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1.
Clin Microbiol Infect ; 30(6): 772-778, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38479702

ABSTRACT

OBJECTIVES: The objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. METHODS: We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement component 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score <5). RESULTS: Bacterial load was quantified in 152 CSF samples. Median age of these patients was 61 years (interquartile range [IQR] 51-68), and 69 of 152 (45%) were female. Median CSF bacterial load was 1.6 × 104 DNA copies/mL (IQR 3.4 × 103-1.2 × 105), and did not correlate with CSF white cell count nor with CSF protein concentrations. Median CSF C5a concentration was 35.8 mg/L (IQR 15.9-105.6), and was moderately correlated with CSF bacterial loads (Spearman's rho = 0.42; p < 0001). High bacterial loads were associated with development of complications, such as circulatory shock (OR per logarithmic increase: 2.4, 95% CI: 2.0-2.9; p < 0.001) and cerebrovascular complications [OR: 1.9, 95% CI: 1.6-2.3; p < 0.001]). High bacterial loads were also associated with unfavourable outcome (OR: 2.8, 95% CI: 2.4-3.3; p < 0.001) and death (OR: 3.1, 95% CI: 2.6-3.8; p < 0.001). In a multivariable regression model including age, immunocompromised state, extrameningeal infection focus, admission Glasgow Coma Scale score and CSF C5a concentration, CSF bacterial load remained an independent predictor of unfavourable outcome (adjusted OR: 2.5, 95% CI: 1.6-3.9; p < 0.001). DISCUSSION: High CSF bacterial load predicts the development of complications and unfavourable outcome in adults with pneumococcal meningitis.


Subject(s)
Bacterial Load , Meningitis, Pneumococcal , Humans , Female , Middle Aged , Male , Meningitis, Pneumococcal/cerebrospinal fluid , Meningitis, Pneumococcal/microbiology , Meningitis, Pneumococcal/mortality , Aged , Prospective Studies , Prognosis , Cerebrospinal Fluid/microbiology , Streptococcus pneumoniae/isolation & purification , Community-Acquired Infections/microbiology , Community-Acquired Infections/cerebrospinal fluid , Adult
2.
Rev Inst Med Trop Sao Paulo ; 61: e24, 2019 Apr 18.
Article in English | MEDLINE | ID: mdl-31017185

ABSTRACT

The cytological and biochemical examination of cerebrospinal fluid (CSF) has been used for the presumed diagnosis of bacterial meningitis until the final microbiological results are achieved. We assessed the ability of CSF lactate in comparison with other CSF parameters to discriminate bacterial and enteroviral community acquired meningitis. We included 1,187 CSF samples of acute community-acquired meningitis, being 662 cases of bacterial and 525 of enteroviral meningitis. Lactate concentration (mg/dL), leukocyte count/mm3, protein (mg/dL), and glucose (mg/dL) were compared between bacterial and viral meningitis. Receiver operator characteristic (ROC) curves were used to assess diagnostic performance. CSF leukocytes, CSF protein and CSF lactate were significantly higher in bacterial meningitis cases (P<0.0001). CSF glucose was significantly lower in bacterial meningitis cases (P<0.0001). CSF lactate showed the best predictive ability with an area under the curve of 0.944 (95% CI 0.929 - 0.959). Considering a cut off of CSF lactate of 30 mg/dL, the sensitivity and specificity for bacterial meningitis were 84.1% and 99%, respectively. In the cytological and biochemical CSF analysis, CSF lactate was the most accurate marker for bacterial meningitis.


Subject(s)
Community-Acquired Infections/cerebrospinal fluid , Enterovirus Infections/diagnosis , Lactic Acid/cerebrospinal fluid , Meningitis, Bacterial/diagnosis , Meningitis, Viral/diagnosis , Biomarkers/cerebrospinal fluid , Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Enterovirus Infections/cerebrospinal fluid , Humans , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Viral/cerebrospinal fluid , ROC Curve , Sensitivity and Specificity
3.
Infect Dis (Lond) ; 50(7): 514-521, 2018 07.
Article in English | MEDLINE | ID: mdl-29490540

ABSTRACT

BACKGROUND: The ability of cerebrospinal fluid (CSF) lactate to distinguish between acute bacterial meningitis (ABM) and aseptic meningitis/encephalitis (AME) is debated. We assessed the diagnostic value of CSF lactate to discriminate between ABM and AME. METHODS: We included 176 patients from a prospective adult cohort with neuroinfections. In total, 51 ABM and 125 AME patients with clinically and/or microbiologically diagnosed acute meningitis were examined with CSF-lactate and traditional markers for infection. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance. RESULTS: In CSF, lactate, leukocytes, fraction of neutrophils, protein and glucose ratio, were significantly different between the ABM and AME groups. CSF lactate had the best diagnostic value, with an area under the curve (AUC) of 0.976 (95%CI 0.966-0.997) and using a cut-off of 3.5 mmol/L a sensitivity of 96% and specificity of 85%. Antibiotic treatment before lumbar puncture had no significant effect on the AUC of CSF lactate. CONCLUSIONS: Compared to traditional CSF-markers, CSF lactate is more accurate to distinguish between ABM and AME.


