Neurobrucellosis.

PURPOSE OF REVIEW: Brucellosis is one of the most common zoonosis worldwide, affecting 500 000 people, annually. Neurobrucellosis incidence is approximately 4%, and it is almost always heterogeneous. As there are no typical clinical features, its diagnosis is frequently misdiagnosing by other infections. RECENT FINDINGS: Neurobrucellosis picture includes meningitis, meningoencephalitis, encephalitis, cranial neuropathies, intracranial hypertension, sinus thrombosis, hemorrhages radiculitis, peripheral neuropathy, myelitis, and psychiatric manifestations. The diagnosis should be based on symptoms and signs suggestive of neurobrucellosis, not explained by other neurological disease, cerebrospinal fluid analysis, a positive Brucella serology or culture, and a response to specific antibiotics, with a significant improvement of cerebrospinal fluid parameters. SUMMARY: Neurobrucellosis can be insidious, and despite its global distribution, it is still unrecognized and frequently goes unreported. The understanding of the current epidemiology is necessary for eradication of the disease in humans, as well as the disease control in animals and prevention based on occupational hygiene and food hygiene.

Neurobrucellosis Presenting with Features of Demyelinating Disorder in a Pediatric Patient.

Brucellosis is an endemic disease in Saudi Arabia, which can present with variable clinical manifestations. It is a zoonotic disease transmitted from animals to humans. Brucellosis is a multisystemic disease that can present with any system involvement; and neurobrucellosis is a serious complication, sometimes leading to permanent neurological deficit, if treatment is not started promptly. Herein, we present a 6-year boy with neurobrucellosis, who developed demyelination of cerebral white matter and presented with fever and seizures. Key Words: Neurobrucellosis, Demyelination, White matter.

Pharmacokinetics of colistin in cerebrospinal fluid after intraventricular administration alone in intracranial infections.

The aim of this study was to investigate the pharmacokinetics of colistin in cerebrospinal fluid (CSF) after intraventricular (IVT) administration of colistin methanesulfonate (CMS) for central nervous system (CNS) infections caused by multidrug-resistant Gram-negative bacteria. Ten patients with CNS infection were treated with CMS (active substance colistin equivalent to 100 000 units, every 24 h) by IVT administration. After 3 days of treatment, the concentration of colistin in the CSF was determined by selective ultra-performance liquid chromatography (UPLC) at 2, 4, 6, 8, 12 and 24 h after CMS administration. A pharmacokinetic analysis was performed using Phoenix WinNonlin. Following IVT administration of CMS, the estimated colistin apparent CSF half-life (t1/2) was 10.46 ± 6.98 h, the average peak colistin concentration (Cmax) was 16.95 ± 7.39 µg/mL and the average time to peak concentration (Tmax) was 4.6 ± 0.97 h. The measured trough concentration (Cmin; colistin concentration in CSF at 24 h after administration of CMS) was 1.12-8.33 µg/mL and the average Cmin was 2.91 ± 2.11 µg/mL. CSF concentrations of colistin were above the minimum inhibitory concentration (MIC) of 0.5 µg/mL at 24 h after IVT administration in all patients. Microbiological cure was observed in all patients. In conclusion, this is the first study of colistin pharmacokinetics in CSF after IVT administration alone in patients with CNS infection. It provides essential data for designing relatively safe and effective CMS dosing regimens.

Case Report: Isolated Central Nervous System Melioidosis from a Non-Endemic Area.

Central nervous system (CNS) melioidosis is a rare neurological infectious disease which carries a high mortality. We describe a previously healthy middle-aged female, who presented to us with left-sided hemiparesis and was on antitubercular therapy from a previous presumed diagnosis of CNS tuberculoma. Non-characteristic imaging picture, multiple negative body fluid cultures, and positive Cerebrospinal fluid galactomannan led to a further delay in diagnosis. Gram stain of the tissue obtained from brain biopsy revealed Gram-negative rods in "safety pin" appearance. By picking up the colonies that appeared on blood agar and MacConkey agar, the identification of the clinical isolates was performed using VITEK® matrix (BioMérieux, Marcy-L'Etoile, France)-assisted laser desorption ionization time-of-flight mass spectrometry (VITEK MALDI TOF MS database version 3.2) which revealed Burkholderia pseudomallei. After the institution of appropriate treatment, she survived but with significant morbidity. A high index of suspicion should be kept for such previously healthy individuals belonging to non-endemic areas, where presentation is suspicious of an infective etiology, but not improving despite appropriate therapy. This may help in early recognition and institution of recommended treatment so that mortality can be avoided.

