共 2 条
Systemic thioridazine in combination with dicloxacillin against early aortic graft infections caused by Staphylococcus aureus in a porcine model: In vivo results do not reproduce the in vitro synergistic activity
被引:10
|作者:
Stenger, Michael
[1
,2
]
Behr-Rasmussen, Carsten
[3
]
Klein, Kasper
[1
]
Gronnemose, Rasmus B.
[1
]
Andersen, Thomas Emil
[1
]
Klitgaard, Janne K.
[1
,4
]
Kolmos, Hans Jorn
[1
]
Lindholt, Jes S.
[2
]
机构:
[1] Univ Southern Denmark, Res Unit Clin Microbiol, Odense, Denmark
[2] Odense Univ Hosp, Dept Cardiothorac & Vasc Surg, Odense, Denmark
[3] Viborg Hosp, Dept Vasc Surg, Viborg, Denmark
[4] Univ Southern Denmark, Dept Biochem & Mol Biol, Odense, Denmark
来源:
PLOS ONE
|
2017年
/
12卷
/
03期
关键词:
EFFLUX PUMP;
RESISTANCE;
ANTIBIOTICS;
ENANTIOMERS;
METABOLISM;
PREVENTION;
MANAGEMENT;
POLYESTER;
DIAGNOSIS;
EFFICACY;
D O I:
10.1371/journal.pone.0173362
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Introduction Conservative treatment solutions against aortic prosthetic vascular graft infection (APVGI) for inoperable patients are limited. The combination of antibiotics with antibacterial helper compounds, such as the neuroleptic drug thioridazine (TDZ), should be explored. Aim To investigate the efficacy of conservative systemic treatment with dicloxacillin (DCX) in combination with TDZ (DCX+TDZ), compared to DCX alone, against early APVGI caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a porcine model. Methods The synergism of DCX+TDZ against MSSA was initially assessed in vitro by viability assay. Thereafter, thirty-two pigs had polyester grafts implanted in the infrarenal aorta, followed by inoculation with 10(6) CFU of MSSA, and were randomly administered oral systemic treatment with either 1) DCX or 2) DCX+TDZ. Treatment was initiated one week postoperatively and continued for a further 21 days. Weight, temperature, and blood samples were collected at predefined intervals. By termination, bacterial quantities from the graft surface, graft material, and perigraft tissue were obtained. Results Despite in vitro synergism, the porcine experiment revealed no statistical differences for bacteriological endpoints between the two treatment groups, and none of the treatments eradicated the APVGI. Accordingly, the mixed model analyses of weight, temperature, and blood samples revealed no statistical differences. Conclusion Conservative systemic treatment with DCX+TDZ did not reproduce in vitro results against APVGI caused by MSSA in this porcine model. However, unexpected severe adverse effects related to the planned dose of TDZ required a considerable reduction to the administered dose of TDZ, which may have compromised the results.
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页数:15
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