Subject(s)
Community-Acquired Infections/diagnosis , Lactic Acid/cerebrospinal fluid , Meningitis, Aseptic/diagnosis , Meningitis, Bacterial/diagnosis , Acute Disease , Adult , Aged , Area Under Curve , Biomarkers/cerebrospinal fluid , Cohort Studies , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/microbiology , Data Accuracy , Diagnosis, Differential , Female , Humans , Male , Meningitis, Aseptic/cerebrospinal fluid , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/microbiology , Middle Aged , Prospective Studies , ROC Curve , Sensitivity and Specificity , Spinal Puncture
4.
Mikrobiyol Bul ; 51(3): 277-285, 2017 Jul.
Article in Turkish | MEDLINE | ID: mdl-28929964

ABSTRACT

In this multicenter prospective cohort study, it was aimed to evaluate the bacterial and viral etiology in community-acquired central nervous system infections by standart bacteriological culture and multiplex polymerase chain reaction (PCR) methods. Patients hospitalized with central nervous system infections between April 2012 and February 2014 were enrolled in the study. Demographic and clinical information of the patients were collected prospectively. Cerebrospinal fluid (CSF) samples of the patients were examined by standart bacteriological culture methods, bacterial multiplex PCR (Seeplex meningitis-B ACE Detection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B streptococci) and viral multiplex PCR (Seeplex meningitis-V1 ACE Detection kits herpes simplex virus-1 (HSV1), herpes simplex virus-2 (HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV6)) (Seeplex meningitis-V2 ACE Detection kit (enteroviruses)). Patients were classified as purulent meningitis, aseptic meningitis and encephalitis according to their clinical, CSF (leukocyte level, predominant cell type, protein and glucose (blood/CSF) levels) and cranial imaging results. Patients who were infected with a pathogen other than the detection of the kit or diagnosed as chronic meningitis and other diseases during the follow up, were excluded from the study. A total of 79 patients (28 female, 51 male, aged 42.1 ± 18.5) fulfilled the study inclusion criteria. A total of 46 patients were classified in purulent meningitis group whereas 33 were in aseptic meningitis/encephalitis group. Pathogens were detected by multiplex PCR in 41 patients. CSF cultures were positive in 10 (21.7%) patients (nine S.pneumoniae, one H.influenzae) and PCR were positive for 27 (58.6%) patients in purulent meningitis group. In this group one type of bacteria were detected in 18 patients (14 S.pneumoniae, two N.meningitidis, one H.influenzae, one L.monocytogenes). Besides, it is noteworthy that multiple pathogens were detected such as bacteria-virus combination in eight patients and two different bacteria in one patient. In the aseptic meningitis/encephalitis group, pathogens were detected in 14 out of 33 patients; single type of viruses in 11 patients (seven enterovirus, two HSV1, one HSV2, one VZV) and two different viruses were determined in three patients. These data suggest that multiplex PCR methods may increase the isolation rate of pathogens in central nervous system infections. Existence of mixed pathogen growth is remarkable in our study. Further studies are needed for the clinical relevance of this result.


Subject(s)
Central Nervous System Bacterial Infections/microbiology , Central Nervous System Viral Diseases/virology , Adolescent , Adult , Aged , Aged, 80 and over , Central Nervous System Bacterial Infections/cerebrospinal fluid , Central Nervous System Viral Diseases/cerebrospinal fluid , Cohort Studies , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Encephalitis/cerebrospinal fluid , Encephalitis/epidemiology , Encephalitis/microbiology , Encephalitis, Viral/cerebrospinal fluid , Encephalitis, Viral/epidemiology , Encephalitis, Viral/virology , Female , Humans , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/epidemiology , Meningitis, Bacterial/microbiology , Meningitis, Viral/cerebrospinal fluid , Meningitis, Viral/epidemiology , Meningitis, Viral/virology , Middle Aged , Multiplex Polymerase Chain Reaction , Prospective Studies , Young Adult
5.
New Microbiol ; 40(3): 170-174, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28513815

