The Potentials of Melatonin in the Prevention and Treatment of Bacterial Meningitis Disease.

Bacterial meningitis (BM) is an acute infectious central nervous system (CNS) disease worldwide, occurring with 50% of the survivors left with a long-term serious sequela. Acute bacterial meningitis is more prevalent in resource-poor than resource-rich areas. The pathogenesis of BM involves complex mechanisms that are related to bacterial survival and multiplication in the bloodstream, increased permeability of blood-brain barrier (BBB), oxidative stress, and excessive inflammatory response in CNS. Considering drug-resistant bacteria increases the difficulty of meningitis treatment and the vaccine also has been limited to several serotypes, and the morbidity rate of BM still is very high. With recent development in neurology, there is promising progress for drug supplements of effectively preventing and treating BM. Several in vivo and in vitro studies have elaborated on understanding the significant mechanism of melatonin on BM. Melatonin is mainly secreted in the pineal gland and can cross the BBB. Melatonin and its metabolite have been reported as effective antioxidants and anti-inflammation, which are potentially useful as prevention and treatment therapy of BM. In bacterial meningitis, melatonin can play multiple protection effects in BM through various mechanisms, including immune response, antibacterial ability, the protection of BBB integrity, free radical scavenging, anti-inflammation, signaling pathways, and gut microbiome. This manuscript summarizes the major neuroprotective mechanisms of melatonin and explores the potential prevention and treatment approaches aimed at reducing morbidity and alleviating nerve injury of BM.

Bacterial meningitis after dental extraction in a 17-year-old horse.

Dental extractions in horses may result in bacteremia, which can lead to systemic complications. Bacterial meningitis following oral cheek tooth extractions in a 17-year-old Thoroughbred gelding is described in this report. The bacterial meningitis was confirmed by histopathology. The gelding was presented for evaluation of intermittent fever, loose feces, and mild colic signs which started 5 days after cheek tooth extraction. This case illustrates a rare complication associated with oral tooth extraction in a horse and highlights the unusual presenting features of meningitis. Key clinical message: Bacterial meningitis secondary to oral cheek tooth extraction should be considered as differential diagnosis; particularly in cases with the development of pyrexia a few days after the procedure.

Méningite bactérienne après extraction dentaire chez un cheval de 17 ans. Les extractions dentaires chez les chevaux peuvent entraîner une bactériémie, ce qui peut amener des complications systémiques. Un cas de méningite bactérienne à la suite d'extractions buccales de dents jugales chez un hongre pur-sang de 17 ans est décrite dans ce rapport. La méningite bactérienne a été confirmée par histopathologie. Le hongre a été présenté pour évaluation d'une fièvre intermittente, de selles molles et de signes de coliques légers qui ont commencé 5 jours après l'extraction de la dent jugale. Ce cas illustre une complication rare associée à l'extraction dentaire orale chez un cheval et met en évidence des caractéristiques inhabituelles de la méningite.Message clinique clé :La méningite bactérienne secondaire à l'extraction buccale des dents jugales doit être considérée comme un diagnostic différentiel, en particulier dans les cas de développement d'une pyrexie quelques jours après l'intervention.(Traduit par Dr Serge Messier).

Clinical Characteristics of Disseminated Strongyloidiasis, Japan, 1975-2017.

Clinical characteristics of disseminated strongyloidiasis, the severest form of strongyloidiasis, are not well described. We conducted a retrospective, consecutive chart review of patients with disseminated strongyloidiasis admitted to Okinawa Chubu Hospital in Okinawa, Japan, during January 1975-December 2017. The 70 patients were classified into 3 clinical phenotypes: dissemination (32 patients [45.7%]), occult dissemination with meningitis caused by enteric organisms (12 patients [17.1%]), and occult dissemination with culture-negative suppurative meningitis (26 patients [37.1%]). Associated mortality rates were 56.3%, 16.7%, and 11.5%, respectively, and sepsis occurred in 40.6%, 58.3%, and 11.5% of cases, respectively. Common symptoms included fever (52.9% of patients), headache (32.9%), and altered mental status (24.3%). Patients were treated with thiabendazole (before 2003) or ivermectin (after 2003). Our findings show that disseminated strongyloidiasis has clinical phenotypes in terms of severity and that identification of occult dissemination, a mild form with prominent neurologic manifestations, is lifesaving.

