Acta Neurochirurgica

, Volume 158, Issue 10, pp 1837–1843 | Cite as

Sequential antimicrobial treatment with linezolid for neurosurgical infections: efficacy, safety and cost study

  • Cecilia Martín-GandulEmail author
  • M. J. Mayorga-Buiza
  • E. Castillo-Ojeda
  • M. J. Gómez-Gómez
  • M. Rivero-Garvía
  • M. V. Gil-Navarro
  • F. J. Márquez-Rivas
  • M. E. Jiménez-Mejías
Clinical Article - Functional



Evidence for the effectiveness of linezolid in neurosurgical infections (NSIs) is growing. The comfortable oral dosage and tolerance of linezolid opens the possibility for sequential antimicrobial treatment (SAT) in stable patients after a period of intravenous treatment.


To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid.


A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3–42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179.


SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources.


Sequential antimicrobial therapy Neurosurgical infection Linezolid 



This study has been conducted within the framework of the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), supported by the Ministerio de Economía y Competitividad (Spanish Ministry of Economy and Competitiveness), the Instituto de Salud Carlos III, project PI13/01744, and co-financed by the European Development Regional Fund “A way to achieve Europe” ERDF.

Compliance with ethical standards


No funding was received for this research.

Conflict of interest


Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Bayston R, Nuradeen B, Ashraf W, Freeman BJ (2007) Antibiotics for the eradication of Propionibacterium acnes biofilms in surgical infection. J Antimicrob Chemother 60:1298–1301CrossRefPubMedGoogle Scholar
  2. 2.
    Bayston R, Ullas G, Ashraf W (2012) Action of linezolid or vancomycin on biofilm in ventriculoperitoneal shunts in vitro. Antimicrob Agents Chemother 56:2842–2845CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bounthavong M, Hsu DI (2012) Cost-effectiveness of linezolid in methicillin-resistant Staphylococcus aureus skin and skin structure infections. Expert Rev Pharmacoecon Outcomes Res 12:683–698CrossRefPubMedGoogle Scholar
  4. 4.
    Bruns AS, Sood N (2009) Community-acquired methicillin-resistant Staphylococcus aureus epidural abscess with bacteremia and multiple lung abscesses: case report. Am J Crit Care 18:86–88CrossRefGoogle Scholar
  5. 5.
    Calik S, Turhan T, Yurtseven T, Sipahi OR, Buke C (2012) Vancomycin versus linezolid in the treatment of methicillin-resistant Staphylococcus aureus meningitis in an experimental rabbit model. Med Sci Monit 18:SC5–SC8CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Chaudhuri A, Martinez-Martin P, Kennedy PG, Andrew Seaton R, Portegies P, Bojar M, Steiner I, EFNS Task Force (2008) EFNS guideline on management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults. Eur J Neurol 15:649–659CrossRefPubMedGoogle Scholar
  7. 7.
    Dinleyici EC, Yarar C, Dinleyici M, Yakut A (2007) Successful treatment with linezolid of meningitis complicated with subdural empyema in a 6-month-old boy. J Trop Pediatr 53:431–433CrossRefPubMedGoogle Scholar
  8. 8.
    Dryden MS (2011) Linezolid pharmacokinetics and pharmacodynamics in clinical treatment. J Antimicrob Chemother 66(Suppl 4):iv7–iv15PubMedGoogle Scholar
  9. 9.
    Gallagher RM, Pizer B, Ellison JA, Riordan FA (2008) Glycopeptide insensitive Staphylococcus aureus subdural empyema treated with linezolid and rifampicin. J Infect 57:410–413CrossRefPubMedGoogle Scholar
  10. 10.
    Grau S, Mateu-de-Antonio J, Soto J, Marin-Casino M, Salas E (2005) Pharmaeconomic evaluation of linezolid versus teicoplanin in bacteremia by Gram-positive microorganisms. Pharm World Sci 27:459–464CrossRefPubMedGoogle Scholar
  11. 11.
