Search PubMed⌕ Search

Biomedical subjects

J J Schentag

Publications and source records attributed to J J Schentag.

At least 127 records · Page 7Linked to original sources
PubMed1989

Clinical significance of antibiotic tissue penetration.

The concentrations achieved by a particular antibiotic in serum and tissues can be predicted from pharmacokinetic data. These predictions must be evaluated in the broader context of the patient's infection, particularly the MIC of the drug for the infecting organism. What is the relevant measurement - the serum concentration or the tissue to serum ratio? Are the serum and/or tissue concentrations achieved at the site of infection sufficiently in excess of the MIC to eradicate the organism? How long are these levels sustained? How often must the drug be given to keep the concentrations sufficiently in excess of the MIC to eradicate the organisms? This presentation will review these questions in the context of the major classes of antibiotics: the beta-lactams, aminoglycosides and quinolones.

Animals↗
PubMed1989

Evaluation of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections. Impact of plasma concentrations, organism, minimum inhibitory concentration, and clinical condition on bacterial eradication.

Fifty patients with gram-negative lower respiratory tract infections were treated with intravenous ciprofloxacin to evaluate efficacy and safety. Relationships between individual pharmacokinetics and clinical and bacteriologic outcome were studied. Ciprofloxacin concentrations in plasma were determined by high-performance liquid chromatography. Respiratory secretion cultures were obtained daily to determine the eradication day of the infecting organism. Susceptibility (minimum inhibitory concentration) to ciprofloxacin and other antimicrobials was determined using standard microdilution techniques. The mean age of the patients was 70 years. They had multiple underlying diseases, and two thirds of them were ventilator dependent at entry. Approximately 50% of the patients had failed previous treatment for the same infections. Patients infected with Enterobacteriaceae or Haemophilus influenzae with minimum inhibitory concentrations of less than 0.25 mg/L responded well to intravenous ciprofloxacin therapy (200 mg every 12 hours). The organisms were eradicated from sputum cultures usually within 1 day after ciprofloxacin therapy was started. Most clinical failures occurred in patients who were infected with Pseudomonas aeruginosa and had multiple underlying diseases. Pseudomonas aeruginosa was isolated from 10 patients with pneumonia, 2 patients with lung abscess, and 1 patient with bronchiectasis. The Pseudomonas isolate acquired resistance during ciprofloxacin treatment in 7 patients with pneumonia and in all of the remaining 3 patients. We conclude that ciprofloxacin is safe and effective at a dosage of 200 mg administered intravenously every 12 hours for nosocomial lower respiratory tract infections caused by Enterobacteriaceae or Haemophilus species. Many patients who had failed previous antibiotic treatment for Enterobacteriaceae infections had good clinical response to ciprofloxacin therapy. Studies using either higher dosages of ciprofloxacin or combination therapy should be conducted to determine if acquired resistance can be avoided in Pseudomonas infections.

Aged↗
PubMed1988

Kinetics and action of N-methylthiotetrazole in volunteers and patients. Population-based clinical comparisons of antibiotics with and without this moiety.

Normal volunteers and patients were studied to determine the relative importance of NMTT and patient risk factors in the production of hypoprothrombinemia. The normal volunteers demonstrated in vivo NMTT production, but the order of magnitude (cefoperazone, moxalactam, and cefotetan in descending order) was different from the usual order of clinical risk. In patients, there was not a NMTT-concentration-versus-effect relationship. Patients who were vitamin K deficient were more sensitive to lower NMTT concentrations than those with normal vitamin K status. In surveillance studies, NMTT-containing antibiotics were nor more frequently associated with hypoprothrombinemia or bleeding than antibiotics that lack this moiety.

Azoles↗
PubMed1988

The effect of renal impairment and haemodialysis on single dose pharmacokinetics of oral enoxacin.

The effect of renal impairment on the single dose pharmacokinetics of oral enoxacin was studied in 28 volunteers with creatinine clearances ranging from less than 15 to 120 ml/min, including patients undergoing chronic haemodialysis. Following an overnight fast, 400 mg of enoxacin was administered orally to each subject. Blood and urine samples were collected at predetermined times for 48 and 72 h, respectively. Plasma and urine samples were assayed for enoxacin and for oxo metabolite concentrations by a specific high performance liquid chromatographic method. Area under the concentration-time curve from time 0 to infinity (AUC0-infinity) was increased in subjects with renal impairment. Plasma half-life (10.6-11.6 h) in volunteers with severe renal impairment was approximately double the 5.2 h half-life found in subjects with normal renal function, and this should result in steady-state enoxacin concentrations approximately double those measured in normal subjects given equivalent doses. Haemodialysis did not remove significant amounts of enoxacin. A significant correlation between creatinine clearance and enoxacin renal clearance was observed (r = 0.97).

