Community-Acquired Meningitis Complicated With Pyogenic Ventriculitis and Hydrocephalus in a Patient With Haematological Malignancy: A Case Report and Literature Review.

Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It may become complicated by conditions such as hydrocephalus, ventriculitis, and cerebral abscess. Here, we describe a case of meningitis that was complicated by pyogenic ventriculitis and hydrocephalus in a patient with diffuse large B-cell lymphoma (DLBCL) who underwent chemotherapy and radiotherapy. The patient presented with acute change in mental status and high-grade fever, with few episodes of non-bloody vomiting. Blood culture and cerebrospinal fluid (CSF) culture grew Streptococcus pneumoniae, which was sensitive to ceftriaxone. CT scan of the head showed ventriculomegaly, pansinusitis, and a large left mastoid effusion. MRI of the brain showed layering in ventricles, hydrocephalus, and dural enhancement consistent with pachymeningitis. She was treated with ceftriaxone for 21 days with a meaningful outcome. She was discharged home with near-baseline mental capacity for further physical therapy.

A 30-year perspective of low-dose dexamethasone, a single dose of mannitol and antiseizures prophylaxis on the prognosis of pneumococcal meningitis.

OBJECTIVES: This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis. METHODS: Data have been prospectively collected for the period1977-2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5-1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin. RESULTS: In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000). CONCLUSIONS: A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.

Effect of the COVID-19 pandemic on clinical characteristics and outcomes of adult pneumococcal meningitis patients - a Dutch prospective nationwide cohort study.

PURPOSE: To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic. METHODS: In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model. RESULTS: We included 1,699 patients in 2006-2020, 50 patients in 2020-2021, and 182 patients in 2021-2023. After March 2020 relatively more alcoholism was reported (2006-2020, 6.1%; 2020-2021, 18%; 2021-2023, 9.7%; P = 0.002) and otitis-sinusitis was less frequently reported (2006-2020, 45%; 2020-2021, 22%; 2021-2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006-2020, 89%; 2020-2021, 74%; 2021-2022, 86%; P = 0.002) and outcomes were worse ('good recovery', 2020-2021, OR 0.5, 95% CI 0.3-0.8). CONCLUSION: During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality.

Adjunctive treatments for pneumococcal meningitis: a systematic review of experimental animal models.

New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal meningitis in order to identify treatments with the most potential to progress to clinical trials. Studies testing therapy adjunctive to antibiotics in animal models of pneumococcal meningitis were included. A literature search was performed using Medline, Embase and Scopus for studies published from 1990 up to 17 February 2023. Two investigators screened studies for inclusion and independently extracted data. Treatment effect was assessed on the clinical parameters disease severity, hearing loss and cognitive impairment and the biological parameters inflammation, brain injury and bacterial load. Adjunctive treatments were evaluated by their effect on these outcomes and the quality, number and size of studies that investigated the treatments. Risk of bias was assessed with the SYRCLE risk of bias tool. A total of 58 of 2462 identified studies were included, which used 2703 experimental animals. Disease modelling was performed in rats (29 studies), rabbits (13 studies), mice (12 studies), gerbils (3 studies) or both rats and mice (1 study). Meningitis was induced by injection of Streptococcus pneumoniae into the subarachnoid space. Randomization of experimental groups was performed in 37 of 58 studies (64%) and 12 studies (12%) were investigator-blinded. Overall, 54 treatment regimens using 46 adjunctive drugs were evaluated: most commonly dexamethasone (16 studies), daptomycin (5 studies), complement component 5 (C5; 3 studies) antibody and Mn(III)tetrakis(4-benzoicacid)porphyrin chloride (MnTBAP; 3 studies). The most frequently evaluated outcome parameters were inflammation [32 studies (55%)] and brain injury [32 studies (55%)], followed by disease severity [30 studies (52%)], hearing loss [24 studies (41%)], bacterial load [18 studies (31%)] and cognitive impairment [9 studies (16%)]. Adjunctive therapy that improved clinical outcomes in multiple studies was dexamethasone (6 studies), C5 antibodies (3 studies) and daptomycin (3 studies). HMGB1 inhibitors, matrix metalloproteinase inhibitors, neurotrophins, antioxidants and paquinimod also improved clinical parameters but only in single or small studies. Evaluating the treatment effect of adjunctive therapy was complicated by study heterogeneity regarding the animal models used and outcomes reported. In conclusion, 24 of 54 treatment regimens (44%) tested improved clinically relevant outcomes in experimental pneumococcal meningitis but few were tested in multiple well-designed studies. The most promising new adjunctive treatments are with C5 antibodies or daptomycin, suggesting that these drugs could be tested in clinical trials.

