- Email: [email protected]
Treatment of Staphylococcus epidermidis Ventriculo–Peritoneal Shunt Infection with Linezolid
Case Reports effective antimicrobials are fluoroquinolones plus rifampicin. Chloramphenicol, doxycycline and trimethoprim are also useful, but less effective [10]. Recent studies have suggested that combinations of doxycycline and quinolone derivatives significantly reduce the mortality rate, and they are considered the mainstay of medical therapy for Q fever endocarditis [10,11]. The role of chloroquine in combination with doxycycline seems to be promising and it is currently under investigation. Chloroquine may increase the lysosomal pH, enhancing doxycycline bactericidal activity. A recent study demonstrated that doxycycline and chloroquine combination for at least 18 months is highly effective, leading to a reduction in the number of relapses [12,13]. The required duration of antimicrobial treatment is also undetermined, and recommendations vary between 1 and 3 years, or lifelong. Quantitative antibody titers should be periodically determined during and after treatment, and therapy should not be discontinued if titers of IgG antibody to phase I antigen remain at 1 : 800 or higher, even with normal results of clinical examination [1,2,10]. If an increase in the antibody levels is seen, the antibiotic therapy is not effective and the patient is at high risk of relapse [10±13]. To conclude, in our patient medical treatment with doxycycline and chloroquine for 2 years led to clinical recovery and significant decrease in titers of antibody to C. burnetii phase I antigen. However, further studies are needed to determine optimal treatment combinations and appropriate duration of antimicrobial therapy in Q fever endocarditis.
129
References 1 Siegman-Igra Y, Kaufman O, Keysary A, Rzotkiewicz S, Shalit I. Q fever endocarditis in Israel and a worldwide review. Scand J Infect Dis 1997; 29: 41±49. 2 Fournier PE, Casalta JP, Piquet P, Tournigand P, Branchereau A, Raoult D. Coxiella burnetii infection of aneurysm or vascular grafts: report of seven cases and review. Clin Infect Dis 1998; 26: 116±121. 3 Dalmau D, Castane J, Alvarez E, Ortega L, Garau J. A case of Q fever endocarditis treated medically: 9 years of follow-up. Infection 1997; 25: 131±132. 4 Raoult D, Marrie T. Q fever. Clin Infect Dis 1995; 20: 489±496. 5 Pierce MA, Saag MS, Dismukes WE, Cobbs CG. Q fever endocarditis. Am J Med Sci 1986; H292: 104±106. 6 Hoen B, Selton-Suty C, Lacassin F et al. Infective endocarditis in patients with negative blood cultures: analysis of 88 cases from a one-year nationwide survey in France. Clin Infect Dis 1995; 20: 501±506. 7 Soriano F, Camacho MT, Ponte C, Gomez P. Serological differentiation between acute (late control) and endocarditis Q fever. J Clin Pathol 1993; 46: 411±414. 8 Peter O, Dupuis G, Bee D, Luthy R, Nicolet J, Burgdorfer W. Enzymelinked immunosorbent assay for diagnosis of chronic Q fever. J Clin Microbiol 1988; 26: 1978±1982. 9 Peacock MG, Philip RN, Williams JC, Faulkner RS. Serological evaluation of Q fever in humans: enhanced phase I titers of immunoglobulins G and A are diagnostic for Q fever endocarditis. Infect Immun 1983; 41: 1089±1098. 10 Levy FY, Drancourt M, Etienne J et al. Comparison of different antibiotic therapy of 32 cases of Q fever endocarditis. Antimicrob Agents Chemother 1991; 35: 533±537. 11 Yebra M, Ortigosa J, Albarran F, Crespo MG. Ciprofloxacin in a case of Q fever endocarditis. N Engl J Med 1990; 323: 614. 12 Raoult D, Drancourt M, Vestris G. Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. Antimicrob Agents Chemother 1990; 34: 1512±1514. 13 Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Djiane J, Brouqui P. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med 1999; 159: 167±173.
doi:10.1053/jinf.2002.0979, available online at http://www.idealibrary.com on
Treatment of Staphylococcus epidermidis VentriculoPeritoneal Shunt Infection with Linezolid C. J. Gill1,2,3, M. A. Murphy1,5 and D. H. Hamer*1,3,4 1
Division of Geographic Medicine and Infectious Diseases; 2Division of Clinical Care Research, New England Medical Center, Boston, USA; 3Tufts University School of Medicine, Boston MA, USA 4 Department of International Health, Boston University School of Public Health, Boston, USA and 5 Rhode Island Hospital, Brown University, Providence, RI, USA * Please address all correspondence to: Davidson H. Hamer, Division of Geographic Medicine and Infectious Disease, Box 7010, New England Medical Center, 750 Washington Street, Boston, MA 02111, USA. Tel.: 617-636-7086; Fax: 617-636-7100; E-mail address: [email protected] (D. H. Hamer).
