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Linezolid for treatment of subdural empyema due to Streptococcus: case reports
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Surgical Neurology 71 (2009) 89 – 91 www.surgicalneurology-online.com
Infection
Linezolid for treatment of subdural empyema due to Streptococcus: case reports Laurent Lefebvre, MD a , Philippe Metellus, MD b , Henry Dufour, MD b , Nicolas Bruder, MD a,⁎ a b Departments of Anesthesiology and Intensive Care, and Neurosurgery, CHU Timone, Université de la Méditerranée, Marseille, France Received 22 May 2007; accepted 17 June 2007
Abstract
Background: Recurring subdural empyema despite adequate surgical drainage and antibiotic treatment is still a life-threatening disease. This is mainly due to poor diffusion of the antibiotic into the subdural space. Case Description: We report 2 cases of recurring subdural empyema due to Streptococcus, after repeat surgery and high-dose antibiotic treatment including β-lactamines and vancomycin. Both patients showed marked clinical and radiologic improvement after introduction of linezolid. There was no drug-related adverse effect despite 36 and 90 days of treatment. Conclusion: Off-label use of linezolid for treatment of subdural empyema due to gram-positive bacteria should be considered after failure of conventional antibiotic treatment. © 2009 Elsevier Inc. All rights reserved.
Keywords:
Subdural empyema; Linezolid; Streptococcus; Sepsis; Neurosurgical
1. Introduction
2. Case 1
Subdural empyema accounts for 15% to 25% of pyogenic intracranial infections. Therapy associates surgical drainage and systemic antibiotics [4]. In the modern era of computed tomographic (CT) scan and surgery, mortality is still high, in 7.7% to 21% of cases [2,8]. The organisms most commonly cultured from subdural infections are aerobic and anaerobic streptococci [4]. These organisms are usually susceptible to most antibiotics, but the diffusion of antimicrobial agents in the subdural space is usually poor. Thus, the treatment requires the use of highdose antibiotics to overcome this poor penetration at the site of infection. β-Lactamase–stable penicillin, thirdgeneration cephalosporin, and metronidazole are most often used antibiotics. We report 2 cases of conventional antibiotic failure despite adequate in vitro susceptibility of the causative organisms and repeat surgery. In these cases, rescue therapy with linezolid was successful.
The first case was that of a 15-year-old adolescent boy without any significant medical history except a facial trauma 2 years before. He was admitted in the hospital for headaches, fever (38.6°C), left-sided hemiparesis, and drowsiness. Clinical examination result revealed neck stiffness. The postcontrast cerebral CT scan disclosed a subdural collection and also a collection in the left maxillary sinus with impaction of a tooth. The patient was operated on the next day for drainage of the subdural collection. The neurosurgeon drained pus from the subdural space via a large craniotomy. The patient was admitted to the intensive care unit. During the first week, the clinical course complicated with the development of seizures and cerebral vein thrombosis. Blood cultures and culture of the subdural collection revealed an infection by Streptococcus constellatus, which is susceptible to amoxicillin and cefotaxime. The treatment combined cefotaxime (16 g/d IV), metronidazole (1500 mg/d), phenytoin, and heparin. The patient was discharged to the neurosurgical ward 7 days after surgery. He had no fever and the hemiparesis had markedly improved. Ten days later, the patient became drowsy and hemiparesis resumed. A cerebral MRI scan showed the reappearance of the subdural collection and a new interhemispheric one. The antibiotic treatment was
Abbreviations: MRI, magnetic resonance imaging; CSF, cerebrospinal fluid. ⁎ Corresponding author. Département d'Anesthésie-réanimation, 13385 Marseille Cedex, France. Tel.: +33 491386547; fax: +33 491385735. E-mail address: [email protected] (N. Bruder). 0090-3019/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2007.06.083