Group B Streptococcus Meningitis in an Infant with Respiratory Syncytial Virus Detection.

We report our experience caring for an infant with respiratory syncytial virus infection (RSV) and group B Streptococcus (GBS) bacteremia and meningitis. Concurrent GBS meningitis and RSV is rare but highlights the importance of correlating clinical symptoms with viral diagnostic testing during the evaluation of infants at risk for serious bacterial infection.

A rare case of purulent meningitis caused by Capnocytophaga canimorsus in the Czech Republic - case report and review of the literature.

BACKGROUND: Invasive infections caused by Capnocytophaga canimorsus are rare. Immunocompromised patients, who report being bitten by or having a close contact with an animal, represent a high-risk group for this infection. There are only few dozens of infections by this bacteria manifesting as purulent meningitis reported worldwide. The reported case is a first reported case of purulent meningitis caused by by Capnocytophaga canimorsus in Czech Republic with only a limited risk factor history. CASE PRESENTATION: The patient, a 74 years old man, was referred to the infectious diseases department of a teaching hospital with clear signs of developing purulent meningitis. His anamnestic data did not show any unusual findings. He was treated for compensated diabetes mellitus type II. The blood cultures were negative and the etiological agent did not grow from the cerebrospinal fluid (CSF) on common media. Eventually, it was identified by detecting pan-bacterial DNA and DNA sequencing. Subsequently, the pathogen was confirmed by anaerobic cultivation from CSF. Only after then the patient recalled being bitten by his German shepherd puppy during play. The patient was successfully treated intravenously by ceftriaxone. CONCLUSIONS: Purulent meningitis caused by Capnocytophaga spp. is a rare disease, but it needs to be considered in patients at risk with pre-existing conditions, who report close contact with or being bitten by an animal. It is important to test for this microbe in cases with negative microbiological results for the more common agents.

Development and verification of a discriminate algorithm for diagnosing post-neurosurgical bacterial meningitis-A multicenter observational study.

OBJECTIVE: To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF)-based routine clinical examinations for post-neurosurgical bacterial meningitis (PNBM) in multicenter post-neurosurgical patients. METHODS: The diagnostic accuracies of routine examinations to distinguish between PNBM and post-neurosurgical aseptic meningitis (PNAM) were evaluated by determining the values of the area under the curve (AUC) of the receiver operating characteristic curve in a retrospective analysis of post-neurosurgical patients in four centers. RESULTS: An algorithm was constructed using the logistic analysis as a classical method to maximize the capacity for differentiating the two classes by integrating the measurements of five variables. The AUC value of this algorithm was 0.907, which was significantly higher than those of individual routine blood/CSF examinations. The predicted value from 70 PNBM patients was greater than the cutoff value, and the diagnostic accuracy rate was 75.3%. The results of 181 patients with PNAM showed that 172 patients could be correctly identified with specificity of 95.3%, while the overall correctness rate of the algorithm was 88.6%. CONCLUSIONS: Routine biomarkers such as CSF/blood glucose ratio (C/B-Glu), CSF lactate (C-Lac), CSF glucose concentration (C-Glu), CSF leukocyte count (C-Leu), and blood glucose concentration (B-Glu) can be used for auxiliary diagnosis of PNBM. The multicenter retrospective research revealed that the combination of the five abovementioned biomarkers can effectively improve the efficacy of the PNBM diagnosis.

Etiology of Pediatric Bacterial Meningitis Pre- and Post-PCV13 Introduction Among Children Under 5 Years Old in Lomé, Togo.

