Laurie L. Briceland

Frequency of Hospitalization after Exposure to Known Drug‐Drug Interactions in a Medicaid Population

A matched‐pair case‐control analysis of Medicaid claims was performed to determine the risks of hospitalization associated with drug‐drug interactions. Patients were hospitalized and controls were not. They were randomly matched based on contemporaneous eligibility for Medicaid benefits. Odds ratios for hospitalization in patients exposed to known drug‐drug interactions were compared with those in patients exposed to one of the interacting agents. When confidence intervals did not overlap, the odds ratio was considered to be significantly increased. Odds ratios were significantly increased for many interacting drug pairs, and were associated with commonly recognized interactions as well as less widely recognized ones. Cimetidine interactions achieved significance only with theophylline. In the Medicaid population, exposure to a number of drug‐drug interactions was associated with a significantly increased risk of hospitalization.

Survey of Antibiotic Control Policies in University-Affiliated Teaching Institutions

OBJECTIVE: To determine the type and extent of antibiotic control policies currently in use in a group of university-affiliated teaching institutions. DESIGN: A survey of antibiotic control policies and procedures (e.g., antibiotic order sheets, formulary restrictions, automatic stop orders for specific indications) was developed. SETTING: The University Hospital Consortium (UHC), a nonprofit group of academic health centers located in 33 states throughout the US. PARTICIPANTS: The survey was mailed to 60 UHC members. RESULTS: The survey was returned by 48 (80%) institutions. Most hospitals use either restrictions (81%) and/or official recommendations (56%) to manage antibiotic use. Antibiotics were restricted most commonly by service or unit (69%), indication (69%), or to the infectious disease service (60%). Antibiotic order sheets are used in 21 (44%) of the hospitals, of which 14 require completion by the prescriber. Monitoring of compliance with established restrictions is primarily the responsibility of the pharmacist processing the order (84%) and/or a clinical pharmacist (53%). When an order does not comply with restrictions or compliance cannot be determined, the prescriber is contacted prior to dispensing in 77% and 83% of the cases, respectively. In cases of noncompliance in which the prescriber refuses to alter an order to meet restrictions, 40% of hospitals refuse to dispense the drug and 35% dispense the drug but refer the case to another authority (infectious disease service or pharmacy and therapeutics committee). CONCLUSIONS: Considering the widespread use of antibiotic control programs, further investigation of the success of such programs in optimizing drug therapy, improving patient outcome, and curtailing the antibiotic budget within and among specific institutions is warranted.

Single Daily Dosing of Aminoglycosides

To evaluate the rationale behind dosing aminoglycosides as a single daily dose versus traditional dosing approaches, we conducted a MEDLINE search to identify all pertinent articles, and also reviewed the references of all articles. Single daily dosing of aminoglycosides is not a new concept, having been examined since 1974. The advantages of this regimen include optimum concentration‐dependent bactericidal activity, longer dosing intervals due to the postantibiotic effect (PAE), and prevention of bacterial adaptive resistance. Because of longer dosing intervals, toxicity may also be delayed or reduced. Costs may be reduced due to decreased monitoring and administration. Clinically, the regimen has been implemented in various patient populations with reported success. Questions remain, however, about optimum dose, peak and trough serum concentrations, and dose adjustment in patients with renal impairment or neutropenia. More clinical experience with this method in large numbers of patients has to be published. Pharmacists can be instrumental in monitoring patients receiving once‐daily therapy and by educating health care professionals as to the rationale behind the therapy.

Sequential parenteral and oral ciprofloxacin regimen versus parenteral therapy for bacteremia : A pharmacoeconomic analysis

Objective To compare, in patients with gram-negative bacteremia, a course of parenteral antibiotic therapy alone with initial parenteral therapy followed by oral ciprofloxacin in terms of the length of hospitalization, clinical effectiveness, toxicity, and cost. Design A prospective, controlled, randomized, open trial in select hospitalized patients. Setting Large metropolitan teaching hospital. Patients Fifty hospitalized patients with proven gram-negative bacteremia were randomized to receive either oral ciprofloxacin (group 1) following a 72-hour initial intravenous antibiotic regimen or to continue parenteral therapy alone (group 2). To compare the length of hospitalization, an additional group of 50 hospitalized patients with bacteremia (not enrolled in the study, group 3) were analyzed. Intervention Parenteral antibiotics for 72 hours followed by continuation of a parenteral regimen or oral ciprofloxacin 750 mg bid. Main Outcome Measures Clinical response, toxicity, and length of hospitalization. Results Clinical resolution was comparable in the 24 group 1 patients receiving intravenous antibiotics followed by oral ciprofloxacin (83%), the 26 group 2 patients receiving parenteral therapy alone (77%), and the 50 comparison patients (76%). There was little toxicity noted in any group, and the initial parenteral antibiotic regimens were similar. The mean numbers of hospital days on antibiotics were 9.1, 11.2, and 10.6 days in groups 1, 2, and 3, respectively (p < 0.05 for group 1 vs. group 2 or 3), and the lengths of hospitalization were 9.8, 15.7, and 12.1 days, respectively (p < 0.05 for group 1 vs. group 2 or 3). Shortening the length of hospitalization and days of antibiotic therapy was associated with a cost savings of up to

Intrathecal Administration of Amikacin for Treatment of Meningitis Secondary to Cephalosporin-Resistant Escherichia Coli

78 000 for group 1 patients. Conclusions Parenteral therapy for 72 hours followed by oral ciprofloxacin significantly shortened both the number of hospital days taking antibiotics and the length of stay compared with parenteral therapy alone. Both regimens were equally effective and safe in the therapy of gram-negative bacteremia, and initial parenteral therapy followed by oral ciprofloxacin was cost-effective.

