PubMed Health⌕ Search

Biomedical subjects

J J Schentag

Publications and source records attributed to J J Schentag.

At least 235 records · Page 13Linked to original sources
PubMed1977

Intravenous theophylline therapy: nomogram guidelines.

We evolved a nomogram for guiding and standardizing intravenous theophylline therapy in hospitalized patients. It provides rapid calculation of a loading dose based on body weight and previous therapy and a maintenance infusion rate related to three categories of expected metabolic activity. The guidelines were prospectively used in the treatment of 72 patients, mainly in a respiratory care unit. The nomogram was successfully used to attain near-steady-state serum concentrations in the therapeutic range of 8 to 20 mg/litre in 72% of patients, with only two patients outside of the range of 5 to 25 mg/litre. These guidelines facilitate initial theophylline dosage in older patients with liver and cardiac disease and provide a rational basis for interpreting serum concentration measurements and adjustment of drug therapy.

Adult↗
PubMed1976

System for clinical pharmacokinetic monitoring of theophylline therapy.

A system was developed for guiding theophylline therapy in acutely ill patients with respiratory disease and for recovery of pharmacokinetic information. A dosage regimen nomogram was designed based on literature data and preliminary pharmacokinetic studies in patients. Using the nomogram, physicians select the loading and infusion dosages based on previous therapy, body weight, age, and cardiac and hepatic status of the patient. Specifications are provided for loading (up to 5.6 mg/kg) and maintenance doses (0.9, 0.68, or 0.45 mg/kg/hr) of aminophylline, handling of i.v. dosage forms, and collection of three initial blood samples. Serum samples were assayed for theophylline by high-performance liquid chromatography for rapid feedback of data to the physician and computer estimation of body clearance values. The usefulness of the nomogram guidelines was examined prospectively in 72 patients. Near-steady-state serum concentrations in the therapeutic range of 8-20 mg/liter were found in 72% of the patients. Only two patients were outside of the range of 5-25 mg/liter. The relationship between the physician's estimate of the patient's clinical status (three classes) and measured body clearance was highly significant (p less than 0.025). A comprehensive data collection format allows further analysis of the factors responsible for the variability in theophylline disposition in patients undergoing therapy.

Adult↗
PubMedDate not supplied

Mental confusion in a patient treated with metronidazole--a concentration-related effect?

We report a case of serious mental confusion, hallucinations, and agitation in a 65 year old man, occurring in close relationship to the intravenous administration of metronidazole. The patient was treated twice, but at different dosages. The confusion and hallucinations occurred at the recommended daily dose of 2.0 g, but did not return at a daily dose of 500 mg. Metronidazole serum concentrations were obtained throughout both courses of therapy; CSF and tissue concentrations were obtained at autopsy. The mental confusion was associated with peak serum concentrations of approximately 40 micrograms/ml. Symptoms resolved within 24-48 hr after stopping metronidazole, and resolution was consistent with a metronidazole half life of 14 hr. We conclude that metronidazole can be associated with a dose- and serum concentration-related mental confusion state, and that this side effect appears completely reversible upon discontinuing the drug.

Aged↗
PubMedDate not supplied

Complexation versus hemodialysis to reduce elevated aminoglycoside serum concentrations.

Seven patients with acutely elevated aminoglycoside serum concentrations were studied comparing the effect of hemodialysis (n = 3) with removal by complexation using ticarcillin or carbenicillin (n = 4). Aminoglycoside serum half-life before intervention averaged 96 hours for the dialysis group and 67 hours for the complexation group. Ticarcillin was used for a minimum of 48 hours, while hemodialysis removal was estimated over 48 hours, which included two 4-hour dialysis periods. Aminoglycoside serum half-life was reduced to an average of 11 hours with hemodialysis, while with complexation using ticarcillin, it was reduced to 12 hours. During the 48-hour comparison period, complexation removed approximately 50% more aminoglycoside than did hemodialysis, primarily because the improved removal technique was sustained over the entire time. Complexation appears to be as effective as continuous hemodialysis in lowering excessive aminoglycoside serum concentrations. Complexation with ticarcillin can be more rapidly initiated, is less expensive and there is a low risk of adverse reactions. This method provides continued treatment of infections in patients with elevated serum concentrations and/or nephrotoxicity who require cessation of aminoglycoside therapy.

