Subdural empyema medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Subdural empyema (also referred to as subdural abscess, pachymeningitis interna, or circumscript meningitis) is a medical emergency. Treatment of subdural empyema requires a multidisciplinary approach involving decompression of the brain matter, drainage of the purulent material, administration of antimicrobial agents active against the causative pathogens. The choice of antibiotics should be based on the predisposing factors for developing empyema and the Gram-stain results of the aspirated pus. Vancomycin should be added to the empiric regimen if Staphylococcus aureus is suspected. Linezolid has been used with success in streptococcal subdural empyema and may be considered in empyema caused by Gram-positive cocci unresponsive to conventional treatment. Metronidazole is recommended for anaerobic infections. For aerobic Gram-negative bacilli, broad spectrum antibiotics (such as cefepime, ceftazidime, or meropenem) should be administered. The optimal duration of therapy remains unclear. Depending on the clinical response, parenteral antibiotics should be continued for 3 to 4 weeks after drainage. Prolonged course of treatment may be required if subdural empyema is accompanied by osteomyelitis.

Medical Therapy

In the treatment of subdural empyema, an early accurate diagnosis, timely surgical intervention and appropriate antibiotic therapy, are essential to a favorable outcome, with no, or the least sequelae possible. As a general rule, the treatment of intracranial or spinal subdural empyema requires both prompt surgical drainage and appropriate antibiotic therapy, an exception being, when there are contraindications for surgery or significant mortality risks. The evacuation of the empyema can be done either by craniotomy or burr hole drainage. Although the pus collection might be localised by imaging studies, and a evacuated by placement of a burr hole, the procedure of choice for evacuation of subdural purulent material is a wide range craniotomy with irrigation of the area. This improves the outcome by allowing wide exposure and adequate exploration, since the goal of the procedure is not only the evacuation of the pus, but also the eradication of the source of the infection. After surgical drainage, the antibiotic therapy should be given parenterically for a period of 3-4 weeks however, complications such as cranial osteomyelitis, may require longer therapy. Because the etiologic agents responsible for the subdural empyema are generally different, in the intracranial and spinal types, the treatments will be different as well:

Intracranial subdural empyema

This subtype may have multiple pathogens involved, therefore initial antibiotic therapy should cover Staphylococcus aureus, microaerophilic and anaerobic streptococci and gram negative organisms.

• Antibiotics for community-acquired subdural empyema should include a combination of:

1. Nafcillin, Oxacillin, or Vancomycin
2. Third generation Cephalosporin
3. Metronidazole

• Patients with hospital-acquired subdural empyema may be infected with different pathogens, such as Pseudomonas spp. or MRSA. Therefore, should receive coverage with the following:

1. Carbapenem
2. Vancomycin
3. (Metronidazole is not necessary for the therapy of anaerobic agents in the presence of Meropenem)

Spinal subdural empyema

Initial antibiotic therapy should be directed to Staphylococcus aureus and Streptococci and should include Nafcillin, Oxacillin or Vancomycin

The definitive pathogen diagnosis is made by Gram's stain and culture of the fluid obtained from the surgical drainage. After this diagnosis has been made, a more pathogen-oriented antibiotic therapy can be given.

Antimicrobial Regimen – Empiric Therapy

• Ampicillin 200 mg/kg/day IV q4h AND
• Cefotaxime 200 mg/kg/day IV q6h

• Ampicillin 200 mg/kg/day IV q4h AND
• Cefotaxime 200 mg/kg/day IV q6h OR Ceftriaxone 100 mg/kg/day IV q12h

• Vancomycin 60 mg/kg/day IV q6h (pediatric) or 2 g/day IV q12h (adult) AND
• Cefotaxime 200 mg/kg/day IV q6h (pediatric) or 12 g/day IV q4h (adult) OR Ceftriaxone 100 mg/kg/day IV q12h (pediatric) or 4 g/day IV q12h (adult) OR Cefepime 150 mg/kg/day IV q8h (pediatric) or 6 g/day IV q8h (adult)

• Ampicillin 200 mg/kg/day IV q4h AND
• Vancomycin 2 g/day IV q12h AND
• Cefotaxime 12 g/day IV q4h OR Ceftriaxone 4 g/day IV q12h OR Cefepime 6 g/day IV q8h

• Ampicillin 200 mg/kg/day IV q4h (pediatric) or 12 g/day IV q4h (adult) AND
• Vancomycin 60 mg/kg/day IV q6h (pediatric) or 2 g/day IV q12h (adult) AND
• Ceftazidime 150 mg/kg/day IV q8h (pediatric) or 6 g/day IV q8h (adult) OR Meropenem 20 mg/kg/day IV q8h (pediatric) or 3 g/day IV q8h (adult)

Subdural Empyema Drug Summary

Nafcillin and Oxacillin

• Group of narrow spectrum antibiotics, of the penicillin class, both penicillinase-resistant. Their mechanism of action is based on binding transpeptidases, thereby blocking the cross-linkage of peptidoglycan. They are also involved in the activation of autolytic enzymes.