130
Case Reports Gram-positive bacterial meningitis frequently complicates ventriculo-peritoneal (VP) shunts used for hydrocephalus. Linezolid, an oxazolidinone, is active against Gram-positive cocci, and has excellent CSF penetration. We present a 22-year-old woman who was cured of a Staphylococcus epidermidis VP shunt infection via shunt removal and # 2002 The British Infection Society intravenous linezolid.
Introduction The management of hydrocephalus often requires the use of ventriculo-peritoneal (VP) shunts to reduce intracranial pressure. Infection of VP shunts occurs in 4.5±7.4% of cases [1±3]. Coagulase-negative staphylococci (CoNS) are the most common pathogens encountered in VP shunt infections [4,5], so empiric therapy often consists of intravenous vancomycin with rifampin [6±8]. Linezolid, a member of the novel class of drugs oxazolidinones, has excellent in vitro activity against a broad range of common Gram-positive organisms including CoNS [9] and achieves excellent cerebrospinal fluid (CSF) penetration [10,11]. We describe a patient with a Staphylococcus epidermidis VP shunt infection who was successfully treated with linezolid.
managed thereafter via intermittent large-volume lumbar puncture. CSF culture subsequently yielded a pure growth of Staphylococcus epidermidis. Based on this information, she was switched to linezolid monotherapy, dosed 600 mg intravenously every 12 hours. The isolate was susceptible to vancomycin but resistant to fluoroquinolones, chloramphenicol, penicillins, tetracyclines, and clindamycin. After completing 32 days of linezolid without symptom recurrence, she underwent removal of two non-functioning lumbar drains from previous surgeries and the implantation of a new lumbar drain. Since discharge, our patient has not had any further episodes of shunt meningitis during one year of follow up.
Case Report
Materials and Methods
A 23-year-old woman with a history of pseudotumor cerebri was admitted with fever and headache, ten days after undergoing a revision of a non-patent VP shunt. Two months prior to admission, her VP shunt had also been replaced due to probable infection. Over her lifetime, she had required 7 shunt replacements and 8 revisions due either to non-patency or infection. She was intolerant of multiple antimicrobial agents including penicillins, sulfonamides, cephalosporins and clindamycin. In addition, she had developed Steven's Johnson syndrome when treated with vancomycin. Physical examination revealed an obtunded young woman with a temperature of 103.6 F and nuchal rigidity. CSF obtained by lumbar puncture showed 593 white blood cells (63% polymorphonuclear leukocytes), elevated protein of 128 mg/dl, and a glucose of 45 mg/dl. Gram stain revealed 3 Gram-positive cocci in clusters. At the time when the current shunt had been placed, CSF cultures had grown `mixed respiratory flora.' Based on these earlier culture results, and the patient's history of reaction to vancomycin, she was initially treated empirically with levofloxacin, fluconazole, rifampin and chloramphenicol. The shunt was removed on admission and her intracranial pressures
Cultures of cerebrospinal fluid were performed according to standard techniques using 5% sheep blood agar, BBL's chocolate II agar, thioglyocolate broth tube and a brain and heart infusion broth. Sensitivities were determined using a `Vitek classic' automated microbiology system. CSF cells counts and chemistries were performed according to standard laboratory protocols.
