Jacob Bodilsen

Stroke in community-acquired bacterial meningitis: a Danish population-based study.

OBJECTIVES Stroke is a serious complication in community-acquired bacterial meningitis (CABM), but the incidence, predispositions, and outcome need further clarification; this pertains in particular to the impact of pre-existing atherosclerosis risk factors. Therefore, we aimed to assess these features in a retrospective population-based cohort study. METHODS We included all patients over 16 years of age with CABM in North Denmark Region, 1998-2010. All data were retrieved from the patient records. A Glasgow Outcome Scale score of 1-4 was defined as an unfavourable outcome and 5 as favourable. RESULTS We identified 152 episodes of CABM. In 22 (14%) of the episodes, the patient had a stroke; 15 strokes were ischaemic, three were haemorrhagic, and four were a combination of both. Age and atherosclerosis risk factors were not significantly associated with stroke. However, stroke was associated with a higher in-hospital mortality (27% vs. 16%; age adjusted risk ratio (age aj. RR) 1.43, 95% confidence interval (CI) 0.67-3.04), unfavourable outcome (86% vs. 37%; age adj. RR 2.09, 95% CI 1.59-2.75), and long-term sequelae among survivors (88% vs. 40%, age adj. RR 2.01, 95% CI 1.53-2.65) compared with patients without stroke. CONCLUSIONS Stroke is a common complication among adult CABM patients and is associated with long-term sequelae and possibly also death. However, stroke seemed not to be related to atherosclerosis risk factors.

Dexamethasone treatment and prognostic factors in community-acquired bacterial meningitis: A Danish retrospective population-based cohort study

Abstract Introduction: The morbidity and mortality in community-acquired bacterial meningitis (CABM) remain substantial and treatment outcomes and predictors of a poor prognosis must be assessed regularly. We aimed to describe the outcome of patients with CABM treated with dexamethasone and to assess the performance of the Dutch Meningitis Risk Score (DMRS). Methods: We retrospectively evaluated all adults with CABM in North Denmark Region, 1998–2012. Outcomes included in-hospital mortality and Glasgow Outcome Scale (GOS) score. A GOS score of 5 was categorized as a favourable outcome and scores of 1–4 as unfavourable. We used logistic analysis to compute relative risks (RRs) with 95% confidence intervals (CIs) for an unfavourable outcome adjusted for age, sex, and comorbidity. Results: We identified a total of 172 cases of CABM. In-hospital mortality was unaffected by the implementation of dexamethasone in 2003 (19% vs 20%). Dexamethasone treatment was associated with a prompt diagnosis of meningitis and a statistically insignificant decrease in the risk of an unfavourable outcome (33% vs 53%; adjusted RR 0.64, 95% CI 0.41–1.01) and in-hospital mortality (15% vs 24%; adjusted RR 0.72, 95% CI 0.35–1.48). Of the risk factors included in the DMRS, we found age and tachycardia to be significantly associated with an unfavourable outcome in the multivariate analyses. Conclusions: Patients treated with dexamethasone were more likely to have a favourable outcome, although statistical significance was not reached. Several parameters included in the Dutch risk score were also negative predictors in our cohort, although the entire risk score could not be validated due to a lack of data.

Mycotic aneurysm caused by Burkholderia pseudomallei in a previously healthy returning traveller

Burkholderia pseudomallei is a common cause of serious, difficult to treat infections in South-East Asia and Northern Australia, but is a rare imported pathogen in the USA and Europe. We report a case of a patient with a mycotic aneurysm caused by B. pseudomallei in a previously healthy returning traveller. The patient presented with 4 weeks of abdominal pain and intermittent fever after a brief vacation in Thailand. The aneurysm was excised and replaced by an autologous deep vein graft, and the patient was treated for 6 months with antibiotics adjusted according to postoperative renal impairment. Twenty-four months after surgery the patient is well and without relapse.