Rapidly Progressive Fatal Pneumococcal Meningitis in a Fully Immunized Child With a History of Facial Bone Fractures.

Meningitis is the inflammation of meninges either septic or aseptic depending on the source of infection. Typical signs and symptoms of meningitis in children include fever, headache, neck stiffness, nuchal rigidity represented by positive Kernig and Brudzinski signs, photophobia, nausea, vomiting, confusion, lethargy, and irritability. Bacterial meningitis is commonly caused by Streptococcus pneumoniae in children over the age of three months. Although there has been a decline in infections due to the introduction of the pneumococcal conjugate and pneumococcal polysaccharide vaccines, there are still reported cases of invasive pneumococcal infections mostly with non-vaccine serotypes. We report a fully immunized six-year-old male patient with a presentation of classic meningitis signs and symptoms who developed rapid progression of disease including sudden and dramatic change in physical exam and subsequent respiratory depression within 12 hours of admission. Our patient had a history of extensive traumatic facial bone fractures six months prior. Our case demonstrates a unique presentation of rapidly progressing pneumococcal meningitis due to a suspected complication of septic thrombophlebitis and subsequent brain herniation in a fully immunized patient six months after a severe traumatic facial injury.

Spatio-temporal brain invasion pattern of Streptococcus pneumoniae and dynamic changes in the cellular environment in bacteremia-derived meningitis.

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by a neuroinflammatory response and the deleterious action of bacterial toxins in the brain. However, little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-derived meningitis mouse model, we combined 3D whole brain imaging with brain microdissection to show that all brain regions were equally affected during disease progression, with the presence of pneumococci closely associated to the microvasculature. In the hippocampus, the invasion provoked microglial activation, while the neurogenic niche showed increased proliferation and migration of neuroblasts. Our results indicate that, even before the outbreak of symptoms, the bacterial load throughout the brain is high and causes neuroinflammation and cell death, a pathological scenario which ultimately leads to a failing regeneration of new neurons.

Impact of direct ICU admission of pneumococcal meningitis in France: a retrospective analysis of a French medico-administrative (PMSI) database.

BACKGROUND: Current guidelines for adult patients with pneumococcal meningitis (PM) recommend initial management in intermediate or intensive care units (ICU), but evidence to support these recommendations is limited. We aimed to describe ICU admission practices of patients with PM. METHODS: We conducted a retrospective analysis of the French medico administrative database of consecutive adult patients with PM and sepsis criteria hospitalized between 2011 and 2020. We defined two groups, "Direct ICU" corresponding to a direct ICU admission and "Delayed ICU" corresponding to a secondary ICU admission. RESULTS: We identified 4052 patients hospitalized for a first episode of PM, including 2006 "Direct ICU" patients (50%) and 2046 "delayed ICU" patients (50%). The patients were mainly males [n = 2260 (56%)] with median age of 61 years [IQR 50-71] and a median Charlson index of 1 [0-3]. Among them, median SAPS II on admission was 46 [33-62], 2173 (54%) had a neurological failure on admission with 2133 (53%) in coma, 654 (16%) with brainstem failure, 488 (12%) with seizures and 779 (19%) with focal signs without coma. PM was frequently associated with pneumonia [n = 1411 (35%)], and less frequently with endocarditis [n = 317 (8%)]. The median ICU length of stay and hospital length of stay were 6 days [2-14] and 21 days [13-38], respectively. In-hospital mortality was 27% (n = 1100) and 640 (16%) patients were secondarily transferred to rehabilitation care unit. Direct ICU group was significantly more severe but after adjustment for age, sex, comorbidities, organ failures on admission and admission from home, direct ICU admission was significantly associated with a lower mortality (Odds ratio 0.67 [0.56-0.80], p < 0.01). This corresponded to one death avoided for 11 PM directly admitted in ICU. CONCLUSIONS: Among patients with PM and sepsis, direct ICU admission was associated with lower mortality rates when compared to delayed admission.

NLRP3 Activation Contributes to Memory Impairment in an Experimental Model of Pneumococcal Meningitis.