ABSTRACT

Infectious meningitis accounts for enormous morbidity worldwide, but there is a paucity of data on its regional epidemiology in resource-constrained settings of sub-Saharan Africa. Here, we present a study on the aetiology of paediatric meningitis in central Côte d'Ivoire. Between June 2012 and December 2013, all cerebrospinal fluid (CSF) samples drawn at the University Teaching Hospital Bouaké were examined for the presence of bacterial and fungal pathogens. A causative agent was detected in 31 out of 833 CSF specimens (3.7%), with the most prevalent pathogens being Streptococcus pneumoniae (n=15) and Neisseria meningitidis (n=5). With the exception of neonates, these two bacteria were the most common agents in all age groups. Of note, only a single case of Haemophilus influenzae meningitis was detected. Hence, this study reports a considerable shift in the epidemiology of paediatric meningitis in central Côte d'Ivoire. Following the implementation of a nation-wide childhood vaccination programme against H. influenzae type b, this pathogen was much less frequently reported than in previous studies. The integration of specific vaccines against S. pneumoniae and N. meningitidis into the childhood vaccination programme in Côted'Ivoire holds promise to further reduce the burden due to infectious meningitis.


Subject(s)
Haemophilus Vaccines/administration & dosage , Haemophilus influenzae type b/immunology , Meningitis, Haemophilus/prevention & control , Meningitis/epidemiology , Adolescent , Age Distribution , Cerebrospinal Fluid/microbiology , Child , Child, Preschool , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/microbiology , Cote d'Ivoire/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Meningitis/cerebrospinal fluid , Meningitis/microbiology , Microbial Sensitivity Tests , Neisseria meningitidis/isolation & purification , Streptococcus pneumoniae/isolation & purification
6.
Brain Behav ; 6(11): e00545, 2016 11.
Article in English | MEDLINE | ID: mdl-27843698

ABSTRACT

OBJECTIVES: Bacterial meningitis is a severe but treatable condition. Clinical symptoms may be ambiguous and current diagnostics lack sensitivity and specificity, complicating diagnosis. Procalcitonin (PCT) is a protein that is elevated in serum in bacterial infection. We aimed to assess the value of PCT in cerebrospinal fluid (CSF) in the diagnosis of bacterial meningitis. METHODS: We included patients with bacterial meningitis, both community acquired and post neurosurgery. We included two comparison groups: patients with viral meningitis and patients who underwent lumbar punctures for noninfectious indications. We calculated mean differences and 95% confidence intervals of procalcitonin in CSF and plasma in patients with and without bacterial meningitis. RESULTS: Average PCT concentrations in CSF were 0.60 ng mL-1 (95% CI: 0.29-0.92) in the bacterial meningitis group (n = 26), 0.81 (95% CI: 0.33-1.28) in community-acquired meningitis (n = 16) and 0.28 (95% CI: 0.10-0.45) in postneurosurgical meningitis (n = 10), 0.10 ng mL-1 (95% CI: 0.08-0.12) in the viral meningitis group (n = 14) and 0.08 ng mL-1 (95% CI: 0.06-0.09) in the noninfectious group (n = 14). Mean difference of PCT-CSF between patients with community-acquired bacterial meningitis and with viral meningitis was 0.71 ng mL-1 (95% CI: 0.17-1.25) and 0.73 ng mL-1 (95% CI: 0.19-1.27) for community-acquired bacterial meningitis versus the noninfectious group. The median PCT CSF: plasma ratio was 5.18 in postneurosurgical and 0.18 in community-acquired meningitis (IQR 4.69 vs. 0.28). CONCLUSION: Procalcitonin in CSF was significantly higher in patients with bacterial meningitis when compared with patients with viral or no meningitis. PCT in CSF may be a valuable marker in diagnosing bacterial meningitis, and could become especially useful in patients after neurosurgery.


Subject(s)
Calcitonin/cerebrospinal fluid , Meningitis, Bacterial/cerebrospinal fluid , Adult , Calcitonin/blood , Community-Acquired Infections/blood , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/diagnosis , Female , Humans , Male , Meningitis, Bacterial/blood , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/microbiology , Meningitis, Viral/blood , Meningitis, Viral/cerebrospinal fluid , Meningitis, Viral/diagnosis , Middle Aged , Prospective Studies
7.
Medicina (B Aires) ; 75(6): 367-72, 2015.
Article in Spanish | MEDLINE | ID: mdl-26707658

