The effect of fluoroquinolone use on the susceptibility of Pseudomonas aeruginosa to fluoroquinolones in U.S. hospitals was studied. Benchmarking surveys were sent annually to pharmacists practicing in U.S. hospitals from 1993 to 1999. Data collected included hospital characteristics, antimicrobial expenditures and use, antimicrobial stewardship activities, and bacterial susceptibilities. Antimicrobial expenditures were normalized for the number of occupied beds (OBs) per year. General linear modeling and repeated-measures mixed-effects modeling were used to determine factors predictive of P. aeruginosa susceptibility to fluoroquinolones. A total of 174 hospitals provided data for fluoroquinolone expenditures and susceptibility of P. aeruginosa; the median number of years of data was 3 (range, 1-6), representing 416 hospital years. Community hospitals contributed a majority of the data. Median fluoroquinolone expenditures increased gradually from $230 per OB in 1993 to $400 per OB in 1998. A 55% increase to $620 per OB occurred in 1999, largely because of increased spending on levofloxacin. Susceptibility to ciprofloxacin was commonly used to assess fluoroquinolone susceptibility. The median susceptibility of P. aeruginosa to ciprofloxacin decreased from 84% to 71%. Increasing expenditures for ofloxacin and levofloxacin, but not ciprofloxacin, were associated with decreasing P. aeruginosa susceptibility to ciprofloxacin. In the final multivariable model, each study year after 1993 and every increase in ofloxacin expenditure of $100 per OB were associated with decreases in P. aeruginosa susceptibility. Data from a benchmarking survey of U.S. hospitals for 1993-1999 revealed increases in levofloxacin expenditures, total fluoroquinolone expenditures, expenditures for nonfluoroquinolone antipseudomonal antimicrobials, and total antimicrobial expenditures in 1999. Increases in expenditures for levofloxacin and ofloxacin were associated with a significant decrease in P. aeruginosa susceptibility to ciprofloxacin.
Pharmacokinetic characteristics and pharmacodynamic properties dictate antimicrobial response and, along with natural immune responses, clinical outcomes. As new agents are developed with long half-lives, we will lose the ability to differentiate between concentration-dependent and time-dependent properties. The area under the inhibitory concentration curve (AUIC) defines drug regimens as a ratio of drug exposure to minimum inhibitory concentration (MIC) and allows them to be compared with each other. With AUIC and agents with long half-lives, these comparisons are possible regardless of chemical classification or concentration or time-dependent activity. Historical examples of reduced drug exposure from decreased doses (i.e., cefaclor, clarithromycin, and ciprofloxacin), and thus low AUIC values, directly correlate with drug resistance. In the face of rising MICs (as is occurring worldwide with Streptococcus pneumoniae), close attention to appropriate dosing and concentration above the MIC may delay and potentially even prevent antibiotic resistance. Creating selective pressure on reliable antibiotics by inappropriately reducing their doses will undoubtedly challenge these agents and may destroy entire drug classes with similar mechanisms of action or resistance.
SOCIETY OF CRITICAL CARE MEDICINE 32ND CRITICAL CARE CONGRESS SAN ANTONIO, TEXAS, USA JANUARY 28-FEBRUARY 2, 2003: ORAL/SANDWICH PRESENTATIONS: Poster Presentation: Clinical Science: Sepsis Infection: PDF Only
Journal Article Vancomycin concentrations associated with red-top and serum-separator collection Get access Maria Dybala, Pharm.D., Maria Dybala, Pharm.D. Pharmacist Sisters Charity Hospital 2157 Main Street Buffalo, NY 14214 mdybala@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar Kristin Gilliland, Pharm.D. Kristin Gilliland, Pharm.D. Pharmacist Mercy Hospital 565 Abbott Road Buffalo, NY 14220 kkg15@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 59, Issue 2, 15 January 2002, Page 196, https://doi.org/10.1093/ajhp/59.2.196 Published: 15 January 2002
790 Glucocorticoids have been an integral component of combination immunosuppressive therapy in renal transplant recipients (RTR). No data has described the influence of gender on the pharmacokinetics or cortisol response of these agents. The purpose of this study was to evaluate the pharmacokinetics and cortisol response of methylprednisolone (MEPN) in female RTR with stable creatinine clearances (CrCl) compared to previously evaluated male RTR. Thirteen premenopausal (PRE) [ages 30-49; CrCl: 52 ± 21 ml/min} and 8 post-menopausal (POST) RTR [ages 40-68; CrCl:55 ± 22 ml/min] receiving chronic MEPN (mean dose; 7 mg) were evaluated over 24-hours. Serial blood samples were collected after 20-30 minute IV infusion of MEPN. This group was compared to 16 male counterparts (CrCl: 81 ± 20 ml/min) receiving chronic MEPN (mean dose: 11.4 mg/day). MEPN and cortisol were analyzed by HPLC with pharmacokinetics parameters generated by WINNONLIN. The mean clearance (CL) of MEPN for the PRE patients was 225 ± 89.4ml/hr/kg compared to 260 ml/hr/kg (p=0.6) in males with no significant difference noted in volume of distribution or half-life between groups. Dose-normalized AUC of MEPN reflected greater drug exposure in PRE RTR (66 ± 20 ng · hr/ml) compared to males (46 ± 20 ng · hr/ml; p=0.174). In the POST patients, the MEPN CL was significantly slower (146 ± 33 ml/hr/kg; p< 0.05) than noted in males. The dose-normalized AUC of MEPN in POST was significantly greater (104 ± 21 ng·hr/ml; p< 0.05) than in male RTR. A defined 24-hour cortisol pattern was noted in 9/13 PRE and 5/9 POST patients. A mean 8 AM cortisol concentration of 111.2 ng/ml in the PRE and 103.4 ng/ml in the POST groups was found. Cortisol declined in a mono-exponential fashion in both groups. Male RTR demonstrated similar cortisol responses and no statistical differences were noted. The results in PRE RTR contradict data documenting a more rapid CL of MEPN in young women with the potential of increased drug exposure. The significant reduction in MEPN CL in the POST group suggest that increased drug exposure may impact on the development of steroid-induced adverse effects. Coupling the defined cortisol response noted in these female RTR with these pharmacokinetic findings, the likelihood of increased adverse effects in women requiring individualized dose adjustments should be considered.
