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Biomedical subjects

D R Guay

Publications and source records attributed to D R Guay.

87 records · Page 5Linked to original sources
PubMed1983

Interference of selected second- and third-generation cephalosporins with creatinine determination.

The interference of selected second- and third-generation cephalosporins and cephalosporin-like antibiotics with serum and urine creatinine determinations was studied. Single determinations of apparent creatinine concentrations in serum, urine, and water samples were measured by three methods--manual, automated dialysis (SMAC 12/60), and direct kinetic (KDA Analyzer). Various concentrations of each cephalosporin were tested for interference with creatinine determinations. Drugs studied were cefoxitin, cefamandole, cefotaxime, ceftazidime, cefoperazone, ceftizoxime, moxalactam, ceftriaxone, and ceforanide. Cephalosporins demonstrating interference with one or more methods were further tested at concentrations representing the range of clinically achievable serum and urine drug concentrations. Cefoxitin, ceforanide, moxalactam, ceftizoxime, and ceftriaxone demonstrated significant interference in the screening tests. In subsequent testing, interference was shown at clinical concentrations of cefoxitin (all three methods) and ceforanide (manual and KDA methods). Where interference occurred, the degree varied with the assay method and the drug concentration. Recommendations are presented for serum and urine sampling for creatinine determinations in patients receiving cefoxitin and ceforanide. Based on the relationship between test interference and concentrations of these drugs achievable in patients with varying degrees of renal dysfunction, only cefoxitin and ceforanide can be expected to cause significant false elevations in vivo. To minimize interference, blood samples should be drawn at the time of minimum drug concentration.

Cephalosporins↗
PubMed1982

Cinoxacin (Cinobac, Eli Lilly & Co.).

Cinoxacin, a synthetic organic acid antibacterial agent, related structurally to nalidixic and oxolinic acid, has been approved for the treatment of initial and recurrent urinary tract infections (UTIs) caused by susceptible gram-negative microorganisms. The role of cinoxacin in the treatment of UTIs, compared with the usual first-line agents, is uncertain at this time. The efficacy of cinoxacin in the treatment of pyelonephritis, compared with these proven agents, has been examined in only small numbers of patients, and cinoxacin is more expensive than these agents. Cinoxacin may prove valuable in the treatment of prostatitis and in the prophylaxis of recurrent UTIs; further study in these areas is warranted. In the routine treatment of acute UTIs, cinoxacin perhaps should be reserved only for those patients with organisms resistant to usual first-line agents or those who fail to respond to therapy with these agents. In this respect, cinoxacin may, in the future, replace nalidixic acid.

Cinoxacin↗
PubMedDate not supplied

Antimicrobial management of Helicobacter pylori-associated gastrointestinal tract disease.

Since the identification of Helicobacter pylori in 1983, this pathogen has become the dominant focus of investigation in a variety of gastrointestinal tract disorders, including peptic ulcer disease, nonulcer dyspepsia, and gastric carcinoma. During the past 7 years, the efficacy of a variety of antimicrobial single, dual, and triple therapy regimens--including the use of acid-suppressive agents, such as proton pump inhibitors, and histamine2-receptor antagonists--in the eradication of H pylori have been investigated. Newer treatment approaches, such as dual therapy (proton pump inhibitor + 1 antimicrobial agent) and 7-day regimens have shown a high degree of success and have the potential to improve compliance. However, the optimal regimen, in terms of cost, efficacy, and tolerability, and optimal length of treatment still remains to be determined.

Antacids↗
PubMedDate not supplied

The emerging role of valproate in bipolar disorder and other psychiatric disorders.