Aged↗
PubMedDate not supplied

Changes in antimicrobial agent usage resulting from interactions among clinical pharmacy, the infectious disease division, and the microbiology laboratory.

Rapid reporting of culture and susceptibility data is the first of several important steps in the successful management of infected patients. As has been said many times, rapidly reported data are of little value unless the patient directly benefits. Benefit requires better overall communication and an action plan linked to timely use of these results. In 1989 the Millard Fillmore Hospital Antibiotic Review Committee developed and implemented a prototype approach to hospital wide antimicrobial management. The formulary was revised and the drug use evaluation process modified to enhance effectiveness and to lower the cost of therapy and inventory. Clinical pharmacy antimicrobial agent management specialists were then recruited to individualize patient treatments to the isolated pathogens in conjunction with the Division of Infectious Diseases. To provide the clinical pharmacy specialists with rapid and clinically useful information, a real-time computer link was created between the pharmacy (antibiotic orders) and the microbiology laboratory (culture results). Customized software was implemented to screen all patients automatically for mismatches between pathogens and drugs, or to screen for doses inappropriate to minimum inhibitory concentration or renal function. Special attention was paid to identification of opportunities to target a more appropriate narrow-spectrum regimen after culture results became available. Changes in antimicrobial regimen or dosage were made by contacting the prescribing physician. Over 90% of the recommended changes were made, and virtually all changed regimens had satisfactory clinical outcome. Real dollar expenditures for antimicrobial agents declined by > $200,000 per year. Prior to the institution of this computerized clinical management strategy, antimicrobial purchases were rising yearly at the rate of 12%-15%. The combined efforts of clinical pharmacy, microbiology, and infectious disease personnel successfully optimized antimicrobial therapy on a hospital wide basis. Antimicrobial agent optimization improved patient outcome, and the cost savings more than covered the costs of the program personnel and software.

Anti-Bacterial Agents↗
PubMedDate not supplied

Role of pharmacokinetics and pharmacodynamics in the design of dosage schedules for 12-h cefotaxime alone and in combination with other antibiotics.

Pharmacodynamic principles have provided important tools to evaluate and compare antimicrobial agents, and well as to guide dosing. For beta-lactams, time above the minimum inhibitory concentration (MIC) has surfaced as the most important factor. However, the area under the inhibitory serum concentration time-curve (AUIC) may be superior when appropriate dosing intervals are selected. Although the target time over the MIC is unclear in humans even when concentrations remain continuously above the MIC, a higher AUIC predicts better clinical outcome up to a maximum. This article provides a pharmacodynamic assessment of 1- and 2-g doses of cefotaxime every 12 h. AUIC24 values and published MIC values for common pathogens (grouped into four groups based on MIC90) were used to predict organisms suitable for treatment with every-12-h regimes. Cefotaxime was inadequate for group 4 organisms including: Pseudomonas aeruginosa, Acienetobacter sp., and Enterococcus sp. Organisms such as Enterobacter cloacae, Serratia marcescens, Staphylococcus aureus, and B. fragilis may be suboptimally treated with cefotaxime every 12 h. Cefotaxime in doses of 1-2 g every 12 h should be useful in patients with normal renal function infected with organisms having MICs < 0.5 microgram/ml. This regimen should obtain AUIC24 values > 125 and ensure adequate time above the MIC. In patients with impaired renal function, because of a longer half-life and higher area under the curve, pathogens with MIC values in the 0.5-2 micrograms/ml range may be treated with cefotaxime every 12 h while maintaining AUICs > 125. Data are also presented for cefotaxime 2 g every 8 h alone and in combination with ofloxacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Pharmacokinetics and extravascular penetration of aztreonam in patients with abdominal sepsis.

