Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant Pseudomonas aeruginosa: A ten-year update

Ijeoma Okoliegbe; Karolin Hijazi; Kim  Cooper; Corinne Ironside; Ian Gould

doi:10.1128/AAC.02483-20

Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant Pseudomonas aeruginosa: A ten-year update

Ijeoma Okoliegbe^* (Corresponding Author), Karolin Hijazi, Kim Cooper, Corinne Ironside, Ian Gould

^*Corresponding author for this work

Aberdeen Royal Infirmary

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Abstract

Background: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa. Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti23 pseudomonals agents and suggest their most synergistic antimicrobial combinations. ii) to determine antimicrobial resistance rates and study inherent trends of antimicrobials over ten years.Methods: A total of 721 multidrug-resistant P. aeruginosa isolates from 183 patients were collated over the study period. Antimicrobial susceptibility and combination testing were carried out using the Etest method. The results were further assessed using the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI).Results: Resistance to almost all antimicrobial agents maintained a similar level during the studied period. Colistin (p<0.001) and tobramycin (p=0.001) were the only antimicrobials with significant increasing isolate susceptibility while an increasing resistance trend was observed for levofloxacin. The most active antimicrobials were colistin, ceftolozane/tazobactam, ceftazidime/avibactam, and gentamicin. All combinations with β-lactam+β-lactamase inhibitors produced some synergistic results. Ciprofloxacin+ceftolozane/tazobactam (40%) and amikacin+ceftazidime (36.7%) were the most synergistic combinations while colistin combinations gave the best median SPBI (50.11). Conclusions: This study suggests that effective fluoroquinolone stewardship should be employed for CF patients. It also presents in vitro data to support the efficacy of novel combinations for use in the treatment of chronic P. aeruginosa infections.

Original language	English
Article number	e02483-20
Number of pages	10
Journal	Antimicrobial Agents and Chemotherapy
Volume	65
Issue number	6
Early online date	5 Apr 2021
DOIs	https://doi.org/10.1128/AAC.02483-20
Publication status	Published - 18 May 2021

Bibliographical note

Acknowledgements
The authors would like to thank the laboratories and clinicians who use the Cystic Fibrosis Antibiotics Susceptibility testing service (CFASS) for their support in sending samples. CFASS is an adult patient testing facility funded by the National Services Division of the Common Services Agency. IMG serves as a consultant to and/ speaker to Pfizer and MSD. All other authors declare no competing interests.

Keywords

Pseudomonas aeruginosa
Cystic Fibrosis
Antimicrobial susceptibility testing
Synergy testing
Etest

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Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant Pseudomonas aeruginosa: A ten-year update. / Okoliegbe, Ijeoma (Corresponding Author); Hijazi, Karolin; Cooper, Kim et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 65, No. 6, e02483-20, 18.05.2021.

Research output: Contribution to journal › Article › peer-review

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AU - Cooper, Kim

AU - Ironside, Corinne

AU - Gould, Ian

N1 - Acknowledgements The authors would like to thank the laboratories and clinicians who use the Cystic Fibrosis Antibiotics Susceptibility testing service (CFASS) for their support in sending samples. CFASS is an adult patient testing facility funded by the National Services Division of the Common Services Agency. IMG serves as a consultant to and/ speaker to Pfizer and MSD. All other authors declare no competing interests.

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N2 - Background: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa. Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti23 pseudomonals agents and suggest their most synergistic antimicrobial combinations. ii) to determine antimicrobial resistance rates and study inherent trends of antimicrobials over ten years.Methods: A total of 721 multidrug-resistant P. aeruginosa isolates from 183 patients were collated over the study period. Antimicrobial susceptibility and combination testing were carried out using the Etest method. The results were further assessed using the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI).Results: Resistance to almost all antimicrobial agents maintained a similar level during the studied period. Colistin (p<0.001) and tobramycin (p=0.001) were the only antimicrobials with significant increasing isolate susceptibility while an increasing resistance trend was observed for levofloxacin. The most active antimicrobials were colistin, ceftolozane/tazobactam, ceftazidime/avibactam, and gentamicin. All combinations with β-lactam+β-lactamase inhibitors produced some synergistic results. Ciprofloxacin+ceftolozane/tazobactam (40%) and amikacin+ceftazidime (36.7%) were the most synergistic combinations while colistin combinations gave the best median SPBI (50.11). Conclusions: This study suggests that effective fluoroquinolone stewardship should be employed for CF patients. It also presents in vitro data to support the efficacy of novel combinations for use in the treatment of chronic P. aeruginosa infections.

AB - Background: Antimicrobial combination therapy is a time/resource- intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by P. aeruginosa. Ten years ago the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam+β-lactamase inhibitor antimicrobial combinations. The aims of this study were i) to compare in vitro activity of these new antimicrobials with other anti23 pseudomonals agents and suggest their most synergistic antimicrobial combinations. ii) to determine antimicrobial resistance rates and study inherent trends of antimicrobials over ten years.Methods: A total of 721 multidrug-resistant P. aeruginosa isolates from 183 patients were collated over the study period. Antimicrobial susceptibility and combination testing were carried out using the Etest method. The results were further assessed using the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI).Results: Resistance to almost all antimicrobial agents maintained a similar level during the studied period. Colistin (p<0.001) and tobramycin (p=0.001) were the only antimicrobials with significant increasing isolate susceptibility while an increasing resistance trend was observed for levofloxacin. The most active antimicrobials were colistin, ceftolozane/tazobactam, ceftazidime/avibactam, and gentamicin. All combinations with β-lactam+β-lactamase inhibitors produced some synergistic results. Ciprofloxacin+ceftolozane/tazobactam (40%) and amikacin+ceftazidime (36.7%) were the most synergistic combinations while colistin combinations gave the best median SPBI (50.11). Conclusions: This study suggests that effective fluoroquinolone stewardship should be employed for CF patients. It also presents in vitro data to support the efficacy of novel combinations for use in the treatment of chronic P. aeruginosa infections.

KW - Pseudomonas aeruginosa

KW - Cystic Fibrosis

KW - Antimicrobial susceptibility testing

KW - Synergy testing

KW - Etest

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DO - 10.1128/AAC.02483-20

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SN - 0066-4804

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JO - Antimicrobial Agents and Chemotherapy

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IS - 6

M1 - e02483-20

ER -

Trends of antimicrobial resistance and combination susceptibility testing of cystic fibrosis multidrug-resistant Pseudomonas aeruginosa: A ten-year update

Abstract

Bibliographical note

Keywords

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