Linezolid in the Treatment of Hemodialysis Patients With Catheter-Related Gram-Positive Bloodstream Infections
Condition: Bacteremia; Gram-Positive Bacterial Infections
MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Bacteremia; Sepsis; Gram-Positive Bacterial Infections
Intervention: Cefazolin IV; Linezolid IV; Vancomycin (IV)
Intervention MeSH terms: Vancomycin; Cefazolin; Linezolid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will treat hemodialysis patients who have a central catheter that is thought to be
      infected with a specific bacteria (Gram positive bacteria).
    

Eligibility criteria:

        Inclusion Criteria:

          -  To be eligible for this study, a patient must provide informed consent and must meet
             all of the following criteria. No study procedures, including any baseline tests,
             should be performed until the patient (or parent/legally acceptable representative, if
             appropriate) legally signs the informed consent form.

          -  Male or female, 18 years of age or older and >= 40 kg body weight

          -  End-stage renal disease patients on hemodialysis with: A) Signs and symptoms of a
             localized catheter-related infection (eg tenderness and/or pain, erythema, swelling,
             purulent exudates within 2 cm of entry site); OR B) A body temperature of >= 38.0 C or
             < 36.0 C (oral equivalent); OR C) A Gram-positive blood culture. If the Gram-positive
             isolate is S. aureus, it must be cultured from at least 1 culture bottle from either
             the peripheral set or the catheter set of culture bottles. For all other Gram-positive
             pathogens (eg, coagulase-negative staphylococci), isolates need to be cultured from at
             least 2 culture bottles of which one must be from the peripheral set. There must be no
             other obvious source of the bacteremia

          -  Presence of at least one of the following systemic signs of infection (may be obtained
             up to 24 hours prior to baseline): *Hypotension, defined as systolic blood pressure
             <90 mmHg or its reduction by >= 40 mmHg from the patient's baseline, in the absence of
             other causes for hypotension; *Tachycardia defined as a pulse rate > 90 beats per
             minute; *Tachypnea defined as a respiratory rate > 20 breaths per minute or PACO2 <32
             torr; *White blood count >10,000 cells/mm3 or < 4,000 cells/mm3, or with a
             differential count showing >10% band neutrophil forms.

          -  Patients on hemodialysis with tunneled or nontunneled catheters including antibiotic
             coated hemodialysis catheters. Patients may have more than one concurrent catheter.

          -  Patients who are willing and able to comply with scheduled visits, treatment plan,
             laboratory tests and other study procedures

        Exclusion Criteria:

          -  Patients presenting with any of the following will not be included in this study:

          -  Catheter-related bloodstream infections caused by Gram-negative bacteria, fungi, mixed
             cultures of Gram negative bacteria and Gram positive bacteria or mixed cultures of
             Gram positive/negative bacteria and fungi

          -  Patients with evidence of other infections resulting in bacteremia, such as clinical
             or radiographic signs of osteomyelitis, endocarditis, skin/skin structure infection,
             pneumonia, urinary tract infection, joint infection, intraabdominal infection, septic
             thrombophlebitis or other infection

          -  Patients in whom the infected catheter cannot be removed

          -  Patients with permanent intravascular devices such as artificial vascular grafts,
             implantable pacemakers or defibrillators; intra-aortic balloon pumps, and left
             ventricular assist device; intravascular transplants such as prosthetic cardiac
             valves; or non-intravascular devices such as peritoneal dialysis catheters; or
             neurosurgical devices such as ventriculo-peritoneal shunts, intra-cranial pressure
             monitors, or epidural catheters, prosthetic cardiac valves, prosthetic vascular
             grafts, or other internal prosthesis

          -  Females of child-bearing potential who are unable or unwilling to take adequate
             contraceptive precautions, have a positive pregnancy result within 24 hours prior to
             study entry, are known to be pregnant, or are currently breastfeeding an infant

          -  Identification of a pathogen resistant to linezolid or vancomycin

          -  Patients who are unlikely to survive through the treatment period and evaluation

          -  Administration of a glycopeptide antibiotic within 5 days prior to enrollment.
             Administration of other potentially effective systemic Gram-positive antibiotics for
             more than 48 hours within 72 hours prior to enrollment unless the pathogen showed drug
             resistance

          -  Previous enrollment in this protocol

          -  Hypersensitivity to linezolid, vancomycin, gentamicin or one of their excipients (or
             aztreonam if non-bacteremic Gram-negative coverage is required)

          -  Concurrent use of another investigational medication or use within 30 days of study
             entry

          -  Patients with pressor and fluid-resistant hemodynamic compromise or pulmonary embolism