Patients with abdominal sepsis were enrolled in a clinical trial of aztreonam vs. tobramycin. All were given clindamycin concomitantly. The pharmacokinetics of aztreonam in 21 patients randomly assigned to receive treatment with aztreonam are reported. The mean age of these patients was 68 years; most had underlying disorders such as malnutrition and cardiac or pulmonary disease. Creatinine clearance (Clcr) ranged from 11.2 to 133.1 ml/min. The usual dose of aztreonam was 2.0 g every 8-12 hr. A single pharmacokinetic study was performed over one dosing interval after steady-state conditions were achieved. In approximately one-half of the patients, peritoneal fluid was collected during the interval between doses. Penetration of aztreonam, as expressed as the ratio of concentration in the peritoneal fluid to that in serum, was higher for aztreonam (0.95:1) than for tobramycin (0.46:1). The ratio of the concentration in peritoneal fluid to the minimum inhibitory concentration (MIC) of the infecting bacteria was also higher for aztreonam. Serum pharmacokinetic data were analyzed by both two-compartment and moment analysis. For both the steady-state volume of distribution (Vdss) and total body clearance (TBC), the values determined by both methods were highly correlated (r = .96, .99, respectively). Average values for Vdss and TBC were 0.28 liters/kg and 80 ml/min. TBC for aztreonam correlated strongly with CLcr and was described by the regression equation TBC = 1.1 (Clcr) + 1.6, r = .87, P less than .01.

Abdomen↗
PubMedDate not supplied

A microcomputer program for tobramycin consult services, based on the two-compartment pharmacokinetic model.

A microcomputer program has been developed to provide assistance to tobramycin clinical pharmacokinetic consult services. Written for the Apple II Plus computer with 64 K memory, one-disk drive, and a dot matrix graphics printer, this software is user-oriented and simple to operate. The program disk contains complete documentation and referenced instructions. Major sections provide empiric dosing recommendations based on population data and allow determination of dosage from measured serum concentrations. The program keeps a record of previous regimens, allows for the entry of the user's own recommendation, and provides complete flexibility for up to 15 dosage and interval changes. In addition to its dosing information and file management capabilities, the program simulates serum concentration profiles based on user-selected one-compartment, two-compartment, or two-compartment prenephrotoxic models. The program prints a consult sheet with concentration vs. time simulation, patient demographic data, and user-entered recommendations and comments. The program provides extensive disk storage capabilities for patient files, with immediate access to facilitate updating and dosing regimen changes as they occur. In addition to providing improvements in empiric dosing capabilities, pharmacokinetic modeling, and data handling, this computer software has been designed to incorporate pharmacokinetic data derived from important subpopulations into the empiric dosing algorithms. This unique aspect enables the program to provide improved empiric dosing regimens for patients who do not fall under the guidelines for any of the conventional aminoglycoside dosing nomograms.

Aging↗
PubMedDate not supplied

Clinical and economic impact of oral ciprofloxacin as follow-up to parenteral antibiotics.

This study assessed the effects of switching to ciprofloxacin hydrochloride in patients initially treated with parenteral antibiotics for respiratory tract (RTI), skin or skin structure (SSS), bone or joint (BJI), or urinary tract infection (UTI). A total of 766 patients from 54 institutions were concurrently monitored and the projected effect of ciprofloxacin on duration of hospitalization and parenteral therapy was assessed based on previous experiences with each type of patient. The median duration of parenteral antibiotic therapy prior to oral ciprofloxacin was 4, 6, 6, and 7.5 days; the median duration of oral ciprofloxacin prior to discharge was 2, 2, 2, and 4 days for UTI, RTI, SSS, and BJI, respectively. It was estimated that more than 70 percent of patients would have continued parenteral antibiotics on an inpatient basis and only 10 percent would have received an alternative oral agent if ciprofloxacin were not available. Use of oral ciprofloxacin significantly affected both duration of parenteral therapy and duration of hospitalization. It was estimated that 16,732 doses of parenteral antibiotics were avoided and, after subtracting the cost of oral ciprofloxacin, resulted in a likely net savings of $187 146.50. An estimated total of 2266 hospital days were saved in 418 patients, resulting in estimated savings of $739 100. Total drug plus hospitalization cost savings were projected to be $980 246.50. Further research is required to determine if, and where, more aggressive intervention will achieve additional cost savings.