BACKGROUND: Pediatric bacterial meningitis (PBM) causes severe morbidity and mortality within Togo. Thus, as a member of the World Health Organization coordinated Invasive Bacterial Vaccine Preventable Diseases network, Togo conducts surveillance targeting Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae, at a sentinel hospital within the capital city, Lomé, in the southernmost Maritime region. METHODS: Cerebrospinal fluid was collected from children <5 years with suspected PBM admitted to the Sylvanus Olympio Teaching Hospital. Phenotypic detection of pneumococcus, meningococcus, and H. influenzae was confirmed through microbiological techniques. Samples were shipped to the Regional Reference Laboratory to corroborate results by species-specific polymerase chain reaction. RESULTS: Overall, 3644 suspected PBM cases were reported, and 98 cases (2.7%: 98/3644) were confirmed bacterial meningitis. Pneumococcus was responsible for most infections (67.3%: 66/98), followed by H. influenzae (23.5%: 23/98) and meningococcus (9.2%: 9/98). The number of pneumococcal meningitis cases decreased by 88.1% (52/59) postvaccine introduction with 59 cases from July 2010 to June 2014 and 7 cases from July 2014 to June 2016. However, 5 cases caused by nonvaccine serotypes were observed. Fewer PBM cases caused by vaccine serotypes were observed in infants <1 year compared to children 2-5 years. CONCLUSIONS: Routine surveillance showed that PCV13 vaccination is effective in preventing pneumococcal meningitis among children <5 years of age in the Maritime region. This complements the MenAfriVac vaccination against meningococcal serogroup A to prevent meningitis outbreaks in the northern region of Togo. Continued surveillance is vital for estimating the prevalence of PBM, determining vaccine impact, and anticipating epidemics in Togo.

Etiology of Bacterial Meningitis Among Children <5 Years Old in Côte d'Ivoire: Findings of Hospital-based Surveillance Before and After Pneumococcal Conjugate Vaccine Introduction.

BACKGROUND: Bacterial meningitis remains a major disease affecting children in Côte d'Ivoire. Thus, with support from the World Health Organization (WHO), Côte d'Ivoire has implemented pediatric bacterial meningitis (PBM) surveillance at 2 sentinel hospitals in Abidjan, targeting the main causes of PBM: Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Neisseria meningitidis (meningococcus). Herein we describe the epidemiological characteristics of PBM observed in Côte d'Ivoire during 2010-2016. METHODS: Cerebrospinal fluid (CSF) was collected from children aged <5 years admitted to the Abobo General Hospital or University Hospital Center Yopougon with suspected meningitis. Microbiology and polymerase chain reaction (PCR) techniques were used to detect the presence of pathogens in CSF. Where possible, serotyping/grouping was performed to determine the specific causative agents. RESULTS: Overall, 2762 cases of suspected meningitis were reported, with CSF from 39.2% (1083/2762) of patients analyzed at the WHO regional reference laboratory in The Gambia. In total, 82 (3.0% [82/2762]) CSF samples were positive for bacterial meningitis. Pneumococcus was the main pathogen responsible for PBM, accounting for 69.5% (52/82) of positive cases. Pneumococcal conjugate vaccine serotypes 5, 18C, 19F, and 6A/B were identified post-vaccine introduction. Emergence of H. influenzae nontypeable meningitis was observed after H. influenzae type b vaccine introduction. CONCLUSIONS: Despite widespread use and high coverage of conjugate vaccines, pneumococcal vaccine serotypes and H. influenzae type b remain associated with bacterial meningitis among children aged <5 years in Côte d'Ivoire. This reinforces the need for enhanced surveillance for vaccine-preventable diseases to determine the prevalence of bacterial meningitis and vaccine impact across the country.

Fatal Meningitis in Patient with X-Linked Chronic Granulomatous Disease Caused by Virulent Granulibacter bethesdensis.

Granulibacter bethesdensis is a pathogen reported to cause recurrent lymphadenitis exclusively in persons with chronic granulomatous disease. We report a case of fatal meningitis caused by a highly virulent G. bethesdensis strain in an adolescent in Europe who had chronic granulomatous disease.

Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with an external ventricular drain.

