Focus On: Meningitis - Beyond Fever, Stiff Neck, and Altered Mental Status

ACEP News
April 2007

By Michael T. Fitch, MD, PhD

Acute bacterial meningitis is a significant source of patient morbidity and mortality even when appropriate antibiotic therapy is initiated. Controversies remain concerning the most accurate and efficient ways to diagnose and treat this life-threatening infection of the central nervous system in the emergency department.¹

The challenge for emergency medicine providers is to diagnose patients with bacterial meningitis accurately and administer antibiotics and adjunctive therapies rapidly to those patients who need them, without unnecessary testing and treatment for patients who do not have the disease.

Studies show that physical examination alone is inadequate to identify meningitis accurately, and when clinicians rely on lumbar puncture results to guide therapy, significant ambiguity can still remain.

When clinicians are making treatment decisions for these patients, there are recent studies that influence treatment guidelines, including the use of systemic steroids as an adjunctive therapy for adult patients receiving antibiotics for suspected bacterial meningitis.

It is important that emergency physicians who are prescribing the initial doses of antibiotics are aware of the current guidelines for antibiotic choices and the use of adjunctive steroids.

Patient History and Physical Examination

Patient diagnosis and treatment decisions would be much easier if everyone with bacterial meningitis presented to the emergency department with fever, stiff neck, and altered mental status. Unfortunately, large retrospective and prospective studies have revealed that just 44%-66% of patients with this disease will present with the so-called classic triad of meningitis.

Providers need to maintain a high index of suspicion to consider the diagnosis even when all of these symptoms are not present simultaneously, and recognize that there is no single aspect of patient history present in all cases. Even fever - while a common aspect of the presenting complaint - is not present in all patients with meningitis.

However, it is somewhat reassuring to learn that the complete absence of fever, stiff neck, altered mental status, and headache makes the diagnosis of bacterial meningitis very unlikely.^2-4

Many emergency physicians may utilize traditional "meningeal signs" as part of their physical examination when evaluating patients for this life-threatening disease. Kernig's sign (flexing the hip and extending the knee to elicit pain in the back and legs), Brudzinski's neck sign (passive head flexion to elicit flexion at the hip), and nuchal rigidity are commonly described maneuvers that were once thought to have diagnostic value for meningitis.

Unfortunately, these classic signs have very low sensitivity and in prospective studies perform very poorly in identifying patients with meningitis.⁵ In those few cases where positive meningeal signs are present, however, providers should heighten their suspicion for disease and promptly initiate further diagnostic testing and consider empiric treatment.

Lumbar Puncture to Diagnose Meningitis

Lumbar puncture (LP) to obtain cerebral spinal fluid (CSF) for laboratory testing is the procedure of choice to diagnose meningitis.

A rarely reported complication of this procedure is cerebral herniation in the presence of a focal space-occupying lesion or brain shift.

While a clear relationship between LP and this unusual complication has never been proven, CT scan of the brain is recommended to identify risks of this theoretical complication in patients under the following circumstances: new onset seizures, altered mental status, an immunocompromised state, papilledema, or focal neurological signs.^1,6

By definition, patients have evidence of meningitis if they have increased numbers of white blood cells (WBC) in the CSF.

A topic of particular interest to emergency physicians is whether the risks of bacterial disease can be accurately assessed based on the laboratory CSF analysis.

Bacterial meningitis is classically described as having greater than 1,000 WBC per mm3 with a predominance of polymorphonuclear cells, elevated protein, and decreased glucose.

This contrasts with typical viral meningitis that may have less than 300 WBC per mm3 with primarily lymphocytes, normal protein, and normal glucose levels in the CSF.

Unfortunately, these "classic" descriptions do not allow practitioners to identify all patients with bacterial meningitis, and even attempts to devise sophisticated scoring systems have been unsuccessful in developing a model useful for clini-cal practice.

