Ramsay Hunt syndrome and concurrent varicella-zoster virus meningitis in Denmark: A nationwide cohort study.

Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.

Brain ventricular dimensions and relationship to outcome in adult patients with bacterial meningitis.

BACKGROUND: Experimental studies suggest that changes in brain ventricle size are key events in bacterial meningitis. This study investigated the relationship between ventricle size, clinical condition and risk of poor outcome in patients with bacterial meningitis. METHODS: Adult patients diagnosed with bacterial meningitis admitted to two departments of infectious diseases from 2003 through 2010 were identified. Clinical and biochemical data as well as cerebral computed tomographic images were collected. The size of the brain ventricles were presented as a Ventricle to Brain Ratio (VBR). Normal range of VBR was defined from an age matched control group. A multivariate analysis was performed to identify predictors of 30-day mortality. RESULTS: One hundred and seven patients were included. Eighty-one patients had a CT scan at the time of diagnosis. VBR was identified as an independent risk factor of 30-day mortality, Mortality Rate Ratio: 6.03 (95 % confidence interval: 1.61-22.64, p = 0.008) for highest versus lowest tertile. A VBR deviating more than 2 standard deviations from the normal range was associated with increased mortality. CONCLUSIONS: Brain ventricles are commonly subject to marked changes in size as a consequence of meningitis. Increased brain ventricle size in the acute phase of bacterial meningitis was associated with increased mortality.

Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia.

BACKGROUND: The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS: Experimental meningitis in rats was induced by intracisternal injection of live pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti-pneumococcal antibodies (n = 14). T2 and diffusion weighted MR images were used to analyze changes in hippocampus volume and water diffusion (ADC). The results were correlated to ADC of the cortex, to ventricular volume, and to the extent of hippocampal apoptosis. RESULTS: Both ADC and the volume of hippocampus were significantly increased in meningitis rats compared to uninfected controls (Kruskal-Wallis test, p = 0.0001, Dunns Post Test, p < 0.05), and were significantly increased in meningitis rats with an early onset bacteremia as compared to meningitis rats with attenuated bacteremia (p < 0.05). Hippocampal ADC and the volume and size of brain ventricles were positively correlated (Spearman Rank, p < 0.05), whereas no association was found between ADC or volume and the extent of apoptosis (p > 0.05). CONCLUSIONS: In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly associated with accompanying bacteremia.

Bacteriophages for the treatment of pseudomonas-infected vascular prosthesis.

We present a case report detailing therapeutic application of two lytic antipseudomonal bacteriophages to treat a chronic relapsing Pseudomonas aeruginosa infection of a prosthetic aortic graft. As there are currently no Danish laboratories offering phages for clinical therapy, and this case, to our knowledge represents the first applied phage therapy in Denmark, the practical and regulatory aspects of offering this treatment option in Denmark is briefly reviewed along with the clinical case.

Noninvasive intracranial pressure monitoring in central nervous system infections.

Intracranial pressure (ICP) monitoring constitutes an important part of the management of traumatic brain injury. However, its application in other brain pathologies such as neuroinfections like acute bacterial meningitis is unclear. Despite focus on aggressive, prompt treatment, morbidity and mortality from acute bacterial meningitis remain high. Increased ICP is well-known to occur in severe neuroinfections. The increased ICP compromise cerebral perfusion pressure and may ultimately lead to brain stem herniation. Therefore, controlling the ICP could also be important in acute bacterial meningitis. However, risk factors for complications due to invasive monitoring among these patients may be significantly increased due to higher age and levels of comorbidity compared to the traumatic brain injury patient from which the ICP treatment algorithms are developed. This narrative review evaluates the different modalities of ICP monitoring with the aim to elucidate current status of non-invasive alternatives to invasive monitoring as a decision tool and eventually monitoring. Non-invasive screening using ultrasound of the optical nerve sheath, transcranial doppler, magnetic resonance imaging or preferably a combination of these modalities, provides measurements that can be used as a decision guidance for invasive ICP measurement. The available data do not support the replacement of invasive techniques for continuous ICP measurement in patients with increased ICP. Non-invasive modalities should be taken into consideration in patients with neuroinfections at low risk of increased ICP.

Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza.

BACKGROUNDAntibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A.METHODSTo probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays.RESULTSInfluenza-specific FcγR-binding antibodies were elevated in Flu-IVIG-infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody.CONCLUSIONThese detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies.TRIAL REGISTRATIONClinicalTrials.gov NCT02287467.FUNDINGFunding for this research was provided by subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.

[Lyme neuroborreliosis in adults].

Lyme neuroborreliosis (LNB) caused by the spirochete bacteria Borrelia burgdorferi sensu lato complex is the most common bacterial neuroinfection in Denmark (180 cases per year). One of the main challenges to LNB is the diagnosis due to its variant manifestations often involving the skin, musculosceletal or nervous system affecting patient morbidity. Recent data shows a diagnostic delay of 21 days in laboratory-confirmed patients in Denmark. The aim of this review is to summarise current state of knowledge concerning clinical manifestations, diagnostic assessment, antibiotic therapy, and prognosis.

Effect of generics on price and consumption of ciprofloxacin in primary healthcare: the relationship to increasing resistance.

BACKGROUND: The introduction of generic versions of drugs has often resulted in an increase in the consumption of the agents involved. In December 2001, generic ciprofloxacin was marketed in Denmark. Our objective was to evaluate, in a community setting, the effect of price on consumption of ciprofloxacin and on ciprofloxacin resistance in Escherichia coli urine isolates. METHODS: We conducted a retrospective ecological study collecting monthly national data on the number of marketed versions and primary healthcare (PHC) sales of ciprofloxacin during January 1995-December 2005. Data were compared with a median price per defined daily dose (DDD) of ciprofloxacin during September 1999-December 2005. Yearly PHC consumption data from seven Danish counties were compared with the antimicrobial resistance profiles of PHC E. coli urine isolates. RESULTS: During 2002, the number of marketed versions increased from 3 to 10, and the median price per DDD decreased by 53%. From 2002 to 2005, the total consumption of oral ciprofloxacin in PHC increased significantly from 0.13 DDD/1000 inhabitant-days to 0.33 DDD/1000 inhabitant-days. During the same period, the frequency of ciprofloxacin resistance increased by 200%. A statistically significant correlation was found between the consumption of ciprofloxacin and the ciprofloxacin resistance rate in E. coli urine isolates, independent of the introduction of generic ciprofloxacin. CONCLUSIONS: After the introduction of generic ciprofloxacin, a significant increase in the total consumption of oral ciprofloxacin in PHC was observed in Denmark. The increase in consumption was significantly correlated with ciprofloxacin resistance in E. coli obtained from urine isolates.

Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis.

BACKGROUND: Bacteremia and systemic complications both play important roles in brain pathophysiological alterations and the outcome of pneumococcal meningitis. Their individual contributions to the development of brain damage, however, still remain to be defined. METHODS: Using an adult rat pneumococcal meningitis model, the impact of bacteremia accompanying meningitis on the development of hippocampal injury was studied. The study comprised of the three groups: I. Meningitis (n = 11), II. meningitis with attenuated bacteremia resulting from iv injection of serotype-specific pneumococcal antibodies (n = 14), and III. uninfected controls (n = 6). RESULTS: Pneumococcal meningitis resulted in a significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected controls (0.02 (0.00-0.02), Mann Whitney test, P = 0.0003). Also, meningitis with an attenuation of bacteremia by antibody treatment resulted in significantly reduced apoptosis (0.08 (0.02-0.20), P = 0.01) as compared to meningitis. CONCLUSIONS: Our results demonstrate that bacteremia accompanying meningitis plays an important role in the development of hippocampal injury in pneumococcal meningitis.

Experimental studies of pneumococcal meningitis.

