Safety, Potential Efficacy, and Pharmacokinetics of PZ-601 in the Treatment of Complicated Skin and Skin Structure Infection

Exclusion Criteria

• •1. Female patients who are pregnant, lactating (breast milk feeding), or planning a pregnancy during the course of the study, or who are of child bearing potential and not using an acceptable method of birth control (ie, surgically sterile, intrauterine device, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive or condom in combination with contraceptive cream, jelly or foam)
• •2. Received more than 24 hours of systemic antibiotic therapy within 96 hours of initiation of study medication for the current episode of cSSSI, unless:
• •* there is evidence of clinical failure following at least 48 hours of prior, non-study systemic therapy OR
• •* there is microbiological evidence of failure (ie, Gram stain reveals WBC and at least one potential pathogen or isolation of an organism resistant to the prior therapy)
• •3. Concomitant conditions requiring antimicrobial therapy that would interfere with the evaluability of the condition under study
• •4. Anticipated need for prolonged antibiotic therapy (ie, \>14 days)
• •5. Topical use of antimicrobials (excluding vaginally or topically administered antifungal agents)
• •6. cSSSI known or suspected to be caused by fungal, parasitic or viral infections
• •7. cSSSI of the following categories:
• •* infected diabetic foot ulcers or decubitus ulcer
• •* multiple infected ulcers at distant sites
• •* involve an ischemic ulcer due to peripheral vascular disease
• •* presence of gangrene of any etiology
• •8. Necrotizing fasciitis or gas gangrene
• •9. Infections resulting from human or animal bites (excluding infections secondary to arthropod bites)
• •10. Known or suspected osteomyelitis or septic arthritis
• •11. Superinfected eczema or other chronic medical conditions (eg, atopic dermatitis, hidradentitis suppurativa) characterized by prominent signs of inflammation for an extended period even after successful bacterial eradication
• •12. Patients who have undergone more than two surgical interventions (defined as surgery that cannot be performed at the bedside) for treatment of cSSSI at the time of enrollment
• •13. Patients who are expected to require more than two surgical interventions (defined as surgery that cannot be performed at the bedside) for treatment of cSSSI during the first 48 hours following study enrollment
• •14. Infections complicated by the presence of prosthetic materials that will not be removed such as permanent intracardiac devices or joint replacement prosthesis
• •15. Moderately or severely impaired renal function with known creatinine clearance \<50 mL/min (based on the Cockcroft-Gault formula using ideal body weight)
• •16. ALT or AST \>3x upper limit of normal or bilirubin \>1.5x upper limit of normal (ULN)
• •17. Neutropenia defined as an absolute neutrophil count \<500/mm3
• •18. Thrombocytopenia defined as a platelet count \<50,000 cells/mm3
• •19. Infection with human immunodeficiency virus and a CD4 count known at the time of enrollment to be \<200 cells/mm3 or another Acquired Immune Deficiency Syndrome (AIDS)-defining illness
• •20. Requiring concomitant administration of systemic corticosteroids greater than 40 mg/day of prednisolone (or equivalent)
• •21. Treatment with cancer chemotherapy, radiotherapy, or potent, non-corticosteroid immunosuppressant drugs (eg, cyclosporine, azathioprine, tacrolimus, immune-modulating monoclonal antibody therapy, etc.) within the 3 months prior to study enrollment
• •22. Concomitant therapy with medications known to lower seizure threshold or those patients with a history of seizure disorder
• •23. Concomitant therapy with medications known to be associated with QTc prolongation potential (eg, Class IA and Class III anti-arrhythmic agents)
• •24. History or significant cardiac disease defined by the following:
• •* New York Heart Association (NYHA) Class III or IV heart failure
• •* History or risk of ventricular arrhythmia (excluding isolated premature ventricular contractions \[PVC's\] or consecutive PVC's \<10 beats), Torsades de Pointes, 2nd or 3rd degree AV block, or QTc interval \>470 mm/sec
• •25. History of any hypersensitivity or allergic reaction to beta-lactam drugs such as carbapenems, penicillins, or cephalosporins
• •26. History of any hypersensitivity or allergic reaction to vancomycin or history of Red Man Syndrome
• •27. Any planned medical intervention or personal event that might interfere with the ability to comply with the study requirements
• •28. Any condition that, in the opinion of the principal investigator, would compromise the safety of the patient or the quality of the data
• •29. Life expectancy of less than 3 months from the time of enrollment
• •30. Use of an investigational drug or device (ie, a drug or device without an FDA approved indication) within the previous 30 days
• •31. Prior participation in this protocol
• •32. Unable or unwilling to adhere to the study-specified procedures and restrictions