Martin Glimåker

Adult Bacterial Meningitis: Earlier Treatment and Improved Outcome Following Guideline Revision Promoting Prompt Lumbar Puncture

BACKGROUND In suspected acute bacterial meningitis (ABM), cerebral computerized tomography (CT) is recommended before lumbar puncture (LP) if mental impairment. Despite guideline emphasis on early treatment, performing CT prior to LP implies a risk of delayed treatment and unfavorable outcome. Therefore, Swedish guidelines were revised in 2009, deleting impaired mental status as a contraindication for LP without prior CT scan. The aim of the present study was to evaluate the guideline revision. METHODS The Swedish quality registry for community-acquired ABM was analyzed retrospectively. Door-to-antibiotic time and outcome were compared among patients treated 2005-2009 (n=394) and 2010-2012 (n=318). The effect of different LP-CT sequences was analyzed during 2008-2012. RESULTS Adequate treatment was started 1.2 hours earlier, and significantly more patients were treated <2 hours from admission 2010-2012 than 2005-2009. Compared with CT before LP, immediate LP resulted in 1.6 hours earlier treatment, significant increase in door-to-antibiotic times of <1 and <2 hours, and a favorable outcome. In 2010-2012, mortality was lower (6.9% vs 11.7%) and the risk of sequelae at follow-up decreased (38% vs 49%) in comparison with 2005-2009. Treatment delay resulted in a significantly increased risk for fatal outcome, with a relative increase in mortality of 12.6% per hour of delay. CONCLUSIONS The deletion of impaired mental status as contraindication for prompt LP and LP without prior CT scan are associated with significantly earlier treatment and a favorable outcome. A revision of current international guidelines should be considered.

Long-term Valacyclovir Suppressive Treatment After Herpes Simplex Virus Type 2 Meningitis: A Double-Blind, Randomized Controlled Trial

BACKGROUND Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications. METHODS One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years. RESULTS The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups. CONCLUSIONS Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.

Neuro-Intensive Treatment Targeting Intracranial Hypertension Improves Outcome in Severe Bacterial Meningitis: An Intervention-Control Study

Objective To evaluate the efficacy of early intracranial pressure (ICP)-targeted treatment, compared to standard intensive care, in adults with community acquired acute bacterial meningitis (ABM) and severely impaired consciousness. Design A prospectively designed intervention-control comparison study of adult cases from September 2004 to January 2012. Patients Included patients were confirmed ABM-cases, aged 16–75 years, with severely impaired mental status on admission. Fifty-two patients, given ICP-targeted treatment at the neuro-intensive care unit, and 53 control cases, treated with conventional intensive care, were included. All the patients received intensive care with mechanical ventilation, sedation, antibiotics and corticosteroids according to current guidelines. Additional ICP-treatment in the intervention group included cerebrospinal fluid drainage using external ventricular catheters (n = 48), osmotherapy (n = 21), hyperventilation (n = 13), external cooling (n = 9), gram-doses of methylprednisolone (n = 3) and deep barbiturate sedation (n = 2) aiming at ICP <20 mmHg and a cerebral perfusion pressure of >50 mmHg. Measurements The primary endpoint was mortality at two months and secondary endpoint was Glasgow outcome score and hearing ability at follow-up at 2–6 months. Outcomes The mortality was significantly lower in the intervention group compared to controls, 5/52 (10%) versus 16/53 (30%; relative risk reduction 68%; p<0.05). Furthermore, only 17 patients (32%) in the control group fully recovered compared to 28 (54%) in the intervention group (relative risk reduction 40%; p<0.05). Conclusions Early neuro-intensive care using ICP-targeted therapy, mainly cerebrospinal fluid drainage, reduces mortality and improves the overall outcome in adult patients with ABM and severely impaired mental status on admission.

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.

Early Diagnosis of Enteroviral Meningitis by a Solid-phase Reverse Immunosorbent Test and Virus Isolation

45 cases of aseptic meningitis/meningoencephalitis were studied with regard to enteroviral etiology by virus isolation and solid-phase reverse immunosorbent test (SPRIST), a cross-reacting test for enterovirus IgM. An etiological diagnosis was reached in 37/45 (82%) patients. Etiological diagnoses other than enteroviruses were found in 8 patients: Borrelia burgdorferi in 4, varicella-zoster virus in 2, herpes simplex virus in 1 and mumps virus in 1 patient. Enteroviruses (echovirus 6, 21 and 30) were isolated from cerebrospinal fluid (CSF) in 26/37 (70%) and from stool samples of 20/21 (95%) of patients with no other etiology. Altogether enteroviruses were isolated from CSF and/or faecal samples in 29 patients. Echovirus 30 dominated as etiologic agent. In 34/40 (85%) of the samples with an enterovirus, a cytopathogenic effect was observed in cell culture within 4 days. In patients with an enterovirus isolate a SPRIST IgM response to echovirus 3, 5, 7 and/or coxsackievirus B3 was detected in 6/13 (46%) sera sampled 3-4 days after the onset of meningeal symptoms and in altogether 17/25 patients (68%). In 4 out of these virus isolation positive and SPRIST negative patients a single serum for SPRIST was available less than 4 days after onset of meningeal symptoms. Antigen from echovirus 5 gave the highest diagnostic yield. The SPRIST IgM test was positive in 2 cases where virus isolation, complement fixation and neutralization tests were negative. Epidemiological data however supported an enteroviral diagnosis in both of them. In conclusion, both SPRIST and virus isolation seem to be valuable for the early diagnosis of enteroviral meningitis.