Administration, Oral↗
PubMed1988

Comparison of two methods for determining in vitro postantibiotic effects of three antibiotics on Escherichia coli.

The postantibiotic effect (PAE) for 10 isolates of Escherichia coli was measured by two methods after 1 h of exposure to ampicillin, ciprofloxacin, or tobramycin. The reference method involved serial colony counting to determine growth after antibiotic exposure in relation to control growth. A spectrophotometric procedure was developed with the Abbott MS-2 research system. This method measured the time to detection of growth after exposure and compared this with the time for growth detection in control chambers having the same initial colony count. A reference curve of time to growth versus log initial CFU per milliliter was used to standardize control growth. PAE was determined after exposure to antibiotic at two and six times the MIC and with inocula ranging from 10(3) to 10(9) CFU/ml. There was a statistically significant correlation between PAE measured by the spectrophotometric and the reference methods, and the residuals about the regression line were normally distributed. The mean PAE determined by both methods was statistically different for tobramycin-exposed, but not for ampicillin- or ciprofloxacin-exposed, organisms. There was a concentration-dependent PAE for ciprofloxacin and tobramycin. The PAEs for ciprofloxacin (151 min) and tobramycin (108 min) at concentrations six times the MIC were prolonged compared with those measured at two times the MIC (69 and 66 min, respectively). PAE was inversely related to the exposed inoculum for ciprofloxacin and tobramycin. The PAE for E. coli exposed to ampicillin was minimal and was not affected by either concentration or inoculum. The MS-2 method for determining PAE yields similar results, but is less laborious than the reference method.

Ampicillin↗
PubMed1988

Pharmacokinetics of cefoperazone (2.0 g) and sulbactam (1.0 g) coadministered to subjects with normal renal function, patients with decreased renal function, and patients with end-stage renal disease on hemodialysis.

The single-dose pharmacokinetics of intravenously administered cefoperazone (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of renal failure. In an open, parallel experimental design, six normal subjects (creatinine clearance, greater than 90 ml/min), two patients with mild renal failure (creatinine clearance, 31 to 60 ml/min), eight patients with moderate renal failure (creatinine clearance, 7 to 30 ml/min), and four functionally anephric patients (creatinine clearance, less than 7 ml/min) were studied. The functionally anephric patients were given two test doses to allow study of drug disposition both on and off hemodialysis. Serial blood and urine samples were collected from time zero to 12 h after dosing in normal subjects and from 0 to 72 h in renal patients. Serum concentrations of both drugs declined biexponentially. For cefoperazone, the terminal elimination half-lives averaged from 1.6 to 3.0 h and were similar in subjects and patients. No cefoperazone pharmacokinetic parameters were appreciably altered by renal failure or hemodialysis, and there was no correlation between the total body clearance of cefoperazone and estimated creatinine clearance. In contrast, the sulbactam total body clearance was highly correlated with estimated creatinine clearance (r = 0.92, P less than 0.01) and was significantly higher in normal volunteers than in the renally impaired groups (P less than 0.01). The sulbactam terminal elimination half-life in functionally anephric patients (9.7 +/- 5.3 h) differed significantly from that of normal volunteers (1.0 +/- 0.2 h) and patients with mild renal failure (1.7 +/- 0.7 h, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The increase in urinary alanine aminopeptidase excretion associated with enflurane anesthesia is increased further by aminoglycosides.

Urinary excretion of alanine aminopeptidase (AAP) is an extremely sensitive indicator of drug-induced renal tubular damage. The urinary excretion of AAP was determined in patients after enflurane anesthesia with or without concurrent aminoglycoside administration to determine if enflurane enhances the nephrotoxic potential of aminoglycosides. Twenty-two patients with normal renal function were studied. Ten received enflurane alone, eight received enflurane plus gentamicin or tobramycin, and four patients who underwent nitrous oxide and narcotic anesthesia were the control group. Preoperative values ranged from 1010 to 2461 microU/24 hour. Urinary AAP excretion increased significantly in both enflurane groups 2 days postoperatively (P less than 0.025). Patients who received both enflurane and aminoglycosides had significantly greater urinary AAP excretion on postoperative day 2 than did patients given enflurane alone: 21,342 +/- 4074 microU/24 hour and 6336 +/- 1496 microU/24 hour, respectively (mean +/- SEM, P less than 0.005). There was no change in AAP excretion in the control group compared to baseline; on day 3 AAP was 1412 +/- 710 microU/24 hour. No changes in blood urea nitrogen or serum creatinine levels were observed. These data suggest that enflurane increases the renal tubular effects of aminoglycosides, possibly increasing the risk of aminoglycoside renal toxicity.