Discussion The majority of intracranial prosthetic device infections are caused by Staphylococcus epidermidis and other coagulase negative staphylococci (CoNS), S. aureus, and, less commonly, nosocomial Gram-negative bacilli and yeasts [5,12,13]. Optimal management includes removal of the infected device [14,15] and treatment with appropriate, organism-specific antibiotics. Gram-positive infections have traditionally been treated with parenteral or intrathecal penicillinase-resistant penicillins, such as nafcillin, or vancomycin combined with rifampin [6±8]. With the increasing prevalence of nosocomial Gram-positive infections due to vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant
Case Reports staphylococci, clinicians have been forced to resort to alternative antibiotics such as the combination of quinupristin/daltopristin (SynercidTM), daptomycin, and, more recently, linezolid (ZyvoxTM). Experimental results using the rabbit meningitis model suggest that linezolid may be useful in this setting [16]. Unfortunately, data directly supporting the use of linezolid in human CNS infections remains largely anecdotal. At the time of this writing, we were able to locate only three reports describing linezolid to treat Gram-positive meningitis, each involving VREF infections in patients without shunts [11,17,18]. We were unable to locate any previous reports on Medline or Pre-Medline of linezolid being used to treat shunt infections. Linezolid possesses several features that make it an attractive agent for CNS infections. Linezolid has almost 100% bioavailability and achieves CSF levels 30±70% of those present in serum [11,19]. By comparison, vancomycin CSF levels are approximately 20% of serum [20±22]. Moreover, linezolid serum levels are comparable by either oral or intravenous routes. This feature may introduce the possibility for oral outpatient therapy of selected, low-risk patients with shunt infections. From the standpoint of antibiotic resistance, linezolid does not display cross-resistance with other antibiotics commonly used for patients with CoNS infections, including vancomycin, daptomycin, quinipristin/daltopristin, fluoroquinolones, lincosamides, streptogramins, tetracyclines and macrolides [23]. Lastly, linezolid has broad activity against many of the pathogens associated with nosocomial meningitis, including methicillinresistant and sensitive strains of both S. aureus and the CoNS [24], penicillin-resistant Streptococcus pneumoniae [16], vancomycin-resistant Enterococcus faecium (VREF) [25], Bacillus spp., Corynebacterium spp., and Leuconostoc spp. [19]. Our success with linezolid in this instance increases our optimism about the future role of this class of drugs for the treatment of shunt meningitis. Formal clinical trials comparing linezolid with vancomycin/rifampin are needed to clarify its role. Additional trials may also be required to explore linezolid's potential as neurosurgical prophylaxis, and as primary treatment of shunt infections when removal of the prosthetic device is impossible. Acknowledgements This work was supported by NIH training grant 5T32AI0738.
131
References 1 Spanu G, Karussos G, Adinolfi D, Bonfanti N. An analysis of cerebrospinal fluid shunt infections in adults. A clinical experience of twelve years. Acta Neurochir (Wien) 1986; 80(3±4): 79±82. 2 Patir R, Mahapatra AK, Banerji AK. Risk factors in postoperative neurosurgical infection. A prospective study. Acta Neurochir (Wien) 1992; 119(1±4): 80±84. 3 Borgbjerg BM, Gjerris F, Albeck MJ, Borgesen SE. Risk of infection after cerebrospinal fluid shunt: an analysis of 884 first-time shunts. Acta Neurochir (Wien) 1995; 136(1±2): 1±7. 4 Bayston R. Hydrocephalus shunt infections. J Antimicrob Chemother 1994; 34(Suppl A): 75±84. 5 George R, Leibrock L, Epstein M. Long-term analysis of cerebrospinal fluid shunt infections. A 25-year experience. J Neurosurg 1979; 51(6): 804±811. 6 Chapman PH, Borges LF. Shunt infections: prevention and treatment. Clin Neurosurg 1985; 32: 652±664. 7 Gombert ME, Landesman SH, Corrado ML, Stein SC, Melvin ET, Cummings M. Vancomycin and rifampin therapy for Staphylococcus epidermidis meningitis associated with CSF shunts: report of three cases. J Neurosurg 1981; 55(4): 633±636. 8 Swanberg L, Tuazon CU. Rifampin in the treatment of serious staphylococcal infections. Am J Med Sci 1984; 287(3): 49±54. 9 Cercenado E, Garcia-Garrote F, Bouza E. In vitro activity of linezolid against multiply resistant Gram-positive clinical isolates. J Antimicrob Chemother 2001; 47(1): 77±81. 