ÇOK İLACA DİRENÇLİ GRAM NEGATİF BAKTERİLERDEKİ SEFTAZİDİM-AVİBAKTAM DUYARLILIĞININ ARAŞTIRILMASI

Yıl 2023, Cilt: 37 Sayı: 3, 103 - 108, 31.12.2023

Emel Akbaş Banu Hümeyra Keskin Hande Kayman Dilek Yekenkurul Emel Çalışkan Şükrü Öksüz İdris Şahin

https://doi.org/10.54962/ankemderg.1406287

Öz

Çoklu ilaca dirençli (MDR) Gram negatif bakteriyel patojenler ciddi mortalite ve morbidite ile seyreden enfeksiyonlara neden olabilirler. Bu izolatların etken olduğu enfeksiyonlarda tedavi seçenekleri sınırlıdır. Çalışmamızda çeşitli klinik örneklerden izole edilen MDR Gram negatif bakterilerde seftazidim-avibaktam duyarlılık oranının araştırılması amaçlanmıştır.
Çalışmaya Düzce Üniversitesi Tıbbi Mikrobiyoloji Laboratuvarında Temmuz 2018-Temmuz 2022 tarihleri arasında çeşitli klinik örneklerden izole edilen Enterobacterales ve Pseudomonas aeruginosa suşları dahil edildi. Tür düzeyinde tanımlama ve antimikrobiyal duyarlılık testleri için klasik yöntemlere ilave olarak otomatize sistem (VITEK 2 Compact /Phoenix) kullanıldı. Bunların içinden MDR olduğu saptanan izolatlarda disk difüzyon yöntemi ile seftazidim-avibaktam (10-4 µ) (Bioanalyse, Türkiye) duyarlılığı araştırıldı.
Çeşitli klinik örneklerden toplam 83 adet MDR Enterobacterales ve 33 adet MDR P. aeruginosa olmak üzere 116 suş izole edildi. İzolatların 45’i (%38.7) seftazidim-avibaktama duyarlı bulundu. Seftazidim-avibaktam duyarlılığı Enterobacterales için %44.6 iken, P. aeruginosa suşlarında %24.2 olarak saptandı.
Sonuç olarak çalışmamızda, MDR Enterobacterales’te en etkili antibiyotik kolistin (p<0.001), ikinci seftazidim-avibaktam (p<0.001) oldu. MDR P. aeruginosa suşlarında da en etkili antibiyotik kolistin (p<0.001) olmakla birlikte; gentamisin, amikasin ve seftazidim-avibaktam duyarlılıklarının benzer olduğu görüldü (p<0.819). Yapılan çalışmalarda P. aeruginosa'nın seftazidim-avibaktama karşı direnç oranlarının diğer Gram-negatif patojenlere göre daha yüksek olduğu gösterilmiştir. Sonuçlarımız seftazidim-avibaktamın MDR-Enterobacterales ile gelişen enfeksiyonların tedavisi için bir alternatif olabileceğini; ancak, MDR-P. aeruginosa suşlarında duyarlılık test sonuçlarının önemli olduğunu düşündürmektedir.

Anahtar Kelimeler

çoklu ilaç direnci, Enterobacterales, P. aeruginosa, seftazidim-avibaktam

Etik Beyan

Düzce Üniversitesi Tıp Fakültesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurul Başkanlığı’ndan 25/04/2022 tarih ve 2022/81 karar numarası ile alınmıştır.

Investigation of Ceftazidime-Avibactam Susceptibility in Multidrug Resistant Gram Negative Bacteria

Öz

Multi-drug resistant (MDR) Gram-negative bacterial pathogens may cause infections with serious mortality and morbidity. Treatment options for infections caused by these isolates are limited. The aim of our study was to investigate the ceftazidime-avibactam susceptibility rate in MDR Gram negative bacteria isolated from various clinical samples.
Enterobacterales and Pseudomonas aeruginosa strains isolated from various clinical samples in Düzce University Medical Microbiology Laboratory between July 2018 and July 2022 were included in the study. In addition to classical methods, an automated system (VITEK 2 Compact /Phoenix) was used for species level identification and antimicrobial susceptibility testing. Ceftazidime-avibactam (10-4 µ) (Bioanalyse, Turkey) susceptibility was investigated by disc diffusion method in the MDR isolates.
A total of 116 strains, including 83 MDR Enterobacterales and 33 MDR-P. aeruginosa, were isolated from various clinical samples. Forty-five (38.7%) of the isolates were susceptible to ceftazidime-avibactam. Ceftazidime-avibactam susceptibility was 44.6% for Enterobacterales and 24.2% for P. aeruginosa strains.
In conclusion, the most effective antibiotic against MDR Enterobacterales was colistin (p<0.001) and, the second was ceftazidime-avibactam (p<0.001) in our study. Although the most effective antibiotic against MDR P. aeruginosa strains was also colistin (p<0.001); the susceptibilities to gentamicin, amikacin and ceftazidime-avibactam were similar (p<0.819). Studies have shown that resistance rates of P. aeruginosa to ceftazidime-avibactam were higher than other Gram negative pathogens. Our results indicate that ceftazidime-avibactam may be an alternative for the treatment of infections caused by MDR-Enterobacterales; However, they suggest that susceptibility test results are important for MDR-P. aeruginosa strains.