Although valproate, a simple branched-chain fatty acid, is generally considered to be an antiepileptic agent, a large literature dating back to 1966 describes its use in primary psychiatric disorders. The significant role that gamma-aminobutyric acid plays in mood provided the rationale to examine valproate in this regard. Numerous uncontrolled as well as placebo- and lithium-controlled studies verified the drug's efficacy in the short-term management of bipolar and schizoaffective disorders. The response appears to be independent of response to traditional therapies such as lithium, neuroleptics, and carbamazepine, and may be maintained for extended periods of time. Valproate should be considered not only in patients with mood disorders who are intolerant of or nonresponsive to traditional therapies, but also in those with rapid cycling, electroencephalographic abnormalities, head trauma antedating the onset of psychiatric illness, or any other factor suggesting an organic component. Preliminary uncontrolled studies suggest that the drug may also eventually play a role in the management of panic disorder and behavioral dyscontrol (agitation, aggression, temper outbursts). Its adverse event profile is well known from years of experience in the management of epilepsy and does not appear to be altered in the presence of psychiatric disorders. Similarly, the drug-drug interaction potential of valproate is reasonably well known, although further research into interactions with psychotropic agents is warranted.

Anticonvulsants↗
PubMedDate not supplied

A fatal overdose with clomipramine.

A death attributed to self administration of toxic amounts of clomipramine is reported. Analysis of post mortem blood showed clomipramine at a concentration of 540 ng/mL and its active metabolite, N-desmethylclomipramine, at a concentration of 580 ng/mL. The corresponding concentrations of the parent compound and metabolite in the urine were only 350 ng/mL and 700 ng/mL, respectively. These blood results are construed to represent minimum lethal concentrations for the two combined compounds.

Chromatography, Gas↗
PubMedDate not supplied

Wide variation in single, daily-dose aminoglycoside pharmacokinetics in patients with burn injuries.

Five to seven mg/kg single, daily-dose aminoglycoside regimens have been recently advocated as effective alternatives to traditional aminoglycoside regimens. The rationale for single, daily-dose aminoglycoside therapy is to produce an optimal ratio between aminoglycoside peak concentrations (Cmax) and pathogen minimal inhibitory concentration to maximize bacterial killing and to produce an aminoglycoside-free period during the 24-hour dosing interval. Single, daily-dose aminoglycoside therapy has not been recommended to date for use in the population of patients with burn injuries. The purpose of this study was to determine the magnitude and variability of aminoglycoside Cmax and the duration of the aminoglycoside-free period after simulated single, daily-dose regimens in patients with burn injuries. Fifty-two patients receiving gentamicin or tobramycin in the burn unit were studied retrospectively to determine the individualized pharmacokinetic parameters and the simulated Cmax and 24-hour after the dose trough minimum concentrations for 5 and 7 mg/kg single, daily-dose aminoglycoside regimens. Patients were only included in the final analysis if they had been treated for burn wound infections and exhibited a calculated creatinine clearance exceeding 60 ml/min (N = 40). Mean [percentage coefficient of variation] Cmax/minimum concentrations were 15.4[30.5]/0.03[200.0] and 21.6[30.6]/0.04[200.0] mg/L for 5 and 7 mg/kg daily doses, respectively. The mean coefficient of variation time to reach an extrapolated concentration of 0.1 mg/L was 15.9[30.8] hours and 17.0[30.6] hours for the 5 and 7 mg/kg daily doses, respectively. Substantial variability in aminoglycoside Cmax and duration of the aminoglycoside-free period was observed. These data suggest that many patients with burn injuries are not candidates for single, daily-dose aminoglycoside therapy because of restrictive creatinine clearance criteria and pronounced variability in length of the aminoglycoside-free interval. If single, daily-dose aminoglycoside therapy is to be used in this patient population, therapeutic drug monitoring is recommended to screen for appropriate candidates and to optimize Cmax and minimal inhibitory concentration ratios and duration of the aminoglycoside-free interval.

Adolescent↗
PubMedDate not supplied

Nontuberculous mycobacterial infections.

