Abstract：
NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with β-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered \"NaHCO3-responsive\" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a β-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a β-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro β-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a β-lactam.
摘要：
NaHCO3反应性是一种新的表型,其中一些耐甲氧西林金黄色葡萄球菌(MRSA)分离物在NaHCO3存在下对苯唑西林和/或头孢唑啉表现出显著较低的最小抑制浓度(MIC)。在心内膜炎动物模型中，NaHCO3反应性与对β-内酰胺的治疗反应相关。我们调查了用β-内酰胺治疗对NaHCO3敏感的菌株是否与菌血症的更快清除有关。CAMERA2试验（耐甲氧西林金黄色葡萄球菌的联合抗生素）随机分配了MRSA血流感染的参与者接受标准治疗，或标准疗法加抗葡萄球菌β-内酰胺（联合疗法）。对于117个CAMERA2MRSA分离株，我们通过肉汤微量稀释测定头孢唑啉和苯唑西林的MIC，有和没有44mM的NaHCO3。在存在NaHCO3的情况下，对头孢唑啉或苯唑西林的MIC降低≥4倍的分离物被认为对该试剂具有“NaHCO3反应性”。我们比较了由NaHCO3反应性和非反应性菌株引起感染的参与者中持续性菌血症的发生率，并分配给β-内酰胺联合治疗。31％（36/117）和25％（21/85）的MRSA分离株对头孢唑啉和苯唑西林有NaHCO3反应，分别。NaHCO3反应表型与序列类型93、SCCmecIVa、和在调控区中的位置-7和-38处具有取代的mecA等位基因。在接受β-内酰胺治疗的参与者中，NaHCO3反应表型与持续性菌血症之间没有关联(头孢唑林，P=0.82；苯唑西林，P=0.81）。在MRSA血流感染的随机临床试验中，具有体外β-内酰胺-NaHCO3反应表型的分离株与独特的遗传特征相关，但在接受β-内酰胺治疗的患者中菌血症持续时间较短。
