Clinical Study of Cefiderocol (S-649266) for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens
Clinical Study of Cefiderocol (S-649266) for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens
The primary objective of this study is to compare all-cause mortality at Day 14 in
 participants receiving cefiderocol with participants receiving the comparator, meropenem, in
 adults with hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial
 pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP) caused by
 Gram-negative pathogens.
Inclusion Criteria:

 -  Subjects 18 years or older at the time of signing informed consent

 -  Subjects who have provided written informed consent or their informed consent has been
 provided by a legally authorized representative

 -  Subjects who meet the clinical diagnosis criteria for hospital-acquired bacterial
 pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or
 healthcare-associated bacterial pneumonia (HCABP)

 -  All subjects must fulfill at least 1 of the following clinical criteria at screening:

 1. New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea,
 tachypnea (eg, respiratory rate > 25 breaths/minute), expectorated sputum
 production, or requirement for mechanical ventilation

 2. Hypoxemia (eg, a partial pressure of oxygen [PaO2] < 60 mm Hg while the subject
 is breathing room air, as determined by arterial blood gas [ABG], or worsening of
 the ratio of the PaO2 to the fraction of inspired oxygen [PaO2/FiO2])

 3. Need for acute changes in the ventilator support system to enhance oxygenation,
 as determined by worsening oxygenation (ABG or PaO2/FiO2) or needed changes in
 the amount of positive end-expiratory pressure

 4. New onset of or increase in (quantity or characteristics) suctioned respiratory
 secretions, demonstrating evidence of inflammation and absence of contamination

 -  All subjects must have at least 1 of the following signs:

 1. Documented fever (ie, core body temperature [tympanic, rectal, esophageal] ≥ 38°C
 [100.4°F], oral temperature ≥ 37.5°C, or axillary temperature ≥ 37°C)

 2. Hypothermia (ie, core body temperature [tympanic, rectal, esophageal] ≤ 35°C
 [95.0°F], oral temperature ≤ 35.5°C and axillary temperature ≤ 36°C)

 3. Leukocytosis with a total peripheral white blood cell (WBC) count ≥ 10,000
 cells/mm³

 4. Leukopenia with total peripheral WBC count ≤ 4500 cells/mm³

 5. Greater than 15% immature neutrophils (bands) noted on peripheral blood smear

 -  All subjects must have a chest radiograph during screening showing the presence of new
 or progressive infiltrate(s) suggestive of bacterial pneumonia. A computed tomography
 (CT) scan in the same time window showing the same findings could also be acceptable

 -  All subjects must have a suspected Gram-negative infection involving the lower
 respiratory tract

 Exclusion Criteria:

 -  Subjects who have known or suspected community-acquired bacterial pneumonia (CABP),
 atypical pneumonia, viral pneumonia, or chemical pneumonia (including aspiration of
 gastric contents, inhalation injury)

 -  Other exclusions based on the prescribing information of meropenem or linezolid, prior
 antibiotic usage, age, and pregnancy.