Bacterial meningitis is considered a life-threatening condition with high mortality rates. In response to the infection, signaling cascades, producing pro-inflammatory mediators trigger an exacerbated host immune response. Another inflammatory pathway occurs through the activation of inflammasomes. Studies highlight the role of the NLR family pyrin domain containing 3 (NLRP3) in central nervous system disorders commonly involved in neuroinflammation. We aimed to investigate the role of NLRP3 and its inhibitor MCC950 on neurochemical, immunological, and behavioral parameters in the early and late stages of experimental pneumococcal meningitis. For this, adult male Wistar rats received an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a placebo. The animals were divided into control/saline, control/MCC950, meningitis/saline, and meningitis/MCC950. Immediately after the meningitis induction, the animals received 140 ng/kg MCC950 via intracisternal injection. For the acute protocol, 24 h after induction, brain structures were collected to evaluate cytokines, NLRP3, and microglia. In the long-term group, the animals were submitted to open field and recognition of new objects tests at ten days after the meningitis induction. After the behavioral tests, the same markers were evaluated. The animals in the meningitis group at 24 h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels. Although free from infection, ten days after meningitis induction, the animals in the meningitis group had elevated cytokine levels and demonstrated behavioral deficits; however, the single dose of NLRP3 inhibitor rescued the behavior deficits and decreased the brain inflammatory profile.

Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood-brain barrier function.

BACKGROUND: Brain pericytes participate in the regulation of cerebral blood flow and the maintenance of blood-brain barrier integrity. Because of their perivascular localization, their receptor repertoire, and their potential ability to respond to inflammatory and infectious stimuli by producing various cytokines and chemokines, these cells are also thought to play an active role in the immune response to brain infections. This assumption is mainly supported by in vitro studies, investigations in in vivo disease models are largely missing. Here, we analysed the role of brain pericytes in pneumococcal meningitis, in vitro and in vivo in two animal models of pneumococcal meningitis. METHODS: Primary murine and human pericytes were stimulated with increasing concentrations of different serotypes of Streptococcus pneumoniae in the presence or absence of Toll-like receptor inhibitors and their cell viability and cytokine production were monitored. To gain insight into the role of pericytes in brain infection in vivo, we performed studies in a zebrafish embryo model of pneumococcal meningitis in which pericytes were pharmacologically depleted. Furthermore, we analyzed the impact of genetically induced pericyte ablation on disease progression, intracranial complications, and brain inflammation in an adult mouse model of this disease. RESULTS: Both murine and human pericytes reacted to pneumococcal exposure with the release of selected cytokines. This cytokine release is pneumolysin-dependent, TLR-dependent in murine (but not human) pericytes and can be significantly increased by macrophage-derived IL-1b. Pharmacological depletion of pericytes in zebrafish embryos resulted in increased cerebral edema and mortality due to pneumococcal meningitis. Correspondingly, in an adult mouse meningitis model, a more pronounced blood-brain barrier disruption and leukocyte infiltration, resulting in an unfavorable disease course, was observed following genetic pericyte ablation. The degree of leukocyte infiltration positively correlated with an upregulation of chemokine expression in the brains of pericyte-depleted mice. CONCLUSIONS: Our findings show that pericytes play a protective role in pneumococcal meningitis by impeding leukocyte migration and preventing blood-brain barrier breaching. Thus, preserving the integrity of the pericyte population has the potential as a new therapeutic strategy in pneumococcal meningitis.

Uncovering the neuroprotective effect of vitamin B12 in pneumococcal meningitis: insights into its pleiotropic mode of action at the transcriptional level.

Background: The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl. Material and methods: Eleven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis. Results: In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug. Conclusion: B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.

Persistent dysexecutive syndrome after pneumococcal meningitis complicated by recurrent ischemic strokes: A case report.

BACKGROUND: Meningitis is a possible complication of pneumococcal infection concerning acute otitis media and sinusitis. It might compromise cognitive function, both for the infection itself and the vascular events that sometimes follow the acute phase. CASE SUMMARY: Here we describe the case of a 32-year-old female patient admitted to the emergency room due to extensive pneumococcal meningitis as a consequence of sinus outbreak. She presented with extensive laminar ischemic damage in the acute phase, resulting in severe cognitive and behavioural impairment. Four years of follow-up, through neuropsychological assessments and neuroradiological investigations, demonstrated the presence of subsequent vascular events, 3 months and 2 years after onset. CONCLUSION: The case is discussed in light of scientific knowledge of the long-term outcomes of this pathology in order to potentially improve diagnosis and promote better outcomes.

