ABSTRACT
CONTEXT: Meningitis is associated with high mortality risk in young infants, yet the optimal treatment regimen is unclear. OBJECTIVES: To systematically evaluate the efficacy of antibiotic regimens to treat meningitis in young infants aged 0 to 59 days on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, WHO Global Index Medicus, and Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials (RCTs) of young infants with meningitis (population) comparing the efficacy of antibiotic regimens (interventions) with alternate regimens (control) on clinical outcomes. DATA EXTRACTION: We extracted data on study characteristics and assessed risk of bias in duplicate. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty of evidence. RESULTS: Of 1088 studies screened, only 2 RCTs were identified. They included 168 infants from 5 countries and were conducted between 1976 and 2015. Neither study compared current World Health Organization-recommended regimens. One multisite trial from 4 countries compared intrathecal gentamicin plus systemic ampicillin/gentamicin to systemic ampicillin/gentamicin and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or adverse events (no events in either trial arm). Another trial in India compared a 10-day versus 14-day course of antibiotics and found no difference in mortality (relative risk, 0.88; 95% confidence interval, 0.41-1.53; 1 trial, n = 98, very low certainty of evidence) or other outcomes. CONCLUSIONS: Trial data on the efficacy of antibiotic regimens in young infant meningitis are scarce. Rigorous RCTs are needed to inform recommendations for optimal antibiotic regimens for meningitis treatment in this vulnerable population, particularly within the context of changing epidemiology and increasing antimicrobial resistance.
Subject(s)
Anti-Bacterial Agents , Meningitis, Bacterial , Humans , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Infant , Infant, Newborn , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/mortality , Randomized Controlled Trials as Topic , Treatment Outcome , Gentamicins/therapeutic use , Gentamicins/administration & dosageABSTRACT
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
Importance: The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain. Objective: To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis. Data Sources: Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality. Study Selection: Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care-associated meningitis, tuberculous meningitis, or missing outcome were excluded. Data Extraction and Synthesis: Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period's year as an estimator variable were used. Main Outcome and Measure: Case fatality ratios of bacterial meningitis. Results: This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157â¯656 episodes. Of the 33â¯295 episodes for which the patients' sex was reported, 13â¯452 (40%) occurred in females. Causative pathogens were reported in 104â¯598 episodes with Neisseria meningitidis in 26â¯344 (25%) episodes, Streptococcus pneumoniae in 26â¯035 (25%) episodes, Haemophilus influenzae in 22â¯722 (22%), other bacteria in 19â¯161 (18%) episodes, and unidentified pathogen in 10â¯336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli, or Streptococcus agalactiae (P < .001). Conclusions and Relevance: In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained.
Subject(s)
Meningitis, Bacterial , Humans , Meningitis, Bacterial/mortality , Meningitis, Bacterial/epidemiology , Global Health/statistics & numerical data , Community-Acquired Infections/mortality , Community-Acquired Infections/microbiology , Female , Male , Risk Factors , AdultABSTRACT
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 poses a significant challenge to public health in low-income nations, such as Ethiopia, with a particular impact on newborns. The magnitude and etiologies of meningitis vary based on geographic location and age of patients. There is limited data regarding the magnitude and etiology of meningitis from Sidama Regional State, Ethiopia. This study aimed to determine the magnitude and bacterial profile of meningitis among newborns aged less than 90 days at Hawassa University Comprehensive Specialized Hospital (HUCSH). METHODS: A retrospective cross-sectional study was conducted among newborns under 90 days who were suspected of meningitis at HUCSH from January 2019 to July 2023, and for whom Cerebrospinal fluid (CSF) culture was performed. At HUCSH, bacteria are isolated and identified using standard microbiological techniques. Socio-demographic characteristics and culture results were extracted from the laboratory register. Data were entered into Excel and exported it to SPSS version 20 for analysis. RESULTS: Overall 1061 newborns suspected of meningitis were included in the study. Among the participants, 767 individuals (72.3%) fell within the age range of 8 to 90 days. Of the total participants, 437 (41.2%) were females. The magnitude of culture-confirmed meningitis was 90(8.5%) 95% CI: 6.8%-10.1%. The magnitude of culture-confirmed meningitis among newborns aged 0-7 days and 8-90 days were 1.6% and 6.9% respectively. The proportion of bacteria among newborns aged 0-7 days and 8-90 days were 18.9% and 81.1% respectively. Coagulase-negative Staphylococci (CONS) were the most common bacteria (n = 26; 28.9%) recovered followed by Acinetobacter species (n = 12, 13.3%), Escherichia coli (n = 9; 10%), and Klebsiella pneumoniae (n = 7; 7.8%). K. pneumoniae was the predominant bacteria among newborns within the age group of 0 to 7 days while Acinetobacter species was the most common among newborns within the 8 to 90 days age group. The prevalence of culture-confirmed neonatal meningitis was found to be greater in male newborns (x2 = 1.74, p = 0.18), newborns aged between 8 to 90 days (x2 = 0.07, p = 3.4), and newborns admitted in 2022 (x2 = 2.4, p = 0.66). CONCLUSIONS: In this study, the overall magnitude of culture-confirmed meningitis was relatively high. Culture-confirmed meningitis was high in newborns within the age range of 8 to 90 days. The most common bacteria were CONS in both age groups followed by Acinetobacter species, E. coli, and K. pneumoniae.
