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J C Rotschafer

Publications and source records attributed to J C Rotschafer.

At least 55 records · Page 3Linked to original sources
PubMed1991

Individualizing amikacin regimens: accurate method to achieve therapeutic concentrations.

Amikacin's pharmacokinetics and dosage requirements were studied in 98 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine levels or normal creatinine clearance. The half-life ranged from 0.7 to 14.4 h in 74 patients who had normal serum creatinine levels and from 0.7 to 7.2 h in 37 patients who had normal creatinine clearance. The necessary daily dose to obtain therapeutic serum concentrations ranged from 1.25 to 57 mg/kg in patients with normal serum creatinine levels and from 10 to 57 mg/kg in patients with normal creatinine clearance. In four patients (4%), a significant change in baseline serum creatinine level (greater than 0.5 mg/dl) occurred during or after treatment, which may have been amikacin-associated toxicity. Overt ototoxicity occurred in one patient. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.

Adult↗
PubMed1990

Assessment of effects of protein binding on daptomycin and vancomycin killing of Staphylococcus aureus by using an in vitro pharmacodynamic model.

Initial clinical trials with daptomycin (2 mg/kg per day) were prematurely suspended because of unexplained treatment failures in patients with bacteremia who were treated with daptomycin, despite in vitro data indicating that the gram-positive cocci causing the infection were susceptible to daptomycin. One explanation for these clinical failures may relate to the relatively high degree of daptomycin protein binding (94%). To evaluate the impact of protein on daptomycin activity, a two-chamber in vitro pharmacodynamic model was used to study and compare the interaction between Staphylococcus aureus (clinical isolate) and either daptomycin or vancomycin, each in the presence and absence of physiologic human albumin concentrations. Low-dose (2 mg/kg) daptomycin, high-dose (6 mg/kg) daptomycin, and 10 mg of vancomycin per kg beta-phase elimination serum-concentration-versus-time curves were simulated by using this in vitro pharmacodynamic model. The bacterial kill rates by all three regimens were decreased in the presence of albumin (P less than 0.0002). The average times required for a 99% kill of the initial S. aureus inocula (approximately 5 x 10(7) CFU/ml) without albumin were 0.81 (low-dose daptomycin), 0.33 (high-dose daptomycin), and 6.18 (vancomycin) h. The average times required for a 99% kill of S. aureus with albumin were 7.66 (low-dose daptomycin), 0.95 (high-dose daptomycin), and 10.52 (vancomycin) h. These data demonstrate that, depending on the concentration of daptomycin, the presence of albumin can profoundly diminish the bactericidal activity of daptomycin.

Daptomycin↗
PubMed1990

Aminoglycosides: another perspective.

Despite the introduction of several new classes of antimicrobial agents, aminoglycosides are still recognized as first-line therapeutic agents in the management of severe gram-negative sepsis. The major obstacle limiting the use of aminoglycoside antibiotics has been, and continues to be, the possibility of drug-induced ototoxicity and nephrotoxicity. This review critically examines the definitions used to establish the diagnosis of aminoglycoside-induced nephrotoxicity and ototoxicity and the clinical significance of these adverse reactions. The review also focuses on the practical and economic issues surrounding therapeutic drug monitoring practices. We conclude that aminoglycoside antibiotics remain an effective and economical form of therapy for severe infections and that if careful criteria are used in the selection of these agents, the benefits of therapy outweigh the risk of toxicity.

Aminoglycosides↗
PubMed1990

Clinical pharmacokinetics of ciprofloxacin.

