PubMed Health⌕ Search

Biomedical subjects

S L Barriere

Publications and source records attributed to S L Barriere.

At least 19 recordsLinked to original sources
PubMed1995

An overview of mortality risk prediction in sepsis.

OBJECTIVE: To review the evolution and development of mortality risk prediction methods as they have been applied to the management of septic patients. DATA SOURCES: Selected relevant articles from the pertinent literature. STUDY SELECTION: Theoretical and clinical data on the mortality risk identification, severity of illness scoring systems, and cytokine levels as they relate to mortality in patients with sepsis. DATA EXTRACTION: All concepts relating to mortality risk prediction, cytokines, severity of illness, and intensive care unit (ICU) mortality were explored and interrelated accordingly. DATA SYNTHESIS: In order to improve the precision of the evaluation of new therapies for the treatment of sepsis, to monitor their utilization and to refine their indications, it has been recommended that mortality risk stratification or severity of illness scoring systems be utilized in clinical trials and in practice. With the increasing influence of managed care on healthcare delivery, there will be an increased demand for techniques to stratify patients for cost-effective allocation of care. Severity of illness scoring systems are widely utilized for patient stratification in the management of cancer and heart disease. However, the use of such systems in patients with sepsis has been limited to application in clinical trial design for assurance of balance among treatment groups. Mortality risk prediction in sepsis has evolved from identification of risk factors, and simple counts of failing organs, to sophisticated techniques that mathematically transform a raw score, comprised of physiologic and/or clinical data, into a predicted risk of death. Most of the developed systems are based on global ICU populations rather than upon sepsis patient databases. A few, newer systems are derived from such databases. However, the overall discriminating ability of the various methods is similar. Mortality prediction has also been carried out from assessments of endotoxin or cytokine (interleukin-1, interleukin-6, tumor necrosis factor) plasma concentrations. While increased levels of these substances have been correlated with increased mortality, difficulties with bioassay and their sporadic appearance in the bloodstream prevent these measurements from being practically applied. The calibration of risk prediction methods comparing predicted with actual mortality across the breadth of risk for a population of patients is excellent, but overall accuracy in individual patient predictions is such that clinical judgment must remain a major part of decision-making. However, as databases of appropriate patient information increase in size and complexity, it may be possible in the future to devise a scoring system that can be relied on to assist in clinical decision-making. CONCLUSIONS: Severity of illness scoring systems are widely used in critically ill patients. However, their use in patients with sepsis has largely been limited to a means of stratification in clinical trials. As newer sepsis therapies become available, it may be possible to use such systems for refining their indications, and monitoring their utilization. Finally, as the databases supporting the systems increase in size and complexity, it may be possible to utilize them in clinical decision-making.

Cytokines↗
PubMed1992

Pharmacology and pharmacokinetics of cefprozil.

Cefprozil is a new orally administered cephalosporin with a spectrum of in vitro activity similar to that of cefuroxime. The pharmacokinetics of cefprozil are linear relative to dose size. Gastrointestinal absorption produces maximal plasma concentrations of approximately 10 mg/L 1-2 hours after administration of an oral dose of 500 mg. Approximately 94% of the dose is absorbed, and 60%-70% is excreted in the urine as unchanged drug. The renal clearance exceeds the glomerular filtration rate, thus suggesting active tubular secretion. Administration with food or antacids produces negligible effects on the rate or extent of absorption. Kinetic disposition in the elderly is similar to that in young healthy individuals, but elimination is slightly slower in infants and children. Because renal impairment, but not hepatic dysfunction, significantly reduces the elimination of cefprozil, it is recommended that the dosage be reduced by 50% in patients whose creatinine clearance is less than 30 mL/min. Penetration of the interstitial fluid by cefprozil is excellent, with concentrations approaching those observed in the plasma. The pharmacokinetic disposition of cefprozil, coupled with its in vitro activity, supports the use of once- or twice-daily dosage regimens.

Age Factors↗
PubMed1992

Serum and blister fluid pharmacokinetics and bactericidal activities of ampicillin-sulbactam, cefotetan, cefoxitin, ceftizoxime, and ticarcillin-clavulanate.

Ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, and ceftizoxime are promoted for the treatment of mixed aerobic-anaerobic bacterial infections. Their activities have been compared in vitro but not in vivo. In order to assess the in vivo activities of these agents in serum and interstitial fluid, we administered single, intravenous doses of these antimicrobial agents to healthy subjects. Concentrations of the antimicrobial agents in serum and suction-induced blister fluid and bactericidal activity were measured by high-pressure liquid chromatography and the standard methodology of the National Committee for Clinical Laboratory Standards, respectively. The organisms used for bactericidal activity tests were one isolate each of Staphylococcus aureus, Klebsiella pneumoniae, and Bacteroides fragilis. Pharmacokinetic parameters in serum and blister fluid were similar to those derived in other investigations. Of note were the high and prolonged concentrations of ticarcillin and cefotetan in blister fluid, despite high-level serum protein binding. The bactericidal activities in serum and blister fluid reflected the relative in vitro activities and kinetic dispositions of the various antimicrobial agents except for the bactericidal activity of cefotetan, which was substantially lower in blister fluid than serum, despite a blister fluid:serum area under the concentration-time curve ratio of 1.5. Similarly, the activity of ticarcillin-clavulanate in blister fluid was also substantially less than would have been predicted by the blister fluid:serum ratio of the area under the concentration-time curve of 1.1, possibly because of the low concentrations of clavulanate in blister fluid. The rankings of the in vivo bactericidal activities of the five drugs were as follows: for S. aureus, ampicillin-sulbactam > ticarcillin-clavulanate > ceftizoxime > cefoxitin > cefotetan; for K. pneumoniae, ceftizoxime > cefotetan > ampicillin-sulbactam = ticarcillin-clavulanate > cefoxitin; and for B.fragilis, ticarcillin-clavulanate > cefotetan > ceftizoxime > ampicillin-sulbactam = cefoxitin.

Adult↗
PubMed1992

Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid.

Cefepime is a new broad-spectrum cephalosporin with excellent gram-positive and gram-negative activity including activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae. The pharmacokinetic disposition of cefepime is similar to that of ceftazidime. We compared the pharmacokinetic characteristics and the extent and duration of bactericidal activity in serum and suction-induced blister fluid after single 2-g intravenous doses of cefepime, ceftazidime, and cefoperazone given to healthy subjects. One clinical isolate each of E. cloacae, P. aeruginosa, and S. aureus was used to assess bactericidal activity. Results of the pharmacokinetic analysis were similar to previously reported data for these drugs. The high serum protein binding of cefoperazone (approximately 90%) contributed to poor blister fluid penetration. The other drugs penetrated well into this fluid compartment. Cefepime showed significantly greater bactericidal activity in serum and blister fluid against E. cloacae than the other study drugs, ceftazidime was significantly better in serum and blister fluid against P. aeruginosa, and cefoperazone was significantly better against S. aureus only in serum. None of the study drugs had significant bactericidal activity in blister fluid against S. aureus. Cefepime is a promising antimicrobial agent for the treatment of infections due to E. cloacae.

Adult↗
PubMed1992

Bacterial resistance to beta-lactams, and its prevention with combination antimicrobial therapy.

The clinical and economic impacts of bacterial resistance are substantial. The development of bacterial resistance during a course of therapy often leads to clinical failure, prolonged hospitalization, increased morbidity, mortality, and increased health care costs. Resistance has been reported to occur most frequently with aminoglycosides, quinolones, and beta-lactam antimicrobials, and often occurs during the course of treatment of gram-negative bacillary infection. Resistance is most commonly due to enzymatic inactivation, permeability changes, or receptor mutation. Strategies for the prevention of resistance include appropriate infection-control practices, judicious use of antimicrobials, enhancement of host defenses, and the use of antimicrobial combinations. Despite success in vitro and in experimental animal models of infection, clinical trials in humans of antimicrobial combinations for the prevention of resistance have yielded mixed results. Use of the most potent agents available, preferably in bactericidal synergistic combinations, may be effective in preventing in vivo emergence of bacterial resistance.

Anti-Bacterial Agents↗
PubMed1992

Gram-negative sepsis, the sepsis syndrome, and the role of antiendotoxin monoclonal antibodies.

