Of Pseudomonas, porins, pumps and carbapenems
Of Pseudomonas, porins, pumps and carbapenems
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DOI：
10.1093/jac/47.3.247
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发表时间：
2001-03-01
影响因子：
5.2
通讯作者：
Livermore, DM
中科院分区：
文献类型：
--
作者：
Livermore, DM
These differences between imipenem and meropenem allow arguments for either compound as ‘the less likely to cause resistance in P. aeruginosa’. The case for imipenem21 argues that, although it selects OprD–mutants, these have a narrow-spectrum insensitivity and remain fully susceptible to other drugs, whereas meropenem resistance co-depends on upregulation of MexA-MexB-OprM, a mechanism that compromises fluoroquinolones as well as other β-lactams. The case for meropenem17, 22 is that substantive resistance is much harder to achieve than to imipenem, since two mutations (loss of OprD and upregulation of MexA-MexB-OprM) are needed rather than one. The likelihood that a cell will simultaneously undergo both mutations is c. 10–14, whereas imipenem-resistant mutants, lacking OprD, emerge at c. 10–7. Although formal analyses of the risk of meropenem resistance emerging during therapy are lacking, there are far fewer case reports than for imipenem, even after 6 years of use. Moreover, there is a greater facility to raise the dosage with meropenem, overcoming low-level resistance.The stronger case is surely that for meropenem, primarily because of the high frequency of emergent imipenem resistance reported by Carmeli et al. 18 If imipenem is preferred as an antipseudomonal carbapenem, there is a strong risk that resistance will emerge and that a subsequent antibiotic will be needed. This, in turn, will exert its own selection pressure. In general the risk of obtaining multi-resistant mutants in such sequential usage is greater than where a drug requiring a double mutation is used in the first instance against a drug-naive bacterial population. 23
