Neu H C
Rev Infect Dis. 1983 Mar-Apr;5 Suppl 1:S9-20. doi: 10.1093/clinids/5.supplement_1.s9.
The discovery of antimicrobial agents had a major impact on the rate of survival from infections. However, the changing patterns of antimicrobial resistance caused a demand for new antibacterial agents. Within a few years of the introduction of penicillin, the majority of staphylococci were resistant to that drug. In the 1960s the production of the semisynthetic penicillins provided an answer to the problem of staphylococcal resistance. In the early 1960s most Escherichia coli were susceptible to the new beta-lactam antibiotic ampicillin; by the end of that decade, plasmid-mediated beta-lactamase resistance was found in 30%-50% of hospital-acquired E. coli. Use of certain agents resulted in the selection of bacteria, such as Klebsiella, that are intrinsically resistant to ampicillin. The original cephalosporins were stable to beta-lactamase, but the use of these agents was in part responsible for the appearance of infections due to Enterobacter species, Citrobacter species, and Pseudomonas aeruginosa. These bacteria, as well as Serratia, were resistant to many of the available beta-lactam agents. Aminoglycosides initially provided excellent activity against most of the facultative gram-negative bacteria. However, the widespread dissemination of the genes that cause production of the aminoglycoside-inactivating enzymes altered the use of those agents. Clearly, the evolution of bacterial resistance has altered the prescribing patterns for antimicrobial agents. Knowledge that beta-lactam resistance to ampicillin or cephalothin is prevalent is causing physicians to select as empiric therapy either a combination of two or more agents or agents to which resistance is uncommon. The new cephalosporins offer a broad spectrum of anti-bacterial activity coupled with low toxicity. However, physicians must closely follow the changing ecology of bacteria when these agents are used, because cephalosporins can also select bacteria resistant to themselves and thereby abolish their value as empiric therapy.
抗菌药物的发现对感染后的存活率产生了重大影响。然而，抗菌药物耐药模式的变化催生了对新型抗菌药物的需求。在青霉素问世后的几年内，大多数葡萄球菌对该药物产生了耐药性。20世纪60年代，半合成青霉素的生产解决了葡萄球菌耐药问题。20世纪60年代初，大多数大肠杆菌对新型β-内酰胺抗生素氨苄西林敏感；到该十年末，在30%-50%的医院获得性大肠杆菌中发现了质粒介导的β-内酰胺酶耐药性。使用某些药物导致了对氨苄西林天然耐药的细菌（如克雷伯菌）的出现。最初的头孢菌素对β-内酰胺酶稳定，但这些药物的使用在一定程度上导致了由肠杆菌属、柠檬酸杆菌属和铜绿假单胞菌引起的感染的出现。这些细菌以及沙雷菌对许多现有的β-内酰胺类药物耐药。氨基糖苷类药物最初对大多数兼性革兰氏阴性菌具有出色的活性。然而，导致氨基糖苷类药物失活酶产生的基因的广泛传播改变了这些药物的使用。显然，细菌耐药性的演变改变了抗菌药物的处方模式。了解氨苄西林或头孢噻吩的β-内酰胺耐药性普遍存在，促使医生选择两种或更多药物的联合使用或选择耐药性不常见的药物作为经验性治疗。新型头孢菌素具有广谱抗菌活性且毒性低。然而，在使用这些药物时，医生必须密切关注细菌生态的变化，因为头孢菌素也可能选择对其自身耐药的细菌，从而使其作为经验性治疗的价值丧失。