The incidence and mortality, pathogenesis, clinical manifestations, and management of sepsis and the sepsis syndrome are reviewed, and the use of antiendotoxin monoclonal antibodies to treat patients with sepsis is discussed. The sepsis syndrome and septic shock are induced by the presence of endotoxin, a lipopolysaccharide found in the outer membrane of gram-negative bacteria. Proper management of gram-negative sepsis includes appropriate antimicrobial therapy, fluids and electrolytes, nutritional support, administration of vasopressors, and mechanical ventilation if necessary. To date, two antiendotoxin monoclonal antibodies have been produced and subjected to extensive clinical testing. HA-1A, a human cell line-derived monoclonal immunoglobulin M (IgM) antibody that contains only a small fragment of murine protein, was tested in one trial. HA-1A significantly reduced mortality in patients with sepsis and gram-negative bacteremia and produced better resolution of major morbidities than placebo in those patients. E5, an IgM antibody produced entirely via murine monoclonal antibody technology, was evaluated in two trials. Results from the first trial showed that E5 significantly reduced mortality in patients with gram-negative infection who were not in refractory shock. In contrast, results from the second trial did not show any significant reduction in mortality among patients with gram-negative infection who received E5. However, resolution of major morbidities occurred more frequently among E5 recipients in both trials. HA-1A and E5 were both well tolerated in the trials. The cost of therapy is expected to be $3000-$4000 per treatment course. The antiendotoxin monoclonal antibodies represent the next step along the path toward important reductions in morbidity and mortality from gram-negative infection. However, the financial implications of the use of HA-1A and E5 are enormous, and stringent patient selection criteria for administration of these products will have to be developed.

Antibodies, Monoclonal↗
PubMed1991

Development of resistance to fleroxacin during therapy of experimental methicillin-susceptible Staphylococcus aureus endocarditis.

The efficacy of fleroxacin was compared with that of vancomycin by using the rabbit model of methicillin-susceptible Staphylococcus aureus endocarditis. Animals received intravenous therapy with fleroxacin, 30 mg/kg every 8 h, or vancomycin, 17.5 mg/kg every 6 h, for 4 days. Both antimicrobial agents effectively cleared bacteremia and significantly reduced bacterial counts in vegetations and tissues compared with those in untreated controls. However, resistance to fleroxacin at 5- and 10-fold the MIC arose in the test strain of S. aureus in 73 and 27%, respectively, of animals that received the drug. Resistant isolates were found mainly in vegetations and were composed of up to 7% of the residual population recovered from that site. We conclude that fleroxacin is as effective as vancomycin in this model of a serious systemic S. aureus infection, but resistance to the drug may develop during therapy. If similar results are found with other strains of S. aureus during therapy with this or other fluoroquinolones, such data, when they are combined with the high incidence of fluoroquinolone resistance among S. aureus isolates being reported from selected institutions, would support the contention that these drugs should not be used as first-line therapeutic agents for S. aureus infections.

Animals↗
PubMed1991

Formulary evaluation of second-generation cephamycin derivatives using decision analysis.

Use of decision analysis in the formulary evaluation of the second-generation cephamycin derivatives cefoxitin, cefotetan, and cefmetazole is described. The rating system used was adapted from one used for the third-generation cephalosporins. Data on spectrum of activity, pharmacokinetics, adverse reactions, cost, and stability were taken from the published literature and the FDA-approved product labeling. The weighting scheme used for the third-generation cephalosporins was altered somewhat to reflect the more important aspects of the cephamycin derivatives and their potential role in surgical prophylaxis. Sensitivity analysis was done to assess the variability of the final scores when the assigned weights were varied within a reasonable range. Scores for cefmetazole and cefotetan were similar and did not differ significantly after sensitivity analysis. Cefoxitin scored significantly lower than the other two drugs. In the absence of data suggesting that the N-methyl thiotetrazole side chains of cefmetazole and cefotetan cause substantial toxicity, these two drugs can be considered the most cost-efficient members of the second-generation cephamycins.

Bacterial Infections↗
PubMed1991

Antimicrobial cost and quality control: challenges in the 1990s.

Increasing constraints on health care reimbursement, competition among hospitals, and new high-cost technologies all contribute to escalation of costs in hospitals. The goal in the 1990s is to provide optimum, cost-effective care for patients without compromising quality. Among many proved methods is an effective formulary system with explicit criteria for use of medications, guidelines for use in specialized circumstances, and suggestions for therapeutic alternatives. This last method of cost control received endorsement from several organizations and offers an important function for hospital pharmacists. Hospital pharmacies can play a major role in minimizing antimicrobial costs and promoting optimum patient care.

Anti-Bacterial Agents↗
PubMed1991

Monotherapy versus combination antimicrobial therapy: a review.

In view of the newer antibiotics that can cover the spectrum of organisms in mixed infections, single agents are now a viable option for antimicrobial therapy. In addition, monotherapy is relatively nontoxic and possibly less costly than combination therapy. Combinations may be more effective in preventing the emergence of resistance, however, and can also provide synergistic effects. They are a necessity in mycobacterial infections, enterococcal endocarditis, and deep-seated pseudomonal infections, as well as in patients with gram-negative bacillary infection with profound granulocytopenia.

