Gram-negative bacterial infections: a look at the past, a view of the present, and a glance at the future

An overview of infections caused by gram-negative bacteria over the past 40 years discloses remarkable changes in their specific etiology and management. These organisms were responsible for disease in the preantibiotic era but at a much lower frequency than at present, and fatality rates were generally high. Bacteria such as Pseudomonas and Serratia, now relatively commonly involved in infection, rarely, if ever, caused disease before antibiotics became available. Although often present in surgical wounds, these organisms clearly were colonizers rather than pathogens. It is clear that the use of potent antimicrobial agents has been responsible for a general decrease in the fatality rates associated with gram-negative bacterial infections. However, it is evident that their use has been involved in the development of potentially lethal complications not seen in the past. Factors presently recognized as playing important roles in the problems associated with the treatment of gram-negative bacterial infections are the increasing number of older and sometimes debilitated patients and the longer survival of individuals with tumors or leukemia who, because of immunosuppression due to disease or treatment, are highly susceptible to invasion by almost any organism. Factors that have increased the magnitude of the problem of treatment of gram-negative bacterial infections include an increasing frequency of bacterial resistance to one or more antibiotics and a tendency of physicians to use more than one drug, sometimes as many as three or four, to treat gram-negative bacterial infections, especially in immunosuppressed people. Such polypharmacy is responsible for the development of suprainfections, some of which are caused by organisms very difficult to eradicate.