Non-central Nervous System Infections Research Articles

FilmArray Meningitis/Encephalitis Panel Impact on Antibiotic Usage in Patients with Suspected Community-Acquired Meningitis

Background: Cerebrospinal fluid (CSF) cultures are commonly performed to evaluate patients with suspected bacterial meningitis. These cultures, however, can take up to 72 hours, leading to delays in antibiotic de-escalation and increased antimicrobial utilization. The turnaround for the BioFire® FilmArray® Meningitis/Encephalitis(FA/ME) panel is less than an hour, which may facilitate early de-escalation. Our study aimed to assess whether the use of FA/ME panels in combination with CSF cultures could impact antimicrobial therapy compared to cultures alone in patients treated for suspected bacterial meningitis. Methods: Our retrospective study included patients from five hospitals in Texas (2017-2023) who received empiric antibiotics for suspected community-acquired meningitis and underwent a lumbar puncture within 96 hours of admission. Patients with ventricular drains, traumatic brain injury, and non-central nervous system infections were excluded. Cases comprised patients who had an FA/ME panel performed, while controls included patients without the panel. Outcomes were defined as the empiric duration of antimicrobial therapy (days) and total days of antibiotic therapy (DOT). Wilcoxon Rank Sum test and multiple linear regression models were applied to assess the relationship between the use of the FA/ME panel and study outcomes. Independent variables comprised demographics, institution type, acuity, clinical presentation, CSF values, and FA/ME panel use. Imputation was performed using multiple imputation by chained equations. Results: A total of 193 patients were included in our study. Seventy-one patients received the FA/ME panel (along with the CSF culture), while 122 patients received the CSF culture alone (controls). The median empiric duration of antibiotic therapy in the cases and controls were 1.71 days and 1.18 days, respectively (p = .160). The median DOT in the cases and controls were eight days and six days, respectively (p = .045). After adjusting for confounders, the FA/ME panel was not significantly associated with changes in the empiric duration of antibiotic therapy (B= 0.18, p = .669, Figure 1) or DOT (B= 1.28, p = .170, Figure 2).Conclusion: Providing FA/ME panel testing without active antimicrobial stewardship interventions did not result in a change in antimicrobial prescribing patterns. The difference from prior literature could be explained by the smaller sample size, limiting the power of the study. Further prospective antimicrobial stewardship efforts should focus on training providers on interpreting FA/ME panel results and providing prospective audits and feedback.

Lipid peroxidation-induced ferroptosis as a therapeutic target for mitigating neuronal injury and inflammation in sepsis-associated encephalopathy: insights into the hippocampal PEBP-1/15-LOX/GPX4 pathway

BackgroundSepsis-associated encephalopathy (SAE) refers to the widespread impairment of brain function caused by noncentral nervous system infection mediated by sepsis. Lipid peroxidation-induced ferroptosis contributes to the occurrence and course of SAE. This study aimed to investigate the relationship between neuronal injury and lipid peroxidation-induced ferroptosis in SAE.MethodsBaseline data were collected from pediatric patients upon admission, and the expression levels of various markers related to lipid peroxidation and ferroptosis were monitored in the serum and peripheral blood mononuclear cells (PBMCs) of patients with SAE as well as SAE model mice. The hippocampal phosphatidylethanolamine-binding protein (PEBP)-1/15-lysine oxidase (LOX)/ glutathione peroxidase 4 (GPX4) pathway was assessed for its role on the inhibitory effect of ferroptosis in SAE treatment.ResultsThe results showed elevated levels of S100 calcium-binding protein beta (S-100β), glial fibrillary acidic protein, and malondialdehyde in the serum of SAE patients, while superoxide dismutase levels were reduced. Furthermore, analysis of PBMCs revealed increased transcription levels of PEBP1, LOX, and long-chain fatty acyl-CoA synthetase family member 4 (ACSL4) in SAE patients, while the transcription levels of GPX4 and cystine/glutamate transporter xCT (SLC7A11) were decreased. In comparison to the control group, the SAE mice exhibited increased expression of S-100β and neuron-specific enolase (NSE) in the hippocampus, whereas the expression of S-100β and NSE were reduced in deferoxamine (DFO) mice. Additionally, iron accumulation was observed in the hippocampus of SAE mice, while the iron ion levels were reduced in the DFO mice. Inhibition of ferroptosis alleviated the mitochondrial damage (as assessed by transmission electron microscopy, hippocampal mitochondrial ATP detection, and the JC-1 polymer-to-monomer ratio in the hippocampus) and the oxidative stress response induced by SAE as well as attenuated neuroinflammatory reactions. Further investigations revealed that the mechanism underlying the inhibitory effect of ferroptosis in SAE treatment is associated with the hippocampal PEBP-1/15-LOX/GPX4 pathway.ConclusionThese results offer potential therapeutic targets for the management of neuronal injury in SAE and valuable insights into the potential mechanisms of ferroptosis in neurological disorders.

