A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

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.

Triad of Terror: Rapidly Progressive Austrian Syndrome in a 62-Year-Old Female.

We report a case of a 62-year-old female presenting with shortness of breath, who was subsequently diagnosed with Austrian syndrome. The patient had a complicated clinical course, including invasive central nervous system pneumococcal disease, pneumococcal bacteremia, and mitral valve vegetation with possible leaflet perforation. Despite aggressive treatment, her condition continued to worsen. We will discuss the clinical features of this disease, approaches to diagnosis and treatment, and outcomes in light of this rare condition.

Takotsubo cardiomyopathy in a 4-year-old female with pneumococcal meningitis.

A previously healthy 4-year-old female presented in cardiogenic shock with pneumococcal meningitis. Findings on echocardiogram raised suspicion for takotsubo cardiomyopathy. With supportive care, left ventricular systolic function normalised. Findings on cardiac imaging helped determine the aetiology and avoid further invasive studies or unnecessary treatment.

Healthy adults with Streptococcus pneumoniae meningitis and Streptococcus pneumoniae subdural abscess: two case reports and a literature review.

We present the cases of two otherwise healthy adults, one with meningitis and another with a subdural abscess, with both conditions attributable to Streptococcus pneumoniae. A 31-year-old man was admitted with a 3-day history of fever, headache, and vomiting. Physical examination revealed intermittent confusion, irritability, and neck stiffness. Cerebrospinal fluid (CSF) culture was positive for S. pneumoniae. Contrast-enhanced magnetic resonance imaging (C-MRI) revealed multiple small lesions on the bilateral frontal lobes. Intravenous ceftriaxone and vancomycin were administered, followed by intravenous moxifloxacin. His symptoms resolved within 3 months. Additionally, a 66-year-old man was admitted for acute fever with confusion, abnormal behavior, and a recent history of acute respiratory infection. Physical examination revealed confusion, neck stiffness, and a positive right Babinski sign. CSF metagenomic analysis detected S. pneumoniae. C-MRI disclosed left occipitotemporal meningoencephalitis with subdural abscesses. Intravenous ceftriaxone was administered for 3 weeks. His condition gradually improved, with resorbed lesions detected on repeat MRI. This study expanded the clinical and imaging spectra of S. pneumoniae meningitis. In healthy adults, S. pneumoniae can invade the brain, but subdural abscess is a rare neuroimaging manifestation. Early diagnosis of S. pneumoniae meningitis by high-throughput sequencing and flexible treatment strategies are necessary for satisfactory outcomes.

A Challenging Case of Streptococcus pneumoniae Meningitis in a 64-Year-Old Woman Who Presented with Symptoms of Cerebellar Hemorrhage.

BACKGROUND There is a recognized association between bacterial meningitis and intracranial hemorrhage. However, acute neurological symptoms at presentation, with confirmation of hemorrhage on imaging, may delay further investigations, including blood culture for diagnosing an infection. This report presents a challenging case of Streptococcus pneumoniae meningitis in a 64-year-old woman who presented with symptoms of cerebellar hemorrhage. CASE REPORT This report describes a 64-year-old woman who had a medical history of untreated diabetes mellitus. She was brought to our hospital with headache and impaired consciousness, complicated with fever. Based on the hemorrhage in the left cerebellar hemisphere detected in the head CT findings, the patient was initially diagnosed with cerebellar hemorrhage. However, a positive blood culture after 12 hours of admission made the physician consider a central nervous system infection as the cause of the hemorrhage and perform a lumbar puncture. Therefore, the patient was diagnosed with acute bacterial meningitis caused by Streptococcus pneumoniae, and antibiotic treatment was started immediately. Although her general condition improved after antibiotic treatment, her mental status did not improve completely. CONCLUSIONS This report highlights that the clinicians should be aware that bacterial meningitis may result in intracranial hemorrhage. Patients with symptoms of a hemorrhagic stroke should be thoroughly investigated to avoid a delay in the treatment of infection.

Rapid progressive destruction of the cochleae in an infant due to pneumococcal meningitis.