Anti-Bacterial Agents↗
PubMed1990

Efficacy of ofloxacin in experimental Staphylococcus aureus endocarditis.

The efficacy of ofloxacin was compared with that of vancomycin in the therapy of experimental Staphylococcus aureus endocarditis. Rabbits infected with either a methicillin-susceptible (MSSA-1199) or a methicillin-resistant (MRSA-494) test strain were treated with ofloxacin (20 mg/kg of body weight every 8 h) or vancomycin (17.5 mg/kg of body weight every 6 h) for 4 days. The antimicrobial agents were found to be equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and in renal and splenic tissue of animals infected with either test strain. The drugs were of equal efficacy in curing MRSA-494 endocarditis. No resistance to ofloxacin emerged in either test strain during therapy. We conclude that in this model ofloxacin is as efficacious as vancomycin and that, unlike for other fluoroquinolones we have evaluated, resistance to the drug does not develop during therapy of this serious S. aureus infection.

Animals↗
PubMed1990

Alteration in the pharmacokinetic disposition of ciprofloxacin by simultaneous administration of azlocillin.

Healthy subjects were given single intravenous doses of ciprofloxacin, azlocillin, and the two drugs simultaneously on separate occasions. High-pressure liquid chromatographic analysis was used to assay the concentrations of both drugs in serum and urine. Pharmacokinetic parameters were calculated by noncompartmental methods. The total body (CL), renal (CLR), and nonrenal (CLNR) clearances; steady-state volume of distribution (Vss); and fractional urinary excretion of ciprofloxacin were all markedly decreased with the simultaneous administration of azlocillin. The disposition of azlocillin was unchanged when it was given with ciprofloxacin compared to when it was given alone. The pharmacokinetic parameters (mean +/- standard deviation) of ciprofloxacin given alone versus in combination with azlocillin were as follows: CL, 52.2 +/- 9.2 versus 33.9 +/- 6.0 liters/h (P less than 0.0005); CLR, 26.5 +/- 4.8 versus 16.2 +/- 4.2 liters/h (P less than 0.0005); CLNR, 25.8 +/- 5.5 versus 17.7 +/- 4.0 liters/h (P less than 0.03); Vss, 224 +/- 30 versus 166 +/- 41 liters (P less than 0.01); fractional urinary excretion, 0.56 +/- 0.06 versus 0.43 +/- 0.04 (P less than 0.002), respectively. This interaction resulted in significantly higher and more prolonged concentrations of ciprofloxacin in serum, which may be beneficial in the treatment of serious gram-negative bacterial infections, but it could also produce greater toxicity or result in more pronounced effects on oxidative drug metabolism of other medications.

Adult↗
PubMed1989

Influence of coadministration on the pharmacokinetics of mezlocillin and cefotaxime in healthy volunteers and in patients with renal failure.

The pharmacokinetic disposition of cefotaxime, desacetyl cefotaxime, and mezlocillin after the administration of each drug singly and in combination was examined in eight healthy volunteers and in five anuric patients with end-stage renal disease (ESRD). In the presence of ESRD, the total body clearance of cefotaxime decreased from 256.7 +/- 41.5 to 65.4 +/- 42.0 ml/min, and its elimination half-life (t1/2) increased from 1.1 to 3.6 hours as compared with healthy volunteers. Concomitant administration of mezlocillin in healthy volunteers decreased the total body clearance of cefotaxime by 42% and increased its steady-state volume of distribution. This reduction in clearance was reflected by a decrease in both renal and nonrenal clearances. In the presence of ESRD, coadministration of mezlocillin increased the t1/2 of cefotaxime to 5.8 hours. Desacetyl cefotaxime accumulated in ESRD with a prolongation of its elimination t1/2 to 18.7 hours from 1.7 hours in healthy volunteers. Desacetyl cefotaxime peak plasma concentrations occurred later with the combination regimen in the presence of ESRD. The clearance of mezlocillin was reduced and t1/2 prolonged in ESRD from 194.6 +/- 31.9 to 76.4 +/- 38.8 ml/min and 1.4 to 2.3 hours, respectively. Concomitant administration of cefotaxime did not alter the pharmacokinetics of mezlocillin. These data suggest that in the presence of normal renal function, lower doses of cefotaxime may be adequate to maintain similar cefotaxime plasma concentrations when mezlocillin is coadministered compared to when cefotaxime is given alone. Additional pharmacodynamic and clinical studies with this combination are warranted to further elucidate the clinical impact of this pharmacokinetic interaction.

Adult↗