CARBAPENEM ANTIBIOTIC DOSE MODE FOR PEDIATRIC PATIENT AT CAN THO CHILDREN’S HOSPITAL

Objective: Analyzing the dose regimen of carbapenem antibiotics used in pediatric patients at Can Tho Children’s Hospital.Objects and methods: retrospective-descriptive study on 140 medical records of patients being treated at departments of Can Tho Children’s Hospital during the period from June 1st, 2020 toDecember 31st, 2020. Results: Regarding the dosage regimen characteristics of meropenem showed that 20.3% and 10.8%of meropenem’s indications for the dose of meropenem for non-central nervous system infections and meningitis treament was appropriate according to the recommendations. Meanwhile, up to63.5% of the dose was higher than the recommended dose and 5.5% of the treatment dose was lower than the recommended dose. Regarding imipenem dosage regimen characteristics from the resultsshowed that 71.2% of the dose of imipenem for the treatment of infections non-central nervous system complied with recommendations according to the literature. However, more than 20% of the recommended dose for patients was lower than recommended dose. Conclusion: The meropenem dose regimen was consistent with the recommendation was low. The imipenem dose regimen was consistent with the relatively high recommendation.

Prospective research of human parechovirus and cytokines in cerebrospinal fluid of young children less than one year with sepsis-like illness: Comparison with enterovirus

BackgroundHuman parechovirus (PeV) and enterovirus are important pathogens that cause viral infection and aseptic meningitis in young children. We aimed to investigate the rate of HPeV and enterovirus detection, and to characterize cytokine profiles in the cerebrospinal fluid (CSF) of young infants with sepsis-like illness or meningitis/encephalitis. Study designThis was a prospective cohort study. CSF samples were collected from 90 infants less than 1 year of age. PeV and enterovirus detection was performed using reverse transcription polymerase chain reaction. Fifteen cytokines in the CSF were measured simultaneously by using multiplex immunoassays. ResultsPeV (PeV-group) and enterovirus (EV-group) were detected in 10 (11.1%) and 12 (13.3%) CSF samples, respectively. Other aseptic meningitis (AM-group) was diagnosed in 22 (24.4%) patients. Forty-six (51.1%) patients exhibited non-central nervous system infection (Ngroup). The PeV-group had the lowest CSF leukocyte (2.1 ± 3.5/mm3, p=0.022) and blood leukocyte (7,953 ± 4,583/mm3, p=0.046) count and Creactive protein levels (0.2 ± 0.1 mg/dL, p=0.036), than did those in the EV- and AM-groups. CSF leukocyte count and protein levels were not significantly different between the PeV- and N-groups. The levels of interleukin (IL)-1β, IL-5, IL-6, IL-12, and IL-17 were higher in the EVgroup; conversely, IL-2, IL-4, IL-7, and IL-13 were higher in the PeVgroup. ConclusionsExaminations to detect PeV in the CSF may help identify the etiological basis of undiagnosed febrile illness in young children. Significant differences in CSF and blood laboratory findings were observed between PeV- and enterovirus-infected children.

Pathological analysis of children with childhood central nervous system infection based on changes in chemokines and interleukin-17 family cytokines in cerebrospinal fluid.