• They are used to treat gram-positive bacteria, particularly staphylococci, however are not indicated in the treatment of MRSA/ORSA.
• They are known to cause hypersensitivity reactions and to interfere with cytochrome P-450. Their use in congestive heart failure and kidney disease patients should also be cautious because of risk of edema.
• The dosage may need to be adjusted in patients suffering from kidney or liver disease.

Vancomycin

• A glycopeptide antibiotic that exerts its activity by inhibiting peptidoglycan synthesis and hence bacterial cell walls. It has bactericidal activity agains most pathogens and bacteriostatic activity agains enterococci.
• A narrow spectrum antibiotic used only for gram-positive bacteria.
• Due to its toxicity (Ototoxicity, Nephrotoxicity and Thrombophlebitis), along with risk of anaphylaxis, Stevens-Johnson syndrome, neutropenia and thrombocytopenia, its use is restricted to multidrug-resistant organisms (MRSA/ORSA, Clostridium difficile).
• In recent years, the emergence of vancomycin-resistant pathogens, has increased the use of antibiotics, such as carbapenem and linezolid.

Cephalosporin

• A bactericidal antibiotic, with a similar mechanism of action as other penicillins, cephalosporins interfere with the synthesis of peptidoglycan of the cell wall, being however less susceptible to penicillinases.
• Used for prophylaxis and treatment of certain bacteria.
• There are 4 generations of cephalosporins: 1st generation are indicated for gram-positive bacteria, while 2nd, 3rd and 4th generations have increased activity against gram negative organisms.
• 1st generation cephalosporins include: cefalexin and cefazolin; 2nd generation: cefuroxime and cefoxitin; 3rd generation: ceftriaxone and cefotaxime; and 4th generation: cefepime and cefquinome.
• Organisms not usually covered by cephalosporins include: Listeria, MRSA and Enterococci.
• Possible adverse effects include: nausea, diarrhea, rash, hypersensitivity reactions, vitamin K deficiency and increased nephrotoxicity of aminoglycosides, when given concomitantly.

Metronidazole

• A nitroimidazole antibiotic, bactericidal against anaerobic organisms, with antiprotozoal activity. It acts by forming free radical metabolites within the bacterial cell, which damages the bacterial DNA. When given with clarithromycin and a proton pump inhibitor, is used in the treatment of ''Helicobacter pylori''.
• Used in the treatment of organisms such as: Clostridium difficile, Entamoeba, Trichomonas, Giardia and Gardnerella vaginalis.
• Possible adverse effects include: nausea, diarrhea, headaches, encephalopathy, cerebellar ataxia, neutropenia and association with thrombophlebitis, when administered intravenously.
• Its use may cause darker red urine.

Carbapenem

• Broad spectrum beta-lactam antibiotic, with a structure which protects it from the action of beta-lactamases. Active against gram-positive cocci, gram-negative rods and anaerobic bacteria, with the exception of intracellular organisms. Administered intravenously.
• Examples of carbapenems include imipenem, meropenem and ertapenem.
• The significant side-effects including gastrointestinal problems, rash and CNS toxicity limit its use.

Other Therapies

• Some patients might present with seizures, either during the acute phase of the subdural empyema, or up to 2 years thereafter. In these patients, therapy with phenytoin might be needed.
• Depending on the severity of the disease and the degree of neurological sequelae, physical and/or speech therapy might be needed.

Phenytoin

• Commonly know as Dilantin, it is used to treat partial seizures or generalised tonic-clonic seizures.
• Its effect is believed to be due to the voltage-dependent blockage of voltage-gated sodium channels. Phenytoin is then able to selectively inhibit pathological hyperexcitability in epilepsy, without affecting ongoing activity. It also has the ability of blocking persistent sodium current, which is of great use in seizure control.
• It has adverse effects,such as: nystagmus, cerebellum atrophy when administered at chronically high levels, megaloblastic anemia, teratogenicity, gingival hyperplasia, hypertrichosis, rash and is also known for causing drug-induced lupus and reversible IgA deficiency.