clinical study of cefiderocol (s-649266) for the treatment of nosocomial pneumonia caused by gram-negative pathogens

Conditions: Healthcare-associated Pneumonia (HCAP); Hospital Acquired Pneumonia (HAP); Ventilator Associated Pneumonia (VAP)

Summary: 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.


Eligibility criteria:
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.

Keywords: hospital-acquired pneumonia (hap) s-649266 linezolid meropenem healthcare-associated pneumonia (hcap) nosocomial pneumonia ventilator-associated pneumonia (vap) gram-negative pathogens pneumonia cefiderocol