    Hiraki Y, Tsuji Y, Hiraike M, Misumi N, Matsumoto K, Morita K, Kamimura H, Karube Y (2012) Correlation between serum linezolid concentration and the development of thrombocytopenia. Scand J Infect Dis 44:60–64CrossRefPubMedGoogle Scholar
  12. 12.
    Huang WC, Lee CH, Liu JW (2010) Clinical characteristics and risk factors for mortality in patients with meningitis caused by S. aureus and vancomycin minimal inhibitory concentrations against these isolates. J Microbiol Immunol Infect 43:470–477CrossRefPubMedGoogle Scholar
  13. 13.
    Kallweit U, Hazheim M, Marklein G, Welt T, Pöhlau D (2007) Successful treatment of methicillin-resistant Staphylococcus aureus using linezolid without removal of intrathecal infusion pump. Case report. J Neurosurg 107:651–653CrossRefPubMedGoogle Scholar
  14. 14.
    Kessler AT, Kourtis AP (2007) Treatment of meningitis caused by methicillin-resistant Staphylococcus aureus with linezolid. Infection 35:271–274CrossRefPubMedGoogle Scholar
  15. 15.
    Kestle JR, Garton HJ, Whitehead WE, Drake JM, Kulkarni AV, Cochrane DD, Muszynski C, Walker ML (2006) Management of shunt infections: a multicenter pilot study. J Neurosurg 105:177–181PubMedGoogle Scholar
  16. 16.
    Lefebvre L, Metellus P, Dufour H, Bruder N (2009) Linezolid for treatment of subdural empyema due to Streptococcus: case reports. Surg Neurol 71:89–91CrossRefPubMedGoogle Scholar
  17. 17.
    Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR (1999) Guideline for prevention of surgical site infection, 1999 Centers for Disease Control and prevention (CDC) hospital infection control practices advisory committee. Am J Infect Control 27:97–132CrossRefPubMedGoogle Scholar
  18. 18.
    Martinez-Lacasa J, Cabellos C, Martos A, Fernández A, Tubau F, Viladrich PF, Liñares J, Gudiol F (2002) Experimental study of the efficacy of vancomycin, rifampicin and dexamethasone in the therapy of pneumococcal meningitis. J Antimicrob Chemother 49:507–513CrossRefPubMedGoogle Scholar
  19. 19.
    McClelland S 3rd, Hall WA (2007) Postoperative central nervous system infection: incidence and associated factors in 2111 neurosurgical procedures. Clin Infect Dis 45:55–59CrossRefPubMedGoogle Scholar
  20. 20.
    Mensa J, Gatell JM, García-Sánchez JE, Letang E, López-Suñé E, Marco F (2014) Guía de terapeútica antimicrobiana. Antares editorial, BarcelonaGoogle Scholar
  21. 21.
    Myrianthefs P, Markantonis SL, Vlachos K, Anagnostaki M, Boutzouka E, Panidis D, Baltopoulos G (2006) Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients. Antimicrob Agents Chemother 50:3971–3976CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Nagashima G, Okamoto N, Okuda M, Nakashima K, Noda M, Itokawa H, Suzuki R, Fujimoto T, Marumo K (2008) Effect of linezolid against postneurosurgical meningitis caused by methicillin-resistant Staphylococcus epidermidis: case report. J Infect Chemother 14:147–150CrossRefPubMedGoogle Scholar
  23. 23.
    Namvar AE, Bastarahang S, Abbasi N, Ghehi GS, Farhadbakhtiarian S, Arezi P, Hosseini M, Baravati SZ, Jokar Z, Chermahin SG (2014) Clinical characteristics of Staphylococcus epidermidis: a systematic review. GMS Hyg Infect Control 9:Doc23PubMedPubMedCentralGoogle Scholar
  24. 24.
    Nau R, Sörgel F, Eiffert H (2010) Penetration of drugs through blood-cerebrospinal fluid/blood–brain barrier for treatment of central nervous system infections. Clin Microbiol Rev 23:858–883CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ntziora F, Falagas ME (2007) Linezolid for the treatment of patients with central nervous system infection. Ann Pharmacother 41:296–308CrossRefPubMedGoogle Scholar
  26. 26.
    Peppard WJ, Johnston CJ, Urmanski AM (2008) Pharmacologic options for CNS infections caused by resistant gram-positive organisms. Expert Rev Anti-Infect Ther 6:83–99CrossRefPubMedGoogle Scholar
