Abstract
Background: Gram-negative nosocomial pneumonia (NP), including hospital-acquired bacterial pneumonia (HABP), ventilated HABP (vHABP), and ventilator-associated bacterial pneumonia (VABP), is a significant cause of morbidity and mortality. Common pathogens, including Enterobacterales and Pseudomonas aeruginosa are highly prevalent in healthcare settings and have few effective treatment options due to high rates of antibacterial resistance. Resistant pathogens are associated with significantly worse outcomes and higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials of patients with NP. This review aimed to collate data on C/T use for HABP/vHABP/VABP infections in real-world clinical practice. Methods: This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative respiratory tract infections (RTIs) up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.Results: Thirty-three studies comprising 658 patients were identified. Pneumonia was the most common infection C/T was used to treat (85%), with a smaller number of unspecified RTIs (9%) and tracheobronchitis (5%) reported. Data on severity of illness and comorbidity were inconsistently reported. The majority of patients had respiratory infections caused by P. aeruginosa (92.8%), of which 88.1% were multidrug-resistant (including extensively drug-resistant or pandrug-resistant). Examination of these studies demonstrated an increase in the percentage of patients receiving the recommended dose of C/T for respiratory infections (3 g q8h or renal impairment-adjusted) over time (36.8% of patients in 2017 to 71.5% in 2020). Clinical success rates ranged from 51.4–100%, with 10 studies (55.6% of studies reporting clinical success) reporting clinical success rates of >70%; microbiological success rates ranged from 57.0–100.0%, with three studies (60.0% of studies reporting microbiological success) reporting microbiological success rates of >70%. Thirty-day mortality ranged from 0.0–33.0%, with nine studies (90% of studies reporting mortality) reporting 30-day mortality of <30%. Conclusions: The studies identified in this review demonstrate that C/T shows similar outcomes as those seen in clinical trials, despite the higher frequency of multidrug-resistant pathogens, and comorbidities/conditions that may have been excluded from the trials.
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