ABSTRACT

Acute bacterial meningitis has a global mortality rate of 135000 cases per year. In Argentina over the last 12 years, the annual incidence rate has been 5.5/100 000. About 20% of patients present neurological sequelae, which are more common in patients aged 60 or older. Our objective here is to determine the clinical characteristics, the most common causes and to measure evolution in patients over 60 years old diagnosed with meningitis and treated at the Hospital de Clinicas José de San Martín. This is a retrospective study based on a review of medical records from 2003 to 2013 that takes into account patients older than 60 who were diagnosed with acute bacterial meningitis acquired in the community by a microbiological diagnosis of CSF or those included due to a high suspicion of bacterial meningitis (pleocitosis > 2000 cells/mm3, proteins > 220 mg/dl, glycorrhachia < 34 mg/dl, glycorrhachia/glucose index < 0.23). Cases of TB meningitis, nosocomial, postoperative and other nonbacterial meningitis were excluded. Sixty nine patients were included, 45 (65%) were women with an average age of 78 ± 10.6 years. Only 40% had the triad of classical meningitis symptoms (stiff neck, fever and altered mental status). In 52% of the patients germs developed in the CSF, the most frequent being Streptococcus pneumoniae present in 47% of cases. Lethality rate was 41%, all of them by methicillin-sensitive Staphylococcus aureus. Only 24 (35%) cases were admitted into intensive care. The main sequelae present were motor disorders (12%) and hearing loss (5%).


Subject(s)
Meningitis, Bacterial/epidemiology , Acute Disease , Aged , Aged, 80 and over , Argentina/epidemiology , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Disease Progression , Female , Humans , Incidence , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/mortality , Meningitis, Pneumococcal/cerebrospinal fluid , Meningitis, Pneumococcal/epidemiology , Middle Aged , Retrospective Studies , Staphylococcal Infections/mortality
8.
J Thromb Haemost ; 13(11): 2076-86, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26340319

ABSTRACT

BACKGROUND: Mortality and morbidity in patients with bacterial meningitis result from the proinflammatory response and dysregulation of coagulation and fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is activated by free thrombin or thrombin in complex with thrombomodulin, and plays an antifibrinolytic role during fibrin clot degradation, but also has an anti-inflammatory role by inactivating proinflammatory mediators, such as complement activation products. OBJECTIVE: To assess the role of TAFI in pneumococcal meningitis. METHODS: We performed a prospective nationwide genetic association study in patients with bacterial meningitis, determined TAFI and complement levels in cerebrospinal fluid (CSF), and assessed the function of TAFI in a pneumococcal meningitis mouse model by using Cpb2 (TAFI) knockout mice. RESULTS: Polymorphisms (reference sequences: rs1926447 and rs3742264) in the CPB2 gene, coding for TAFI, were related to the development of systemic complications in patients with pneumococcal meningitis. Higher protein levels of TAFI in CSF were significantly associated with CSF complement levels (C3a, iC3b, and C5b-9) and with more systemic complications in patients with bacterial meningitis. The risk allele of rs1926447 (TT) was associated with higher levels of TAFI in CSF. In the murine model, consistent with the human data, Cpb2-deficient mice had decreased disease severity, as reflected by lower mortality, and attenuated cytokine levels and bacterial outgrowth in the systemic compartment during disease, without differences in the brain compartment, as compared with wild-type mice. CONCLUSIONS: These findings suggest that TAFI plays an important role during pneumococcal meningitis, which is likely to be mediated through inhibition of the complement system, and influences the occurrence of systemic complications and inflammation.


Subject(s)
Carboxypeptidase B2/physiology , Meningitis, Meningococcal/cerebrospinal fluid , Meningitis, Pneumococcal/cerebrospinal fluid , Polymorphism, Single Nucleotide , Adult , Aged , Animals , Brain Damage, Chronic/etiology , Carboxypeptidase B2/cerebrospinal fluid , Carboxypeptidase B2/deficiency , Carboxypeptidase B2/genetics , Cerebral Hemorrhage/etiology , Community-Acquired Infections/blood , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/complications , Community-Acquired Infections/genetics , Complement C3a/cerebrospinal fluid , Complement C3b/cerebrospinal fluid , Complement Membrane Attack Complex/cerebrospinal fluid , Cytokines/blood , Female , Fibrinolysis , Humans , Male , Meningitis, Meningococcal/blood , Meningitis, Meningococcal/complications , Meningitis, Meningococcal/genetics , Meningitis, Pneumococcal/blood , Meningitis, Pneumococcal/complications , Meningitis, Pneumococcal/genetics , Mice , Mice, Inbred C57BL , Middle Aged , Respiratory Insufficiency/etiology , Shock, Septic/etiology , Treatment Outcome
9.
Int J Infect Dis ; 39: 39-43, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26299186

ABSTRACT

OBJECTIVES: Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. METHODS: This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4. RESULTS: Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001). CONCLUSION: Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis.


