9.1 Approach to undifferentiated fever in adults

Step 3: look for the ‘at-risk’ patient

If no diagnosis is forthcoming after the first two steps, the next task is to identify the ‘at-risk’ patient who may not appear overtly ill but who, nonetheless, requires medical intervention. This applies particularly to those with treatable diseases that can progress rapidly, such as bacterial meningitis, bacteraemia and toxic shock syndromes.

Four sets of pointers are helpful in identifying these ‘at-risk’ patients: the type of patient (host characteristics), exposure history, the nature of the non-specific symptoms and how rapidly the illness evolves.

Clinical pointers: type of patient

Clinical manifestations of infections are often subtle or non-specific in young children, the elderly and the immunocompromised. The threshold for intervention in these patients should be lowered. The issue of fever in children is not addressed in this chapter.

Elderly patients

Elderly patients with infections often do not mount much of a febrile response and fever may be absent in 20–30% of these patients [3].

Infectious diseases in the elderly, as in the very young, often present with non-specific or atypical symptoms and signs and may progress rapidly [4].

In adult patients with unexplained fever, up to one-third may have bacteraemia or focal bacterial infection. This proportion is even higher in those over the age of 50 [1]. In the elderly, a fever>38°C indicates a possible serious infection [5] and is associated with increasing risk of death [6].

The urinary tract is the most frequent site of infection and source of bacteraemia; symptoms of urinary tract infection are frequently absent in the elderly. The respiratory tract is the next most common site of infection; fever and malaise may be the only clues of pneumonia in the elderly. Urinalysis and chest X-ray will identify about half of occult infections [1].

An unexplained fever in a person over the age of 50 should be regarded as being caused by a bacterial infection until proved otherwise and is generally an indication for admission to hospital.

Alcoholic patients

Alcoholic patients present with multiple problems, many of which cause fever. Most are caused by infections, the commonest of which is pneumonia. Multiple infections may occur at the same time [7].

Non-infectious causes of fever frequently coexist with infections and conditions such as subarachnoid haemorrhage, alcoholic withdrawal and alcoholic hepatitis and require admission.

The initial history and physical examination in the alcoholic may be unreliable and diagnosis may be difficult.

Alcoholic patients with fever for which no obvious cause is found should be admitted to hospital for investigations and observation.

Injecting drug users

The risk of injecting drug users acquiring serious or unusual infections is high through repeated self-injection with non-sterile illicit substances, the use of contaminated needles and syringes and poor attention to skin cleansing prior to injections [8].

Many intravenous drug users presenting with fever have a serious infection. Some have obvious focal infections, such as cellulitis and pneumonia. Others present simply with fever and the presence of bacteraemia and endocarditis must be suspected.

Clinical assessment cannot differentiate trivial from potentially serious conditions in these patients [8]. A history of chills, rigors and sweats strongly suggest the presence of a transient or ongoing bacteraemia. Back pain may be a subtle symptom of endocarditis or vertebral osteomyelitis.

It is difficult to distinguish the patient with endocarditis from other drug users with fever due to another cause. Hospitalization of febrile injecting drug users would be prudent if 24-hour follow up is not possible. Intravenous drug use in the previous 5 days is a predictor of occult major infection and is an indication for admission to hospital [9].

Patients with diabetes mellitus

Diabetic patients are more prone to developing certain bacterial infections [1]. A diabetic patient with an unexplained fever is more likely to have an occult bacterial infection than a non-diabetic patient. In general, an insulin-dependent diabetic patient, especially if aged over 50, with fever and no obvious source of infection, should be investigated and preferably admitted.

Febrile neutropaenic patients

Febrile neutropaenic patients (absolute neutrophil count<500/μL or<1000/μL and falling rapidly) must be hospitalized regardless of their clinical appearance. Infections may become fulminant within hours in these patients and the clinical manifestations of their infective illnesses are frequently modified by the underlying disease, therapy received and coexisting problems.

Splenectomized patients

Splenectomized patients with fever must be very carefully assessed because of their increased risk of overwhelming bacterial infection. If the fever cannot be readily explained, admission for intravenous antibiotics is usually indicated.

