Severe Central Nervous System Infection Research Articles

Brainstorm: A case of granulomatous encephalitis

Background: Free-living amoebas (FLAs) can cause severe and fatal central nervous system infections that are difficult to diagnose. Methods: We present the case of a 74-year-old immunocompetent woman admitted for focal neurological symptoms with enhancing lesions in the right cerebellar hemisphere. A first cerebral biopsy showed granulomatous inflammation, but no microorganisms were identified. After transient clinical improvement, she eventually deteriorated 4 months after initial presentation, with an MRI confirming multiple new masses affecting all cerebral lobes. Results: A second brain biopsy revealed granulomatous and acute inflammation with organisms containing a large central nucleus with prominent karyosome, consistent with FLAs. Immunohistochemical and polymerase chain reaction assays performed at CDC were positive for Acanthamoeba spp, confirming the diagnosis of granulomatous amoebic encephalitis (GAE) caused by Acanthamoeba spp. The patient was treated with combination therapy recommended by CDC, but died a few days later. Upon histopathological rereview, amoebic cysts and trophozoites were identified by histochemical and immunohistochemical methods in the first cerebral biopsy. Conclusion: FLA infections can be challenging to diagnose because of the low incidence, non-specific clinical and radiological presentation, lack of accessible diagnostic tools, and clinicians’ unfamiliarity. This case highlights the importance of recognizing FLA as a potential cause of granulomatous encephalitis, even in the absence of risk factors, as early treatment might be associated with favourable outcomes in case reports. When suspected, CDC laboratories offer tests to confirm the diagnosis promptly.

Multiple-organ dysfunction in children with central nervous system infections

BACKGROUND: Multiple-organ dysfunction syndrome is one of the most dangerous complications of critical illness in children, which helps determine the disease outcomes.
 AIM: This study aimed to examine the features of multiple-organ dysfunction syndrome in children with severe central nervous system (CNS) infection and identify factors that determine disease outcomes.
 MATERIALS AND METHODS: This single-center, retrospective, observational study enrolled 98 patients, which included 66 (67%) boys and 32 (33%) girls. The average age was 3.6 ± 2.5 years. The Glasgow coma scale (GCS) score was 8.8 ± 2.4 points. Shock was diagnosed in 43 (44%) patients. The average treatment duration in the intensive care unit (ICU) was 9.5 ± 6.2 days, the duration of mechanical ventilation was 6.0 ± 3.9 days, and the mortality rate was 9%. Depending on the outcome, the children were divided into groups I (recovery, n = 88) and II (death, n = 10). All indicators were recorded in the first 12 h from ICU admission.
 RESULTS: The most pronounced phenomena of cardiovascular dysfunction, such as decreased Teicholtz ejection fraction (62.3 L/min), were observed when the pSOFA scale score was 10 points, which was statistically significant when compared with the indicators in children with a pSOFA scale score of 8 points. In all patients, regardless of age, a negative correlation of moderate strength was found between the pSOFA scale score and the Teicholtz ejection fraction, and it was pronounced in children aged 7–17 years (R = –0.41; p = 0.008). A positive correlation was found between heart rate and pSOFA scale score in children aged 7–17 years (R = 0.72; p = 0.009). In the evaluation of the discriminatory ability of the pSOFA scale and Phoenix sepsis scores regarding the outcome on the first day of treatment in the ICU, the latter has greater prognostic significance (area under the curve, 0.866 vs 0.838; sensitivity, 76% vs 72%; specificity, 82% vs 79%).
 CONCLUSIONS: Low cardiac output syndrome and systemic hypoxia are key factors associated with fatal outcomes in children with severe CNS infections. The high clinical significance of the ejection fraction in predicting the outcomes of severe CNS infections in children, regardless of age, allows the use of this parameter for goal-oriented therapy.