Compared with nalidixic acid, ciprofloxacin is representative of a newer, more potent class of quinolones, termed the fluoroquinolones. It is available in both oral and parenteral dosage forms. The primary target of quinolone activity appears to be the bacterial DNA gyrase enzyme, which is a member of the class of type II topoisomerases. Bacterial do not acquire resistance to fluoroquinolones through mechanisms that are plasmid or R-factor mediated and, additionally, the quinolones do not appear to be vulnerable to degradation by bacterial inactivating mechanisms. Rather, bacterial resistance to ciprofloxacin occurs either through chromosomal mutation in the target enzyme DNA gyrase or through mutations that alter drug permeability into the bacterial cell. Ciprofloxacin and the fluoroquinolones in general are no more likely to select resistant mutant than are aminoglycosides or beta-lactam antibiotics. Ciprofloxacin displays in vitro activity against most Gram-negative and many Gram-positive pathogenic bacteria, many of which are resistant to a wide range of antibiotics. This finding is of considerable potential clinical significance. High pressure liquid chromatography (HPLC) and microbiological agar diffusion assays have been routinely used to quantify ciprofloxacin concentrations in biological fluids. Both methods are reproducible and accurate for serum but HPLC is recommended for other specimens because of the presence of microbiologically active metabolites. Absorption after oral administration is rapid and can be satisfactorily described as a zero-order process; peak serum ciprofloxacin concentrations (Cmax) are reached in approximately 1 to 2 hours. Concomitant administration of food does not cause clinically significant impairment of absorption and may be helpful in minimising gastric distress caused by the drug. A linear relationship between serum ciprofloxacin concentrations and the dose administered either orally or intravenously has been reported. The absolute bioavailability of ciprofloxacin is approximately 70%. The volume of distribution is large with a steady-state range after oral or intravenous dosing of 1.74 to 5.0 L/kg reflecting penetration of the drug into most tissues. Nonrenal clearance accounts for approximately 33% of the elimination of ciprofloxacin; to date, 4 metabolites have been identified. A first-pass effect has been reported but is thought to be clinically unimportant. Faecal recovery of ciprofloxacin accounts for approximately 15% of an intravenous dose. Nonrenal elimination includes metabolic degradation, biliary excretion and transluminal secretion across the enteric mucosa. Glomerular filtration and tubular secretion account for approximately 66% of the total serum clearance. The terminal disposition half-life (t1/2) is about 3 to 4 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Ciprofloxacin↗
PubMed1989

Current immunization practices. 1. Polio, diphtheria, tetanus, pertussis, measles, mumps, rubella, and influenza.

When used appropriately, immunization can effectively prevent many infections and diseases. Some vaccines, such as that for polio, are believed to produce lifelong immunity. Others, such as those for tetanus and diphtheria, may require that a booster injection be given upon exposure to assure full immunity. Still others, such as that for influenza, confer immunity for only a limited time. Inoculation is not without risk, particularly in immunosuppressed, allergic, febrile, or pregnant patients. However, in otherwise healthy patients, serious sequelae are so rare that they are far overshadowed by the enormous benefits of immunization.

Child↗
PubMed1989

Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients.

Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake-Peterson, and manufacturer's) were simulated in 37 patients. Ten serum samples were obtained after a 1-hour intravenous infusion of 6.2-20 mg/kg total body weight. A preinfusion serum sample was obtained from patients not studied on the first dose. Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration-time data. These data were fitted to a two-compartment, open-infusion model. Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple-dose simulated pharmacokinetics and each patient's pharmacokinetic values using the regimen suggested by each of the five methods. Steady-state serum concentrations, predicted systemic clearance by each method (except Lake-Peterson), and the daily dose for each patient recommended by each method were determined. All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction. The Matzke method recommended the largest dosage. Using each of the methods, only 3-16% of patients would have achieved recommended peak and trough serum concentrations. In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations. We suggest that the Lake-Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further.

Adult↗
PubMed1989

Suboptimal effect of daptomycin in the treatment of bacteremias.

We have reported two cases involving bacteremic patients who failed to respond adequately to the investigational agent daptomycin. Despite apparent sensitivity of the organisms, therapy was unsuccessful in both patients using the recommended dosage. The sponsor of daptomycin is currently reevaluating the recommendation and may be revising their dosage guidelines in the future.

Anti-Bacterial Agents↗
PubMed1989

Clinical assessment of a published model to predict aminoglycoside-induced nephrotoxicity.

During the past decade, several patient risk factors have been identified as contributing to the development of aminoglycoside nephrotoxicity. Sawyers et al. recently published a method for estimating the probability of aminoglycoside nephrotoxicity on an individual patient basis. The present work represents a refinement of previous publications and has not been tested with the common variations used in aminoglycoside dosing. The purpose of this study was to determine both the qualitative and quantitative value of this method in predicting aminoglycoside induced nephrotoxicity. Eighty-three patients (47 male, 36 female) meeting the inclusion criteria of Sawyers et al. were entered into the study. Patient risk factors (age, sex, initial 1-h postinfusion aminoglycoside serum level, initial calculated creatinine clearance, duration of therapy, and presence of liver disease) were entered into a logistic regression analysis to determine the individual patient's risk of developing nephrotoxicity. These calculated probability scores were then compared with the observed nephrotoxicity in specific groups within our patient sample to see how effectively the model quantitatively performed. Twelve patients (14.5%) developed nephrotoxicity. The model predicted only 5 of the 12 patients developing nephrotoxicity (sensitivity or true positive = 42%). In the nonnephrotoxic group, the model accurately predicted only 38 of 71 patients (specificity or true negative = 54%). These data suggest that the model may accurately quantitate the number of patients likely to develop nephrotoxicity from a specific group but is unable to discriminate specific patients at risk of developing aminoglycoside-induced nephrotoxicity.

