ABSTRACT
BACKGROUND: To inform World Health Organization guidelines for the management of serious bacterial infection (SBI) (suspected or confirmed sepsis, pneumonia, or meningitis) in infants aged 0-59 days. OBJECTIVE: To conduct an "overview of systematic reviews" to: (1) understand which systematic reviews have examined diagnosis and management of SBI in infants aged 0-59 days in the last 5 years; and (2) assess if the reviews examined PICOs (population, intervention, comparator, outcomes) and regimens currently being recommended in low and middle income countries (LMICs) by the World Health Organization. DATA SOURCES: MEDLINE; Embase; Cochrane Library; Epistemonikos; PROSPERO. STUDY SELECTION: Systematic reviews of randomized controlled trials or observational studies of infants aged 0-59 days examining diagnostic accuracy and antibiotic regimens for SBI from January 1, 2018 to November 3, 2023. DATA EXTRACTION: Dual independent extraction of study characteristics, PICOs, and methodological quality. RESULTS: Nine systematic reviews met our criteria. Two reviews examined diagnostic accuracy for sepsis, and no reviews examined pneumonia or meningitis. Five reviews examined antibiotic effectiveness (sepsis [n = 4]; pneumonia [n = 1]), and no reviews examined meningitis. One review examined antibiotic duration for sepsis and one for meningitis, and no reviews for pneumonia. Only 4 of the 9 systematic reviews met criteria for high-quality. LIMITATIONS: Our review was limited to the last 5 years to inform current guideline updates. CONCLUSIONS: Few studies have examined antibiotic regimens currently being used in LMICs and quality is of concern in many studies. More high-quality data are needed to inform management of SBI in newborns, especially in LMICs.
Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Humans , Infant , Infant, Newborn , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/diagnosis , Systematic Reviews as Topic , Global Health , Developing Countries , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/therapy , Practice Guidelines as Topic , Sepsis/drug therapy , Sepsis/diagnosis , Sepsis/therapyABSTRACT
OBJECTIVES: Diagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population of children suspected of a central nervous system (CNS) infection, we performed external validation. METHODS: We performed a systematic literature review in Medline to identify articles on the development, refinement or validation of a prediction model for BM, and validated these models in a prospective cohort of children aged 0-18 years old suspected of a CNS infection. PRIMARY AND SECONDARY OUTCOME MEASURES: We calculated sensitivity, specificity, predictive values, the area under the receiver operating characteristic curve (AUC) and evaluated calibration of the models for diagnosis of BM. RESULTS: In total, 23 prediction models were validated in a cohort of 450 patients suspected of a CNS infection included between 2012 and 2015. In 75 patients (17%), the final diagnosis was a CNS infection including 30 with BM (7%). AUCs ranged from 0.69 to 0.94 (median 0.83, interquartile range [IQR] 0.79-0.87) overall, from 0.74 to 0.96 (median 0.89, IQR 0.82-0.92) in children aged ≥28 days and from 0.58 to 0.91 (median 0.79, IQR 0.75-0.82) in neonates. CONCLUSIONS: Prediction models show good to excellent test characteristics for excluding BM in children and can be of help in the diagnostic workup of paediatric patients with a suspected CNS infection, but cannot replace a thorough history, physical examination and ancillary testing.
Subject(s)
Central Nervous System Infections , Meningitis, Bacterial , Humans , Meningitis, Bacterial/diagnosis , Child , Prospective Studies , Central Nervous System Infections/diagnosis , Child, Preschool , Infant , Adolescent , Infant, Newborn , Area Under Curve , ROC Curve , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
The rapid and accurate diagnosis of meningitis is critical for preventing severe complications and fatalities. This study addresses the need for accessible diagnostics in the absence of specialized equipment by developing a novel diagnostic assay. The assay utilizes dual-priming isothermal amplification (DAMP) with unique internal primers to significantly reduce non-specificity. For fluorescence detection, the dye was selected among Brilliant Green, Thioflavin T, and dsGreen. Brilliant Green is preferred for this assay due to its availability, high fluorescence level, and optimal sample-to-background (S/B) ratio. The assay was developed for the detection of the primary causative agents of meningitis (Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae), and tested on clinical samples. The developed method demonstrated high specificity, no false positives, sensitivity comparable to that of loop-mediated isothermal amplification (LAMP), and a high S/B ratio. This versatile assay can be utilized as a standalone test or an integrated assay into point-of-care systems for rapid and reliable pathogen detection.
