Focus On: Emergent Evaluation and Management of Bacterial Meningitis

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ACEP News
May 2008

By Erin N. Quattromani, MD, and Amer Z. Aldeen, MD

Learning Objectives

After reading this article, the physician should be able to:

  • Use the history and physical examination to determine which patients suspected of having bacterial meningitis need further evaluation and diagnostic testing (such as CT scan, lumbar puncture, etc.).
  • Interpret CSF findings typical of bacterial meningitis and recognize that atypical results do not rule out the diagnosis.
  • Initiate treatment in cases of suspected bacterial meningitis BEFORE the definitive diagnosis is made.
  • Target antibiotic therapy to the most likely pathogens based on age and risk factors.

Bacterial meningitis is defined as infection of the arachnoid mater, subarachnoid space, and the cerebrospinal fluid (CSF).1 It is among the most common infectious causes of death in the world. Incidence in the United States is reported to be more than 3/100,000 per year.1

Described initially by Hippocrates as vague meningeal irritation, it was more precisely defined by Ibn Sina (Avicenna) in the 11th century.2 The disease was uniformly fatal until the advent of antimicrobial therapy, but even now combined mortality and serious morbidity approach 50%.1,3

Poor outcomes caused by bacterial meningitis often stem from delays in diagnosis and treatment.4 Initial evaluation of patients with bacterial meningitis usually occurs in emergency departments.5 Therefore, it is critically important for emergency physicians to diagnose accurately and treat promptly patients with bacterial meningitis to achieve optimal patient outcomes.

Pathogenesis

The two main mechanisms by which bacteria breach the blood brain barrier (BBB) to infect the meninges are direct spread and bacteremia. Contiguous infection (from a source such as the sinuses or middle ear), trauma, neurosurgery, or indwelling medical devices can lead to direct spread of bacteria into the central nervous system (CNS). Nasopharyngeal colonization from infected droplets of respiratory secretions or a distant localized infection (lungs, urine, etc.) with subsequent bloodstream invasion can cause the predisposing bacteremia. Bacterial infiltration of the BBB causes meningeal infection, which is characterized by inflammation, increased permeability of the BBB, cerebral vasculitis, edema, and increased intracranial pressure.

Etiology

The responsible pathogens are typically encapsulated bacteria; the bacterial capsule helps evade the host's complement system. In community-acquired meningitis, Streptococcus pneumoniae (pneumococcus) is the most common pathogen since routine immunization of infants with Haemophilus type b conjugate vaccine began in 1992.3,5 However, the decrease in incidence of H. influenzae meningitis is seen only in vaccinated infants and children; H. influenzae remains among the common culprits in adult patients.3

Along with pneumococcus and H. influenzae, Neisseria meningitidis (meningococcus), Listeria monocytogenes, and group B streptococci account for nearly all of community-acquired cases in patients up to age 60.6 Meningococcus primarily affects younger adults and is associated with individuals living in crowded spaces, such as dormitories and military barracks.3,6 Listeria burdens persons at the extremes of age, pregnant women, and immunocompromised patients.3

Causative organisms in nosocomial meningitis are usually gram-negative bacilli, especially from the Enterobacteriaceae family, Staphylococcus aureus, and coagulase-negative staphylococci.3 Major risks for nosocomial meningitis include neurosurgery or head trauma within the previous month, indwelling medical devices, and CSF leak.3

Diagnosis

The classic symptoms of meningitis are fever, stiff neck, and headache.3,7,8 Headaches associated with meningitis are typically nonpulsatile, nonfocal, and severe.7 Altered mental status in a patient with fever, even in the absence of headache or stiff neck, should still prompt concern for meningitis.3,7,8 Rash (petechial, purpuric, or even maculopapular) in the setting of headache and stiff neck is an alarming sign of meningococcal or pneumococcal disease.7

Unfortunately, the individual components of a patient's history have low sensitivity and specificity for establishing the diagnosis of meningitis. The presence of neck pain has 28% sensitivity and head-ache just 50%. Reported specificities for a nonpulsatile or a generalized headache are 15% and 50%, respectively.7

