Home care pharmacy: extending clinical pharmacy services beyond infusion therapy.

A clinical pharmacy program was developed at an established home health care (HHC) agency to demonstrate the need for clinical pharmacy services in the HHC population and to explore opportunities for providing pharmaceutical care beyond infusion-related therapies. Initial experiences of this pilot project are described. Patients were found to be primarily elderly (mean age, 70 years) and to use a substantial number of medications. While only 11% of patients referred to the agency required infusion therapy, multiple opportunities for pharmacist involvement in patient care were identified and a variety of projects were undertaken. A drug information service was developed, a retrospective evaluation of patients with congestive heart failure led to an interventional study, a cisapride intervention was implemented, home vancomycin monitoring was assessed, pharmaceutical care services were provided to patients enrolled in a long-term home care program, a pain management initiative was begun, adverse drug reactions were identified and reported, and pharmacists participated in agency policy development. Preliminary data suggest that pharmacist involvement positively affected patient care. Drug information was provided on 232 occasions. Cisapride was discontinued in five patients with contraindications to the agent. Comprehensive pharmacotherapy assessments were performed on 29 long-term-care patients, generating 129 therapy recommendations of which 33% were accepted. Pharmacists working with a home care agency identified numerous opportunities for improving patient care. Many of the patients receiving home care services were elderly, took a substantial number of medications, and were at risk for drug-related problems and suboptimal therapy.

Once-daily aminoglycosides in the treatment of gram-positive endocarditis.

OBJECTIVE: To examine the role of once-daily aminoglycosides (ODA) in the treatment of gram-positive endocarditis. DATA SOURCES: A MEDLINE search was conducted from January 1984 to August 1998, and a Current Contents search was performed from September 1998 to December 1998, using endocarditis or aminoglycoside as key words. In addition, relevant articles were cross-referenced to screen for additional information. DATA EXTRACTION: Data published in English regarding the use of aminoglycosides in endocarditis are cited. Emphasis was placed on animal and human studies, but in vitro studies and review articles are also included. DATA SYNTHESIS: Endocarditis and the pharmacology of aminoglycosides are briefly reviewed. ODA is an alternative to conventional dosing in the treatment of endocarditis. Extensive work in endocarditis has been done recently in animals and humans to add to our understanding. Limited clinical data exist to support the theoretical advantages of increased efficacy, reduced toxicity, and potential cost savings versus traditional synergistic aminoglycoside dosing. Optimal monitoring of ODA remains undefined. CONCLUSIONS: Routine use of ODA for the treatment of endocarditis is not yet advocated. Promising supporting evidence and speculation of success of ODA in gram-positive endocarditis justify well-designed trials to further define its role in therapy.

Vancomycin peak serum concentration monitoring.

Vancomycin is a glycopeptide antibiotic commonly used in the treatment of gram-positive bacterial infections. With the rising prevalence of resistant gram-positive bacterial infections in healthcare institutions and the advent of attempts to curb escalating medical cost, vancomycin is being used with increasing frequency in the homecare setting for infection management. In view of its variability in pharmacokinetics and the potential for toxicities, serum concentrations often are measured. This article reviews the pharmacology of vancomycin and suggests a practical approach to serum concentration monitoring in homecare.

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.

Streptogramins and their potential role in geriatric medicine.

Despite advances in antimicrobial chemotherapy over recent decades, morbidity and mortality secondary to infection continues to rise. In addition, the incidence of infection caused by resistant organisms has also increased. Concurrently, the elderly are living longer than prior generations, often with disabling chronic diseases. The more debilitated of the geriatric population are at greater risk for infection, and more likely to acquire or develop antimicrobial resistant organisms. Gram-positive organisms are a source of resistance and commonly cause infection in older patients. Whereas resistance is a concern in all patients, in the elderly this is magnified by limitations in treatment options because of differences in pharmacokinetics and tolerance as compared with younger counterparts. Pharmacokinetic differences include changes in drug distribution and may arise as a result of diminished end organ function. Age-related decreases in renal function often impact on commonly prescribed antimicrobials. In addition, the elderly are more susceptible to drug-drug interactions because polypharmacy is common in this patient population. Streptogramins may offer a useful alternative in the treatment of infections in the elderly due to their coverage of organisms commonly causing infections in this population and because of their favourable pharmacokinetic profiles. While published experience is limited, streptogramins are not appreciably eliminated by the kidney and, therefore, they are less subject to age-related changes in renal elimination. What is required is multi-dose pharmacokinetic analysis of streptogramins in geriatric populations and subset analysis of patient use data on file. The following will provide the reader with the most recently presented data on streptogramin use and their potential. While focusing on potential use in the elderly, we have cited data and issues which we believe will be relevant in the geriatric population.

Quinupristin-dalfopristin (RP 59500): an injectable streptogramin combination.