This thesis summarizes experimental meningitis research conducted at Statens Serum Institut in collaboration with the Copenhagen HIV programme and the Danish Research Centre for Magnetic Resonance between 2001 and 2007. Previous experimental studies had shown that the host inflammatory response in invasive infections contributed significantly to an extremely poor outcome despite initiation of efficient antimicrobial chemotherapy. Consequently, we aimed to investigate and clarify how the course of disease in pneumococcal meningitis was modulated by local meningeal inflammation and concomitant systemic infection and inflammation. Experimental studies were based on the development of a rat model of pneumococcal meningitis, refined and optimized to closely resemble the human disease, mimicking disease severity, outcome, focal- and global brain injury and brain pathophysiology. These endpoints were evaluated by the development of a clinical score system, definition of outcomes and measurement of hearing loss by otoacoustic emission. The investigation of in-vitro and in-vivo brain pathology with histology and MRI revealed an injury pattern similar to that found clinically. Additionally, MRI enabled the study of parameters closely related to the cerebral pathophysiology of meningitis (brain oedema, blood brain barrier (BBB) permeability, focal brain injury and hydrocephalus). Modulation of the inflammatory host response was achieved by initiation of treatment prior to infection: 1) G-CSF treatment increased the peripheral availability of leukocytes, 2) Selectin blocker fucoidin attenuated meningeal leukocyte accumulation and 3) A serotype specific Ab augmented systemic pneumococcal phagocytosis. The studies revealed a dual role of the inflammatory response in pneumococcal meningitis. Whilst focal brain injury appeared to result from local meningeal infectious processes, clinical disease severity and outcome appeared determined by systemic infection. Furthermore systemic disease contributed significantly to BBB permeability and brain ventricle expansion. Ventricle expansion was also associated with clinical appearance. An augmented systemic host response limited pneumococcal bacteraemia and protected from fatal outcome, but did not reduce occurrence of focal brain injury. Thus, our findings suggest that meningitis sequelae arise from local disease complications whereas fatal outcome is accelerated by systemic infection. Understanding of the relationship and interplay between septicaemia, intracranial pressure, ventricle expansion and brain edema could help optimize the treatment of these disease complications by, for example, improved systemic infection control. New therapeutic approaches to improve survival and neurological outcome from pneumococcal meningitis may be achieved through identification of the pathogen factors that initiate and prolong extensive systemic and local inflammation. Investigation of genomic differences and protein expression between pneumococcal serotypes or between identical serotypes with different virulence are considered crucial to this progress. Future progress may also be achieved by disease prevention with pneumococcal vaccines. Randomized trials of treatment strategies including bacteriostatic agents, antioxidants or more specific anti-inflammatory agents are realistic possibilities in the near future.

The effect of S. pneumoniae bacteremia on cerebral blood flow autoregulation in rats.

In the present study, we studied the effect of bacteremia on cerebral blood flow (CBF) autoregulation in a rat model of pneumococcal bacteremia and meningitis. Anesthetized rats were divided into five groups (A to E) and inoculated with pneumococci intravenously and normal saline intracisternally (group A, N=10); saline intravenously and pneumococci intracisternally (group B, N=10); pneumococci intravenously and pneumococci intracisternally (group C, N=5); saline intravenously, antipneumococcal antibody intravenously (to prevent bacteremia), and pneumococci intracisternally (group D, N=10); or saline intravenously and saline intracisternally (group E, N=10), respectively. Positive cultures occurred in the blood for all rats in groups A, B, and C, and in the cerebrospinal fluid for all rats in groups D and E. Twenty-four hours after inoculation, CBF was measured with laser-Doppler ultrasound during incremental reductions in cerebral perfusion pressure (CPP) by controlled hemorrhage. Autoregulation was preserved in all rats without meningitis (groups A and E) and was lost in 24 of 25 meningitis rats (groups B, C, and D) (P<0.01). In group A, the lower limit was higher than that of group E (P<0.05). The slope of the CBF/CPP regression line differed between the meningitis groups (P<0.001), being steeper for group B than groups C and D, with no difference between these two groups. The results suggest that pneumococcal bacteremia in rats triggers cerebral vasodilation, which right shifts the lower limit of, but does not entirely abolish, CBF autoregulation in the absence of meningitis, and which may further aggravate the vasoparalysis induced by concomitant pneumococcal meningitis.

In vivo study of experimental pneumococcal meningitis using magnetic resonance imaging.