Cerebral vasculitis as a complication of pneumococcal meningitis: A cohort study.

OBJECTIVE: Cerebral vasculitis (CV) is a severe complication of pneumococcal meningitis (PM); whether dexamethasone use can reduce its occurrence remains to be determined. METHODS: This is a retrospective observational bicentric study analyzing all adults with proven PM hospitalized between January 2002 and December 2020 in two tertiary hospitals. Extrapolating from a standardized definition of primary angiitis of the central nervous system, we defined CV as worsened neurological symptoms associated with compatible imaging. All images were analyzed by a radiologist, and two neurologists reviewed all inconclusive cases of suspected CV for adjudication. Factors associated with CV were analyzed, including dexamethasone use. A subgroup analysis was limited to patients with a lumbar puncture at PM diagnosis. RESULTS: Among 168 patients with PM, 49 (29.2%) had CV, occurring after a median of 8 days (IQR 5-13) of PM diagnosis. In multivariate analysis (N = 151), initial CRP was associated with CV (OR 1.28 per 50-unit increase, p = 0.003), which was marginally linked with delayed hospital admission more than 48 hours after first symptoms (OR 2.39, p = 0.06) and prior NSAID intake (OR 2.94, p = 0.05). Dexamethasone administration did not impact CV occurrence. In 133 patients having undergone lumbar puncture, CSF protein level > 4.4 g/L (OR 4.50, p = 0.006) was associated with CV. CONCLUSIONS: In our cohort, CV was a frequent and severe complication of PM, often occurring in association with unduly delayed medical care, high CRP at admission, and high levels of protein in CSF.

Trends in laboratory-confirmed bacterial meningitis (2012-2019): national observational study, England.

Background: Bacterial meningitis is associated with significant morbidity and mortality worldwide. We aimed to describe the epidemiology, aetiology, trends over time and outcomes of laboratory-confirmed bacterial meningitis in England during 2012-2019. Methods: UK Health Security Agency routinely receives electronic notifications of confirmed infections from National Health Service hospital laboratories in England. Data were extracted for positive bacterial cultures, PCR-positive results for Neisseria meningitidis or Streptococcus pneumoniae from cerebrospinal fluid and positive blood cultures in patients with clinical meningitis. Findings: During 2012-19, there were 6554 laboratory-confirmed cases. Mean annual incidence was 1.49/100,000, which remained stable throughout the surveillance period (p = 0.745). There were 155 different bacterial species identified, including 68.4% (106/1550) Gram-negative and 31.6% (49/155) Gram-positive bacteria. After excluding coagulase-negative staphylococci (2481/6554, 37.9%), the main pathogens causing meningitis were Streptococcus pneumoniae (811/4073, 19.9%), Neisseria meningitidis (497/4073, 12.2%), Staphylococcus aureus (467/4073, 11.5%), Escherichia coli (314/4073, 7.7%) and group B streptococcus (268/4073, 6.6%). Pneumococcal meningitis incidence increased significantly during 2012-9, while meningococcal, group A streptococcal and tuberculous meningitis declined. Infants aged <3 months had the highest mean incidence (55.6/100,000; 95% CI, 47.7-63.5) driven mainly by group B streptococci, followed by 3-11 month-olds (8.1/100,000; 95% CI 7.1-9.0), where pneumococcal and meningitis predominated. The 30-day case-fatality rate (CFR) was 10.0% (71/6554). Group A streptococcal meningitis had the highest CFR (47/85, 55.3%). The probability of surviving at 30 days was 95.3% (95% CI, 93.4-97.3%) for infants and 80.0% for older adults (77-84%). Interpretation: The incidence of bacterial meningitis has remained stable. The high CFR highlights a need for prevention through vaccination. Funding: PHE.

Streptococcus pneumoniae Serotype 23B Causing Asymptomatic Sinusitis Complicated by Endocarditis and Meningitis: Sequela of a Non-vaccine Serotype.

We describe a rare case of a Streptococcus pneumoniae (S. pneumoniae) infection causing mitral valve endocarditis and bacterial meningitis in a previously healthy young adult male in his 20s who presented with altered mentation. Though our patient did not endorse any respiratory issues, we suspected the paranasal sinuses to have been the cryptic primary source of disseminated infection into the respiratory system and meninges due to incidental mucosal thickening being found on imaging. Blood and cerebrospinal fluid analyses and cultures revealed the proliferation of S. pneumoniae serotype 23B, despite our patient having previously received appropriate pneumococcal vaccinations in his childhood without delinquency. Ultimately, surgical replacement of the mitral valve, as well as a course of ceftriaxone, was indicated for this patient, in which full resolution of symptoms was achieved upon discharge.