Subject(s)
Meningitis, Bacterial , Humans , Ethiopia/epidemiology , Infant, Newborn , Female , Male , Infant , Cross-Sectional Studies , Retrospective Studies , Meningitis, Bacterial/epidemiology , Meningitis, Bacterial/microbiology , Hospitals, University , Hospitals, Special , Bacteria/isolation & purification , Bacteria/classificationABSTRACT
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
Streptococcus suis (S. suis) is an important gram-positive pathogen and an emerging zoonotic pathogen that causes meningitis in swine and humans. Although several virulence factors have been characterized in S. suis, the underlying mechanisms of pathogenesis are not fully understood. In this study, we identified Zinc metalloproteinase C (ZmpC) probably as a critical virulence factor widely distributed in S. suis strains. ZmpC was identified as a critical facilitator in the development of bacterial meningitis, as evidenced by the detection of increased expression of TNF-α, IL-8, and matrix metalloprotease 9 (MMP-9). Subcellular localization analysis further revealed that ZmpC was localized to the cell wall surface and gelatin zymography analysis showed that ZmpC could cleave human MMP-9. Mice challenge demonstrated that ZmpC provided protection against S. suis CZ130302 (serotype Chz) and ZY05719 (serotype 2) infection. In conclusion, these results reveal that ZmpC plays an important role in promoting CZ130302 to cause mouse meningitis and may be a potential candidate for a S. suis CZ130302 vaccine.
Subject(s)
Meningitis, Bacterial , Serogroup , Streptococcal Infections , Streptococcus suis , Swine Diseases , Streptococcus suis/pathogenicity , Streptococcus suis/enzymology , Animals , Streptococcal Infections/veterinary , Streptococcal Infections/microbiology , Swine , Swine Diseases/microbiology , Mice , Meningitis, Bacterial/veterinary , Meningitis, Bacterial/microbiology , Female , Virulence Factors/metabolism , Virulence Factors/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Humans , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Mice, Inbred BALB C , Metalloendopeptidases/metabolism , Metalloendopeptidases/geneticsABSTRACT
BACKGROUND: Bacterial meningitis can cause a life-threatening increase in intracranial pressure (ICP). ICP-targeted treatment including an ICP monitoring device and external ventricular drainage (EVD) may improve outcomes but is also associated with the risk of complications. The frequency of use and complications related to ICP monitoring devices and EVDs among patients with bacterial meningitis remain unknown. We aimed to investigate the use of ICP monitoring devices and EVDs in patients with bacterial meningitis including frequency of increased ICP, drainage of cerebrospinal fluid (CSF), and complications associated with the insertion of ICP monitoring and external ventricular drain (EVD) in patients with bacterial meningitis. METHOD: In a single-center prospective cohort study (2017-2021), we examined the frequency of use and complications of ICP-monitoring devices and EVDs in adult patients with bacterial meningitis. RESULTS: We identified 108 patients with bacterial meningitis admitted during the study period. Of these, 60 were admitted to the intensive care unit (ICU), and 47 received an intracranial device (only ICP monitoring device N = 16; EVD N = 31). An ICP > 20 mmHg was observed in 8 patients at insertion, and in 21 patients (44%) at any time in the ICU. Cerebrospinal fluid (CSF) was drained in 24 cases (51%). Severe complications (intracranial hemorrhage) related to the device occurred in two patients, but one had a relative contraindication to receiving a device. CONCLUSIONS: Approximately half of the patients with bacterial meningitis needed intensive care and 47 had an intracranial device inserted. While some had conservatively correctable ICP, the majority needed CSF drainage. However, two patients experienced serious adverse events related to the device, potentially contributing to death. Our study highlights that the incremental value of ICP measurement and EVD in managing of bacterial meningitis requires further research.
