow Coma Scale (GCS) were collected. NPAR was calculated by dividing the neutrophil percentage by serum albumin levels. Statistical analysis was performed using SPSS 22.0 for T-test (two-tailed) and Pearson Correlation. Results were presented as mean±SD (95% CI) with a significance level of p<0.05. Results: The mean age of patients was 27 years. The mean GCS score was 11±1.59, serum albumin levels were 3.44±0.5 mg/dl, neutrophil percentage was 75.6±7.2%, and the neutrophil-to-albumin ratio (NPAR) was 0.22±0.03. Common symptoms such as fever, neck rigidity, and headache were present in all cases, while seizures were observed in 36 cases. Conclusion: The study indicated a significant correlation between elevated NPAR levels and cases of infectious meningitis, suggesting NPAR as a potential diagnostic marker.

Clinical research progress on intrathecal glucocorticoids in the treatment of infections: A review.

In some infectious diseases, pathogenic microorganisms can directly or indirectly cause significant inflammatory reactions in the central nervous system, leading to severe neurological dysfunction, such as suppurative meningitis, tuberculous meningitis, and febrile infections. related epilepsy syndrome, etc. In these diseases, adjuvant administration of glucocorticoids is necessary to inhibit the release of proinflammatory cytokines, and intrathecal administration can deliver the drug more directly to the target. In this article, the authors studied intrathecal glucocorticoids for the treatment of infectious inflammatory reactions in terms of pharmacological effects and mechanisms, pharmacokinetics, clinical application, and safety. The authors concluded that the article could help provide new treatment strategies for infectious diseases.

Evaluation of antibacterial activity of selected plant extracts against Serratia marcescens

Abstract BACKGROUND: Serratia marcescens is a well-known Gram-negative, rod-shaped bacterium commonly found in soil, animal skin, hospital environment, and plant-based raw materials. It is an opportunistic pathogen that causes serious infections, including pneumonia, bloodstream infection, wound infection, meningitis, and respiratory and urinary tract infections. Due to multiple resistant strains of S. marcescens being identified, new and effective plant-based antimicrobial compounds/drugs against S. marcescens must be searched. The present study is focused to explore the Stem of Neem (Azadirachta indica), Seed of Nirgundi (Vitex negundo) and Clove buds (Syzygium aromaticum) for their antibacterial activity against the isolated S. marcescens. METHODS: The S. marcescens was isolated from the garden soil of CARI Jhansi and identified based on various morphological and biochemical tests. We also checked the antibiotic profile of isolated S. marcescens. The ethanolic and methanolic extracts of the selected plant parts were prepared and explored for their antibacterial activity against S. marcescens using the disc diffusion method. RESULTS: The antibiotic profile of S. marcescens showed resistance to multiple broad-spectrum antibiotics, including erythromycin, rifampicin, chloramphenicol, and narrow-spectrum antibiotic vancomycin. At the same time, it was sensitive to kanamycin, streptomycin, ciprofloxacin, and ofloxacin. We observed that both methanolic and ethanolic extracts of clove buds were effective, while only the ethanolic extract of Nirgundi seed and Neem stem were found to be effective against S. marcescens. CONCLUSION: From this study, we conclude that both methanolic and ethanolic extracts of Clove buds, while only the ethanolic extract of Nirgundi seed and Neem stem, were found effective and showed significant inhibition of growth of S. marcescens.

An opportunistic pathogen under stress: how Group B Streptococcus responds to cytotoxic reactive species and conditions of metal ion imbalance to survive.

Group B Streptococcus (GBS; also known as Streptococcus agalactiae) is an opportunistic bacterial pathogen that causes sepsis, meningitis, pneumonia, and skin and soft tissue infections in neonates and healthy or immunocompromised adults. GBS is well-adapted to survive in humans due to a plethora of virulence mechanisms that afford responses to support bacterial survival in dynamic host environments. These mechanisms and responses include counteraction of cell death from exposure to excess metal ions that can cause mismetallation and cytotoxicity, and strategies to combat molecules such as reactive oxygen and nitrogen species that are generated as part of innate host defence. Cytotoxicity from reactive molecules can stem from damage to proteins, DNA, and membrane lipids, potentially leading to bacterial cell death inside phagocytic cells or within extracellular spaces within the host. Deciphering the ways in which GBS responds to the stress of cytotoxic reactive molecules within the host will benefit the development of novel therapeutic and preventative strategies to manage the burden of GBS disease. This review summarizes knowledge of GBS carriage in humans and the mechanisms used by the bacteria to circumvent killing by these important elements of host immune defence: oxidative stress, nitrosative stress, and stress from metal ion intoxication/mismetallation.