BACKGROUND: Magnetic Resonance Imaging (MRI) methods were evaluated as a tool for the study of experimental meningitis. The identification and characterisation of pathophysiological parameters that vary during the course of the disease could be used as markers for future studies of new treatment strategies. METHODS: Rats infected intracisternally with S. pneumoniae (n = 29) or saline (n = 13) were randomized for imaging at 6, 12, 24, 30, 36, 42 or 48 hours after infection. T1W, T2W, quantitative diffusion, and post contrast T1W images were acquired at 4.7 T. Dynamic MRI (dMRI) was used to evaluate blood-brain-barrier (BBB) permeability and to obtain a measure of cerebral and muscle perfusion. Clinical- and motor scores, bacterial counts in CSF and blood, and WBC counts in CSF were measured. RESULTS: MR images and dMRI revealed the development of a highly significant increase in BBB permeability (P < 0.002) and ventricle size (P < 0.0001) among infected rats. Clinical disease severity was closely related to ventricle expansion (P = 0.024). Changes in brain water distribution, assessed by ADC, and categorization of brain 'perfusion' by cortex DeltaSI(bolus) were subject to increased inter-rat variation as the disease progressed, but without overall differences compared to uninfected rats (P > 0.05). Areas of well-'perfused' muscle decreased with the progression of infection indicative of septicaemia (P = 0.05). CONCLUSION: The evolution of bacterial meningitis was successfully followed in-vivo with MRI. Increasing BBB-breakdown and ventricle size was observed in rats with meningitis whereas changes in brain water distribution were heterogeneous. MRI will be a valuable technique for future studies aiming at evaluating or optimizing adjunctive treatments.

Cerebral blood flow autoregulation in early experimental S. pneumoniae meningitis.

We studied cerebral blood flow (CBF) autoregulation and intracranial pressure (ICP) during normo- and hyperventilation in a rat model of Streptococcus pneumoniae meningitis. Meningitis was induced by intracisternal injection of S. pneumoniae. Mean arterial blood pressure (MAP), ICP, cerebral perfusion pressure (CPP, defined as MAP - ICP), and laser-Doppler CBF were measured in anesthetized infected rats (n = 30) and saline-inoculated controls (n = 30). CPP was either incrementally reduced by controlled hemorrhage or increased by intravenous norepinephrine infusion. Twelve hours postinoculation, rats were studied solely during normocapnia, whereas rats studied after 24 h were exposed to either normocapnia or to acute hypocapnia. In infected rats compared with control rats, ICP was unchanged at 12 h but increased at 24 h postinoculation (not significant and P < 0.01, respectively); hypocapnia did not lower ICP compared with normocapnia. Twelve hours postinoculation, CBF autoregulation was lost in all infected rats but preserved in all control rats (P < 0.01). Twenty-four hours after inoculation, 10% of infected rats had preserved CBF autoregulation during normocapnia compared with 80% of control rats (P < 0.01). In contrast, 60% of the infected rats and 100% of the control rats showed an intact CBF autoregulation during hypocapnia (P < 0.05 for the comparison of infected rats at normocapnia vs. hypocapnia). In conclusion, CBF autoregulation is lost both at 12 and at 24 h after intracisternal inoculation of S. pneumoniae in rats. Impairment of CBF autoregulation precedes the increase in ICP, and acute hypocapnia may restore autoregulation without changing the ICP.

A comparison of antibiotic use in children between Canada and Denmark.

