Recognizing bacterial meningitis

A 32-year-old software engineer presents with headaches and fever for the past two days. A fever of 105.5°F forced him to cancel a business trip. The patient complains of the worst headache of his life. He is otherwise healthy and sees you only for annual checkups. Physical exam is significant for obvious distress (he needs to lie in the room without any lights on). He is febrile to 104.9°F in your office and has a stiff neck, raising his legs when you lift his head on the exam table. His neurologic exam is normal, and his wife, who brought him to the office, has noticed no evidence of confusion or somnolence. Skin exam is also normal. What is the diagnosis?

Bacterial meningitis is an uncommon but serious event in clinical practice. Its presentation is dramatic, and rapid diagnostics are essential in order to obtain necessary information for treatment as well as prognosis. Bacterial infection of the meninges is the worst-case scenario but is potentially treatable if picked up early, putting extra pressure on the clinician to act quickly. Viral infections are usually less serious but more common, needing only supportive care (with one important exception to be discussed later).

Epidemiologic studies estimate the incidence of bacterial meningitis to be about three cases per 100,000 population in the United States. Predisposing risk factors include diabetes mellitus, alcohol abuse, and other infections (e.g., sinusitis, otitis media, or pneumonia). Infection of the meninges and subarachnoid space occurs when the pia mater, arachnoid space, or dural meninges are broached by an invasive pathogen, leading to the clinical findings of meningitis. The more usual organisms include Streptococcus pneumoniae, Hemophilus influenzae, and Neisseria meningitidis; others include Listeria monocytogenes and some more unusual bacteria.  

Sudden onset

Patients typically present with a sudden illness characterized by fever, neck pain, and altered mental status (see table below). Photophobia is a hallmark feature, as is nuchal rigidity. In this case, pain occurs not only on passive motion of the neck but also with associated meningeal irritation, which results in spontaneous flexion of the hips during passive flexion of the neck (Brudzinski sign) or inability to fully extend the knees when the hips are flexed at 90° (Kernig test). While these bedside tests are enshrined in medical school textbooks, modern data have suggested that they are neither sensitive nor specific. Extrameningeal signs are nonspecific except for purpura, which can be the most dramatic and frightening associated exam finding. Purpura is highly suggestive of meningococcal infection but seen only on rare occasions.

Laboratory and radiographic analysis

Baseline lab results can be normal and without evidence of leukocytosis or azotemia. Cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) is essential for the diagnosis of meningitis. The rare but serious consequence of LP is transtentorial herniation, which leads to rapid neurologic deterioration and death. This complication has been known anecdotally since the earliest use of LP, but modern series estimate occurrence in <1% of patients with bacterial meningitis. In addition, it is difficult to know if the herniation was a sequela of meningeal inflammation severity or a consequence of the procedure itself. Therefore, it is common clinical practice to obtain tomographic imaging of the brain to exclude mass effect or hydrocephalus (although robust studies at academic medical centers have shown this to be an unnecessary step that delays therapy by up to one hour and CSF analysis by up to two hours). Guidelines issued in 2004 by the Infectious Diseases Society of America recommend imaging only in patients with additional worrisome clinical factors, such as known immunocompromised state, previous history of central nervous system (CNS) disease, abnormal neurologic exam, or evidence of increased intracranial pressure (ICP) with papilledema (see table below).




A common sequela of LP is post-procedure headache, which may sometimes be worse than the initial presenting complaints. The headache is believed to be caused by a low-level CSF leak at the site of the puncture and usually resolves with time. Observational data suggest that the risk of post-procedure headache can be reduced by keeping the patient supine for four to six hours after the LP has been performed. Other adjunct measures include oral and/or IV hydration. Caffeine has been used successfully in some circumstances. If all else fails, something called the “blood patch” can be performed by an anesthesiologist. In this unusual intervention, the patient's blood is phlebotomized and then immediately injected into the subarachnoid space, providing immediate relief. This procedure has been done for decades, but there are few clinical data to support its efficacy.

The CSF should be analyzed for evidence of meningeal inflammation. If at all possible, ICP should be estimated with bedside manometry performed on the supine resting patient during the LP. Elevated pressures (normal ICP is one-sixth of a patient's systolic BP, i.e., approximately 20 mm Hg) are highly suggestive of bacterial meningitis and may have prognostic value if more than twice the normal level (>40 mm Hg). Routine studies should include protein and glucose determinations, WBC count and differential, and Gram's stain and culture (see table below). Because the culture results are so crucial and the pathogens are exquisitely sensitive to antibiotics, the sample should be obtained prior to antibiotic administration. Use of polymerase chain reaction (PCR) for bacterial pathogens, although promising in the research setting, is not recommended at this time because of technical obstacles. If a timely LP cannot be done (either because of imaging-related delay or other complicating factors), blood cultures should be obtained and antibiotics given at once, despite the decrease in yield of CSF cultures. The approach to those with HIV infection or chronic immunosuppression because of solid organ or bone marrow transplantation is best handled with the assistance of a specialist.

