Potential Role of Pharmacokinetics, Pharmacodynamics, and Computerized Databases in Controlling Bacterial Resistance | Infection Control & Hospital Epidemiology | Cambridge Core (original) (raw)

Abstract

Bacterial resistance to antibiotics continues to be a problem, in spite of increased knowledge of resistance mechanisms. Due to the multifactorial nature of bacterial resistance, studies that evaluate the association between antimicrobial exposure and emergence of resistance may fail to find a relationship unless other factors, in particular the association between patient-pathogen pharmacokinetics (PK) and pharmacodynamics (PD) and the emergence of bacterial resistance, are evaluated as well. It has been hypothesized that, in conjunction with good infection control practices, cycling of antimicrobial agents may prove to be effective in reducing resistance emergence.

There is some indication that there may be a relationship between the level of antibiotic exposure and the probability of emergence of bacterial resistance. As shown in our companion article in this supplement, factors associated with ciprofloxacin resistance in Pseudomonas aeruginosa included increased length of stay prior to isolation, exposure to ciprofloxacin, and respiratory tract site of bacterial isolation. However, in patients who received ciprofloxacin therapy, when exposure was at an area under the 24-hour inhibitory concentration curve (AUIC24)>110 (μg·h/mL)/μg/mL, resistance was decreased to 11%, a rate similar to that seen in respiratory isolates not exposed to ciprofloxacin (7%).

While the length of time the patient spends in the hospital and the site of infection cannot be controlled, by using PK and PD principles for dosing of ciprofloxacin, the emergence of ciprofloxacin resistance in P aeruginosa may be reduced. Prospective antibiotic-cycling studies may help to determine not only the impact of antibiotic cycling on the institution's antibiogram but also, through the use of PK and PD principles, may help to determine appropriate dosing schedules for antibiotics in order to reduce the probability of emergence of bacterial resistance.

References

1.Schlaes, DM, Gerding, DN, John, JF Jr, Craig, WA, Bornstein, DL, Duncan, RA, et al. Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals. Infect Control Hosp Epidemiol 1997;18:275–291.Google Scholar

2.McGowan, JE Jr. Antimicrobial resistance in hospital organisms and its relation to antibiotic use. Rev Infect Dis 1983;5:1033–1048.Google Scholar

3.Olson, B, Weinstein, RA, Nathan, C, Gaston, MA, Kabins, SAEpidemiology of endemic Pseudomonas aeruginosa: why infection control efforts have failed. J Infect Dis 1987;150:808–816.Google Scholar

4.Schentag, JJ, Hyatt, JM, Carr, JR, Paladino, JABirmingham, MC, Zimmer, GS, et al. Genesis of methicillin-resistant Staphylococcus aureus (MRSA), how treatment of MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and the importance of antibiotic management and infection control. Clin Infect Dis 1998;26:1204–1214.Google Scholar

5.McGowan, JE Jr. Is antimicrobial resistance in hospital microorganisms related to antibiotic use? Bull NY Acad Med 1987;63:253–268.Google Scholar

6.Thomas, JK, Forrest, A, Bhavnani, SM, Hyatt, JM, Cheng A Ballow, CH, et al. Pharmacodynamic evaluation of factors associated with the development of bacterial resistance in acutely ill patients during therapy. Antimkrob Agents Chemother 1998;42:521–527.Google Scholar

7.Levy, SB. Balancing the drug-resistance equation. Trends Microbiol 1994;2:341–342.Google Scholar

8.Forrest, A, Chodosh, S, Amantea, MA, Collins, DA, Schentag, JJ. Pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis. J Antimkrob Chemother 1997;40(suppl A):45–57.Google Scholar

9.Forrest, A, Nix, DE, Ballow, CH, Goss, TF, Birmingham, MC, Schentag, JJ. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimkrob Agents Chemother 1993;37:1073–1081.Google Scholar

10.Drusano, GL. Infection in the intensive care unit: beta-lactamase-mediated resistance among Enterobacteriaceae and optimal antimicrobial dosing. Clin Infect Dis 1998;27(suppl 1):S111–S116.Google Scholar

11.Hyatt, JM, Schentag, JJ. Pharmacodynamic modeling of risk factors for ciprofloxacin resistance in Pseudomonas aeruginosa. Infect Control Hosp Epidemiol 2000;21(suppl.):S9–S11.CrossRef Google Scholar PubMed

12.John, JF Jr, Fishman, NO. Programmatic role of the infectious diseases physician in controlling antimicrobial costs in the hospital. Clin Infect Dis 1997;24:471–485.CrossRef Google Scholar PubMed

13.Gerding, DN. Antimicrobial cycling: lessons learned from the aminoglycoside experience. Infect Control Hosp Epidemiol 2000;21(suppl):S12–S17.Google Scholar

14.Ballow, CH, Schentag, JJ. Trends in antibiotic utilization and bacterial resistance. Report of the National Nosocomial Resistance Surveillance Group. Diagn Microbiol Infect Dis 1992;15(suppl):37S–42S.CrossRef Google Scholar PubMed

15.Gerding, DN, Larson, TA, Hughes, RA, Weiler, M, Shanholtzer, C, Peterson, LR. Aminoglycoside resistance and aminoglycoside usage: ten years of experience in one hospital. Antimkrob Agents Chemother 1991;35:1284–1290.Google Scholar

16.Schentag, JJ. Antibiotic dosing—does one size fit all? JAMA 1998;279:159–160.Google Scholar