On physical exam, the clinical triad of fever, neck stiffness, and altered mental status are concurrently present in less than two-thirds of patients.7 Fever is the most common of these classic signs, with a reported sensitivity of 85%.7 More than 95% of patients exhibit at least two of these signs on presentation.7,8 The absence of all three can effectively rule out meningitis in virtually 100% of patients.7 The presence of seizures, hypotension, or altered mental status portends a particularly poor prognosis.3

Physical exam maneuvers traditionally have been used to evaluate neck stiffness by eliciting meningeal irritation. Kernig sign involves flexing the hip and extending the knee in a supine position; pain in the back or leg is recorded as a positive finding.7,9 A positive Brudzinski sign is recorded when there is flexion at the hips after passive flexion of the neck in the supine position.7,9 Together, these maneuvers have reportedly low sensitivity (5%) but high specificity (95%).9

Even a positive test, however, should be interpreted with caution, especially in the elderly. One author found that 13% of acute-care patients and 35% of geriatric patients had nuchal rigidity despite the absence of meningitis, likely owing to presence of cervical arthritis and spondylosis among older patients.10 Because of their low sensitivity and false positives among the elderly, the Kernig and Brudzinski signs have limited clinical utility.7,9,11

On the other hand, the jolt accentuation test is an excellent maneuver to help rule out meningitis in a low-risk, nontoxic patient with headache and fever.7,11 The patient rotates his or her head horizontally at a frequency of two rotations per second; a positive test is the exacerbation of an existing headache. The jolt accentuation test has a sensitivity of 97% and specificity of 60% for the presence of CSF pleocytosis.11 Therefore, a negative test essentially can exclude meningitis in patients with fever and headache, and a positive result aids in the decision to proceed with lumbar puncture (LP).7,11

Routine blood work is often obtained but frequently unrevealing. Blood cultures should be drawn in all patients, especially when CSF cannot be obtained prior to administration of antibiotics. However, the gold-standard diagnostic procedure is CSF analysis by LP, which should be obtained in all patients with suspected meningitis unless contraindicated.5


Table 1. Common CSF Findings in Meningitis3

Index Normal Bacterial Viral Fungal (tuberculosis)
WBC/mcL <5 >1,000 <1,000 <1,000
Differential <15% neutrophils >80% neutrophils <15% neutrophils <15% neutrophils
Glucose (mg/dL) 45-65 reduced normal reduced
CSF: blood glucose 0.6 reduced normal reduced
Protein (mg/dL) 20-45 >250 50-250 >250
Opening pressure (cm/H20) <20 Normal to high Normal to high Normal to high
Source: Erin N. Quattromani, M.D., and Amer Z. Aldeen, M.D.

Common findings from the CSF in bacterial meningitis include a cloudy appearance, elevated opening pressure (> 20 cm H2O), elevated white blood cell (WBC) count with a neutrophilic predominance, elevated protein, and reduced glucose.3 Table 1 reflects the typical CSF findings to help differentiate bacterial from viral and fungal meningitis. Gram stain identifies the organism in approximately 80% of cases, although this is reduced to 60% when the patient has been pretreated with antibiotics or if the organism is a gram-negative bacillus.3

Not every patient with bacterial meningitis has the complete constellation of typical CSF findings. Distinguishing bacterial from viral infection can be challenging. The CSF WBC count may be below 100/?L in approximately 15% of acute bacterial meningitis cases, and a lymphocytic predominance is present in 10%.3 Furthermore, glucose levels may be normal in 50% of cases, and protein levels can reflect typical viral findings (< 200 mg/dL) in 40%.3

Therefore, it is still prudent to treat, admit, and observe patients who present with clinical signs of acute meningitis (especially if they appear toxic), even if initial CSF findings are not suggestive of bacterial disease.8

Poor prognostic indicators for bacterial meningitis include altered mental status, age older than 60 years, and seizures upon presentation.3 Laboratory findings of leukopenia, thrombocytopenia, and elevated CSF protein also indicate a worse prognosis (Table 2).3 In addition, mortality is higher in cases of pneumococcus and Listeria compared to meningococcus, owing to the persistence of potent biologic activity in the debris of killed bacteria.12,13


Table 2. Prognostic Factors in Bacterial Meningitis3

Risk Factor Mortality With
Risk Factor
Mortality Without
Risk Factor
Altered mental status 49% 16%
Age >60 years 37% 17%
Seizures within 24 hours 72% 18%
CSF protein >250 mg/dL 32% 4%
Leukopenia 63% 11%
Hemoglobin <11 mg/dL 16% 5%
Platelets <100k 25% 6%
Source: Erin N. Quattromani, M.D., and Amer Z. Aldeen, M.D.