The application value of metagenomic next-generation sequencing technology in the diagnosis and treatment of neonatal infectious meningitis – a single center retrospective case-control study

ABSTRACT Objective This retrospective study was conducted to investigate the application value of metagenomics next generation sequencing (mNGS) technology in the diagnosis and treatment of neonatal infectious meningitis. Methods From 1 January 2020 to 31 December 2022, 73 newborns suspected of infectious meningitis were hospitalized. After screening by inclusion and exclusion criteria, 69 newborns were subsequently included in the study, containing 27 cases with positive mNGS result and 42 cases with negative mNGS result. Furthermore, according to the diagnosis of meningitis, mNGS positive group and mNGS negative group were further divided into infectious meningitis with mNGS (+) group (n = 27) and infectious meningitis with mNGS (-) group (n = 26), respectively. Results (1) Compared with cerebrospinal fluid (CSF) culture, mNGS has better diagnostic value [positive predictive value (PPV) = 100.00% (27/27), negative predictive value (NPV) = 38.10% (16/42), agreement rate = 62.32% (43/69), area under the curve (AUC) = 0.750, 95% confidence interval (CI): 0.636–0.864]. (2) There were significant differences in the onset age, age at first CSF test, CSF leukocyte count, CSF glucose, positive rate of CSF culture, blood leukocyte count, procalcitonin (PCT), C-reaction protein (CRP), age at first mNGS test and adjusting anti-infective medication in the comparison between infectious meningitis with mNGS (+) group and infectious meningitis with mNGS (-) group (p < 0.05). (3) mNGS could help improve the cure rate [crude odds ratio (OR) = 3.393, 95%CI: 1.072–10.737; adjusted OR = 15.580, 95%CI: 2.114–114.798]. Conclusion Compared with classic meningitis detection methods, mNGS has better PPV, NPV, agreement rate, and AUC. mNGS could help improve the cure rate.

An umbrella review of the diagnostic value of next-generation sequencing in infectious diseases.

An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs). This umbrella analysis aimed to assess the potential risk of bias in existing SRs and to summarize the published diagnostic values of NGS in different IDs. We searched PubMed, Embase, and the Cochrane Library until September 2023 for SRs assessing the diagnostic validity of NGS for IDs. Two investigators independently determined review eligibility, extracted data, and evaluated reporting quality, risk of bias, methodological quality, and evidence certainty in the included SRs. Eleven SRs were analyzed. Most SRs exhibited a moderate level of reporting quality, while a serious risk of bias was observed in all SRs. The diagnostic performance of NGS in detecting pneumocystis pneumonia and periprosthetic/prosthetic joint infection was notably robust, showing excellent sensitivity (pneumocystis pneumonia: 0.96, 95% CI 0.90-0.99, very low certainty; periprosthetic/prosthetic joint infection: 0.93, 95% CI 0.83-0.97, very low certainty) and specificity (pneumocystis pneumonia: 0.96, 95% CI 0.92-0.98, very low certainty; periprosthetic/prosthetic joint infection: 0.95, 95% CI 0.92-0.97, very low certainty). NGS exhibited high specificity for central nervous system infection, bacterial meningoencephalitis, and tuberculous meningitis. The sensitivity to these infectious diseases was moderate. NGS demonstrated moderate sensitivity and specificity for multiple infections and pulmonary infections. This umbrella analysis indicates that NGS is a promising technique for diagnosing pneumocystis pneumonia and periprosthetic/prosthetic joint infection with excellent sensitivity and specificity. More high-quality original research and SRs are needed to verify the current findings.

Rhabdomyolysis and Neuroleptic Malignant Syndrome in a Postrenal Transplant Patient: Is Desidustat a Culprit?

We report a case of a 46-year-old female – a postrenal transplant patient, having developed rhabdomyolysis and neuroleptic malignant syndrome (NMS), after 2.5 months of desidustat initiation – for anemia. Post renal transplant anemia (PTA) is common among renal transplant recipients. Apart from treating it with iron supplements, folic acid, andrecombinant human erythropoietin (EPO), novel agents like hypoxia-inducible factor–prolyl hydroxylase domain (HIF–PHI) are also used, with a very few studies available on its efficacy and safety in PTA patients. Anemia occurring in the first 6 months is called early PTA – occurring most commonly due to iron deficiency, while anemia occurring after 6 months is called late PTA – associated with impaired graft function. The optimal target of hemoglobin in transplant recipients is 12.5–13 gm/dl, which is higher than targets in chronic kidney disease patients. NMS is a life-threatening emergency – mainly seen in patients on antipsychotic medications. It needs to be differentiated from other closely related conditions such as central nervous system infections (meningitis and encephalitis), tetanus, heatstroke, serotonin syndrome, and thyrotoxicosis. Desidustat is an oral HIF–PHI that stimulates erythropoiesis by preventing EPO degradation. Its adverse effects include high blood pressure, myocardial infarction, heart failure, high potassium, and dizziness; however, there is only one case report of rhabdomyolysis associated with desidustat, and none of NMS. It is, therefore, important to be aware of this potential severe side effect of the drug that was not known earlier so that practicing physicians can be vigilant of the same.

