Stein Gary E, Schooley Sharon L, Peloquin Charles A, Kak Vivek, Havlichek Daniel H, Citron Diane M, Tyrrell Kerin L, Goldstein Ellie J C
Department of Medicine, Michigan State University, B320 Life Sciences Building, East Lansing, MI 48824-1317, USA.
Ann Pharmacother. 2005 Mar;39(3):427-32. doi: 10.1345/aph.1E484. Epub 2005 Feb 8.
Linezolid is an oxazolidinone antimicrobial with excellent oral bioavailability and tissue penetration and is active against multidrug-resistant skin/soft tissue pathogens.
To study the pharmacokinetics and antibacterial activity of linezolid against selective skin/soft tissue pathogens in obese patients.
We obtained multiple serum samples from 7 obese patients (>50% over their calculated ideal body weight) receiving oral linezolid 600 mg every 12 hours for treatment of cellulitis. Following a minimum of 3 doses, serum concentrations of linezolid were measured in each subject prior to (trough) and 1 and 6 hours after a dose. These samples were then tested against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (linezolid minimum inhibitory concentrations [MICs] 1.0, 2.0, 4.0 microg/mL) and one strain each of vancomycin-resistant Enterococcus faecium (VRE) (MIC 2.0 microg/mL), Bacteroides fragilis (MIC 2.0 microg/mL), and Peptostreptococcus magnus (MIC 1.0 microg/mL). Serum inhibitory titers (SITs) and bactericidal titers (SBTs) were measured at each time point, and the median activity for these 7 patients was calculated.
Mean linezolid serum concentrations were 4.2, 12.3, and 7.2 microg/mL at these respective time points. Median SITs for 12 hours (100% of the dosing interval) were observed against each organism with the exception of the least susceptible strain of MRSA (MIC 4.0 microg/mL); serum inhibitory activity was observed only at the one-hour time point against this isolate. Furthermore, prolonged (> or =6 h) median SBTs were observed against one isolate of MRSA (MIC 1.0 microg/mL) as well as the strain of VRE and P. magnus.
Serum concentrations of oral linezolid in this patient population were diminished compared with those of healthy volunteers, but still provided prolonged serum inhibitory activity against common pathogens associated with skin/soft tissue infections. One treatment concern would be an obese patient receiving oral linezolid who was infected with a less susceptible (MIC > or =4.0 microg/mL) strain of S. aureus. Bactericidal activity was also observed against selective pathogens.
利奈唑胺是一种恶唑烷酮类抗菌药物，口服生物利用度高，组织穿透力强，对多重耐药皮肤/软组织病原体具有活性。
研究利奈唑胺对肥胖患者选择性皮肤/软组织病原体的药代动力学和抗菌活性。
我们从7名肥胖患者（超过其计算出的理想体重50%以上）中获取多个血清样本，这些患者每12小时口服600mg利奈唑胺治疗蜂窝织炎。在至少服用3剂后，在每个受试者给药前（谷浓度）以及给药后1小时和6小时测量利奈唑胺的血清浓度。然后将这些样本针对耐甲氧西林金黄色葡萄球菌（MRSA）的临床分离株（利奈唑胺最低抑菌浓度[MIC]为1.0、2.0、4.0μg/mL）以及一株耐万古霉素粪肠球菌（VRE）（MIC为2.0μg/mL）、脆弱拟杆菌（MIC为2.0μg/mL）和大消化链球菌（MIC为1.0μg/mL）进行检测。在每个时间点测量血清抑制滴度（SIT）和杀菌滴度（SBT），并计算这7名患者的中位活性。
在这些相应时间点，利奈唑胺的平均血清浓度分别为4.2、12.3和7.2μg/mL。除最不敏感的MRSA菌株（MIC为4.0μg/mL）外，对每种微生物在12小时（给药间隔的100%）观察到中位SIT；仅在1小时时间点对该分离株观察到血清抑制活性。此外，对一株MRSA（MIC为1.0μg/mL）以及VRE和大消化链球菌菌株观察到中位SBT延长（≥6小时）。
与健康志愿者相比，该患者群体中口服利奈唑胺的血清浓度有所降低，但仍对与皮肤/软组织感染相关的常见病原体提供了延长的血清抑制活性。一个治疗方面的担忧是肥胖患者口服利奈唑胺时感染了较不敏感（MIC≥4.0μg/mL）的金黄色葡萄球菌菌株。还观察到对选择性病原体的杀菌活性。