Subject(s)
Glucose/cerebrospinal fluid , Meningitis/cerebrospinal fluid , Meningitis/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/diagnosis , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Young Adult
10.
J Infect ; 69(5): 424-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24973553

ABSTRACT

BACKGROUND: Penetration and concentration of vancomycin is still an elusive and complex issue particularly in Cerebrospinal Fluid (CSF). The aim of this study was to clarify the penetration of this antimicrobial agent in CSF during meningeal inflammation. METHODS: In a prospective study, adult patients, with clinical and CSF analysis compatible with acute meningitis, who received vancomycin (15 mg/kg loading and 30 mg/kg daily maintenance dose) with ceftriaxone (4 gr/daily) were enrolled. CSF analysis including vancomycin trough levels before the fourth maintenance dose and during the 8-10th days of treatment, and simultaneous serum levels were performed by High-Pressure Liquid Chromatography (HPLC). RESULTS: Twenty-seven patients (18 men, 9 women; mean age of 39.4 ± 14.7) were enrolled. The first serum trough level of vancomycin was 13.82 ± 1.28 mg/l. The mean of corresponding trough level in CSF was 11.2 ± 1.41 mg/l. The serum and CSF trough levels revealed positive linear correlation (r: 0.60) and was significant at the 0.01 level (P: 0.004). The penetration CSF/serum ratio was 0.811 ± 0.082 (coefficient of variation: 10.1%). The second trough levels of serum and CSF in (14 patients) vancomycin were 13.32 ± 1.02 and 10.64 ± 1.21, respectively. The serum and CSF trough levels revealed positive linear correlation (r: 0.71). The serum and CSF concentrations revealed no variation compared to the first trough levels. CONCLUSION: Vancomycin has appropriate concentration in CSF during the treatment of meningitis and do not decrease along with the alleviation of meningeal inflammation in spite of concerns in this regard.


Subject(s)
Anti-Bacterial Agents/blood , Anti-Bacterial Agents/cerebrospinal fluid , Meningitis, Bacterial/drug therapy , Vancomycin/blood , Vancomycin/cerebrospinal fluid , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/blood , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/microbiology , Female , Humans , Iran , Male , Meningitis, Bacterial/blood , Meningitis, Bacterial/cerebrospinal fluid , Middle Aged , Vancomycin/therapeutic use , Young Adult
12.
S Afr Med J ; 103(12): 906-9, 2013 Sep 03.
Article in English | MEDLINE | ID: mdl-24300626

ABSTRACT

BACKGROUND: Community-acquired bacterial meningitis (CABM) is a life-threatening condition that is common among immunocompromised individuals. Intravenous ceftriaxone, of which Rocephin (ROC) is the originator brand, is recommended as first-line therapy in South Africa. Despite concerns regarding therapeutic equivalence with generic agents, this is the first study that has been conducted comparing clinical pharmacokinetics (PK) of a generic ceftriaxone formulation with the originator. OBJECTIVE: To compare the PK and safety of Aspen Ceftriaxone (AC) and ROC in the treatment of adult CABM.Methods. A total of 63 eligible patients were randomised 1:1 to receive 2 g of either medication twice daily for a duration based on the identity of the causative organism and their physician's clinical judgment. The primary endpoint of this study was the comparison of clinical PK, specifically the concentrations of each drug in the cerebrospinal fluid with corresponding paired plasma samples. While this study was underpowered to assess efficacy, safety could be evaluated on the basis of reported adverse events. RESULTS: The two patient groups were epidemiologically similar. There were no statistically significant differences in PK between either agent, nor any difference with regard to safety. CONCLUSION: AC can be considered as equivalent to ROC with regard to PK and safety in patients with CABM.


Subject(s)
Ceftriaxone , Community-Acquired Infections/drug therapy , Drugs, Generic , Meningitis, Bacterial/drug therapy , APACHE , Administration, Intravenous , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Biological Availability , Ceftriaxone/administration & dosage , Ceftriaxone/adverse effects , Ceftriaxone/pharmacokinetics , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/microbiology , Dose-Response Relationship, Drug , Double-Blind Method , Drug Monitoring , Drugs, Generic/administration & dosage , Drugs, Generic/adverse effects , Drugs, Generic/pharmacokinetics , Female , Humans , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/microbiology , Middle Aged , Therapeutic Equivalency , Treatment Outcome
14.
Rev Neurol ; 56(1): 13-8, 2013 Jan 01.
Article in Spanish | MEDLINE | ID: mdl-23250677

ABSTRACT

INTRODUCTION: Listeria monocytogenes is the third most common cause of community-acquired bacterial meningitis in adults. AIMS: To describe the characteristics of meningitis caused by Listeria (LM) in adults and to compare them with those of meningitis due to other causations (nLM). PATIENTS AND METHODS: A retrospective analysis of a series of hospital cases was conducted, including patients aged between ≥ 14 years diagnosed with LM in a referral hospital between 1982 and 2011. RESULTS: The study involves 16 cases of LM, 12.1% of the cases of community-acquired meningitis with an identified aetiology. Predisposing factors were age (mean of 65 versus 52 years; p = 0.019) and immunosuppression/comorbidity (62.5% versus 3.4%; p < 0.001), treatment with corticoids (37.5%) and chronic liver disease (25%) being the most frequent. The classical triads of acute bacterial meningitis, clinical features and analysis of the cerebrospinal fluid (CSF) were observed in 50 and 75% of the cases, respectively. Patients with LM presented lower leukocyte counts in CSF, a lower percentage of neutrophils, a greater frequency of lymphocytic pleocytosis and a lower frequency of Gram stain positive than those with nLM. The mortality rate was 12.5%, similar to that of patients with nLM. CONCLUSIONS: LM mainly affects patients who are immunosuppressed or with comorbidity, as well as elderly patients, although it may occur in the absence of risk factors. Clinically it does not differ from other causes of meningitis, but the initial CSF study may suggest it. Its mortality rate is similar to that of meningitis due to other aetiologies.


