Bacterial Meningitis Case File

Bacterial Meningitis Case File

Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS

Case 30

An otherwise healthy 19-year-old man is brought to the emergency department (ED) by his roommate who states that he has “not been acting right” for the past 24 hours. Per the roommate, the patient had complained of a headache 2 days prior to arrival, and has been progressively somnolent and confused since then. The patient has no past medical history and does not take any medications. His roommate states that the patient is a college student who does not use any illegal drugs and occasionally drinks alcohol. Review of systems is positive for headache and altered mental status as stated above as well as a tactile fever for the past 2 days. Additional review of systems is unobtainable as the patient is unable to answer any questions. On physical examination the patient is noted to be febrile to 38.5°C (101°F) orally, with a heart rate of 120 beats per minute, blood pressure of 114/69, and a respiratory rate of 20 breaths per minute. His oxygen saturation is 98% on room air. The head and neck examination are significant for dry mucous membranes and nuchal rigidity. His cardiopulmonary examination is within normal limits with the exception of tachycardia. The abdomen is soft and nontender. His skin is noted to be warm and well perfused without any rash. The neurologic examination is significant for an altered mental status with a Glasgow coma score (GCS) of 10 (eyes open to voice [3], patient moans to painful stimuli [2], and localizes painful stimuli [5]). The motor examination is symmetric, and the patient appears to be sensate in all extremities. His reflexes are 2+ bilaterally throughout the upper and lower extremities with downgoing toes. Laboratory studies reveal a leukocytosis of 24,000/mm³ with a left shift, and are otherwise unremarkable. A CT scan is completed which shows no mass, shift, bleed, or edema.

⯈ What is the most likely diagnosis?

⯈ What is the next diagnostic study of choice?

⯈ What is the most appropriate treatment of this condition?

ANSWER TO CASE: 30

Bacterial Meningitis

Summary: This is a 19-year-old man who presents with the classic triad for bacterial meningitis—fever, neck stiffness, and altered mental status.

• Most likely diagnosis: Bacterial meningitis
• Next diagnostic study: Lumbar puncture
• Appropriate treatment: Intravenous antibiotics ± steroids

ANALYSIS

Objectives

1. Understand the diagnostic and therapeutic approach to bacterial meningitis including when to obtain neuroimaging, when to perform a lumbar puncture, and what empiric therapies to initiate.
2. Recognize the clinical presentation of acute bacterial meningitis.

Considerations

Bacterial meningitis is an inflammation of the leptomeninges (pia/arachnoid/duramaters) from infection of the arachnoid space, characteristically accompanied by white blood cells in the cerebrospinal fluid. It is one of the ten most common potentially devastating infections and can affect both adults and children. Mortality rates have been reported as high as 50% in some series, yet most cohorts appear to have mortality between 10% and 30%. Of patients who survive, approximately 25% will go on to have a permanent neurologic deficit. It is incumbent upon the emergency physician to consider this diagnosis in patients presenting with any combination of the following signs and symptoms: fever, altered mental status, nuchal rigidity and headache. Although the classic triad includes fever, altered mental status, and nuchal rigidity, only 44% to 50% of patients will present with all three features. Almost all patients (99%-100% in the largest study published) have headache plus at least one of these three clinical signs. Fever is present in 79% to 95% of patients at presentation and another 4% will develop fever within 24 hours of presentation. Altered mental status (typically confusion or lethargy) is present in 78% to 83% of patients with 16% to 22% responsive to only painful stimuli and 6% unresponsive to all stimuli. Nuchal rigidity is present in 83% to 94% of patients on initial examination, and often persists for more than one week after treatment and resolution of infection.

Altered mental status (AMS) in an otherwise healthy individual can be caused by a number of serious illnesses including infectious, metabolic, toxicologic, and neurologic etiologies. As with any seriously ill emergency department patient, the initial priorities include managing the ABCs (airway, breathing, and circulation), including airway protection, as needed for a depressed level of consciousness. This patient presents with a GCS of 10, yet appears to be protecting his airway on initial examination.

