Linezolid Alone or Combined With Carbapenem Against Methicillin-resistant Staphylococcus Aureus (MRSA) in Ventilator-associated Pneumonia

Pneumonia, Ventilator-Associated Clinical Trial

Official title:

Linezolid Alone or Combined With Carbapenem Against Methicillin-resistant Staphylococcus Aureus (MRSA) in Vitro and in Ventilator-associated Pneumonia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01356472
• Other study ID #: MRSA-VAP YANG ZT CN
• Status: Not yet recruiting
• Phase: Phase 4
• First received: May 17, 2011
• Last updated: May 18, 2011
• Start date: June 2011

Study information

• Verified date: April 2011
• Source: Ruijin Hospital
• Contact: Zhi-Tao Yang, M.D.
• Phone: 008613611965436
• Email: yangzhitao[@]hotmail.fr
• Is FDA regulated: No
• Health authority: China: Ethics CommitteeChina: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Methicillin-resistant Staphylococcus Aureus
• Pneumonia
• Pneumonia, Ventilator-Associated
• Staphylococcal Infections

Intervention

Drug:
• Imipenem/cilastatin
the intervention group was designed for combined linezolid plus imipenem for treating MRSA VAP

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Ruijin Hospital	Pfizer

References & Publications (5)

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. — View 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. — View 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. Epub 2001 Jan 26. — View 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. Epub 2005 Sep 29. — View 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. Epub 2002 May 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRSA eradication	The investigators study the efficacy of Linezolid combined with Imipenem to treat the MRSA VAP, the investigators proposed the 7th day's MRSA eradication would be better than Linezolid alone.	7 th day	No
Secondary	MRSA eradication		14th day	No
Secondary	mortality		28th day	No