Development of mucoadhesive microspheres for intranasal delivery of fluconazole as an alternative treatment of cryptococcal meningitis infection in patients with acquired immunodeficiency

Cryptococcal meningitis is a deadly disease with few treatment options. Its incidence is still high and closely linked to the HIV/AIDS epidemic. This study aimed to develop a mucoadhesive microsphere delivery system for fluconazole for the intranasal route. Microspheres of mucoadhesive fluconazole formulation variables such as different amounts of drug concentration and polymer concentration were prepared by a simple emulsion-crosslinking method.The prepared microspheres' surface was characterised by SEM (Scanning electron microscopy) and evaluated for particle size, entrapment efficiency, production yield, infrared spectroscopic study, in-vitro muco-adhesion, and in-vitro drug release. The results showed that formula 1 is the optimal mucoadhesive microsphere preparation, with a particle size of 56.375m, a spherical surface shape, an entrapment efficiency of 99.96%, and a greater mucoadhesive capability during 6-hour evaluation. Furthermore, wash-off examination revealed that the mucoadhesive ability of this delivery system has a long duration and may release the active material at the right time. The result of the researches suggesting that the formulation of mucoadhesive microspheres of fluconazole could be used to treat cryptococcal meningitis infection in HIV/AIDS patients.

TB LAMP assay, a beneficial tool for the diagnosis of Tubercular meningitis in resource-limited settings.

Tubercular meningitis (TBM) is a serious public health problem in developing countries as it leads to significant mortality and residual neurological sequelae. The estimated mortality due to TBM in India is 1.5 per 100,000 population. In resource-limited settings, only the Ziehl-Neelsen (ZN) stain, which has very little sensitivity, is available. The World Health Organization recommended the Loop Mediated Isothermal Amplification (TB LAMP) assay for pulmonary tuberculosis only. We evaluated this test for tubercular meningitis as well. In a cross-sectional study of 2-year duration, we have taken 239 cerebrospinal fluid samples from suspected cases of tubercular meningitis patients. ZN staining along with Mycobacteria Growth Indicator Tube (MGIT) TB culture, Xpert MTB/RIF Ultra assay, and commercial TB LAMP assay were performed for each sample. Out of 239 samples, 40 samples (16.73%) were found TB LAMP assay positive, 48 samples (20.08%) were found Xpert ultra-assay positive, 12 samples (5.02%) were MGIT TB culture positive and acid-fast bacillus smear positive in ten samples (4.18 %). Out of 12 MGIT-positive samples, all samples (100%) were TB LAMP and Xpert ultra positive and one sample (8.33%) was ZN smear positive. In 199 negative samples from the TB LAMP assay, eight samples were positive by Xpert, none by MGIT TB culture and AFB smear. Sensitivity and specificity were found as 100% and 87.66%, respectively, for the TB LAMP assay. TB LAMP assay is a rapid, cost-effective, sensitive, and specific test for tubercular meningitis infection in resource-limited settings.

A Retrospective Study on UTI by Myroides Species: An Emerging Drug Resistant Nosocomial Pathogen.

Myroides (M.) species are ubiquitous in the environment and cause a variety of infections like urinary tract infections (UTI), sepsis, meningitis, cholecystitis, pneumonia, and soft tissue infections, especially among immunocompromised populations. These are usually resistant to multiple antibiotics. This study aimed to demonstrate the clinical profile, underlying comorbidities, and antimicrobial susceptibility of Myroides isolates obtained from nosocomial UTI cases. A sudden rise in the isolation of Myroides spp. from the repeated urine samples of admitted patients alerted us to conduct this retrospective observational study. Urine cultures that grew M. species were included in this study. Antibiotic susceptibility was performed and the patient's clinical data was analyzed. A total of 14 Myroides spp. isolates were obtained from urine culture. The maximum number of cases (71.4%) were from the Nephrology ward and ICUs. The average (mean) age of patients was 46 years (range 2-80 years). All patients were catheterized. All isolates were multidrug resistant. Minocycline and doxycycline were the only drugs found effective in this study. Myroides species are emerging rare pathogens that can cause UTI in immunocompromised and catheterized patients. Minocycline may be used for treating such infections. Sahu C, Chaudhary R, Bhartiya C, Patel SS, Bhatnagar N. A Retrospective Study on UTI by Myroides Species: An Emerging Drug Resistant Nosocomial Pathogen. Indian J Crit Care Med 2024;28(4):399-403.