Hearing outcomes in children with pneumococcal meningitis in the PCV13 era.

INTRODUCTION: Streptococcus pneumoniae, is associated with the highest incidence of post-meningitic SNHL. The exact impact of 13-valent pneumococcal conjugate vaccine (PCV) on pediatric SNHL from pneumococcal meningitis is unknown. We aimed to identify clinical factors associated with post-meningitic SNHL (pmSNHL) from pneumococcal meningitis and describe its rates based on three time periods: pre-PCV, PCV-7 and PCV13 eras. METHODS: A retrospective case-control study was performed for patients 18 years and younger diagnosed with pneumococcal meningitis from January 1, 2010 to December 31, 2020 at Children's Hospital Colorado. Demographic and clinical risk factors between those with or without SNHL were compared. Detailed hearing outcomes of those with resulting SNHL are described. RESULTS: 23 patients with CSF cultures or Meningitis/Encephalitis Panel positive for pneumococcal meningitis were identified. Twenty patients both survived the infection and had audiologic evaluation. Six patients had pmSNHL, with 50 % affected bilaterally. The rate of pmSNHL from S. pneumoniae in the PCV-13 era at our institution was similar to historical rates from the pre-PCV and PCV-7 eras. Similar proportions of patients with pmSNHL completed PCV vaccination (66.7 %) compared to those without (71.4 %). Non-PCV-13 serotypes were responsible 83 % of patients with pmSNHL versus 57 % of patients without pmSNHL. CONCLUSIONS: Despite high rates of PCV-13 uptake in our cohort, pmSNHL was still common, severe, and commonly associated with non-PCV-13 serotypes. Non-PCV-13 serotypes may be contributing to the persistently high rate of post-meningitic SNHL and the severity of SNHL. Newer pneumococcal conjugate vaccines with expanded serotypes may help mitigate the SNHL associated with pneumococcal meningitis.

Risk factors and pathogen characteristics associated with unfavorable outcomes among adults with pneumococcal meningitis in Japan, 2006 to 2016.

PURPOSE: In this study, we aimed to clarify the risk factors associated with unfavorable outcomes in adults with pneumococcal meningitis (PnM). METHODS: Surveillance was conducted between 2006 and 2016. Adults with PnM (n = 268) were followed up for outcomes within 28 days after admission using the Glasgow Outcome Scale (GOS). After classifying the patients into the unfavorable (GOS1-4) and favorable (GOS5) outcome groups, i) the underlying diseases, ii) biomarkers at admission, and iii) serotype, genotype, and antimicrobial susceptibility for all isolates were compared between both groups. RESULTS: Overall, 58.6% of patients with PnM survived,15.3% died, and 26.1% had sequelae. The number of living days in the GOS1 group was highly heterogeneous. Motor dysfunction, disturbance of consciousness, and hearing loss were the commonest sequelae. Of the underlying diseases identified in 68.9% of the PnM patients, liver and kidney diseases were significantly associated with unfavorable outcomes. Of the biomarkers, creatinine and blood urea nitrogen, followed by platelet and C-reactive protein had the most significant associations with unfavorable outcomes. There was a significant difference in the high protein concentrations in the cerebrospinal fluid between the groups. Serotypes 23F, 6C, 4, 23A, 22F, 10A, and 12F were associated with unfavorable outcomes. These serotypes were not penicillin-resistant isolates possessing three abnormal pbp genes (pbp1a, 2x, and 2b), except for 23F. The expected coverage rate of the pneumococcal conjugate vaccine (PCV) was 50.7% for PCV15 and 72.4% for PCV20. CONCLUSIONS: In the introduction of PCV for adults, the risk factors for underlying diseases should be prioritized over age, and serotypes with unfavorable outcomes should be considered.

Steroid Rebound Phenomenon as a Cause of Delayed Cerebral Vasospasm in Post-Splenectomy Pneumococcal Meningitis: A Case Report.