Subject(s)
Haemophilus influenzae , Meningitis, Bacterial , Molecular Diagnostic Techniques , Neisseria meningitidis , Nucleic Acid Amplification Techniques , Streptococcus pneumoniae , Neisseria meningitidis/genetics , Neisseria meningitidis/isolation & purification , Nucleic Acid Amplification Techniques/methods , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/isolation & purification , Humans , Haemophilus influenzae/genetics , Haemophilus influenzae/isolation & purification , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/microbiology , Molecular Diagnostic Techniques/methods , Sensitivity and SpecificityABSTRACT
Updating the vaccination recommendations against meningococci and pneumococci, in particular the introduction of the B vaccine as the standard vaccination for infants from January 2024 and the adaptation of the pneumococcal vaccination strategy for infants and adults aged 60 and over with the latest conjugate vaccines (PCV13, PCV15, PCV20).Emphasis on the need for rapid diagnostic lumbar puncture and simultaneous serum and cerebrospinal fluid analysis to increase diagnostic precision. The introduction of procalcitonin (PCT) in serum as an additional biomarker to differentiate between bacterial and viral meningitis.The use of multiplex PCR as a supplement, not a replacement, for standard diagnostics to speed up pathogen identification.Adaptation of antibiotic recommendations based on the current resistance situation, in particular for meningococcal meningitis, consideration of penicillin G only after resistance testing.Clarification of the areas and duration of use of dexamethasone in bacterial meningitis, particularly in pneumococcal meningitis and the controversial data situation in Listeria meningitis.New findings on the safe use of heparin in septic sinus thrombosis without increased risk of hemorrhage.
Subject(s)
Community-Acquired Infections , Meningoencephalitis , Humans , Community-Acquired Infections/diagnosis , Meningoencephalitis/diagnosis , Meningoencephalitis/microbiology , Anti-Bacterial Agents/therapeutic use , Infant , Practice Guidelines as Topic , Adult , Middle Aged , Meningitis, Bacterial/diagnosis , Procalcitonin/blood , Meningococcal Vaccines/therapeutic useABSTRACT
BACKGROUND Except for neonates, streptococci other than Streptococcus pneumoniae are a rare cause of acute bacterial meningitis. Streptococcus constellatus is a member of the Streptococcus anginosus group of gram-positive streptococci. It is a commensal microbe of the mucosae of the oral cavity, gastrointestinal tract, and urogenital tract. Rarely, it becomes pathogenic and causes contiguous or distant infections after mucosal damage. This report describes a 19-year-old immunocompetent man who developed bacterial meningitis, lung abscess, and brainstem infarct secondary to Streptococcus constellatus. CASE REPORT A 19-year-old immunocompetent man presented to the Emergency Department with a 4-week history of headache and neck pain. He was febrile on arrival. Physical examination revealed ataxia, upper-limb discoordination, and a positive Brudzinski sign. Cerebrospinal fluid and blood cultures were positive for Streptococcus constellatus, identified by matrix-assisted laser desorption ionization - time of flight mass spectrometry. Computed tomography of the chest demonstrated a lung abscess measuring 7×3.5×3 cm. A magnetic resonance imaging scan of the head revealed a 1.8×0.7 cm acute infarct in the right pons. The patient was treated initially with intravenous ceftriaxone and vancomycin before culture and sensitivity results, in addition to intravenous dexamethasone. After culture and sensitivities resulted, antibiotics were transitioned to a 4-week course of intravenous penicillin. The patient survived with no neurological consequences upon discharge. CONCLUSIONS Streptococcus constellatus should be suspected as an etiological agent for bacterial meningitis and other rare complications such as brainstem infarction and lung abscess, even in immunocompetent patients.
Subject(s)
Immunocompetence , Lung Abscess , Meningitis, Bacterial , Streptococcal Infections , Streptococcus constellatus , Humans , Male , Streptococcal Infections/diagnosis , Streptococcal Infections/complications , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Streptococcus constellatus/isolation & purification , Young Adult , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapy , Lung Abscess/microbiology , Lung Abscess/diagnosis , Brain Stem Infarctions , Anti-Bacterial Agents/therapeutic useABSTRACT
BACKGROUND: Meningitis can be caused by a variety of pathogenic microorganisms, which can lead to higher mortality and disability rates. However, the clinical manifestations of suppurative meningitis are often atypical in infants and young children, which makes early clinical diagnosis difficult.PAR and LAR are considered as a novel inflammatory biomarker and have been applied in tumors, IgA nephropathy, sepsis. OBJECTIVE: To investigate the application of platelet/albumin (PAR) and lactate dehydrogenase/albumin (LAR) in refractory suppurative meningitis in infants. METHODS: The relevant clinical data of 107 children with suppurative meningitis were retrospectively analyzed, and were divided into common group (82 cases) and refractory group (25 cases) according to the severity of the disease according to the relevant clinical consensus. The relevant clinical data and laboratory examination of the children in the two groups were compared. The diagnostic value of PAR and LAR in children with refractory suppurative meningitis was analyzed and multivariate Logistic regression analysis was performed. RESULT: The PAR of children with suppurative meningitis in refractory group was lower than that in common group (P < 0.05), while LAR was higher than that in common group (P < 0.05). Meanwhile, multivariate Logistic regression analysis showed that LAR and cerebrospinal fluid glucose ≤ 1.5mmo/L were risk factors for poor prognosis (OR > 1, P < 0.05). PAR was a protective factor (OR < 1, P < 0.05). CONCLUSION: PAR and LAR can be used for early diagnosis of refractory suppurative meningitis in children as protective and risk factors, respectively.
