The Effect of an Antimicrobial Restriction Program on Pseudomonas aeruginosa Resistance to B-Lactams in a Large Teaching Hospital

Randolph E. Regal, Pharm.D., Daryl D. DePestel, Pharm.D., Heather L. VandenBussche, Pharm.D.


Pharmacotherapy. 2003;23(5) 

In This Article

Abstract and Introduction

Study Objectives: To compare the use of -Lactams and subsequent Pseudomonas aeruginosa sensitivity patterns before and after implementation of a clinical pharmacist-facilitated antimicrobial restriction program in August 1997.
Design: Retrospective consecutive data collection.
Setting: Large university-affiliated medical center.
Intervention: The study results are the accumulation of the daily intervention activities of the antimicrobial restriction program. Data on antimicrobial grams purchased/1000 patient-days and susceptibility patterns were collected and analyzed retrospectively.
Measures and Main Results: Annual grams of ceftazidime, piperacillin, piperacillin-tazobactam, and other antipseudomonal -Lactams purchased/1000 patient-days were compared during the 2 full calendar years before the antimicrobial restriction program (1995-1996) with the 4 full calendar years after the program was implemented (1998-2001). Pseudomonas aeruginosa resistance trends for the antipseudomonal -Lactams, ciprofloxacin, and tobramycin also were compared for the 2 years before the program (1995-1996) with the last 2 years of the program (2000-2001). A 44% reduction in ceftazidime use was documented; ostensibly, minimal changes occurred in the overall use of piperacillin and piperacillin-tazobactam. During the same time period, ceftazidime resistance fell from 24% to 11.8% (p<0.001), whereas piperacillin resistance fell from 32.5% to 18.5% (p<0.001). Imipenem resistance declined from 20.5% to 12.3% (p<0.001) with an 18% reduction in use. Aztreonam resistance declined from 29.5% to 16.5% (p<0.001) despite a 57% increase in use. No changes in resistance to either ciprofloxacin or tobramycin were found.
Conclusion: Through an antimicrobial restriction program, a dramatic reduction in ceftazidime use was achieved with judicious use of other antipseudomonal antimicrobials, which resulted in reduced resistance of P. aeruginosa to other -Lactams.

Optimal control and treatment of Pseudomonas aeruginosa infections have been a focal point of antimicrobial control, research, and development efforts. Concern over this pathogen reflects its virulence, relative intrinsic resistance to antimicrobials, and ubiquity in places that harbor the critically ill. The organism is known for its ability to obtain and maintain resistance to antimicrobials through such measures as reduced outer-membrane permeability, multidrug efflux pumps, and antimicrobial-degrading enzymes such as -Lactamases.[1] The cephalosporins, particularly the third-generation agents, are known to induce and select for a variety of -Lactamases and other resistance mechanisms that impart multiresistant qualities to the strains in which they are conferred.[2,3,4] Therefore, it is reasonable to extrapolate that institutional overuse of third-generation cephalosporins could result in a population of more resistant strains of P. aeruginosa within that particular locale.

When the University of Michigan Health System (UMHS) started its antimicrobial restriction program in 1997, only limited data supported the notion that curtailing cephalosporin use could attenuate or reverse microbial resistance. Since that time, however, numerous published studies have shown that when broad-spectrum penicillins are used instead of third-generation cephalosporins, reductions in methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum -Lactamase-producing Klebsiella species, and other resistant gram-negative rods may ensue.[5,6,7,8,9] However, of the cephalosporin-sparing studies published and reviewed for this article, only one6 was able to show a statistically significant improvement in P. aeruginosa resistance trends. Given the morbidity and mortality implications of P. aeruginosa in the hospital setting, it is important to determine whether further support can be given to these findings. Therefore, we sought to assess the effect of ceftazidime use reduction, in conjunction with regulation of other antipseudo-monal agents, on resistance of P. aeruginosa to ceftazidime and other -Lactams.