Other immunocompromised patients

Fever in transplant patients (renal, hepatic or cardiac) and those with HIV infection is not an absolute indication for admission, but the threshold of intervention should be considerably lowered and they are best assessed by their usual treating doctors.

Patients recently discharged from hospital may have hospital-acquired infections or infections caused by multiresistant organisms. Recent operations or procedures may be a clue to the site of infection.

Clinical pointers: exposure history

Overseas travellers or visitors

Returned travellers or overseas visitors may have diseases such as malaria and typhoid fever that need early diagnosis and treatment. Any fever in a traveller returned from a malaria-endemic area should be regarded as due to malaria until proved otherwise.

Influenza in febrile returned travellers is a concern to EDs worldwide. Outbreaks of avian influenza occur periodically in bird populations throughout Asia. Although the virus does not typically infect humans, direct bird-to-human transmission of H5N1 influenza has been documented. The virus is highly pathogenic and the mortality of the disease is high. Travellers acquiring influenza overseas may also introduce this infection. Most cases occur within 2–4 days after exposure, but incubation is as long as 8 days. Suspected influenza infection requires isolation and respiratory precautions. The peak season is generally during the winter months, but can vary, especially in the tropics [10].

Although rare, viral haemorrhagic fever in returned travellers represents a true medical emergency and a serious public health threat. Viral haemorrhagic fevers are caused by several distinct families of virus, including Ebola and Marburg, Lassa fever, the New World arenaviruses (Guanarito, Machupo, Junin, and Sabia) and Rift Valley fever and Crimean Congo haemorrhagic fever viruses. Most exist in Africa, the Middle East or South America. Although some types cause relatively mild illnesses, many can cause severe, life-threatening disease. Viral haemorrhagic fever should be considered in any febrile patient who has returned from an area in which viral haemorrhagic fever was endemic, especially if they have come into contact with blood or other body fluids from a person or animal infected with viral haemorrhagic fever or worked in a laboratory or animal facility handling viral haemorrhagic fever specimens. All these infections have incubation periods of up to 2–3 weeks, so it may be possible to exclude viral haemorrhagic fever on epidemiological grounds alone. Isolation measures should be instituted immediately in these persons [11].

Staff working in emergency departments should be aware of regional outbreaks of unusual pathogens. These are reported by State and National Departments of Health. Returning travellers who are unwell will commonly go directly to an emergency department and this may be a critical point to limit further spread.

Contact with animals

A contact history with animals, either at work or at home, is frequently the clue to a zoonosis, particularly if the illness is a perplexing fever of several days’ duration. The occurrence of multiple cases at work or at home should also make one suspect these infections early.

Contact with meningococcal and Haemophilus meningitis

Close contacts of patients with these infections have a high risk of acquiring the same infections. Early symptoms may be subtle and a high index of suspicion must be maintained.

Clinical pointers: non-specific clinical features (Table 9.1.1)

There are several non-specific clinical features whose presence should suggest the possibility of sepsis. These warrant careful scrutiny even when the patient does not appear toxic. They are by no means specific indicators of serious problems and there will be many false positives. However, ignoring them is frequently the cause of missed or delayed diagnosis of sepsis.

Severe pain in muscles, neck or back

Severe muscle pain, even in the absence of overt fever, may be an early symptom of meningococcaemia, staphylococcal or streptococcal bacteraemia. It is also a feature of myositis and necrotizing fasciitis.

Impairment of conscious state

A change in conscious state may be the sole presenting manifestation of sepsis, especially in the elderly.

Vomiting

Unexplained vomiting, especially in association with headache or abdominal pain, should raise concern. Vomiting without diarrhoea should not be attributed to a gastrointestinal infection. It is a common symptom of CNS infections and occult sepsis.

Severe headache in the presence of a normal CSF

This is especially important in a person who seldom gets headaches. Severe headache in a febrile patient with normal CSF should not be diagnosed as a viral infection; many focal infections, e.g. pneumonia and bacterial enteritis, may also present in this manner. CSF may be normal in cerebral abscess and in the prodromal phase of bacterial meningitis.