Human herpesvirus-6 infection in a critically ill and immunocompetent patient: a case report

BackgroundHuman herpesvirus-6 is a rare infection in an immunocompetent adult. In existing literature, there is a dearth of knowledge that mainly exists as case reports and case series.Case PresentationIn this case report, we described a 29-year-old female of Myanmarese descent patient from Myanmar who presented with altered mental status and non-specific respiratory and gastrointestinal symptoms. She was initially treated for pneumonia and discharged well. However, she re-presented to the hospital and was subsequently treated for severe central nervous system infection. Cerebrospinal fluid studies detected human herpesvirus-6 polymerase chain reaction with associated high serum human herpesvirus-6 concentration. This infection also triggered hemophagocytic lymphohistiocytosis. Treatment was initiated against both human herpesvirus-6 infection and hemophagocytic lymphohistiocytosis, and she responded to antiviral treatment and steroids, respectively.ConclusionThis case study highlights the need for prompt diagnosis and treatment of this severe disease and the dangerous complications. Additionally, the authors share insights on the diagnostic challenges faced in the treatment of this patient.

Changing rates but persisting seasons: patterns of enterovirus infections in hospitalizations and outpatient visits in Denmark 2015-2022

BackgroundEnteroviruses (EV) constitute a diverse group of viruses manifesting a broad spectrum of clinical presentations in humans ranging from mild skin manifestations to more severe central nervous system (CNS) infection. Severe infections are reported with increased frequency globally, albeit the burden of diseases and the evolution of circulating viruses is largely unknown. We aimed to systematically explore contemporary trends in hospitalizations attributed to EV infections using national hospitalization discharge data.MethodsWe utilized the Danish National Patient Register which holds information on all contacts to Danish hospitals. We covered eight full years (2015-2022). Length-of-stay and administrative procedure codes were used to distinguish hospital admissions from outpatient visits. We utilized burden of disease estimates and distribution statistics.ResultsWe identified 1029 hospitalizations and 1970 outpatient visits due to EV infections. The hospital admissions were primarily associated with CNS-infections (n=570, 55.4%) and skin (n=252, 24.5%), with variation over the studied period. The admitted patients were predominately children (43.8%) though patients were identified in all ages. The clinical manifestation was associated with age, with CNS infections dominating in the neonates and adults, and skin infections dominating in children 1-2 years (17.2%). Outpatient visits were predominantly observed among children 1-2 years (55.0%), presenting with skin symptoms (77.9%). We show a seasonal pattern of EV infections with summer/fall peaks and markedly impact on the EV hospitalization burden related to COVID-19 mitigation measures including national lockdown periods. 25% of hospital admissions occurred during 2020-2022.ConclusionEV infections caused both hospital admissions and outpatient visits in the period studied, predominately among children aged 1-2 years. Overall, skin infections dominated the outpatient visits, while the majority of hospital admissions were due to CNS infections. The pandemic period did not change the seasonal pattern of EV infections but notably lowered the number of admissions to hospital with CNS infection and raised the number of outpatient admissions with skin infection.

Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia during remission induction chemotherapy: a single-center retrospective study.

