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J F Inciardi

Publications and source records attributed to J F Inciardi.

9 recordsLinked to original sources

The relationship between antecedent antibiotic use and resistance to extended-spectrum cephalosporins in group I beta-lactamase-producing organisms.

Gram-negative pathogens are increasingly resistant to extended-spectrum cephalosporins (ESCs). Using a prospective, case-controlled observational study, we examined the prevalence and the risk factors for development of resistance to ESCs in group I beta-lactamase-producing organisms. Of the 386 isolates of Enterobacter species, Pseudomonas aeruginosa, Citrobacter species, and Serratia marsescens from 340 consecutive patients, 70 (18.1%) were resistant to ESCs; the highest rates of resistance were found among Citrobacter freundii (40.9%), Enterobacter cloacae (31.1%), and Enterobacter aerogenes isolates (18.9%). Patients' prior antibiotic use and the mean number of antibiotics used were significantly greater in association with resistant vs. susceptible isolates. Resistance was associated with prior use of ceftizoxime or cefotaxime (P = .008), ceftazidime (P = .004), and piperacillin (P = .001). Other antibiotics were not associated with resistance. Resistance was less frequent in patients receiving ESCs and an aminoglycoside. We conclude that prior use of ESCs is associated with the isolation of resistant group I beta-lactamase-producing organisms. Concomitant use of an aminoglycoside may decrease this risk.

Adult

Assessing random error in the international normalized ratio.

Changes in the international normalized ratio (INR) following warfarin administration may be explained not only by the attendant anticoagulant effect but also, in part, by random errors normally associated with laboratory assays. Thus, a patient's true INR will differ from the reported value by some random error related to the variability in the prothrombin time (PT) assay. By employing a statistical technique known as the delta method, the error expected in an INR for a particular institution can be estimated by taking the product of the international sensitivity index (ISI) and the coefficient of variation (CV) for the PT assay.

Drug Monitoring

Nonparametric approach to population pharmacokinetics in oncology patients receiving aminoglycoside therapy.

A nonparametric expectation maximization approach to the study of population pharmacokinetics is described for an aminoglycoside antibiotic. The method is used to explore population estimates for gentamicin clearance (liters per hour per creatinine clearance) and volume of distribution (liters per kilogram) in tumor patients. Joint and marginal probability distributions are plotted and further characterized by using standard descriptors such as mean, median, mode, standard deviation, skewness, and kurtosis. Results of additional analyses using hematologic or solid tumor subpopulations agree with those of a recent larger study which found no significant pharmacokinetic differences between these groups. Nonparametric maximum-expectation analyses are convenient and allow exploratory analysis of population estimates directly from routine laboratory information.

Adult

Setting confidence intervals for drug concentrations from pharmacokinetic parameters.

OBJECTIVE: To describe and illustrate a convenient method of forecasting drug concentrations with confidence intervals (CIs) using the means and standard deviations of relevant pharmacokinetic parameters (e.g., clearance and volume of distribution). DESIGN: Using summary statistics from previously published reports, a Monte Carlo technique employing a SAS random number generator creates an arbitrarily large "sample" of each pharmacokinetic parameter. A related "sample" of drug concentrations is provided by inserting the parameters into the appropriate model. A point estimate of the mean drug concentration with a CI is calculated using standard statistical methods. Both the one- and two-compartment body models are illustrated using previous investigations of gentamicin and lidocaine, respectively. RESULTS: One-compartment simulations describe CIs for gentamicin concentrations that vary widely depending on the source of the clearance and volume of distribution parameters. Lidocaine CIs using a two-compartment analysis indicate a range of concentrations quite different from the expected mean. CONCLUSIONS: CIs provide a perspective of drug therapy that is considerably more informative than a simple point estimate of the mean concentration.

Confidence Intervals

The effect of acetaminophen on zidovudine metabolism in HIV-infected patients.

The concomitant administration of acetaminophen to HIV-positive patients receiving zidovudine (AZT) therapy has previously been thought to increase the likelihood of the toxicity of AZT due to increased serum levels, resulting from hypothesized metabolic competition. We measured serum AZT and metabolite levels by HPLC in HIV-infected patients taking regular doses of AZT with and without acetaminophen administration. In all patients, serum levels of AZT and the glucuronidated metabolite (GAZT) were similar with and without acetaminophen administration. AZT serum levels were not increased (p less than 0.05). We believe that the rationale for withholding acetaminophen from patients receiving AZT should be re-evaluated.

Acetaminophen

Effects of 3'-deoxycytidine on rRNA synthesis in toad bladder: analysis of response to aldosterone.

Previous studies showed that aldosterone augments transepithelial active Na+ transport and the incorporation of [3H]uridine into polyadenylated RNA (poly(A)(+)-RNA) (putatively mRNA) early in the latent period. Soon thereafter, incorporation of [methyl-14C] groups, as well as [3H]uridine into rRNA is also increased. To evaluate the role of rRNA in mineralocorticoid action, the inhibitor 3'-deoxycytidine was used in studies on the urinary bladder of the toad Bufo marinus. 3'-deoxycytidine suppressed the incorporation of [methyl-14C] and [3H]uridine into nuclear precursors of rRNA and subunits of cytoplasmic rRNA. In contrast, 3'-deoxycytidine inhibited incorporation of ]3H]uridine into cytoplasmic poly(A)(+)-RNA minimally. In control experiments, 3'-deoxycytidine had no significant effect on Na+ transport, measured as the short-circuit current (scc), when given alone. 3'-Deoxycytidine also had no significant effect on the aldosterone-dependent increase in scc. In the presence of 3'-deoxycytidine, aldosterone enhanced both the scc and the incorporation of [3H]uridine into poly(A)(+)-RNA significantly. We conclude that during the first 3 h, the mineralocorticoid action of aldosterone is not sensitive to inhibition of rRNA synthesis. Previous studies, however, implicate mRNA synthesis in this early response.

Aldosterone

Estimating phenytoin concentrations by the Sheiner-Tozer method in adults with pronounced hypoalbuminemia.

OBJECTIVE: To assess the performance of the Sheiner-Tozer equation when used to evaluate total phenytoin concentrations in patients with pronounced hypoalbuminemia. DESIGN: Patients with phenytoin concentrations drawn at least 5 days after initiation of therapy and with serum albumin concentrations of less than 25 g/L were identified during routine daily monitoring. Phenytoin samples were frozen at -30 degrees C, batched, and later thawed for total and free phenytoin assay. Separation of free phenytoin concentration was performed at 37 degrees C using a Centrifree micropartition filter. SETTING: A 400-bed university teaching hospital. PATIENTS: Twenty-nine adults with hypoalbuminemia receiving phenytoin therapy. Patients receiving drugs known to displace phenytoin, or those with renal failure, abnormal liver enzymes, or increased bilirubin concentrations were excluded. MAIN OUTCOME MEASURE: Precision and bias of the normalized result using the Sheiner-Tozer equation were assessed with respect to observed phenytoin concentrations. RESULTS: The Sheiner-Tozer equation underpredicts the measured free concentration by approximately 12.4%. The equation provides a small but statistically significant bias (-2.7 mg/L) and a root mean squared error significantly different from 0. For most of our patients these departures appear small enough to warrant an initial empiric appraisal of hypoalbuminemia using the Sheiner-Tozer method. CONCLUSIONS: The Sheiner-Tozer equation can normalize total phenytoin concentrations reliably in patients with low albumin concentrations at our institution.

Adult