10 Anonymous. Zyvox (Linezolid) Comprehensive Reviews, April 2000. Pharmacia and Upjohn, 2000: pp. 1±32. 11 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(5): 375±379. 12 Kaufman BA, Tunkel AR, Pryor JC, Dacey RG, Jr. Meningitis in the neurosurgical patient. Infect Dis Clin North Am 1990; 4(4): 677± 701. 13 Morris A, Low DE. Nosocomial bacterial meningitis, including central nervous system shunt infections. Infect Dis Clin North Am 1999; 13(3): 735±750. 14 Walters BC, Hoffman HJ, Hendrick EB, Humphreys RP. Cerebrospinal fluid shunt infection. Influences on initial management and subsequent outcome. J Neurosurg 1984; 60(5): 1014±1021. 15 Nicholas JL, Kamal IM, Eckstein HB. Immediate shunt replacement in the treatment of bacterial colonisation of Holter valves. Dev Med Child Neurol Suppl 1970; 22(Suppl 22): 110. 16 Cottagnoud P, Gerber CM, Acosta F, Cottagnoud M, Neftel K, Tauber MG. Linezolid against penicillin-sensitive and -resistant pneumococci in the rabbit meningitis model. J Antimicrob Chemother 2000; 46(6): 981±985. 17 Hachem R, Afif C, Gokaslan Z, Raad I. Successful treatment of vancomycin-resistant Enterococcus meningitis with linezolid. Eur J Clin Microbiol Infect Dis 2001; 20(6): 432±434. 18 Zeana C, Kubin CJ, Della-Latta P, Hammer SM. Vancomycinresistant Enterococcus faecium meningitis successfully managed with linezolid: case report and review of the literature. Clin Infect Dis 2001; 33(4): 477±482. 19 Diekema DI, Jones RN. Oxazolidinones: a review. Drugs 2000; 59(1): 7±16. 20 Ahmed A, Jafri H, Lutsar I et al. Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporinresistant pneumococcal meningitis. Antimicrob Agents Chemother 1999; 43(4): 876±881. 21 Lutsar I, McCracken GH Jr, Friedland IR. Antibiotic pharmacodynamics in cerebrospinal fluid. Clin Infect Dis 1998; 27(5): 1117±1127, quiz 1128±1119. 22 Reiter PD, Doron MW. Vancomycin cerebrospinal fluid concentrations after intravenous administration in premature infants. J Perinatol 1996; 16(5): 331±335.
132
Case Reports
23 Fang CT, Chang SC, Chen YC, Hsieh SM, Hsieh WC. In vitro activity of linezolid against clinical Gram-positive bacterial isolates from Taiwan: an area with a high prevalence of antibiotic resistance. Int J Antimicrob Agents 2001; 18(3): 267±270.
24 Cuny C, Witte W. In vitro activity of linezolid against staphylococci. Clin Microbiol Infect 2000; 6(6): 331±333. 25 Levison ME, Mallela S. Increasing antimicrobial resistance: therapeutic implications for enterococcal infections. Curr Infect Dis Rep 2000; 2(5): 417±423.
129
References 1 Siegman-Igra Y, Kaufman O, Keysary A, Rzotkiewicz S, Shalit I. Q fever endocarditis in Israel and a worldwide review. Scand J Infect Dis 1997; 29: 41±49. 2 Fournier PE, Casalta JP, Piquet P, Tournigand P, Branchereau A, Raoult D. Coxiella burnetii infection of aneurysm or vascular grafts: report of seven cases and review. Clin Infect Dis 1998; 26: 116±121. 3 Dalmau D, Castane J, Alvarez E, Ortega L, Garau J. A case of Q fever endocarditis treated medically: 9 years of follow-up. Infection 1997; 25: 131±132. 4 Raoult D, Marrie T. Q fever. Clin Infect Dis 1995; 20: 489±496. 5 Pierce MA, Saag MS, Dismukes WE, Cobbs CG. Q fever endocarditis. Am J Med Sci 1986; H292: 104±106. 6 Hoen B, Selton-Suty C, Lacassin F et al. Infective endocarditis in patients with negative blood cultures: analysis of 88 cases from a one-year nationwide survey in France. Clin Infect Dis 1995; 20: 501±506. 7 Soriano F, Camacho MT, Ponte C, Gomez P. Serological differentiation between acute (late control) and endocarditis Q fever. J Clin Pathol 1993; 46: 411±414. 8 Peter O, Dupuis G, Bee D, Luthy R, Nicolet J, Burgdorfer W. Enzymelinked immunosorbent assay for diagnosis of chronic Q fever. J Clin Microbiol 1988; 26: 1978±1982. 9 Peacock MG, Philip RN, Williams JC, Faulkner RS. Serological evaluation of Q fever in humans: enhanced phase I titers of immunoglobulins G and A are diagnostic for Q fever endocarditis. Infect Immun 1983; 41: 1089±1098. 10 Levy FY, Drancourt M, Etienne J et al. Comparison of different antibiotic therapy of 32 cases of Q fever endocarditis. Antimicrob Agents Chemother 1991; 35: 533±537. 11 Yebra M, Ortigosa J, Albarran F, Crespo MG. Ciprofloxacin in a case of Q fever endocarditis. N Engl J Med 1990; 323: 614. 12 Raoult D, Drancourt M, Vestris G. Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. Antimicrob Agents Chemother 1990; 34: 1512±1514. 13 Raoult D, Houpikian P, Tissot Dupont H, Riss JM, Arditi-Djiane J, Brouqui P. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine. Arch Intern Med 1999; 159: 167±173.