Administration, Oral↗
PubMedDate not supplied

Mathematical examination of dual individualization principles (II): The rate of bacterial eradication at the same area under the inhibitory curve is more rapid for ciprofloxacin than for cefmenoxime.

OBJECTIVE: To compare two antibiotics at equal ranges of area under the inhibitory curve (AUIC) exposure to determine if the rate of bacterial eradication differed between these antibiotics. DESIGN: Retrospective comparison of two previously collected studies of similar patients with nosocomial pneumonia. SETTING: Hospitalized patients, most intubated in critical care units with nosocomial pneumonia. PARTICIPANTS: Patients treated with either i.v. ciprofloxacin (n = 74) or the i.v. third-generation cephalosporin cefmenoxime (n = 43) were compared for their length of treatment required to eradicate bacterial pathogens from their respective infection sites, using serial cultures from the site of infection. All patients were also assessed for clinical outcomes. Serum samples were obtained to evaluate individual patient antibiotic pharmacokinetics, which were used to model pharmacodynamics of response. The HPLC assay used for each antibiotic had interday coefficients of variation < 10 percent. Serum concentration versus time profiles were fit using the computer program ADAPT II to determine pharmacokinetic parameters for each patient. The primary drug exposure measure that related to response was the AUIC, calculated as steady-state AUC0-24/minimum inhibitory concentration. RESULTS: AUIC values in the patients ranged from 6.0 to more than 7000, yet the AUIC value was highly predictive of time to bacterial eradication (p < 0.001). Although more than 75 percent of patients eventually achieved eradication of pathogens from tracheal aspirate cultures, ciprofloxacin and cefmenoxime differed significantly in the time required to sterilize these cultures. At appropriate AUIC values (> 250) for ciprofloxacin, the median time to eradication was two days, while cefmenoxime (also at AUIC values > 250) required six days to achieve the same result. CONCLUSIONS: We conclude that the more rapid in vitro bacterial killing, which is characteristic of ciprofloxacin at optimal AUIC values, can manifest in vivo as more rapid clearance of bacteria from the respiratory tract of patients, even when both agents are controlled for initial antibacterial exposure (i.e., same AUIC).

Anti-Bacterial Agents↗
PubMedDate not supplied

Effects of the concomitant administration of tamsulosin (0.8 mg/day) on the pharmacokinetic and safety profile of theophylline (5 mg/kg): a placebo-controlled evaluation.

We performed a single-blind, sequential-design study to investigate the effects of concomitant oral tamsulosin 0.8 mg/day on the pharmacokinetics and safety of intravenous theophylline 5 mg/kg in healthy subjects. Ten healthy volunteers aged 19-39 years received placebo on study days 0, 1, 2 and 10 and tamsulosin on days 3-9. Theophylline was administered intravenously on days 1 and 9. Theophylline and tamsulosin pharmacokinetic data were determined following administration of the drugs on days 1 and 9 and day 9, respectively. No differences were observed in theophylline pharmacokinetic parameters with and without concomitant tamsulosin, and there were no abnormalities in tamsulosin pharmacokinetic data. Some significant changes in vital signs and a number of mild adverse reactions were reported, but the overall safety profile of tamsulosin and theophylline was acceptable. The results of the study suggest that no dose adjustment in tamsulosin is necessary when it is administered concomitantly with theophylline.

Administration, Oral↗
PubMedDate not supplied

Use of benchmarking techniques to justify the evolution of antibiotic management programs in healthcare systems.

