Brain abscess

Management
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By John E Greenlee MD

Therapy of brain abscess involves prompt administration of appropriate antibiotics, surgical drainage or removal where indicated, and control of cerebral edema. No controlled trials comparing antibiotic regimens in brain abscess exist (Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy 2000). However, antibiotics used for brain abscess fall into 4 major groups (Table 1).

Table 1. Antibiotics for Empiric Therapy of Brain Abscess

Suspected Organism

Recommended Antibiotic

 

Streptococci and other Gram-positive organisms excluding S aureus

 

Penicillin, vancomycin, ceftriaxone, or cefotaxime

Staphylococcus aureus

• Vancomycin, until sensitivity to Oxacillin or Nafcillin is confirmed

 

• Oxacillin or Nafcillin (Oxacillin is less apt to produce thrombophlebitis at the infusion site)

 

• Use vancomycin if patient is allergic to penicillin

 

Gram-negative organisms excluding Pseudomonas aeruginosa

 

Ceftriaxone or cefotaxime

Pseudomonas aeruginosa

 

Ceftazidime

Bacteroides species

Metronidazole

Many abscesses contain a mixed culture of organisms, requiring 2 or more agents (Mishra et al 2014). Although many workers will initially use a third generation cephalosporin alone (Brouwer et al 2014a; Brouwer et al 2014b), initial therapy, where the source of infection is unknown, should consider the combined use of vancomycin or oxacillin, plus ceftriaxone, plus either metronidazole or, less optimally, chloramphenicol (Levy et al 1986; Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy 2000; Tunkel et al 2000; Kowlessar et al 2006). Vancomycin should be used until nafcillin or oxacillin resistance sensitivity is confirmed, in particular in abscesses arising after neurosurgical procedures or head trauma. Vancomycin should also be used in patients known to be allergic to penicillin. Successful antibiotic therapy of brain abscess with ceftriaxone and metronidazole alone has been reported (Jansson et al 2004), and a report suggests that treatment with carbapenems may result in lower mortality than treatment with ceftriaxone and metronidazole (Martin-Canal et al 2010). In this study, meropenem was significantly less likely to be associated with seizures than was imipenem. Cefuroxime has been used to treat surgically drained abscesses caused by S aureus (Norgaard et al 2003), and linezolid has been used to treat abscesses caused by methicillin-resistant Staphylococcus aureus (MRSA) and by Peptostreptococcus (Salin et al 2006; Naesens et al 2009). However, the efficacy of these regimens have not been established where there is possibility of cure by antibiotic therapy alone, and Norgaard and colleagues (Norgaard et al 2003) did not encounter methicillin-resistant strains of S aureus. Ceftazidime should be used in place of ceftriaxone if Pseudomonas aeruginosa is strongly suspected (Kastenbauer et al 2004). Intracranial mass lesions in patients with AIDS should be treated initially as being due to Toxoplasma gondii, with sulfadiazine and pyrimethamine (Price 1997). The antibiotic regimen used in a given patient may need to be revised as data become available from cultured abscess material. Length of therapy is determined by patient course and follow-up MRI or CT. In general, antibiotics should be continued for at least 8 weeks if surgery is not undertaken, or at least 4 weeks if the abscess is drained or excised. Completion of antibiotic therapy on an outpatient basis has been used with success in carefully selected patients (Tice et al 1999).

Surgical therapy of brain abscess may involve aspiration or excision (Osenbach and Loftus 1992; Hakan et al 2006; Helweg-Larsen et al 2012). Aspiration, particularly under stereotactic CT or MRI guidance, is becoming increasingly favored because it is less traumatic to the central nervous system than is excision and carries a lower risk of subsequent seizures (Mamelak et al 1995; Chacko and Chandy 1997; Barlas et al 1999; Nakajima et al 1999; Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy 2000; Kollias and Bernays 2001; Unal et al 2005). Aspiration also provides a less traumatic approach to abscesses involving an eloquent area of the brain or the brainstem (Fuentes et al 2001). Aspiration removes the purulent center of the abscess, rendering the abscess more amenable to antibiotic therapy, and often effectively reduces intracranial pressure. Recurrence of the abscess may require repeat aspiration. However, no controlled trial of aspiration versus excision has been reported, and excision should be considered in large or multiloculated abscesses, abscesses that do not respond to aspiration and may be necessary in cases in which ventricular rupture is considered imminent (Fritz and Nelson 1997). Excision is also indicated in cases in which there is a foreign body, in which there is gas within the abscess, or in abscesses due to Nocardia (Fritz and Nelson 1997). Cerebellar abscesses may cause obstructive hydrocephalus and may hence require placement of a ventricular shunt to avoid further increase in intracranial pressure (Nadvi et al 1997). Although brain abscess with intraventricular rupture has an 80% fatality rate, survival has been reported following open craniotomy with debridement of abscess cavity and ventricular lavage, followed by 6 weeks of intravenous antibiotics, intraventricular gentamicin twice daily for 6 weeks, and intraventricular drainage for 6 weeks (Zeidman et al 1995). Although many neurosurgeons have instilled antibiotics directly into the abscess cavity, the efficacy of this procedure is not known.

