Pitart C, Marco F, Keating T A, Nichols W W, Vila J
Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
AstraZeneca Pharmaceuticals, Infection Innovative Medicines, Waltham, Massachusetts, USA.
Antimicrob Agents Chemother. 2015;59(6):3059-65. doi: 10.1128/AAC.05136-14. Epub 2015 Mar 9.
Ceftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200 Enterobacteriaceae and 25 Pseudomonas aeruginosa strains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistant Enterobacteriaceae strains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBL Escherichia coli (MIC90 of 0.25 mg/liter), ESBL Klebsiella pneumoniae (MIC90 of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90 of 1 mg/liter), non-ESBL E. coli (MIC90 of ≤0.125 mg/liter), non-ESBL K. pneumoniae (MIC90 of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90 of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistant P. aeruginosa strains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90 of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtained in vitro from two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90 values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains of Enterobacteriaceae and P. aeruginosa were ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affect Enterobacteriaceae and P. aeruginosa susceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.
采用肉汤微量稀释法，对从本机构收集的200株耐氟喹诺酮类的肠杆菌科细菌和25株铜绿假单胞菌（包括具有超广谱β-内酰胺酶[ESBL]表型的菌株和对头孢他啶耐药的菌株）进行头孢他啶-阿维巴坦及对照抗生素测试。同时还研究了对氟喹诺酮类的最低抑菌浓度（MIC）及耐药机制。99%的耐氟喹诺酮类肠杆菌科菌株在头孢他啶-阿维巴坦MIC≤4毫克/升时被抑制（以单独使用头孢他啶的CLSI敏感断点作为参考）。头孢他啶-阿维巴坦对产ESBL的大肠埃希菌（MIC90为0.25毫克/升）、产ESBL的肺炎克雷伯菌（MIC90为0.5毫克/升）、对头孢他啶耐药的产AmpC酶菌属（MIC90为1毫克/升）、非产ESBL的大肠埃希菌（MIC90≤0.125毫克/升）、非产ESBL的肺炎克雷伯菌（MIC90为0.25毫克/升）以及对头孢他啶不耐药的产AmpC酶菌属（MIC90≤0.5毫克/升）均具有很高的活性。96%的耐氟喹诺酮类铜绿假单胞菌菌株在头孢他啶-阿维巴坦MIC≤8毫克/升时被抑制（以单独使用头孢他啶的CLSI敏感断点作为参考），MIC90为8毫克/升。此外，从测试的每个菌种中分别从两株菌株体外获得耐氟喹诺酮类突变体，一株对头孢他啶敏感，另一株是对头孢他啶MIC高但对头孢他啶-阿维巴坦敏感的β-内酰胺酶产生菌。由此，可以评估氟喹诺酮类耐药性对头孢他啶-阿维巴坦活性的影响。头孢他啶-阿维巴坦对耐氟喹诺酮类的肠杆菌科细菌和铜绿假单胞菌突变体菌株的MIC90值分别≤4毫克/升和≤8毫克/升。我们得出结论，氟喹诺酮类耐药性的存在并不影响肠杆菌科细菌和铜绿假单胞菌对头孢他啶-阿维巴坦的敏感性；也就是说，不存在交叉耐药性。