OBJECTIVE: To apply basic benchmarking techniques to hospital antibiotic expenditures and clinical pharmacy personnel and their duties, to identify cost savings strategies for clinical pharmacy services. DESIGN: Prospective survey of 18 hospitals ranging in size from 201 to 942 beds. Each was asked to provide antibiotic expenditures, an overview of their clinical pharmacy services, and to describe the duties of clinical pharmacists involved in antibiotic management activities. Specific information was sought on the use of pharmacokinetic dosing services, antibiotic streamlining, and oral switch in each of the hospitals. RESULTS: Most smaller hospitals (< 300 beds) did not employ clinical pharmacists with the specific duties of antibiotic management or streamlining. At these institutions, antibiotic management services consisted of formulary enforcement and aminoglycoside and/or vancomycin dosing services. The larger hospitals we surveyed employed clinical pharmacists designated as antibiotic management specialists, but their usual activities were aminoglycoside and/or vancomycin dosing services and formulary enforcement. In virtually all hospitals, the yearly expenses for antibiotics exceeded those of Millard Fillmore Hospitals by $2,000-3,000 per occupied bed. In a 500-bed hospital, this difference in expenditures would exceed $1.5 million yearly. Millard Fillmore Health System has similar types of patients, but employs clinical pharmacists to perform streamlining and/or switch functions at days 2-4, when cultures come back from the laboratory. CONCLUSIONS: The antibiotic streamlining and oral switch duties of clinical pharmacy specialists are associated with the majority of cost savings in hospital antibiotic management programs. The savings are considerable to the extent that most hospitals with 200-300 beds could readily cost-justify a full-time clinical pharmacist to perform these activities on a daily basis. Expenses of the program would be offset entirely by the reduction in the actual pharmacy expenditures on antibiotics.

Aminoglycosides↗
PubMedDate not supplied

Renal tubular enzyme effects of clarithromycin in comparison with gentamicin and placebo in volunteers.

This study assessed the potential nephrotoxicity of clarithromycin in comparison with gentamicin and placebo. Increased urinary excretion of alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) served as markers of renal tubular injury. The study utilised a multiple-dose, double-blind, randomised, parallel group design. 14 healthy male subjects received 1 of 3 treatment regimens: (a) clarithromycin 500 mg orally every 12h for 13 doses and intravenous placebo every 8h (n = 5); (b) oral placebo every 12h and intravenous placebo every 8h (n = 4); and (c) intravenous gentamicin 1.7 mg/kg every 8h for 19 doses and oral placebo every 12h (n = 5). 24h urine collections were obtained daily for determinations of AAP and NAG activities. Gentamicin produced statistically significant increases (p less than 0.0001) in AAP and NAG excretion, with increases as early as the first and second day of dosing. Clarithromycin, when compared with placebo, did not produce significant elevations in AAP or NAG activity. On the basis of these data, it is unlikely that usual doses of clarithromycin have significant potential for causing nephrotoxicity.

Acetylglucosaminidase↗
PubMedDate not supplied

Obesity as a risk factor in drug-induced organ injury. V. Toxicokinetics of gentamicin in the obese overfed rat.

Obese human patients and obese overfed rats treated chronically with gentamicin suffer greater renal injury than nonobese patients and control animals. To understand the mechanism of this heightened susceptibility to the nephrotoxic effects of gentamicin, this study examines the plasma-time course and renal uptake of gentamicin in control and obese overfed rats following a single bolus dose. Gentamicin was administered ip to control rats at 30 mg/kg total body mass and to obese rats at 30 mg/kg ideal body mass plus 40% of excess body mass. Following gentamicin dosing, only 1 of 11 concentration-time points taken over 6/hr postdosing was different between control and obese groups. In addition, the area under the plasma concentration curve extrapolated to infinite time was not different between obese and control rats (mean +/- SD of 4.47 +/- 0.85 vs. 4.13 +/- 0.35 mg.min.ml-1, p greater than 0.5). The gentamicin plasma concentrations after 6 hr were less than 1 microgram/ml and not different between the groups; however, the concentration of gentamicin in the kidneys was 33% greater in obese than control rats at this time (324 +/- 66.9 vs. 244 +/- 34.7 micrograms/g, p less than 0.05). The fraction of dose and the total amount of drug that accumulated in the kidneys were also greater in the obese rats (42 and 72% increases). Considered with the results of previous studies, it appears that obese overfed rats sustain more severe nephrotoxicity following comparable plasma gentamicin exposure because of increased renal uptake and/or retention of drug.