Subject(s)
Meningitis, Listeria/epidemiology , Acute Disease , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Community-Acquired Infections/pathology , Comorbidity , Drug Resistance, Multiple, Bacterial , Female , HIV Infections/epidemiology , Hospitals, University/statistics & numerical data , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Length of Stay/statistics & numerical data , Leukocytosis/etiology , Liver Diseases/epidemiology , Male , Meningitis/cerebrospinal fluid , Meningitis/epidemiology , Meningitis/pathology , Meningitis, Listeria/cerebrospinal fluid , Meningitis, Listeria/drug therapy , Meningitis, Listeria/pathology , Middle Aged , Neoplasms/drug therapy , Neoplasms/epidemiology , Opportunistic Infections/cerebrospinal fluid , Opportunistic Infections/drug therapy , Opportunistic Infections/epidemiology , Opportunistic Infections/pathology , Retrospective Studies , Risk Factors , Spain/epidemiology , Tertiary Care Centers/statistics & numerical data , Tomography, X-Ray Computed
15.
Lancet ; 380(9854): 1684-92, 2012 Nov 10.
Article in English | MEDLINE | ID: mdl-23141617

ABSTRACT

Rapid diagnosis and treatment of acute community-acquired bacterial meningitis reduces mortality and neurological sequelae, but can be delayed by atypical presentation, assessment of lumbar puncture safety, and poor sensitivity of standard diagnostic microbiology. Thus, diagnostic dilemmas are common in patients with suspected acute community-acquired bacterial meningitis. History and physical examination alone are sometimes not sufficient to confirm or exclude the diagnosis. Lumbar puncture is an essential investigation, but can be delayed by brain imaging. Results of cerebrospinal fluid (CSF) examination should be interpreted carefully, because CSF abnormalities vary according to the cause, patient's age and immune status, and previous treatment. Diagnostic prediction models that use a combination of clinical findings, with or without test results, can help to distinguish acute bacterial meningitis from other causes, but these models are not infallible. We review the dilemmas in the diagnosis of acute community-acquired bacterial meningitis, and focus on the roles of clinical assessment and CSF examination.


Subject(s)
Meningitis, Bacterial/diagnosis , Acute Disease , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Decision Support Techniques , Diagnosis, Differential , Humans , Medical History Taking/methods , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/drug therapy , Physical Examination/methods , Spinal Puncture/methods , Tomography, X-Ray Computed
16.
J Neurol ; 259(2): 225-36, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21706150

ABSTRACT

UNLABELLED: The aim of the study was to assess adjunctive intravenous dexamethasone in adult community-acquired bacterial meningitis (BM) in daily practice. Analysis of consecutive patients (1990-2009) with acute community-acquired bacterial meningitis in a single centre in Zagreb, Croatia, N = 304. Adjusted relative risks [RR, dexamethasone vs. no dexamethasone (control)] of Glasgow Outcome Scale (GOS) = 1 (death) and GOS = 5 (full recovery) at discharge/end of specific treatment were estimated considering demographics; co-morbidity; BM pathogenesis and on-admission characteristics, and cerebrospinal fluid (CSF) inflammation markers; causative agent and antibiotic use. Two hundred forty (79%) patients had proven BM (43.1% Streptococcus pneumoniae, any other agent ≤ 8.2%). No independent effects of dexamethasone on GOS = 1 or GOS = 5 were observed in the entire cohort (dexamethasone n = 119, control n = 185; RR = 1.06, 95% CI 0.77-1.45 and RR = 0.99, CI 0.83-1.20, respectively), microbiologically proven disease (dexamethasone n = 104, control n = 136; RR = 0.97, CI 0.69-1.38 and RR = 1.03, CI 0.82-1.28), pneumococcal disease (dexamethasone n = 71, control n = 60; RR = 0.95, CI 0.53-1.70 and RR = 0.82, CI 0.57-1.18), and also in other BM, subgroups based on consciousness disturbance, CSF markers, prior use of antibiotics and timing of appropriate antibiotic treatment. CSF markers did not predict the outcomes. CONCLUSIONS: Our experience does not substantiate the reported benefits of adjunctive dexamethasone in adult BM. Socio-economic and methodological factors do not seem to explain this discrepancy. Empirical use of dexamethasone in this setting appears controversial.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Community-Acquired Infections/drug therapy , Dexamethasone/therapeutic use , Meningitis, Bacterial/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents , Chemotherapy, Adjuvant , Community-Acquired Infections/cerebrospinal fluid , Female , Glasgow Outcome Scale , Humans , Inflammation/cerebrospinal fluid , Inflammation/drug therapy , Male , Meningitis, Bacterial/cerebrospinal fluid , Middle Aged , Recovery of Function/drug effects , Young Adult
17.
Neuroradiology ; 51(11): 723-9, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19618175