Treatment

Antibiotics are essential to the treatment of bacterial meningitis. The initial choice should be governed by the patient's age and allergies, as well as resistance patterns of pathogens (Table 3). Vancomycin plus a third-generation cephalosporin are the mainstays of treatment in most cases of community-acquired bacterial meningitis.5,14 In patients who are older than 50 years, immunocompromised, or alcoholics, ampicillin should be added for listerial infection.14 Coverage for Pseudomonas should be added in nosocomial cases.3,5,14

In addition to antibiotics, steroids should be given in virtually all suspected cases of bacterial meningitis.15 Intravenous dexamethasone (0.15 mg/kg) is given just prior to or concomitantly with antibiotic administration, and continued every 6 hours for the next 4 days. Steroids have been shown to reduce overall mortality and neurological sequelae from meningitis, probably by attenuating the intense inflammatory response in the CNS.15 While this is particularly true for pneumococcus, steroids should be continued regardless of the culprit bacterial pathogen.15


Table 3. Empiric Antibiotic Therapy for Suspected Bacterial Meningitis in Adults3,5,14

Age Pathogens Empiric Antibiotics Penicillin Alternative
=50 years Meningococcus,
pneumococcus,
Haemophilus influenzae
3rd generation cephalosporin
(ceftriaxone) + vancomycin
Meropenem,
chloramphenicol,
fluoroquinolones
>50 years Pneumococcus, listeria,
gram-negative bacilli
3rd generation cephalosporin
(ceftriaxone) + vancomycin
+ ampicillin
Trimethoprim/sulfa
+ fluoroquinolone
Hospital-Acquired Staphylococci,
gram-negative bacilli,
pneumococcus
Ceftazidime or cefepime
+ vancomycin
Meropenem
Source: Erin N. Quattromani, M.D., and Amer Z. Aldeen, M.D.

Controversies

Management of bacterial meningitis involves several crucial questions regarding the optimal timing of therapy.

First, given that the diagnosis of bacterial meningitis can be definitively made only by CSF analysis, does early antibiotic administration before LP affect culture results and thereby compromise targeted therapy? Second, does the performance of diagnostic testing such as computed tomography (CT) and LP significantly delay antibiotic therapy? Lastly, does delayed therapy produce worse clinical outcomes?

In a retrospective pediatric study, results confirmed previous suspicions that early antibiotics do, in fact, reduce culture yields: Parenteral antibiotics can complete sterilization of meningococcus in the CSF within 2 hours of therapy and pneumococcus within 4 hours.16 However, if the patient's clinical presentation mandates a head CT prior to LP, an average of 6 hours lapses between presentation and parenteral antibiotics.17

Furthermore, postponement of antibiotics for more than 3 hours after presentation to the hospital has been demonstrated as the strongest indicator of 3-month mortality for patients with pneumococcal meningitis.4 Therefore, the emergency physician should begin antibiotics and steroids before sending a patient to CT in preparation for an LP.

Another controversy in today's practice is deciding which patients need a head CT prior to LP.

One of the greatest fears passed down in emergency medicine dogma is the risk of brain herniation upon sudden release of increased intracranial pressure from LP. The true incidence of this devastating complication is unknown and is based mostly on retrospective observational data.5 Regardless, neuro-imaging should be obtained prior to LP in patients with abnormal neurological exams.

The Infectious Disease Society of America (IDSA) recommends obtaining a head CT prior to LP for patients who meet any of these criteria: immunocompromised state, history of CNS disease (mass lesion, stroke, or focal infection), new-onset seizure within 1 week of presentation, papilledema, abnormal level of consciousness, or focal neurologic deficit.5

These studies highlight the need for a structured approach to the management of patients suspected of having bacterial meningitis. If a CT is deemed to be necessary on clinical grounds, the emergency physician should perform tasks in the following strict order: blood cultures, steroids, antibiotics, CT, and LP.5,14,18

Conclusion

Acute bacterial meningitis is a medical emergency requiring rapid evaluation, diagnosis, and management. When fever is observed in the setting of headache, neck stiffness, or altered mental status, the emergency physician should consider the diagnosis. A negative jolt accentuation test may be used in low-risk, nontoxic febrile headache patients to eliminate the need for further evaluation.