Adolescent↗
PubMed1989

Evaluation of a two-compartment Bayesian forecasting program for predicting vancomycin concentrations.

The application of a two-compartment Bayesian forecasting program for vancomycin was tested retrospectively in 45 adult patients with stable renal function. Serial blood samples from 25 of these patients were used to determine population-based parameter estimates. The predictive performance of the Bayesian program was assessed by using both non-steady-state and steady-state vancomycin concentrations as feedback information. Overall, the program tended to underpredict peak and trough steady-state vancomycin serum concentrations. A larger mean prediction error (ME) was seen when non-steady-state feedback serum concentrations were used compared with using population-based parameter estimates (no feedback). In contrast, a marked improvement in ME (peaks: -1.03 versus -2.61; troughs: -1.60 versus -2.07) was seen when steady-state feedback serum concentrations were used compared with no feedback data. Precision improved when either feedback serum concentrations were used to predict steady-state peak and trough vancomycin concentrations. The results from this clinical evaluation demonstrate that the initial pharmacokinetic parameter estimates for a two-compartment Bayesian model provided accurate prediction of steady-state vancomycin concentrations. Prediction bias and precision were improved when steady-state vancomycin concentrations were used to determine individualized pharmacokinetic parameters.

Adult↗
PubMed1989

Individualizing vancomycin dosage regimens: one- versus two-compartment Bayesian models.

The absolute and relative predictive performances of one- and two-compartment Bayesian forecasting models were evaluated and compared. Initial population parameters were derived from 25 adult patients with stable renal function and who were being treated for presumed or documented gram-positive infections. The performance of each model was compared using these population parameters with and without steady-state or non-steady-state feedback concentrations to predict future peak and trough concentrations in an additional 20 patients. Both models tended to underpredict vancomycin peak and trough concentrations obtained at steady state. The use of a two-compartment model resulted in statistically less bias and more precise predictions of vancomycin peak concentrations when either population parameters or non-steady-state concentrations were used for future predictions. No difference in model performance was observed when steady-state concentrations were used to predict future steady-state concentrations. The results of this evaluation demonstrate that the two-compartment Bayesian model is less biased and more precise in determining future vancomycin serum concentrations given only population parameters or non-steady-state feedback information. No difference in model performance could be discerned when steady-state concentrations were used as feedback information.

Adolescent↗
PubMed1988

Therapeutic update on glycopeptide and lipopeptide antibiotics.

Glycopeptide antibiotics in the form of vancomycin have been available for almost 30 years. In the past, vancomycin usually was reserved as an alternative agent to treat staphylococcal and streptococcal infection in patients with a penicillin allergy or hemodialysis shunt infection. With the increasing frequency of both methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, now it is often used as a first-line agent. Over a 10-year period, vancomycin sales have increased by almost $1 hundred million. Several new glycopeptide and lipopeptide antibiotics are in various stages of evaluation. While vancomycin resistance to date is a rare phenomenon, these drugs represent a potentially more potent and safer antibiotic alternative to vancomycin. Teicoplanin and daptomycin are two of these investigational agents.

Bacterial Infections↗
PubMed1988

Vancomycin pharmacokinetics in patients with various degrees of renal function.

The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function. Patients were categorized into three groups based on measured creatinine clearance (CLCR): groups 1, 2, and 3 had 24-h CLCRs of greater than 70, 40 to 70, and 10 to 39 ml/min per 1.73 m2, respectively. After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients. Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m2) and a lower renal vancomycin clearance (CLR) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m2) than in group 1. No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed. Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function. Stepwise multiple linear regression analysis revealed that CLCR was the strongest predictor of vancomycin CL (r = 0.77, P less than 0.001) and vancomycin CLR (r = 0.87, P less than 0.001). Age did not significantly improve these correlations once CLCR was included. The relationship of vancomycin CL and CLCR was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227CLCR + 5.67, where CLCR is standardized to milliliters per minute per 70 kg. The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CLCR of the patient.

Adult↗
PubMed1988

Bacterial vaccines for splenectomized patients.

The spleen is an important organ in the defense of the body against pathogenic bacteria. Major functions of the spleen include antibody production and mechanical filtration of blood. Anatomically or functionally asplenic individuals are at increased risk of fulminant infection by encapsulated bacteria, particularly Streptococcus pneumoniae, Hemophilus influenzae, and Neisseria meningitidis. Polysaccharide vaccines are available against some strains of these pathogenic bacteria. More data are required to define specific age and risk groups. A search for better and more immunogenic vaccines, which may prove effective in a wider variety of patients, is currently under way. Although the current vaccines are not always effective and future revaccination may increase the incidence of adverse effects, most asplenic persons should receive the currently available vaccines to minimize their risk of life-threatening infection.

