Karbapenem dirençli Pseudomonas aeruginosa suşlarına karşı sefiderokol, imipenem/relebaktam ve diğer antibiyotiklerin in vitro etkinliklerinin karşılaştırılması

Amaç: Karbapenemler ciddi Pseudomonas aeruginosa enfeksiyonlarının tedavisinde sıklıkla kullanılmaktadır. Bununla birlikte, karbapenemlere dirençli P. aeruginosa izolatları son yıllarda artış göstermiş ve bir halk sağlığı tehdidi haline gelmiştir. Bu çalışmanın amacı çeşitli klinik örneklerden izole edilen karbapenem dirençli P. aeruginosa suşlarına karşı sefiderokol, imipenem/relebaktam ve diğer antibiyotiklerin in vitro etkinliklerinin karşılaştırılmasıdır. Yöntem: Çalışmaya 92 adet karbapenem dirençli P. aeruginosa izolatı (CLSI ve EUCAST kriterlerine göre tamamı imipenem dirençli; CLSI kriterlerine göre tamamı meropenem dirençli; EUCAST kriterlerine göre 84’ü meropenem dirençli, 8’i ‘I - duyarlı, yüksek dozda’) dahil edilmiştir. İzolatların sefiderokol, imipenem/relebaktam, imipenem, aztreonam, siprofloksasin, levofloksasin ve gentamisine karşı duyarlılıklarının saptanması amacıyla disk difüzyon testi kullanılmıştır. İzolatların meropenem, piperasilin/tazobaktam ve seftazidime karşı duyarlılıklarının saptanması amacıyla gradiyent difüzyon testi kullanılmış, CLSI ve EUCAST kriterlerine göre değerlendirilmiştir. Bulgular: Test edilen antibiyotikler arasında, izolatlara karşı in vitro etkinliği en yüksek antibiyotik sefiderokol olarak bulunmuştur. CLSI kriterlerine göre izolatların tamamı sefiderokole duyarlı olarak saptanırken; EUCAST kriterlerine göre izolatların %97,8’i sefiderokole duyarlı olarak saptanmıştır. Sefiderokolden sonra etkinliği en yüksek antibiyotik gentamisin olup izolatların %87,0’si duyarlıdır. CLSI kriterlerine göre izolatların %66,3’ü, EUCAST kriterlerine göre ise %73,9’u imipenem/relebaktama duyarlı bulunmuştur. İzolatlara karşı in vitro etkinliği en düşük antibiyotik levofloksasindir. CLSI ve EUCAST kriterlerine göre izolatların sırasıyla %70,7’si ve %82,6’sı levofloksasine dirençlidir. Sonuç: Sefiderokol karbapenem dirençli P. aeruginosa enfeksiyonlarının tedavisi için bir seçenek olabilir.

Comparison of in vitro activities of cefiderocol, imipenem/relebactam and other antibiotics against carbapenem-resistant Pseudomonas aeruginosa isolates

Objective: Carbapenems are commonly used in treatment of severe infections caused by Pseudomonas aeruginosa. However, carbapenem-resistant P. aeruginosa isolates have increased in recent years and have become a public health threat. The objective of this study was to compare in vitro activities of cefiderocol, imipenem/relebactam and other antibiotics against clinical isolates of carbapenem-resistant P. aeruginosa. Methods: A total of 92 carbapenem-resistant P. aeruginosa isolates (all isolates were resistant to imipenem according to both CLSI and EUCAST; all isolates were resistant to meropenem according to CLSI; 84 isolates were resistant and 8 isolates were ‘I - Susceptible, increased exposure’ to meropenem according to EUCAST) were included in the study. Susceptibility of isolates to cefiderocol, imipenem/relebactam, imipenem, aztreonam, ciprofloxacin, levofloxacin and gentamicin were determined by disk diffusion method. Susceptibility of isolates to meropenem, piperacillin/tazobactam and ceftazidime were determined by gradient diffusion method. Results were interpreted according to CLSI and EUCAST criteria. Results: The most active antibiotic tested against isolates were cefiderocol. All isolates were susceptible to cefiderocol using CLSI criteria, whereas 97.8% of isolates were susceptible to cefiderocol using EUCAST criteria. Gentamicin was the most active antibiotic after cefiderocol. Eighty-seven percent of isolates were susceptible to gentamicin. The imipenem/relebactam susceptibility rate among isolates were 66.3% and 73.9% according to CLSI and EUCAST criteria, respectively. Levofloxacin showed the lowest in vitro activity against isolates. The levofloxacin resistance rate among isolates were 70.7% and 82.6% according to CLSI and EUCAST criteria, respectively. Conclusion: Cefiderocol may be an option for treatment of infections caused by carbapenem-resistant P. aeruginosa.