This study investigated the clinical characteristics, cranial magnetic resonance imaging (MRI) features, MRI follow-up, and prognosis of children with acute lymphoblastic leukemia (ALL) who developed posterior reversible encephalopathy syndrome (PRES) during remission induction chemotherapy. We analyzed the age, gender, PRES symptoms and signs, cranial MRI findings, therapeutic effect, and prognosis of children with ALL who developed PRES during chemotherapy from January 2010 to December 2013 at the Hematology Oncology Center of Beijing Children's Hospital. Changes in cranial MRI findings were analyzed, and intelligence (IQ) and cognitive function were evaluated using the Wechsler Scale and the Wisconsin Card Score Test after the children completed chemotherapy. There were 850 children with newly diagnosed ALL in this period; 13 (1.5%), 6 boys and 7 girls, developed PRES. All were diagnosed as B-cell ALL. The median age at PRES onset was 7 years (2-11 years). The median day of PRES onset was day 28 (day 17-34) of remission induction chemotherapy. Of the 13 children with PRES onset and seizures, 4 had visual disturbances and 2 had consciousness disturbances. Cranial MRI showed hyperintensity in the subcortical white matter on T2-weighted axial and fluid-attenuated inversion recovery (FLAIR) images. The lesion locations were as follows: occipital lobe, 12 (92.3%) patients; frontal lobe, 7 (53.8%) patients; temporal lobe, 5 (38.4%) patients; parietal lobe, 3 (23.1%) patients; and cerebellum, 1 (7.7%) patient. There were 8 (61.5%) patients with vasogenic edema and 5 (38.5%) with cytotoxic edema. After treatment, all children recovered within one month, when their PRES symptoms were relieved, they continued to receive chemotherapy. However, 1 child (1.07%) died of severe central nervous system infection one year after PRES treatment, and 3 (25%) had recurrent seizures and were diagnosed with epilepsy after three months of PRES treatment. Their cranial MRIs showed cytotoxic edema, which was acute stage on day 15, with aggravated lesions on cranial MRI. The cranial MRI lesions returned to normal at one month in 3 (23.1%) patients, at three months in 6 (46.1%) patients, at one year in 8 (61.5%) patients, and at two years in 12 (92.3%) patients. The 12 surviving children all returned to school, and their full-scale, verbal, and performance IQs were normal, with no significant differences in intelligence or cognitive function compared with children with ALL without PRES during the same period. PRES can occur during remission induction chemotherapy treatment of children with ALL, but the incidence is low. Cranial MRI can be used for diagnosis and to characterize lesions. The children recover about a month after treatment, and cranial MRI lesions return to normal within two years. The time for complete resolution of MRI lesions differs, and children with cytotoxic edema have worse prognosis with sequelae, such as epilepsy, which requires close monitoring. PRES does not affect intelligence or cognitive development.

Analysis of Vacuum-Assisted Closure-Assisted Antibiotic Irrigation in Treatment of Severe Neurosurgical Central Nervous System Infections.

Objective: Severe neurosurgical central nervous system infections (sNCNSIs) are among the most serious complications of neurosurgical disease. Conventional methods have shown a poor prognosis. This study aims to analyze the clinical characteristics of vacuum-assisted closure (VAC) in sNCNSIs with the help of antibiotic irrigation treatment. Patients and Methods: A retrospective study was performed for patients diagnosed with sNCNSIs. A VAC device was placed on the incision after debridement and the surgical cavity was rinsed with antibiotic agents in the VAC group. Meanwhile the surgical cavity was drained after debridement in the control group. Medical data were reviewed and analyzed. Results: Twenty-eight patients met the inclusion criteria, including 18 cases in the VAC group and 10 cases in the control group. The basic medical data showed no differences. Bacteria was isolated from 24 (85.7%) patients. The cure rate was significantly higher in the VAC group (p < 0.05). The cure rate in patients with multi-drug-resistant (MDR) infections was significantly higher in patients treated with VAC therapy (p < 0.05). The prognosis evaluated by Glasgow Outcome Score (GOS) between the two groups showed significant difference (p < 0.05). No re-infection in the VAC group occurred in the follow-up period. Conclusions: It is suggested that VAC-assisted antibiotic irrigation is safe and effective for patients with severe NCNSIs and can improve the prognosis dramatically. The results can provide a new effective and reasonable therapeutic strategy for patients with sNCNSIs.

Successful Treatment of Carbapenem-Resistant Klebsiella pneumoniae Meningitis with Combination Therapy of Meropenem and Amikacin

Introduction: The widespread use of carbapenems increased the prevalence of Carbapenem-resistant Enterobacteriaceae with subsequent increases in mortality due to extremely limited treatment options. Following neurosurgical procedures, carbapenem-resistant Klebsiella pneumoniae (CRKP) is the main cause of central nervous system (CNS) infections. The optimal antimicrobial treatment of such infections has not yet been defined. Case Presentation: We present a 4-month-old boy with an extra-ventricular drain-related central nervous system (CNS) infection with CRKP. Although meropenem minimum inhibitory concentration (MIC) for the bacterial isolate was ≥ 16 mg/L and it harbored blaNDM, blaVIM, and blaOXA-48-like Carbapenemase genes, this infection was effectively treated with a combination therapy of intravenous (IV) double dose extended infusion of meropenem in addition to amikacin. Conclusions: This successful treatment regimen for CRKP-causing meningitis may pave the way to manage severe CNS infections with extensive-drug-resistant bacteria in infants and children without inserting an external drain or intra-thecal antibiotic administration.

