Comparative in vitro antipseudomonal activity of ceftolozane/tazobactam against Pseudomonas aeruginosa isolates from children with cystic fibrosis

The respiratory tract of patients with Cystic fibrosis (CF) is often chronically or persistently infected by the opportunistic pathogens like Pseudomonas aeruginosa (PA)[1], [2], [3]. CF pulmonary exacerbations are often considered due to such infections, so patients are exposed to repeated courses of antibiotics, selecting for PA resistant to multiple antipseudomonal antimicrobials[4], [5], [6]. The treatment of CF pulmonary exacerbation due to chronic/recurrent infections with resistant PA isolates that can form biofilms becomes challenging[6]. To meet this challenge in pediatric patients with CF, new antipseudomonal drugs with potent activity against resistant pathogens may be used off-label in terms of age, indication, and dosage[3, 7].

Ceftolozane/tazobactam (C/T) (Merck & Co., Inc, USA) is a relatively new antipseudomonal cephalosporin/ beta-lactamase inhibitor combination antibiotic approved by the FDA in 2014[8, 9]. Ceftolozane itself inhibits cell wall synthesis, thereby exerting bactericidal activity; tazobactam inhibits many beta-lactamases, allowing ceftolozane's bactericidal activity against many ESBL-producing Enterobacterales and Pseudomonas species[8].

Several studies have shown an increased activity of C/T against resistant Pseudomonas isolates[4, 5, [10], [11], [12], [13], [14]]. A few studies have compared C/T with other antipseudomonal drugs, mostly on limited number of isolates[15], [16], [17], [18], [19] from general populations. Comparative data are even less complete for C/T antipseudomonal activity versus other major antipseudomonal drugs among PA isolates derived specifically from pediatric patients with CF[6].

The primary objective of this multi-center study was to evaluate and compare the in vitro activity of C/T to ten comparator antimicrobials against PA isolates obtained from pediatric patients with CF from 2015 to 2020 at three freestanding pediatric centers in the United States (one each from the Southwest, Midwest, and Northwest).

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