Emerging Gram-Negative Antibiotic Resistance: Daunting Challenges, Declining Sensitivities, and Dire Consequences

Abstract

Emerging antibiotic resistance has created a major public health dilemma, compounded by a dearth of new antibiotic options. Multidrug-resistant Gram-negative organisms have received less attention than Gram-positive threats, such as methicillin-resistant Staphylococcus aureus, but are just as menacing. Pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii employ a variety of resistance mechanisms and are associated with dangerous nosocomial outbreaks. In some cases these pathogens have expressed resistance to all clinically available compounds. The emergence of extended-spectrum β-lactamase-producing organisms in the community has raised alarm. Furthermore, the carbapenems, currently the most successful class of antibiotics, are showing signs of vulnerability. While the search for new antibiotic options continues, there is urgent need to employ strategies that will slow the development of resistance to the current armamentarium, such as avoiding prolonged antibiotic use or under-dosing, using pharmacokinetic and pharmacodynamic principles to choose dosing regimens, and encouraging early and aggressive empirical therapy, followed by de-escalation and narrowing the antimicrobial spectrum when culture results become available.