PDF

___

1. Aktaş Z, Satana D, Kayacan C, Can B, Gönüllü N, Küçükbasmacı O. Antibiotic susceptibility rates and beta-lactam resistance mechanisms of Pseudomonas aeruginosa strains. Mikrobiyol Bul, 2012; 46 (3): 386-97.
2. Çekin Y, Karagöz A, Kızılateş F, Çekin AH, Öztoprak Çuvalcı N, Bülbüller N, et al. Evaluation of a hospital outbreak related to carbapenem-resistant Pseudomonas aeruginosa. Mikrobiyol Bul, 2013; 47 (4): 619-27.
3. Er H, Altındiş M, Aşık G, Demir C. Molecular epidemiology of beta-lactamases in ceftazidime-resistant Pseudomonas aeruginosa isolates. Mikrobiyol Bul, 2015; 49 (2): 156-65.
4. Yu Zhang, Xiao-Li Chen, Ai-Wei Huang, Su-Ling Liu, Wei-Jiang Liu, Ni Zhang, et al. Mortality attributable to carbapenem-resistant Pseudomonas aeruginosa bacteremia: a meta-analysis of cohort studies. Emerg Microbes Infect, 2016; 5 (3): e27.
5. Lob SH, Karlowsky JA, Young K, Motyl MR, Hawser S, Kothari ND, et al. Activity of imipenem/relebactam against MDR Pseudomonas aeruginosa in Europe: SMART 2015-17. J Antimicrob Chemother, 2019; 74 (8): 2284-88.
6. Heo YA. Imipenem/Cilastatin/Relebactam: A Review in Gram-Negative Bacterial Infections. Drugs, 2021; 81 (3): 377-88.
7. Iregui A, Khan Z, Landman D, Quale J. Activity of cefiderocol against enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii endemic to medical centers in New York City. Microb Drug Resist, 2020; 26 (7): 722-26.
8. El-Lababidi RM, Rizk JG. Cefiderocol: A siderophore cephalosporin. Ann Pharmacother, 2020; 54 (12): 1215-31.
9. Yamano Y. In vitro activity of cefiderocol against a broad range of clinically important Gram-negative bacteria. Clin Infect Dis, 2019; 69 (Suppl 7): S544-S551.
10. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209445s002lbl.pdf (Erişim tarihi: 24.08.2021).
11. Mirza HC, Hortaç E, Koçak AA, Demirkaya MH, Yayla B, Güçlü AÜ, et al. In vitro activity of ceftolozane-tazobactam and ceftazidime-avibactam against clinical isolates of meropenem-non-susceptible Pseudomonas aeruginosa: A two-centre study. J Glob Antimicrob Resist, 2020; 20: 334-338.
12. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 30th ed. CLSI supplement M100. Wayne, PA: CLSI; 2020.
13. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 11.0, 2021. http://www.eucast.org.
14. https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed (Erişim tarihi: 26.08.2021)
15. Hackel MA, Tsuji M, Yamano Y, Echols R, Karlowsky JA, Sahm DF. In vitro activity of the siderophore cephalosporin, cefiderocol, against carbapenem-nonsusceptible and multidrug-resistant isolates of Gram-Negative bacilli collected worldwide in 2014 to 2016. Antimicrob Agents Chemother, 2018; 62 (2): e01968-17.
16. Morris CP, Bergman Y, Tekle T, Fissel JA, Tamma PD, Simner PJ. Cefiderocol Antimicrobial Susceptibility testing against multidrug-resistant Gram-Negative bacilli: a comparison of disk diffusion to broth microdilution. J Clin Microbiol, 2020; 59 (1): e01649-20.
17. Karlowsky JA, Lob SH, Young K, Motyl MR, Sahm DF. Activity of imipenem/relebactam against Pseudomonas aeruginosa with antimicrobial-resistant phenotypes from seven global regions: SMART 2015-2016. J Glob Antimicrob Resist, 2018; 15: 140-147.
18. Pfaller MA, Sader HS, Rhomberg PR, Flamm RK. In vitro activity of delafloxacin against contemporary bacterial pathogens from the United States and Europe, 2014. Antimicrob Agents Chemother, 2017; 61 (4): e02609-16.
19. Tuon FF, Cieslinski J, Rodrigues SDS, Serra FB, Paula MD. Evaluation of in vitro activity of ceftolozane-tazobactam against recent clinical bacterial isolates from Brazil-the EM200 study. Braz J Infect Dis, 2020; 24 (2): 96-103.