Immediately reversible causes of altered mental status, such as hypoglycemia, hypoxia, and drug intoxication should be recognized and treated during the initial examination. If a reversible cause of AMS is not identified, and bacterial meningitis is suspected, prompt diagnosis and treatment is critical.

Additional findings that may raise ones concerns for the diagnosis of meningitis include seizures, focal neurologic deficits, rash, septic arthritis, papilledema and photophobia. Seizures have been described in 15% to 30% of patients and are most commonly associated with infections due to Streptococcus pneumoniae. Focal neurological deficits are seen in 10% to 35% of patients with Listeria monocytogenes as part of a rhombencephalitis syndrome including ataxia with or without nystagmus, and cranial nerve palsies. Neisseria meningitidis may cause palpable purpura in 11% to 64% of patients, and concomitant septic arthritis in 7% to 11%. Papilledema and/or photophobia are rarely present, having been described in less than 5% of cases.

Approach To:

Suspected Bacterial Meningitis

CLINICAL APPROACH

The approach to suspected bacterial meningitis involves appropriate use of diagnostic studies and therapeutic interventions in a timely manner. Although no randomized controlled trial exists to prove it, the best experimental and observational data suggest that time to antibiotics has a profound effect on clinical outcomes. Therefore, our goal in the emergency department is to maintain a high index of suspicion and not delay treatment while diagnostic studies are being completed.

Diagnosis

The cornerstone of the diagnosis of meningitis is analysis of the cerebrospinal fluid (CSF), which is obtained by lumbar puncture (LP). LP can confirm the presence of inflammatory cells in the CSF, identify the causative organism by Gram stain and culture, and help in ruling out other potential causes of the patient’s symptoms (idiopathic intracranial hypertension or pseudotumor cerebri, subarachnoid hemorrhage, autoimmune disease, etc). When it is expected that there will be a significant delay in obtaining the LP, it is recommended to obtain blood cultures and then initiate treatment with antibiotics with or without dexamethasone, prior to obtaining the CSF (see the section Treatment). A common cause for delay of diagnosis is the time it takes to obtain a computed tomography (CT) scan of the head. The goal of CT scanning prior to performing an LP is to identify those patients that may be at risk of brain herniation during the procedure. Current Infectious Diseases Society of America (IDSA) guidelines for CT before LP include patients who present with altered mental status or a depressed level of consciousness, focal findings on neurologic examination, or a handful of other specific risk factors (Table 30–1). All other patients can safely have an LP performed without an antecedent CT scan.

^aIncluding HIV, AIDS, post-transplant, on immunosuppressant medications.

^bIncluding mass lesions, strokes, focal infection, surgery.

Administration of antibiotics has minimal effect on chemistry and cytology of CSF, but can reduce the yield of Gram stain and culture. In fact, administration of antibiotics can result in sterile CSF cultures within an hour in patients suffering from meningococcal infections. Pneumococcal infections, however, will typically remain culture positive up to 4 to 10 hours after administration of parenteral antibiotics. Importantly, Gram stains can positively identify an organism in 10% to 15% of patients who have sterile cultures after antibiotic administration.

Identification of the causative organism allows clinicians to safely narrow the spectrum of antimicrobial therapy. However, in the emergency department we are often unable to know with certainty what organism will eventually be identified, and are therefore required to initiate empiric therapy on the basis of epidemiologic data and local resistance patterns. Gram stain of the CSF is successful in identifying the microorganism in approximately 80% of cases. As Gram stain results are typically available 1 to 2 days before culture results, it is helpful to know the Gram-stain pattern of the most common organisms. The presence of gram-positive diplococci suggests Streptococcus pneumoniae infection, while gram-negative diplococci suggest Neisseria meningitidis infection. Small pleomorphic gram-negative coccobacilli suggests Haemophilus influenzae, while gram-positive rods and coccobacilli suggest Listeria monocytogenes infection. Additional cases will be identified by culture of the CSF and blood; yet this information is rarely available during the initial emergency department presentation. Additional analyses of the CSF should include opening pressure (which can be the only abnormality present in cases of cryptococcal meningitis), CSF protein, CSF glucose, cell count with differential, and CSF lactate. Unfortunately, despite all of these tests it can still be quite difficult to distinguish between the possible causes of meningitis (bacterial, viral, tubercular, neoplasms, autoimmune, etc) (Table 30–2). Therefore, most patients with CSF pleocytosis (presence of an elevated number of WBCs) should be admitted to the hospital and treated for meningitis while awaiting the results of CSF culture.