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changed to a combination of ceftazidime, vancomycin, (3-5 g/d to achieve blood concentrations between 20 and 25 mg/L), and metronidazole. However, the patient became unresponsive 24 days after admission and was operated on again to drain the subdural collection. The patient's neurologic status improved transiently after the operation but then rapidly worsened. The patient was still febrile (38.1°C-38.5°C). The control cerebral MRI scan 12 days after the second operation showed recurrence of the subdural collection. The cultures of the operative samples were sterile. At this time, it was decided to replace the antibiotic treatment by linezolid (600 mg twice a day) only (37 days after admission). Eight days after the introduction of linezolid, the patient's clinical status improved dramatically. He was alert again, had no fever, and resumed oral feeding. Thirty-four days after the antibiotic change, the patient's state of consciousness was normal. He was able to walk without assistance despite a slight residual hemiparesis. The MRI scan showed disappearance of the subdural collections. The total duration of the linezolid treatment was 36 days. There was no adverse effect from the drug. Six months after discharge from the hospital, the patient had made a complete recovery and the cerebral MRI scan finding was normal. 3. Case 2 A 59-year-old female patient was admitted to the intensive care unit after a coma associated with fever. Her medical history included an epidermoid carcinoma of the base of the tongue treated 2 years before with radiotherapy, and she was considered stable. Clinical examination results revealed a sepsis syndrome associated with left mydriasis and left-sided hemiparesis. The cerebral CT scan showed a subdural empyema and a temporal brain abscess on the right side, associated with a mandibular bone necrosis and collection. The CSF was turbid. The CSF white blood cell count was 534/mm3. The Gram stain examination results and the culture of the CSF were negative. The patient was operated on the next day after admission in the hospital. Gram-positive strains were identified on the subdural samples. The subdural cultures isolated S constellatus, which is susceptible to amoxicillin. Initially, the antibiotic treatment consisted of cefotaxime (16 g/d), metronidazole (1.5 g/d), amikacin (1 g/d), and vancomycin (3 g/d). This antibiotic treatment was changed 4 days after admission for a combination of amoxicillin (16 g/d) and metronidazole (1.5 g/d). Eight days after surgery, the neurologic status was unchanged, but the patient had seizures treated with phenytoin. The patient was operated on again to drain a residual subdural empyema. On the following days, the patient remained febrile (38°C-38.4°C) and the level of consciousness decreased. The antibiotic treatment was stopped and replaced by linezolid (600 mg twice a day) 12 days after admission. Eight days after the introduction of linezolid, the septic syndrome had
resolved and hemiparesis began to improve. The subdural empyema disappeared 21 days after linezolid treatment, and there was only a residual temporal brain abscess. The patient was discharged from the intensive care unit 46 days after admission. The duration of linezolid treatment was 90 days. No adverse effect due to linezolid was noted. The patient needed prolonged hospitalization for swallowing disorders requiring a tracheostomy and physical therapy. She was discharged from the hospital 10 months after admission. The cerebral CT scan finding was normal. 4. Discussion Subdural empyema is still a severe pathology. Patients with a decreased level of consciousness have an increased mortality and more severe neurologic sequelae. Sinusitis, head trauma or surgery, and meningitis are the most common causes. Surgical drainage is imperative, but the optimal mode of surgery is still debated. In a retrospective review on 699 patients, Nathoo et al [8] found a better outcome for patients undergoing a large craniotomy compared to craniectomy or burr holes for drainage of the empyema. However, their study was based on historical control groups making this conclusion questionable. In our 2 patients, despite a large craniotomy, the therapy failed, needing reoperation and antibiotic change. Two hypotheses may explain the resistance to treatment: mutation of the bacteria or poor diffusion of the antibiotic through the blood-brain barrier into the subdural space. Mutation of the bacteria cannot be ruled out. However, in both cases, there was no microbiologic evidence of this hypothesis despite repeated blood cultures and subdural cultures after reoperation. A more likely hypothesis