In this study, the pathologies of acute meningitis and encephalopathy were investigated, and biomarkers useful as prognostic indices were searched for. The subjects were 31 children with meningitis, 30 with encephalopathy, and 12 with convulsions following gastroenteritis. Control group consisted of 24 children with non-central nervous system infection. Cerebrospinal fluid cytokine analysis was performed. Chemokines significantly increased in the bacterial meningitis group compared with those in viral meningitis and encephalopathy groups. On comparison of interleukin(IL)-17, it increased in cases with status epilepticus in influenza-associated encephalopathy group. In the rotavirus encephalopathy and convulsions following gastroenteritis groups, IL-17 particularly increased in the convulsions following gastroenteritis group. IL-8 increased in all cases irrespective of the causative virus. In the encephalopathy group, IL-8 may serve as a neurological prognostic index. IL-17 was increased in the convulsions following gastroenteritis group, particularly in cases with status epilepticus, suggesting its involvement as a convulsion-related factor.

Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) levels in the cerebrospinal fluid of children with influenza-associated encephalopathy

To search for an index of neurologic prognosis of children with influenza-associated encephalopathy (IAE), involvement of angiogenesis-related growth factors in the pathology was investigated. The subjects were 11 IAE patients, 6 patients with bacterial meningitis (BM), and 24 patients with non-central nervous system infection as a control group admitted to our hospital. The correlation between the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) levels in cerebrospinal fluid and the relationship with an index of inflammatory marker, interleukin (IL)-6, were investigated. Using the Pediatric Cerebral Performance Categories (PCPC) score as a prognostic indicator, we evaluated the association between the biomarkers and neurologic prognosis. PDGF significantly increased in the IAE group compared with that in the BM group. Cerebrospinal fluid VEGF and PDGF increased in all IAE and BM patients compared with that in the control group, and VEGF and PDGF were positively correlated in the 2 groups. No correlation was found between the cerebrospinal fluid VEGF and PDGF levels and IL-6 level in the IAE group, whereas a correlation was found in the BM group. All these factors increased in patients with poor neurologic prognosis. It is possible that the disease state of IAE can be evaluated based on vascular endothelial disorder-related markers.

Correlation of Vancomycin Dosing to Serum Concentrations in Pediatric Patients: A Retrospective Database Review

Appropriate antimicrobial dosing maximizes therapeutic benefit while minimizing development of antimicrobial resistance. Common pediatric references recommend vancomycin dosing of 40 mg/kg/day divided every 6 to 8 hours for non-central nervous system infections, while some clinicians report utilizing higher initial doses to optimize efficacy. This study compares vancomycin serum concentrations following traditional dosing of 10 mg/kg/dose every 6 to 8 hours versus 15 to 20 mg/kg/dose every 6 to 8 hours. Retrospective database review of vancomycin serum concentrations in pediatric patients. Three hundred fifty-seven patients were analyzed. The mean peak concentration of the 10 mg/kg groups every 6 and every 8 hours were below 25 mg/L, whereas the mean peak concentrations of the 15 mg/ kg groups every 6 and 8 hours were within the 25-40 mg/L range (p < 0.001). The mean trough concentration of the 10 mg/kg group every 6 hours was within the 5-15 mg/L range while the 10 mg/kg group dosed every 8 hours was below target. However, the mean trough concentrations of the 15 mg/kg group dosed every 6 and 8 hours were both within the 5-15 mg/L range (p < 0.001). Vancomycin doses of 15 mg/kg every 6 to 8 hours produce peak and trough serum concentrations within target range more often than 10 mg/kg every 6 to 8 hours.

LUMBOPERITONIAL SHUNT INFECTION DUE TO CHRYSEOBACTERIUM INDOLOGENES

Chryseobacterium indologenes central nervous system infection has not been reported. We present a case of lumboperitoneal shunt infection caused by C. indologenes successfully treated with trimethoprim-sulfamethoxazole and rifampin in a pediatric patient. Forty-three additional cases of C. indologenes non-central nervous system infections reported in the English medical literature were reviewed. Risk factors for C. indologenes infections include underlying medical illnesses, underlying immunocompromising conditions and presence of indwelling intravascular devices.