Lumbar puncture with CSF analysis composes optimal testing, but treatment with steroids and antibiotics should always be initiated before the definitive diagnosis is made. Early antibiotic administration is the key to reducing morbidity and mortality from this potentially devastating illness.

References

  1. Tunkel A.R., Scheld W.M. Pathogenesis and pathophysiology of bacterial meningitis. Clin. Microbiol. Rev. 1993;6:118-36.
  2. Skinner P. Unani-Tibbi. Encyclopedia of Alternative Medicine. Available at: http://findarticles.com/p/articles/mi_g2603/is_0007/ai_2603000716. Accessed 2/1/08.
  3. 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.
  4. Auburtin M., Wolff M., Charpentier J., et al. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care units with pneumococcal meningitis: The PNEUMOREA prospective multicenter study. Crit. Care Med. 2006;34:2758-65.
  5. Tunkel A.R., Hartman B.J., Kaplan S.L., et al. Infectious Disease Society of America practice guidelines for management of bacterial meningitis. Clin. Infect. Dis. 2004;39:1267-84.
  6. Schuchat A., Robinson K., Wenger J.D., et al. Bacterial meningitis in the United States in 1995. N. Engl. J. Med. 1997;337:970-6.
  7. 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.
  8. Van de Beek D., de Gans J., Spargaard L., et al. Clinical features and prognostic factors in adults with bacterial meningitis. N. Engl. J. Med. 2004;351:1849-59.
  9. Thomas K.E., Hasbun R., Jekel J., Quagliarello V.J. The diagnostic accuracy of Kernig's sign, Brudzinski sign, and nuchal rigidity in adults with suspected meningitis. Clin. Infect. Dis. 2002;35:46-52.
  10. Puxty J.A., Fox R.A., Horan M.A. The frequency of physical signs usually attributed to meningeal irritation in elderly patients. J. Am. Geriatr. Soc. 1983;31:590-2.
  11. Uchihara T., Tsukagoshi H. Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis. Headache 1991;31:167-71.
  12. Baraff L.J., Lee S.I., Schriger D.L. Outcomes of bacterial meningitis in children: a meta-analysis. Pediatr. Infect. Dis. J. 1993;12:389-94.
  13. Tuomanen E., Hengstler B., Rich R., et al. Nonsteroidal anti-inflammatory agents in the therapy for experimental pneumococcal meningitis. J. Infect. Dis. 1987;155:985-90.
  14. Fitch M.T., van de Beek D. Emergency diagnosis and treatment of adult meningitis. Lancet Infect. Dis. 2007;7:191-200.
  15. De Gans J., van de Beek D., et al. Dexamethasone in adults with bacterial meningitis. N. Engl. J. Med. 2002;347:1549-56.
  16. Kanegaye J.T., Soliemanzadeh P., Bradley J.S. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001;108:1169-74.
  17. Proulx N., Fréchette D., Toye B., et al. Delays in the administration of antibiotics are associated with mortality from adult acute bacterial meningitis. QJM 2005;98:291-8.
  18. Talan D.A., Hoffman J.R., Yoshikawa T.T., Overturf G.D. Role of empiric parenteral antibiotics prior to lumbar puncture in suspected bacterial meningitis. Rev. Infect. Dis. 1998;10:365-76.

Contributors

Dr. Quattromani is a resident physician in the department of emergency medicine at Northwestern University Feinberg School of Medicine. Dr. Aldeen is assistant residency director and an attending physician in the department of emergency medicine at Northwestern University Feinberg 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. Quattromani, Dr. Aldeen, 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: Emergent Evaluation and Management of Bacterial Meningitis" 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: Emergent Evaluation and Management of Bacterial Meningitis" 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. The College disclaims any liability or responsibility for the consequences of any actions taken in reliance on those statements or opinions.

Emergent Evaluation and Management of Bacterial Meningitis CME

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