Subject(s)
Biomarkers , L-Lactate Dehydrogenase , Humans , Female , Male , Retrospective Studies , Infant , Biomarkers/blood , Biomarkers/cerebrospinal fluid , L-Lactate Dehydrogenase/blood , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/blood , Platelet Count , Prognosis , Risk Factors , Serum Albumin/analysis , Logistic ModelsSubject(s)
Meningitis, Bacterial , Recurrence , Humans , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/complications , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/etiology , Meningocele/diagnosis , Meningocele/complications , Meningocele/etiology , Encephalocele/diagnosis , Encephalocele/etiology , Female , Male , Surgical Wound Dehiscence/diagnosis , Surgical Wound Dehiscence/complications , Surgical Wound Dehiscence/etiology , Surgical Wound Dehiscence/microbiologyABSTRACT
Sensorineural hearing loss is a well-known complication of Streptococcus pneumoniae meningitis. Given the propensity for fibrosis and ossification of the cochlea in bacterial meningitis, implantation must be performed in a timely fashion because a delayed attempt at implantation can frustrate obtaining an optimal technical result or lead to an inability to implant. Obtaining optimal audiometric outcomes is reliant on early hearing screening in patients with streptococcal meningitis. In the absence of standardized protocols, audiometric testing is often overlooked or delayed in the workup and management of meningitis. Our institution implemented a meningitis protocol with a particular focus on timing of audiometric testing in patients with meningitis. We present a patient diagnosed with streptococcal meningitis in the first week of life. Early hearing screening allowed the diagnosis of profound unilateral sensorineural hearing loss and subsequent cochlear implantation at 10 weeks of age, the youngest described in the medical literature. Despite early implantation, there was cochlear fibrosis at the time of implantation. Fortunately, the majority of electrodes were implanted to achieve a serviceable hearing outcome. Serial magnetic resonance imaging scans were obtained because of her contralateral ventriculoperitoneal shunt that allowed unique visualization of the progression of cochlear fibrosis over time. This case demonstrates the importance of including audiometric testing in a standardized meningitis protocol to diagnose hearing loss in a timely and accurate way and to achieve optimal long-term hearing outcomes.
Subject(s)
Cochlear Implantation , Hearing Loss, Sensorineural , Humans , Female , Infant , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/diagnosis , Meningitis, Pneumococcal/complications , Meningitis, Pneumococcal/diagnosis , Audiometry , Meningitis, Bacterial/complications , Meningitis, Bacterial/diagnosis , Magnetic Resonance ImagingABSTRACT
Infection is a major cause of treatment-related morbidity and mortality in pediatric acute lymphoblastic leukemia (ALL). Most children with ALL who develop life-threatening bacterial infections do so during induction therapy. We describe a rare case of ALL presenting simultaneously with Streptococcus agalactiae group B Streptococcus bacteremia and meningitis in a 3-year-old girl. She received appropriate antimicrobial therapy and a 2-drug early induction regimen consisting of vincristine and dexamethasone, leading to slow neurologic recovery and a favorable initial response to anti-neoplastic therapy as evidenced by minimal residual disease of 1.12% on day 15 of induction.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Dexamethasone , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Streptococcal Infections , Streptococcus agalactiae , Humans , Female , Child, Preschool , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/diagnosis , Vincristine/administration & dosage , Vincristine/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Bacteremia/drug therapy , Bacteremia/microbiologyABSTRACT
BACKGROUND: Infectious 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. METHODS: Here 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). RESULTS: Our 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. CONCLUSIONS: This 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.
Subject(s)
Encephalitis , Humans , Prognosis , Child , Encephalitis/diagnosis , Encephalitis/microbiology , Encephalitis/virology , Encephalitis/drug therapy , Child, Preschool , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/drug therapy , Male , Female , Metagenomics/methods , Infant , High-Throughput Nucleotide Sequencing , RNA/geneticsABSTRACT
RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.
