Epidural abscess 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

Epidural abscess is a rare suppurative infection resulting in pus loculation in the cranial cavity or the spinal canal. Treatment of epidural abscess generally involves a combined medical and surgical approach. For cranial epidural abscess, the choice of antibiotics should be based on the host factors and the Gram-stain results of the drained abscess. Vancomycin should be added to the empiric regimen if Staphylococcus aureus is suspected. Linezolid may be considered in epidural abscess caused by Gram-positive cocci unresponsive to conventional treatment. Metronidazole is recommended for anaerobic infections. Broad spectrum antibiotics (such as cefepime, ceftazidime, or meropenem) should be administered to treat aerobic Gram-negative bacilli. Empirical antimicrobial therapy for spinal epidural abscess should cover Staphylococcus (vancomycin pending susceptibility testing) and aerobic Gram-negative bacilli (cefepime, ceftazidime, or meropenem). Regimen should be adjusted as culture results and susceptibility testing permit. Antimicrobial therapy is usually continued for 4 to 6 weeks after surgical drainage or for 6 to 8 weeks if osteomyelitis is present. Patients with tuberculous epidural abscess must receive a 12-month course of antituberculous therapy.

Medical Therapy

Several studies have reached the conclusion that the best approach to therapy of epidural abscess, either intracranial or spinal, is a combination of surgical drainage along with prolonged systemic antibiotics (6-12 weeks, IV followed by PO). Due to the importance of preoperative neurologic status, along with the unpredictable progression of neurologic impairment, for the neurological outcome of the patient, decompressive laminectomy and debridement of infected tissues, in the case of SEA, and burr hole placement or craniotomy, in the case of IEA, should take place as early as possible. However, in certain clinical scenarios, medical therapy may be the only treatment indicated for that particular case, these include:

• decompressive laminectomy declined by the patient
• high operative risk
• paralysis unlikely reversible, due to being present for more than 24 to 36 hours. Sometimes, in these situations emergency laminectomy is still performed, not to restore the lost function, but to treat the abscess and prevent a sepsis episode
• panspinal infection, therefore the laminectomy would be impracticable. In this case, the physician might consider a limited laminectomy or laminotomy with catheter insertion at the top and bottom of the spinal canal, for drainage and irrigation.

There are several reported cases in which patients recovered from epidural abscess, without surgical treatment, following simple diagnostic aspiration with antibiotic therapy. In these patients however, there was no neurologic deficit related to the abscess or it was simply accompanied by minor weakness at initial presentation. Besides the antibiotic therapy, this conservative approach also includes:

• close neurologic monitoring strategy, defined before treatment initiation
• follow-up MRI to evaluate the status of the abscess and confirm its resolution
• immediate surgery, in case of neurologic deterioration.

The indication for a specific antibiotic should be given by the results of blood cultures or a CT-guided aspiration of the abscess. However, until blood culture results are obtained, the patient should be on empirical antibiotic therapy. The efficacy of the antibiotic treatment, as well as its duration, may be determined by monitoring the evolution of the ESR, CRP, pain and function, along with resolution of radiographic changes.

Intracranial Epidural Abscess

The empiric antibiotic therapy for this type of abscess is similar to the one used for subdural empyema and should be continued for 3 to 6 weeks after surgery, or longer in case of osteomyelitis. This should cover:

• Staphylococci
• Streptococci
• Gram negative bacilli

This regimen must include:

• Penicillin with anti-staphylococcal activity or Vancomycin in case of suspicion of MRSA
• Third-generation cephalosporin
• This regimen might also include Metronidazole

Spinal Epidural Abscess

Initial antibiotic therapy for this type of abscess should target staphylococci and aerobic gram negative bacilli, particularly in patients with history of IV drug use or spinal procedures. The treatment should last for a period of 4 to 6 weeks, or longer, up to 8 weeks, in case there is contiguous osteomyelitis. Therefore, the antibiotic regimens for the unknown organism of intracranial epidural abscess may also be applied to the spinal epidural abscess.

Epidural Abscess 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.

Antimicrobial Regimen

Epidural abscess

• Spinal epidural abscess

• Empiric antimicrobial therapy

• Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 weeks AND Ceftriaxone 2 g Iv q24h for 2–4 weeks, then PO to complete 6–8 weeks

Note (1): Decompressive laminectomy in conjunction with long-term antibiotic therapy tailored to culture results is required.

Note (2): For critically ill patients, a vancomycin loading dose of 20–25 mg/kg may be considered.

• Pathogen-directed antimicrobial therapy

• Penicillin-susceptible Staphylococcus aureus or Streptococcus

• Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks

• Methicillin-susceptible Staphylococcus aureus or Streptococcus

• Preferred regimen: Cefazolin 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Nafcillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Oxacillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
• Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks

• Methicillin-resistant Staphylococcus aureus (MRSA)

• Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 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.

• Streptococcus

• Preferred regimen: Penicillin G 3–4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Ampicillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks

• Enterococcus

• Preferred regimen: Penicillin G 3–4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Ampicillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks

• Enterobacteriaceae

• Preferred regimen: Ceftriaxone 1–2 g IV q12h for 2–4 weeks, then PO to complete 6–8 weeks OR Cefotaxime 2 g IV q6–8h for 2–4 weeks, then PO to complete 6–8 weeks

• Gram-negative bacteria

• Preferred regimen:Ceftazidime 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Cefepime 2 g IV q12h for 2–4 weeks, then PO to complete 6–8 weeks
• Alternative regimen: Ciprofloxacin 400 mg IV q12h for 2–4 weeks, then PO to complete 6–8 weeks {{or]] Levofloxacin 750 mg IV q24h for 2–4 weeks, then PO to complete 6–8 weeks OR Moxifloxacin 400 mg IV q24h for 2–4 weeks, then PO to complete 6–8 weeks

• Anaerobes

• Preferred regimen: Metronidazole 500 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks

• Staphylococcus, Gram-negative bacteria, and anaerobes (mixed infection)

• Preferred regimen: Ampicillin-Sulbactam 3 g IV q6h for 2–4 weeks, then PO to complete 6–8 weeks OR Ticarcillin-Clavulanate 3.1 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Piperacillin-Tazobactam 3.375 g IV q4–6h for 2–4 weeks, then PO to complete 6–8 weeks
• Alternative regimen: Imipenem 500–1000 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks OR Meropenem 1–2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks