California Northstate University College of Pharmacy, Elk Grove, CA, USA.
University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA.
J Antimicrob Chemother. 2021 Sep 15;76(10):2610-2614. doi: 10.1093/jac/dkab211.
Enterococcus faecalis commonly produce aminoglycoside-modifying enzymes (AMEs) and are implicated in polymicrobial infections.
To determine if AME-producing E. faecalis is capable of protecting Enterobacteriaceae and Pseudomonas aeruginosa from gentamicin exposure.
Two Klebsiella pneumoniae isolates, two Escherichia coli isolates, and two Pseudomonas aeruginosa isolates were investigated in monoculture time-kill experiments, and each Gram-negative organism was also evaluated during co-culture with either AME-producing or AME-deficient E. faecalis. A pharmacokinetic/pharmacodynamics analysis that utilized Log Ratio Areas and a Hill-type mathematical model was used to determine if the maximal killing or potency of gentamicin against the Gram-negative organisms was altered by the presence of the E. faecalis.
The maximal killing and potency of gentamicin was the same during monoculture and co-culture experiments for both K. pneumoniae isolates and one E. coli isolate (P > 0.05). In contrast, the maximal killing of gentamicin was attenuated against one E. coli isolate and both P. aeruginosa isolates during co-culture with E. faecalis (P < 0.05). The potency of gentamicin was variable against the three aforementioned isolates. Against the E. coli isolate, the potency of gentamicin was significantly reduced by the presence of either E. faecalis isolate (EC50 95% CI = 4.23-4.43 mg/L monoculture versus 3.86-4.19 mg/L and 3.55-3.96 mg/L during co-culture with AME-producing and AME-deficient E. faecalis, respectively). The potency of gentamicin increased or decreased for P. aeruginosa depending on which E. faecalis isolate was investigated.
The AME-producing E. faecalis did not provide a consistent protective effect from aminoglycosides for the Gram-negative pathogens.
粪肠球菌通常会产生氨基糖苷类修饰酶（AMEs），并与多微生物感染有关。
确定产 AME 的粪肠球菌是否能够保护肠杆菌科和铜绿假单胞菌免受庆大霉素的影响。
在单培养时间杀伤实验中研究了 2 种肺炎克雷伯菌分离株、2 种大肠埃希菌分离株和 2 种铜绿假单胞菌分离株，并且在与产 AME 或无 AME 的粪肠球菌共培养时，还评估了每种革兰氏阴性菌。利用对数比面积和 Hill 型数学模型进行药代动力学/药效学分析，以确定粪肠球菌的存在是否改变了革兰氏阴性菌对抗生素的最大杀伤或效力。
在单培养和共培养实验中，两种肺炎克雷伯菌分离株和一种大肠埃希菌分离株的最大杀菌和庆大霉素效力相同（P>0.05）。相比之下，在与粪肠球菌共培养时，一种大肠埃希菌分离株和两种铜绿假单胞菌分离株的最大庆大霉素杀菌作用减弱（P<0.05）。庆大霉素对上述三种分离株的效力各不相同。对于大肠埃希菌分离株，产 AME 粪肠球菌的存在显著降低了庆大霉素的效力（EC50 95%CI=4.23-4.43mg/L 单培养与 3.86-4.19mg/L 和 3.55-3.96mg/L 共培养）。产 AME 粪肠球菌的存在增加或降低了铜绿假单胞菌对庆大霉素的效力，具体取决于所研究的粪肠球菌分离株。
产 AME 的粪肠球菌对革兰氏阴性病原体没有提供一致的氨基糖苷类抗生素保护作用。
