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从含有临床相关浓度抗真菌药物的血培养物中高效回收耳念珠菌及其他五种重要医学菌种。

Efficient Recovery of Candida auris and Five Other Medically Important Species from Blood Cultures Containing Clinically Relevant Concentrations of Antifungal Agents.

作者信息

Posteraro Brunella, Menchinelli Giulia, Ivagnes Vittorio, Cortazzo Venere, Liotti Flora Marzia, Falasca Benedetta, Fiori Barbara, D'Inzeo Tiziana, Spanu Teresa, De Angelis Giulia, Sanguinetti Maurizio

机构信息

Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Roma, Italy.

Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

出版信息

Microbiol Spectr. 2023 Jan 30;11(2):e0410422. doi: 10.1128/spectrum.04104-22.

Abstract

Candida auris and other species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei) are important causes of bloodstream infection. Early or prolonged treatment with antifungal agents is often required. The inhibitory effect of antifungal agents in the patients' bloodstream may compromise the sensitivity of blood culture (BC) to diagnose and/or monitor patients with candidemia. Using a clinical BC simulation model, we compared antimicrobial drug-neutralizing BC media in BacT/Alert FA PLUS (FAP) or Bactec Plus Aerobic/F (PAF) bottles with non-neutralizing BC media in Bactec Mycosis IC/F (MICF) bottles to allow growth in the presence of 100%, 50%, or 25% peak serum level (PSL) antifungal concentrations. In total, 117 organism/antifungal combinations were studied, and growth was detected after incubating bottles into BacT/Alert VIRTUO or Bactec FX BC systems. Compared to control (without antifungal) bottles, both FAP and PAF bottles with 100% PSL antifungal concentrations allowed 100% recovery for C. auris, C. glabrata, and C. parapsilosis, whereas recovery was below 100% for C. albicans, C. krusei, and C. tropicalis. MICF bottles were less efficient at 100%, 50%, or 25% PSL antifungal concentrations, for all species, except for C. auris. While azoles and amphotericin B did not hinder growth in FAP or PAF bottles, echinocandins allowed C. auris, C. glabrata, and C. parapsilosis to grow in FAP, PAF, or MICF bottles. Overall, the maximum time to detection was 4.6 days. Taken together, our findings emphasize the reliability of BCs in patients undergoing antifungal treatment for candidemia. While echinocandins remain the preferred antifungal therapy for candidemia, bloodstream infections caused by C. auris, C. glabrata, or, at a lesser extent, C. parapsilosis may be difficult to treat with these antifungal agents. This is in view of the high propensity of the above-mentioned species to develop antifungal resistance or tolerance during treatment. Azoles and amphotericin B are possible alternatives. Thus, optimizing the recovery of from BCs is important to exclude the likelihood of negative BCs for species, owing to the inhibitory effect of antifungal agents present in the blood sample with which BCs are inoculated. Consistently, our results about the recovery of medically important species (including C. auris) from simulated BCs in BacT/Alert FAP, Bactec PAF, or Bactec MICF bottles containing clinically relevant antifungal concentrations add support to this research topic, as well as to the use of BCs for monitoring the clinical and therapeutic course of candidemia.

摘要

耳念珠菌及其他菌种(白色念珠菌、光滑念珠菌、近平滑念珠菌、热带念珠菌和克柔念珠菌)是血流感染的重要病因。通常需要尽早或长期使用抗真菌药物进行治疗。抗真菌药物在患者血流中的抑制作用可能会影响血培养(BC)对念珠菌血症患者进行诊断和/或监测的敏感性。我们使用临床血培养模拟模型,将BacT/Alert FA PLUS(FAP)或Bactec Plus Aerobic/F(PAF)瓶中的抗菌药物中和血培养培养基与Bactec Mycosis IC/F(MICF)瓶中的非中和血培养培养基进行比较,以观察在100%、50%或25%的峰值血清水平(PSL)抗真菌浓度下的生长情况。总共研究了117种微生物/抗真菌药物组合,并将培养瓶放入BacT/Alert VIRTUO或Bactec FX血培养系统中孵育后检测到生长情况。与对照(无抗真菌药物)瓶相比,含有100% PSL抗真菌浓度的FAP和PAF瓶对耳念珠菌、光滑念珠菌和近平滑念珠菌的回收率均为100%,而白色念珠菌、克柔念珠菌和热带念珠菌的回收率低于100%。对于所有菌种,除了耳念珠菌外,在100%、50%或25% PSL抗真菌浓度下,MICF瓶的效率较低。虽然唑类和两性霉素B不会阻碍FAP或PAF瓶中的生长,但棘白菌素能使耳念珠菌、光滑念珠菌和近平滑念珠菌在FAP、PAF或MICF瓶中生长。总体而言,最长检测时间为4.6天。综上所述,我们的研究结果强调了血培养在念珠菌血症抗真菌治疗患者中的可靠性。虽然棘白菌素仍然是念珠菌血症的首选抗真菌治疗药物,但由耳念珠菌、光滑念珠菌或在较小程度上由近平滑念珠菌引起的血流感染可能难以用这些抗真菌药物治疗。这是因为上述菌种在治疗过程中极易产生抗真菌耐药性或耐受性。唑类和两性霉素B是可能的替代药物。因此,优化血培养的回收率对于排除因接种血培养的血样中存在抗真菌药物的抑制作用而导致某些菌种血培养结果为阴性的可能性非常重要。同样,我们关于在含有临床相关抗真菌浓度的BacT/Alert FAP、Bactec PAF或Bactec MICF瓶中从模拟血培养中回收重要医学菌种(包括耳念珠菌)的结果,为该研究主题以及使用血培养监测念珠菌血症的临床和治疗过程提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3748/10100679/ec6d49f92837/spectrum.04104-22-f001.jpg

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