Adult↗
PubMed1988

Lack of effect of cimetidine on the metabolism of quinidine: effect on renal clearance.

The disposition and urinary recovery of unchanged quinidine, (3S)-3-hydroxyquinidine, 2'-oxoquinidinone and quinidine-N-oxide was studied in 5 normal volunteers following a single oral dose of quinidine sulfate (400 mg) with and without cimetidine pre-treatment (1.2 g/day for 7 days). Total amounts of parent compound or metabolites excreted in the urine following cimetidine pre-treatment were not significantly different from that excreted during quinidine alone. Cimetidine reduced the mean apparent oral clearance of quinidine (+/- s.e.m.) by 33% from 23.7 +/- 2.5 to 15.9 +/- 1.7 l/h (p less than 0.05). This 33% decline in oral clearance paralleled the 33% decline in renal clearance of unchanged quinidine which decreased from 56.7 +/- 13.3 to 38.3 +/- 3.3 ml/min. The reduction in quinidine renal clearance associated with cimetidine pre-treatment, although failing to achieve statistical significance, partially accounted for the observed decrease in mean apparent oral clearance. This suggests that cimetidine may compete for renal tubular secretion of unchanged quinidine and its metabolites rather than alter the oxidative metabolism of quinidine.

Adult↗
PubMed1987

Oral ciprofloxacin in the treatment of serious soft tissue and bone infections. Efficacy, safety, and pharmacokinetics.

Forty-eight patients were enrolled in a clinical study of oral ciprofloxacin for the treatment of soft tissue or bone infections. Patients received 500 to 750 mg of ciprofloxacin every 12 hours. In the predominantly older population studied, there were 13 patients with osteomyelitis, 24 diabetic patients with soft tissue infection and probable osteomyelitis, and 11 patients with other soft tissue infections. Infecting pathogens included Pseudomonas aeruginosa in 25 patients, Serratia species in nine patients, Staphylococcus aureus in 13 patients, and other aerobic gram-negative rods in 21 patients. Clinical response (defined as resolution or improvement) was noted in 84 percent of patients with non-diabetic osteomyelitis, in 79 percent of patients with diabetic infections, and in 91 percent of patients with soft tissue infections. Microbiologic outcome was very favorable in 75 percent of cases, and Pseudomonas responded as well as any other pathogen. Pharmacokinetic properties of ciprofloxacin were evaluated in 12 patients, and the data were analyzed using both compartmental and non-compartmental analyses. Mean values for compartmental rate constants (hours-1) were as follows: absorption rate constant = 1.15; intercompartmental rate constants, k12 = 0.48, and k21 = 0.58; elimination rate constant = 0.46; distribution rate constant = 1.31; and terminal elimination rate constant = 0.19. The apparent volume of distribution at steady state/bioavailability was 196 liters and total body clearance/bioavailability was 45.9 liters/hour. The mean time to peak concentration was 1.3 hours. The mean peak concentration as determined by compartmental fitting (2.4 micrograms/ml) underestimated the observed peak (3.2 micrograms/ml) by 24.8 percent. Clearance of ciprofloxacin was similar regardless of the method used to fit the data, whereas the volume of distribution was significantly different when the two analysis techniques were compared. Ciprofloxacin was well tolerated, with the most frequent adverse reactions being rash, gastrointestinal intolerance, and increased levels of liver enzymes, each of which occurred in five patients.

Administration, Oral↗
PubMed1987

Dual individualization of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections.

