Jones R N
Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Am J Med. 1996 Jun 24;100(6A):3S-12S. doi: 10.1016/s0002-9343(96)00102-7.
The selection of drug-resistant pathogens in hospitalized patients with serious infections such as pneumonia, urinary tract infections (UTI), skin and skin-structure infections, and primary or secondary bacteremia has generally been ascribed to the widespread use of antimicrobial agents. Issues of concern regarding gram-negative bacilli include the expression of extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumonias and constitutive resistance in some Enterobacteriaceae caused by Bush group 1 beta-lactamases. Current concerns with gram-positive pathogens are increasing multidrug resistance in methicillin-resistant Staphylococcus aureus, enterococci, and coagulase-negative staphylococci, and increasing incidence of penicillin-resistant Streptococcus pneumoniae. Contemporary treatment strategies for pneumonia in hospitalized patients mandate early empiric therapy for the most likely gram-positive and gram-negative pathogens. Newer beta-lactams, such as fourth-generation cephalosporins, may be useful in the treatment of pneumonia, including those cases associated with bacteremia. Combination beta-lactam/beta-lactamase inhibitor drugs, an aminoglycoside co-drug, or a carbapenem may also be indicated. The initial treatment of UTI in the hospital setting also may be empirically treated with the newer cephalosporins, combination broad-spectrum penicillins plus an aminoglycoside, a quinolone, or a carbapenem. Current problems in treating UTI include the emergence of extended spectrum beta-lactamase-producing Escherichia coli, the tendency of fluoroquinolones both to select for resistant strains of major UTI pathogens and to induce cross-resistance among different drug classes, and beta-lactam and vancomycin resistance of enterococci and coagulase-negative staphylococci. Treatment of skin and skin-structure infections is complicated by the coexistence of gram-positive and gram-negative infections, which may be drug resistant. Both fourth-generation beta-lactams and carbapenems may have in vitro activity against these pathogens; however, where these drugs--with their increased spectra and lower affinity for beta-lactamases and less susceptibility to beta-lactamase hydrolysis--fit into the therapeutic armamentarium remains to be determined. Initial clinical studies appear to be promising, nonetheless. The ability of both nosocomial and community-acquired pathogens to develop resistance to powerful broad-spectrum agents presents a great challenge for prescribing patterns and in the development of new drugs to be relatively resistant to inactivation.
在患有严重感染（如肺炎、尿路感染、皮肤及皮肤结构感染、原发性或继发性菌血症）的住院患者中，耐药病原体的产生通常归因于抗菌药物的广泛使用。与革兰氏阴性杆菌相关的问题包括产超广谱β-内酰胺酶的大肠杆菌和肺炎克雷伯菌的出现，以及某些肠杆菌科细菌因布什1组β-内酰胺酶导致的固有耐药性。目前对革兰氏阳性病原体的担忧在于耐甲氧西林金黄色葡萄球菌、肠球菌和凝固酶阴性葡萄球菌的多重耐药性增加，以及耐青霉素肺炎链球菌的发病率上升。住院患者肺炎的当代治疗策略要求针对最可能的革兰氏阳性和革兰氏阴性病原体进行早期经验性治疗。新型β-内酰胺类药物，如第四代头孢菌素，可能对肺炎治疗有用，包括那些伴有菌血症的病例。β-内酰胺类/β-内酰胺酶抑制剂联合用药、氨基糖苷类联合用药或碳青霉烯类药物也可能适用。医院环境中尿路感染的初始治疗也可经验性地使用新型头孢菌素、广谱青霉素联合氨基糖苷类、喹诺酮类或碳青霉烯类药物。目前尿路感染治疗中的问题包括产超广谱β-内酰胺酶大肠杆菌的出现、氟喹诺酮类药物既选择主要尿路感染病原体的耐药菌株又诱导不同药物类别间交叉耐药的趋势，以及肠球菌和凝固酶阴性葡萄球菌对β-内酰胺类和万古霉素的耐药性。皮肤及皮肤结构感染的治疗因革兰氏阳性和革兰氏阴性感染并存且可能耐药而变得复杂。第四代β-内酰胺类药物和碳青霉烯类药物在体外可能对这些病原体有活性；然而，这些药物——因其扩大的抗菌谱、对β-内酰胺酶较低的亲和力以及对β-内酰胺酶水解的较低敏感性——在治疗药物库中的地位仍有待确定。尽管如此，初步临床研究似乎很有前景。医院获得性和社区获得性病原体对强效广谱药物产生耐药性的能力，给处方模式以及开发相对不易失活的新药带来了巨大挑战。