BACKGROUND: Owing to its antibacterial properties, ceftaroline could be attractive for prevention or treatment of bacterial post-neurosurgical meningitis/ventriculitis. However, few data are available concerning its meningeal concentrations. OBJECTIVES: To investigate ceftaroline CSF pharmacokinetics in ICU patients with an external ventricular drain (EVD). METHODS: Patients received a single 600 mg dose of ceftaroline as a 1 h intravenous infusion. Blood and CSF samples were collected before and 0.5, 1, 3, 6, 12 and 24 h after the end of the infusion. Concentrations were assayed in plasma and CSF by LC-MS/MS. A two-step compartmental pharmacokinetic analysis was conducted. Ceftaroline plasma data were first analysed, and thereafter plasma parameters estimated and corrected for protein binding of 20% were fixed to fit unbound CSF concentrations. In the final model, parameters for both plasma and CSF data were simultaneously estimated. RESULTS: Nine patients with an EVD were included. The Cmax was 18.29 ± 3.33 mg/L in plasma (total concentrations) and at 0.22 ± 0.17 mg/L in CSF (unbound concentration). The model-estimated CSF input/CSF output clearance ratio was 9.4%, attesting to extensive efflux transport at the blood-CSF barrier. CONCLUSIONS: Ceftaroline CSF concentrations are too low to ensure prophylactic protection against most pathogens with MICs between 1 and 2 mg/L, owing to its limited central distribution.

Risk of Meningitis in Infants Aged 29 to 90 Days with Urinary Tract Infection: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the risk of bacterial meningitis in infants aged 29-90 days with evidence of urinary tract infection (UTI). METHODS: PubMed (MEDLINE), Embase, and the Cochrane Library were systematically searched for studies reporting rates of meningitis in infants aged 29-90 days with abnormal urinalysis or urine culture. Observational studies in infants with evidence of UTI who underwent lumbar puncture (LP) reporting age-specific event rates of bacterial meningitis and sterile cerebrospinal fluid pleocytosis were included. Prevalence estimates for bacterial meningitis in infants with UTI were pooled in a random effects meta-analysis. RESULTS: Three prospective and 17 retrospective cohort studies were included in the meta-analysis. The pooled prevalence of concomitant bacterial meningitis in infants with UTI was 0.25% (95% CI, 0.09%-0.70%). Rates of sterile pleocytosis ranged from 0% to 29%. Variation in study methods precluded calculation of a pooled estimate for sterile pleocytosis. In most studies, the decision to perform a LP was up to the provider, introducing selection bias into the prevalence estimate. CONCLUSIONS: The risk of bacterial meningitis in infants aged 29-90 days with evidence of UTI is low. A selective approach to LP in infants identified as low risk for meningitis by other clinical criteria may be indicated.

Risk of Serious Bacterial Infection in Infants Aged ≤60 Days Presenting to Emergency Departments with a History of Fever Only.

OBJECTIVE: To compare the risk of serious bacterial infection between infants aged ≤60 days who are febrile in the emergency department (ED) and those who have only a history of fever and are afebrile on arrival to the ED. STUDY DESIGN: In this secondary analysis of a multicenter prospective study using data collected between December 2008 and May 2013, we compared the rate of serious bacterial infection (urinary tract infection [UTI], bacteremia, and/or bacterial meningitis) between infants who have a history of fever but are afebrile on arrival to the ED and those with fever documented in the ED (rectal temperature ≥38.0 °C) using relative risk (RR) with 95% CI. Stratified analyses were performed for age (≤28 and 29-60 days) and serious bacterial infection type. Infants born prematurely and those with a clinical focal infection or serious illness were excluded. RESULTS: A total of 3825 infants (mean age, 35.2 days; 56.9% male) were included. Of the 1233 (32.2%) who were afebrile in the ED, 108 (8.8%) had a serious bacterial infection (UTI, n = 94 [7.6%]; bacteremia, n = 19 [1.5%]; bacterial meningitis, n = 8 [0.6%]). Of the 2592 infants (67.8%) who were febrile in the ED, 331 (12.8%) had a serious bacterial infection (UTI, n = 285 [11.0%]; bacteremia, n = 61 [2.4%]; bacterial meningitis, n = 17 [0.7%]). The RR for serious bacterial infection for afebrile vs febrile infants was 0.68 (95% CI, 0.56-0.84). A lower risk of serious bacterial infection was also seen among afebrile vs febrile infants aged ≤28 days (RR, 0.69; 95% CI, 0.52-0.93) and age 29-60 days (RR, 0.67; 95% CI, 0.50-0.89). CONCLUSIONS: The prevalence of serious bacterial infection is lower in infants aged ≤60 days with a history of fever compared with those who are febrile on arrival to the ED. The small risk reduction in this group is unlikely to alter decision making.

