Castanheira Mariana, Duncan Leonard R, Rhomberg Paul R, Sader Helio S
JMI Laboratories, North Liberty, Iowa, USA.
JMI Laboratories, North Liberty, Iowa, USA.
Diagn Microbiol Infect Dis. 2017 Dec;89(4):305-309. doi: 10.1016/j.diagmicrobio.2017.08.011. Epub 2017 Aug 24.
The aim of this study was to evaluate the in vitro activity of cefepime-tazobactam cation-adjusted Mueller-Hinton broth (CA-MHB) supplemented with 0.85% sodium chloride (NaCl) or 50% human serum in comparison to standard CA-MHB when testing KPC-producing isolates. A total of 209 contemporary Enterobacteriaceae clinical isolates carrying bla were tested, and cefepime-tazobactam (tazobactam at fixed 8mg/L) activity was enhanced 2-fold when tested in CA-MHB supplemented with 0.85% NaCl or 50% human serum (MIC, 8/32mg/L for both media) compared to standard CA-MHB (MIC, 16/64mg/L). Cefepime-tazobactam at a concentration of ≤16mg/L, which is the pharmacokinetics/pharmacodynamics tentative susceptibility breakpoint based on a high dosing regimen of cefepime-tazobactam (2g-2g q8h 90-minute infusion), inhibited 79.4-80.4% of Enterobacteriaceae isolates carrying bla in MHB supplemented with 0.85% NaCl or 50% human serum. A similar decrease in MIC values was observed when cefepime alone was tested against a subset of the isolates (n=54) in CA-MHB supplemented with 50% human serum or 0.85% NaCl; however, imipenem activity against these 54 organisms was similar or 2-fold higher in CA-MHB supplemented with 0.85% of NaCl (MIC, 8/16mg/L) or with 50% human serum (MIC and MIC, 16mg/L) compared standard CA-MHB (MIC, 8/16mg/L). In summary, cefepime-tazobactam MIC values against Enterobacteriaceae isolates carrying bla were consistently lower in media supplemented with human serum or NaCl, which better mimics physiological conditions. These results suggest that this carbapenem-sparing candidate agent has potential to be used to treat infections caused by KPC-producing Enterobacteriaceae.
本研究的目的是在检测产KPC菌株时，评估与标准阳离子调整的穆勒-欣顿肉汤（CA-MHB）相比，添加0.85%氯化钠（NaCl）或50%人血清的头孢吡肟-他唑巴坦阳离子调整的穆勒-欣顿肉汤（CA-MHB）的体外活性。共检测了209株携带bla的当代肠杆菌科临床分离株，与标准CA-MHB（MIC，16/64mg/L）相比，在添加0.85% NaCl或50%人血清的CA-MHB中检测时，头孢吡肟-他唑巴坦（他唑巴坦固定浓度为8mg/L）的活性提高了2倍（两种培养基的MIC均为8/32mg/L）。基于头孢吡肟-他唑巴坦的高剂量方案（2g-2g q8h 90分钟输注），头孢吡肟-他唑巴坦浓度≤16mg/L（这是药代动力学/药效学暂定敏感断点）在添加0.85% NaCl或50%人血清的MHB中抑制了79.4-80.4%携带bla的肠杆菌科分离株。当在添加50%人血清或0.85% NaCl的CA-MHB中对一部分分离株（n=54）单独检测头孢吡肟时，观察到MIC值有类似下降；然而，与标准CA-MHB（MIC，8/16mg/L）相比，亚胺培南对这54株菌的活性在添加0.85% NaCl（MIC，8/16mg/L）或50%人血清（MIC和MIC，16mg/L）的CA-MHB中相似或高2倍。总之，在添加人血清或NaCl的培养基中，头孢吡肟-他唑巴坦对携带bla的肠杆菌科分离株的MIC值始终较低，这更好地模拟了生理条件。这些结果表明，这种碳青霉烯类药物节省候选药物有潜力用于治疗由产KPC的肠杆菌科引起的感染。