Long term survival, health, social functioning, and education in patients with European Lyme neuroborreliosis: nationwide population based cohort study

Abstract Objective To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population. Design Nationwide population based cohort study using national registers. Setting Denmark. Participants All Danish residents diagnosed during 1986-2016 as having Lyme neuroborreliosis (n=2067), defined as a positive Borrelia burgdorferi intrathecal antibody test and a clinical diagnosis of Lyme borreliosis, and a comparison cohort from the general population matched on sex and date of birth (n=20 670). Main outcome measures Mortality rate ratios, incidence rate ratios of comorbidities, and differences in educational and social outcomes. Results Mortality among patients with Lyme neuroborreliosis was not higher than in the general population (mortality rate ratio 0.90, 95% confidence interval 0.79 to 1.03). Lyme neuroborreliosis patients had increased risk of haematological (incidence rate ratio 3.07, 2.03 to 4.66) and non-melanoma skin cancers (1.49, 1.18 to 1.88). At diagnosis, Lyme neuroborreliosis patients had slightly higher employment and lower disability pension rates. After five years, patients and comparison cohort members had similar numbers of hospital contacts (difference −0.22, 95% confidence interval −0.45 to 0.02, in-hospital days/year; 0.37, −0.10 to 0.83, outpatient visits/year), employment rates (difference 1.5%, −2.1% to 5.1%), income (difference −1000, −20 000 to 18 000, Danish kroner), days of sick leave (difference −0.3, −3.5 to 3.0, per year), rates of receipt of a disability pension (difference −0.9%, −3.2% to 1.3%), and number of children (difference –0.10, −0.27 to 0.08). More patients were married (difference 4.8%, 2.2% to 7.4%) and had completed high school education (difference 7%, 1% to 12%). Conclusion A verified diagnosis of Lyme neuroborreliosis had no substantial effect on long term survival, health, or educational/social functioning. Nevertheless, the diagnosis decreased labour market involvement marginally and was associated with increased risk of haematological and non-melanoma skin cancers.

Azithromycin vs. Placebo for the Clinical Outcome in Campylobacter concisus Diarrhoea in Adults: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial

Campylobacter concisus has been associated with prolonged mild diarrhoea, but investigations regarding the efficacy of antimicrobial treatment have not been reported previously. We initiated a phase 3, single-centre, randomized, double-blinded, placebo-controlled study comparing the efficacy of 500 mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days. If symptoms persisted at day ten, the patient was offered cross-over study treatment of three days and another ten-day follow-up period. The primary efficacy endpoint was the clinical response, defined as time to cessation of diarrhoea (<3 stools/day or reversal of accompanying symptoms). Our estimated sample size was 100 patients. We investigated a total of 10,036 diarrheic stool samples from 7,089 adult patients. Five-hundred and eighty-eight C. concisus positive patients were assessed for eligibility, of which 559 were excluded prior to randomization. The three main reasons for exclusion were duration of diarrhoea longer than 21 days (n = 124), previous antibiotic treatment (n = 113), and co-pathogens in stools (n = 87). Therefore, 24 patients completed the trial with either azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16–19). One person in the azithromycin group and four from the placebo group chose to continue with crossover medication after the initial ten-day period. In the azithromycin group, there was a mean of seven days (95% CI: 5–9) to clinical cure and for the placebo group it was ten days (95% CI: 6–14) (OR—3 (95% CI: -7–1). We observed no differences in all examined outcomes between azithromycin treatment and placebo. However, due to unforeseen recruitment difficulties we did not reach our estimated sample size of 100 patients and statistical power to conclude on an effect of azithromycin treatment was not obtained. Trial Registration: Clinicaltrials.gov identifier: NCT01531218.

Cutaneous melioidosis in a healthy Danish man after travelling to South-East Asia

A healthy Danish man presented with infected prepatellar bursitis 8 months after being involved in a car accident in Malaysia resulting in exposure of a laceration of his knee to stagnant water. Tissue samples grew Burkholderia pseudomallei and diagnostic work up revealed no secondary foci. The patient was successfully treated with surgical debridement and 3 months of oral trimethoprim-sulfamethoxazole. At 6 months follow-up the patient was without relapse.

