Antimicrobial Stewardship Programs: Effects on Clinical and Economic Outcomes and Future Directions

Resistance

Another goal of ASPs is the prevention of antimicrobial resistance, an area where the evidence generally suggests benefit associated with ASP interventions. Resistance rates to common troublesome organisms, such as methicillin-resistant S. aureus (MRSA), imipenem-resistant P. aeruginosa , and extended-spectrum β-lactamase (ESBL)–producing Klebsiella spp were significantly reduced in a meta-analysis; ESBL-producing E. coli infections were not, however [22]. An ITS study found significantly reduced MRSA resistance, as well as reduced Pseudomonal resistance to imipenem-cilastin and levofloxacin (all P < 0.001), but no significant changes with respect to piperacillin/tazobactam, cefepime, or amikacin resistance [32]. This study also noted increased E. coli resistance to levofloxacin and ceftriaxone (both P < 0.001). No significant changes in resistance were noted for vancomycin-resistant enterococci. It may be a reasonable expectation that decreasing inappropriate antimicrobial use may decrease long-term antimicrobial resistance; but as most studies only span a few years, only the minute changes in resistance are understood [23]. Longer duration studies are needed to better understand resistance outcomes.

Of note is a phenomenon known as the “squeezing the balloon” effect. This can be associated with ASPs, potentially resulting in paradoxically increased resistance [43]. That is, when usage restrictions are placed on certain antibiotics, the use of other non-restricted antibiotics may increase, possibly leading to increased resistance of those non-restricted antibiotics [22] (“constraining one end [of a balloon] causes the other end to bulge … limiting the use of one class of compounds may be counteracted by corresponding changes in prescribing and drug resistance that are even more ominous” [43]). Karanika et al [22] took this phenomonen into consideration, and assessed restricted and non-restricted antimicrobial consumption separately. They found a reduction in consumption for both restricted and non-restricted antibiotics, which included “high potential resistance” antibiotics, specifically carbapenems and glycopeptides. In the study conducted by Cairns et al [28], a similar effect was observed; while the use of other classes of antibiotics decreased (eg, cephalosporins and aminoglycosides), the use of β–lactam–β–lactamase inhibitor combinations actually increased by 48% (change in use: +48.2% [95% CI 21.8%–47.9%]). Hohn et al [26] noted an increased usage rate of carbapenems, even though several other classes of antibiotics had reduced usage. Unfortunately, neither study reported resistance rates, so the impact of these findings is unknown. Finally, Jenkins et al [32] assessed trends in antimicrobial use as changes in rates of consumption. Among the various antibiotics assessed in this study, the rate of flouroquinolone use decreased both before and after the intervention period, although the rate of decreased usage slowed post-ASP (the change in rate post-ASP was +2.2% [95% CI 1.4%–3.1%], P < 0.001). They observed a small (but significant) increase in resistance of E. coli to levofloxacin pre- vs. post-intervention (11.0% vs. 13.9%, P < 0.001); in contrast, a significant decrease in resistance of P. aeruginosa was observed (30.5% vs. 21.4%, P < 0.001). While these examples help illustrate the concept of changes in antibiotic usage patterns associated with an ASP, at best they approximate the “squeezing the balloon” effect since these studies present data for antibiotics that were either restricted or for which restriction was not clearly specified. The “squeezing the balloon” effect is most relevant for the unintended, potentially increased usage of non-restricted drugs secondary to ASP restrictions. Higher resistance rates among certain drug classes observed in the context of this effect would constitute a drawback to an ASP program.