BACKGROUND: High rates of antibiotic prescribing in children lead to antibiotic resistance in the community. Surveillance on utilization rates and comparisons with other jurisdictions are methods for benchmarking. Surveillance on antibiotic use is well established in Europe, including Denmark, but until recently, similar data from Canada were lacking. OBJECTIVE: To compare pediatric antibiotic prescribing rates in British Columbia, Canada, with those in Denmark. METHODS: Population-based data on antibiotic prescriptions from British Columbia and Denmark were obtained from 1999 to 2003 for children less than 15 years of age. Annual trends in prescription rates per 1000 children were analyzed by using generalized linear models for all children less than 15 years of age; they were stratified by age group (0-4, 5-9, 10-14 y) for all antibiotics. Class-specific trends were also evaluated for penicillins, cephalosporins, macrolides, sulfonamides and trimethoprim, tetracyclines, and fluoroquinolones. RESULTS: From 1999 to 2003, the overall British Columbia prescription rate was significantly higher than that of Denmark (p < 0.0001) at all age stratifications. In 2003, the British Columbia prescription rate was twice that of Denmark, at 608 versus 385 prescriptions per 1000 children, respectively. In both jurisdictions, the majority of antibiotics used were penicillins (Anatomical Therapeutic Chemical class J01C). However, in British Columbia, most penicillins used were extended-spectrum (83% in 2003); in Denmark, 34% of penicillins used in 2003 were extended-spectrum and 56% were beta-lactamase sensitive. In British Columbia, use of penicillins (-4.5%), cephalosporins (-5.5%), trimethoprim/sulfamethoxazole (-36%), and tetracycline (-1.6%) decreased over time, whereas in Denmark, use of penicillins increased by 11% over time and non-penicillin antibiotics remained stable. A significant increase in macrolide consumption was seen in British Columbia due to use of clarithromycin and azithromycin; in contrast, macrolide consumption declined in Denmark. CONCLUSIONS: Compared with Denmark, the antibiotic prescription rate for children is substantially higher in British Columbia. In addition, there has been a significant increase in the use of macrolides, especially the second-generation agents, in British Columbia compared with the use in Denmark. Further studies are required to delineate reasons for antibiotic prescribing patterns in these 2 jurisdictions.

Global development of resistance--secondary publication.

Antibiotic resistance is an increasing problem world wide, although in some areas the increase in resistance is slow, as in the Nordic countries. Multiresistant staphylococci, Enterobacteriaceae and Mycobacterium tuberculosis are already causing increased morbidity, mortality and huge costs in health budgets. New effective antibiotics will not be available for the next 10-15 years, since the pharmaceutical industry has lost interest in antibiotics. The major determinant in this field, in order to save the activity of the known antibiotics, is the control of antibiotic use.

Pneumococcal meningitis with normal cerebrospinal biochemistry and no pneumococci at microscopy, mimicking a stroke: a case report.

BACKGROUND: Bacterial meningitis commonly presents with symptoms such as headache, impaired consciousness, neck stiffness, and fever. In most cases, cerebrospinal fluid analysis will yield white cell counts >100/mm3. Atypical presentations occur, especially in the very young or very elderly and the immunocompromised. We report an unusual case of pneumococcal meningitis in a healthy 78-year-old Danish woman who presented with clinical features mimicking a stroke with normal cerebrospinal fluid parameters and without microscopic evidence of bacteria. CASE PRESENTATION: The patient was admitted after being found unconscious on her bed. Upon admittance, she was considered confused, with a temperature of 39.4 °C and slight neutrophilic leukocytosis, but no neck stiffness. A neurological examination revealed bilateral horizontal nystagmus, unstable eye movements, and suspected right-sided gaze paralysis. Cerebrospinal fluid analysis revealed normal parameters, and the microscopy result was negative for bacteria. The most likely diagnosis was considered to be stroke with concomitant infection. However, cerebrospinal fluid and blood cultures subsequently were rapidly positive for pneumococci. Neither immunodeficiency nor blood contamination was considered a likely cause of this discrepancy. CONCLUSIONS: This case emphasizes the need to consider a multidisciplinary approach and empirical meningitis treatment until diagnostic results from microbiological cultures are obtained.

Cerebrospinal fluid pleocytosis in infectious and noninfectious central nervous system disease: A retrospective cohort study.

