Therapeutic interchange of fluoroquinolones at a medical center.
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Anti-Infective Agents↗
Biomedical subjects
B M Lomaestro
Publications and source records attributed to B M Lomaestro.
Fluoroquinolone-induced renal failure.
Fluoroquinolones are generally well tolerated, clinically useful antimicrobials. This paper highlights rare, but potentially serious, adverse effects involving the kidney. Other antimicrobials have long been known to cause various forms of nephrotoxicity occurring as allergic interstitial nephritis, granulomatous interstitial nephritis, necrotising vasculitis, allergic tubular nephritis or a tubular necrosis. A Medline search (1985 to May 1999) of ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, trovafloxacin, enoxacin, sparfloxacin, grepafloxacin, gatifloxacin, clinafloxacin and moxifloxacin was conducted to ascertain the incidence and features of fluoroquinolone nephrotoxicity. Unfortunately, the data primarily consist of case reports and temporally related events. The incidence of these adverse effects is hard to estimate, and the cause may be multifactorial. While the use of ciprofloxacin appears to increase the risk, this may be due to its longer and more widespread use when compared with the newer agents.
Anti-Infective Agents↗
Update on the pharmacotherapy of obesity.
OBJECTIVE: To review recent developments in the pharmacotherapy of obesity, including the agents currently approved for use in the management of obesity and those under development. DATA SOURCES: A MEDLINE search from January 1990 to July 1997 was conducted to identify English literature available on the pharmacotherapy of obesity. The search was supplemented by a review of the bibliographies of identified literature. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. When available, double-blind, placebo-controlled trials were used preferentially. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, clinical trial data regarding efficacy, adverse effects, pharmacokinetics, drug interactions, and contraindications where information was available. Study design, selected population, results, and adverse effect information were included. DATA SYNTHESIS: The anorexiants currently available or under development for the management of obesity regulate food intake and satiety via the adrenergic and/or serotonergic pathways. Clinical trials have shown a 10-15% weight loss can typically be anticipated; however, little long-term safety and efficacy data are available. Adverse events tend to be mild and self-limiting, but serious adverse events can occur. Treatment options under development include thermogenic agents, digestive inhibitors, and analogs and antagonists of hormones that regulate food intake and satiety. CONCLUSIONS: Several mechanisms to control weight are currently under investigation for the management of obesity. Since obesity is a chronic condition, further studies should be conducted to evaluate the long-term safety and efficacy of these agents and the role of combination therapy using different modalities.
Adrenergic Agents↗
Update on drug interactions with azole antifungal agents.
OBJECTIVE: To review and update the incidence, mechanism, and clinical relevance of drug interactions with itraconazole, ketoconazole, and fluconazole. DATA SOURCES: Literature was identified by MEDLINE search (from January 1990 to May 1997) using the name of each antifungal and the term "interaction" as MeSH headings. Abstracts were identified by literature citation and by review of Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to 1996. STUDY SELECTION: Randomized, controlled, double-blind studies were emphasized; however, uncontrolled studies and case reports were also included. In vitro data were selected from literature review and citations. DATA EXTRACTION: Data were evaluated with respect to study design, clinical relevance, magnitude of interaction, and recommendations provided. DATA SYNTHESIS: The incidence of fungal infections and consequent azole antifungal usage continues to increase. By virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal enzyme systems), azoles have been investigated and implicated in several drug interactions. The magnitude of interactions can vary from trivial to potentially fatal, and also vary with specific azole and interactant. CONCLUSIONS: The azole antifungal agents represent a commonly used class of agents with a broad range of potential interactions. Recent data have increased our understanding of drug--drug interactions with azoles. Pharmacists are in a unique position to identify these interactions and to intervene to decrease their morbidity and improve patient care.
Animals↗
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.
Aged↗
Medication-prescribing errors in a teaching hospital. A 9-year experience.