is insufficient penetration of antibiotics at the site of infection. This was the reason why we choose to replace the antibiotic treatment by linezolid, a drug that has been shown to have a good penetration into the CSF. Linezolid is the first of a new class of antibiotics, the oxazolidinones. It has shown bacteriostatic activity against almost all gram-positive bacteria, and also mycobacteria and Nocardia. The CSF penetration of linezolid is good, with a CSF-plasma ratio of 0.7:2.7 in vivo [5,10,13]. However, these results have been obtained in patients with meningitis, which increases the permeability of the bloodbrain barrier. Shaikh et al [10] reported stable concentrations of linezolid in the CSF until day 19 of therapy, suggesting that the penetration of the drug into the CSF was unaffected by the meningeal inflammation. Linezolid has also a good penetration in bone [6], an important feature for the treatment of subdural empyema that may be associated with skull osteitis. In the literature, few patients have been treated with linezolid for CNS infections [5,9,10,12]. Most cases were meningitis, ventriculitis, or ventriculoperitoneal shunt infections. We found only 12 cases of brain abscess. We found only 1 case of subdural empyema, due to Staphylococcus, treated with linezolid among the 10 cases reported by
L. Lefebvre et al. / Surgical Neurology 71 (2009) 89–91
Rupprecht and Pfister [9]. As in our patients, this case showed marked clinical and radiologic improvement with linezolid after failure of ceftriaxone, oxacillin, metronidazole, and tobramycin. In the literature, the reason for linezolid treatment was resistance to vancomycin in some cases [10] but more often initial antimicrobial treatment failure or severe adverse effects. In all case reports but one [9], linezolid was associated with good clinical outcome. Of course, a publication bias because of the lack of report of treatment failure is possible. An advantage of linezolid is its good oral bioavailability. This is particularly important for prolonged antibiotic treatment because switching from the intravenous to the oral route may reduce the number of complications due to venous catheterization and decrease costs of hospitalization [7]. Our first patient had only 4 days of intravenous treatment and the second one, 10 days. There are no data to support a specific duration of antibiotic therapy in subdural empyema. However, most patients are treated for 3 to 4 weeks after surgical drainage [4]. Some patients need a longer duration of treatment, as was the case in our patients. This may be a problem because the maximal duration of linezolid therapy is limited to 28 days. Prolonged treatment may cause myelosuppression and especially thrombocytopenia [3], peripheral and optic neuropathy [1], and hyperlactatemia due to mitochondrial toxicity [11], although long-term treatment has been reported without significant adverse effects [9]. In conclusion, linezolid should be considered for secondline antibiotic therapy for subdural empyema due to grampositive bacteria, as it has already been reported for the treatment of meningitis and brain abscesses. Treatment duration for more than 4 weeks needs close monitoring of the patient because of the risk of drug-related adverse effects. References [1] Bressler AM, Zimmer SM, Gilmore JL, Somani J. Peripheral neuropathy associated with prolonged use of linezolid. Lancet Infect Dis 2004;4:528-31. [2] Dill SR, Cobbs CG, McDonald CK. Subdural empyema: analysis of 32 cases and review. Clin Infect Dis 1995;20:372-86. [3] French G. Safety and tolerability of linezolid. J Antimicrob Chemother 2003;51(Suppl 2):ii45-ii53. [4] Hartman B, Helfgott D, Weingarten K. Subdural empyema and suppurative intracranial phlebitis. In: Scheld WM, Whitley R, Marra C, editors. Infections of the central nervous system. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 523-35. [5] Krueger WA, Kottler B, Will BE, et al. Treatment of meningitis due to methicillin-resistant Staphylococcus epidermidis with linezolid. J Clin Microbiol 2004;42:929-32. [6] Lovering AM, Zhang J, Bannister GC, et al. Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement. J Antimicrob Chemother 2002;50:73-7. [7] McCollum M, Rhew DC, Parodi S. Cost analysis of switching from i.v. vancomycin to p.o. linezolid for the management of methicillinresistant Staphylococcus species. Clin Ther 2003;25:3173-89.
