Effective antibiotics in combination against extreme drug-resistant Pseudomonas aeruginosa with decreased susceptibility to polymyxin B.
Effective antibiotics in combination against extreme drug-resistant Pseudomonas aeruginosa with decreased susceptibility to polymyxin B.
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DOI：
10.1371/journal.pone.0028177
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kwa AL
中科院分区：
文献类型：
--
作者：
Lim TP;Lee W;Tan TY;Sasikala S;Teo J;Hsu LY;Tan TT;Syahidah N;Kwa AL
新加坡出现了对多粘菌素B （PB）敏感性降低的极端耐药铜绿假单胞菌（XDR-PA），在免疫功能低下的宿主中引起感染。在新抗生素问世之前，联合治疗可能是唯一可行的治疗选择。本研究的目的是评估各种抗生素对当地XDR-PA分离株的体外活性。2006年至2007年间系统收集了新加坡所有公立医院的PA分离株。根据CLSI指南测定mic。所有鉴定的XDR-PA分离株均采用基于pcr的方法进行基因分型。时间杀伤研究（TKS）在基线时约105 CFU/ml，使用临床可达到的非结合浓度的阿米卡星(A)、左氧氟沙星(L)、美罗培南(M)、利福平(R)和PB单独或联合使用。杀灭活性（主要终点）定义为在24小时内菌落计数比初始接种量减少≥3 log10 CFU/ml。收集22株临床XDR-PA分离株，PB MIC 2 ~ 16µg/ml。克隆分型鉴定出5个克隆群，9个分离株表现出克隆多样性。在TKS中，美罗培南加PB、阿米卡星加美罗培南、阿米卡星加利福平、阿米卡星加PB在24小时分别对8/22、3/22、1/22和6/22株菌株有杀菌活性。对于其余10株双药联合均未达到抑菌活性的菌株，只有ARP和AMP的三抗生素联合分别对7/10和6/10株菌株具有抑菌活性。持续杀灭效果≥99.9%的杀菌活性对于根除XDR-PA感染至关重要，特别是在免疫功能低下的宿主中。这些发现强调了开发针对广泛耐药pa的联合治疗方案的难度，表明至少需要3种抗生素联合使用，而且疗效取决于菌株。
Extreme drug-resistant Pseudomonas aeruginosa (XDR-PA) with decreased susceptibility to polymyxin B (PB) has emerged in Singapore, causing infections in immunocompromised hosts. Combination therapy may be the only viable therapeutic option until new antibiotics become available. The objective of this study is to assess the in vitro activity of various antibiotics against local XDR-PA isolates. PA isolates from all public hospitals in Singapore were systematically collected between 2006 and 2007. MICs were determined according to CLSI guidelines. All XDR-PA isolates identified were genotyped using a PCR-based method. Time-kill studies (TKS) were performed with approximately 105 CFU/ml at baseline using clinically achievable unbound concentrations of amikacin (A), levofloxacin (L), meropenem (M), rifampicin (R) and PB alone and in combination. Bactericidal activity (primary endpoint) was defined as a ≥3 log10 CFU/ml decrease in the colony count from the initial inoculum at 24 hours. 22 clinical XDR-PA isolates with PB MIC 2–16 µg/ml were collected. From clonal typing, 5 clonal groups were identified and nine isolates exhibited clonal diversity. In TKS, meropenem plus PB, amikacin plus meropenem, amikacin plus rifampicin, amikacin plus PB exhibited bactericidal activity in 8/22, 3/22, 1/22 and 6/22 isolates at 24 hours respectively. Against the remaining ten isolates where none of the dual-drug combination achieved bactericidal activity against, only the triple-antibiotic combinations of ARP and AMP achieved bactericidal activity against 7/10 and 6/10 isolates respectively. Bactericidal activity with sustained killing effect of ≥99.9% is critical for eradicating XDR-PA infections, especially in immunocompromised hosts. These findings underscore the difficulty of developing combination therapeutic options against XDR-PA, demonstrating that at least 3 antibiotics are required in combination and that efficacy is strain dependant.
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影响因子：
14.2
作者：
Magiorakos, A. -P.;Srinivasan, A.;Monnet, D. L.
通讯作者：
Monnet, D. L.
DOI：
10.1016/j.ijantimicag.2010.11.014
发表时间：
2010-12-01
影响因子：
10.8
作者：
Giamarellou, Helen
通讯作者：
Giamarellou, Helen
影响因子：
9.4
作者：
Koh, TH;Wang, GCY;Sng, LH
通讯作者：
Sng, LH
影响因子：
9.4
作者：
Pitout, JDD;Gregson, DB;Church, DL
通讯作者：
Church, DL
影响因子：
4.3
作者：
Mikulska, Malgorzato;Del Bono, Valerio;Viscoli, Claudio
通讯作者：
Viscoli, Claudio