BACKGROUND: Improved understanding of medication prescribing errors should be useful in the design of error prevention strategies. OBJECTIVE: To report analysis of a 9-year experience with a systematic program of detecting, recording, and evaluating medication-prescribing errors in a teaching hospital. METHODS: All medication-prescribing errors with potential for adverse patient outcome detected and averted by staff pharmacists from January 1, 1987, through December 31, 1995, were systematically recorded and analyzed. Errors were evaluated by type of error, medication class involved, prescribing service, potential severity, time of day, and month. Data were analyzed to determine changes in medication-prescribing error frequency and characteristics occurring during the 9-year study period. RESULTS: A total of 11,186 confirmed medication-prescribing errors with potential for adverse patient consequences were detected and averted during the study period. The annual number of errors detected increased from 522 in the index year 1987 to 2115 in 1995. The rate of errors occurring per order written, per admission, and per patient-day, all increased significantly during the study duration (P < .001). Increased error rates were correlated with the number of admissions (P < .001). Antimicrobials, cardiovascular agents, gastrointestinal agents, and narcotics were the most common medication classes involved in errors. The most common type of errors were dosing errors, prescribing medications to which the patient was allergic, and prescribing inappropriate dosage forms. CONCLUSIONS: The results of this study suggest there may exist a progressively increasing risk of adverse drug events for hospitalized patients. The increased rate of errors is possibly associated with increases in the intensity of medical care and use of drug therapy. Limited changes in the characteristics of prescribing errors occurred, as similar type errors were found to be repeated with increasing frequency. New errors were encountered as new drug therapies were introduced. Health care practitioners and health care systems must incorporate adequate error reduction, prevention, and detection mechanisms into the routine provision of care.
Drug Prescriptions↗
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.
Animals↗
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.
Adult↗
Glutathione in health and disease: pharmacotherapeutic issues.
OBJECTIVE: To review the current research and importance of glutathione (GSH) therapy in health and disease and to provide a basic overview of the widespread use and interest in this compound. DATA IDENTIFICATION: Articles were obtained via a MEDLINE search of the term glutathione in conjunction with specific disease states mentioned, and via extensive review of references found in articles identified by computer search. STUDY SELECTION: Emphasis was placed on the most recent research, human research, and in discussing multiple disease states. DATA EXTRACTION: The literature was reviewed for methodology, quality, and practical aspects of interest to clinical pharmacists. DATA SYNTHESIS: GSH is a tripeptide of extreme importance as a catalyst, reductant, and reactant. It continues to be investigated in diverse areas such as acute respiratory distress syndrome, toxicology, AIDS, aging, oncology, and liver disease. Despite the widespread clinical interest in GSH, we were not able to identify an in-depth review of this compound in the pharmacy literature. CONCLUSIONS: The list of potential indications for modulation of GSH is extensive and broad. This review introduces clinicians to what GSH is, its basic chemistry, and some areas of active research.
Acquired Immunodeficiency Syndrome↗
Absorption interactions with fluoroquinolones. 1995 update.
The utility of the fluoroquinolone class of antibiotics is rapidly expanding due to their favourable pharmacokinetic profile and the continuing development of new compounds. These agents are often used for indications not successfully treated with other orally available antimicrobials in the past, or for 'step-down' therapy in patients originally treated with intravenous agents. As the usage of these agents expands for serious systemic infections, knowledge of absorptive interactions with fluoroquinolones becomes paramount. Fluoroquinolones are often utilised in dosages and against modestly susceptible pathogens which allow a narrow margin for acceptable decreases in bioavailability. Chelation interactions with multivalent cations can result in inactivation of the fluoroquinolone with ramifications in vitro and in vivo. Chelation interactions have been reported to occur in between 22 and 76% of patients prescribed fluoroquinolones. Concurrent administration of magnesium-aluminum antacids and sucralfate has the greatest effect on the bioavailability of quinolones followed by iron, calcium and zinc. Spacing doses of fluoroquinolones and interactants has been suggested as a method of ensuring adequate quinolone absorption, but this can make optimal administration of the cation interactant difficult, if not impossible.
