The next step in the management of CNS infections is to start antibiotic treatment. Antibiotics should be started immediately after completing the physical exam, even before obtaining a CT scan and performing an LP. Importantly, timely administration of appropriate antimicrobial therapy improves both morbidity and mortality. A retrospective case record study of 119 patients diagnosed with adult acute bacterial meningitis aged greater than or equal to 16 years assessed the association between meningitis mortality and door-to-antibiotic time. If appropriate antibiotic therapy was delayed 6–8 h mortality rose to 45% and if delayed to the 8–10 h range the mortality increased to 75% [20]. In ICU patients with community acquired pneumococcal meningitis, in-hospital antibiotic delay exceeding 3 h was the strongest indicator of mortality, with a 14-fold increase in the mortality risk over the group receiving antibiotics in less than 3 h of admission [3]. Another study found that in the first 12 h from admission, the odds for an unfavorable outcome increased 30% with every hour that antibiotics were delayed [17].

The significant predictors for delay in initiation of antibiotics were found to be no antibiotic prior to transfer from another hospital; the diagnostic–treatment sequence of CT of the head followed by lumbar puncture followed by antibiotics; partial meningitis treatment; and absence of the meningitis triad at presentation/atypical presentation, lack of fever, and patients with concomitant pneumonia [3, 20].

Choice of initial antimicrobial therapy will differ between institutions based on formulary availability; generally speaking, for adult patients with normal renal function, the empiric regimen of choice includes:

There is evidence for the use of dexamethasone in bacterial meningitis, particularly in CNS infections caused by Streptococcus pneumoniae. One trial enrolled 301 patients with the treatment group receiving 10 mg of dexamethasone every 6 h for 4 days [8]. Note that the first dose was given prior to, or at the time of, antibiotic administration. The trial demonstrated significant improvement in outcome in those patients receiving dexamethasone. This improvement in outcome and decrease in mortality was almost exclusively in the group of patients that were identified as having pneumococcus. Analysis for different bacteria causing meningitis showed that patients with meningitis due to Streptococcus pneumoniae (S. pneumoniae) treated with corticosteroids had a lower death rate (29.9% versus 36.0%), while no effect on mortality was seen in patients with Haemophilus influenzae (H. influenzae) and Neisseria meningitidis (N. meningitidis) meningitis. Dexamethasone increased the rate of recurrent fever, but was not associated with other adverse events [4].

In situations where it is clearly evident that the suspected organism is not S. pneumoniae, dexamethasone may be withheld. Otherwise, empiric use of dexamethasone until cultures return is reasonable [11]. The Infectious Disease Society of America’s practice guidelines state: “some authorities would initiate dexamethasone in all adults with suspected bacterial meningitis because the etiology of meningitis is not always ascertained at initial evaluation” [26]. Patients should be given 10 mg of IV dexamethasone immediately and every 6 h thereafter for a duration of 4 days [8]. Ideally, the steroid should be given prior to or at the start of antibiotic therapy [11, 26]. The rationale for dosing the dexamethasone prior to antibiotic administration is to diminish the inflammatory response triggered by endotoxins from bacterial lysis that occurs following antibiotic administration.

Early on in the workup of this type of patient an emergent non-contrast head CT should be ordered. In the management of the patient with a suspected CNS infection, certain findings on head CT such as subarachnoid or intraparenchymal hemorrhage or mass lesion which adequately explain the patient’s neurologic deficits will abort the workup for CNS infection and the provider should proceed with management of the alternate diagnosis found on the CT. The initial antimicrobial orders can then be canceled as they will not significantly affect the ongoing management of a bleed or lesion.

If the patient’s head CT is grossly normal, the provider should proceed with lumbar puncture as soon as possible. Various studies have been done on CSF analysis after antibiotic administration and show that even the most antibiotic-sensitive pathogens will still be present and culturable in CSF for the first 4 h after antibiotic administration. Collection of CSF for culture and immunohistochemical testing for viral and other rarer pathogens will be the single greatest driver of antimicrobial therapy adjustment going forward, as it is always best to narrow your antimicrobial regimen as early as possible to avoid very real medication side effects.

Ideally a lumbar puncture (LP) would be performed prior to antibiotic administration. Administration of antibiotics prior to performing an LP raises the issue of the diagnostic value of the CSF examination. Gram stain has 92% sensitivity and greater than 99% specificity in diagnosing bacterial or fungal meningitis in those who have received no treatment [9]. Michael et al. show that CSF culture is still likely to be positive in adults with bacterial meningitis if the LP is performed within a few hours of starting the antibiotics. Beyond 4 h, the chance of positive cultures drops significantly, and beyond 8 h, no culture was positive [18]. Another study also found that beyond 4 h after antibiotic administration, chances of a positive CSF culture are low [14].

Performing a lumbar puncture before obtaining a head computed tomography (CT) is a source of controversy due to the risk of brain herniation which may occur in patients with elevated intracranial pressure and or mass-occupying lesions. A CT scan of the brain is typically not required or needed to diagnose bacterial meningitis, but it is useful in excluding other diagnoses. CT is also useful for excluding mass-occupying lesions that might complicate the lumbar puncture done for diagnosis. There is minimal evidence supporting the need for a CT scan of the brain prior to LP. Somewhere between 3% and 5% of patients with meningitis develop fatal herniation syndromes within the first 7 days of hospitalization, around 60% of those within the first hours post LP [10]. There are also studies demonstrating that normal CT scans do not eliminate the risk for herniation nor do abnormal CT scans predict herniation after LP [12].

Head CT should be expedited prior to lumbar puncture in patients with any of the following: altered mental status, focal neurologic deficits, papilledema or loss of venous pulsations on fundoscopic examination, new onset seizures or a history of CNS disease such as stroke or intracranial mass lesions, and known or suspected immunosuppression [26]. Unfortunately, from a diagnostic standpoint, most patients who present with symptoms consistent with acute bacterial meningitis will likely meet criteria for a head CT prior to LP.

There are many differential diagnoses for patients with suspected CNS infection (Table 13.3). Bacterial meningitis is at the top, followed by non-bacterial meningitis, usually referred to as aseptic meningitis (a vast majority of which are viral). Patients with aseptic meningitis have clinical and laboratory evidence for meningeal inflammation inconsistent with bacterial infection and bacterial cultures of CSF that are negative. Encephalitis and intracranial abscess or empyema can have similar presentations. Additional etiologies include other non-bacterial infections (mycobacteria, e.g., tuberculosis and other mycobacterium (very rare), fungi, protozoa, e.g., amoeba, trypanosomes, malaria, toxoplasma, and helminths (parasitic worms), e.g., trichinosis, cysticercosis), but these are quite rare. There are also noninfectious causes of meningeal symptoms which include subarachnoid hemorrhage, postictal state, complex migraine headache, brain tumors, carcinomatosis, cysts, illicit drug, or alcohol intoxication. Although rare, there are also prescription drug-related cases of aseptic meningitis, also known as chemical meningitis, including from antibiotics, particularly trimethoprim-sulfamethoxazole, trimethoprim alone, and amoxicillin; NSAIDs, especially ibuprofen; immunosuppressive immunomodulatory drugs including monoclonal antibodies, (mainly tumor necrosis factor inhibitors) and intravenous immunoglobulins; and the antiepileptics lamotrigine and carbamazepine [19].

Most of these patients will require ICU care and monitoring, even if mechanical ventilation or hemodynamic support with vasopressors is not needed.