  27. 27.
    Plosker GL, Figgitt DP (2005) Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections. Pharmacoeconomics 23:945–964CrossRefPubMedGoogle Scholar
  28. 28.
    Portillo ME, Corvec S, Borens O, Trampuz A (2013) Propionibacterium acnes: an underestimated pathogen in implant-associated infections. Biomed Res Int. 804391Google Scholar
  29. 29.
    Rivero-Garvía M, Márquez-Rivas J, Jiménez-Mejías ME, Neth O, Rueda-Torres AB (2011) Reduction in external ventricular drain infection rate. Impact of a minimal handling protocol and antibiotic-impregnated catheters. Acta Neurochir (Wien) 153:647–651CrossRefGoogle Scholar
  30. 30.
    Rupprecht TA, Pfister HW (2005) Clinical experience with linezolid for the treatment of central nervous system infections. Eur J Neurol 12:536–542CrossRefPubMedGoogle Scholar
  31. 31.
    Schel WM, Whitley RJ, Marra CM (2014) Infections of the central nervous system. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  32. 32.
    Sipahi OR, Bardak S, Turhan T, Arda B, Pullukcu H, Ruksen M, Aydemir S, Dalbasti T, Yurtseven T, Zileli M, Ulusoy S (2011) Linezolid in the treatment of methicillin-resistant staphylococcal post-neurosurgical meningitis: a series of 17 cases. Scand J Infect Dis 43:757–764CrossRefPubMedGoogle Scholar
  33. 33.
    Sipahi OR, Bardak-Ozcem S, Turhan T, Arda B, Ruksen M, Pullukcu H, Aydemir S, Dalbasti T, Yurtseven T, Sipahi H, Zileli M, Ulusoy S (2013) Vancomycin versus linezolid in the treatment of methicillin-resistant Staphylococcus aureus meningitis. Surg Infect 14:357–362CrossRefGoogle Scholar
  34. 34.
    Sousa D, Llinares P, Meijide H, Gutiérrez JM, Miguez E, Sánchez E, Castelo L, Mena A (2011) Clinical experience with linezolid for the treatment of neurosurgical infections. Rev Esp Quimioter 24:42–47PubMedGoogle Scholar
  35. 35.
    Stevens NT, Greene CM, O’Gara JP, Bayston R, Sattar MT, Farrell M, Humphreys H (2012) Ventriculoperitoneal shunt-related infections caused by Staphylococcus epidermidis: pathogenesis and implications for treatment. Br J Neurosurg 26:792–797CrossRefPubMedGoogle Scholar
  36. 36.
    Tsuji Y, Yukawa E, Hiraki Y, Matsumoto K, Mizoguchi A, Morita K, Kamimura H, Karube Y, To H (2013) Population pharmacokinetic analysis of linezolid in low body weight patients with renal dysfunction. J Clin Pharmacol 53:967–973CrossRefPubMedGoogle Scholar
  37. 37.
    Villani P, Regazzi MB, Marubbi F, Viale P, Pagani L, Cristini F, Cadeo B, Carosi G, Bergomi R (2002) Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections. Antimicrob Agents Chemother 46:936–937CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zhan R, Zhu Y, Shen Y, Shen J, Tong Y, Yu H, Wen L (2014) Post-operative central nervous system infections after cranial surgery in China: incidence, causative agents, and risk factors in 1,470 patients. Eur J Clin Microbiol Infect Dis 33:861–866CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Cecilia Martín-Gandul
    • 1
    • 2
    Email author
  • M. J. Mayorga-Buiza
    • 3
  • E. Castillo-Ojeda
    • 4
  • M. J. Gómez-Gómez
    • 2
  • M. Rivero-Garvía
    • 1
    • 3
  • M. V. Gil-Navarro
    • 5
  • F. J. Márquez-Rivas
    • 1
    • 3
  • M. E. Jiménez-Mejías
    • 1
    • 2
  1. 1.Instituto de Biomedicina de Sevilla (IBIS)University Hospital Virgen del Rocío/CSIC/University of SevilleSevilleSpain
  2. 2.Infectious Diseases, Microbiology and Preventive Medicine UnitUniversity Hospital Virgen del RocíoSevilleSpain
  3. 3.Neurosurgery ServiceUniversity Hospital Virgen del RocíoSevilleSpain
  4. 4.University of Seville/Spanish National Research CouncilSevilleSpain
  5. 5.Clinical Pharmacy ServiceUniversity Hospital Virgen del RocíoSevilleSpain

Personalised recommendations