91
[8] Nathoo N, Nadvi SS, van Dellen JR, Gouws E. Intracranial subdural empyemas in the era of computed tomography: a review of 699 cases. Neurosurgery 1999;44:529-35. [9] Rupprecht TA, Pfister HW. Clinical experience with linezolid for the treatment of central nervous system infections. Eur J Neurol 2005;12:536-42. [10] Shaikh ZH, Peloquin CA, Ericsson CD. Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: case report and literature review. Scand J Infect Dis 2001;33: 375-9. [11] Soriano A, Miro O, Mensa J. Mitochondrial toxicity associated with linezolid. N Engl J Med 2005;353:2305-6. [12] Viale P, Pagani L, Cristini F, et al. Linezolid for the treatment of central nervous system infections in neurosurgical patients. Scand J Infect Dis 2002;34:456-9. [13] Villani P, Regazzi MB, Marubbi F, et al. Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections. Antimicrob Agents Chemother 2002;46:936-7.
Commentary Subdural empyema defines a pyogenic disorder involving the subdural space, an area bounded externally by the dura mater and internally by the arachnoid, which is lined by a single layer of endothelial cells. Because of the absence of septations, inflammatory disease can spread rapidly and widely over the convexities of the brain. Fever, headache and focal neurologic signs, meningitis, and sepsis characterize its symptoms. Both aerobic and anaerobic streptococci are responsible for more than 70% to 80% of infections and result in the use of β-lactams and metronidazole in first-line therapy, which can result in failure of treatment. Recent studies with linezolid, a synthetic oxazolidinone, in patients with meningitis demonstrate excellent CNS antimicrobial trough levels of 1.7 to 1.9 μg/mL after 2 and 19 days of therapy. The drug has a very high volume of distribution, suggesting good penetration into extravascular sights. Linezolid is cleared primarily by the kidney with a half-life of about 5 hours, which allows for twice-daily dosing. Lefebvre et al presented 2 cases of S constellatus subdural empyema that responded completely to linezolid after having failed therapy with ceftriaxone, metronidazole, and vancomycin. Because of good oral bioavailability, prolonged therapy with oral linezolid is a feasible alternative to intravenous therapy. Future studies using linezolid for CNS infections are anticipated. Lawrence A. Cone, MD Department of Medicine Eisenhower Medical Center Rancho Mirage, CA 92270, USA
Surgical Neurology 71 (2009) 89 – 91 www.surgicalneurology-online.com
Infection
Linezolid for treatment of subdural empyema due to Streptococcus: case reports Laurent Lefebvre, MD a , Philippe Metellus, MD b , Henry Dufour, MD b , Nicolas Bruder, MD a,⁎ a b Departments of Anesthesiology and Intensive Care, and Neurosurgery, CHU Timone, Université de la Méditerranée, Marseille, France Received 22 May 2007; accepted 17 June 2007
Abstract
Background: Recurring subdural empyema despite adequate surgical drainage and antibiotic treatment is still a life-threatening disease. This is mainly due to poor diffusion of the antibiotic into the subdural space. Case Description: We report 2 cases of recurring subdural empyema due to Streptococcus, after repeat surgery and high-dose antibiotic treatment including β-lactamines and vancomycin. Both patients showed marked clinical and radiologic improvement after introduction of linezolid. There was no drug-related adverse effect despite 36 and 90 days of treatment. Conclusion: Off-label use of linezolid for treatment of subdural empyema due to gram-positive bacteria should be considered after failure of conventional antibiotic treatment. © 2009 Elsevier Inc. All rights reserved.
Keywords:
Subdural empyema; Linezolid; Streptococcus; Sepsis; Neurosurgical
1. Introduction
2. Case 1
Subdural empyema accounts for 15% to 25% of pyogenic intracranial infections. Therapy associates surgical drainage and systemic antibiotics [4]. In the modern era of computed tomographic (CT) scan and surgery, mortality is still high, in 7.7% to 21% of cases [2,8]. The organisms most commonly cultured from subdural infections are aerobic and anaerobic streptococci [4]. These organisms are usually susceptible to most antibiotics, but the diffusion of antimicrobial agents in the subdural space is usually poor. Thus, the treatment requires the use of highdose antibiotics to overcome this poor penetration at the site of infection. β-Lactamase–stable penicillin, thirdgeneration cephalosporin, and metronidazole are most often used antibiotics. We report 2 cases of conventional antibiotic failure despite adequate in vitro susceptibility of the causative organisms and repeat surgery. In these cases, rescue therapy with linezolid was successful.