OBJECTIVE: To review the epidemiology, clinical manifestations, diagnosis, and treatment of nontuberculous mycobacterial infections other than Mycobacterium avium complex (MAC). DATA SOURCES: A MEDLINE search of English-language literature pertaining to nontuberculous mycobacteria other than MAC was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Information judged by the author to be pertinent was selected for discussion. DATA SYNTHESIS: Mycobacterial infections, including those caused by nontuberculous mycobacteria other than MAC, have assumed greater importance over the past decade, due in part to the changing spectrum of immunosuppression as manifested by organ transplantation and HIV infection. Many pathogenic nontuberculous mycobacteria have been identified that are associated with a wide variety of localized, organ-specific, and systemic infections. Of concern, these organisms exhibit variable, species-specific susceptibility to traditional antimycobacterial drugs and other antimicrobials. In addition, long treatment courses and adjunctive surgical therapy are often required to effect cure. Important antimicrobials for the management of these infections include cefoxitin, imipenem/cilastatin, aminoglycosides (other than streptomycin), tetracyclines, macrolides, and trimethoprim/sulfamethoxazole, as well as traditional antimycobacterials. CONCLUSIONS: Nontuberculous mycobacteria have assumed an increasing role in disease etiology in both nonimmunocompromised and immunocompromised individuals. Advent of rapid diagnostic techniques and susceptibility testing has allowed the clinician to identify these organisms and initiate effective treatment on a more timely basis with an improved chance for cure. Few therapeutic agents are available for treatment of these infections, many of which are not considered classic antimycobacterials.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Clinical pharmacokinetics of vancomycin.

Vancomycin utilisation has increased dramatically in the last 10 years due to the increasing clinical significance of infections with methicillin-resistant staphylococci. Recent studies have focused on characterising the disposition of vancomycin in patients and assessing the relationship between serum concentrations and therapeutic as well as adverse effects. Although vancomycin is not appreciably absorbed from the intact gastrointestinal tract, several recent case reports have documented the attainment of therapeutic and potentially toxic vancomycin serum concentrations following oral administration to patients with pseudomembranous colitis. The disposition of parenterally administered vancomycin has been best characterised by a triexponential model. The half-life of the initial phase (t1/2 pi) is approximately 7 minutes, that of the second phase (t1/2 alpha) is approximately 0.5 to 1 hour, while the terminal elimination half-life (t1/2 beta) ranges from 3 to 9 hours in subjects with normal renal function. The volume of the central compartment (Vc) in adults is approximately 0.15 L/kg while the steady-state volume of distribution (Vdss) ranges from 0.39 to 0.97 L/kg. More than 80% of a vancomycin dose is excreted unchanged in the urine within 24 hours after administration, and the concentration of vancomycin in liver tissue and bile has been reported to be at or below detection limits. Vancomycin renal clearance approximates 0.5 to 0.8 of simultaneously determined creatinine or 125I-iothalamate clearances, suggesting that the primary route of renal excretion is glomerular filtration. Recently, non-renal factors such as hepatic conjugation have been proposed as an important route of vancomycin elimination. However, these data are difficult to reconcile with other studies showing minimal non-renal clearance of vancomycin in subjects with end-stage renal disease. As yet, the disposition of vancomycin in patients with hepatic disease has not been adequately defined. Only limited data are available regarding the concentrations of vancomycin in biological fluids other than plasma. The penetration of vancomycin into cerebrospinal fluid (CSF) in patients with and without meningitis has been quite variable. Although early studies suggested that adequate CSF concentrations may not be achieved in subjects with uninflamed meninges, more recent investigations have reported contradictory results. Therapeutic concentrations of vancomycin, i.e. greater than 2.5 mg/L, have, however, been reported in ascitic, pericardial, pleural and synovial fluids. Tissue concentrations of vancomycin have exceeded simultaneous serum concentrations in heart, kidney, liver and lung sp

Adult↗
PubMedDate not supplied

Aztreonam, a new monobactam antimicrobial.

