Has the era of untreatable infections arrived?
Has the era of untreatable infections arrived?
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DOI：
10.1093/jac/dkp255
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发表时间：
2009-09-01
影响因子：
5.2
通讯作者：
Livermore, David M.
中科院分区：
文献类型：
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作者：
Livermore, David M.
抗生素耐药性是一个主要的公共卫生问题，人们担心我们很快就会用完抗生素。在现实中，情况更加复杂，对某些病原体有改善，但对另一些病原体却恶化了。针对耐甲氧西林金黄色葡萄球菌（MRSA）——最引人注目的病原体——的治疗选择范围正在扩大，达托霉素、利奈唑胺和替加环素都已上市，而替拉万星、头孢双普罗、头孢他林和达巴万星预计也将上市。肠球菌有一个更大的问题，特别是如果，如心内膜炎，需要杀菌活性，分离物具有高水平的氨基糖苷耐药性；然而，达托霉素、替拉万辛和拉苏培南都具有杀灭潜力。对于肠杆菌科，广谱β -内酰胺酶、AmpC酶和喹诺酮类药物耐药性的快速和令人不安的传播迫使对碳青霉烯类药物的依赖增加，对这些药物的耐药性通过金属、KPC和OXA-48 β -内酰胺酶的传播缓慢积累。克服这些机制的未来选择包括各种新的p -内酰胺酶抑制剂组合，但这些都不能克服目前循环的所有碳青霉烯酶类型。包括碳青霉烯类的多重耐药在非发酵菌中比在肠杆菌科中更为常见，主要取决于鲍曼不动杆菌中的OXA碳青霉烯酶和铜绿假单胞菌的染色体突变组合。虽然人们对改性的、毒性更低的多粘菌素衍生物和铁载体单巴塔姆BAL30072感兴趣，但在这方面还没有高级开发的药物，它对鲍曼不动杆菌和马铃薯伯克霍尔德菌复合体的成员具有令人印象深刻的活性。最后一个令人惊讶的问题是淋病奈瑟菌，其中每一种良好的口服药物都被依次侵蚀，而且口服氧亚胺类头孢菌素的储备现在很少，正在出现低水平的耐药性。
Antibiotic resistance is a major public health concern, with fears expressed that we shortly will run out of antibiotics. In reality, the picture is more mixed, improving against some pathogens but worsening against others. Against methicillin-resistant Staphylococcus aureus (MRSA)-the highest profile pathogen-the range of treatment options is expanding, with daptomycin, linezolid and tigecycline all launched, and telavancin, ceftobiprole, ceftaroline and dalbavancin anticipated. There is a greater problem with enterococci, especially if, as in endocarditis, bactericidal activity is needed and the isolate has high-level aminoglycoside resistance; nevertheless, daptomycin, telavancin and razupenem all offer cidal potential. Against Enterobacteriaceae, the rapid and disturbing spread of extended-spectrum beta-lactamases, AmpC enzymes and quinolone resistance is forcing increased reliance on carbapenems, with resistance to these slowly accumulating via the spread of metallo-, KPC and OXA-48 beta-lactamases. Future options overcoming some of these mechanisms include various novel P-lactamase-inhibitor combinations, but none of these overcomes all the carbapenemase types now circulating. Multiresistance that includes carbapenems is much commoner in non-fermenters than in the Enterobacteriaceae, depending mostly on OXA carbapenemases in Acinetobacter baumannii and on combinations of chromosomal mutation in Pseudomonas aeruginosa. No agent in advanced development has much to offer here, though there is interest in modified, less-toxic, polymyxin derivatives and in the siderophore monobactam BAL30072, which has impressive activity against A. baumannii and members of the Burkholderia cepacia complex. A final and surprising problem is Neisseria gonorrhoeae, where each good oral agent has been eroded in turn and where there is now little in reserve behind the oral oxyimino cephalosporins, to which low-level resistance is emerging.