Subject(s)
Anti-Bacterial Agents , Scrub Typhus , Humans , Scrub Typhus/diagnosis , Scrub Typhus/drug therapy , Scrub Typhus/complications , Male , Adolescent , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Doxycycline/therapeutic use , Doxycycline/administration & dosage , Orientia tsutsugamushi/isolation & purification , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/microbiologyABSTRACT
A 43-year-old man was admitted to our department due to fever and headache. The cerebrospinal fluid analysis confirmed bacterial meningitis. Campylobacter species were isolated from blood cultures on the third day of admission. The patient was treated with meropenem (MEPM) and discharged on the 17th day. However, he experienced a recurrence of meningitis and was readmitted on the 68th day, initiating MEPM therapy. Campylobacter fetus was isolated from cerebrospinal fluid cultures on the 74th day. MEPM was continued until the 81st day, followed by one month of minocycline (MINO) therapy. The patient had an uneventful recovery without further recurrence. This case highlights the potential for recurrence of Campylobacter fetus meningitis approximately two months after the resolution of the initial infection. In addition to carbapenem therapy for at least two weeks, the adjunctive administration of MINO may be beneficial.
Subject(s)
Anti-Bacterial Agents , Campylobacter Infections , Campylobacter fetus , Meningitis, Bacterial , Meropenem , Minocycline , Recurrence , Humans , Male , Adult , Campylobacter fetus/isolation & purification , Campylobacter Infections/drug therapy , Campylobacter Infections/complications , Campylobacter Infections/diagnosis , Campylobacter Infections/microbiology , Meropenem/administration & dosage , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/diagnosis , Anti-Bacterial Agents/administration & dosage , Time Factors , Minocycline/administration & dosage , Treatment Outcome , Thienamycins/administration & dosage , Drug Therapy, CombinationABSTRACT
Acute pyogenic meningitis is a medical emergency. Bacteria are the major causative agents of pyogenic meningitis with Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis being the most common. Here, we describe a case of bacterial meningoencephalitis caused by Streptococcus porcinus. To our knowledge this is the first case described in literature. The patient was treated with ceftriaxone and supportive treatment.
Subject(s)
Anti-Bacterial Agents , Ceftriaxone , Meningoencephalitis , Streptococcal Infections , Streptococcus , Humans , Meningoencephalitis/microbiology , Meningoencephalitis/drug therapy , Meningoencephalitis/diagnosis , Anti-Bacterial Agents/therapeutic use , Streptococcal Infections/microbiology , Streptococcal Infections/drug therapy , Streptococcal Infections/diagnosis , Ceftriaxone/therapeutic use , Streptococcus/isolation & purification , Streptococcus/classification , Male , Treatment Outcome , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/diagnosisABSTRACT
Introduction: Streptococcus suis is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with S. suis can present with sepsis, meningitis, or arthritis. Compared to common pathogens, such as Meningococcus, Streptococcus pneumoniae, and Haemophilus influenzae, S. suis infections in humans have been reported only rarely. Methods: This case report described a 57-year-old man who presented with impaired consciousness and fever following several days of backache. He was a butcher who worked in an abattoir and had wounded his hands 2 weeks prior. The patient was dependent on alcohol for almost 40 years. S. suis was detected in the cerebrospinal fluid by metagenomic next-generation sequencing. Although he received adequate meropenem and low-dose steroid therapy, the patient suffered from bilateral sudden deafness after 5 days of the infection. The final diagnosis was S. suis meningitis and sepsis. Results: The patient survived with hearing loss in both ears and dizziness at the 60-day follow-up. Discussion: We reported a case of S. suis infection manifested as purulent meningitis and sepsis. Based on literature published worldwide, human S. suis meningitis shows an acute onset and rapid progression in the nervous system. Similar to bacterial meningitis, effective antibiotics, and low-dose steroids play important roles in the treatment of human S. suis meningitis.
Subject(s)
Meningitis, Bacterial , Streptococcal Infections , Streptococcus suis , Humans , Streptococcus suis/isolation & purification , Male , Middle Aged , Streptococcal Infections/drug therapy , China , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/diagnosis , Anti-Bacterial Agents/therapeutic use , Sepsis/drug therapy , Hearing Loss, Sudden/etiology , Hearing Loss, Sudden/drug therapyABSTRACT
A case of neonatal sepsis caused by Edwardsiella tarda, an uncommon pathogen typically associated with aquatic lifeforms, is described. The infant presented in septic shock with seizures and respiratory failure and was found to have meningitis, ventriculitis and a brain abscess requiring drainage. Only a small number of case reports of neonatal E. tarda infection, several with sepsis with poor auditory or neurodevelopmental outcomes or meningitis, have been described in the literature. This case report suggests that E. tarda, while uncommon, can be a cause of serious central nervous system disease in the neonatal population and that an aggressive approach to pursuing and treating complications may lead to improved neurodevelopmental outcomes.