Cytokines and Adhesion Molecules Expression in the Brain in Human Cerebral Malaria

Although the role of systemic proinflammatory cytokines, IL-1beta and TNF-alpha, and their up-regulation of adhesion molecules, ICAM-1, VCAM-1 and E-Selectin, in the pathogenesis of cerebral malaria (CM) is well established, the role of local cytokine release remain unclear. Immunohistochemistry (IHC) was used to compare the expression of ICAM-1, VCAM-1, E-Selectin, IL-1beta, TNF-a and TGF-beta at light microscopic level in cerebral, cerebellar and brainstem postmortem cryostat sections from 10 CM, 5 severe malarial anemia (SMA), 1 purulent bacterial meningitis (PBM), 2 non-central nervous system infections (NCNSI) and 3 non-infections (NI) deaths in Ghanaian children. Fatal malaria and Salmonella sepsis showed significantly higher vascular expression of all 3 adhesion molecules, with highly significant co-localization with sequestration in the malaria cases. However, there was negligible difference between CM and SMA. TGF-beta showed intravascular and perivascular distribution in all cases, but expression was most intense in the PBM case and CM group. TNF-alpha and IL-1beta showed prominent brain parenchymal staining, in addition to intravascular and perivascular staining, in only the PBM case and CM group. The maximal expression of all 6 antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation is a feature of fatal malaria and Salmonella sepsis, with adhesion molecule expression being highly correlated with sequestration. IL-1beta and TNF-alpha are upregulated in only cases with neurodegenerative lesions, whilst TGF-beta is present in all cases. Both cytokines and adhesion molecules were maximally upregulated in the cerebellar sections of the malaria cases.

Outpatient therapy of serious pediatric infections with ceftriaxone

Convalescent outpatient parenteral antibiotic therapy with ceftriaxone was evaluated in an uncontrolled study of 101 children with documented serious bacterial infections, including meningitis. Criteria for outpatient therapy were established to assure that risks of complications from the illness were minimal at the time of discharge from the hospital. Daily physician visits and motivated, capable parents were considered essential in outpatient management. Ceftriaxone was given once daily to children with non-central nervous system infections and once or twice daily intravenously to children with meningitis. The mean durations of therapy for children with non-central nervous system infections and with meningitis were 2.4 and 4.6 days, respectively. No child enrolled in this study was readmitted to the hospital for medical or social reasons. Probable complications of treatment included diarrhea in 13% of children with meningitis and in 6% of children with non-central nervous system infections. One child with meningitis developed pseudomembranous colitis. For children who are infected with bacteria that are highly susceptible to ceftriaxone, single daily dose outpatient therapy is a reasonable option for management if a good clinical response to initial treatment is demonstrated and the risks of complications of the disease process are negligible.

In Vitro Susceptibility of Haemophilus influenzae to Sulfamethoxazole-Trimethoprim and Cefaclor, Cephalexin, and Cephradine

Sulfamethoxazole-trimethoprim and three oral cephalosporins, cefaclor, cephalexin, and cephradine, were evaluated in vitro as possible alternatives to chloramphenicol in the treatment of non-central nervous system infections due to ampicillin-resistant Haemophilus influenzae. Sixty-four isolates of H. influenzae, including 31 beta-lactamase-positive strains, were tested by the agar dilution method. All strains were inhibited by 0.78/0.039 mug sulfamethoxazole-trimethoprim per ml and by 0.78 mug of chloramphenicol per ml. At 6.25 mug/ml, 100, 11, and 3% of all strains were inhibited by cefaclor, cephalexin, and cephradine, respectively. Thus, on the basis of drug concentrations presumably achievable in serum, 100% of strains were susceptible to sulfamethoxazole-trimethoprim, chloramphenicol, and cefaclor. However, a considerable inoculum effect was noted with both beta-lactamase-positive and -negative strains, when tested with sulfamethoxazole-trimethoprim; the minimal inhibitory concentrations of cefaclor were only slightly affected. Also, synergistic effects of sulfamethoxazole-trimethoprim, sulfamethoxazole-erythromycin, and sulfamethoxazole-cefaclor were seen when combinations were tested against both beta-lactamase-positive and -negative strains, as determined by minimal inhibitory concentrations measured by the broth dilution method and by killing curve analyses. These results support further evaluation of these combinations and of cefaclor alone for the treatment of non-central nervous system infections due to H. influenzae.