Cerebrospinal Fluid Concentrations of Meropenem and Vancomycin in Ventriculitis Patients Obtained by TDM-Guided Continuous Infusion

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

A New Look at the Genus Solobacterium: A Retrospective Analysis of Twenty-Seven Cases of Infection Involving S. moorei and a Review of Sequence Databases and the Literature

Solobacterium moorei is an anaerobic Gram-positive bacillus present within the oral and the intestinal microbiota that has rarely been described in human infections. Besides its role in halitosis and oral infections, S. moorei is considered to be an opportunistic pathogen causing mainly bloodstream and surgical wound infections. We performed a retrospective study of 27 cases of infections involving S. moorei in two French university hospitals between 2006 and 2021 with the aim of increasing our knowledge of this unrecognized opportunistic pathogen. We also reviewed all the data available in the literature and in genetic and metagenomic sequence databases. In addition to previously reported infections, S. moorei had been isolated from various sites and involved in intra-abdominal, osteoarticular, and cerebral infections more rarely or not previously reported. Although mostly involved in polymicrobial infections, in seven cases, it was the only pathogen recovered. Not included in all mass spectrometry databases, its identification can require 16S rRNA gene sequencing. High susceptibility to antibiotics (apart from rifampicin, moxifloxacin, and clindamycin; 91.3%, 11.8%, and 4.3% of resistant strains, respectively) has been noted. Our global search strategy revealed S. moorei to be human-associated, widely distributed in the human microbiota, including the vaginal and skin microbiota, which may be other sources for infection in addition to the oral and gut microbiota.

Odontogen frontoparial epidural and subdural empyema complicated with frontal intracerebral abscess and Covid

Introduction: Cerebral infections (frontoparietal extradural and subdural empyema) following a dental abscess and multiple sinusitis is a rare and potentially devastating entity even in the era of modern diagnosis and treatment. Case presentation: We present a patient with parietal epidural and subdural empyema and intracerebral frontal abscess, sinusitis and dental abscess, chronic consumer of alcohol and with neglected diabetes mellitus. He was initially diagnosed with encapsulated hematoma and sinusitis. The pus obtained at the intervention was certified by our laboratory as sterile with the consequent difficulty in antibiotic treatment and who induced a longer antibiotic treatment, a second surgical intervention for an encapsulated frontal abscess, a longer hospitalisation and favoured contamination with Covid 19. Despite these, the patient had a finally good evolution. Conclusions: A frontoparietal extradural and subdural empyema and an intracerebral frontal abscess produced by a dental abscess and sinusitis is a rare and potentially lethal complication. The multidisciplinary approach between radiologist, neurosurgeon, otolaryngologist, dentist, microbiologists is mandatory for a proper diagnosis and treatment of these pathologies.

Disease Entities in Mucormycosis

Mucormycosis is an emerging life-threatening fungal infection caused by Mucorales. This infection occurs mainly in immunocompromised patients, especially with hematological malignancy, transplantation, or diabetes mellitus. Rhino-orbito-cerebral and pulmonary mucormycosis are the predominant forms. Interestingly, location is associated with the underlying disease as pulmonary mucormycosis is more frequent in hematological malignancy patients whereas rhino-orbito-cerebral mucormycosis is associated with diabetes. Cutaneous mucormycosis results from direct inoculation, mainly after trauma or surgery. Gastro-intestinal mucormycosis occurs after ingestion of contaminated food or with contaminated device and involves the stomach or colon. Disseminated disease is the most severe form and is associated with profound immunosuppression. Uncommon presentations with endocarditis, osteoarticluar or isolated cerebral infections are also described. Finally, health-care associated mucormycosis is a matter of concern in premature newborns and burn units. Clinical symptoms and CT scan findings are not specific, only the early reversed halo sign is associated with pulmonary mucormycosis. Circulating Mucorales DNA detection is a recent promising diagnostic tool that may lead to improving the diagnosis and prompting therapeutic initiation that should include antifungal treatment, correction of the underlying disease and surgery when feasible.

Understanding Refugees' Health

According to the United Nations Refugee Agency (UNHCR), 65.6 million people have been forcibly displaced worldwide. Several factors have a major influence on asylum seekers' health; so, their health profile is markedly different from that of the population in the country of asylum. The aim of this study is to review the major issues physicians need to be aware of when treating asylum seekers, with a special focus on the neurological problems of asylum seekers and refugees. The major impact factors on refugees' health are linked to experiences and exposure (1) in the country of origin, (2) in refugee camps and en route to Europe, and (3) in the process of immigration into the host country and living in European asylum centers. Refugees' health is also affected by psychological problems and by infectious diseases. Additionally, chronic diseases resulting in polymorbidity, cancer, and neurological diseases are easy to overlook and demand special attention. Neurological injuries/diseases may be traumatic (e.g., spinal cord injuries), posttraumatic (e.g., chronic pain syndromes), the result of cerebral infections, or the consequences of starvation (e.g., epilepsy, ataxia, and paraesthesia). The main challenges for physicians are lack of awareness of the asylum seekers' specific health care problems, language and intercultural communication problems, as well as access and integration of asylum seekers into the health care system. The health issues of asylum seekers are manifold and challenging to physicians. Awareness of these conditions is mandatory to ensure good clinical practice for this patient population, which has a huge burden in chronic, infectious, mental, and neurological diseases.

Neuropathology

This chapter discusses neuropathology, including nervous system malformations, epilepsy, head injury, cerebral infarction, intracerebral haemorrhage, subarachnoid haemorrhage, meningitis, cerebral infections, multiple sclerosis, Guillain–Barré syndrome, myasthenia gravis, Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, Parkinson’s disease, Huntington’s disease, motor neurone disease, Creutzfeldt–Jacob disease, astrocytomas (including glioblastoma), oligodendroglioma, ependymoma, meningioma, medulloblastoma, primary CNS lymphomas, and cerebral metastases.

Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis

ABSTRACTPrimary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales. Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted.

Biomarkers of Brain Injury in Cerebral Infections

BACKGROUND Central nervous system (CNS) infections present a major burden of disease worldwide and are associated with high rates of mortality and morbidity. Swift diagnosis and initiation of appropriate treatment are vital to minimize the risk of poor outcome; however, tools are lacking to accurately diagnose infection, assess injury severity, and predict outcome. Biomarkers of structural neurological injury could provide valuable information in addressing some of these challenges. CONTENT In this review, we summarize experimental and clinical research on biomarkers of neurological injury in a range of CNS infectious diseases. Data suggest that in both adults and children, the biomarkers S100B and neuron-specific enlose (NSE), among others, can provide insight into the pathophysiology of CNS infection and injury severity, evolution, and response to treatment. Research into the added utility of combining a panel of biomarkers and in assessing biomarker association with clinical and radiological outcomes warrants further work. Various factors, including age, the establishment of normative values, and comparison of biomarker concentrations across different testing platforms still present challenges in biomarker application. SUMMARY Research regarding the value of biomarkers in CNS infections is still in its infancy. However, early evidence supports their utility in diagnosis and prognosis, and potentially as effective surrogate end points in the assessment of novel interventions.