Potential role of pharmacokinetics, pharmacodynamics, and computerized databases in controlling bacterial resistance

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 (microg x h/mL)/microg/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.