Choosing the therapy for neurological infection with rapidly growing mycobacteria.

The management of neurological infections due to non-tubercular mycobacteria is extremely challenging because of scarce literature, issues with penetration, lack of easily available susceptibility platforms and adverse effects associated with long term therapy. We report a case of a young girl with neurological infection due to rapidly growing mycobacteria to discuss the factors that should be considered while choosing the therapy for such rare and persistent infections.

Intrathecal Antibacterial and Antifungal Therapies.

Intrathecal administration of anti-infectives is indicated in central nervous system infections by multiresistant pathogens when drugs that can reach adequate cerebrospinal fluid (CSF) concentrations by systemic therapy are not available. Antibiotics that readily pass the blood-brain and blood-CSF barriers and/or that have low toxicity allowing an increase in the daily dosage should not be used for intrathecal therapy. Intrathecal therapy is accompanied by systemic treatment. Antibacterials indispensable for intrathecal therapy include aminoglycosides, colistin, daptomycin, tigecycline, and vancomycin. Limited experience suggests the utility of the antifungals amphotericin B and caspofungin. Intraventricular administration ensures distribution throughout the CSF compartment, whereas intralumbar dosing often fails to attain adequate antibiotic concentrations in the ventricles. The individual dose is determined by the estimated size of the CSF space and by the estimated clearance from CSF. For moderately lipophilic anti-infectives with a molecular weight above approximately 1,000 g/mol, as well as for hydrophilic drugs with a molecular weight above approximately 400 g/mol, one daily dose is normally adequate. The ventricular drain should be clamped for 15 to 120 min to facilitate the distribution of the anti-infective in the CSF space. Therapeutic drug monitoring of the trough levels is necessary only in cases of therapeutic failure.

Evaluation of a micro/nanofluidic chip platform for diagnosis of central nervous system infections: a multi-center prospective study.

Central nervous system infection (CNSI) is a significant type of infection that plagues the fields of neurology and neurosurgical science. Prompt and accurate diagnosis of CNSI is a major challenge in clinical and laboratory assessments; however, developing new methods may help improve diagnostic protocols. This study evaluated the second-generation micro/nanofluidic chip platform (MNCP-II), which overcomes the difficulties of diagnosing bacterial and fungal infections in the CNS. The MNCP-II is simple to operate, and can identify 44 genus or species targets and 35 genetic resistance determinants in 50 minutes. To evaluate the diagnostic accuracy of the second-generation micro/nanofluidic chip platform for CNSI in a multicenter study. The limit of detection (LOD) using the second-generation micro/nanofluidic chip platform was first determined using six different microbial standards. A total of 180 bacterium/fungi-containing cerebrospinal fluid (CSF) cultures and 26 CSF samples collected from CNSI patients with negative microbial cultures were evaluated using the MNCP-II platform for the identification of microorganism and determinants of genetic resistance. The results were compared to those obtained with conventional identification and antimicrobial susceptibility testing methods. The LOD of the various microbes tested with the MNCP-II was found to be in the range of 250-500 copies of DNA. For the 180 CSF microbe-positive cultures, the concordance rate between the platform and the conventional identification method was 90.00%; eight species attained 100% consistency. In the detection of 9 kinds of antibiotic resistance genes, including carbapenemases, ESBLs, aminoglycoside, vancomycin-related genes, and mecA, concordance rates with the conventional antimicrobial susceptibility testing methods exceeded 80.00%. For carbapenemases and ESBLs-related genes, both the sensitivity and positive predictive values of the platform tests were high (>90.0%) and could fully meet the requirements of clinical diagnosis. MNCP-II is a very effective molecular detection platform that can assist in the diagnosis of CNSI and can significantly improve diagnostic efficiency.

Infectious Myelitis.

