The widespread use of broad-spectrum antibiotics has led to emergence of an
tibiotic-resistant strains of many Gram-negative organisms. This problem is
particularly serious in critically ill patients, especially those with ven
tilator-associated pneumonia, Extensive antibiotic resistance has developed
in Gram-negative bacteria, due both to innate resistance in some species a
nd the fact that they are highly adept at acquiring antibiotic-resistant de
terminants from each other. Antibiotic resistance develops through the foll
owing three basic mechanisms: alteration of the drug target, prevention of
drug access to the target (including actively removing the drug from the ba
cteria), and drug inactivation. Certain Gram-negative microorganisms are pa
rticular problems in the intensive care unit, including Pseudomonas aerugin
osa, Acinetobacter spp,, Stenotrophomonas maltophilia, and the Enterobacter
iaceae. The combination of an increasing population at risk, and the natura
l virulence and adaptability of Gramnegative bacteria guarantees that criti
cal care physicians will face a persistent and increasing challenge from th
ese pathogens.