Unexplained rash

An unexplained rash in a febrile patient should be regarded as meningococcaemia until proved otherwise, even in the absence of headache or CSF pleocytosis.

Jaundice

Jaundice in the febrile patient is associated with a greatly increased risk of death, admission to ICU and prolonged hospital stay [6]. Jaundice in a febrile patient is unlikely to be due to viral hepatitis, but occurs in serious bacterial infections, such as bacteraemia, cholangitis, pyogenic liver abscess and malaria.

Sore throat or dysphagia

Severe sore throat or dysphagia with a normal-looking throat is frequently the presenting symptom of Haemophilus influenzae epiglottitis in adults.

Repeated rigors

Although repeated rigors may occur in some viral infections, they should generally be regarded as indicators of sepsis, in particular abscesses, bacteraemia, endocarditis, cholangitis and pyelonephritis.

Clinical pointers: evolution of illness (Table 9.1.2)

How rapidly the illness evolves is often an indication of its severity. Previously healthy individuals do not seek medical attention unless they are worried. Notice should be taken of any person seeking help within 24 hours of the onset of illness or a person whose illness appears to have progressed rapidly within 24–48 hours (e.g. from being up and about to being bedridden). Similarly, the patient who presents to the ED on more than one occasion over a 24–48-hour period warrants a careful work-up.

Step 4: a final caveat

A major concern in the management of undifferentiated fever in adults is missing the diagnosis of meningococcal bacteraemia when the patient does not appear ill on presentation.

Clinical investigations

Most febrile patients seen in the ED justify a fever work-up.

Full blood examination is of limited use. White cell count (>15×10⁹/L), marked left shift, neutropaenia or thrombocytopaenia are pointers to a possible bacteraemia or occult bacterial infections, but they may also be seen in viral infections [12]. Similarly, non-specific markers of inflammation, such as C-reactive protein and erythrocyte sedimentation rate, have not been shown to be useful in predicting outcomes for febrile patients in the ED [13].

Urinalysis and urine culture should be done in febrile adults over the age of 50 unless the pathology clearly lies in another body system. However, if the history does not suggest urinary sepsis and the dipstick urinalysis is normal, then urine cultures are usually negative [14].

A chest X -ray is usually indicated unless a definite diagnosis has been made, e.g. chickenpox, tonsillitis.

Blood cultures should be done in anyone suspected of having bacteraemia, endocarditis or meningitis, in compromised patients with a fever, all febrile patients over the age of 50 and, possibly, in anyone with an unexplained high fever. It should be noted that only 5% of blood cultures in this setting will be positive and less than 2% will alter clinical management [15]. In general, a patient considered ‘sick enough’ to warrant blood cultures should be admitted to hospital or followed up within 24 hours.

Disposition

Patients who have any of the following features are in need of resuscitation, followed by work-up and admission: shock, coma/stupor, cyanosis, profound dyspnoea, continuous seizures and severe dehydration.

With few exceptions, the following groups of febrile adults should be investigated and admitted:

In general, there should be close liaison with the admitting unit and the issue of empirical therapy for septic patients should be discussed. For the dangerously ill, e.g. those with septic shock or bacterial meningitis, antibiotics should be commenced almost immediately.

There is an increasing tendency to start antibiotics in the ED as soon as possible to reduce the length of hospital stay. Time to antibiotic therapy is used as a key performance indicator for the ED, e.g. for febrile immunocompromised patients.

Patients who do not require intervention after the basic work-up in the ED are discharged home after a period of observation. Because of the time taken to interview the patient, perform investigations and wait for the results, the patient will usually have been observed for 1–2 hours and progression or lack of progression may be a help in deciding what to do. During observation one must be aware that the apparent improvement of the patient may be the result of pain relief or a fall in temperature due to antipyretics.

Arrangement must be made for the patient to be reviewed by their general practitioner or at the hospital. This is an essential component of the care of a febrile patient seen in an ED.

There is no easy way of detecting occult bacterial sepsis. The infectious process is a dynamic one and the doctor must maintain contact with the patient or family during the 24–72 hours following the initial visit.