Myelitis refers to inflammation of the spinal cord which can result in a spectrum of neurologic impairment. Infectious pathogens are an important etiologic category, and can result in myelitis through direct pathogenic effect or through immune-mediated parainfection; this review focuses on the former category. The spectrum of clinical manifestations is summarized and a diagnostic workup provided to aid clinicians in developing an approach to patients presenting with symptoms suggestive of infectious myelitis. This is followed by an overview of the important viral, bacterial, parasitic, and fungal causes of infectious myelitis. The typical presentations, diagnostic modalities, and treatment approaches are outlined for key pathogens culprit in infectious myelitis to allow clinicians to promptly recognize and diagnose specific infectious etiologies of myelitis.

A case report of community-acquired Pseudomonas aeruginosa pneumonia complicated with MODS in a previously healthy patient and related literature review.

BACKGROUND: Pseudomonas aeruginosa is an unusual pathogen in community-acquired pneumonia, especially in previously healthy adults, but often indicates poor prognosis. CASE PRESENTATION: We report a previously healthy patient who developed severe community-acquired pneumonia (CAP) caused by P. aeruginosa. He deteriorated to septic shock and multiple organ dysfunction syndrome (MODS) quickly, complicated by secondary hematogenous central nervous system (CNS) infection. After 1 month of organ support and antipseudomonal therapy, he had significant symptomatic improvement and was discharged from hospital. During treatment, the pathogen developed resistance to carbapenems quickly and the antibiotic regimen was adjusted accordingly. CONCLUSIONS: According to our case and related literature review, we conclude that more attention should be paid to community-acquired Pseudomonas aeruginosa pneumonia, because of its rapid progression and poor prognosis.

Ventriculitis associated with extraventricular drainage: etiology, diagnosis and treatment focused on neurocritic care units.

Ventriculitis after extraventricular drainage is a very important neurosurgical complication in neurocritical care units. It is necessary to make an early diagnosis, given that the morbidity and mortality secondary to it can be variable, and complicate the evolution of neurocritical patients. Despite this, ventriculostomy continues to be an important pillar in monitoring and treatment. Given the urgency of ventriculitis associated with multiresistant germs, new antimicrobial drugs have emerged as part of the treatment, as intraventricular routes have been proposed within the new investigations. However, the foregoing does not yet have sufficient bases to be able to support it. The present review was carried out with the aim of contributing to an early diagnosis and treatment of ventriculitis associated with extra ventricular drainage in neurocritical patients, and in this way to contribute to improve survival and prevent fatal outcomes in these patients.

La ventriculitis posterior a un drenaje extraventicular constituye una complicación neuroquirúrgica muy importante en las unidades de cuidados neurocríticos. Se hace necesario realizar un diagnóstico precoz, dado que la morbimortalidad secundaria a esta puede ser variable y complicar la evolución de los pacientes neurocríticos. A pesar de esto, la ventriculostomía continúa siendo un pilar importante en el monitoreo y el tratamiento. Ante la urgencia de ventriculitis asociadas a gérmenes multirresistentes han surgido nuevos fármacos antimicrobianos como parte del tratamiento, al igual que se han propuesto vías intraventriculares dentro de las nuevas investigaciones. Sin embargo, lo anterior aún no tiene bases suficientes para poder ­sustentarlo. La presente revisión se realizó con el objetivo de contribuir a un diagnóstico precoz y al tratamiento de la ventriculitis asociada a drenaje extraventricular en pacientes neurocríticos, y de esta forma poder mejorar la sobrevida y prevenir desenlaces fatales en estos pacientes.

Pharmacokinetic considerations in selecting optimal antibiotic therapy for Mycoplasma pneumoniae encephalitis.

Effective antimicrobial therapy depends on several factors including degree of activity against the pathogen, antibiotic resistance, and when relevant, optimal tissue penetration factors. Central nervous system (CNS) infections illustrate these points well. The pharmacokinetic (PK) parameters important in antibiotic blood cerebrospinal fluid barrier (BCB) penetration that is important in meningitis are different and do not predict blood brain barrier (BBB) penetration. Recently, we had a case of Mycoplasma pneumoniae encephalitis (MPE) which prompted a review of the antibiotic PK determinants of BBB penetration which differ markedly from those of BCB penetration important in encephalitis. Using MPE as an illustrative example, this article reviews host and drug factors of therapeutic importance in optimally treating MPE.