High diagnostic yield by CSF-PCR for entero- and herpes simplex viruses and TBEV serology in adults with acute aseptic meningitis in Stockholm

Acute aseptic meningitis (AAM) affects 10–20/100,000 inhabitants per years in Sweden. Up to the beginning of the 1980s the diagnoses were made by virus isolation and/or determination of viral antibodies in serum. The development of PCR for detection of viruses in CSF samples has increased the sensitivity and diagnostic efficiency considerably. We investigated the aetiology of AAM and the diagnostic efficiency in an adult population in Stockholm, using a limited first-line combination of microbiological assays. CSF and serum samples, consecutively collected in 419 patients with clinical symptoms of AAM in northern Stockholm during 1999–2004, were included. PCR assays for herpes simplex virus (HSV) DNA and enterovirus (EV) RNA in the CSF as well as ELISA for IgM in serum to tick-borne encephalitis virus (TBEV) were performed routinely. A viral diagnosis was obtained in 255 of the 419 cases (62%) with these routinely performed assays. Clinical findings in combination with additional diagnostic tests resulted in an overall aetiological yield of 72%. EV was the major causative agent (27%) followed by TBEV (21%) and HSV-2 (19%). We conclude that consistent use of CSF-PCR for EV and HSV and TBEV serology established a diagnosis in the majority of AAM patients.

Septicemia Caused by Staphylococcus saprophyticus

Staphylococcus saprophyticus is a common cause of acute urinary tract infection (UTI) in young women. Septicemia has not been reported in patients without signs of immunodeficiency. We report 2 such cases in previously healthy 19- and 33-year-old women. Thus, this microbe may give rise to invasive infection and should be considered when coagulase-negative staphylococci are isolated from blood cultures in patients with symptoms of UTI.

Bacteraemia caused by Actinobaculum schaalii: An overlooked pathogen?

Abstract Actinobaculum schaalii is a uropathogen resistant to ciprofloxacin and trimethoprim–sulfamethoxazole. It requires a long culture time and specific conditions, and is therefore easily overgrown by other bacteria and regarded as part of the normal bacterial flora. We review 17 cases of A. schaalii bacteraemia, demonstrating its invasive potential. A. schaalii should always be ruled out as causative agent in patients with urinary tract infection or urosepticaemia with treatment failure.

Neuron-Specific Enolase Is Correlated to Compromised Cerebral Metabolism in Patients Suffering from Acute Bacterial Meningitis; An Observational Cohort Study.

Introduction Patients suffering from acute bacterial meningitis (ABM) with a decreased level of consciousness have been shown to have an improved clinical outcome if treated with an intracranial pressure (ICP) guided therapy. By using intracranial microdialysis (MD) to monitor cerebral metabolism in combination with serum samples of biomarkers indicating brain tissue injury, S100B and Neuron Specific Enolase (NSE), additional information might be provided. The aim of this study was to evaluate biomarkers in serum and MD parameters in patients with ABM. Methods From a prior study on patients (n = 52) with a confirmed ABM and impaired consciousness (GCS ≤ 9, or GCS = 10 combined with lumbar spinal opening pressure > 400 mmH2O), a subgroup of patients (n = 21) monitored with intracerebral MD and biomarkers was included in the present study. All patients were treated in the NICU with intracranial pressure (ICP) guided therapy. Serum biomarkers were obtained at admission and every 12 hours. The MD parameters glucose, lactate, pyruvate and glycerol were analyzed. Outcome was assessed at 12–55 months after discharge from hospital. Mann-Whitney U-Test and Wilcoxon matched-pairs signed rank test were applied. Results The included patients had a mean GCS of 8 (range, 3–10) on admission and increased ICP (>20 mmHg) was observed in 62% (n = 13/21) of the patients. Patients with a lactate:pyruvate ratio (LPR) >40 (n = 9/21, 43%) had significantly higher peak levels of serum NSE (p = 0.03), with similar, although non-significant observations made in patients with high levels of glycerol (>500 μmol/L, p = 0.11) and those with a metabolic crisis (Glucose <0.8 mmol/L, LPR >25, p = 0.09). No associations between serum S100B and MD parameters were found. Furthermore, median MD glucose levels decreased significantly between day 1 (0–24h) and day 3 (48–72h) after admission to the NICU (p = 0.0001). No correlation between MD parameters or biomarkers and outcome was found. Conclusion In this observational cohort study, we were able to show that cerebral metabolism is frequently affected in patients with ABM. Furthermore, patients with high LPR (LPR>40) had significantly higher levels of NSE, suggesting ongoing deterioration in compromised cerebral tissue. However, the potential clinical impact of MD and biomarker monitoring in ABM patients will need to be further elaborated in larger clinical trials.

Lumbar puncture in adult bacterial meningitis: time to reconsider guidelines?

Because of concerns about lumbar puncture (LP) induced cerebral herniation, current guidelines recommend cerebral computerised tomography (CT) before LP in adults with suspected acute bacterial meningitis (ABM) and impaired consciousness.1 2 But this risks delaying ABM treatment, despite guideline emphasis on early treatment based on symptoms and median “door to antibiotic” durations of two to four hours in adults.3 4 Rapid treatment …