Patients with fever>39°C must be seen within 24 hours. Review by a doctor within 6–12 hours may be necessary in those who have had a lumbar puncture and is advisable in those who have had blood cultures taken. A verified phone number should be clearly recorded in the medical history.

All febrile patients discharged from the ED should be encouraged to seek review if there is any adverse change to their condition. A patient re-presenting to the ED has provided an opportunity to ensure that they are being managed appropriately and to rectify any errors.

Fever due to most common viral infections will resolve by about 4 days. Many other infections will be diagnosed when new symptoms or signs appear.

If fever persists beyond 4–5 days without any localizing symptoms or signs, a less common infection or non-infective cause should be suspected and the patient should be thoroughly investigated. In this situation, the threshold of admission to hospital should be low.

The establishment of ED short-stay units allows fast-track treatment and observation, usually for 24–48 hours, for carefully selected febrile patients who are not suitable for immediate discharge home.

Future research directions

9.2 Meningitis

Classification

Meningitis is usually classified according to the aetiology or location as bacterial, aseptic (viral, tuberculous, fungal or chemical) or spinal (where the infection specifically affects the spinal meninges).

Aetiology

Bacterial

Bacterial meningitis is a serious cause of morbidity and mortality in all age groups. The causes vary according to age, as shown in Table 9.2.1. Neisseria meningitidis serogroups A and C tend to cause endemic cases of meningitis, especially in Aboriginal populations, whereas serogroup B is more commonly associated with epidemics [1]. There has been an increase in the incidence of penicillin-resistant Streptococcus pneumoniae, especially in children [2].

Aseptic

Aseptic meningitis may be either due to an immune response to a systemic infection (usually viral) or to a chemical insult.

Viral

Enteroviruses are the most common cause of meningitis, often in clusters of cases. Herpes viruses often cause meningitis as part of a more generalized infection of the brain (meningoencephalitis) or as part of an immune response to a systemic infection. A generalized viraemia may also cause aseptic meningitis, owing to an immune reaction without direct infection.

Fungal

Fungal causes of meningitis, especially that due to Cryptococcus neoformans, tend to occur in immunocompromised patients, such as those with HIV/AIDS or those on immunosuppressant medication or cancer chemotherapy. It can occur in immunocompetent individuals as well, particularly the elderly.

Tuberculous

Tuberculous meningitis is rare in industrialized countries, but can occur in all age groups. It tends to follow an insidious course, with a lack of classic signs and symptoms. Diagnosis is often difficult, owing to the low yield from CSF staining and the 4-week time frame required to culture the organism. Suspicion should be high in patients with immunocompromise or chronic illness. It tends to have a high mortality.

Spinal

Spinal meningitis is usually bacterial and due to direct spread from a localized infection in the spine.

Epidemiology

The epidemiology of meningitis is different for groups according to age, as well as immunocompetence:

Pathogenesis

Initially, there is colonization of the infectious agent, commonly in the nasopharynx in the case of the enteroviruses and bacteria, such as meningococcus and Hib. Other infections may spread from already established foci, such as otitis media or sinusitis (e.g. pneumococcus). There is either haematogenous or local spread to the meninges and subarachnoid space, with inflammation of this area and the production of a purulent exudate approximately 2 hours after invasion of the area. The inflammatory response is initiated by bacterial subcapsular components, such as lipoteichoic acid in S. pneumoniae, a lipo-oligosaccharide in H. influenzae and other Gram-negative endotoxins. These substances stimulate the release of cytokines, such as interleukin-1 and -6, tumour necrosis factor (TNF) and arachidonic acid metabolites, as well as the complement cascade. There is a subsequent increase in neutrophil and platelet activity, with increased permeability of the blood–brain barrier. This response is often worse after the initial destruction of bacteria by antibiotics. If left untreated, fibrosis of the meninges may occur. In viral and aseptic meningitis, there is a more limited inflammatory response, with mild-to-moderate infiltration of lymphocytes. In the more chronic causes, such as fungi or tuberculosis, the exudate is fibrinous, the main cells being a mixture of lymphocytes, monocytes/macrophages and plasma cells. The base of the brain is most commonly affected.