Dual individualization is the integration of patient-specific pharmacokinetic parameters with the pharmacodynamics (concentration versus response) of the infecting pathogen. This technique allows description of the time of in vivo bacterial eradication, and allows estimation of optimal dosages using small numbers of seriously ill patients. In an ongoing study, 11 patients with nosocomial lower respiratory tract infections were given 200 mg of intravenous ciprofloxacin every 12 hours. Ten blood samples were taken after the first dose, with additional peaks and troughs measured on Day 4 and at the end of treatment. Bacterial isolates had minimal inhibitory concentrations (MICs) determined by standard microdilution techniques. In the 11 patients, there were 14 bacterial isolates, of which seven were Pseudomonas aeruginosa and the remainder were other pathogens. Ciprofloxacin MICs ranged from 0.008 to 1.0 microgram/ml. The pharmacokinetics of ciprofloxacin in these patients varied with renal function, and average peak serum concentrations ranged from 1.7 to 4.9 micrograms/ml. Eradication of bacteria from tracheal aspirates occurred between Days 1 and 7, except in four patients in whom the organism persisted. Correlations were observed between the day of eradication and the length of time ciprofloxacin concentrations remained above the minimal inhibitory concentration (MIC). Essentially all bacteria with MICs of less than 0.25 were eradicated. Of the non-eradicated bacteria, most had either MICs of more than 0.25, or less than 100 percent time above the MIC. The clinical response was satisfactory. It is concluded that 200 mg of intravenous ciprofloxacin every 12 hours is highly effective for bacteria with MICs less than 0.25 microgram/ml, but higher dosages may be required to eradicate organisms with higher MICs.

Aged↗
PubMed1987

Determinants of antibiotic-associated hypoprothrombinemia.

Hypoprothrombinemia is a relatively uncommon event in the hospitalized patient. When it does occur, it often is associated with surgery, dietary vitamin K deficiency, renal dysfunction, malignancy, and broad-spectrum antibiotic therapy. Several mechanisms have been proposed to account for antibiotic-associated hypoprothrombinemia, including eradication of gastrointestinal bacteria, direct inhibition of vitamin K-dependent coagulation, and indirect inhibition of coagulation. The anecdotal reports and comparative studies of antibiotic-associated hypoprothrombinemia were reviewed; these usually implicated broad-spectrum or the use of several antibiotics. The increased frequency of hypoprothrombinemia associated with moxalactam and cefoperazone also raises questions about the role of their N-methylthiotetrazole (NMTT) side chains. The hypoprothrombinemia associated with NMTT antibiotics does not occur in healthy volunteers and is rare in patients without complicating conditions. Although NMTT inhibits vitamin K-dependent carboxylation in vitro, the parent cephalosporins do not. It is not clear whether NMTT-containing antibiotics liberate sufficient amounts of NMTT in vivo to antagonize clotting in patients. Thus, although moxalactam, and possibly cefoperazone, may in some cases be responsible for increases in prothrombin time, most important question for further study is whether the newer NMTT-containing antibiotics pose a risk of hypoprothrombinemia that is greater than that of antibiotics lacking this side chain.

Animals↗
PubMed1987

Effect of multiple dose oral ciprofloxacin on the pharmacokinetics of theophylline and indocyanine green.

Interaction between ciprofloxacin and theophylline was studied in eight male volunteers, who were randomly divided into two groups. All subjects were given intravenous theophylline and indocyanine green (ICG) on study days 0, 7 and 14. Group I subjects received ciprofloxacin 750 mg orally every 12 h on days 1-7. Group II subjects received ciprofloxacin 750 mg every 12 h on days 6-14. No significant changes in ICG clearance or half-life were noted. A significant increase in theophylline half-life and volume of distribution was observed (P less than 0.05); however, clearance was not significantly decreased (P = 0.1). A potentially clinically significant interaction was detected in three subjects whose theophylline clearance decreased by 42-113%. Until further clinical experience is gained, we advise caution when these agents are coadministered. Some adjustment in theophylline dosage may be required; therefore, these patients should have serum theophylline concentration measurements and careful clinical assessment for theophylline toxicity.

Administration, Oral↗
PubMed1987

Inhibition of theophylline clearance by coadministered ofloxacin without alteration of theophylline effects.