Treatment

The most important element of treatment after stabilization of the ABCs is initiation

of appropriate antimicrobial therapy. The most common organisms to cause

Abbreviations: CSF = cerebrospinal fluid; PMN = Polymorphonuclear leukocyte; WBC = white blood cells; Ag = antigen.

^aViral meningitis typically has a lymphocyte predominance; however, in the first 48 hours PMNs may predominate.

bacterial meningitis in adult patients are Neisseria meningitidis and Streptococcus pneumoniae. Initial therapy should include a third generation cephalosporin in a sufficient dose to achieve adequate CSF concentration. Ceftriaxone or cefotaxime at a dose of 2 g is typically recommended in the United States. As a result of an increasing worldwide prevalence of drug resistant Streptococcus pneumoniae, most authorities now recommend a dose of vancomycin along with the third-generation cephalosporin until a resistance profile can be obtained.

Patients who are older than 50 years of age, alcoholic, or immunocompromised are at higher risk for additional organisms including Listeria monocytogenes, Haemophilus influenzae, and aerobic gram-negative bacilli, and should therefore have ampicillin added to the empiric antibiotic regimen. Patients less than 1 month of age are at risk for infection with Streptococcus agalactiae, Klebsiella sp, E coli, and L monocytogenes and require yet another empiric regimen (Table 30–3).

In addition to adequate antimicrobial therapy, a number of recent studies have shown improved outcomes with adjunctive dexamethasone either before or with the first dose of antibiotics. The theory is that meningitis leads to significant morbidity and mortality as a result of the inflammatory response in the CSF. This response can be heightened when antimicrobials are administered, which will lead to bacterial

^aCeftriaxone or cefotaxime.

Data from Tunkel A, Hartman B, Kaplan S, et al. Practice guidelines for the management of bacterial meningitis.

Clin Infect Dis. 2004;39:1267-1284.

lysis and release of additional inflammatory mediators. Administering a dose of corticosteroids (dexamethasone 0.15mg/kg IV every 6h) with or before the first dose of antibiotics may attenuate the inflammatory response. If antibiotics have already been initiated as an outpatient or before steroid administration, the subsequent addition of dexamethasone has no demonstrated efficacy and may cause harm.

The evidence supporting the use of dexamethasone is based largely on a single randomized double-blinded placebo-controlled trial that compared dexamethasone 10 mg IV q6h × 4 d versus placebo in 301 adults with bacterial meningitis (suspected disease plus either cloudy CSF, a positive Gram stain, or >1000 WBC/mm³). In this trial, the number needed to treat (NNT) to prevent an unfavorable outcome was 10 and the NNT to prevent death was 12.5. There was, however, some heterogeneity in the results, with the greatest benefit found in those patients with an intermediate GCS of 8 to 11 and those with disease ultimately found to be due to Streptococcus pnuemoniae. For most patients, a single dose of dexamethasone is unlikely to be harmful, and in general most authorities recommend that if you are giving antibiotics for suspected bacterial meningitis, it should be preceded or accompanied by a dose of dexamethasone.

Once a patient is diagnosed with bacterial meningitis, family members and close contacts (such as this patient’s roommate) are often concerned about whether they should receive antibiotic prophylaxis to prevent them from developing a similar infection. Current CDC guidelines recommend antibiotic prophylaxis (typically with a fluoroquinolone or rifampin) for close contacts (anyone in the same household or day-care center or anyone in direct contact with the patient’s oral secretions) of patients with meningitis due to Neisseria meningitidis. Antibiotics for close contacts of patients with meningitis due to Haemophilus influenzae are no longer recommended if all contacts 4 years of age or younger are fully vaccinated against Hib disease. Given the high morbidity and mortality of meningococcal infections, vaccination against N meningitidis is recommended for freshmen college students who live in dormitories, as they are at moderately increased risk of contracting this disease.