Clinical features, etiologies, and outcomes of central nervous system infections in intensive care: A multicentric retrospective study in a large Brazilian metropolitan area

PurposeThe goal of this study was to investigate severe central nervous system infections (CNSI) in adults admitted to the intensive care unit (ICU). We analyzed the clinical presentation, causes, and outcomes of these infections, while also identifying factors linked to higher in-hospital mortality rates. Materials and methodsWe conducted a retrospective multicenter study in Rio de Janeiro, Brazil, from 2012 to 2019. Using a prediction tool, we selected ICU patients suspected of having CNSI and reviewed their medical records. Multivariate analyses identified variables associated with in-hospital mortality. ResultsIn a cohort of 451 CNSI patients, 69 (15.3%) died after a median 11-day hospitalization (5–25 IQR). The distribution of cases was as follows: 29 (6.4%) had brain abscess, 161 (35.7%) had encephalitis, and 261 (57.8%) had meningitis. Characteristics: median age 41 years (27–53 IQR), 260 (58%) male, and 77 (17%) HIV positive. The independent mortality predictors for encephalitis were AIDS (OR = 4.3, p = 0.01), ECOG functional capacity limitation (OR = 4.0, p < 0.01), ICU admission from ward (OR = 4.0, p < 0.01), mechanical ventilation ≥10 days (OR = 6.1, p = 0.04), SAPS 3 ≥ 55 points (OR = 3.2, p = 0.02). Meningitis: Age > 60 years (OR = 234.2, p = 0.04), delay >3 days for treatment (OR = 2.9, p = 0.04), mechanical ventilation ≥10 days (OR = 254.3, p = 0.04), SOFA >3 points (OR = 2.7, p = 0.03). Brain abscess: No associated factors found in multivariate regression. ConclusionsPatients' overall health, prompt treatment, infection severity, and prolonged respiratory support in the ICU all significantly affect in-hospital mortality rates. Additionally, the implementation of CNSI surveillance with the used prediction tool could enhance public health policies.

Parechovirus Neonatal Meningitis: A Case Report

Neonatal meningitis is a serious, potentially life- threatening condition that requires prompt diagnosis and treatment. Bacterial pathogens are usual suspects; however, viral cause should not be overlooked. We report a case of Parechovirus neonatal meningitis in an 8 days old male infant, emphasizing the importance of considering uncommon viral pathogens in the diagnostic work up. Human Parechovirus belongs to the family of Picornaviridae virus. It is very uncommon and has been associated with a benign clinical course of respiratory and gastrointestinal infection in most cases, however, it is emerging as one of the causes for emergency admission of neonates in hospital due to certain serotypes. The HPeV type 3 has been found mostly in children and young infants presenting with meningitis and sepsis like illness. Infants with severe Central Nervous System (CNS) infections are at an increased risk of long-term sequelae. In this case we describe the clinical presentation, diagnostic challenges, management and outcome of this rare infection. An 8 days old baby presented to our emergency department with sepsis like illness. He was admitted in neonatal unit for further investigations and management. Despite initial presentation the inflammatory markers were normal. Symptomatic-supportive treatment was given till baby made full recovery. Antibiotics were discontinued after 48 hours as culture was negative for bacteria. This case highlights the importance of considering Parechovirus as possible cause of neonatal meningitis when inflammatory markers are normal and plan the management appropriately.

