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 is a medical emergency. Treatment of subdural empyema requires a combined medical and surgical approach. Empiric antimicrobial therapy depends on the location of the infection (intracranial vs. spinal) and whether it was community-acquired or hospital-acquired.
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.[1] The evacuation of the empyema can be done either by craniotomy or burr hole drainage.[2] 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. [1] 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: [3]
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. [1]
- Antibiotics for community-acquired subdural empyema should include a combination of:
- Nafcillin, Oxacillin, or Vancomycin
- Third generation Cephalosporin
- 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:
- Carbapenem
- Vancomycin
- (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.
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.[3]
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[3], 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[3] 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.[3]
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.[4]
- 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.
Antimicrobial Regimen
- Empiric antimicrobial therapy
- Metronidazole is recommended if anaerobes are suspected. Metronidazole is not necessary for antianaerobic activity if Meropenem is used.
- For coverage of aerobic Gram-negative bacilli, empiric therapy with Cefepime, Ceftazidime, or Meropenem is appropriate.
- Depending on the clinical response, parenteral antimicrobial therapy should be administered for 3 to 4 weeks after drainage. Parenteral or oral therapy is frequently continued for up to a total of 6 weeks of therapy.
- A longer course of treatment (minimum of 6–8 weeks) may be required if the patient has accompanying osteomyelitis.
- Consider adjunctive medications including prophylactic anticonvulsants, corticosteroids, and mannitol if clinically indicated.
- Intracranial subdural empyema with unclear source of infection
- Preferred regimen: (Nafcillin 2 g IV q4h for 3-4 weeks OR Oxacillin 2 g IV q4h for 3-4 weeks) AND (Ceftriaxone 2 g IV q12h for 3-4 weeks OR Cefotaxime 8–12 g/day IV q4–6h for 3-4 weeks) AND Metronidazole 7.5 mg/kg IV q6h for 3-4 weeks
- Note: Vancomycin 30–45 mg/kg/day IV q8–12h should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.
- Intracranial subdural empyema associated with sinusitis or otitis media
- Preferred regimen: (Nafcillin 2 g IV q4h for 3-4 weeks OR Oxacillin 2 g IV q4h for 3-4 weeks) AND (Ceftriaxone 2 g IV q12h for 3-4 weeks OR Cefotaxime 8–12 g/day IV q4–6h for 3-4 weeks) AND Metronidazole 7.5 mg/kg IV q6h for 3-4 weeks
- Note: Vancomycin 30–45 mg/kg/day IV q8–12h should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.
- Intracranial subdural empyema after cranial trauma
- Preferred regimen: Nafcillin 2 g IV q4h for 3-4 weeks OR Oxacillin 2 g IV q4h for 3-4 weeks
- Note: Vancomycin should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.
- Intracranial subdural empyema after neurosurgical procedures
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 3-4 weeks AND Ceftazidime 2 g IV q8h for 3-4 weeks
- Intracranial subdural empyema in neonates (usually associated with meningitis)
- Infants < 1 month
- Preferred regimen: Ampicillin 200 mg/kg/day IV q4h for 3-4 weeks AND Cefotaxime 200 mg/kg/day IV q6h for 3-4 weeks
- Infants 1–3 months
- Preferred regimen: Ampicillin 200 mg/kg/day IV q4h for 3-4 weeks AND (Cefotaxime 200 mg/kg/day IV q6h for 3-4 weeks OR Ceftriaxone 100 mg/kg/day IV q12h for 3-4 weeks)
- Infants > 3 months
- Preferred regimen: Vancomycin 60 mg/kg/day IV q6h for 3-4 weeks AND (Cefotaxime 200 mg/kg/day IV q6h for 3-4 weeksOR Ceftriaxone 100 mg/kg/day IV q12h for 3-4 weeks OR Cefepime 150 mg/kg/day IV q8h for 3-4 weeks)
- Spinal subdural empyema
- Preferred regimen: Nafcillin 2 g IV q4h for 3-4 weeks OR Oxacillin 2 g IV q4h for 3-4 weeks
- Note: Vancomycin 30–45 mg/kg/day IV q8–12h should be used in place of nafcillin or oxacillin if MRSA is suspected or if penicillin allergy is present.
- Pathogen-directed antimicrobial therapy
- Staphylococcus aureus, methicillin-resistant (MRSA)[7]
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to vancomycin therapy.
References
- ↑ 1.0 1.1 1.2 Agrawal, Amit; Timothy, Jake; Pandit, Lekha; Shetty, Lathika; Shetty, J.P. (2007). "A Review of Subdural Empyema and Its Management". Infectious Diseases in Clinical Practice. 15 (3): 149–153. doi:10.1097/01.idc.0000269905.67284.c7. ISSN 1056-9103.
- ↑ Longo, Dan L. (Dan Louis) (2012). Harrison's principles of internal medici. New York: McGraw-Hill. ISBN 978-0-07-174889-6.
- ↑ 3.0 3.1 3.2 3.3 3.4 Greenlee JE (2003). "Subdural Empyema". Curr Treat Options Neurol. 5 (1): 13–22. PMID 12521560.
- ↑ Rogawski MA, Löscher W (2004). "The neurobiology of antiepileptic drugs". Nat Rev Neurosci. 5 (7): 553–64. doi:10.1038/nrn1430. PMID 15208697.
- ↑ Osborn, Melissa K.; Steinberg, James P. (2007-01). "Subdural empyema and other suppurative complications of paranasal sinusitis". The Lancet. Infectious Diseases. 7 (1): 62–67. doi:10.1016/S1473-3099(06)70688-0. ISSN 1473-3099. PMID 17182345. Check date values in:
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(help) - ↑ Greenlee, John E. (2003-01). "Subdural Empyema". Current Treatment Options in Neurology. 5 (1): 13–22. ISSN 1092-8480. PMID 12521560. Check date values in:
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(help) - ↑ Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; J Rybak, Michael; Talan, David A.; Chambers, Henry F.; Infectious Diseases Society of America (2011-02-01). "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (3): –18-55. doi:10.1093/cid/ciq146. ISSN 1537-6591. PMID 21208910.