Absorption↗
PubMedDate not supplied

The partitioning of cimetidine into canine cerebrospinal fluid.

The pharmacokinetics and cerebrospinal fluid (CSF) partitioning of cimetidine were studied in the dog. Four healthy male mongrel dogs were given a 22 mg/kg iv dose of cimetidine. The dogs demonstrated metabolic and pharmacokinetic characteristics similar to human volunteers, as the total body clearance of cimetidine averaged 7.5 ml/min/kg in the dog as compared to 7.7 ml/min/kg in humans. Autopsy tissue concentrations were similar to those measured in humans. There were no statistical differences between dogs and humans in any pharmacokinetic parameters. Cimetidine sulfoxide was the major metabolite in the dog, similar to that in humans. Cimetidine CSF partitioning, as determined by the ratio of cimetidine CSF:serum area under the curve was 0.125 +/- 0.03. Cimetidine appears to enter the CSF by passive diffusion, and is removed by passive diffusion, CSF bulk flow, and possibly by an active transport process. We conclude that the dog is an appropriate animal to investigate cimetidine pharmacokinetics and is a suitable model for examining the CSF uptake of H2-antagonists.

Animals↗
PubMedDate not supplied

Neutropenia associated with beta-lactam antibiotics.

Two patients who developed neutropenia while receiving beta-lactam antibiotics are presented, and the literature on beta-lactam-induced neutropenia is reviewed. A 55-year-old white woman was admitted to the hospital with a white blood cell (WBC) count of 8700/cu mm (68% neutrophils, 12% neutrophil bands, 0% eosinophils, 14% lymphocytes, 5% monocytes). Moxalactam 2 g i.v. (as the disodium salt) every eight hours was started on hospital day 15 after a postoperative fever failed to respond to a regimen of intravenous tobramycin and clindamycin. The patient again had surgery on hospital day 27, and the moxalactam regimen was continued postoperatively. Approximately one week later the patient's WBC count had dropped to 1900/cu mm (8% neutrophils, 14% neutrophil bands, 6% eosinophils, 54% lymphocytes, 16% monocytes); moxalactam was discontinued, and the WBC count gradually increased after substitution of tobramycin and clindamycin for moxalactam. The second patient was a 75-year-old white man who was being treated with intravenous tobramycin and cefoxitin for a hospital-acquired pneumonia. Ticarcillin 3 g i.v. (as the disodium salt) every four hours was added to this regimen on hospital day 23 after sputum cultures revealed Pseudomonas aeruginosa; four days previously, the WBC count had been 25,100/cu mm (64% neutrophils, 31% neutrophil bands, 1% eosinophils, 3% lymphocytes, 0% monocytes). The WBC count on hospital day 36 was 11,900/cu mm (39% neutrophils, 33% neutrophil bands, 11% eosinophils, 10% lymphocytes, 6% monocytes). Two days later it had dropped to 3700/cu mm (2% neutrophils, 0% neutrophil bands, 53% eosinophils, 24% lymphocytes, 16% monocytes), and ticarcillin was discontinued. The WBC count gradually increased and returned to normal within three days after discontinuing ticarcillin. Neutropenia associated with the administration of beta-lactam antibiotics appears to result from an immunologic reaction characterized by rapid destruction of peripheral neutrophils. Among penicillin analogs, penicillinase-resistant penicillins are involved most frequently, especially in pediatric patients receiving dosages of 150 mg/kg/day or greater. Two case reports have implicated ticarcillin as a cause of neutropenia; moxalactam has not been associated with this adverse effect in previous literature reports. Discontinuation of the suspected agent and initiation of an alternative antibiotic regimen is recommended as initial treatment of this condition since recovery usually occurs within days after discontinuing the offending drug.

Aged↗