ABSTRACT

INTRODUCTION: Here, we analyzed the frequency, morphological pattern, and imaging characteristics of focal lesions as a consequence of community-acquired bacterial meningitis. We hypothesized that diffusion-weighted imaging combined with contrast-enhanced imaging, serial scanning, and multimodal vascular studies would provide further insight into the pathological basis of such parenchymal lesions in bacterial meningitis. METHODS: We reviewed clinical and imaging data (i.e., magnetic resonance tomography, magnetic resonance angiography, computed tomography angiography, digital subtraction angiography) of 68 adult patients admitted to our neurological intensive care unit between March 1998 and February 2009 with the diagnosis of community-acquired bacterial meningitis. RESULTS: We identified seven patients with parenchymal lesions. These lesions could be attributed to four morphological patterns: (1) territorial cerebral ischemia, (2) perforating vessels ischemia, (3) ischemia of presumed cardiac origin, and (4) isolated cortical lesions. Whereas the patterns (1) and (2) were associated with vasculopathy of large- and medium-sized vessels (as shown by cerebral vascular imaging), vessel imaging in (3) and (4) did not show abnormal findings. CONCLUSION: Our study implies that parenchymal lesions in acute bacterial meningitis are mainly ischemic and due to involvement of large-, medium-, and small-sized arteries of the brain. Diffusion-weighted imaging combined with conventional, CT-, or MR-based cerebral angiography revealed the underlying pathophysiological mechanisms in the majority of patients. Furthermore, we detected two patients with isolated bilateral cortical involvement and normal vessel imaging. These lesions might represent ischemia due to the involvement of small pial and intracortical arteries.


Subject(s)
Brain Ischemia/pathology , Brain/blood supply , Brain/pathology , Meningitis, Bacterial/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Angiography, Digital Subtraction , Brain/diagnostic imaging , Brain Ischemia/cerebrospinal fluid , Brain Ischemia/diagnostic imaging , Cerebral Angiography , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/diagnostic imaging , Community-Acquired Infections/pathology , Diffusion Magnetic Resonance Imaging , Female , Follow-Up Studies , Humans , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/diagnostic imaging , Middle Aged , Tomography, X-Ray Computed , Young Adult
18.
Intern Med ; 48(7): 537-43, 2009.
Article in English | MEDLINE | ID: mdl-19336955

ABSTRACT

OBJECTIVE: To derive and validate a clinical prediction model with high sensitivity for differentiating aseptic meningitis (AM) patients from bacterial meningitis (BM) patients. METHODS: We developed the model using the derivation cohort in a community rural hospital in Okinawa and assessed its performance using the validation cohort in a metropolitan urban hospital in Tokyo. There were 66 (39.5%) and 5 (17.9%) adult patients with BM among the derivation (n=167) and the validation cohort (n=28), respectively. Recursive partitioning analysis was used to determine the important classification variables and to develop a sensitive model to safely exclude BM. RESULTS: The model produced high- and low-risk groups based on the following: 1) Gram stain, 2) CSF neutrophil percent < or =15%, 3) CSF neutrophil count < or =150 cells/mm(3), and, 4) mental status change. Among the derivation cohort, there were 65 patients with BM in the high-risk group (n=76), while only one patient with BM was noted (sensitivity, 99%) in the low-risk group (n=91). Among the validation cohort, there were 5 patients with BM in the high-risk group (n=7), while no patient was classified with BM (sensitivity, 100%) in the low-risk group (n=21). CONCLUSION: This simple and sensitive model might be useful to safely identify low-risk patients for BM who would not require antibiotic treatment.