Streptococcus Oralis meningitis from right sphenoid Meningoencephalocele and cerebrospinal fluid leak.

BACKGROUND: Streptococcus oralis belongs to the Streptococcus mitis group and is part of the normal flora of the nasal and oropharynx (Koneman et al., The Gram-positive cocci part II: streptococci, enterococci and the 'Streptococcus-like' bacteria. Color atlas and textbook of diagnostic microbiology, 1997). Streptococcus oralis is implicated in meningitis in patients with decreased immune function or from surgical manipulation of the central nervous system. We report a unique case of meningitis by Streptococcus oralis in a 58-year-old patient with cerebral spinal fluid leak due to right sphenoid meningoencephalocele. CASE PRESENTATION: A 58-year-old female presented in the emergency department due to altered mental status, fevers, and nuchal rigidity. Blood cultures were positive for Streptococcus oralis. Magnetic resonance stereotactic imaging of head with intravenous gadolinium showed debris in lateral ventricle occipital horn and dural thickening/enhancement consistent with meningitis. There was also a right sphenoidal roof defect, and meningoencephalocele with cerebrospinal fluid leak as a result. The patient was treated with ceftriaxone and had endoscopic endonasal repair of defect. She had complete neurologic recovery 3 months later. CONCLUSIONS: Cerebrospinal fluid leak puts patients at increased risk for meningitis. Our case is unique in highlighting Streptococcus oralis as the organism implicated in meningitis due to cerebrospinal fluid leak.

Severe bacterial meningitis due to an enterothecal fistula in a 6-year-old child with Currarino syndrome: evaluation of surgical strategy with review of the literature.

Meningitis is a rare but serious complication in patients with Currarino syndrome. We present a 6-year-old girl with a fulminant meningitis due to an enterothecal fistula involving the anterior sacral meningocele. Initial treatment consisted of broad-spectrum intravenous antibiotic therapy and laparoscopic construction of a deviating double-loop ileostomy. This was followed by an elective posterior neurosurgical approach with a sacral laminectomy, evacuation of the empyema, and securing the disconnection of the anterior meningocele from the thecal sac, 10 days after initial hospital admission. The girl made a good postoperative recovery. The treatment strategy in the setting of meningitis due to an inflamed anterior meningocele is discussed and the available literature on the topic is reviewed.

Prospective study evaluating post-operative central nervous system infections following cranial surgery.

AIMS: To evaluate the efficacy of our methods for decreasing the incidence of post-operative central nervous system infections (PCNSI) and to assess the type of microbiology and risk factors associated with PCNSI. METHODS: This prospective study was performed at First Affiliated Hospital, College of Medicine, Zhejiang University, which is a major medical centre in eastern China. The study included adult patients who underwent cranial surgery from January 2014 to October 2015 at this institution and survived for more than 7 days . The demographic information and clinical data of the patients were recorded for every operation and the incidence of PCNSI and the type of microbiology were analysed separately for patients undergoing craniotomy and those undergoing cranial burr-hole surgery. Prior to initiation of the study, our research team had developed and implemented a series of methods for reducing infection rates in our department. RESULTS: A total of 1,616 cranial surgery procedures were assessed in the present study; 1,236 craniotomy/craniectomy operations and 380 cranial burr-hole surgery operations. Of these procedures, 29 were complicated by PCNSI (27 cases with meningitis/ventriculitis and two with intracranial abscess/empyema). The overall incidence of PCNSI was 1.8%, while the incidence of craniotomy/craniectomy operations was 2.0% (25 cases) and that of burr-hole surgery operations was 1.1% (four cases); the most common microorganism was Staphylococcus. Of the patients who underwent cranial burr-hole surgery, the only independent risk factor for PCNSI was the absence of prophylactic antibiotics. There were no independent risk factors for craniotomy/craniectomy operations. CONCLUSIONS: In the present large-sample study, the incidence of PCNSI was 1.8%, which was dramatically lower than that of a previous study performed by our research group.

[Etiology, Prognosis and Risk Factors of 181 Adult Community-acquired Acute Bacterial Meningitis].