Presentation

History

There are some differences in the history with different causes of meningitis, which may allow an early differential diagnosis to be made. There are no pathognomonic single symptoms or signs for meningitis, so a high index of suspicion is necessary.

The combination of fever, headache, meningism and mental obtundation is found in approximately 85% of cases of bacterial meningitis [9]. It is also a common pattern in viral or aseptic meningitis, where obtundation is less of a feature. In fungal or tuberculous meningitis, these symptoms are much less common (less than 40% of cases of cryptococcal meningitis). Elderly patients or those who have had recent neurosurgery may present with subtle or mild symptoms and lack a fever [10].

The headache is usually severe and unrelenting. It may be either global or located in a specific area. The main symptoms of meningism are nuchal rigidity (neck stiffness) and photophobia. The nuchal rigidity is something more than merely pain on movement of the neck. It is clinically important when the patient complains of a painful restriction of movement in the sagittal plane (i.e. forwards and backwards only). Up to 35% of cases have associated nausea and vomiting.

As a general rule, the height of the fever is a poor indication of the possible cause, although the fever may often only be mild in tuberculous or fungal meningitis or in bacterial meningitis that has been partially treated by antibiotics. The spectrum of mental obtundation can range from mild confusion, to bizarre behaviour, delirium or coma. The severity of obtundation is a good indication of the severity of the illness.

Focal neurological signs occur in around 10–20% of cases of bacterial meningitis, but are also associated with cerebral mass lesions, such as toxoplasmosis or brain abscess. They are also a feature of tuberculous meningitis. Seizures are relatively uncommon (13–30%), but may occasionally be the only sign of meningitis if the patient has been partially treated with oral antibiotics.

There may also be associated systemic symptoms. Myalgias and arthralgias are often associated with viral causes, but may also be the sole presenting symptom in meningococcal meningitis. HIV/AIDS patients may show stigmata associated with that disease.

The course of the illness may also indicate the cause. Meningococcal or pneumococcal meningitis is often characterized by a rapid, fulminating course, often going from initial symptoms to death over an interval of hours. Viral causes tend to be a slower course over days. Fungal or tuberculous meningitis shows a more chronic course over days to weeks, with milder symptoms.

Risk factors for meningitis include the extremes of age, pre-existing sinusitis or otitis media, recent neurosurgery, CSF shunts, splenectomy, immunological compromise and chronic diseases such as alcoholism, cancer, connective tissue disorders, chronic renal failure and hepatic cirrhosis.

Examination

The physical examination will often reflect symptoms elicited in the history, with fever, physical evidence of meningism, stigmata of AIDS, etc.

As stated above, neck stiffness is only clinically significant when it occurs in the sagittal plane. There will be a restriction of both passive and active movement. Other tests to elicit meningism include Kernig’s sign and Brudzinski’s sign, although these are only present in 50% of adult cases of bacterial meningitis. Kernig’s sign is elicited by attempting to extend the knee of a leg that has been flexed at the hip with the patient lying supine and the other leg flat on the bed. The sign is positive if the knee cannot be fully extended due to spasm in the hamstrings. The test can be falsely positive in patients with shortening of the hamstrings or other problems involving the legs or lumbar spine. In Brudzinski’s sign, flexing the head causes the thighs and knees to also flex. It can also be tested in children by the inability to touch the nose with the flexed hips and knees in the sitting position. These are both late signs.

Focal neurological signs should be a cause for concern, as they can indicate a poor prognosis.

Papilloedema is rare and late, as is a bulging fontanelle in infants and should alert one to alternative diagnoses.

A rash, often starting as a macular or petechial rash on the limbs, is seen in sepsis due to N. meningitidis and S. pneumoniae. A petechial rash is a particularly serious sign and is an indication to start antibiotics immediately. A maculopapular rash is also a feature of viral causes.