The pharmacology, pharmacokinetics, activity, and potential clinical role of quinupristin-dalfopristin (RP 59500) are described. Quinupristin-dalfopristin is the first injectable formulation of the streptogramin antibiotics. Streptogramin drug products are each composed of two chemically distinct compounds, which when administered together act synergistically by inhibiting bacterial protein synthesis. Quinupristin-dalfopristin has shown activity in vitro against many strains of streptococci and staphylococci, including methicillin- and erythromycin-resistant strains of staphylococci. The combination is more active against Enterococcus faecium than Enterococcus faecalis. It has also shown activity in vitro against certain gram-negative organisms and anaerobes. The mean maximum blood concentration at the end of a one-hour infusion ranged from 0.95 mg/L for a 1.4-mg/kg dose to 24.2 mg/L for a 29.4-mg/kg dose; there was a linear correlation between dose and mean area under the concentration-time curve. Mean half-life ranged from 1.27 to 1.53 hours. The drug is under investigation in the United States in Phase III trials. Of 60 evaluable patients with documented bacteremia involving E. faecium resistant to vancomycin, 40 (67%) had a favorable clinical response. Of 11 patients with bacteremia caused by methicillin-resistant Staphylococcus aureus, 78% had a favorable response. The efficacy of quinupristin-dalfopristin in treating resistant infections has also been suggested by smaller studies and case reports. The drug may be useful in the prophylaxis of endocarditis. Adverse reactions are generally mild and transient. Quinupristin-dalfopristin may be useful in treating serious gram-positive infections, but more clinical study is needed.

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 $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.

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 cutailing the antibiotic budget within and among specific institutions is warranted.

Dosing adjustment of 10 antimicrobials for patients with renal impairment.

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

Recent advances: antiinfectives.

OBJECTIVE: To update readers on the significant changes in infectious diseases pharmacotherapy. DATA SOURCES: An Index Medicus and Iowa Drug Information Service search (1993-1994) of English-language literature pertaining to the selected topic areas was performed. Additional information from abstracts presented at scientific meetings were identified by the authors. STUDY SELECTION AND DATA EXTRACTION: All identified studies were screened and those judged relevant to the update were evaluated. DATA SYNTHESIS: New or clinically significant data since 1992 that related to peptic ulcer disease, microbial resistance (e.g., Enterococcus spp., Streptococcus pneumoniae, Mycobacterium tuberculosis, Candida albicans), immunomodulators, and AIDS were evaluated and compared with previous data. CONCLUSIONS: There have been several exciting and significant changes in infectious diseases pharmacotherapy evident from this review.

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.

Fluconazole for antifungal prophylaxis in chemotherapy-induced neutropenia.

Fluconazole is compared with other agents for antifungal prophylaxis in patients with chemotherapy-induced neutropenia. Fluconazole is an attractive alternative for antifungal prophylaxis because of its activity against many Candida species, long half-life, good patient tolerability, and minimal associated toxicity. The results of clinical trials suggest that fluconazole is superior to placebo and oral polyenes in preventing superficial fungal infection in neutropenic patients; however, its efficacy against systemic infection is not as strongly supported. Fluconazole use may increase emergence of resistant yeasts, particularly Candida krusei and Torulopsis glabrata. The cost of fluconazole 50 mg/day is similar to the costs of other antifungals used for prophylaxis; however, fluconazole 400 mg/day (the most frequently studied dose in neutropenic patients) is considerably more expensive. Comparative clinical trials between fluconazole and other antifungals are needed to determine which is superior for prophylaxis. Fluconazole is effective for prophylaxis against superficial fungal infection and may be an attractive alternative therapeutic regimen in patients undergoing bone marrow transplantation. In other neutropenic patients, such as those with leukemia, the superiority of fluconazole has not been substantiated; therefore, it is not recommended over other agents, such as clotrimazole and ketoconazole, at this time.

Accuracy of penicillin allergy reporting.

The consistency of penicillin allergy documentation in the patient chart, pharmacy profile, and medication administration record was assessed, along with the correctness of the self-reported patient history of penicillin allergy. One hundred fifty adult inpatients with a reported penicillin allergy were interviewed about their allergy. Questions included length of time since the allergic reaction, symptoms of the reaction, and whether rechallenge was ever attempted. Patients were classified into categories of (1) more severe allergy, (2) less severe allergy, or (3) intolerance on the basis of results of the interview. The patient pharmacy profile, chart, and medication administration record were reviewed to determine whether the allergy label was present. Patients who received antimicrobials during their hospitalization were evaluated. Of 117 patients, 82.9% were classified as allergic and 17.1% as intolerant. The allergy was documented in 98.7% of patient charts and 96.7% of medication administration records. The symptoms of the allergic reaction were described in the chart for only 34% of patients. Agents substituted for penicillin were potentially more toxic in 70.4% of cases, equally effective in all cases, and more costly in 55.5% of cases. Most, but not all, patients labeled as penicillin allergic had a history consistent with an allergy to the drug. Pharmacists can help ensure accurate allergy documentation by evaluating patients and educating both patients and health care professionals.

Intrathecal administration of amikacin for treatment of meningitis secondary to cephalosporin-resistant Escherichia coli.

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 patient's 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.