doi:10.1053/jinf.2002.0979, available online at http://www.idealibrary.com on
Treatment of Staphylococcus epidermidis VentriculoPeritoneal Shunt Infection with Linezolid C. J. Gill1,2,3, M. A. Murphy1,5 and D. H. Hamer*1,3,4 1
Division of Geographic Medicine and Infectious Diseases; 2Division of Clinical Care Research, New England Medical Center, Boston, USA; 3Tufts University School of Medicine, Boston MA, USA 4 Department of International Health, Boston University School of Public Health, Boston, USA and 5 Rhode Island Hospital, Brown University, Providence, RI, USA * Please address all correspondence to: Davidson H. Hamer, Division of Geographic Medicine and Infectious Disease, Box 7010, New England Medical Center, 750 Washington Street, Boston, MA 02111, USA. Tel.: 617-636-7086; Fax: 617-636-7100; E-mail address: [email protected] (D. H. Hamer).
130
Case Reports Gram-positive bacterial meningitis frequently complicates ventriculo-peritoneal (VP) shunts used for hydrocephalus. Linezolid, an oxazolidinone, is active against Gram-positive cocci, and has excellent CSF penetration. We present a 22-year-old woman who was cured of a Staphylococcus epidermidis VP shunt infection via shunt removal and # 2002 The British Infection Society intravenous linezolid.
Introduction The management of hydrocephalus often requires the use of ventriculo-peritoneal (VP) shunts to reduce intracranial pressure. Infection of VP shunts occurs in 4.5±7.4% of cases [1±3]. Coagulase-negative staphylococci (CoNS) are the most common pathogens encountered in VP shunt infections [4,5], so empiric therapy often consists of intravenous vancomycin with rifampin [6±8]. Linezolid, a member of the novel class of drugs oxazolidinones, has excellent in vitro activity against a broad range of common Gram-positive organisms including CoNS [9] and achieves excellent cerebrospinal fluid (CSF) penetration [10,11]. We describe a patient with a Staphylococcus epidermidis VP shunt infection who was successfully treated with linezolid.
managed thereafter via intermittent large-volume lumbar puncture. CSF culture subsequently yielded a pure growth of Staphylococcus epidermidis. Based on this information, she was switched to linezolid monotherapy, dosed 600 mg intravenously every 12 hours. The isolate was susceptible to vancomycin but resistant to fluoroquinolones, chloramphenicol, penicillins, tetracyclines, and clindamycin. After completing 32 days of linezolid without symptom recurrence, she underwent removal of two non-functioning lumbar drains from previous surgeries and the implantation of a new lumbar drain. Since discharge, our patient has not had any further episodes of shunt meningitis during one year of follow up.
