Antibiotic Utilization Strategies to Limit Antimicrobial Resistance

Daniel P. Raymond, MD, Shawn J. Pelletier, MD, Robert G. Sawyer, MD


Semin Respir Crit Care Med. 2002;23(5) 

In This Article

Abstract and Introduction


Antimicrobial resistance is now being recognized as a major factor determining morbidity, mortality, and cost in the intensive care unit (ICU). Various strategies to limit its spread have evolved with our understanding and are based on four basic principles: infection prevention, infection eradication, containment of resistant species, and optimization of antibiotic utilization. The optimization of antibiotic utilization, at its most basic level, is the appropriate use of antibiotics and the limitation of unnecessary antibiotic administration/exposure consisting of appropriate diagnosis, acquiring appropriate culture and sensitivity data, implementing the most appropriate treatment, selecting appropriate antibiotics, and dosing appropriately. In addition various antibiotic utilization strategies including antibiotic utilization guidelines, formulary restriction, and antibiotic cycling or rotation have evolved from our understanding of the impact of changes in antibiotic utilization on subsequent antibiotic susceptibility patterns. These strategies can be utilized as a part of a multidisciplinary approach to limit the appearance and dissemination of antimicrobial resistance in our ICUs.

Objectives: Upon completion of this article, the reader should be able to: (1) summarize the four basic strategies to limit antimicrobial resistance; (2) discuss the main principles of optimizing antibiotic utilization; and (3) discuss several antibiotic utilization strategies that may limit antimicrobial resistance.
Accreditation: The University of Michigan is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.
Credits: The University of Michigan designates this educational activity for a maximum of 1.0 hour in category one credits toward the AMA Physicians Recognition Award.


The increasing prevalence of antimicrobial-resistant pathogens has become well recognized over the past decade. More than half of the greater than 2 million nosocomial infections occurring annually in the United States are due to antibiotic-resistant organisms with an estimated impact of more than 70,000 lives and $5 to $10 billion dollars annually.[1,2] The association of antimicrobial resistance with increased morbidity, mortality, and cost is well documented.[1,2,3,4,5,6,7,8,9,10] Various strategies to limit antimicrobial resistance have evolved with our understanding and are based on four basic principles: containment of resistant species (e.g., isolation and colonization surveillance), infection prevention (e.g., appropriate use of antibiotic prophylaxis, vaccination, and limited utilization of invasive devices), infection eradication (e.g., appropriate diagnosis and treatment), and optimizing antibiotic utilization.

Optimizing antibiotic utilization, or antibiotic stewardship, offers a promising and perhaps necessary means of limiting the spread of antibiotic resistance. Recognizing that antibiotic misuse is rampant[11,12,13] and prior antibiotic administration is an important risk factor for the development of antibiotic-resistant infection,[14,15,16,17,18] the most basic goal of antibiotic stewardship is the appropriate utilization of antibiotic therapy. This involves accurately identifying infectious episodes using standardized definitions, obtaining appropriate culture and sensitivity data, applying appropriate treatment modalities, selecting the most appropriate antibiotic for therapy when indicated, and dosing antibiotics appropriately. In addition to selecting the most appropriate antibiotic utilizing knowledge of hospital-specific and unit-specific antibiotic susceptibility patterns, treatment includes removal of invasive devices and prosthetic material, drainage of collections, and debridement of devitalized tissues. Equally important is avoiding inappropriate antibiotic use such as treatment of bacterial colonization (e.g., open wounds, colonized sputum), contamination (e.g., skin contaminants in blood cultures), or noninfectious causes of inflammation (e.g., pancreatitis).

Beyond the goal of achieving appropriate antibiotic utilization, various strategies have developed that entail the manipulation of antibiotic use to decrease the rate of antibiotic resistance. These strategies are based on the observation that alterations in antibiotic utilization are associated with alterations in antibiotic resistance patterns, presumably through alterations in antibiotic selection pressures. One of the earlier illustrations of this theory is the work by Gerding and colleagues[19] who, due to high rates of gentamicin resistance among gram-negative bacilli, substituted amikacin for gentamicin in the hospital formulary at two separate points in a 10-year time period at the Minneapolis Veterans Affairs Medical Center. A retrospective review of this 10-year period revealed a significant decline in the rate of gentamicin resistance among gram-negative bacilli following each substitution (12.0-6.4% following the first substitution and 9.7-5.8% following the second, p < 0.05 for both). Kollef et al[20] later studied the effects of a scheduled change in empiric antibiotic coverage of suspected gram-negative rod infection from ceftazidime to ciprofloxacin in 680 patients who had undergone cardiac surgery during two 6-month periods. The study revealed a significant reduction in the incidence of ventilator-associated pneumonia (VAP) (relative risk of VAP during the second 6-month period: 0.58; 95% CI 0.35 to 0.95; p = 0.028) presumably due to a significant reduction in VAP caused by antibiotic-resistant gram-negative bacilli (relative risk: 0.23; 95% C.I. 0.07 to 0.80; p = 0.013). Additionally they were able to demonstrate improved antibiotic susceptibility profiles for gram-negative isolates (48.8% resistant vs 20.0%; p = 0.05) but did not demonstrate a difference in crude mortality (5.1% vs 8.0%; p = 0.1) or mortality attributed to VAP caused by antibiotic-resistant gram-negative rods (1.7% vs 0.6%; p = 0.3) although this was not a primary end point. A number of additional reports have been published that further document the relationship between changes in antimicrobial utilization and antibiotic susceptibility.[21,22,23,24,25,26,27,28,29] Strategies that have evolved, including implementation of antibiotic guidelines/protocols, formulary restriction, and antibiotic cycling or rotation attempt to exploit this observation with the goal of reducing overall antibiotic resistance.