Therapy to cover the possibilities

Empiric therapy should begin as soon as possible. Antimicrobial choices will cover the usual suspects and will be modified once Gram's stain and culture data become available. The use of dexamethasone, once considered controversial, has become the standard of care. Dexamethasone should be administered as soon as possible, as this agent has been shown to reduce morbidity as well as mortality in well-controlled trials in children as well as adults in many clinical settings. The greatest benefit was seen in those patients with pneumococcal meningitis and worsened disease severity, so the use of corticosteroids in others may not be as important.

A diagnosis of bacterial meningitis requires respiratory isolation for 24 hours because of the possibility of meningococcal infection. If the clinician has evidence (e.g., Gram's stain, CSF culture, or other clinical data) to suggest alternative causes, respiratory isolation may be discontinued. In the case of meningococcal disease, close contacts, defined as household members or those who were directly exposed to oral secretions (including respiratory therapists and other health-care personnel), should be offered chemoprophylaxis with rifampin, ciprofloxacin, ceftriaxone, or azithromycin. Additional information is available from the CDC (MMWR. 2005;54[RR07]:1-21, along with a 2007 update for patients aged 11-18 years, both accessed January 7, 2009).

In persons with evidence of neurologic involvement, consider herpes simplex virus (HSV). HSV does not typically cause meningitis. (A rare disease known as Mollaret's meningitis may be associated with HSV; its prognosis is excellent.) However, HSV encephalitis can sometimes begin with headache, fever, and neurologic changes with little evidence on CNS imaging or the expected hemorrhagic pleiocytosis described in most clinical series. PCR for HSV has become widely available and allows for rapid testing from spinal fluid. Untreated, HSV encephalitis can be fatal. IV acyclovir is safe, so its addition to empiric therapy in the proper clinical context is encouraged until more information is obtained in  patients whose Gram's stain is negative. HSV is the only viral CNS infection that warrants empiric therapy. Other viral causes of meningitis, which outweigh bacterial causes by a factor of almost 10 in the general community, have a more benign course and are without any proven therapeutic options.

Guided by the clinical course

Response to antimicrobial therapy is the most important determinant of additional clinical steps. If there is decline in neurologic status over the next 48 hours, CNS imaging is essential to evaluate for evidence of ICP increase that would suggest meningoencephalitis. This may be the course of a bacterial process, or it may be suggestive of an alternative etiology if no bacterial infection has yet been identified. Increasing ICP in the setting of bacterial meningitis is difficult to manage clinically, but monitoring in the ICU is necessary. A lumbar drain or ventriculostomy has been lifesaving in select cases. 

Rapid deterioration that continues to frank coma or intractable seizures may indicate subdural empyema. This can be seen in the setting of otitis media, mastoiditis, or sinusitis and is best diagnosed with MRI. Surgical drainage by craniotomy is the treatment of choice.

Cranial-nerve palsies may also occur as a result of increased ICP or local meningeal inflammation. Eighth-nerve palsies are the most common permanent neurologic sequelae in pneumococcal meningitis (seen in up to 14% of cases), but their incidence can be reduced with the appropriate use of corticosteroids. Cochlear implants are usually required once the infection has been cleared.

Finally, if CNS imaging is unremarkable but the patient does not improve or demonstrates clinical deterioration, repeat LP may help to identify drug-resistant pneumococci. This is especially important in areas where penicillin-resistant organisms are endemic.

Once the patient has been stabilized and the pathogen has been isolated, therapy is narrowed to the appropriate agent, which is always administered IV because of the high doses necessary for CSF penetration. Cases attributable to meningococcus or Hemophilus influenzae can be treated for as few as seven days. Pneumococcal meningitis requires 14 days of parenteral therapy. The management of other etiologies of bacterial meningitis warrant consultation with a specialist.

Closing thoughts

Bacterial meningitis is a rare but serious infection with potentially devastating consequences. Diagnosis should be made using available bedside techniques as well as laboratory and imaging modalities. Antimicrobial therapy should be initially broad-based with the addition of corticosteroids to reduce morbidity and mortality. Rapid diagnosis can be lifesaving if treatment begins promptly.

Dr. Spak is an infectious diseases staff physician at Baylor University Medical Center in Dallas.