Subject(s)
Brain Abscess , Cerebral Ventriculitis , Edwardsiella tarda , Enterobacteriaceae Infections , Neonatal Sepsis , Humans , Infant, Newborn , Anti-Bacterial Agents/therapeutic use , Brain Abscess/microbiology , Cerebral Ventriculitis/microbiology , Cerebral Ventriculitis/diagnosis , Cerebral Ventriculitis/drug therapy , Edwardsiella tarda/isolation & purification , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/complications , Enterobacteriaceae Infections/drug therapy , Meningitis/microbiology , Meningitis/diagnosis , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/complications , Neonatal Sepsis/microbiology , Neonatal Sepsis/diagnosisABSTRACT
Although vaccination and antimicrobial treatment have significantly impacted the frequency and outcomes of meningitis in children, meningitis remains a critical can't-miss diagnosis for children, where early recognition and appropriate treatment can improve survival and neurologic outcomes. Signs and symptoms may be nonspecific, particularly in infants, and require a high index of suspicion to recognize potential meningitis and obtain the cerebrospinal fluid studies necessary for diagnosis. Understanding the pathogens associated with each age group and specific risk factors informs optimal empirical antimicrobial therapy. Early treatment and developmental support can significantly improve the survival rates and lifelong neurodevelopment of children with central nervous system infections.
Subject(s)
Anti-Bacterial Agents , Humans , Child , Infant , Child, Preschool , Anti-Bacterial Agents/therapeutic use , Meningitis/diagnosis , Meningitis/therapy , Meningitis/etiology , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapy , Risk FactorsABSTRACT
Bacterial meningitis is an acute infection which requires rapid diagnosis and treatment due to the high mortality and serious consequences of the disease. The purpose of this study was to design a homemade multiplex PCR and a novel fluorescence biosensor on chip (FBC) to detect three important agents of meningitis including Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), and Haemophilus influenzae (H. influenzae). The homemade multiplex PCR can diagnose three bacterial species simultaneously. Fabrication of FBC was carried out based on the deposition of lead nanoparticles on a quartz slide using the thermal evaporation method. Then, the SH-Cap Probe/Target ssDNA /FAM-Rep probe was loaded on lead film. The evaluation of the fluorescence reaction when the probes bind to the target ssDNA was assessed by a Cytation 5 Cell Imaging Multimode Reader Bio-Tek. The limit of detections (LOD) in homemade PCR and FBC to identify S. pneumoniae were 119 × 102 CFU/mL (0.27 ng/µL) and 380 CFU/mL (9 pg/µL), respectively. The LODs of homemade PCR and FBC for detection of N. meningitidis were 4.49 CFU/mL (1.1 pg/µL) and 13 × 103 CFU/mL (30 pg/µL), respectively. Our results confirmed the LODs of homemade PCR and FBC in detection of H. influenzae were 15.1 CFU/mL (30 fg/µL) and 41 × 102 CFU/mL (90 pg/ µL), respectively. Both techniques had appropriate sensitivity and specificity in detection of S. pneumoniae, N. meningitidis and H. influenzae.
Subject(s)
Biosensing Techniques , Haemophilus influenzae , Meningitis, Bacterial , Multiplex Polymerase Chain Reaction , Neisseria meningitidis , Streptococcus pneumoniae , Neisseria meningitidis/isolation & purification , Neisseria meningitidis/genetics , Biosensing Techniques/methods , Streptococcus pneumoniae/isolation & purification , Streptococcus pneumoniae/genetics , Haemophilus influenzae/isolation & purification , Haemophilus influenzae/genetics , Humans , Multiplex Polymerase Chain Reaction/methods , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/microbiology , Limit of Detection , DNA, Bacterial/genetics , Sensitivity and SpecificityABSTRACT
BACKGROUND AND OBJECTIVES: Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. METHODS: This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. RESULTS: We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1ß, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1ß, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. CONCLUSION: The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition.
Subject(s)
Meningitis, Bacterial , Neutrophils , Humans , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/diagnosis , Retrospective Studies , Prognosis , Female , Male , Adult , Middle Aged , Case-Control Studies , Peroxidase/cerebrospinal fluid , Aged , Biomarkers/cerebrospinal fluid , Young AdultABSTRACT
Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.