GENERAL POINTS

Bacterial meningitis is an inflammatory response due to infection of the leptomeninges and subarachnoid space. This is characterised by the clinical syndrome of fever, headache, neck stiffness and CSF pleocytosis. Despite the existence of antibiotic therapy, patients continue to suffer significant morbidity and mortality.

The bacterial organisms are usually not confined to the brain and meninges and frequently cause systemic illness, for example, severe sepsis, shock, acute respiratory distress syndrome, and bleeding disorders such as disseminated intravascular coagulation.^1,2

A variety of other pathogens cause meningeal inflammation, resulting in very similar clinical presentations. Bacterial infections must be treated urgently and appropriately to limit ongoing central nervous system (CNS) damage. It is also important to treat the complications of meningitis such as seizures and raised intracranial pressure (ICP).

Where possible, spinal fluid examination following a lumbar puncture is required in order to confirm the diagnosis and establish the pathogenic organism responsible. A CSF examination may be contraindicated if there are signs of raised ICP, including:

These features raise the possibility of an undiagnosed cerebral mass lesion which, in turn, could cause cerebral herniation if lumbar puncture is performed. A computed tomography (CT) brain scan is required prior to CSF examination in order to explore this possibility and lessen but not obviate the risk of cerebral herniation. Even if the CT brain scan is normal, ICP may still be raised. The importance of performing a safe CSF examination must be balanced against the need to commence immediate treatment in each individual patient.^3,4

AETIOLOGY

The main causes of meningitis are spread by droplet infection or exchange of saliva. Meningitis may occur when pathogenic organisms colonise the nasopharynx and reach the blood–brain barrier. Meningitis can occur as a result of infection in the middle ear, sinus or teeth, leading to secondary meningeal infection. Most bacteria obtain entry into the CNS via the haematogenous route. As the organisms multiply, they release cell wall products and lipopolysaccharide, and generate a local inflammatory reaction which in itself also releases inflammatory mediators. The net result of the release of cytokines, tumour necrosis factor and other factors is associated with a significant inflammatory response. Vasculitis of CNS vessels, thrombosis, cell damage and exudative material all contribute to vasogenic and cytotoxic oedema, altered blood fiow and cerebral perfusion pressure. Later on infarction and raised ICP occur.⁵

The inflammatory events seen with infection are summarised in Figure 47.1.

Figure 47.1 Cascade of events in meningitis. IL-1, interleukin-1; TNF, tumour necrosis factor; PAF, platelet-activating factor; ICP, intracranial pressure; CPP, cerebral perfusion pressure.

ORGANISMS

Acute bacterial meningitis can be caused by many species of bacteria, although three organisms are commonly reported:

Until the advent of the meningitis vaccination programme, H. infiuenzae type B was the most common cause of bacterial meningitis. Recently S. pneumoniae and N. meningitidis have been considered the main causes, although one study suggested that Listeria monocytogenes is the second most common isolate in adult population. The occurrence of pneumococcal strains which are resistant to penicillin has also influenced the epidemiology of meningitis.⁶

NOSOCOMIAL INFECTIONS

Common systemic nosocomial pathogens such as Escherichia coli, Pseudomonas spp., Klebsiella and Acinetobacter spp. account for a high percentage of nosocomial infections of the meninges.

IMMUNOCOMPROMISED HOSTS

In the immunocompromised patient with meningitis (e.g. human immunodeficiency virus: HIV), fungal viral and cryptocococal meningitis should be considered.⁷

NEUROSURGERY AND TRAUMA

Infections following skull trauma are frequently caused by Staphylococcus aureus and S. epidermidis, which should be considered in those with shunts or other intracranial devices.

CLINICAL PRESENTATION

The history may reveal evidence of trauma or infection. Meningitis usually presents with an acute onset of:

However, in the immunocompromised, elderly or infant patient, non-specific features such as a low-grade fever or mild behavioural change may be all that is apparent. Many of the classic symptoms are late manifestations of meningitis: preceding trivial early symptoms such as leg pain or cold hands may not immediately suggest the more serious underlying diagnosis.

It is important to identify from the history reported about preceding trauma, upper respiratory tract infection or ear infection. Symptoms may develop over hours or days. Specific infections relate partly to an individual’s age.