The first case was that of a 15-year-old adolescent boy without any significant medical history except a facial trauma 2 years before. He was admitted in the hospital for headaches, fever (38.6°C), left-sided hemiparesis, and drowsiness. Clinical examination result revealed neck stiffness. The postcontrast cerebral CT scan disclosed a subdural collection and also a collection in the left maxillary sinus with impaction of a tooth. The patient was operated on the next day for drainage of the subdural collection. The neurosurgeon drained pus from the subdural space via a large craniotomy. The patient was admitted to the intensive care unit. During the first week, the clinical course complicated with the development of seizures and cerebral vein thrombosis. Blood cultures and culture of the subdural collection revealed an infection by Streptococcus constellatus, which is susceptible to amoxicillin and cefotaxime. The treatment combined cefotaxime (16 g/d IV), metronidazole (1500 mg/d), phenytoin, and heparin. The patient was discharged to the neurosurgical ward 7 days after surgery. He had no fever and the hemiparesis had markedly improved. Ten days later, the patient became drowsy and hemiparesis resumed. A cerebral MRI scan showed the reappearance of the subdural collection and a new interhemispheric one. The antibiotic treatment was
Abbreviations: MRI, magnetic resonance imaging; CSF, cerebrospinal fluid. ⁎ Corresponding author. Département d'Anesthésie-réanimation, 13385 Marseille Cedex, France. Tel.: +33 491386547; fax: +33 491385735. E-mail address: [email protected] (N. Bruder). 0090-3019/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2007.06.083
90
L. Lefebvre et al. / Surgical Neurology 71 (2009) 89–91
changed to a combination of ceftazidime, vancomycin, (3-5 g/d to achieve blood concentrations between 20 and 25 mg/L), and metronidazole. However, the patient became unresponsive 24 days after admission and was operated on again to drain the subdural collection. The patient's neurologic status improved transiently after the operation but then rapidly worsened. The patient was still febrile (38.1°C-38.5°C). The control cerebral MRI scan 12 days after the second operation showed recurrence of the subdural collection. The cultures of the operative samples were sterile. At this time, it was decided to replace the antibiotic treatment by linezolid (600 mg twice a day) only (37 days after admission). Eight days after the introduction of linezolid, the patient's clinical status improved dramatically. He was alert again, had no fever, and resumed oral feeding. Thirty-four days after the antibiotic change, the patient's state of consciousness was normal. He was able to walk without assistance despite a slight residual hemiparesis. The MRI scan showed disappearance of the subdural collections. The total duration of the linezolid treatment was 36 days. There was no adverse effect from the drug. Six months after discharge from the hospital, the patient had made a complete recovery and the cerebral MRI scan finding was normal. 3. Case 2 A 59-year-old female patient was admitted to the intensive care unit after a coma associated with fever. Her medical history included an epidermoid carcinoma of the base of the tongue treated 2 years before with radiotherapy, and she was considered stable. Clinical examination results revealed a sepsis syndrome associated with left mydriasis and left-sided hemiparesis. The cerebral CT scan showed a subdural empyema and a temporal brain abscess on the right side, associated with a mandibular bone necrosis and collection. The CSF was turbid. The CSF white blood cell count was 534/mm3. The Gram stain examination results and the culture of the CSF were negative. The patient was operated on the next day after admission in the hospital. Gram-positive strains were identified on the subdural samples. The subdural cultures isolated S constellatus, which is susceptible to amoxicillin. Initially, the antibiotic treatment consisted of cefotaxime (16 g/d), metronidazole (1.5 g/d), amikacin (1 g/d), and vancomycin (3 g/d). This antibiotic treatment was changed 4 days after admission for a combination of amoxicillin (16 g/d) and metronidazole (1.5 g/d). Eight days after surgery, the neurologic status was unchanged, but the patient had seizures treated with phenytoin. The patient was operated on again to drain a residual subdural empyema. On the following days, the patient remained febrile (38°C-38.4°C) and the level of consciousness decreased. The antibiotic treatment was stopped and replaced by linezolid (600 mg twice a day) 12 days after admission. Eight days after the introduction of linezolid, the septic syndrome had