The widespread adoption of pneumococcal conjugate vaccines has reduced the incidence of Streptococcus pneumoniae infections, but has also led to the emergence of infections due to non-vaccine serotypes. A 15-month-old girl was referred to our hospital with suspected meningitis. S. pneumoniae was isolated from her cerebrospinal fluid. She was initially treated with a combination of cefotaxime and vancomycin, followed by ampicillin and vancomycin. After 7 days, the patient's condition improved and she was transferred to the general ward; however, her mother noted signs of hearing difficulties. On the 16th day of admission, we performed an auditory brainstem response test, which suggested severe bilateral hearing impairment. This was confirmed using an auditory steady-state response test after consulting with otolaryngologists. Magnetic resonance imaging revealed fibrosis of both cochleae with labyrinthitis. The patient underwent emergency cochlear implantation at a different hospital. The S. pneumoniae isolate was later identified to be serotype 10A with a PBP2x mutation, which is not covered by the conjugate vaccine and has reduced cephalosporin susceptibility. This case was characterized by highly rapid cochlear destruction, and an earlier otolaryngologist consultation may have provided a more well-organized surgery plan. Pediatricians are urged to promptly consult with otolaryngologists for patients with similar indications.

Clinical Features and Outcomes of Streptococcus pneumoniae Meningitis in Children: A Retrospective Analysis of 26 Cases in China.

BACKGROUND: Streptococcus pneumoniae is an important cause of pediatric meningitis. OBJECTIVE: The aim of this study was to analyze the clinical features and outcomes of children with pneumococcal meningitis at our hospital in China, so as to provide basis for improving the clinical treatment effect. METHODS: This retrospective analysis included patients aged <16 years treated for pneumococcal meningitis at the Department of Neurology, Children's Hospital of Shanxi (January 2014-February 2016). Clinical data were extracted from the medical records. Patients were followed up for 6 months after discharge. RESULTS: The analysis included 26 children aged 2 months to 13 years, with 17 (65.4%) aged <3 years. Presenting symptoms included fever (100%), lethargy (100%), impaired consciousness (88.5%), neck stiffness (69.2%), seizures (53.8%), and headache (50.0%). All patients had positive cerebrospinal fluid (CSF) cultures. The final treatment was vancomycin combined with a third-generation cephalosporin or other antibiotics in 25 patients. Eleven patients (42.3%) were recovered, 3 (11.5%) had neurological sequelae, and 12 (46.2%) died. Impaired consciousness (p = 0.035), cerebral hernia (p = 0.037), respiratory failure (p = 0.004), heart failure (p = 0.044), septic shock (p = 0.037), low CSF white blood cell count (p = 0.036), high CSF protein levels (p = 0.028), low white blood cell count (p = 0.036), and low blood neutrophil ratio (p = 0.016) are associated with a poor prognosis to pneumococcal meningitis. CONCLUSION: Pneumococcal meningitis is associated with a poor prognosis in many children. Poor prognosis might be related to early ineffective antibiotic therapy, a combination of systemic failure, neurological problems, and changed inflammatory response. It is important to rapid initiation of appropriate antibiotic therapy if meningitis is suspected.

Delayed cerebral thrombosis complicating bacterial meningitis.

BACKGROUND: Delayed cerebral thrombosis has been described as a potential cause of cerebrovascular complications in patients with bacterial meningitis. We report a case of delayed cerebral thrombosis in a 63-year-old woman admitted for pneumococcal meningitis. Initially, there was a good clinical evolution under treatment with steroids and antibiotics. On day 8 after admission, she was found with a decreased level of consciousness. Her neurological condition gradually worsened. Repeated brain imaging showed extensive ischemic lesions. Despite treatment with high-dose corticosteroids, the patient died. METHODS: A literature search was conducted. Data on patient characteristics, diagnosis, treatment and outcome were collected. RESULTS: To date, 28 cases with delayed cerebral thrombosis following bacterial meningitis have been reported. Streptococcus pneumoniae was the pathogen in 89% of cases. Clinical deterioration occurred in all patients, with a duration varying from 5 to 40 days between admission and deterioration. Most common symptom was altered consciousness (83%), followed by hemiparesis (52%). Brain imaging typically shows new infarctions (96%). Fifty-six percent of patients were treated with corticosteroids after deterioration. Outcome was poor with mortality rate of 46%. CONCLUSION: Delayed cerebral thrombosis presents as a clinical deterioration, typically a sudden decline in consciousness, more than 5 days after meningitis onset. Brain imaging shows new widespread ischemic lesions. Diagnosis should be made carefully, based on clinical findings and brain imaging, after excluding endocarditis. The underlying etiology remains unknown. When delayed cerebral thrombosis is suspected, high-dose corticosteroids should be started empirically. The prognosis remains poor with high mortality rates.