Investigations

Lumbar puncture

A CSF sample via a lumbar puncture (LP) is an important source of information for making the diagnosis and determining the likely aetiology and treatment. As the procedure may be time-consuming, treatment should not be delayed if there will be more than a 20-minute delay before the lumbar puncture and there is a reasonable clinical suspicion that a bacterial cause is present. Blood cultures should be taken prior to the administration of antibiotics.

Indications

Precautions

The main features to note during lumbar puncture are the opening pressure and the physical appearance of the CSF. The sample should be sent for Gram staining, culture, sensitivities, polymerase chain reaction (PCR) analysis for bacteria and Herpes simplex virus, a cell count and protein and glucose levels. If fungal meningitis is suspected, an India-ink stain and cryptococcal antigen screen should be requested. If tuberculous meningitis is suspected, multiple 5 mL samples of CSF will be required to increase the likelihood of a positive result. If there has been prior administration of antibiotics, a bacterial antigen screen should also be requested.

Turbid CSF is indicative of a significant number of pus cells and is an indication for immediate administration of antibiotics. The patient should usually rest supine for a few hours after the procedure to prevent a worsening of the headache. This has been known to occur up to 24 hours following the procedure. The evidence for the benefits of enforced rest after lumbar puncture is equivocal.

The pattern of cell counts and glucose and protein levels is shown in Table 9.2.2. This can act as a guide only and the clinician needs to be guided by the complete clinical picture.

A leucocyte count (WCC) of more than 1000/μL with a predominantly neutrophilic pleocytosis is considered positive for bacterial meningitis. Ten per cent of cases, especially early in the course of the illness, may have a predominance of lymphocytes. As a general rule, bacterial meningitis is characterized by a raised CSF protein and a low CSF glucose level. The ratio of CSF to serum glucose levels is also lowered. The combination of CSF glucose<1.9 mmol/L, CSF to serum glucose ratio<0.23, CSF protein>2.2 g/L and either a total WCC>2000/μL or a neutrophil count of>1180/μL has been shown to have a 99% certainty of diagnosing bacterial meningitis [11]. Aseptic meningitis will often have cell counts near the normal range. This does not exclude infection with less common agents, such as herpes viruses or L. monocytogenes.

CT scan

CT scanning of the brain is indicated as a prelude to lumbar puncture in the presence of focal neurological signs, mental obtundation or abnormal posturing. It must be noted though, that a normal CT does not exclude the risk of cerebral herniation in bacterial meningitis [12] and, therefore, those with the above signs should have lumbar puncture delayed until they are conscious and stable.

Microbiology

Apart from microscopy and culture of CSF, there are a number of other methods that may allow the causative organism to be identified.

Skin lesion aspirate

In cases where a petechial rash is present, Gram staining or culture from some of the skin lesions may yield the causative organism. This has a reported sensitivity of 30–70%.

Throat swab

Throat swabs are useful in identifying a bacterial cause spread by nasopharyngeal carriage and should be performed in a case of suspected bacterial meningitis.

Polymerase chain reaction

This potentially allows identification of the causative organism and even the serotype for organisms, such as meningococcus. The test can be performed on CSF or EDTA blood samples and may remain positive for up to 72 hours after the commencement of antibiotics. In CSF, the reported sensitivity is 89% with a specificity of 100% and in blood a sensitivity of 81% with a specificity of 97% [13].

Serology

Tests to detect IgM to specific organisms are available for meningococcus and some viruses. For meningococcus, the test has a sensitivity and specificity of 97% and 95%, but is only reliable in adults and children over 4 years old and takes 5–7 days after onset of the illness to reach diagnostic levels.

Antigenic studies

Latex agglutination, immunoelectrophoresis or radioimmunoassay techniques can be used to screen for antigens from S. pneumoniae, Hib, group B streptococcus (S. agalactiae), Escherichia coli K1, N. meningitidis and C. neoformans. The tests can be performed on serum, CSF or urine. Serum or urine samples tend to allow greater sensitivities (around 96–99%) than CSF (82–99%). The test is no more sensitive in untreated cases than either a positive Gram-stain or the presence of CSF pleocytosis [14]. The main purpose of antigenic studies is in allowing rapid identification of the causative organism in cases confirmed by the CSF findings or in cases where partial treatment with antibiotics renders the CSF sterile on culture. In many laboratories, these tests have been superseded by PCR methods.