Pneumococcal meningitis as an overwhelming post-splenectomy infection (OPSI) has a higher risk of neurological complications and is sometimes life-threatening. In acute pneumococcal meningitis, four days of dexamethasone is widely used for the prevention of neurological complications. Herein, we report a 68-year-old woman with the diagnosis of pneumococcal meningitis as OPSI. With adequate antibiotics and dexamethasone, her symptoms gradually improved. However, after dexamethasone withdrawal, her consciousness got worse and got into a coma. Brain magnetic resonance imaging revealed acute cerebral infarctions in the bilateral middle cerebral artery territory with multiple vascular stenoses and hydrocephalus. Vascular stenoses improved by follow-up, suggesting cerebral vasospasm. There were no suggestive findings of cerebral vasculitis. Follow-up cerebrospinal fluid analysis showed remained pleocytosis with no bacteria, which could not suggest meningitis recurrence. Since steroid therapy was rapidly withdrawn, we diagnosed that the cerebral vasospasm was due to the steroid rebound phenomenon. The steroid rebound phenomenon due to the excessive immune response to bacterial microstructures has been reported in pneumococcal meningitis. Especially, the present case was asplenia and the usual dexamethasone use would not adequately suppress the immune response to bacterial microstructures. Since pneumococcal meningitis as OPSI has a higher risk of neurological complications, clinicians should consider longer and more cautious steroid tapering.

Multiplex PCR to Streptococcus pneumoniae serotype identification directly in cerebrospinal fluid samples.

Streptococcus pneumoniae causes invasive diseases of significant public health concern, such as meningitis. The culture of cerebrospinal fluid (CSF) samples, the standard technique for meningitis diagnoses, is not always positive. Consequently, meaningful information about the etiological agent is lost, which can compromise effective epidemiological surveillance and the improvement of immunization policies. This study aims to standardize a method to genotype pneumococcus in the CSF samples which could mitigate the absence of isolated strains, and also evaluate the prediction of this assay. We applied eight multiplex PCR (mPCR) assays to CSF samples paired with the Quellung reaction applied to the isolated strains. We also compared different master mix kits in the mPCR. Moreover, a retrospective study was conducted with CSF samples considered pneumococcus positive due to the presence of the lytA gene. Results showed that genotyping by the mPCR correlated 100% with the Quellung reaction, and genotyping was dependent on the master mix applied. In the retrospective study (2014-2020), 73.4% were successfully genotyped. The analyses of the receiver operating characteristic curve showed that the cycle threshold (Ct value) around 30 for the lytA gene had a 75% positive chance of successful genotyping, whereas with a Ct value > 35, the chance was 12.5%. Finally, we observed that genotype 19A was prevalent in the period (12%), information unknown until now due to the lack of isolated strains. Therefore, the mPCR of CSF samples can efficiently predict S. pneumoniae serotypes, especially in the absence of isolated strains, which can be a great tool for pneumococcal serotype surveillance.

Improving Pneumococcal Vaccination Rates in Cochlear Implant Programs: A Systematic Review and Meta-analysis.

OBJECTIVE: To review the literature on pneumococcal vaccination compliance rates among cochlear implant (CI) patients and to examine the utility of intervention programs on increasing vaccination rates. DATA SOURCES: PubMed, Scopus, and CINAHL. REVIEW METHODS: A systematic review was performed following PRISMA guidelines. Studies of pneumococcal vaccination rates at baseline and before and after the implementation of a quality improvement (QI) intervention were included. A total of 641 studies were screened, and 13 studies met inclusion criteria. Meta-analyses of pneumococcal vaccination rates pre- and post-QI intervention in CI patients were performed. RESULTS: A total of 12,973 children and adults were included. The baseline PCV13 and PPSV23 vaccination rates were 53.45% (95% CI, 37.02%-69.51%) and 42.53% (95% CI, 31.94%-53.48%), respectively. Comparing children and adults, PCV13 and PPSV23 baseline vaccination rates were not statistically significant. The PPSV23 vaccine rate after QI initiatives was significantly higher than the baseline rate at 83.52% (95% CI, 57.36%-98.46%). After these interventions, patients had a 15.71 (95% CI, 4.32-57.20, P < .001) increased odds of receiving PPSV23 vaccination compared to before QI implementation. CONCLUSIONS: The baseline rates of PCV13 and PPSV23 are highly variable and lower than expected, given current vaccination recommendations for CI patients. QI programs appear successful in increasing compliance rates with the PPSV23 vaccination; however, they are still far from full compliance. Further intervention programs with stricter surveillance, monitoring, and follow-up systems are needed to achieve improved compliance with the PCV13 and PPSV23 vaccination in CI recipients.