Cerebrovascular complications in patients with community-acquired bacterial meningitis: occurrence and associated factors in the COMBAT multicenter prospective cohort

BackgroundCommunity-acquired bacterial meningitis is a rare but severe central nervous system infection that may be associated with cerebrovascular complications (CVC). Our objective is to assess the prevalence of CVC in patients with community-acquired bacterial meningitis and to determine the first-48 h factors associated with CVC.MethodsWe analyzed data from the prospective multicenter cohort study (COMBAT) including, between February 2013 and July 2015, adults with community-acquired bacterial meningitis. CVC were defined by the presence of clinical or radiological signs (on cerebral CT or MRI) of focal clinical symptom. Factors associated with CVC were identified by multivariate logistic regression.ResultsCVC occurred in 128 (25.3%) of the 506 patients in the COMBAT cohort (78 (29.4%) of the 265 pneumococcal meningitis, 17 (15.3%) of the 111 meningococcal meningitis, and 29 (24.8%) of the 117 meningitis caused by other bacteria). The proportion of patients receiving adjunctive dexamethasone was not statistically different between patients with and without CVC (p = 0.84). In the multivariate analysis, advanced age (OR = 1.01 [1.00-1.03], p = 0.03), altered mental status at admission (OR = 2.23 [1.21–4.10], p = 0.01) and seizure during the first 48 h from admission (OR = 1.90 [1.01–3.52], p = 0.04) were independently associated with CVC.ConclusionsCVC were frequent during community-acquired bacterial meningitis and associated with advanced age, altered mental status and seizures occurring within 48 h from admission but not with adjunctive corticosteroids.

MNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study.

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up (r = -0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.

Management of neonatal central nervous system viral infections: Knowledge gaps and research priorities.

Congenital CMV, enteroviruses, human parechovirus and herpes simplex virus are all common causes of severe central nervous system (CNS) infection in neonates. The introduction of screening (i.e. newborn hearing screening programme), integration of molecular syndromic testing (i.e. multiplex polymerase chain reaction assays) and increase in sexually transmitted infections (i.e. anogenital herpes) have contributed to increases in each of these infections over the last decade. However, therapeutic options are highly limited in part due to the lack of epidemiological data informing trials. This review will describe our current understanding of the clinical burden and epidemiology of these severe neonatal CNS infections, outline the novel antiviral and vaccines in the pipeline and suggest future research studies which could help develop new therapeutics.

Murine models of neonatal susceptibility to a clinical strain of enterovirus A71

Enterovirus A71 (EV-A71) is neurotropic and one of the primary enteric pathogens responsible for severe central nervous system infection in infants and young children. Neonatal mice are ideal models for studying the pathogenesis of infection caused by EV-A71. In this study, we assessed the susceptibility of neonatal BALB/c, C57BL/6, ICR, Kunming, and NIH mice to a clinically isolated EV-A71 strain. One-day-old mice were challenged with a clinical isolate of EV-A71 via intraperitoneal injection, then observed for 13 days for mortality, body-weight changes, and limb paralysis. RT-qPCR was performed to quantify viral RNA in the brain, spinal cord, skeletal muscle, and lungs of BALB/c and C57BL/6 mice. The expression of murine scavenger receptor class B member 2 (mSCARB2) was measured by western blotting. Finally, lesions were assessed by histological examination. We found that neonatal BALB/c and C57BL/6 mice were both susceptible to EV-A71, leading to decreased survival rate, greater body weight loss, and prominent hind-limb paralysis. Tissue viral loads of C57BL/6J mice were markedly higher than those of BALB/c mice, indicating that EV-A71 replicated more efficiently in C57BL/6 mice. Increased expression of mSCARB2 was observed 5 days after infection in C57BL/6 mice, which coincided with the peak in EV-A71 replication. Histological examination indicated that infection caused obvious pathogenic lesions. In conclusion, C57BL/6 are most susceptible to infection caused by EV-A71 and can be used as a model for studying its pathogenesis and test therapeutic options.