Anahtar Kelimeler

ceftazidime-avibactam, Enterobacterales, multidrug resistance, P. aeruginosa

Etik Beyan

It was obtained from Düzce University Faculty of Medicine, Non-Interventional Clinical Research Ethics Committee with the decision number 2022/81 dated 25/04/2022

Kaynakça

• Al-Kofide H, Alhammad A, Alruwaili A, et al. Multidrug-resistant and extensively drug-resistant Enterobacteriaceae: Prevalence, treatments, and outcomes – a retrospective cohort study. Infect Drug Resist. 2020;13:4653-62.
• Bassetti M, Peghin M, Pecori D. The management of multidrug-resistant Enterobacteriaceae. Curr Opin Infect Dis. 2016;29(6) 583-594.
• Hoşbul T, Aydoğan C, Kaya S, et al. Ceftazidime-avibactam ve colistin’in karbapeneme dirençli Pseudomonas aeruginosa klinik izolatlara karşı in vitro aktivitesi. J Ist Fac Med. 2022;85(3):355-61.
• Karlowsky JA, Kazmierczak KM, Bouchillon SK, de Jonge BLM, Stone GG, Sahm DF. In vitro activity of ceftazidime-avibactam against clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa collected in Asia-Pacific countries: Results from the INFORM Global Surveillance Program, 2012 to 2015. Antimicrob Agents Chemother. 2018;62(7): e02569-17.
• Katchanov J, Asar L, Klupp E-M, et al. Carbapenem-resistant Gram-negative pathogens in a German university medical center: Prevalence, clinical implications and the role of novel β-lactam/β-lactamase inhibitor combinations. PLoS One. 2018;13(4):e0195757.
• Kaya S, Hoşbul T, Albay A, Gümral R, Aydogan C, Bedir O. Karbapenem Dirençli Klebsiella pneumoniae klinik izolatlarına karşı seftazidim-avibaktam ve kolistinin in vitro etkinliği. Mikrobiyol Bul. 2022;56(2):218-29.
• Kempf M, Arhin FF, Stone G, Utt E. Ceftazidime-avibactam activity against Gram-negative respiratory isolates collected between 2018 and 2019. J Glob Antimicrob Resist. 2022;31:239-47.
• Kim T, Lee SC, Bae M, et al. In vitro activities and inoculum effects of ceftazidime-avibactam and aztreonam-avibactam against carbapenem-resistant Enterobacterales isolates from South Korea. 2020;9(12):912.
• Kiratisin P, Kazmierczak K, Stone GG. In vitro activity of ceftazidime/avibactam and comparators against carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates collected globally between 2016 and 2018. J Glob Antimicrob Resist. 2021;27:132-41.
• Kiratisin P, Kempf M, Stone G, Utt E. Ceftazidime-avibactam and comparators against Pseudomonas aeruginosa isolates collected globally and in each geographical region between 2017–2020. J Glob Antimicrob Resist. 2023;34:113-8.
• Magiorakos A-P, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18(3):268-81.
• Mataraci Kara E, Yilmaz M, Istanbullu Tosun A, Özbek Çelik B. Evaluation of the synergy of ceftazidime/avibactam in combination with colistin, doripenem, levofloxacin, tigecycline, and tobramycin against OXA-48 producing Enterobacterales. J Chemother. 2020;32(4):171-8.
• Ozger HS, Evren E, Yildiz SS, et al. Ceftazidime - Avibactam susceptibility among carbapenem-resistant Enterobacterales in a pilot study in Turkey. Acta Microbiol Immunol Hung. 2021;68(4):256-261.
• Sader HS, Castanheira M, Duncan LR, Flamm RK. Antimicrobial Susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa Isolates from United States Medical Centers Stratified by Infection Type: Results from the International Network for Optimal Resistance Monitoring (INFORM) Surveillance Program, 2015–2016. Diagn Microbiol Infect Dis. 2018;92(1):69-74.
• Sharma R, Park TE, Moy S. Ceftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination for the Treatment of Resistant Gram-negative Organisms. Clin Ther. 2016;38(3):431-44.
• Shirley M. Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. Drugs. 2018;78(6):675-92.
• Stone GG, Smayevsky J, Kazmierczak K. Longitudinal analysis of the in vitro activity of ceftazidime-avibactam vs. Pseudomonas aeruginosa, 2012–2016. Diagn Microbiol Infect Dis. 2020;96(1):114835.
• Tängdén T, Giske CG. Global dissemination of extensively drug‐resistant carbapenemase‐producing E nterobacteriaceae: clinical perspectives on detection, treatment and infection control. J Intern Med. 2015;277(5):501-12.
• The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 9.0, 2019. http://www.eucast.org.
• Wang Y, Wang J, Wang R, Cai Y. Resistance to ceftazidime-avibactam and underlying mechanisms. J Glob Antimicrob Resist. 2020;22:18-27.
• Zou C, Wei J, Shan B, Chen X, Wang D, Niu S. In vitro activity of ceftazidime-avibactam and aztreonam-avibactam against carbapenem-resistant Enterobacteriaceae isolates collected from three secondary hospitals in Southwest China between 2018 and 2019. Infect Drug Resist. 2020;1(13):3563–8.