While low blood glucose and high WBC counts in the CSF have been suggested to predict bacterial meningitis,6 there have been a number of documented cases of bacterial meningitis in the absence of these CSF findings that would traditionally predict this life-threatening disease.^{2, 3, 7-9}

Therefore, in the setting of cere-bral spinal fluid pleocytosis, there appears to be no single variable that can reliably exclude bacterial meningitis.

Empiric Therapy for Bacterial Meningitis

Patients with bacterial meningitis continue to have high rates of morbidity and mortality even when appropriate antibiotic therapy is administered.

No clear guidelines exist for how quickly antibiotics should be given, but there are some data to suggest that early antibiotic treatment in the emergency department may be beneficial. In patients with suspected bacterial meningitis, antibiotics are recommended to be given intravenously immediately after a promptly performed LP, and if any diagnostic testing is to be done prior to LP (such as CT scan), then blood cultures should be obtained and antibiotics started immediately.

A combination of broad spectrum agents is recommended empirically until culture information is available to guide subsequent antimicrobial therapy (see table). Age-based risk stratification along with local patterns of resistance should be taken into consideration when selecting antibiotics for initial treatment.

A third-generation cephalosporin (ceftriaxone or cefotaxime) is recommended because of excellent CSF penetration and a broad spectrum of activity. Multidrug-resistant Streptococcus pneumoniae is present in as many as 35% of isolates in some parts of the country, and vancomycin is recommended in addition to the cephalosporin to increase coverage. Listeria monocytogenes has a higher incidence in patients who are older than 50 years, and ampicillin is also added for additional coverage in this population and in any patient in whom this pathogen is suspected.

Steroids to Treat Bacterial Meningitis

Emergency medicine providers should be aware of the current recommendations for IV steroids to be given at the time of the first dose of antibiotics in all adult patients with suspected bacterial meningitis.

Inflammatory responses within the central nervous system can lead to significant morbidity and mortality in patients with bacterial meningitis, even when appropriate antibiotics are administered. Therefore, dexamethasone (10 mg IV) is recommended as an adjunctive therapy to treat the intense inflammatory response to bacterial infection in the central nervous system; it is given every 6 hours for the first 4 days of treatment. This is the only pharmacologic agent that has demonstrated clinical efficacy with improved mortality and neurological outcome in patients with bacterial meningitis when used in conjunction with appropriate antibiotic agents.

A large, prospective, randomized, double-blind, multicenter, placebo-controlled trial of adults with bacterial meningitis demonstrated that IV dexamethasone improved patient outcomes.¹⁰ Dexamethasone (10 mg IV) or placebo was given with or just before the first dose of antibiotics and was continued every 6 hours for 4 days. The primary outcome for this study was a clinically relevant end point using the Glasgow Outcome Scale to determine favorable versus unfavorable clinical outcomes.

The use of steroids demonstrated a significant reduction in risk of unfavorable clinical outcome and an overall improvement in mortality without increased steroid side effects such as gastrointestinal bleeding.

Subgroup analysis showed a significant benefit for patients with Streptococcus pneumoniae, the most common pathogen that carries significant risks of morbidity and mortality.¹⁰

Systematic analysis of multiple trials finds additional support for dexamethasone as an adjunctive treatment for adults with bacterial meningitis.¹¹

It is important that emergency physicians familiarize themselves with the guidelines for adjunctive steroid treatment, as current recommendations state that the timing of administration is critical and the first dose needs to be before or at the same time as antibiotic treatment is initiated.

The option for using adjunctive steroids is not available later in the patient's treatment course if the initial opportunity for administration is not utilized.

Therefore, emergency physicians who are ordering empiric antibiotic treatment for suspected bacterial meningitis should strongly consider administering 10 mg of dexamethasone to be given concurrently.

Conclusions

The diagnosis of meningitis can be very challenging for emergency physicians, and it requires combining historical and physical examination findings to form an overall clinical impression.

Many patients with disease will not present with classic signs and symptoms, and physical examination alone has been shown to be insufficient to diagnose meningitis.