Recognition and Outcomes of Pneumococcal Meningitis in 2 Tertiary Pediatric Hospitals Since the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine.

OBJECTIVES: The aims of the study were to analyze the demographics, presentation, laboratory findings, and complications of pediatric Streptococcus pneumoniae meningitis since the introduction of the 13-valent pneumococcal conjugate vaccine, to improve recognition, and to minimize patient morbidity and mortality. METHODS: This study used a retrospective analysis of pediatric pneumococcal meningitis cases at 2 tertiary healthcare systems in the Southeastern United States from 2010 to 2018. RESULTS: We describe 21 cases of pneumococcal meningitis. All patients presented with fever, 95% had altered mental status by history or examination, and 48% had meningeal signs. Forty-three percent had seen another provider within 48 hours of admission. Forty-eight percent had delay in lumbar puncture (LP) of more than 6 hours after antibiotic administration, decreasing rates of positive cerebrospinal fluid cultures from 100% to 40% (P < 0.001). Decision to delay LP was due to either low suspicion for meningitis (n = 4) or clinical instability (n = 6) and was associated with lower rates of meningeal signs (P = 0.014) and higher rates of altered mental status on examination (P = 0.031). Fourteen patients (67%) were up-to-date on pneumococcal immunization. Serotypes were determined in 16 cases, with 2 patients (13%) immunized against the strain that infected them. Primary outcomes included seizures (48%), hearing loss (48%), cranial nerve palsy (33%), and death (5%). Delay in LP with low suspicion for meningitis was associated with longer hospital length of stay approaching statistical significance (P = 0.053). CONCLUSIONS: Pneumococcal meningitis remains a relevant and potentially fatal disease despite widespread use of 13-valent pneumococcal conjugate vaccine. Its diagnosis is often delayed during interactions with physicians, which may put patients at increased risk for poor clinical outcomes.

Comparison of Culture, Antigen Test, and Polymerase Chain Reaction for Pneumococcal Detection in Cerebrospinal Fluid of Children.

BACKGROUND: Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance. METHODS: CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested. RESULTS: Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for >10 weeks. CONCLUSIONS: While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.

Serum cytokine profile of pediatric patients with laboratory confirmed pneumococcal meningitis.

BACKGROUND: Streptococcus pneumoniae infection is a leading cause of bacterial meningitis in children with severe sequelae. Cytokines are important molecules in regulating of host inflammatory and anti-inflammatory responses. So far, the cytokine profile of bacterial meningitis caused by single pathogen has been rarely reported. The aim of this study was to explore serum cytokine profile in pediatric patients with pneumococcal meningitis (PM) and its clinical relevance which could be considered as a valuable tool for differential diagnosis of PM. METHODS: During 2015-2018, 95 children with laboratory-confirmed PM were included. Of them, 63 had serum samples at admission. Ten cytokines including TNF-α, IL-12p40, IL-17A, IL-1ß, IFN-γ, GM-CSF, IL-10, CXCL-1, IL-8 and IL-13 were measured by multiplex immunoassay in sera of 63 PM patients and 55 age-matched healthy controls (HCs). Level of serum cytokines was compared with different clinical features of patients. RESULTS: Significantly higher level of IL-10 was observed in patients than HCs (median, 2.19 vs. 1.92 pg/mL, p = 0.017). Significantly lower levels of serum IL-12p40, IL-17A and IL-1ß were observed in patients than HCs (median, 0.68 vs. 10.12 pg/mL, p < 0.0001; 1.14 vs. 1.14 pg/mL, p = 0.004; 1.00 vs. 5.09 pg/mL, p < 0.0001, respectively). No difference was found in levels of other cytokines between patients and controls. A negative correlation was noticed between percentages of blood neutrophils and concentrations of IL-10 (p = 0.048, r = -0.25). Significantly lower levels of IL-12p40 and CXCL-1 were observed in PM patients with sepsis than those without (median 0.68 vs. 1.64 pg/mL, p = 0.026; 7.25 vs. 12.84 pg/mL, p = 0.043, respectively). CONCLUSIONS: Our results suggested that there might be significant changes in serum pro-inflammatory and anti-inflammatory cytokines in PM children and that the determination of these cytokines may have limited value for evaluation of clinical outcome of pediatric PM.