Bacterial Vaccines↗
PubMed1988

Use of vancomycin and tobramycin polymethylmethacrylate impregnated beads in the management of chronic osteomyelitis.

Over the past several years there has been a growing interest in the use of locally implanted beads containing antibiotics for the treatment of chronic osteomyelitis. This method has been popularized in Europe and, with few exceptions, gentamicin has been the only antibiotic used. There have been only a few reports from the U.S. and there is little information regarding the pharmacokinetics of antibiotics used in this fashion. To our knowledge this is the first report using vancomycin. Three patients with chronic osteomyelitis were treated with vancomycin and/or tobramycin polymethylmethacrylate beads. These beads were extemporaneously compounded and implanted for up to six weeks. From the site of bead implantation local fluid aliquots were collected for the measurement of antibiotic concentrations. In two patients, initial tobramycin concentrations exceeded 400 mg/L. In one patient receiving vancomycin, initial localized concentrations were approximately 100 mg/L. In all three patients therapeutic concentrations of localized antibiotic were maintained with immeasurable systemic concentrations throughout the period of bead placement. Localized antibiotic therapy for the management of chronic osteomyelitis represents a potential therapeutic alternative to long-term parenteral therapy. Data presented here suggest that other antibiotics, such as vancomycin and tobramycin, can be used successfully in polymethylmethacrylate beads and provide preliminary facts for future investigations of such applications.

Adult↗
PubMed1988

Teicoplanin: an investigational glycopeptide antibiotic.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, adverse effects, and clinical uses of teicoplanin are reviewed. Teicoplanin, a novel glycopeptide that is similar to vancomycin, was isolated in the mid-1970s. A fermentation product of Actinoplanes teicomyceticus, teicoplanin is a structurally complex compound made up of six fatty-acid components attached to a common aglycone. Teicoplanin's mechanism of action, like that of vancomycin, is inhibition of cell-wall biosynthesis. In vitro activity is comparable to that of vancomycin and includes staphylococci, streptococci, corynebacterium, listeria, and anaerobic cocci. Resistance to teicoplanin has been reported with coagulase-negative staphylococci. Teicoplanin is 50 to 100 times more lipophilic than vancomycin. Teicoplanin is poorly absorbed after oral administration but is 90% bioavailable when administered intramuscularly. The drug distributes widely into body tissue and is eliminated primarily renally. Optimal dosing regimens and therapeutic serum drug concentrations have not been well established. Reported adverse effects have included irreversible ototoxicity, allergic reactions with maculopapular rash and eosinophilia, pain at intramuscular injection site, and elevation of aminotransferases. Initial clinical trials have yielded conflicting results in gram-positive bacteremia, endocarditis, osteomyelitis, and soft-tissue infections. Teicoplanin has shown promise in surgical and dental prophylaxis. Comparative trials with vancomycin and other antimicrobial agents must be completed before teicoplanin's role as a therapeutic agent in the treatment of systemic gram-positive infections is defined.

Animals↗
PubMed1987

Observed differences in amikacin pharmacokinetic parameters and dosage recommendations determined by enzyme immunoassay and fluorescence polarization immunoassay.

Enzyme immunoassay (EIA) and fluorescence polarization immunoassay (FPIA) methods are commercially available for quantitation of serum amikacin concentration. The purpose of this study was to determine if the two assay methods were comparable and would provide the same estimates for pharmacokinetic parameters and dosage recommendations. A total of 73 amikacin serum samples were used to evaluate the two assay techniques. Forty-four of these samples, obtained from 10 patients, were used to evaluate the comparability of pharmacokinetic parameters and dosage regimens. The correlation coefficient between the two assay methods was 0.98 (y = 1.03x + 0.64). There were substantial differences in assay performance noted in samples less than 10 mg/L, 10-20 mg/L, and greater than 20 mg/L, typical concentration ranges for serum sampling used in pharmacokinetic analysis. A difference of approximately 10% was observed in the determination of amikacin half-life, total body clearance, and dosage calculation. A 7% difference was noted in the volume of distribution. A significant difference (p less than 0.05) in volume of distribution and dosage recommendations was noted. Although the two methods for determining amikacin serum concentrations appear to be interchangeable on the basis of the in vitro comparison, significant differences were observed between the two assays in pharmacokinetic parameters and dosage recommendations.

Amikacin↗