The chemistry, in vitro activity, pharmacokinetics, adverse reactions, and clinical use of the monobactam antimicrobial aztreonam are reviewed. Aztreonam, an investigational agent nearing approval in the United States and Canada, is the first in a class of monobactam antimicrobials to be evaluated extensively in vitro and in vivo. It has a narrow spectrum of activity, encompassing only aerobic gram-negative microorganisms including Pseudomonas aeruginosa and most multiply resistant Enterobacteriaceae. Aztreonam has no useful activity against gram-positive or anaerobic microorganisms. In preliminary studies, aztreonam achieved high tissue concentrations and was usually well tolerated. Approximately 65-75% of an administered dose is excreted unchanged into the urine, and the elimination half-life is 1.6-2.2 hours in subjects with normal renal function. Dosage should be adjusted in patients with renal impairment. Aztreonam was shown equivalent to gentamicin and cefamandole for treating serious urinary-tract infections and produced cure rates greater than 85% in gonococcal, lower respiratory tract, orthopedic, serious urinary tract, acute uncomplicated lower urinary-tract, gynecologic, and intraabdominal infections. Development of resistance during therapy may be less likely with aztreonam than with other new cephalosporins. Aztreonam will probably have an important role in antimicrobial therapy, but much further study is necessary to assess clinical efficacy and toxicity. The clinical importance of aztreonam's superior activity under anaerobic conditions compared with aminoglycosides and the theoretical reduced alteration in GI colonization resistance must be assessed in controlled trials. Evaluation of aztreonam versus ceftazidime, the carbapenems, and the carboxyquinolones is needed, and the likelihood of gram-positive superinfection, especially with enterococci, must be further assessed.

Animals↗
PubMedDate not supplied

Comparison of bioavailability and pharmacokinetics of cimetidine in subjects with normal and impaired renal function.

The bioavailability and pharmacokinetics of cimetidine were studied following single oral and intravenous doses in subjects with severely impaired renal function (SIRF) and normal renal function (NRF). Eight subjects with NRF and five patients with SIRF participated. Multiple blood samples were obtained up to 1440 minutes following both doses. Urine was also collected for 24 hours after each dose. The bioavailability of cimetidine was not significantly different between the two groups (78 +/- 15% in patients with SIRF and 62 +/- 17% in the NRF subjects). In subjects with NRF, a mean of 50.4% of the i.v. dose was excreted renally as unchanged drug and the mean serum half-life (t1/2) was 2.00 hours. The mean total body and renal clearances were 710.0 and 370.7 ml/min, respectively. In the SIRF group, a mean of 1.7% of the i.v. dose was excreted renally unchanged, and the mean t1/2 was 12.71 hours. The total body and renal clearances were 147.1 and 2.5 ml/min, respectively. Nonrenal clearance was 62% lower in the subjects with SIRF than in the NRF subjects. There is no significant difference in bioavailability of cimetidine between the patients with NRF and SIRF. The significantly lower nonrenal clearance of the patients with SIRF suggests that cimetidine metabolism may be impaired in uremic patients.

Administration, Oral↗
PubMedDate not supplied

Developing drug use evaluation criteria for parenteral fluoroquinolones.

The basic tenet of pharmaceutical care asserts that the delivery of optimal, cost-effective pharmacotherapy can be best achieved by identifying, resolving, and preventing drug-related problems. Drug use evaluation (DUE) is one of the primary tools used to achieve these ends. Fluoroquinolone antimicrobials meet Joint Commission criteria for targeting for DUE: the drugs are used in populations at high risk for adverse drug reactions, quality assurance or infection control committees target them for DUE, the drugs are costly, they may be suspected or known to be used inappropriately, and they are prescribed frequently. Outside this supplement, no published DUE criteria for parenteral fluoroquinolones currently exist. Suggested criteria include use in patients who would otherwise be candidates for oral fluoroquinolone therapy (for which published criteria exist) but who cannot use the oral route of administration due to gastrointestinal conditions predisposing to malabsorption or unavailability of the oral route; for severe infections due to gram-negative pathogens; as a replacement for aminoglycosides when ototoxicity or nephrotoxicity is a substantial risk; targeting to resistant pathogens (i.e., not as empiric therapy); and targeting to therapeutic use only (not for prophylaxis). The DUE process is crucial for ensuring safe, effective, appropriate, and economical drug therapy. It is an effective mechanism for evaluating the use of new agents and as an educational tool for clinicians in the postmarketing period.