The influence of multiple doses of ofloxacin (ORF 18489) on the disposition of theophylline was studied in 15 male volunteers. Subjects were confined in the Clinical Research Unit for 13 days and given a xanthine-free diet. A single dose (3 mg/kg) of theophylline was given orally, and blood samples were collected at fixed time intervals for 36 h. The concentrations of theophylline were measured with TDX (Abbott Diagnostics, Irving, Tex.), and clearance was calculated. Theophylline clearance was used to individualize subsequent doses to achieve average steady-state theophylline concentrations in plasma of 10 mg/liter. Individualized theophylline doses were administered every 8 h until steady-state conditions were reached. Theophylline clearance was determined again at steady state and on days 7 and 8. On day 8, ofloxacin (400 mg every 12 h) was given concomitantly with theophylline. Theophylline clearance was measured again on day 12, after the last theophylline dose. Administration of ofloxacin for 1 day did not change theophylline clearance, but coadministration for 4 days significantly decreased theophylline clearance by 12.1% (P less than 0.05). The area under the concentration-time curve for theophylline increased 9.9% (P less than 0.05), and average steady-state concentrations in plasma increased 10.3% (P less than 0.05). Despite changes in clearance, adverse effects of theophylline did not increase during coadministration of ofloxacin. Although statistically significant, the interaction between ofloxacin and theophylline is unlikely to be of major clinical importance.

Adolescent↗
PubMed1987

Single-dose accumulation pharmacokinetics of tobramycin and netilmicin in normal volunteers.

The two-compartment tissue accumulation pharmacokinetics of tobramycin and netilmicin were compared in 11 normal volunteers by using a crossover design. After each 1.0-mg/kg (body weight) dose, serum was collected for 96 h, and complete 24-h urine collections were obtained for a total of 30 days. Two months of washout were required before crossover. Concentrations in serum and urine were measured by radioimmunoassay, and concentrations in serum and urinary excretion rates were simultaneously fitted to a two-compartment pharmacokinetic model. Netilmicin exhibited significantly lower total body clearance (48 versus 90 ml/min) and longer terminal elimination half-life (161 versus 96 h) than tobramycin. As a result of these pharmacokinetic differences, the predicted tissue accumulation of netilmicin at steady state was significantly higher than that of tobramycin (P less than 0.05). Relative rates of aminoglycoside nephrotoxicity probably depend on both the differential tissue uptake (accumulation) and the concentration of the aminoglycoside which produces intracellular toxicity. Because the steady-state tissue accumulation of netilmicin is nearly 2.5 times greater than that of tobramycin, its potency in the production of intracellular toxicity needs to be that much less for the two agents to produce the same incidence of clinical nephrotoxicity.

Adult↗
PubMed1987

A clinical pharmacy-oriented drug surveillance network: I. Program description.

The limitations of the new drug development process, particularly in regard to the evaluation of drug safety, have resulted in a need for monitoring drug experience in the postmarketing period. Although a number of systems have evolved to perform postmarketing surveillance, each has important limitations, suggesting the need for an alternative, innovative approach that would permit rapid identification of potential problems and support studies of multiple drugs and/or disease states in patient populations large enough to permit identification of uncommon, but significant adverse drug reactions. This has led to the organization of a nationwide network of clinical pharmacists with an active role in patient-care monitoring to collect information regarding the safety and effectiveness of drugs. At the present time there are 383 clinical pharmacists from all 50 states participating in the network. These individuals collectively monitor more than 150,000 inpatient hospital beds, more than 40,000 nursing home beds, and more than 800,000 ambulatory care visits per year. Participating clinical pharmacists, using standardized data collection forms, perform concurrent monitoring of drug-therapy outcome in targeted patient populations. Careful analysis and interpretation of this information will yield clinically relevant information regarding the outcome of drug therapy under actual clinical conditions.

Computer Communication Networks↗
PubMed1987

A clinical pharmacy-oriented drug surveillance network: II. Results of a pilot project.

A nationwide network of clinical pharmacists has been organized for the purpose of collecting drug experience data generated during the routine clinical care of patients. In order to assess the utility of this network a pilot project was performed to obtain a cross-sectional view of antibiotic utilization in the U.S. and to identify potential problems with a more widespread implementation of this program. One hundred eleven pharmacists enrolled in the drug surveillance network participated in this survey and collected information on more than 2000 patients treated with antimicrobial agents over approximately a three-month period (February-April 1987). The most common sites of infection were the lung, genitourinary tract, skin and soft tissue, and the abdomen, and accounted for approximately 75 percent of infections. Overall, the aminoglycosides, the first-generation cephalosporins, and the aminopenicillins remain the most commonly used antibiotics and represent approximately 50 percent of antimicrobials used in the surveyed population. The results of this pilot project suggest that the use of a nationwide network of clinical pharmacists is a promising source of clinically relevant drug experience data. The ability to concurrently evaluate patients and link information regarding patient demographics, drug therapy regimens, diagnosis, and clinical outcomes fills an important gap in our knowledge of clinical drug utilization.

Adult↗