Cases like the one described are not uncommon. The microorganisms associated with infections that were relatively easy to treat (e.g., acute cystitis, Clostridium difficile colitis) a decade ago are becoming increasingly resistant to both conventional and late-generation antibiotic therapies.

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Antimicrobial-resistant infections are associated with a host of problems. In addition to increasing morbidity and mortality, antimicrobial resistant infections lead to higher health-related costs and challenge our ability to contain the spread of infection.

Furthermore, with the high rate of global travel, antimicrobial resistance (AMR) has no boundaries and jeopardizes national and international health and economic security.1 Nurse practitioners and physician assistants routinely diagnose and treat infections, so it is critical that they understand AMR and how it impacts their practice.

The purpose of this article is to (1) briefly review AMR, (2) discuss current trends in prescribing antibiotics and AMR, (3) review principles of appropriate antibiotic prescribing, and (4) discuss the concept of “antibiotic stewardship” and how NPs and PAs can become involved in the antibiotic stewardship campaign.

History of AMR

AMR is by no means a new phenomenon. Shortly after discovering penicillin in 1928, Alexander Fleming also observed AMR2 and warned about its dangers in his 1945 Nobel prize acceptance speech,3 just as penicillin was being introduced into health care. Since then, AMR has grown exponentially, and for the past decade, it has been recognized as a major global health threat by both the Centers for Disease Control and Prevention4,5 and the World Health Organization.1,6

Simply put, AMR is the failure of microorganisms (i.e., bacteria, fungi, viruses, some parasites) to be eliminated or curtailed by antibiotics to which they were previously sensitive (i.e., responsive). AMR is a naturally occurring phenomenon. Over time, microorganisms that are exposed to a particular antimicrobial agent will develop resistance mechanisms to that agent. These mechanisms are then transferable to other microorganisms, even some that have never been directly exposed to antibiotics.

Clinicians can accelerate the development of AMR by putting more antibiotics into the environment; conversely, we can slow the rate of AMR by curtailing antibiotic use. However, whenever antibiotics are used (even appropriately for legitimate infections), AMR will develop. Microorganisms will find a way to survive.7

AMR is always in a state of transition.5 As antibiotic exposure varies, rates of AMR increase and decrease. Mechanisms by which microorganisms develop antibiotic resistance are often associated with a “fitness cost” that makes it more difficult for microorganisms to survive and reproduce.

As antibiotic pressure diminishes, many microorganisms will gradually lose their antibiotic-resistant mechanisms; however, this loss of resistance occurs much more slowly than development of resistance.7 For example, widespread use of second-generation macrolides (e.g., azithromycin [Zithromax], clarithromycin [Biaxin]) have resulted in an increase in macrolide-resistant strains of Streptococcus pneumoniae.8-10 However, at least one study has demonstrated that several years after macrolides were discontinued in a particular community, S. pneumoniae resistance to macrolides diminished precipitously.11

Although all microorganisms are subject to AMR, there are several highly resistant microorganisms of which clinicians need to be aware, including the gram-negative species E. coli, Neisseria gonorrhoeae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Campylobacter jejuni, all of which are becoming increasingly resistant to broad-spectrum, late-generation antibiotics.

Highly resistant gram-positive bacteria include Enterococcus faecalis, Enterococcus faecium, S. pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, and C. difficile.12 In addition, Acinetobacter baumannii is a highly resistant gram-positive organism that we are seeing more frequently as infected soldiers return from Iraq.5,12

A number of social, agricultural, and ecological factors have been linked to the rise in AMR rates observed over the past two decades;13 however, poor hand hygiene and inappropriate antibiotic use for acute respiratory infections (ARIs) that are primarily viral in etiology (e.g., acute nonstreptococcal pharyngitis, acute sinusitis, and acute bronchitis) have also contributed to the increase in AMR.14

Fortunately, the rates of inappropriate antibiotic prescribing for viral ARIs have declined somewhat over the past decade.15-19 However in children younger than age 14 years, clinicians continue to prescribe antibiotics more than 50% of the time for ARIs that are primarily viral in etiology.20 In addition, recent studies indicate an increase in the use of broad-spectrum antibiotics for ARIs.15,21

Antibiotic prescribing habits of NPs and PAs

A few studies have examined antibiotic prescribing habits for ARIs of NPs and PAs and have generally found no differences between physician and NP/PA prescribing rates. Although one study reported that NPs and PAs prescribed antibiotics for ARIs significantly more than physicians (52.5 vs. 39.0%, P=.05),22 the study was limited by a disproportionately low number of NP and PA visits compared to physician visits (194,000 physician visits vs. 5,000 NP or PA visits).23

Other studies that have compared antibiotic prescribing for ARIs among physicians, NPs, and PAs have no found differences in prescribing rates.24,25 In addition, a study comparing antibiotic prescribing patterns for viral ARIs between physicians and NPs found no significant differences between the two groups.26 Even if there are no differences in how antibiotics are prescribed, the data overwhelmingly indicate that clinicians continue to make inappropriate decisions about antibiotics (both in quantity and type).