Subject(s)
Critical Care , Drainage , Intracranial Pressure , Meningitis, Bacterial , Humans , Male , Middle Aged , Female , Intracranial Pressure/physiology , Drainage/methods , Drainage/adverse effects , Adult , Aged , Prospective Studies , Critical Care/methods , Cohort Studies , Monitoring, Physiologic/methods , Intracranial Hypertension/surgery , Ventriculostomy/methods , Ventriculostomy/adverse effectsABSTRACT
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
BACKGROUND: Bacterial meningitis (BM) poses a serious threat to infant health. We assessed cranial ultrasound (CUS) changes in infants with BM as possible predictors of the neurological sequelae of BM. METHODS: We retrospectively assigned 132 infants diagnosed with BM from 2007 to 2021. Neuroimaging characteristics and cerebral blood flow (CBF) profiles identified using CUS were analysed and compared between the groups during the acute and postacute phases of BM. RESULTS: Overall, 102 infants with CUS and outcome data were recruited. 37/102 (36.3%) infants with neurological developmental impairments comprised the group with sequelae. Abnormal CUS findings increased the risk of sequelae during the postacute phase compared with the acute phase of BM. Prolonged white matter hyperechogenicity was an independent risk factor for sequelae. The CBF profiles of the group with sequelae showed that anterior cerebral artery resistance and pulsatility indices decreased during the acute phase, whereas the mean flow velocity of the middle cerebral artery significantly increased during the postacute phase. Changes in the CBF profiles did not significantly differ in the group without sequelae. CONCLUSIONS: Serial CUS can facilitate the prognostic assessment of infants aged <90 days with BM. Prolonged white matter hyperechogenicity, brain volume loss and cerebral perfusion disorders contribute to the risk of sequelae.
Subject(s)
Meningitis, Bacterial , Humans , Meningitis, Bacterial/diagnostic imaging , Meningitis, Bacterial/physiopathology , Retrospective Studies , Male , Female , Infant , Prognosis , Infant, Newborn , Cerebrovascular Circulation/physiology , Echoencephalography , Brain/diagnostic imaging , Brain/pathology , Ultrasonography/methodsABSTRACT
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 man in his 40s with type 2 diabetes mellitus had persistent right-sided watery nasal discharge for 6 months following cerebrospinal fluid (CSF) leak repair at another hospital, prompting his visit to us due to recurring symptoms. Imaging revealed a CSF leak from the mid-clivus for which revision endoscopic CSF leak repair was done. Regrettably, he developed postoperative meningitis caused by multidrug-resistant (MDR) Klebsiella pneumoniaeManaging this complex case was a challenging task due to the pathogen's resistance to conventional drugs and the scarcity of scientific evidence. We initiated a culture-guided combination regimen with ceftazidime, avibactam, aztreonam and tigecycline. This decision stemmed from meticulous literature review and observed antibiotic synergy while testing for this organism.After 4 weeks of vigilant treatment, the patient's symptoms improved significantly, and CSF cultures were sterile. We present our approach to effectively confront and manage a challenging instance of postoperative MDR bacterial meningitis.
Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Klebsiella Infections , Klebsiella pneumoniae , Meningitis, Bacterial , Humans , Male , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/microbiology , Anti-Bacterial Agents/therapeutic use , Cerebrospinal Fluid Leak/therapy , Adult , Postoperative Complications/drug therapy , Postoperative Complications/microbiology , Ceftazidime/therapeutic use , Ceftazidime/administration & dosage , Cranial Fossa, Posterior/surgery , Aztreonam/therapeutic use , Aztreonam/administration & dosage , Tigecycline/therapeutic use , Tigecycline/administration & dosage , Drug Combinations , Azabicyclo CompoundsABSTRACT
Background: Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200 children with suspected meningitis were admitted to hospital in Halabja Governorate, Iraq. No outbreak of meningitis had been reported previously in that region. Aims: To investigate the aetiology and epidemiology of meningitis among children in Halabja Governorate, Iraq, and expedite clinical management and prevention. Methodology: Blood and cerebrospinal fluid specimens were collected from 197 children admitted to Halabja Paediatric and Maternity Teaching Hospital from 1 March to 1 July 2023 and analysed. The sample t-test was used to compare the haematological, serological and biochemical characteristics of the samples. Results: The majority (76.6%) of the children were aged 2-9 years and 54% were males. The clinical manifestations of the disease were fever (100.0%), headache (89.0%), vomiting (85.7%), and photophobia (72.4%); none of the children had convulsions. The mean values for both neutrophil count and C-reactive protein were statistically significantly raised (P < 0.05) and the red blood cells, white blood cells and neutrophil counts, and lactate dehydrogenase values were statistically significantly raised (P < 0.05). The causative organism was enterovirus (98.5%), with sporadic cases of streptococcal meningitis (1.5%). All the patients recovered fully. Conclusion: The rapid diagnosis of the disease was crucial to the therapeutic and prevention control measures for the outbreak. Although it is still unclear how and where this outbreak started, contaminated drinking water and transmission among children in nurseries and schools are suspected. Further investigations are recommended to determine the source of the enterovirus and identify the virus species and serotypes.