Anti-Infective Agents↗
PubMedDate not supplied

Antihypertensive drug use in the long-term care facility: a pilot study and review of the literature.

The overuse and cost of drugs in long-term care facilities are of significant concern. To quantify potential overuse of antihypertensive agents, we conducted a retrospective chart review in four long-term care facilities. We analyzed data in 550 patient records to identify residents receiving drugs for the sole indication of hypertension. Of the 550 records, 49 (9%) residents qualified. Of these, 20 (41%) had all recorded blood pressures less than 140/90 mm Hg for the 6 months before review, and 32 (65%) had all blood pressures less than 160/90 mm Hg. Given this degree of blood pressure control and the reported success of withdrawing antihypertensive drugs from the elderly in whom the disorder is well controlled, a reevaluation of antihypertensive therapy in residents of long-term care facilities appears to be justified.

Aged↗
PubMedDate not supplied

QTc-interval prolongation associated with slow intravenous erythromycin lactobionate infusions in critically ill patients: a prospective evaluation and review of the literature.

Intravenous erythromycin has recently been associated with significant QTc interval prolongation, torsades de pointes, and sudden cardiac death. The prolonged the QTc interval attributed to erythromycin typically is associated with rapid infusion rates in excess of 10 mg/minute. We prospectively assessed the relationship between QTc interval prolongation and erythromycin administration by slow intravenous infusion (mean rate 8.9 +/- 3.5 mg/minute, range 3.9-16.7 mg/minute). Electrocardiographic (ECG) rhythm strips were prospectively obtained in 44 critically ill patients receiving intravenous antibiotics (22 received erythromycin and 22 ceftazidime, cefuroxime, cefotaxime, ceftriaxone, or ampicillin-sulbactam as controls). The ECG recordings were obtained immediately before and within 15 minutes after drug infusions. Only the first available set of ECG strips were evaluated. Two controls had evidence of hepatic dysfunction; no patients receiving erythromycin did. The QTc interval was calculated using Bazett's formula by two blinded investigators. For controls, mean +/- 1 SD (range) QTc intervals were 423 +/- 96 (300-550) msec at baseline and 419 +/- 96 (280-610) msec after infusion (p = 0.712). In contrast, in the erythromycin group, the interval was significantly prolonged from 524 +/- 105 (360-810) msec at baseline to 555 +/- 134 (400-980) msec after infusion (p = 0.034). No patients experienced a dysrhythmia as a consequence of erythromycin infusion. Despite slow rates of infusion, QTc interval prolongation was significant. The clinical importance of this finding remains to be determined.

Adult↗
PubMedDate not supplied

Repaglinide, a novel, short-acting hypoglycemic agent for type 2 diabetes mellitus.

Repaglinide is a new, short-acting, insulin-releasing agent recently approved for the monotherapy of type 2 diabetes mellitus, and in combination with metformin in patients failing repaglinide or metformin monotherapy. Repaglinide appears to trigger insulin release by regulating adenosine triphosphate-sensitive potassium channels on the surface of pancreatic beta cells, which in turn affect calcium influx, the principal mediator of insulin release. Repaglinide mainly affects postprandial plasma glucose concentrations. It reduces glycosylated hemoglobin concentrations by 1-2% U. The agent's short duration of action may lessen the risk of long-lasting hypoglycemia and of down-regulation of beta cell sensitivity (the latter promoting secondary drug failure), although data are sparse in this regard. Its major adverse effect is hypoglycemia. Its role in the therapy of type 2 diabetes is unclear at present, vis-à-vis its use instead of or in combination with other antidiabetic agents other than metformin. The need for multiple daily doses, based on its brief duration of action, may be a barrier to compliance.

Carbamates↗