Prediction of the outcomes of severe central nervous system infections in children

Prediction of the outcomes of severe central nervous system infections in children

Frequency of Meningococcal Meningitis Susceptibility Associated TLR4 +896 A/G (rs4986790) Allele in the Saudi Population

Meningococcal meningitis (MM) is a severe central nervous system (CNS) infection that occurs primarily in children. MM can damage brain areas associated with hearing, learning, reasoning, focus, and memory. Genetic changes, including single nucleotide polymorphisms (SNPs), which compromise pathogen recognition increase the risk and severity of MM. There is little data on how the variation in the frequency of the rs4986790 polymorphism in the Toll-like receptor 4 (TLR4) gene may affect the population of Saudi Arabia. This study sought to determine the allelic frequency and distribution of the TLR4 rs4986790 A/G polymorphism in the Saudi population and compare the data to other global populations. Data from epidemiological studies conducted in various ethnic groups were extracted using PUBMED (Medline) and similar web databases. An estimated 5.88% of the Saudi population harbors the TLR4 rs4986790 G variant allele. This differed significantly from the frequencies in populations in China (p=0.0002), Japan (p=0.0001), Korea (p=0.0001), and Mexico (p=0.01). The TLR4 rs4986790 polymorphism variant allele has a unique pattern in the Saudi population, which may be the result of racial differences. These findings could assist in the risk assessment of people harboring the TLR4 +896 GG genotype susceptible to MM in the Saudi population.

Understanding global changes of the mouse brain proteome after vaginal infection with HSV-2 using a label-free shotgun approach.

Herpes simplex virus type 2 (HSV-2) is a common human pathogen that establishes lifelong latency in neurons of the nervous system. The number of severe central nervous system infections caused by the virus has increased recently. However, the pathogenesis of HSV-2 infection in the nervous system is not fully understood. Here, we demonstrated global proteomic changes in the brain tissue in BALB/c mice vaginally infected with HSV-2. Data are available via ProteomeXchange with identifier PXD034186. A total of 249 differentially expressed proteins were identified in infected brain tissue. The GO and KEGG enrichment analysis of these proteins indicated that they were mainly involved in the regulation of synapse formation and synaptic excitability. In addition, genes affecting autophagy, the development of other neurodegenerative diseases, and signaling pathways relevant to other neurologic diseases were identified. Additional experiments, comparing the brain tissue of asymptomatic and symptomatic mice showed a differential expression of proteins involved in synapse formation and synaptic transmission. Others were involved in autophagy, addiction, and signaling pathways of other neurologic diseases. These results suggest that changes in synaptic structure and function, as well as autophagy, may be related to the development of neurologic abnormalities that follow HSV-2 infection. We also identified a protein GluN2A encoded by Grin2a was continuously expressed at high levels after infection. We propose that GluN2A may be a key molecule in the pathogenesis of HSV-2-induced neurologic diseases.

Isolation and characterization of phage display-derived scFv antibodies against human parechovirus 1 VP0 protein

Human parechoviruses (PeVs) are common viruses that are associated with a variety of diseases from mild gastrointestinal and respiratory symptoms to severe central nervous system infections. Until now there has not been antibodies for visualizing parechovirus infection. We used E. coli recombinant PeV-A1-VP0 protein as a target in phage display single chain variable fragment (scFv) antibody library panning. Three rounds of panning allowed identification and isolation of several candidate scFv clones, which tested positive in enzyme-linked immunosorbent assay (ELISA) against VP0. Three scFv clones (scFv-55, -59 and -71) with different CDR-3 sequences were further purified and tested in ELISA, Western blot and immunofluorescence microscopy (IFA) against a set of PeV-A1 isolates and a few isolates representing PeV types 2–6. In IFA, all three scFv binders recognized twenty PeV-A1 isolates. ScFv-55 and -71 also recognized clinical representatives of PeV types 1–6 both in IFA and in capture ELISA, while scFv-59 only recognized PeV-A1, -A2 and -A6. PeV-A1-VP0 (Harris strain) sequence was used to generate a peptide library, which allowed identification of a putative unique conformational antibody epitope with fully conserved flanking regions and a more variable core VVTYDSKL, shared between the scFv antibodies. Sequencing of the VP0 region of virus samples and sequence comparisons against parechoviral sequences in GenBank revealed 107 PeV-A1, -A3, -A8, -A17, -A (untyped) sequences with this exact epitope core sequence, which was most dominant among PeV-A1 isolates. These data suggest the first-time isolation of broad range phage display antibodies against human parechoviruses that may be used in diagnostic antibody development.

