AI Summary & Key Takeaways
AI InsightIn conclusion, in our study it was observed that CT, a novel beta-lactam/beta-lactamase inhibitor, did not sufficiently affect A.baumannii isolates, but was able to induce synergistic interaction in combination with TGC, AK and MIN.
📌 3 Key Takeaways
Abstract
Acinetobacter species lead to nosocomial infections in immunocompromised patients hospitalized in intensive care units or services. Acinetobacter baumannii is a bacterium that is difficult to treat because it is intrinsically resistant to many antibiotics and can develop resistance afterwards. This situation limits the use of existing antibiotics and directs the clinician to new agents, different treatment options and the use of various antibiotic combinations. The aim of this study was to determine the sensitivities of doripenem (DOR), tigecycline (TGC), minocycline (MIN), amikacin (AK) and a newly developed agent ceftolozane-tazobactam (CT) in multidrug resistant A.baumannii strains which were isolated from inpatients in intensive care units and to investigate the in vitro interactions of CT/DOR, CT/TGC, CT/MIN and CT/AK combinations by using antibiotic gradient test method. Thirty-five A.baumannii strains isolated from various clinical specimens (blood, urine, sputum, tracheal aspirate, wound, abscess and catheter) between January 2017 and July 2017 were included in the study. Strains isolated from inpatients in intensive care units and resistant to at least three antibiotic classes were selected. The identification of A.baumannii isolates and the determination of routine antibiotic susceptibility profile were performed according to EUCAST 2017 criteria by the use of BD Phoenix 100 (Becton Dickinson, USA) automated system. Minimum inhibitor concentration values of CT, DOR, TGC, MIN, AK and combinations of CT with four other antibiotics (CT/DOR, CT/TGC, CT/MIN and CT/AK) were determined by antibiotic gradient test method. Fractional inhibitor concentration index (FICI) was used to determine the interactions of the combinations in vitro. According to the data obtained; the FICI was evaluated as synergy if FICI ≤ 0.5, additive if 0.5 > FICI ≤ 1, indifferent (unidentified interaction) if 1 < FICI < 2 and antagonist interaction if FICI ≥ 2. According to FICI results of the antibiotic combinations, the highest synergistic interaction was observed between CT/TGC as 11.4%. No synergistic interaction was observed between CT/DOR antibiotics. The highest additive interaction rates were between CT/AK (60%) and CT/MIN (45.7%), while no additive interaction between CT/DOR was observed. Antagonist interaction was observed in CT/DOR (71.4%) combination only. In conclusion, in our study it was observed that CT, a novel beta-lactam/beta-lactamase inhibitor, did not sufficiently affect A.baumannii isolates, but was able to induce synergistic interaction in combination with TGC, AK and MIN. CT should be carefully monitored in clinical use because of the antagonist interaction detected with DOR.
Özet
Acinetobacter türleri yoğun bakım ünitelerinde veya servislerde yatan immün sistemi baskılanmış hastalarda nozokomiyal enfeksiyonlara neden olmaktadır. Acinetobacter baumannii, birçok antibiyotiğe intrensek dirençli olması ve sonradan direnç geliştirebilmesi nedeniyle tedavisinde zorluk yaşanan bir bakteridir. Bu durum mevcut antibiyotiklerin kullanımını kısıtlamakta, klinisyeni yeni ilaçlara, farklı tedavi seçeneklerine ve çeşitli antibiyotik kombinasyonlarına yönlendirmektedir. Bu çalışmanın amacı, yoğun bakım ünitelerinde yatan hastalardan izole edilen çok ilaca dirençli A.baumannii izolatlarında; doripenem (DOR), tigesiklin (TGC), minosiklin (MIN), amikasin (AK) ve yeni geliştirilen bir ilaç olan seftolozan-tazobaktam (CT)’ın duyarlılığını antibiyotik gradiyent test yöntemiyle belirlemek, sonrasında ise CT/DOR, CT/TGC, CT/MIN ve CT/AK kombinasyonlarının in vitro etkileşimlerini antibiyotik gradiyent test yöntemiyle araştırmaktır. Hastanemizde Ocak 2017-Temmuz 2017 tarihleri arasında çeşitli klinik örneklerden (kan, idrar, balgam, trakeal aspirat, yara, apse ve kateter) izole edilen 35 A.baumannii izolatı çalışmaya alınmıştır. Bu izolatlar, yoğun bakım ünitelerinde yatmakta olan hastalardan elde edilmiş ve en az üç antibiyotik sınıfına direnç gösteren bakteriler arasından seçilmiştir. A.baumannii izolatlarının tanımlanması ve rutin antibiyotik duyarlılık profilinin belirlenmesi BD Phoenix 100 (Becton Dickinson, ABD) otomatize sistemi ile EUCAST 2017 önerileri doğrultusunda gerçekleştirilmiştir. A.baumannii izolatlarına karşı CT, DOR, TGC, MIN ve AK’ın hem tek başına hem de CT’nin diğer dört antibiyotikle ikili kombinasyonlarının