Cerebrospinal fluid (CSF) analysis is the most important tool for assessing central nervous system (CNS) disease. An elevated CSF leukocyte count rarely provides the final diagnosis, but is almost always an indicator of inflammation within the CNS.The present study investigated the variety of diseases associated with CSF pleocytosis.CSF analyses were identified through the biochemical database used in the capital region of Denmark in the period from 2003 to 2010. In patients >15 years, clinical diagnoses associated with the finding of a CSF leukocyte count >10 × 10 cells/L were obtained from discharge records and patient files.A total of 1058 CSF samples from 1054 patients were included in the analysis. The median age was 50 (interquartile range: 36-67) and 53% were male. Eighty-one different diagnoses were identified in 1058 cases with an elevated CSF leukocyte count, besides unknown causes. Infections were the most common cause of CSF pleocytosis (61.4%) followed by miscellaneous causes (12.7%), vascular (9.7%), neurodegenerative (7%), neoplastic (5%), and inflammatory conditions (4.2%). Only infections presented with leukocyte counts >10,000 × 10/L. Infections represented 82.6% of all cases with a leukocyte count >100 × 10/L whereas 56.3% of cases with at leukocyte counts <100 × 10/L were dominated by disease not related to infection.The present study may serve as a reminder to clinicians of what diseases and disease categories to suspect when patients present with CSF biochemistry indicating CNS inflammation.

Improved outcome of bacterial meningitis associated with use of corticosteroid treatment.

Background The aim of this study was to evaluate the clinical outcome of patients with bacterial meningitis following the introduction of dexamethasone treatment in Denmark. Methods Adult patients with bacterial meningitis, admitted from 2003-2010 to two different university hospitals, were included retrospectively. Data at clinical presentation, Glasgow outcome scale (GOS), cerebrospinal fluid and blood biochemistry were collected. Relative risk (RR) with 95% confidence interval (CI) was computed by Cox proportional hazard regression analysis. Results One hundred and forty-seven patients were included in the study. The population had a median age of 62 years and 31% had an immunosuppressive co-morbidity. Eighty-nine patients had an unfavourable outcome (GOS score = 1-4). Adjuvant treatment with corticosteroids (RR = 0.48; 95% CI = 0.30-0.76) was associated with a favourable outcome (GOS score = 5), while altered mental status (RR = 2.36; 95% CI = 1.17-4.78) and age (RR = 1.03; 95% CI = 1.01-1.04) per year increment was associated with an unfavourable outcome. Adjuvant corticosteroid treatment did not affect short- or long-term survival. Short-term mortality was influenced by age (RR = 1.06; 95% CI = 1.04-1.09). Long-term mortality was influenced by age (RR = 1.06; 95% CI = 1.03-1.08) and female sex (RR = 1.81; 95% CI = 1.05-3.14). Conclusion This study indicated that adjuvant corticosteroid treatment in acute bacterial meningitis improves the outcome and can safely be administered in an elderly population with high levels of immunosuppressive co-morbidity.

Blocking of leukocyte accumulation in the cerebrospinal fluid augments bacteremia and increases lethality in experimental pneumococcal meningitis.

The role of leukocyte accumulation in the cerebrospinal fluid (CSF) in the evolution of the pathophysiological changes that occur in bacterial meningitis is unclear. Here, we investigate how leukocyte recruitment to the CSF, modulated by the leukocyte blocker fucoidin, affects the extent of brain damage and outcome in pneumococcal meningitis in rats treated with ceftriaxone from 28 h after infection. Rats treated with fucoidin from time of infection had an excess risk of a fatal outcome compared to rats not receiving fucoidin (25/63 versus 5/34, p=0.012), whereas the risk of cortical damage in surviving animals was comparable (16/44 versus 9/29, p=0.8). Pre-treatment with fucoidin attenuated CSF pleocytosis 24 h after infection (median 400 versus 800x10(6) cells/l, p=0.01) without affecting CSF bacterial counts (2.3x10(5) versus 3.6x10(5) CFU/ml, p=0.54). A significant increase in blood bacterial counts was found among rats pre-treated with fucoidin (median 9.6x10(2) versus 5.2x10(2) CFU/ml, p=0.03). Furthermore, blood bacterial count was found to be an important predictor of fatal outcome as shown by multivariate logistical regression analysis (OR 4.43, 95% CI [1.16-17.0] p=0.03). In summary, blocking leukocyte entry to the central nervous system in experimental pneumococcal meningitis compromises the survival prognosis but does not affect the risk of brain damage or level of infection in this compartment. Conversely, poorer prognosis was associated with an increase in bacterial load in blood, suggesting that leukocyte blockage affects the host's ability to control systemic infection.