Pentamidine-Associated Nephrotoxicity and Hyperkalemia in Patients with Aids

OBJECTIVE: To report a case of gram-negative bacillary meningitis (GNBM) secondary to cephalosporin-resistant Escherichia coli that was treated with intrathecal and intravenous amikacin and intravenous imipenem/cilastatin (I/C). CASE SUMMARY: A patient who had undergone two recent neurosurgical procedures developed GNBM and bacteremia. He was treated empirically with ceftazidime. Both bloodstream and cerebrospinal fluid isolates were identified as E. coli, resistant to third-generation cephalosporins, penicillins, tobramycin, and gentamicin. The patient was subsequently treated with intravenous and intrathecal amikacin plus intravenous I/C He experienced subjective and objective improvement on days 2–4 of antimicrobial therapy; two generalized tonic-clonic seizures occurred on days 7 and 12. Intrathecal amikacin was discontinued after 6 days, and intravenous amikacin and I/C were discontinued after 23 and 27 days, respectively. The patients mental status did not completely return to premeningitis baseline. DISCUSSION: Third-generation cephalosporins are the treatment of choice for GNBM. In the case reported herein, bacterial resistance to these agents prompted the use of a therapy that has not been well studied and is also considered to be less safe and perhaps less efficacious. Treatment of GNBM with an intrathecally administered aminoglycoside or with intravenous I/C plus an aminoglycoside is reviewed. CONCLUSIONS: Patients with GNBM secondary to third-generation cephalosporin-resistant organisms may require therapies that may be less effective and more toxic. Further study of alternative agents is warranted.

Dosing adjustment of 10 antimicrobials for patients with renal impairment.

The incidences of pentamidine-associated nephrotoxicity and hyperkalemia were determined from a retrospective review of records in AIDS patients using standard definitions for both toxicities. There were 37 patients, mean age 35.6 ± 7.7 years and mean initial creatinine clearance (Clcr) 96 mL/min (1.6 mL/s). The mean pentamidine dose was 255 ± 60 mg/d (3.87 + 0.33 mg/kg/d). The mean total dose was 2900± 1600 mg given over 11.6± 5.9 days (range 3–21 d). In 28 patients who were nephrotoxic (8 mild, 6 moderate, 14 severe), 27 episodes were possibly or probably pentamidine-associated. Total dose and days to nephrotoxicity onset were 1570 ± 710 mg and 6.4 ± 2.8 days (range 2–15 d), respectively. Nine patients became hyperkalemic (one required countermeasures) and all cases were pentamidine-associated. Total dose and days to hyperkalemia onset were 2510 ± 1460 mg and 9.2 ± 4.9 days (range 3–16 d), respectively. Mean baseline potassium increased and Clcr decreased significantly during therapy (from 4.2 to 4.9 mEq/L and from 96 to 70 mL/min, respectively). No correlation between nephrotoxicity or hyperkalemia and initial renal function was found, but significant correlations were found between the total pentamidine dose or duration and the percent of renal function remaining. AIDS patients have a high incidence of pentamidine-associated nephrotoxicity (up to 73 percent) and hyperkalemia (24 percent) with a trend to earlier onset of the former.

Once-Daily Aminoglycosides in the Treatment of Gram-Positive Endocarditis

Objective: To describe a program of creatinine clearance–based dosage adjustment of 10 renally eliminated antimicrobial agents and to discuss the utility of such a program in a hospital as a method of quality assurance (by ensuring that patients with renal impairment receive generally accepted dosage adjustments), based on pharmacodynamic principles. Methods: Consecutive patients prescribed any of 10 targeted renally eliminated antibiotics were included. Recommendations for dosage adjustment were made to the prescriber based on a calculated creatinine clearance. Additional adjustments in drug therapy were performed, including dosage recommendations of nontargeted drugs, simplification of antibiotic regimens, and conversion of intravenous to oral therapy. A cost analysis was performed. Results: During a 6-month study period, 160 dosage changes (7.6% of total number screened) were recommended in 137 patients receiving the targeted antimicrobial agents. Prescribers accepted 147 recommendations (91.9%). A dosage change recommendation was necessary more than 12% of the time for acyclovir, ceftazidime, and imipenem/cilastatin. A cost avoidance of

Recent Advances: Antiinfectives

11 702.08 was realized. Ancillary drug recommendations that were offered and accepted during the program realized a cost avoidance of

Formulary conversion of cefoxitin usage to cefotetan: experience at a large teaching hospital.

6613.75. Conclusions: This dosage adjustment program using pharmacodynamic principles was successful in optimization of dosing, potential minimization of morbidity caused by excessive dosing, and demonstration of direct and potentially indirect cost avoidance. A dosing program for patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.