Neurological signs can be present with meningitis but signs such as nuchal rigidity, or a positive Kernig’s sign (pain and hamstring spasm resulting from attempts to straighten, the leg with the hip fiexed) are not universally found. A number of recent studies have shown that the classic signs were present in less than 50% of cases. Systemic signs may occur most often in meningococcal disease, where a haemorrhagic, petechial or purpuric rash may be observed. Digital gangrene or skin necrosis may occur. Some patients are severely septic, with acute respiratory distress syndrome and disseminated intravascular coagulation.

Approximately 25% of patients have a seizure during the course of the illness. Differential diagnosis may include subarachnoid haemorrhage, migraine, encephalitis and tumour.

INVESTIGATIONS

The patient with suspected bacterial meningitis requires immediate blood cultures and should be given empirical intravenous (IV) antibiotics if there is likely to be any delay in further assessment (Table 47.1).

Table 47.1 Cerebrospinal fluid changes in meningitis

CEREBROSPINAL FLUID FINDINGS

A CSF examination is a vitally important investigation which may definitively confirm the diagnosis of bacterial meningitis. In this regard its value should should not be dismissed. Concern about the risks of coning following lumbar puncture should be considered in the context of patients’ symptoms where the presence of seizures, focal neurological signs and papilloedema may suggest raised ICP. Neuroimaging may provide some level of reassurance that it is safe to proceed with a lumbar puncture; however, the clinican should be aware that all factors need to be taken into consideration.

Bacterial meningitis is suggested when there is:

An urgent Gram stain and microbiological culture are mandatory. The Gram stain is usually positive in approximately 50–60% of cases. A CSF examination shortly after empirical antibiotics does not necessarily decrease the diagnostic sensitivity of CSF culture. Polymerase chain reaction (PCR) techniques can be used to detect different organisms. A throat swab should be routinely taken. The clinical decision-making process that determines whether somebody does or does not have bacterial meningitis cannot be modelled easily and depends on multiple factors including clinical, laboratory findings and observation of the patient over time.

Blood cultures comprise an important investigation in patients with meningitis, as spread is haematogenous, and a number of sets of cultures should be sent. It is advisable to check routinely a full blood count clotting profile (to exclude disseminated intravascular coagulation) and biochemistry, including blood glucose level. A chest X-ray and blood gases should be performed to identify systemic involvement. Obviously, relevant areas such as infected sinuses or ears should be examined if there is an indication that they are implicated.

MANAGEMENT

Antibiotics should be started as early as possible and broad-spectum coverage is recommended until bacterial identifcation is made (Table 47.2). The selection of antibiotics is influenced by the clinical situation in conjunction with known allergies or local patterns of antibiotic resistance and the CSF findings. Delays in administering antibiotics are a significant risk factor for a poor prognosis. In the absence of a known organism, empirical choice for antibiotics has been complicated by the development of resistant strains. Penicillin G, ampicillin and third-generation cephalosporins are typical first-line agents. Until recently, ampicillin was appropriate for pneumococcal, meningococcal and Listeria infections. The emergence of resistant strains influences local antibiotic practice. If there is a history of recent head injury, a broad-spectrum cephalosporin may be indicated with vancomycin. Discussions with local microbiology services are recommended. If the CSF examination identifies the organism, then specific regimens can be prescribed (Table 47.3).

Table 47.2 Empiric antibiotics for meningitis

Table 47.3 General recommendation for known organisms*

* Always check local sensitiviity as resistance patterns are variable.

It is more difficult to select an appropriate empirical antibiotic in the immunocompromised patient. When the organism has been identified and sensitivity results are available, it may be necessary either to change the antibiotic or to rationalise those being given.⁸

In all cases, it is important to monitor the clinical response to therapy and, if necessary, antibiotics should be reviewed and appropriately altered once antibiotic sensitivities are known or a patient is not considered to be improving. A repeat CSF examination should be performed if there is concern about antibiotic sensitivity or selection. In those with penicillin-resistant pneumococcal meningitis, a CSF examination 48 hours after presentation is recommended to ensure bacteriological improvement. Antibiotics should be given for 10–14 days, although a shorter course may be adequate in some circumstances. Intrathecal antibiotics are not recommended.