PDF(Pubmed)
Abstract：
UNASSIGNED: We sought to evaluate the pharmacodynamics of β-lactam antibacterials against polymicrobial communities of clinically relevant gram-positive and gram-negative pathogens.
UNASSIGNED: Two Enterococcus faecalis isolates, two Staphylococcus aureus isolates, and three Escherichia coli isolates with varying β-lactamase production were evaluated in static time-killing experiments. Each gram-positive isolate was exposed to a concentration array of ampicillin (E. faecalis) or cefazolin (S. aureus) alone and during co-culture with an E. coli isolate that was β-lactamase-deficient, produced TEM-1, or produced KPC-3/TEM-1B. The results of the time-killing experiments were summarized using an integrated pharmacokinetic/pharmacodynamics analysis as well as mathematical modelling to fully characterize the antibacterial pharmacodynamics.
UNASSIGNED: In the integrated analysis, the maximum killing of ampicillin (Emax) against both E. faecalis isolates was ≥ 4.11 during monoculture experiments or co-culture with β-lactamase-deficient E. coli, whereas the Emax was reduced to ≤ 1.54 during co-culture with β-lactamase-producing E. coli. In comparison to monoculture experiments, culturing S. aureus with KPC-producing E. coli resulted in reductions of the cefazolin Emax from 3.25 and 3.71 down to 2.02 and 2.98, respectively. Two mathematical models were created to describe the interactions between E. coli and either E. faecalis or S. aureus. When in co-culture with E. coli, S. aureus experienced a reduction in its cefazolin Kmax by 24.8% (23.1%RSE). Similarly, β-lactamase-producing E. coli preferentially protected the ampicillin-resistant E. faecalis subpopulation, reducing Kmax,r by 90.1% (14%RSE).
UNASSIGNED: β-lactamase-producing E. coli were capable of protecting S. aureus and E. faecalis from exposure to β-lactam antibacterials.
UNASSIGNED: Two Enterococcus faecalis isolates, two Staphylococcus aureus isolates, and three Escherichia coli isolates with varying β-lactamase production were evaluated in static time-killing experiments. Each gram-positive isolate was exposed to a concentration array of ampicillin (E. faecalis) or cefazolin (S. aureus) alone and during co-culture with an E. coli isolate that was β-lactamase-deficient, produced TEM-1, or produced KPC-3/TEM-1B. The results of the time-killing experiments were summarized using an integrated pharmacokinetic/pharmacodynamics analysis as well as mathematical modelling to fully characterize the antibacterial pharmacodynamics.
UNASSIGNED: In the integrated analysis, the maximum killing of ampicillin (Emax) against both E. faecalis isolates was ≥ 4.11 during monoculture experiments or co-culture with β-lactamase-deficient E. coli, whereas the Emax was reduced to ≤ 1.54 during co-culture with β-lactamase-producing E. coli. In comparison to monoculture experiments, culturing S. aureus with KPC-producing E. coli resulted in reductions of the cefazolin Emax from 3.25 and 3.71 down to 2.02 and 2.98, respectively. Two mathematical models were created to describe the interactions between E. coli and either E. faecalis or S. aureus. When in co-culture with E. coli, S. aureus experienced a reduction in its cefazolin Kmax by 24.8% (23.1%RSE). Similarly, β-lactamase-producing E. coli preferentially protected the ampicillin-resistant E. faecalis subpopulation, reducing Kmax,r by 90.1% (14%RSE).
UNASSIGNED: β-lactamase-producing E. coli were capable of protecting S. aureus and E. faecalis from exposure to β-lactam antibacterials.
摘要：
■我们试图评估β-内酰胺抗菌药物对临床相关革兰氏阳性和革兰氏阴性病原体的多微生物群落的药效学。
■两个粪肠球菌分离株，两个金黄色葡萄球菌分离株，在静态时间杀伤实验中评估了三种具有不同β-内酰胺酶产量的大肠杆菌分离株。将每个革兰氏阳性分离物暴露于氨苄青霉素的浓度阵列（E.粪肠)或头孢唑啉(S.金黄色葡萄球菌）单独和与β-内酰胺酶缺陷的大肠杆菌分离物共培养期间，产生TEM-1，或产生KPC-3/TEM-1B。使用整合的药代动力学/药效学分析以及数学建模来总结时间杀伤实验的结果，以充分表征抗菌药效学。
■在综合分析中，在单培养实验或与β-内酰胺酶缺陷型大肠杆菌共培养期间，氨苄西林对两个粪肠球菌分离株的最大杀灭率(Emax)≥4.11，而在与产β-内酰胺酶的大肠杆菌共培养期间，Emax降低至≤1.54。与单一文化实验相比，用产生KPC的大肠杆菌培养金黄色葡萄球菌导致头孢唑啉Emax分别从3.25和3.71降低至2.02和2.98。创建两个数学模型来描述大肠杆菌与粪肠球菌或金黄色葡萄球菌之间的相互作用。当与大肠杆菌共培养时，金黄色葡萄球菌的头孢唑啉Kmax降低了24.8%(23.1%RSE)。同样，产β-内酰胺酶的大肠杆菌优先保护耐氨苄青霉素的粪肠球菌亚群，降低Kmax,r下降90.1%（14%RSE）。
■产生β-内酰胺酶的大肠杆菌能够保护金黄色葡萄球菌和粪肠球菌免于暴露于β-内酰胺抗菌剂。
■两个粪肠球菌分离株，两个金黄色葡萄球菌分离株，在静态时间杀伤实验中评估了三种具有不同β-内酰胺酶产量的大肠杆菌分离株。将每个革兰氏阳性分离物暴露于氨苄青霉素的浓度阵列（E.粪肠)或头孢唑啉(S.金黄色葡萄球菌）单独和与β-内酰胺酶缺陷的大肠杆菌分离物共培养期间，产生TEM-1，或产生KPC-3/TEM-1B。使用整合的药代动力学/药效学分析以及数学建模来总结时间杀伤实验的结果，以充分表征抗菌药效学。
■在综合分析中，在单培养实验或与β-内酰胺酶缺陷型大肠杆菌共培养期间，氨苄西林对两个粪肠球菌分离株的最大杀灭率(Emax)≥4.11，而在与产β-内酰胺酶的大肠杆菌共培养期间，Emax降低至≤1.54。与单一文化实验相比，用产生KPC的大肠杆菌培养金黄色葡萄球菌导致头孢唑啉Emax分别从3.25和3.71降低至2.02和2.98。创建两个数学模型来描述大肠杆菌与粪肠球菌或金黄色葡萄球菌之间的相互作用。当与大肠杆菌共培养时，金黄色葡萄球菌的头孢唑啉Kmax降低了24.8%(23.1%RSE)。同样，产β-内酰胺酶的大肠杆菌优先保护耐氨苄青霉素的粪肠球菌亚群，降低Kmax,r下降90.1%（14%RSE）。
■产生β-内酰胺酶的大肠杆菌能够保护金黄色葡萄球菌和粪肠球菌免于暴露于β-内酰胺抗菌剂。
