Magnus Brink

Heparin-binding protein: A diagnostic marker of acute bacterial meningitis*

Background:The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis. Objective:In this study we investigated whether heparin-binding protein levels in cerebrospinal fluid could be used as a diagnostic marker for acute bacterial meningitis. Design:One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed. Setting and Patients:Cerebrospinal fluid samples were collected from 174 patients with suspected central nervous system infection. Thirty-seven patients with acute community-acquired bacterial meningitis, four patients with neurosurgical bacterial meningitis, 29 patients with viral meningitis or encephalitis, seven patients with neuroborreliosis, and 97 control patients were included. Interventions:None. Measurements and Main Results:Cerebrospinal fluid samples were analyzed for the concentrations of heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear cells. Heparin-binding protein levels were significantly higher (p < .01) in patients with acute bacterial meningitis (median 376 ng/mL, range 12–858 ng/mL) than in patients with viral central nervous system infection (median 4.7 ng/mL, range 3.0–41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2–10 ng/mL) or in control patients with a normal cerebrospinal fluid cell count (median 3.5 ng/mL, range 2.4–8.7 ng/mL). In the prospectively studied group, a heparin-binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a specificity of 99.2%, and positive and negative predictive values of 96.2% and 100%, respectively, in diagnosing acute bacterial meningitis. The area under the receiver-operating characteristic curve for heparin-binding protein was 0.994, which was higher than for the other investigated parameters. Conclusion:Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.

Early lumbar puncture in adult bacterial meningitis--rationale for revised guidelines.

Abstract Current international guidelines recommend cerebral computerized tomography (CT) before lumbar puncture (LP) in many adults with suspected acute bacterial meningitis (ABM), due to concern about LP-induced cerebral herniation. Despite guideline emphasis on early treatment based on symptoms, performing CT prior to LP implies a risk of delayed ABM treatment, which may be associated with a fatal outcome. Firm evidence for LP-induced herniation in adult ABM is absent and brain CT cannot discard herniation. Thus, the recommendation to perform CT before LP may contribute to an avoidable delay of LP and ABM treatment. The inappropriate use of the diagnostic treatment sequence of brain CT scan, followed by LP, followed by antibiotics and corticosteroids should be avoided in adults with suspected ABM by omitting needless contraindications for LP, thus eliminating an unnecessary fear of immediate LP. Revised Swedish guidelines regarding early LP are presented, and the background documentation and reasons for omitting impaired consciousness, new onset seizures, and immunocompromised state as contraindications to LP are discussed.

Respiratory support during the influenza A (H1N1) pandemic flu in Sweden

Acute respiratory insufficiency characterised critically ill patients during the influenza A (H1N1) pandemic 2009–2010. Detailed understanding of disease progression and outcome in relation to different respiratory support strategies is important.

Detection of Tick-Borne Encephalitis Virus RNA in Urine

Tick-borne encephalitis (TBE) is a viral zoonosis of increasing incidence in Eurasia, and diagnosis relies mainly on the detection of IgM antibodies in serum. We here present two cases of TBE, of four patients tested, in which we have detected TBE virus (TBEV) RNA in urine with real-time PCR during

Outcome of 8-hour dosing intervals with beta-lactam antibiotics in adult acute bacterial meningitis

The outcome of dosing with beta-lactam antibiotics at 8-h intervals for adult patients with community-acquired acute bacterial meningitis was retrospectively analysed at Sahlgrenska University Hospital, Gothenburg, Sweden. 80 medical records were identified for a 6-y period from 1999 to 2004. The most common pathogens noted were Streptococcus pneumoniae (47.5%), Neiseria meningitidis (12.5%), and Listeria monocytogenes (5.0%). Other bacteria were diagnosed in 16.3% of all episodes, but the bacteriological aetiology remained unknown in 18.8%. 79 episodes of bacterial meningitis were treated with beta-lactam antibiotics at 8-h dosing intervals. The mortality rate in these patients was 6.3%, with an incidence of permanent neurological deficiencies of 24.1%. Our study shows that a low mortality rate can be achieved using beta-lactam antibiotics at longer dosing intervals than usually recommended by international guidelines.