resolved and hemiparesis began to improve. The subdural empyema disappeared 21 days after linezolid treatment, and there was only a residual temporal brain abscess. The patient was discharged from the intensive care unit 46 days after admission. The duration of linezolid treatment was 90 days. No adverse effect due to linezolid was noted. The patient needed prolonged hospitalization for swallowing disorders requiring a tracheostomy and physical therapy. She was discharged from the hospital 10 months after admission. The cerebral CT scan finding was normal. 4. Discussion Subdural empyema is still a severe pathology. Patients with a decreased level of consciousness have an increased mortality and more severe neurologic sequelae. Sinusitis, head trauma or surgery, and meningitis are the most common causes. Surgical drainage is imperative, but the optimal mode of surgery is still debated. In a retrospective review on 699 patients, Nathoo et al [8] found a better outcome for patients undergoing a large craniotomy compared to craniectomy or burr holes for drainage of the empyema. However, their study was based on historical control groups making this conclusion questionable. In our 2 patients, despite a large craniotomy, the therapy failed, needing reoperation and antibiotic change. Two hypotheses may explain the resistance to treatment: mutation of the bacteria or poor diffusion of the antibiotic through the blood-brain barrier into the subdural space. Mutation of the bacteria cannot be ruled out. However, in both cases, there was no microbiologic evidence of this hypothesis despite repeated blood cultures and subdural cultures after reoperation. A more likely hypothesis is insufficient penetration of antibiotics at the site of infection. This was the reason why we choose to replace the antibiotic treatment by linezolid, a drug that has been shown to have a good penetration into the CSF. Linezolid is the first of a new class of antibiotics, the oxazolidinones. It has shown bacteriostatic activity against almost all gram-positive bacteria, and also mycobacteria and Nocardia. The CSF penetration of linezolid is good, with a CSF-plasma ratio of 0.7:2.7 in vivo [5,10,13]. However, these results have been obtained in patients with meningitis, which increases the permeability of the bloodbrain barrier. Shaikh et al [10] reported stable concentrations of linezolid in the CSF until day 19 of therapy, suggesting that the penetration of the drug into the CSF was unaffected by the meningeal inflammation. Linezolid has also a good penetration in bone [6], an important feature for the treatment of subdural empyema that may be associated with skull osteitis. In the literature, few patients have been treated with linezolid for CNS infections [5,9,10,12]. Most cases were meningitis, ventriculitis, or ventriculoperitoneal shunt infections. We found only 12 cases of brain abscess. We found only 1 case of subdural empyema, due to Staphylococcus, treated with linezolid among the 10 cases reported by
L. Lefebvre et al. / Surgical Neurology 71 (2009) 89–91
Rupprecht and Pfister [9]. As in our patients, this case showed marked clinical and radiologic improvement with linezolid after failure of ceftriaxone, oxacillin, metronidazole, and tobramycin. In the literature, the reason for linezolid treatment was resistance to vancomycin in some cases [10] but more often initial antimicrobial treatment failure or severe adverse effects. In all case reports but one [9], linezolid was associated with good clinical outcome. Of course, a publication bias because of the lack of report of treatment failure is possible. An advantage of linezolid is its good oral bioavailability. This is particularly important for prolonged antibiotic treatment because switching from the intravenous to the oral route may reduce the number of complications due to venous catheterization and decrease costs of hospitalization [7]. Our first patient had only 4 days of intravenous treatment and the second one, 10 days. There are no data to support a specific duration of antibiotic therapy in subdural empyema. However, most patients are