Community-acquired meningitis in adults caused by Escherichia coli in Denmark and The Netherlands

OBJECTIVES We aimed to examine risk factors, presenting characteristics and complications of Escherichia coli community-acquired bacterial meningitis in adults. METHODS Observational cohort study of adults > 16 years of age with cerebrospinal fluid culture-positive E. coli meningitis in Denmark and the Netherlands. Exclusion criteria were primary brain abscess, previous neurosurgery and nosocomial infections. We analysed baseline characteristics, concomitant infections and neurological complications. Outcome was assessed using the Glasgow Outcome Scale score (GOS) at discharge with GOS 1-4 categorised as unfavourable outcome. RESULTS We identified 36 patients with a median age of 69 years (interquartile range 61-83) of whom 15 (42%) were females. Immuno-compromise was present in 11 (31%) patients. Nineteen (53%) patients had concomitant infections consisting of urinary tract infections in 13 (36%), pneumonia in three (9%) and septic arthritis in two (6%). Bacteraemia with E. coli was found in 26 of 34 (76%) patients. Thirteen patients died (36%) and unfavourable outcome at discharge occurred in 23 (64%). Deaths were attributed to systemic complications in 12 (92%) patients. CONCLUSION Community-acquired E. coli meningitis in adults is a severe disease that primarily occurs in elderly patients with concomitant infections and an immunocompromised state. Outcome is often poor and mainly caused by systemic complications.

Cerebrospinal fluid lactate as a marker to differentiate between community-acquired acute bacterial meningitis and aseptic meningitis/encephalitis in adults: a Danish prospective observational cohort study

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.

Anti-infective treatment of brain abscess

ABSTRACT Introduction: Brain abscess is an uncommon and potentially life-threatening infection of the CNS that can be caused by a range of different pathogens including bacteria, fungi, and parasites. A multidisciplinary approach is important and anti-infective treatment remains crucial. Here, we review anti-infective treatment of brain abscess. Areas covered: We used the terms ‘(Brain abscess[ti] AND (antibiotic* OR treatment)) NOT case report’), to conduct a search in the PubMed. Additional papers were identified by cross-reference checking and by browsing textbooks of infectious diseases and neurology. Commentary: Empiric treatment of bacterial brain abscess consists of cefotaxime and metronidazole with the addition of vancomycin if meticilline-resistant Staphylococcus aureus is suspected. For severely immuno-suppressed patients, for example transplant recipients, voriconazole and trimethoprim-sulfamethoxazole or sulfadiazine should be added. Increased knowledge of the pharmacokinetic profile of anti-infective treatments may help to improve the treatment of brain abscess. Future studies should address efficacy and safety of continuous abscess drainage, mode of anti-infective administration (continuous vs. bolus), and anti-infective treatments in immuno-suppressed patients.

Positive predictive value of ICD-10 diagnosis codes for brain abscess in the Danish National Patient Registry

Purpose To evaluate the positive predictive value (PPV) of ICD-10 diagnosis codes for brain abscess in the Danish National Patient Registry (DNPR). Patients and methods We examined medical records of all patients with a first-time diagnosis code of brain abscess in the DNPR from 2007 to 2016. Patients were categorized with either confirmed or disproved brain abscess using a priori defined criteria. We computed the PPV as the proportion of confirmed diagnoses. Results We identified 709 patients, of whom the medical records could not be retrieved for 15 patients, leaving 694 for further analyses. Of these, 444 had a confirmed brain abscess and 250 had another proven diagnosis, including 47 cases of intracranial empyema. The overall PPV was 64% (95% CI: 60–68) ranging from 24% to 96% among the different codes evaluated. By including only patients with either 1) both a diagnosis and surgical procedure code for brain abscess or 2) patients admitted to hospital with certain primary diagnosis codes (DG060[C,E,F] or DG079B) without newly diagnosed central nervous system (CNS) cancer, spondylodiscitis/intraspinal abscess, or procedure codes for evacuation of intracranial empyema, the PPV increased to 84% (95% CI 80–87) and 89% (395/444) of all confirmed cases were identified. Conclusion The overall PPV of diagnosis codes for brain abscess in the DNPR was moderate. However, by exclusion of newly diagnosed CNS tumors, spondylodiscitis/intraspinal abscess, and intracranial empyemas, the PPV was high and therefore suitable for future registry-based studies of brain abscess.