Augmented Renal Clearance in Severe Infections-An Important Consideration in Vancomycin Dosing: A Narrative Review.

Vancomycin is a hydrophilic antibiotic widely used in severe infections, including bacteremia and central nervous system (CNS) infections caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci and enterococci. Appropriate antimicrobial dosage regimens can help achieve the target exposure and improve clinical outcomes. However, vancomycin exposure in serum and cerebrospinal fluid (CSF) is challenging to predict due to rapidly changing pathophysiological processes and patient-specific factors. Vancomycin concentrations may be decreased for peripheral infections due to augmented renal clearance (ARC) and increased distribution caused by systemic inflammatory response syndrome (SIRS), increased capillary permeability, and aggressive fluid resuscitation. Additionally, few studies on vancomycin’s pharmacokinetics (PK) in CSF for CNS infections. The relationship between exposure and clinical response is unclear, challenging for adequate antimicrobial therapy. Accurate prediction of vancomycin pharmacokinetics/pharmacodynamics (PK/PD) in patients with high interindividual variation is critical to increase the likelihood of achieving therapeutic targets. In this review, we describe the interaction between ARC and vancomycin PK/PD, patient-specific factors that influence the achievement of target exposure, and recent advances in optimizing vancomycin dosing schedules for severe infective patients with ARC.

Polymicrobial Anaerobic Meningitis Detected by Next-Generation Sequencing: Case Report and Review of the Literature

BackgroundAnaerobic meningitis is a severe central nervous system infection associated with significant neurological sequelae and high mortality. However, the precise detection of causative pathogen(s) remains difficult because anaerobic bacteria are difficult to culture. Next-generation sequencing is a technology that was developed recently and has been applied in many fields. To the best of our knowledge, the use of next-generation sequencing for cerebrospinal fluid analysis in the diagnosis of anaerobic meningitis has been rarely reported.Case presentationHere, we report a case of polymicrobial anaerobic meningitis diagnosed using next-generation sequencing of cerebrospinal fluid in a 16-year-old girl. Five species of anaerobic bacteria (Porphyromonas gingivalis, Prevotella enoeca, Campylobacter rectus, Fusobacterium uncleatum, and Actinomyces israelii) were detected by next-generation sequencing and treated with antibacterial agents (ceftriaxone, vancomycin, and metronidazole). The patient responded well to antibacterial treatment. Further inspection revealed bone destruction at the base of the skull, which further confirmed that these bacteria had originated from the oral cavity. One month later, the patient's condition improved significantly. At the same time, we performed a literature review on anaerobic meningitis using studies published in the last 20 years.ConclusionsThis case emphasizes the importance of applying metagenomic next-generation sequencing to clinch the clinical diagnosis for patients with central nervous system infection. Metagenomic next-generation sequencing has been reported to be an important diagnostic modality for identifying uncommon pathogens.

Does Tigecycline Have a Place in Therapy for Rickettsial Infection of the Central Nervous System?

This brief report documents the safety and efficacy of high-dose tigecycline as a salvage-therapy in in a case series of five patients with serious central nervous system (CNS) rocky mountain spotted fever (RMSF). These severily ill patients were unable to take any oral drug therapy, parenteral doxycycline was unavailable and absorption of oral doxycycline was a concern in these critically ill patients. As far as we know, we report the successfull use of tigecycline for the treatment of rickettsial meningitis for the first time in Italy. We suggest more studies on tigecycline in severe CNS infections from Rickettsia species and multi-drug resistant bacteria, especially the use of tigecycline at higher than standard doses in these life-threathening infectious diseases.