The availability of CT and MRI imaging has made it possible, in selected cases, to treat brain abscesses with antibiotics alone (Obana and Rosenblum 1992; Osenbach and Loftus 1992; Mamelak et al 1995; Fulgham et al 1996; Hsiao et al 2011). Abscesses at the stage of cerebritis do not contain material that can be drained. In many cases, surgery may be deferred if the abscess is less than 2.5 cm in diameter and if the patient is neurologically stable. This recommendation is not based on controlled trials, however, and abscesses treated with antibiotics alone must be followed with great care, and a follow-up MRI or CT should be obtained within 24 to 48 hours after initiation of therapy. It is extremely important to remember that abscesses may enlarge despite antibiotic therapy (Mamelak et al 1995). For this reason, frequent follow-up MRI or CT is essential if a decision is made to treat with antibiotics alone. Intervals between subsequent CT and MRI studies are determined in part by the patient's neurologic status but should not be greater than 3 to 5 days in the first 2 weeks. MRI and CT may remain abnormal for many weeks despite apparent clinical recovery (Kastenbauer et al 2004; Kowlessar et al 2006).

Several additional therapeutic issues must be faced in the patient with brain abscess (Tunkel et al 2000; Kastenbauer et al 2004). Cerebral edema may require emergent treatment with hyperventilation, mannitol, or dexamethasone. Hyperventilation is used short-term to a pCO2 of less than 28 torr. Mannitol may be given as a 20% solution with an initial dose of 0.5 to 1.0 g/kg over 10 minutes followed by 0.25 to 0.5 g/kg every 3 to 5 hours. The patient should be catheterized before mannitol is begun, and careful attention should be given to serum electrolytes and osmolality. Dexamethasone is effective in reducing vasogenic edema, and a short course of 10 mg intravenously initially followed by 4 mg intravenously every 4 to 6 hours should be considered where control of intracranial pressure is of major concern over time. Use of a transcranial or intraventricular pressure monitor may be invaluable in guiding therapy. Inappropriate secretion of antidiuretic hormone or development of diabetes insipidus may require strict attention to fluid and electrolyte balance. Administration of 5% dextrose in water, without other electrolytes, may lead to profound hyponatremia. Subcutaneous heparin should be considered in patients remaining at bed rest for extended periods of time. Adjacent or remote sources of infection, including sinuses, middle ear, mastoid, and teeth may also require antibiotic or surgical therapy. Seizures may be treated with intravenous diazepam, 10 mg, or lorazepam, 4 mg, given over 2 minutes and repeated after 15 minutes if seizures persist. Therapy with these short-acting agents should be followed by a loading dose of intravenous fosphenytoin given as the equivalent of 10 to 15 mg/kg phenytoin in normal saline at a rate no faster than 50 mg/min (1 mg/kg per minute in neonates). If phenytoin is used rather than fosphenytoin, the electrocardiogram and blood pressure should be monitored during administration. Alternate agents to control seizures include intravenous levetiracetam or valproic acid. It should be noted, however, that there are no comparative data as to the efficacy of these 3 agents in achieving seizure control. Maintenance therapy with phenytoin or other longer-term anticonvulsants should be continued once seizures are controlled. Midazolam, propofol, phenobarbital, or other agents may be required to control seizures unresponsive to phenytoin. Onset of seizures that may occur weeks to months after recovery may require late initiation of therapy with phenytoin or other agents. Careful withdrawal of anticonvulsants should be considered after 2 years in those patients who have seizures early in their course but remain seizure-free and without focal neurologic deficits or electroencephalographic abnormalities.

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
Pregnancy
Anesthesia
References cited
Contributors