COMPREHENSION QUESTIONS

30.1 A 30-year-old man presents with altered mental status, fever, and nuchal rigidity. You suspect bacterial meningitis. Which of the following is the appropriate order of your actions?

A. Head CT, lumbar puncture, blood cultures, steroids, antibiotics

B. Blood cultures, head CT, lumbar puncture, steroids, antibiotics

C. Blood cultures, steroids, antibiotics, head CT, lumbar puncture

D. Lumbar puncture, blood cultures, steroids, antibiotics, head CT

E. Head CT, blood cultures, steroids, antibiotics, lumbar puncture

30.2 Which of the following are the appropriate empiric antibiotics to administer to a 65-year-old man with suspected bacterial meningitis?

A. Vancomycin alone

B. Vancomycin and ceftriaxone

C. Vancomycin and ceftriaxone and amoxicillin

D. Vancomycin and ceftriaxone and ampicillin

30.3 Approximately what percentage of patients with bacterial meningitis present with the classic triad of fever, neck stiffness, and altered mental status?

A. <50%

B. Between 51%-75%

C. Between 76%-99%

D. >99%

ANSWERS

30.1 C. Neuroimaging is indicated in this patient prior to lumbar puncture given his altered mental status. Given the high suspicion for bacterial meningitis, antibiotic administration should not be delayed for the head CT. It is expected that one would obtain blood cultures and administer dexamethasone prior to the antibiotics in this case.

30.2 D. All adults with suspected bacterial meningitis get a third-generation cephalosporin and most institutions advocate for vancomycin to cover drug-resistant Streptococcus pneumoniae. Ampicillin is added because this patient is older than the age of 50.

30.3 A. Although the triad in the question is considered classic, studies have found that it is only present in less than half of the cases. If headache is added to the other 3, then at least 2 of the 4 symptoms are present in approximately 95% of patients.

CLINICAL PEARLS

⯈ The classic triad of fever, neck stiffness, and a change in mental status is present in less than 50% of patients with bacterial meningitis.

⯈ Younger patients that are otherwise healthy do not require neuroimaging prior to LP if they have a normal neurologic examination including mental status.

⯈ Initial antimicrobial therapy in adults should include a third-generation cephalosporin and vancomycin to cover drug-resistant S pneumoniae.

⯈ Patients older than 50 years, alcoholics, and immunocompromised patients should have ampicillin added to the empiric antimicrobial therapy to cover L monocytogenes.

⯈ Dexamethasone prior to or with the first dose of antibiotics has been shown to decrease neurologic sequelae as well as mortality among adults with bacterial meningitis.

References

Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med. 1998;129:862. 

Attia J, Hatala R, Cook DJ, Wong JG. The rational clinical examination. Does this adult patient have acute meningitis? JAMA. 1999;282:175. 

de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Eng J Med. 2002;347(20):1549-1556. 

Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Eng J Med. 1993;328:21. 

Geisleler PJ, Nelson KE, Levin S, et al. Community-acquired purulent meningitis: a review of 1,316 cases during the antibiotic era, 1954-1976. Rev Infect Dis. 1980;2:725. 

Hasbun R, Abrahams J, Jekel J, et al. Computed Tomography of the head before lumbar puncture in adults with suspected meningitis. N Eng J Med. 2001;345(24):1727-1733. 

Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics. 2001;108:1169. 

Talan DA, Hoffman JR, Yoshikawa TT, Overtuft GD. Role of empiric parenteral antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art. Rev Infect Dis. 1988;10:365. 

Tunkel A, Hartman B, Kaplan S, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-1284. 

van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Eng J Med. 2004;351(18):1849-1859. 

van de Beek D, de Gans J, Tunkel A, et al. Community-acquired bacterial meningitis in adults. N Eng J Med. 2006;354(1):44-53. 

Whitney C, Farley M, Hadler J, et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Eng J Med. 2000;343(26):1917-1924.

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