OBJECTIVE: To understand the etiology, clinical prognosis and risk factors of adult community-acquired acute bacterial meningitis (ABM) and provide the evidence for clinical diagnosis and treatment. METHODS: We performed a retrospective study of 181 clinically diagnosed hospitalized patients with community-acquired adult ABM from Jan.2010 to Jan.2018. The patients were categorized as non-elderly (16≤age<65 years old, n=156 ) and elderly (age≥65 years old, n=25) group. The etiology, clinical features, prognosis and risk factors of the two groups were compared. RESULTS: Sixty-four of 181 patients (35.4%) had pathogens detected. The most common pathogens were Streptococcus pneumoniae (17.9%), Listeria monocytogenes (13.4%) and Klebsiella pneumoniae (10.5%). The mortality of the elderly group was higher than that of the non-elderly group (P<0.05). Univariate analysis showed that there was a significant difference between the elderly group and the non-elderly group in the incidence of hypertension, hypokalemia, pulmonary infection, ear-nose-throat ( ENT) infection, cerebrospinal fluid (CSF) protein concentration, head CT abnormalities and mortality. Logistic regression analysis showed that pulmonary infection and temperature ≥38.5 ℃ were independent risk factors for poor prognosis in the non-elderly group. CSF pressure ≥200 mmH2O was a independent risk factors for poor prognosis in the elderly group. CONCLUSION: The pathogens that cause acute bacterial meningitis in adult community are mainly Streptococcus pneumoniae, Listeria monocytogenes and Klebsiella pneumoniae.Pulmonary infection and temperature ≥38.5 ℃ are independent risk factors of poor prognosis in the non-elderly patients, as CSF pressure ≥200 mmH2O a independent risk factor in the elderly patients.

[Clinical features of Enterococcus faecium meningitis in children].

OBJECTIVE: To summarize the clinical features of Enterococcus faecium meningitis in children. METHODS: The clinical data of nine children with Enterococcus faecium meningitis were analyzed. RESULTS: In all the nine children, Enterococcus faecium was isolated from blood, cerebrospinal fluid, or peripherally inserted central catheters; 6 (67%) patients were neonates, 2 (22%) patients were younger than 6 months, and 1 (11%) patient was three years and four months of age. In those patients, 56% had high-risk factors before onset, which included intestinal infection, resettlement of drainage tube after surgery for hydrocephalus, skull fracture, perinatal maternal infection history, and catheter-related infection. The main symptoms were fever and poor response. In those patients, 22% had seizures; no child had meningeal irritation sign or disturbance of consciousness. The white blood cell count and level of C-reactive protein were normal or increased; the nucleated cell count in cerebrospinal fluid was normal or mildly elevated; the protein level was substantially elevated; the glucose level was decreased. The drug sensitivity test showed that bacteria were all sensitive to vancomycin and the vancomycin treatment was effective. Only one child had the complication of hydrocephalus. CONCLUSIONS: Enterococcus faecium meningitis occurs mainly in neonates and infants. The patients have atypical clinical features. A high proportion of patients with Enterococcus faecium meningitis have high-risk factors. Enterococcus faecium is sensitive to vancomycin.

[Drainage-associated meningitis in neurocritical care patients. The results of a five-year prospective study]. / Drenazh-assotsiirovannye meningity u patsientov otdeleniia neiroreanimatsii. Rezul'taty piatiletnego prospektivnogo nabliudeniia.