Case Report
Materials and Methods
A 23-year-old woman with a history of pseudotumor cerebri was admitted with fever and headache, ten days after undergoing a revision of a non-patent VP shunt. Two months prior to admission, her VP shunt had also been replaced due to probable infection. Over her lifetime, she had required 7 shunt replacements and 8 revisions due either to non-patency or infection. She was intolerant of multiple antimicrobial agents including penicillins, sulfonamides, cephalosporins and clindamycin. In addition, she had developed Steven's Johnson syndrome when treated with vancomycin. Physical examination revealed an obtunded young woman with a temperature of 103.6 F and nuchal rigidity. CSF obtained by lumbar puncture showed 593 white blood cells (63% polymorphonuclear leukocytes), elevated protein of 128 mg/dl, and a glucose of 45 mg/dl. Gram stain revealed 3 Gram-positive cocci in clusters. At the time when the current shunt had been placed, CSF cultures had grown `mixed respiratory flora.' Based on these earlier culture results, and the patient's history of reaction to vancomycin, she was initially treated empirically with levofloxacin, fluconazole, rifampin and chloramphenicol. The shunt was removed on admission and her intracranial pressures
Cultures of cerebrospinal fluid were performed according to standard techniques using 5% sheep blood agar, BBL's chocolate II agar, thioglyocolate broth tube and a brain and heart infusion broth. Sensitivities were determined using a `Vitek classic' automated microbiology system. CSF cells counts and chemistries were performed according to standard laboratory protocols.
Discussion The majority of intracranial prosthetic device infections are caused by Staphylococcus epidermidis and other coagulase negative staphylococci (CoNS), S. aureus, and, less commonly, nosocomial Gram-negative bacilli and yeasts [5,12,13]. Optimal management includes removal of the infected device [14,15] and treatment with appropriate, organism-specific antibiotics. Gram-positive infections have traditionally been treated with parenteral or intrathecal penicillinase-resistant penicillins, such as nafcillin, or vancomycin combined with rifampin [6±8]. With the increasing prevalence of nosocomial Gram-positive infections due to vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant
Case Reports staphylococci, clinicians have been forced to resort to alternative antibiotics such as the combination of quinupristin/daltopristin (SynercidTM), daptomycin, and, more recently, linezolid (ZyvoxTM). Experimental results using the rabbit meningitis model suggest that linezolid may be useful in this setting [16]. Unfortunately, data directly supporting the use of linezolid in human CNS infections remains largely anecdotal. At the time of this writing, we were able to locate only three reports describing linezolid to treat Gram-positive meningitis, each involving VREF infections in patients without shunts [11,17,18]. We were unable to locate any previous reports on Medline or Pre-Medline of linezolid being used to treat shunt infections. Linezolid possesses several features that make it an attractive agent for CNS infections. Linezolid has almost 100% bioavailability and achieves CSF levels 30±70% of those present in serum [11,19]. By comparison, vancomycin CSF levels are approximately 20% of serum [20±22]. Moreover, linezolid serum levels are comparable by either oral or intravenous routes. This feature may introduce the possibility for oral outpatient therapy of selected, low-risk patients with shunt infections. From the standpoint of antibiotic resistance, linezolid does not display cross-resistance with other antibiotics commonly used for patients with CoNS infections, including vancomycin, daptomycin, quinipristin/daltopristin, fluoroquinolones, lincosamides, streptogramins, tetracyclines and macrolides [23]. Lastly, linezolid has broad activity against many of the pathogens associated with nosocomial meningitis, including methicillinresistant and sensitive strains of both S. aureus and the CoNS [24], penicillin-resistant Streptococcus pneumoniae [16], vancomycin-resistant Enterococcus faecium (VREF) [25], Bacillus spp., Corynebacterium spp., and Leuconostoc spp. [19]. Our success with linezolid in this instance increases our optimism about the future role of this class of drugs for the treatment of shunt meningitis. Formal clinical trials comparing linezolid with vancomycin/rifampin are needed to clarify its role. Additional trials may also be required to explore linezolid's potential as neurosurgical prophylaxis, and as primary treatment of shunt infections when removal of the prosthetic device is impossible. Acknowledgements This work was supported by NIH training grant 5T32AI0738.
