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Long attributed to the presence of a relatively impermeable outer membrane (OM) that restricts the ready entry of antimicrobials into the cell, the intrinsic multidrug resistance of results, in fact, from the synergistic activity of the outer membrane barrier and the operation of broadly specific multidrug efflux systems that together limit antimicrobial accumulation in this organism. Chromosomally encoded multidrug efflux systems of the resistance-nodulation-division (RND) family appear to be the most significant regarding export of and, thus, resistance to clinically important antimicrobials in and, indeed, other gram-negative pathogens. Characterized by resistance to all aminoglycosides and often associated with reduced aminoglycoside accumulation, such resistance was attributed to reduced uptake owing to reduced permeability and, as such, was typically referred to as ‘’impermeability resistance.’’ Characterized by decreased susceptibility to all aminoglycosides and loss of the resistance phenotype in the absence of drug, this reversible pan-aminoglycoside resistance is referred to as adaptive resistance. Intriguingly, resistance appears to result from reduced aminoglycoside accumulation, reminiscent of impermeability resistance. A locus involved in the synthesis of periplasmic glucans, ndvB, has recently been implicated in biofilm resistance to several agents, particularly tobramycin. In one retrospective study correlating β-lactam resistance rates with β-lactam use, overall resistance to β-lactams decreased when use of ceftazidime and cefotaxime was curtailed in favor of cefepime.

Citation: Poole K. 2005. , p 355-366. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch26

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Antimicrobial Peptides
Fourth Generation Cephalosporins
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Table 1.

Efflux determinants of antimicrobial resistance in

Modified from Poole ( ).

Antimicrobial efflux systems are identified according to the families of bacterial drug efflux systems to which they belong. Resistance-nodulation-division (RND) family pumps are typically tripartite and include as additional components the membrane fusion protein (MFP) and the outer membrane factor (OMF). The multidrug and toxic compound extrusion (MATE) and small multidrug resistance (SMR) family drug pumps described to date in are single-component pumps.

wt/+, efflux system is known to be expressed in wild-type (wt) cells (under laboratory growth conditions). wt/− mutant/++, efflux system is expressed in wt cells, but expression is enhanced in resistant strains. wt/− mutant/+, efflux system is not expressed in wt cells but is expressed in resistant strains. In instances where the nature of the mutation leading to enhanced efflux gene expression is known, the gene is indicated along with the relative level of gene expression.

AG, aminoglycosides; BAC, benzalkonium chloride; BL, β-lactams; CM, chloramphenicol; CIP, ciprofloxacin; ER, erythromycin; FQ, fluoroquinolones; ML, macrolides; NOR, norfloxacin; NV, novobiocin; SM, sulfonamides; TC, tetracycline; TG, tigecycline; TS, triclosan; TP, trimethorpim. In instances where only one member of a class of antimicrobial has been tested or is known to be a substrate for a given pump, that member is identified. Where several members of an antimicrobial class are known to be substrates, the class is identified rather than the actual compounds tested.

Efflux of triclosan but not the other antimicrobials is provided by MexJK-OpmH.

Citation: Poole K. 2005. , p 355-366. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch26
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Table 2.

Summary of recent studies documenting the incidence of antimicrobial resistance in clinical isolates of

Citation: Poole K. 2005. , p 355-366. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch26
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Table 3.

β-Lactamases of

See reference for more details.

Citation: Poole K. 2005. , p 355-366. In White D, Alekshun M, McDermott P (ed), Frontiers in Antimicrobial Resistance. ASM Press, Washington, DC. doi: 10.1128/9781555817572.ch26

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