Impact of Antibiotic Resistance in Gram-negative Bacilli on Empirical and Definitive Antibiotic Therapy

Serious infections with gram-negative pathogens continue to be associated with considerable mortality. Increasing antibiotic resistance in organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae is contributing to difficulties with choosing antibiotics to prescribe for these infections. Optimization of therapy against these organisms starts with the initial empirical antibiotic choice. Surveillance data and hospital or unit antibiograms may inform this decision, although individualization of the initial regimen on the basis of prior antibiotic use and prior isolation of resistant pathogens may be more important. Combinations of antibiotics are often required empirically, and "combination antibiograms" may need to be developed for this purpose. Preliminary data suggest that extending the time over which a dose of antipseudomonal beta-lactam antibiotics is infused may improve clinical outcomes; however, this idea remains to be confirmed in randomized trials. The role of direct susceptibility testing in aiding more-rapid initiation of appropriate antibiotic therapy is also being studied. When identification and susceptibility testing is complete, the antibiotic regimen for infections due to gram-negative pathogens can be "fine tuned." On some occasions, this fine tuning necessitates the introduction of "salvage" antibiotics, such as colistin or tigecycline; on others, it necessitates de-escalation and early termination of therapy. The lack of new antibiotic options against gram-negative pathogens underscores the need for optimization of current therapies and prevention of the spread of these organisms.