AIM: to determine the incidence rate and risk factors for drainage-associated meningitis in neurocritical care patients. MATERIAL AND METHODS: The prospective study included 539 patients who spent more than 48 h at the Department of Neurocritical Care and underwent external ventricular drainage. The incidence rate and risk factors for drainage-associated meningitis were evaluated. RESULTS: Over a 5-year period, 2140 patients have been hospitalized to the Department of Critical and Intensive Care (DCIC) for more than 48 h; of these, 539 patients underwent external ventricular drainage (EVD). Drainage-associated meningitis developed in 99 patients, which amounted to 19.8 (CI 16.3-23.3) per 100 patients with drainage and 18.3 (CI 14.3-22.2) per 1000 days of drainage. The incidence rate of drainage-associated meningitis did not significantly correlate with different neurosurgical diseases, but there was a tendency for meningitis to predominate in EVD patients with vascular pathology of the central nervous system (CNS). The rate of artery catheterization for direct measurement of systemic BP and the use of vasopressor agents were significantly higher in the group of patients with drainage-associated meningitis (p<0.05). ALV was used in 98 (99%) of 99 patients with drainage-associated meningitis; respiratory support was used in 325 (80.8%) patients without meningitis (p<0.01). An analysis of the ventricular drainage duration revealed a significantly (p<0.05) larger number of days of using EVD in the group of patients with drainage-associated meningitis. In most critical care patients (57.6%), meningitis developed during the first week of drainage. Cerebrospinal fluid leakage occurred significantly more frequently in patients with drainage-associated meningitis than in patients with EVD and without meningitis (p<0.01). Based on a microbiological examination, the etiology of drainage-associated meningitis was established in 57.1% of cases. The leading pathogens were coagulase-negative staphylococci (48.3%) and Acinetobacter baumannii (18.3%). CONCLUSION: The incidence rate of drainage-associated meningitis was 19.8 per 100 patients and 18.3 per 1000 days of drainage. The risk factors significantly predominating in patients with drainage-associated meningitis include the duration of drainage, association with external CSF leakage, as well as factors associated with indicators of the overall severity of the condition.

Population Pharmacokinetics and Dosing Regimen Optimization of Meropenem in Cerebrospinal Fluid and Plasma in Patients with Meningitis after Neurosurgery.

Meropenem is used to manage postneurosurgical meningitis, but its population pharmacokinetics (PPK) in plasma and cerebrospinal fluid (CSF) in this patient group are not well-known. Our aims were to (i) characterize meropenem PPK in plasma and CSF and (ii) recommend favorable dosing regimens in postneurosurgical meningitis patients. Eighty-two patients were enrolled to receive meropenem infusions of 2 g every 8 h (q8h), 1 g q8h, or 1 g q6h for at least 3 days. Serial blood and CSF samples were collected, and concentrations were determined and analyzed via population modeling. Probabilities of target attainment (PTA) were predicted via Monte Carlo simulations, using the target of unbound meropenem concentrations above the MICs for at least 40% of dosing intervals in plasma and at least of 50% or 100% of dosing intervals in CSF. A two-compartment model plus another CSF compartment best described the data. The central, intercentral/peripheral, and intercentral/CSF compartment clearances were 22.2 liters/h, 1.79 liters/h, and 0.01 liter/h, respectively. Distribution volumes of the central and peripheral compartments were 17.9 liters and 3.84 liters, respectively. The CSF compartment volume was fixed at 0.13 liter, with its clearance calculated by the observed drainage amount. The multiplier for the transfer from the central to the CSF compartment was 0.172. Simulation results show that the PTAs increase as infusion is prolonged and as the daily CSF drainage volume decreases. A 4-hour infusion of 2 g q8h with CSF drainage of less than 150 ml/day, which provides a PTA of >90% for MICs of ≤8 mg/liter in blood and of ≤0.5 mg/liter or 0.25 mg/liter in CSF, is recommended. (This study has been registered at ClinicalTrials.gov under identifier NCT02506686.).

Human meningitis due to Streptococcus suis in Lomé, Togo: a case report.

BACKGROUND: Streptococcus suis is a zoonotic pathogen which represents the leading cause of meningitis in Southeast Asia and an emerging pathogen in the Western world, the main risk factor for infection being contact with pigs. In Africa, the prevalence of S. suis infections in swine and humans is largely unrecognized, with only one recent report of a limited case series. CASE PRESENTATION: We describe a human case of meningitis due to S. suis in a 32-year-old man living in Togo. The patient had no particular medical history and no risk factors for immunodeficiency but reported regular contact with pork products. Using specific immunological and molecular methods, we characterized the isolate as S. suis serotype 2, ST1, one the most prevalent and virulent clone worldwide. The outcome was favorable after one week of adapted antibiotic therapy but the patient was left with severe hearing disorders. CONCLUSIONS: This work highlights the emergence of this pathogen in Africa and reinforces the need for accurate epidemiological and surveillance studies of S. suis infections and for educating clinicians and exposed groups in non-endemic countries.