Clinical trial NCT01356472: Linezolid Alone or Combined With Carbapenem Against Methicillin-resistant Staphylococcus Aureus (MRSA) in Ventilator-associated Pneumonia
Official title: Linezolid Alone or Combined With Carbapenem Against Methicillin-resistant Staphylococcus Aureus (MRSA) in Vitro and in Ventilator-associated Pneumonia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Methicillin-resistant Staphylococcus Aureus
Pneumonia, Ventilator-Associated
Keywords: Methicillin-resistant Staphylococcus aureus
Pneumonia, Ventilator-Associated
linezolid
imipenem/cilastatin
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2011-05-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: As previous studies showed that the synergy between linezolid and carbapenem in vitro and in vivo (animal studies), our study is aim to investigate the activity of linezolid, alone and in combination with carbapenem against methicillin-resistant Staphylococcus aureus (MRSA) in ventilator-associated pneumonia (VAP) patients.

Detailed description: Linezolid is the only commercially available oxazolidinone, the first new class of antibiotic to be developed in the last three decades. Although it is predominantly bacteriostatic, linezolid has good in vitro and in vivo activity against MRSA . However, several studies did not show that linezolid was superior to any of glycopeptides in treatment of MRSA pneumonia. Moreover, combination therapy against MRSA is argued when several in vitro and in vivo studies showed synergy between linezolid and carbapenem or fosfomycin or rifampicin, while vancomycin and linezolid in combination should be avoided. our study is aim to investigate the activity of linezolid, alone and in combination with carbapenem against methicillin-resistant Staphylococcus aureus (MRSA) in ventilator-associated pneumonia (VAP) patients.

Eligibility criteria: Inclusion Criteria:

* Pneumonia, Ventilator-associated

  * the presence of new or persistent radiographic features
  * fever higher than 38°C
  * leukocytosis (≥11.0 ×109/L) or neutropenia (≤3.5×109/L)
  * purulent endotracheal
  * increasing oxygen requirements
* Endotracheal aspiration culture show methicillin-resistant S. aureus positive

Exclusion Criteria:

* immunocompromised patients (postorgan transplantation or human immunodeficiency virus-infected or neutropenic \[≤1×109/L absolute neutrophils\], or patients receiving corticosteroids \>20 mg/d for 6 months)
* colonized chronically with methicillin-resistant S. aureus
* pregnancy
* endotracheal aspiration culture showed no MRSA

Primary outcomes:
measure: MRSA eradication
timeFrame: 7 th day
Secondary outcomes:
measure: MRSA eradication
timeFrame: 14th day
measure: mortality
timeFrame: 28th day
Other outcomes:
Locations:
Study officials:
affiliation: Emergency intensive care unit, Ruijin Hospital
name: Er-Zhen Chen, M.D. & Ph.D.
role: STUDY_DIRECTOR
affiliation: Respiratory intensive care unit, Ruijin Hospital
name: Hong-Ping Qu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Microbiology laboratory, Ruijin Hospital
name: Yu-Xing Ni, M.D. & Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Emergency Department, Ruijin Hospital
name: Zhi-Tao Yang, M.D.
role: STUDY_CHAIR
References:
citation: Jacqueline C, Navas D, Batard E, Miegeville AF, Le Mabecque V, Kergueris MF, Bugnon D, Potel G, Caillon J. In vitro and in vivo synergistic activities of linezolid combined with subinhibitory concentrations of imipenem against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2005 Jan;49(1):45-51. doi: 10.1128/AAC.49.1.45-51.2005.
citation: Jacqueline C, Caillon J, Grossi O, Le Mabecque V, Miegeville AF, Bugnon D, Batard E, Potel G. In vitro and in vivo assessment of linezolid combined with ertapenem: a highly synergistic combination against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2006 Jul;50(7):2547-9. doi: 10.1128/AAC.01501-05.
citation: Rubinstein E, Cammarata S, Oliphant T, Wunderink R; Linezolid Nosocomial Pneumonia Study Group. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis. 2001 Feb 1;32(3):402-12. doi: 10.1086/318486. Epub 2001 Jan 26.
citation: Shorr AF, Kunkel MJ, Kollef M. Linezolid versus vancomycin for Staphylococcus aureus bacteraemia: pooled analysis of randomized studies. J Antimicrob Chemother. 2005 Nov;56(5):923-9. doi: 10.1093/jac/dki355. Epub 2005 Sep 29.
citation: Stevens DL, Herr D, Lampiris H, Hunt JL, Batts DH, Hafkin B. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis. 2002 Jun 1;34(11):1481-90. doi: 10.1086/340353. Epub 2002 May 13.