Lumbar puncture should therefore be utilized when sufficient diagnostic uncertainty remains, and caution should be exercised when interpreting results to differentiate likely viral versus bacterial disease.

Systemic steroids are an important adjunctive treatment for bacterial meningitis and should be administered along with the first doses of broad spectrum empiric antibiotics in the emergency department.

References

1. Fitch M.T., van de Beek D. Emergency Diagnosis and Treatment of Adult Meningitis. The Lancet Infectious Diseases 2007;7:191-200.
2. Durand M.L., Calderwood S.B., Weber D.J., et al. Acute bacterial meningitis in adults. A review of 493 episodes. N. Engl. J. Med. 1993;328:21-8.
3. van de Beek D., de Gans J., Spanjaard L., et al. Clinical features and prognostic factors in adults with bacterial meningitis. N. Engl. J. Med. 2004;351:1849-59.
4. Attia J., Hatala R., Cook D.J., Wong J.G. The rational clinical examination. Does this adult patient have acute meningitis? JAMA 1999;282:175-81.
5. Thomas K.E., Hasbun R., Jekel J., Quagliarello V.J. The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in adults with suspected meningitis. Clin. Infect. Dis. 2002;35:46-52.
6. Straus S.E., Thorpe K.E., Holroyd-Leduc J. How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis? JAMA 2006;296:2012-22.
7. Sigurdardottir B., Bjornsson O.M., Jonsdottir K.E., et al. Acute bacterial meningitis in adults. A 20-year overview. Arch. Intern. Med. 1997;157:425-30.
8. Pizon A.F., Bonner M.R., Wang H.E., Kaplan R.M. Ten years of clinical experience with adult meningitis at an urban academic medical center. J. Emerg. Med. 2006;30:367-70.
9. Hussein A.S., Shafran S.D. Acute bacterial meningitis in adults. A 12-year review. Medicine (Baltimore) 2000;79:360-8.
10. de Gans J., van de Beek D. Dexamethasone in adults with bacterial meningitis. N. Engl. J. Med. 2002;347:1549-56.
11. van de Beek D., de Gans J., McIntyre P., Prasad K. Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev 2007:CD004405.

Contributors

Dr. Michael T. Fitch is an assistant professor in the department of emergency medicine and a member of the neuroscience program faculty at Wake Forest University School of Medicine, Winston-Salem, N.C. He has received faculty funding support from the Brooks Scholars in Academic Medicine award at the Wake Forest University School of Medicine. Medical Editor Dr. Robert C. Solomon is an attending emergency physician at Trinity Health System in Steubenville, Ohio, and clinical assistant professor of emergency medicine at the West Virginia School of Osteopathic Medicine.

Disclosures

In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards and American College of Emergency Physicians policy, contributors and editors must disclose to the program audience the existence of significant financial interests in or relationships with manufacturers of commercial products that might have a direct interest in the subject matter.

Dr. Fitch and Dr. Solomon have disclosed that they have no significant relationships with or financial interests in any commercial companies that pertain to this educational activity.

"Focus On: Meningitis--Beyond Fever, Stiff Neck, and Altered Mental Status" has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME).

ACEP is accredited by the ACCME to provide continuing medical education for physicians. ACEP designates this educational activity for a maximum of one Category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he or she actually spent in the educational activity.

"Focus On: Meningitis - Beyond Fever, Stiff Neck, and Altered Mental Status" is approved by ACEP for one ACEP Category 1 credit.

Disclaimer

ACEP makes every effort to ensure that contributors to College-sponsored programs are knowledgeable authorities in their fields. Participants are, nevertheless, advised that the statements and opinions expressed in this article are provided as guidelines and should not be construed as College policy.

The material contained herein is not intended to establish policy, procedure, or a standard of care. The views expressed in this article are those of the contributors and not necessarily the opinion or recommendation of ACEP.

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Focus On: Meningitis - Beyond Fever, Stiff Neck, and Altered Mental Status CME Quiz