Oval window perilymph fistula in child with recurrent meningitis and unilateral hearing loss.

A 2-year-old boy presented to Ears, Nose and Throat (ENT) surgeons with unilateral hearing loss. Following a prodrome of upper respiratory tract infection (URTI), he developed two episodes of pneumococcal meningitis in quick succession. This case demonstrates an unusual cause of perilymph fistula diagnosed on imaging and confirmed surgically. He had failed the Newborn Hearing Screening Programme and was therefore referred to audiology, who confirmed profound sensorineural hearing loss in the right ear. MRI showed incomplete partitioning (type 1) of the right cochlea, suggesting cerebrospinal fluid (CSF) leak from the region of the stapes. Exploratory tympanotomy confirmed this, and proceeded to CSF leak repair, obliteration of the Eustachian tube, subtotal petrosectomy, abdominal fat grafting and blind sac closure. Although middle ear effusions are common; particularly in children with recent URTI, the possibility of otogenic CSF leak needs to be considered, especially in cases of recurrent meningitis.

Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage.

Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.

Medullary Infarction Leading to Locked-In Syndrome Following Lumbar Puncture in a Patient with Basilar Invagination.

BACKGROUND: Lumbar puncture is a common procedure that can be safely performed in most patients. Certain populations may have increased risk for complications following lumbar puncture, but the significance of basilar invagination is often underappreciated. CASE DESCRIPTION: A 45-year-old woman with basilar invagination received multiple lumbar punctures in the workup of acute meningitis. Preprocedural computed tomography was obtained. Following lumbar puncture, the patient developed locked-in syndrome. Magnetic resonance imaging obtained several days later demonstrated severe compression and infarction of the medulla and inferior cerebellum by the odontoid process and ectopic cerebellar tonsils. The patient was transferred but at this point, surgical decompression was not possible. She did not regain significant neurologic function. CONCLUSIONS: Basilar invagination is a risk factor for devastating neurologic complications following lumbar puncture. Awareness of this complication and prompt recognition of its occurrence may prevent future morbidity of lumbar puncture in patients with basilar invagination.

Diagnostic Yield of Pneumococcal Antigen Detection in Cerebrospinal Fluid for Diagnosis of Pneumococcal Meningitis Among Children in China.

OBJECTIVE: To determine the diagnostic accuracy of pneumococcal antigen detection in diagnosis of pneumococcal meningitis in children. METHODS: Purulent meningitis was diagnosed according to European Society for Clinical Microbiology and Infectious Diseases (ESCMID) guideline between July 2014 and June 2016. Along with a cerebrospinal fluid (CSF) culture, pneumococcal antigen detection in cerebrospinal fluid (CSF) was performed, and further identification of pathogens was done with 16S rDNA-PCR and high-throughput sequencing. RESULTS: CSF samples collected from 184 children (median age of 1.92 mo). CSF culture was used as the gold standard. 46 (25%) had positive results for culture and 10 (5.4%) were pneumococci; 34 (18.5%) were pneumococcal antigen positive. The sensitivity and specificity of pneumococcal antigen detection were 100% (95% CI: 89.4%-100%) and 86.2% (95% CI: 96.4%-99.9%), respectively. 92.3% (12/13) were confirmed by nucleic acid detection to be pneumococci. CONCLUSIONS: Pneumococcal antigen detection in CSF has adequate sensitivity and specificity in diagnosing pneumococcal meningitis.