an open-label, randomized, and comparative study to evaluate the efficacy and safety of cefoperazone/sulbactam in comparison to cefepime for the treatment of hospital-acquired pneumonia and healthcare-associated pneumonia

Conditions: Pneumonia

Summary: this is a phase iii, multi-center, open-label, comparative and randomized study in evaluating the efficacy and safety of cefoperazone/sulbactam versus cefepime for the treatment of hospital-acquired pneumonia and healthcare-associated pneumonia. the investigator will determine the total duration of study therapy, as clinically indicated. the minimum duration of study therapy will be 7 days and the maximum allowable duration of study therapy will be 21 days.

patients fulfill inclusion/exclusion criteria will be randomly assigned (in a 1:1 ratio)to receive intravenous cefoperazone/sulbactam or intravenous cefepime for 7\~21days. vitamin k1 10mg will be administered to cefoperazone/sulbactam group every 24 hours. the assessment of clinical sign and symptoms of pneumonia and microbiological tests will be performed at early post-therapy visit and test-of-cure visit.

Eligibility criteria:
inclusion criteria: * male or female patients aged ≧18 years old * patients with nosocomial bacterial pneumonia at least 48 hours after hospitalization or patients with healthcare-associated pneumonia(hcap\*). * clinical findings at least two of the following signs: 1. cough 2. fever: axillary temperature \> 37.5℃ or tympanic temperature \> 38.5℃ 3. hypothermia: axillary temperature \< 34℃ or tympanic temperature \< 35℃ 4. purulent sputum production or respiratory secretion 5. total peripheral white blood cell (wbc) count \> 10,000/mm3; or \> 15% band forms, regardless of total peripheral white count; or leucopenia with total wbc \< 4500/mm3 6. auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony) 7. hypoxemia (defined as a partial o2 pressure \<60 mmhg while the patient was breathing normal air or a decrease in the partial o2 pressure of ≧25% from an initial value) * radiographic findings the chest radiograph should show the presence of a new or progressive infiltration on the chest x-ray film * microbiologic criteria if sputum specimen is available and collected, both tests are mandatory with at least one of the following results is positive: (1) within 24 hours prior to, or at the time of enrollment, all patients should have had a culture and susceptibility testing of respiratory secretions or sputum to study drugs (2)gram stain of respiratory secretions or sputum * patient must be able to sign a written informed consent form prior to the start of the study procedures. if any patient is unable to give consent, it must be obtained from the patient's legal representative * subject has not received more than 24 hours of a parenteral antibacterial drug for the current pneumonia. if subject has received more than 24 hours of a parenteral antibacterial drug, he/she must be declared as treatment failure. exclusion criteria: * woman who are pregnant (determined by urine test) or lactating state * patients with known bronchial obstruction or a history of postobstructive pneumonia. (this does not exclude patients who have chronic obstructive pulmonary disease) * a neutrophil count \<1000/mm3 * patients with pneumonia due to viral, fungal, or mycobacterial infection. * patients who were known to have been infected with human immunodeficiency virus * documented legionella pneumonia * patients were infected with gram negative (g-) microorganism known to be resistant to one of the study antibiotics during trial * subjects with sputum gram stain of pmn\>25, epithelial cell \<10, and gram positive (g+) cocci in cluster predominant and phagocytosis * patients who have received any other investigational drug within 30 days prior to enrollment * patients who have received medications like cefoperazone, cefoperazone/sulbactam and cefepime within 30 days prior to enrollment * patients with abnormal pre-therapy laboratory data: aspartate aminotransferase (ast), alanine aminotransferase (alt) ≧ 3x uln (upper limit of normal); or serum creatinine, urea nitrogen \> 3x uln * a history of hypersensitivity to penicillins, cephalosporins, carbapenems or j-lactam/j-lactamase inhibitors * severe disease (eg. septic shock, acute respiratory distress syndrome, and multiple organ failure) which may limit survival during therapy and follow-up period, or confound the results of the study as judged by the investigator

Keywords: pneumonia