General investigations

Full blood count (FBC), urea and electrolyte counts (UEC), blood cultures, erythrocyte sedimentation rate (ESR) and a throat swab can assist in building an overall picture.

Blood cultures should be taken prior to parenteral antibiotics, especially in patients where lumbar puncture has been delayed. One study found that blood cultures grew the causative organism in 86% of proven cases of bacterial meningitis and that the combination of blood culture, CSF Gram staining and antigen testing identified the cause in 92% of cases [15].

Differential diagnosis

Management

Management depends on the likely causative agents, as well as the severity of the illness.

General

Patients should rest in bed, particularly following a lumbar puncture. A quiet, darkened room will be beneficial to those with headache or photophobia. Simple analgesics may be used to treat the headache, with or without codeine. Opiates may be required in severe headache.

Sedation may be necessary if the patient is very agitated or delirious. Suitable drugs are diazepam 5–10 mg IV or midazolam 2–10 mg IV or IM, with or without the addition of an antipsychotic, such as haloperidol 5–20 mg IV or IM, or chlorpromazine 12.5–50 mg IV or IM.

Seizures should be treated appropriately, initially with a benzodiazepine, then maintenance with phenytoin or phenobarbitone. Meningitis can occasionally be associated with status epilepticus, which should be treated in the standard way.

Patients with raised intracranial pressure may need pressure monitoring and measures to reduce the pressure, such as nursing the patient 30° head up and the administration of hyperosmotic agents, such as mannitol. Hyperventilation is controversial as it may reduce intracerebral pressure at the expense of reduced cerebral perfusion. Obstructive hydrocephalus requires appropriate neurosurgical treatment with CSF shunting.

If septic shock has intervened, it should be treated in the usual way, with IV fluids and inotropes.

Antimicrobials

The choice of antimicrobial agent will be determined by the likely causative organism and is therefore determined primarily by age and immune status. It is important that antibiotic therapy is not delayed by investigations such as lumbar puncture or CT and should be administered as soon as the diagnosis is made. Table 9.2.3 shows the recommended choice of antimicrobial for different situations and organisms. Table 9.2.4 shows the recommended dosage of each. As a general rule, the combination of a third-generation cephalosporin and benzylpenicillin will cover most organisms in all age groups. It is important to note that there is emerging resistance to penicillins in S. pneumoniae (currently 7.6% of isolates in Australia). If Gram-positive diplococci are found or S. pneumoniae is identified on antigen or PCR testing, vancomycin should be added to the therapy.

Steroids

Steroids have been shown to improve the prognosis of bacterial meningitis in both adults and children. There is a reduction in complications, such as sensorineural deafness and short-term neurological deficits (in high-income countries). The most benefit appears to be derived with infections from H. influenzae and S. pneumoniae. No clear mortality benefit has been established. Steroids are usually administered as dexamethasone 0.15 mg/kg IV q 6 h (up to 10 mg), started before or with the first dose of antibiotics and continued for 4 days. The main adverse effect is gastrointestinal bleeding, which may be reduced by limiting treatment to 2 days [17].

Disposition

All cases of bacterial meningitis require admission for IV antibiotics, as well as supportive therapy. They often require intensive therapy, especially if septic shock has supervened. Viral meningitis will usually require supportive therapy only, but this may require admission. Mild cases of viral or aseptic meningitis, with a clear diagnosis, can be safely sent home.

Prognosis

Over the last 20 years, the mortality of bacterial meningitis has ranged from 6 to 20% and is higher in the very young or the very old. Meningitis in immunocompromised individuals carries a high mortality of up to 50%. Bacterial meningitis in children can lead to a number of long-term sequelae, such as sensorineural hearing loss, learning difficulties, motor problems, speech delay, hyperactivity, blindness, obstructive hydrocephalus and recurrent seizures. These sequelae are less common in adults.

Prevention

Prophylaxis should be offered in cases of H. influenzae type b, or Meningococcus infection to:

9.3 Septic arthritis