131
References 1 Spanu G, Karussos G, Adinolfi D, Bonfanti N. An analysis of cerebrospinal fluid shunt infections in adults. A clinical experience of twelve years. Acta Neurochir (Wien) 1986; 80(3±4): 79±82. 2 Patir R, Mahapatra AK, Banerji AK. Risk factors in postoperative neurosurgical infection. A prospective study. Acta Neurochir (Wien) 1992; 119(1±4): 80±84. 3 Borgbjerg BM, Gjerris F, Albeck MJ, Borgesen SE. Risk of infection after cerebrospinal fluid shunt: an analysis of 884 first-time shunts. Acta Neurochir (Wien) 1995; 136(1±2): 1±7. 4 Bayston R. Hydrocephalus shunt infections. J Antimicrob Chemother 1994; 34(Suppl A): 75±84. 5 George R, Leibrock L, Epstein M. Long-term analysis of cerebrospinal fluid shunt infections. A 25-year experience. J Neurosurg 1979; 51(6): 804±811. 6 Chapman PH, Borges LF. Shunt infections: prevention and treatment. Clin Neurosurg 1985; 32: 652±664. 7 Gombert ME, Landesman SH, Corrado ML, Stein SC, Melvin ET, Cummings M. Vancomycin and rifampin therapy for Staphylococcus epidermidis meningitis associated with CSF shunts: report of three cases. J Neurosurg 1981; 55(4): 633±636. 8 Swanberg L, Tuazon CU. Rifampin in the treatment of serious staphylococcal infections. Am J Med Sci 1984; 287(3): 49±54. 9 Cercenado E, Garcia-Garrote F, Bouza E. In vitro activity of linezolid against multiply resistant Gram-positive clinical isolates. J Antimicrob Chemother 2001; 47(1): 77±81. 10 Anonymous. Zyvox (Linezolid) Comprehensive Reviews, April 2000. Pharmacia and Upjohn, 2000: pp. 1±32. 11 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(5): 375±379. 12 Kaufman BA, Tunkel AR, Pryor JC, Dacey RG, Jr. Meningitis in the neurosurgical patient. Infect Dis Clin North Am 1990; 4(4): 677± 701. 13 Morris A, Low DE. Nosocomial bacterial meningitis, including central nervous system shunt infections. Infect Dis Clin North Am 1999; 13(3): 735±750. 14 Walters BC, Hoffman HJ, Hendrick EB, Humphreys RP. Cerebrospinal fluid shunt infection. Influences on initial management and subsequent outcome. J Neurosurg 1984; 60(5): 1014±1021. 15 Nicholas JL, Kamal IM, Eckstein HB. Immediate shunt replacement in the treatment of bacterial colonisation of Holter valves. Dev Med Child Neurol Suppl 1970; 22(Suppl 22): 110. 16 Cottagnoud P, Gerber CM, Acosta F, Cottagnoud M, Neftel K, Tauber MG. Linezolid against penicillin-sensitive and -resistant pneumococci in the rabbit meningitis model. J Antimicrob Chemother 2000; 46(6): 981±985. 17 Hachem R, Afif C, Gokaslan Z, Raad I. Successful treatment of vancomycin-resistant Enterococcus meningitis with linezolid. Eur J Clin Microbiol Infect Dis 2001; 20(6): 432±434. 18 Zeana C, Kubin CJ, Della-Latta P, Hammer SM. Vancomycinresistant Enterococcus faecium meningitis successfully managed with linezolid: case report and review of the literature. Clin Infect Dis 2001; 33(4): 477±482. 19 Diekema DI, Jones RN. Oxazolidinones: a review. Drugs 2000; 59(1): 7±16. 20 Ahmed A, Jafri H, Lutsar I et al. Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporinresistant pneumococcal meningitis. Antimicrob Agents Chemother 1999; 43(4): 876±881. 21 Lutsar I, McCracken GH Jr, Friedland IR. Antibiotic pharmacodynamics in cerebrospinal fluid. Clin Infect Dis 1998; 27(5): 1117±1127, quiz 1128±1119. 22 Reiter PD, Doron MW. Vancomycin cerebrospinal fluid concentrations after intravenous administration in premature infants. J Perinatol 1996; 16(5): 331±335.
132
Case Reports
23 Fang CT, Chang SC, Chen YC, Hsieh SM, Hsieh WC. In vitro activity of linezolid against clinical Gram-positive bacterial isolates from Taiwan: an area with a high prevalence of antibiotic resistance. Int J Antimicrob Agents 2001; 18(3): 267±270.
24 Cuny C, Witte W. In vitro activity of linezolid against staphylococci. Clin Microbiol Infect 2000; 6(6): 331±333. 25 Levison ME, Mallela S. Increasing antimicrobial resistance: therapeutic implications for enterococcal infections. Curr Infect Dis Rep 2000; 2(5): 417±423.