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. 2021 Jun;34(3):228-237.
doi: 10.37201/req/019.2021. Epub 2021 Mar 1.

Antimicrobial activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa recovered during the Study for Monitoring Antimicrobial Resistance Trends (SMART) program in Spain (2016-2018)

R Cantón  1 , E Loza, R M Arcay, E Cercenado, F J Castillo, R Cisterna, L Gálvez-Benítez, F González Romo, A Hernández-Cabezas, J Rodríguez-Lozano, A I Suárez-Barrenechea, F Tubau, J Díaz-Regañón, D López-Mendoza; SMART-Spain Working Group
Affiliations

Antimicrobial activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa recovered during the Study for Monitoring Antimicrobial Resistance Trends (SMART) program in Spain (2016-2018)

R Cantón et al. Rev Esp Quimioter. 2021 Jun.

Abstract
in English, Spanish

Objective: To analyse the susceptibility to ceftolozane-tazobactam and comparators in Enterobacterales and Pseudomonas aeruginosa isolates recovered from intraabdominal (IAI), urinary (UTI), respiratory (RTI) and bloodstream infection (BSI) in the SMART (Study for Monitoring Antimicrobial Resistance Trends) study.

Methods: The susceptibility of 5,351 isolates collected in 11 Spanish hospitals (2016-2018) were analysed (EUCAST-2020 criteria) by broth microdilution and were phenotypically studied for the presence of extended-spectrum beta-lactamases (ESBL). Ceftolozane-tazobactam and/or carbapenem resistant isolates were genetically characterized for ESBL and carbapenemases.

Results: Escherichia coli was the most frequent pathogen (49.3% IAI, 54.9% UTI, 16.7% RTI and 50% BSI), followed by Klebsiella pneumoniae (11.9%, 19.1%, 13.1% and 15.4%, respectively). P. aeruginosa was isolated in 9.3%, 5.6%, 32% and 9%, respectively. The frequency of isolates with ESBLs (2016-2017) was: 30.5% K. pneumoniae, 8.6% E. coli, 2.3% Klebsiella oxytoca and 0.7% Proteus mirabilis. Ceftolozane-tazobactam was very active against non-ESBL-(99.3% susceptible) and ESBL-(95.2%) producing E. coli being less active against K. pneumoniae (98% and 43.1%, respectively) isolates. CTX-M-15 was the most prevalent ESBL in E. coli (27.5%) and K. pneumoniae (51.9%) frequently associated with OXA-48-like carbapenemase. Overall, 93% of P. aeruginosa isolates were susceptible to ceftolozane-tazobactam, preserving this activity (>75%) in isolates resistant to other beta-lactams except in those resistant to meropenen or ceftazidime-avibactam. GES-5, PER-1, VIM-1/2 were the most prevalent enzymes in isolates resistant to ceftolozane-tazobactam.

Conclusions: Ceftolozane-tazobactam showed high activity rates against isolates recovered in the SMART study although it was affected in K. pneumoniae and P. aeruginosa isolates with ESBL and/or carbapenemases.

Objetivo: Analizar la sensibilidad a ceftolozano-tazobactam y antimicrobianos comparadores en Enterobacterales y Pseudomonas aeruginosa procedentes de infecciones intraabdominales (IIA), urinarias (ITU) y respiratorias (ITR) y bacteriemias del estudio SMART (Study for Monitoring Antimicrobial Resistance Trends).

Métodos: Se analizó (EUCAST-2020) la sensibilidad de 5.351 aislados recogidos en 11 hospitales españoles (2016-2018) mediante microdilución en caldo y se estudió fenotípicamente la presencia de betalactamasas de espectro extendido (BLEE). En aislados resistentes a ceftolozano-tazobactam y/o carbapenémicos se caracterizaron las BLEE y carbapenemasas.

Resultados: . Escherichia coli fue el patógeno más frecuente (49,3% IIA, 54,9% ITU, 16,7% ITR y 50% bacteriemia), seguido de Klebsiella pneumoniae (11,9%, 19,1%, 13,1% y 15,4%, respectivamente). P. aeruginosa se aisló en el 9,3%, 5,6%, 32% y 9%, respectivamente. La frecuencia de aislados con BLEE (2016-2017) fue: 30,5% K. pneumoniae, 8,6% E. coli, 2,3% Klebsiella oxytoca y 0,7% Proteus mirabilis. Ceftolozanotazobactam fue muy activo en E. coli no productor (sensibilidad 99,3%) y productor de BLEE (95,2%) y menos activo en K. pneumoniae (98% y 43,1%, respectivamente). CTX-M-15 fue la BLEE más prevalente en E. coli (27,5%) y K. pneumoniae (51,9%) frecuentemente asociada con OXA-48-like. Un 93% de los aislados de P. aeruginosa fueron sensibles a ceftolozanotazobactam, que mantuvo su actividad (>75%) en aislados resistentes a otros betalactámicos excepto en los resistentes a meropenen o ceftazidima-avibactam. GES-5, PER-1, VIM-1/2 fueron las enzimas más prevalentes en aislados resistentes a ceftolozano-tazobactam.

Conclusiones: Ceftolozano-tazobactam mostró elevada sensibilidad frente a los aislados del estudio SMART, aunque disminuyó en K. pneumoniae y P. aeruginosa con BLEE y/o carbapenemasas.

Keywords: Ceftolozane-tazobactam; Enterobacterales; Pseudomonas aeruginosa; surveillance study.

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Conflict of interest statement

RC and EC have collaborated in educational meetings sponsored by MSD, Spain and Pfizer. He has also research grants from MSD. JDR and DLM are employees of MSD, Spain. All other authors declare that they have no conflicts of interest regarding this publication.

Figures

Figure 1
Figure 1
MIC distribution of ceftolozane-tazobactam in non-ESBL and ESBL producing Escherichia coli (A) and Klebsiella pneumoniae (B) isolates recovered in Spain in the SMART study (2016 and 2017). Ceftolozane-tazobactam susceptibility was calculated using EUCAST-2020 breakpoints [18]. Breakpoints are indicated with a line.
Figure 2
Figure 2
MIC distribution of ceftolozane-tazobactam in Pseudomonas aeruginosa isolates recovered in Spain in the SMART study (2016-2018). Ceftolozane-tazobactam susceptibility was calculated using EUCAST-2020 breakpoints [18]. Breakpoints are indicated with a line.
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References

    1. Friedman ND, Temkin E, Carmeli Y. The negative impact of antibiotic resistance. Clin Microbiol Infect 2016; 22:416–22. doi: 10.1016/j.cmi.2015.12.002. - DOI - PubMed
    1. Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, et al. . Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis. 2019; 19:56-66. doi: 10.1016/S1473-3099(18)30605-4. - DOI - PMC - PubMed
    1. Cantón R, Huarte R, Morata L, Trillo-Mata JL, Muñoz R, González J, et al. . Determining the burden of infectious diseases caused by carbapenem-resistant gram-negative bacteria in Spain. Enferm Infecc Microbiol Clin. 2020: S0213-005X(20)30191-9. doi: 10.1016/j.eimc.2020.04.009. - DOI - PubMed
    1. World Health Organization Global . Action Plan on Antimicrobial Resistance. 2015. https://www.who.int/antimicrobial-resistance/publications/global-action-...) - PubMed
    1. Interagency Coordination Group on Antimicrobial Resistance . No time to wait: securing the future from drug-resistant infections. Report of the Secretary-General of the United Nations. April 2019. (https://www.who.int/antimicrobial-resistance/interagency-coordination-gr...)

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