Everaert Annelien, Coenye Tom
Laboratory of Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Antimicrob Resist Infect Control. 2016 Nov 16;5:44. doi: 10.1186/s13756-016-0142-3. eCollection 2016.
Bacteria belonging to the complex (Bcc) are an important cause of chronic respiratory tract infections in cystic fibrosis patients. Intrinsic resistance to a wide range of antimicrobial agents, including a variety of β-lactam antibiotics, is frequently observed in Bcc strains. Resistance to β-lactams is most commonly mediated by efflux pumps, alterations in penicillin-binding proteins or the expression of β-lactamases. β-lactamase inhibitors are able to restore the in vitro activity of β-lactam molecules against a variety of Gram-negative species, but the effect of these inhibitors on the activity of β-lactam treatment against Bcc species is still poorly investigated.
In the present study, the susceptibility of a panel of Bcc strains was determined towards the β-lactam antibiotics ceftazidime, meropenem, amoxicillin, cefoxitin, cefepime and aztreonam; alone or in combination with a β-lactamase inhibitor (clavulanic acid, sulbactam, tazobactam and avibactam). Consequently, β-lactamase activity was determined for active β-lactam/β-lactamase inhibitor combinations.
Clavulanic acid had no effect on minimum inhibitory concentrations, but addition of sulbactam, tazobactam or avibactam to ceftazidime, amoxicillin, cefoxitin, cefepime or aztreonam leads to increased susceptibility (at least 4-fold MIC-decrease) in some Bcc strains. The effect of β-lactamase inhibitors on β-lactamase activity is both strain- and/or antibiotic-dependent, and other mechanisms of β-lactam resistance (besides production of β-lactamases) appear to be important.
Considerable differences in susceptibility of Bcc strains to β-lactam antibiotics were observed. Results obtained in the present study suggest that resistance of Bcc strains against β-lactam antibiotics is mediated by both β-lactamases and non-β-lactamase-mediated resistance mechanisms.
属于洋葱伯克霍尔德菌复合体（Bcc）的细菌是囊性纤维化患者慢性呼吸道感染的重要病因。在Bcc菌株中经常观察到对多种抗菌药物具有内在抗性，包括多种β-内酰胺抗生素。对β-内酰胺类药物的抗性最常见是由外排泵、青霉素结合蛋白的改变或β-内酰胺酶的表达介导的。β-内酰胺酶抑制剂能够恢复β-内酰胺分子对多种革兰氏阴性菌的体外活性，但这些抑制剂对β-内酰胺类药物治疗Bcc菌株活性的影响仍研究不足。
在本研究中，测定了一组Bcc菌株对β-内酰胺抗生素头孢他啶、美罗培南、阿莫西林、头孢西丁、头孢吡肟和氨曲南的敏感性；单独使用或与β-内酰胺酶抑制剂（克拉维酸、舒巴坦、他唑巴坦和阿维巴坦）联合使用。随后，测定了活性β-内酰胺/β-内酰胺酶抑制剂组合的β-内酰胺酶活性。
克拉维酸对最低抑菌浓度没有影响，但在头孢他啶、阿莫西林、头孢西丁、头孢吡肟或氨曲南中添加舒巴坦、他唑巴坦或阿维巴坦会使一些Bcc菌株的敏感性增加（最低抑菌浓度至少降低4倍）。β-内酰胺酶抑制剂对β-内酰胺酶活性的影响因菌株和/或抗生素而异，并且β-内酰胺抗性的其他机制（除β-内酰胺酶产生外）似乎也很重要。
观察到Bcc菌株对β-内酰胺抗生素的敏感性存在显著差异。本研究获得的结果表明，Bcc菌株对β-内酰胺抗生素的抗性是由β-内酰胺酶和非β-内酰胺酶介导的抗性机制共同介导的。
