Advanced Concepts

The first antibiotics isolated were natural secretions from fungi and other organisms. Synthetic modifications of these natural agents were designed to increase the spectrum of activity (ability to kill more organisms) and to overcome resistance. For example, cephalosporins include first-generation agents, ceph-alothin and cefazolin active against Staphylococcus, Streptococcus, and some Enterobacteriaceae. A second generation of cephalosporins, cefamondole, cefoxitin, and cefuroxime, is active against more Enterobacteriaceae and organisms resistant to p-lactam antibiotics. A third generation, cefotaxime, ceftriaxone, and ceftazidime, is active against P. aeruginosa as well as many Enterobacteriaceae and organisms resistant to p-lactam antibiotics. The fourth generation, cefepime, is active against an extended spectrum of organisms resistant to p-lactam antibiotics.

numbers below the detection levels of routine laboratory sensitivity testing methods.

There are several ways in which microorganisms develop resistance (Table 12.6). First of all, bacteria can produce enzymes that inactivate the agent. Examples of this resistance mechanism are seen in S. aureus and

Table 12.5 Mode of Action of Antimicrobial Agents

Mode of Action


Disrupts cell wall

Beta-lactams (penicillins and

synthesis or integrity


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