Comparation of vancomycin penetration into cerebrospinal fluid in postoperative intracranial infection and community-acquired meningitis patients.

WHAT IS KNOWN AND OBJECTIVE: To compare the penetration of vancomycin into cerebrospinal fluid (CSF) in patients with postoperative intracranial infection and community-acquired meningitis, and to identify related factors influencing the penetration in these two diseases. METHODS: The concentrations of vancomycin in serum and CSF were determined by enzyme amplified immunoassay, and the CSF-to-serum ratios were calculated. The correlation between CSF-to-serum ratios of vancomycin and CSF elements was analyzed. RESULTS AND DISCUSSION: In postoperative intracranial infection patients and community-acquired meningitis patients, the vancomycin concentration in CSF was 1.90 ± 1.29 mg/L and 2.47 ± 1.15 mg/L, while the CSF-to-serum ratio was 0.19 ± 0.12 and 0.26 ± 0.12, respectively. There was a significant correlation between vancomycin serum concentration and bodyweight (P < 0.05). The CSF-to-serum ratio in postoperative intracranial infection patients was correlated to white blood cell count in CSF. However, in community-acquired meningitis patients, no relationship was seen with regards to CSF white blood cell count, protein or glucose. WHAT IS NEW AND CONCLUSION: Cerebrospinal fluid vancomycin penetration was similar in postoperative intracranial infection and community-acquired meningitis patients. The CSF-to-serum ratio was only correlated to CSF white blood cell count in postoperative intracranial infection patients.

Multi-systemic melioidosis: a clinical, neurological, and radiological case study from Hainan Province, China.

BACKGROUND: Melioidosis is a tropical disease caused by Burkholderia pseudomallei (B. pseudomallei). It can infect any organ system and lead to multiple abscesses. A few studies reported that central nervous system (CNS) is also involved. We present a diabetic patient with multi-systemic melioidosis that affected the CNS, thorax, and spleen. The aim was to study the clinical and radiological features of melioidosis and enhance understanding of the disease. CASE PRESENTATION: A 38-year-old male presented with cough and expectoration mixed with blood for several days. Chest computed tomography (CT) showed a patchy opacity in his left lung, and multiple low-density lesions in his spleen. After 10 days of antibiotics treatment, his clinical symptoms improved and he was discharged from the hospital. But 8 months later, the patient experienced sudden onset of left limb weakness and seizure and was re-admitted to the hospital. Brain CT indicated a low-density lesion over the right frontal lobe, and magnetic resonance imaging (MRI) indicated a well-enhanced lobulated lesion with multiple diffusion restriction areas in the lesion. He had a neuronavigation-guided open surgery but no malignancy was found. B. pseudomallei was cultured from the operative samples. After 4 months of systemic and intraventricular antibiotic administration treatment, he recovered complete consciousness with left hemiparesis. CONCLUSIONS: Multi-systemic melioidosis may present atypical clinical, neurological, and radiological manifestations. It is extremely important to accurately diagnose before treatment is selected. CNS melioidosis in early stage manifests similar symptoms to malignancy or stroke. It might mislead to a false diagnose. Diffusion weighted imaging (DWI) can help in differentiate abscesses from cystic tumours.

Anterior spinal cord syndrome as a rare complication of acute bacterial meningitis in an adult.

Acute bacterial meningitis is not an uncommon central nervous system infection. In severe cases, it can be associated with various neurological or systemic complications. However, acute spinal cord dysfunction rarely occurs. We report a case of bacterial meningitis complicated with spinal cord infarction despite adequate treatment with antibiotics and corticosteroid therapy. He had residual paraplegia and was fully dependent in the activity of daily living.

Central Nervous System Infections.

Infections of the nervous system are potential life-threatening and are caused by pathogens such as bacteria, viruses, and fungi. Prompt recognition and treatment of a central nervous system (CNS) infection is crucial for patient survival, as these infections have a high morbidity and mortality. CNS infections include meningitis, encephalitis, and brain abscesses. This article seeks to detail the etiology, clinical course, diagnostic challenges, and treatment of CNS infections organized by infectious agent.

Pharmacokinetics and pharmacodynamics of linezolid in plasma/cerebrospinal fluid in patients with cerebral hemorrhage after lateral ventricular drainage by Monte Carlo simulation.