Subject(s)
Community-Acquired Infections/diagnosis , Meningitis, Aseptic/diagnosis , Meningitis, Bacterial/diagnosis , Adult , Aged , Algorithms , Anti-Bacterial Agents/therapeutic use , Cerebrospinal Fluid/cytology , Cerebrospinal Fluid/microbiology , Cerebrospinal Fluid Proteins/analysis , Cohort Studies , Community-Acquired Infections/blood , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/epidemiology , Diagnosis, Differential , Gentian Violet , Glucose/cerebrospinal fluid , Hospitals, Rural/statistics & numerical data , Hospitals, Urban/statistics & numerical data , Humans , Japan/epidemiology , Leukocyte Count , Meningitis, Aseptic/blood , Meningitis, Aseptic/cerebrospinal fluid , Meningitis, Aseptic/epidemiology , Meningitis, Bacterial/blood , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/epidemiology , Meningitis, Bacterial/microbiology , Middle Aged , Models, Theoretical , Phenazines , Predictive Value of Tests , Risk , Sensitivity and Specificity , Unnecessary Procedures , Young Adult
19.
Enferm Infecc Microbiol Clin ; 27(1): 33-6, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19218001

ABSTRACT

INTRODUCTION: An adult with community-acquired Capnocytophaga canimorsus meningitis presented with a subacute course, deafness, and a predominantly lymphocytic CSF cell count. METHODS: Eighteen reported cases of C. canimorsus meningitis in adults were analyzed. RESULTS: In about half the cases, CSF contained less than 1,000 leukocytes/microL or lymphocyte percentages 30%. These figures differ from those usually seen in meningitis caused by the classic meningeal pathogens. CONCLUSIONS: C. canimorsus should be included among the causes of sporadic lymphocytic meningitis in adults, in particular if the presentation involves deafness.


Subject(s)
Bites and Stings/complications , Capnocytophaga/pathogenicity , Community-Acquired Infections/microbiology , Gram-Negative Bacterial Infections/microbiology , Hearing Loss, Bilateral/etiology , Hearing Loss, Sensorineural/etiology , Meningitis, Bacterial/microbiology , Ampicillin/administration & dosage , Ampicillin/therapeutic use , Animals , Bites and Stings/microbiology , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/complications , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Dogs , Gram-Negative Bacterial Infections/cerebrospinal fluid , Gram-Negative Bacterial Infections/complications , Gram-Negative Bacterial Infections/epidemiology , Hand Injuries/complications , Hand Injuries/microbiology , Humans , Leukocytosis/cerebrospinal fluid , Leukocytosis/etiology , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/complications , Meningitis, Bacterial/epidemiology , Middle Aged , Wound Infection/complications , Wound Infection/microbiology
20.
QJM ; 101(3): 225-30, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18234734

ABSTRACT

BACKGROUND: Increased levels of cerebrospinal fluid (CSF) 14-3-3 proteins have been reported in acute bacterial meningitis. We tested the hypothesis that CSF 14-3-3 protein levels are substantially increased in acute bacterial meningitis and decreased after anti-microbial therapy, and that CSF 14-3-3 protein levels can predict treatment outcomes. METHODS: We examined serial pan-CSF 14-3-3 (14-3-3-P) protein and five major isoform (beta, gamma, epsilon, eta, zeta) levels in 29 adult community-acquired bacterial meningitis (ACABM) patients. The CSF 14-3-3 protein levels were also evaluated in 12 aseptic meningitis patients during the study period. RESULTS: All of the meningitis patients had a positive result on admission. Levels of CSF 14-3-3 protein in ACABM cases were significantly increased initially, and substantially decreased thereafter. Most of those who survived (survivors = 25 and non-survivors = 4) had nearly cleared their 14-3-3 protein from the CSF before discharge. Conversely, patients who died never cleared their CSF 14-3-3 protein. The median value of CSF 14-3-3-P and 14-3-3 gamma, 14-3-3 eta and 14-3-3 epsilon isoforms on admission in the bacterial meningitis group were 173.7, 137.7, 42.2 and 9.1, respectively, which were statistically significant than those of the aseptic meningitis group (48.4, 39.6, 2.5 and 0, respectively). Stepwise logistic regression analysis showed only CSF 14-3-3 gamma isoform on admission was independently associated with outcome (P = 0.05, OR = 0.991). CONCLUSION: Serial 14-3-3 protein gamma isoform actually meets the major requirements for outcome prediction in the treatment of ACABM patients. Assay of the 14-3-3 protein gamma isoform should be added as a neuro-pathologic marker among the panel of conventional CSF parameters.


Subject(s)
14-3-3 Proteins/cerebrospinal fluid , Meningitis, Bacterial/cerebrospinal fluid , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/cerebrospinal fluid , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/drug therapy , Community-Acquired Infections/mortality , Female , Humans , Leukocyte Count , Logistic Models , Male , Meningitis, Aseptic/cerebrospinal fluid , Meningitis, Aseptic/drug therapy , Meningitis, Aseptic/mortality , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/mortality , Middle Aged , Prognosis , Prospective Studies , Protein Isoforms/cerebrospinal fluid , ROC Curve , Survival Rate
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