treated for 3 to 4 weeks after surgical drainage [4]. Some patients need a longer duration of treatment, as was the case in our patients. This may be a problem because the maximal duration of linezolid therapy is limited to 28 days. Prolonged treatment may cause myelosuppression and especially thrombocytopenia [3], peripheral and optic neuropathy [1], and hyperlactatemia due to mitochondrial toxicity [11], although long-term treatment has been reported without significant adverse effects [9]. In conclusion, linezolid should be considered for secondline antibiotic therapy for subdural empyema due to grampositive bacteria, as it has already been reported for the treatment of meningitis and brain abscesses. Treatment duration for more than 4 weeks needs close monitoring of the patient because of the risk of drug-related adverse effects. References [1] Bressler AM, Zimmer SM, Gilmore JL, Somani J. Peripheral neuropathy associated with prolonged use of linezolid. Lancet Infect Dis 2004;4:528-31. [2] Dill SR, Cobbs CG, McDonald CK. Subdural empyema: analysis of 32 cases and review. Clin Infect Dis 1995;20:372-86. [3] French G. Safety and tolerability of linezolid. J Antimicrob Chemother 2003;51(Suppl 2):ii45-ii53. [4] Hartman B, Helfgott D, Weingarten K. Subdural empyema and suppurative intracranial phlebitis. In: Scheld WM, Whitley R, Marra C, editors. Infections of the central nervous system. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 523-35. [5] Krueger WA, Kottler B, Will BE, et al. Treatment of meningitis due to methicillin-resistant Staphylococcus epidermidis with linezolid. J Clin Microbiol 2004;42:929-32. [6] Lovering AM, Zhang J, Bannister GC, et al. Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement. J Antimicrob Chemother 2002;50:73-7. [7] McCollum M, Rhew DC, Parodi S. Cost analysis of switching from i.v. vancomycin to p.o. linezolid for the management of methicillinresistant Staphylococcus species. Clin Ther 2003;25:3173-89.
91
[8] Nathoo N, Nadvi SS, van Dellen JR, Gouws E. Intracranial subdural empyemas in the era of computed tomography: a review of 699 cases. Neurosurgery 1999;44:529-35. [9] Rupprecht TA, Pfister HW. Clinical experience with linezolid for the treatment of central nervous system infections. Eur J Neurol 2005;12:536-42. [10] Shaikh ZH, Peloquin CA, Ericsson CD. Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: case report and literature review. Scand J Infect Dis 2001;33: 375-9. [11] Soriano A, Miro O, Mensa J. Mitochondrial toxicity associated with linezolid. N Engl J Med 2005;353:2305-6. [12] Viale P, Pagani L, Cristini F, et al. Linezolid for the treatment of central nervous system infections in neurosurgical patients. Scand J Infect Dis 2002;34:456-9. [13] Villani P, Regazzi MB, Marubbi F, et al. Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections. Antimicrob Agents Chemother 2002;46:936-7.
Commentary Subdural empyema defines a pyogenic disorder involving the subdural space, an area bounded externally by the dura mater and internally by the arachnoid, which is lined by a single layer of endothelial cells. Because of the absence of septations, inflammatory disease can spread rapidly and widely over the convexities of the brain. Fever, headache and focal neurologic signs, meningitis, and sepsis characterize its symptoms. Both aerobic and anaerobic streptococci are responsible for more than 70% to 80% of infections and result in the use of β-lactams and metronidazole in first-line therapy, which can result in failure of treatment. Recent studies with linezolid, a synthetic oxazolidinone, in patients with meningitis demonstrate excellent CNS antimicrobial trough levels of 1.7 to 1.9 μg/mL after 2 and 19 days of therapy. The drug has a very high volume of distribution, suggesting good penetration into extravascular sights. Linezolid is cleared primarily by the kidney with a half-life of about 5 hours, which allows for twice-daily dosing. Lefebvre et al presented 2 cases of S constellatus subdural empyema that responded completely to linezolid after having failed therapy with ceftriaxone, metronidazole, and vancomycin. Because of good oral bioavailability, prolonged therapy with oral linezolid is a feasible alternative to intravenous therapy. Future studies using linezolid for CNS infections are anticipated. Lawrence A. Cone, MD Department of Medicine Eisenhower Medical Center Rancho Mirage, CA 92270, USA