OBJECTIVE: We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage. MATERIALS AND METHODS: Ten patients with cerebral hemorrhage after lateral ventricular drainage with stroke-associated pneumonia who were given linezolid were enrolled. Plasma and cerebrospinal fluid (CSF) samples were taken at appropriate intervals after the first administration of linezolid and assayed by high-performance liquid chromatography (HPLC). Then, PK parameters were estimated, and a Monte Carlo simulation was used to calculate the probability of target attainments (PTAs) for linezolid achieving the PK/PD index at different minimal inhibitory concentrations (MICs). RESULTS: The maximum concentration of linezolid in plasma and CSF was reached at 1.00 h and 3.10 h, respectively. The average penetration of linezolid in CSF was 56.81%. If the area under the plasma concentration vs time curve from zero to the final sampling time (AUC0-24 h)/MIC ≥ 59.1 was applied as a parameter, the PTA of linezolid in plasma could provide good coverage (PTA ≥ 90%) only for pathogens with a MIC of ≤2 µg/mL, whereas it could be achieved in CSF with a MIC of ≤1 µg/mL. If %T > MIC ≥ 40% was applied as a parameter, the PTA of linezolid in plasma/CSF could provide good coverage if the MIC was ≤4 µg/mL. CONCLUSIONS: For patients with infection of the central nervous system and who are sensitive to the drug, the usual dosing regimens of linezolid can achieve a good therapeutic effect. However, for critically ill or drug-resistant patients, an increase in dose, the frequency of administration, or longer infusion may be needed to improve the curative effect.

Anti-infective treatment of brain abscess.

INTRODUCTION: Brain abscess is an uncommon and potentially life-threatening infection of the CNS that can be caused by a range of different pathogens including bacteria, fungi, and parasites. A multidisciplinary approach is important and anti-infective treatment remains crucial. Here, we review anti-infective treatment of brain abscess. Areas covered: We used the terms '(Brain abscess[ti] AND (antibiotic* OR treatment)) NOT case report'), to conduct a search in the PubMed. Additional papers were identified by cross-reference checking and by browsing textbooks of infectious diseases and neurology. COMMENTARY: Empiric treatment of bacterial brain abscess consists of cefotaxime and metronidazole with the addition of vancomycin if meticilline-resistant Staphylococcus aureus is suspected. For severely immuno-suppressed patients, for example transplant recipients, voriconazole and trimethoprim-sulfamethoxazole or sulfadiazine should be added. Increased knowledge of the pharmacokinetic profile of anti-infective treatments may help to improve the treatment of brain abscess. Future studies should address efficacy and safety of continuous abscess drainage, mode of anti-infective administration (continuous vs. bolus), and anti-infective treatments in immuno-suppressed patients.

Clinical management of non-faecium non-faecalis vancomycin-resistant enterococci infection. Focus on Enterococcus gallinarum and Enterococcus casseliflavus/flavescens.

Enterococcus gallinarum and Enterococcus casseliflavus/flavescens are enterococci intrinsically resistant to vancomycin belonging to the E. gallinarum group. They are responsible mainly for healthcare-associated infections, in particular bloodstream, urinary tract and surgical wound infections. Diseases due to these bacteria are significantly increasing worldwide, as they are prone to cause infection in patients with concurrent hepatobiliary or oncohematological disorders. Along with their distinguishing vancomycin resistance, due to a chromosomally-encoded VanC operon, their additional intrinsic resistance to many antibiotics other than glycopeptides limits the therapeutic choices. In addition, their intrinsic vancomycin resistance, unlike the vancomycin resistance of Enterococcus faecalis and Enterococcus faecium caused by transmissible plasmids, poses different infection control issues. We focused on the therapeutic and infection control issues of clinical syndromes caused by E. gallinarum and E. casseliflavus/flavescens. We propose therapeutic algorithms on bloodstream infections, endocarditis, central nervous system infections, endophthalmitis and urinary tract infections. The implementation of infection control measures in cases of E. gallinarum and E. casseliflavus/flavescens infection or colonization should be evaluated on a case-by-case basis, especially for epidemic outbreaks or for isolates supposed to harbor a potential transmissible vancomycin-resistance phenotype.