Time window for positive cerebrospinal fluid broad-range bacterial PCR and Streptococcus pneumoniae immunochromatographic test in acute bacterial meningitis

Abstract Background: Reliable microbiological tests are essential for the diagnosis of acute bacterial meningitis (ABM). In this study we investigated the time period after the start of antibiotic therapy during which culture, polymerase chain reaction (PCR) and the immunochromatographic test (ICT) are able to detect bacteria in cerebrospinal fluid (CSF). Methods: The study was performed on CSF samples from adults with ABM admitted to the Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden, from January 2007 to April 2014. In addition to the initial lumbar puncture (LP), the participants underwent one or two more LPs during 10 days following the start of antibiotics. The analyses performed on the CSF samples were culture, PCR and ICT. Results: The study comprised 70 CSF samples from 25 patients with ABM. A bacterium could be identified by CSF culture in 44%, by blood culture in 58% and by PCR in 100% of the patients. There were no positive CSF cultures in samples taken later than the day of starting antibiotics. PCR was positive in 89% on days 1–3, 70% on days 4–6 and 33% on days 7–10. For cases of pneumococcal meningitis, the ICT was positive in 88% on days 1–3, 90% on days 4–6 and 75% on days 7–10. Conclusions: This study shows that PCR is highly sensitive for bacterial detection in CSF samples taken up to 1 week into antibiotic therapy. The ICT is highly sensitive for the detection of pneumococci in CSF samples taken during the first week of antibiotic treatment.

Venous lactate levels can be used to identify patients with poor outcome following community-onset norovirus enteritis.

Abstract Background: Norovirus enteritis (NVE) can be fatal in frail patients. High blood lactate levels indicate hypoperfusion and predict mortality in many infectious diseases. The objective was to determine the frequency and association with mortality of elevated lactate levels in patients with community-onset NVE. Methods: A retrospective cohort study was performed. All hospitalized adult patients with community-onset NVE verified by polymerase chain reaction during the period August 2008 to June 2009 were included. Vital signs and venous lactate on arrival, co-morbid conditions, and time of death were registered. The outcome measure was 30-day all-cause mortality. Results: Eighty-two patients with a median age of 77 y (interquartile range (IQR) 53–86 y) were included, of whom 47 (57%) were female and 49 (60%) had at least 1 major co-morbid condition. Lactate levels were above the upper limit of normal (ULN; 1.6 mmol/l) in 45 patients (55%). The overall 30-day mortality rate was 7% (6/82). Mortality was 18% (5/28) with lactate ≥ 2.4 mmol/l (> 50% above the ULN) on admission compared to 2% (1/54) with lactate < 2.4 mmol/l (p < 0.05). Patients who died had a higher median lactate level compared to survivors: 4.5 (IQR 2.7–7.9) mmol/l vs 1.7 (IQR 1.3–2.5) mmol/l, respectively (p < 0.01). The adjusted odds ratio for death within 30 days for a 1 mmol/l increase in lactate was 2.5 (95% confidence interval 1.003–6.3, p = 0.049). Conclusions: We observed a high proportion of patients with elevated lactate levels in community-onset NVE. Lactate elevation could predict mortality. Measurement of blood lactate may be a valuable tool in the clinical management of patients with a suspected norovirus infection.

A series of severe necrotising soft-tissue infections in a regional centre in Sweden.

Necrotising soft‐tissue infections (NSTIs) are rare conditions with high morbidity and mortality. Patients with NSTIs are often transferred to tertiary hospitals, but the question of whether the potential benefits of highly specialised care outweigh the risks associated with inter‐hospital transfers has been raised.

Reactivation of herpes simplex type 1 in pneumococcal meningitis

BACKGROUND Acute bacterial meningitis (ABM) and herpes simplex type 1 (HSV-1) encephalitis are two rare but serious infections affecting the central nervous system (CNS). Concurrent bacterial and viral CNS infection has occasionally been reported. OBJECTIVES To illustrate the possibility of intrathecal infection with both Streptococcus pneumonia and HSV-1 by presenting a case and to examine whether herpesvirus reactivation is common in ABM. STUDY DESIGN We report a case diagnosed with HSV-1 reactivation in the cerebrospinal fluid (CSF) during treatment for pneumococcal ABM. A retrospective analysis of CSF samples from 21 patients with ABM was performed, with analysis of DNA from HSV-1 and four other neurotropic herpesviruses. RESULTS All 21CSF samples were negative for HSV-1, HSV-2, varicella zoster-virus, Epstein-Barr virus and human herpesvirus 6 DNA by PCR. CONCLUSIONS Although herpesvirus infection does not seem to be a common phenomenon in ABM we suggest that HSV-1 reactivation could be kept in mind if patients with ABM show symptoms or signs compatible with encephalitis.