Absorption↗
Continuing problem of ciprofloxacin administered with interacting drugs.
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Administration, Oral↗
Effect of multiple staggered doses of calcium on the bioavailability of ciprofloxacin.
OBJECTIVE: To determine the effect on the relative bioavailability (Fr) of a staggered single dose of ciprofloxacin given two hours after a morning dose of calcium carbonate given three times daily over the three previous days. DESIGN: Thirteen male volunteers participated in this randomized, nonblinded, crossover investigation; 12 subjects were included in the final analysis. SETTING: Data collection and ciprofloxacin administration occurred at Albany Medical Center, a tertiary-care teaching institution. Calcium carbonate administration was on an outpatient basis. RESULTS: For 12 volunteers, the mean +/- SD Fr of ciprofloxacin staggered with calcium was 0.87 +/- 0.23 (noncompartmental model) and 0.98 +/- 0.27 (compartmental model). Other statistically significant findings were a decrease in the time to maximum concentration of ciprofloxacin staggered with calcium in serum compared with ciprofloxacin alone (from 1.76 +/- 0.54 to 1.23 +/- 0.52 h in the noncompartmental model; p < 0.05), and a decrease in the same parameter (from 1.92 +/- 0.96 to 0.77 +/- 0.53 in the compartmental model; p < 0.005). Maximum concentration of ciprofloxacin staggered with calcium was decreased in the noncompartmental model compared with ciprofloxacin alone (from 2.11 +/- 0.72 to 1.60 +/- 0.33, respectively; p < 0.05). The elimination half-life and area under the concentration-time curve of ciprofloxacin were not significantly altered. CONCLUSIONS: Repeated doses of calcium carbonate, administered two hours before ciprofloxacin, did not significantly alter the Fr of this fluoroquinolone.
Adolescent↗
Timeliness of medication administration in hemodialysis inpatients: drug use evaluation.
Inpatients at the Albany Medical Center Hospital in Albany, New York are transported from their ward to the hemodialysis unit for their dialytic procedures. The time involved is several hours. An investigation into the timeliness of medication administration during this off-the-ward period was prospectively conducted. Twenty-eight dialytic procedures (for eight different patients), including 127 scheduled medication administrations, were included in the final data. A total of 108 (85%) of audited medication administrations were given more than 1 hour early, 1 hour late, or not at all. Recommendations for corrective action are proposed.
Drug Administration Schedule↗
Pleurodesis with solution prepared from quinacrine hydrochloride tablets.
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Adult↗
Errors in prescribing methotrexate.
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Arthritis, Rheumatoid↗
Effect of staggered dose of calcium on the bioavailability of ciprofloxacin.
The effect on ciprofloxacin's bioavailability (F) of calcium carbonate given 2 h before ciprofloxacin administration in 12 male volunteers was studied. The relative F with calcium was 0.98, maximum concentration of drug in serum increased significantly from 1.98 to 2.42 mg/liter (P = 0.039), and time to maximum concentration of drug in serum decreased from 1.82 to 1.26 h (P = 0.038). Thus, a single calcium carbonate dose, administered 2 h before ciprofloxacin, does not alter the F of this quinolone.
Adult↗
Quinolone-cation interactions: a review.
The quinolone class of antibiotics is enjoying a recent resurgence in interest and use due to the development of improved compounds. Norfloxacin, ciprofloxacin, and, most recently, ofloxacin have been marketed. Enoxacin and other agents are in various stages of investigation. These newer compounds are often used for indications not successfully treated by the original quinolones, or in some cases, not optimally treated with any previously available oral antibiotic. A potential problem with the increasing use of quinolone-type antibiotics for systemic illness is the chelation and inactivation of these compounds by several cations. One outcome of these potential interactions is a possible reduction in bioavailability and effectiveness of quinolone compounds. A review of the literature on quinolone-cation interactions, in vivo and in vitro significance, and recommendations to avoid potential problems are provided.
4-Quinolones↗