Comparison of Teicoplanin and Vancomycin in Initial Empirical Antibiotic Regimen for Febrile Neutropenic Patients

• The primary efficacy parameter will be the Response according to the following
• definitions:
• Success: All signs and symptoms have resolved and there were no additional
• systemic antibiotics added to the study drug regimen. There were no systemic
• antifungals nor antivirals/antiparasitic drugs added within 72 hrs of start of
• study drug. For MDIs, there was no recurrence of the causative pathogen within
• 4 to 6 days after study drug discontinuation. A patient with recurrent fever
• after the EOT visit will be defined as a success as long as there is no
• additional anti-Gram(+) drugs administered within 4 to 6 days after study drug
• discontinuation.
• Failure: Death attributed to infection; clinical deterioration or microbiologic
• failure on study drug regimen; persistence of symptoms; addition of new anti-Gram(+)
• agent for persistent symptoms or new infection; resistant isolate. Addition of
• an antiviral, an antiparasitic (for a specific indication) or of an antifungal
• drug will not be considered as a failure if added 72hrs after start of study
• medication. Indeterminate: Absence of criteria enabling success/ failure a
• assessment (this definition apply to patients who are randomized but not treated
• or to patients lost to follow-up).Whenever a patient is categorized a failure,
• this classification will apply to subsequent assessments.

• Safety will be assessed for all randomized patients who received at least one dose
• of study medication. The assessment will include the incidence rate of clinical
• adverse events, and changes in laboratory values from baseline measurements. The
• incidence of adverse events by body system will be summarized by causality,
• severity, and relationship to study drug. Summaries of adverse clinical events
• ill also be presented separately by gender, race and age group.

• Infection
• Febrile Neutropenia

• Drug: Teicoplanin
• Drug: Vancomycin

• Active Comparator: 1, Vancomycin
  Vancomycin
  Intervention: Drug: Vancomycin
• Active Comparator: 2, Teicoplanin
  Teicoplanin
  Intervention: Drug: Teicoplanin

Inclusion Criteria:

• Will initiate study drug treatment in the hospital;
• Has a life expectancy exc. 1 month.Is male or a non-pregnant, non-lactating female, who is post-menopausal, surgically sterilized; or has been using one or more birth control methods for at least two months prior to study entry.
• Effective contraception must continue for at least 30 days after treatment discontinuation;

Exclusion Criteria:

• Has a history of suspected or documented Type I hypersensitivity reaction (e.g. anaphylactic or anaphylactoid shock, respiratory distress from bronchospasm or rash) to glycopeptides (vancomycin or teicoplanin), aminoglycosides, b-lactams or cephalosporins
• Has renal dysfunction requiring dialysis ;
• Has neutropenia associated with a syndrome that is not generally thought to be associated with a high risk of bacterial infection (e.g., chronic benign neutropenia);
• Is in blast crisis of chronic myeloid leukemia;
• Has a known underlying immunocompromising disease likely to interfere with the evaluation of therapeutic response, such as infection with human immunodeficiency virus (HIV) ;
• Had isolation and identification of a specific pathogen suspected to be responsible for fever ;Has documented colonization with vancomycin-resistant Enterococcus faecium or with Enterococcus faecalis
• Had received more than one dose of a systemic (whether oral or parenteral) antibiotic within 3 calendar days preceding the initial therapy for this episode of fever;
• Has received oral vancomycin for prophylaxis of Gram-positive infection;
• Requires addition of anti-viral, anti-anaerobic or anti-fungal coverage at the same time as study medication; however, antiviral or antifungal prophylaxis is allowed, provided that it is not started at the same time than study medication.
• Has suspected, invasive fungal disease (e.g. image of necrotic pneumonia), peri-rectal infection, liver abscess, or necrotizing enterocolitis (typhlitis).
• Had a negative serum or urine laboratory pregnancy test (for all women except those post-menopausal or surgically sterilized).
• The patient has one of the following:Leukemia, lymphoma, Hodgkin's disease, solid tumors or who had undergone bone marrow transplantation (for any reason)
• Had neutropenia at the time of initiation of initial empiric antibiotic therapy, defined as <500 neutrophils/mm3 of blood; or if ³500 but <1,000 neutrophils/mm3 and expected to fall below 500 neutrophils/mm3 within 48 hours.
• Has at least one of the following conditions:
• clinically obvious, serious catheter-related infections. For a patient with documented catheter-related infection due to an organism other than coagulase negative staphylococci, the catheter has been removed within 24 hours of identification (removal over a guidewire is permitted).
• Intensive chemotherapy that produces substantial mucosal damage (i.e., high-dose cytarabine (> 1 g/m2/day, which increases the risk for penicillin resistant streptococcal infections, particularly those due to viridans streptococci);
• prophylaxis with quinolones before the onset of the febrile episode; known colonization with pneumococci that are resistant to penicillin and -cephalosporins or methicillin-resistant S. aureus; a blood culture positive for gram-positive bacteria before final identification and susceptibility