TY - JOUR

T1 - Antimicrobial resistance of Pseudomonas aeruginosa in a cystic fibrosis population after introduction of a novel cephalosporin/β-lactamase inhibitor combination

AU - Katzenstein, Terese L.

AU - Faurholt-Jepsen, Daniel

AU - Qvist, Tavs

AU - Jensen, Peter Østrup

AU - Pressler, Tacjana

AU - Johansen, Helle Krogh

AU - Kolpen, Mette

N1 - Publisher Copyright: © 2023 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.

PY - 2023

Y1 - 2023

N2 - Ceftolozane-tazobactam is a new β-lactam/β-lactamase inhibitor combination approved by the U.S. Food and Drug Administration in 2019 for the treatment of hospital-acquired and ventilator-associated pneumonia. The combination is a particularly potent inhibitor of penicillin-binding proteins with higher affinity than other β-lactam agents. Persons with cystic fibrosis (pwCF) often harbour resistant Gram-negative bacteria in the airways and need antibiotics to prevent declining lung function. To test whether the introduction of ceftolozane-tazobactam in the period 2015–2020 led to a bacterial population level increase in cephalosporin resistance in a Danish CF population. In vitro, activity of ceftolozane-tazobactam was evaluated by susceptibility testing of clinical Pseudomonas aeruginosa isolated from pwCF from January 1, 2015, to June 1, 2020. Six thousand three hundred thirty two isolates collected from 210 adult pwCF were included. Thirty pwCF were treated with ceftolozane-tazobactam at least once. Ceftolozane-tazobactam exposure did not increase cephalosporin resistance on an individual or population level. However, resistance to ceftolozane-tazobactam was recorded despite no prior exposure in four pwCF. Compared to ceftazidime, ceftolozane-tazobactam had a better in vitro activity on P. aeruginosa. The percentage of non-mucoid P. aeruginosa isolates susceptible to ceftolozane-tazobactam were higher or equal to 5 other β-lactams. Ceftolozane-tazobactam expands the armamentaria against P. aeruginosa with acceptable levels for a selection of drug resistance.

AB - Ceftolozane-tazobactam is a new β-lactam/β-lactamase inhibitor combination approved by the U.S. Food and Drug Administration in 2019 for the treatment of hospital-acquired and ventilator-associated pneumonia. The combination is a particularly potent inhibitor of penicillin-binding proteins with higher affinity than other β-lactam agents. Persons with cystic fibrosis (pwCF) often harbour resistant Gram-negative bacteria in the airways and need antibiotics to prevent declining lung function. To test whether the introduction of ceftolozane-tazobactam in the period 2015–2020 led to a bacterial population level increase in cephalosporin resistance in a Danish CF population. In vitro, activity of ceftolozane-tazobactam was evaluated by susceptibility testing of clinical Pseudomonas aeruginosa isolated from pwCF from January 1, 2015, to June 1, 2020. Six thousand three hundred thirty two isolates collected from 210 adult pwCF were included. Thirty pwCF were treated with ceftolozane-tazobactam at least once. Ceftolozane-tazobactam exposure did not increase cephalosporin resistance on an individual or population level. However, resistance to ceftolozane-tazobactam was recorded despite no prior exposure in four pwCF. Compared to ceftazidime, ceftolozane-tazobactam had a better in vitro activity on P. aeruginosa. The percentage of non-mucoid P. aeruginosa isolates susceptible to ceftolozane-tazobactam were higher or equal to 5 other β-lactams. Ceftolozane-tazobactam expands the armamentaria against P. aeruginosa with acceptable levels for a selection of drug resistance.

KW - Ceftolozane + tazobactam

KW - cystic fibrosis

KW - Pseudomonas aeruginosa

U2 - 10.1111/apm.13331

DO - 10.1111/apm.13331

M3 - Journal article

C2 - 37294911

AN - SCOPUS:85161305842

VL - 131

SP - 419

EP - 425

JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica

SN - 0903-4641

IS - 8

ER -