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Biomedical subjects

E M Bailey

Publications and source records attributed to E M Bailey.

At least 19 recordsLinked to original sources

Thermal injury in rats alters glucose utilization by skin, wound, and small intestine, but not by skeletal muscle.

The effects of thermal injury in rats on glucose utilization (Rg) by skin, wound, small intestine, and muscle in vivo has been determined using 2-[18F]-fluoro-2-deoxy-D-glucose (18FDG) 6 hours, 24 hours, and 3 weeks after injury. These results were compared with serum glucose and insulin levels at the same time points and with hexokinase activity in the tissues. Thermal injury had no significant effects on serum glucose levels; however, serum insulin levels were lower than sham values 6 hours after injury, the same as sham values 24 hours after injury, and significantly higher than sham values 3 weeks after injury. Rg of unburned skin was not changed at 6 or 24 hours after injury, but was increased at 3 weeks after injury. The Rg of the wound was almost zero at 6 and 24 hours after injury; however, at 3 weeks after injury, the wound area had a Rg two to three times higher than that of the normal skin of sham animals. Small intestine Rg was decreased 6 and 24 hours after injury, but was essentially normal by 3 weeks after injury. The Rg of muscle was unchanged at all of the time points tested. Total Rg was significantly higher in the animals 3 weeks after injury, with the increase primarily due to the increases in skin and wound. The increases in Rg were associated with changes in tissue hexokinase activity. The present data suggest that thermal injury to rats results in dramatic alterations in glucose utilization by the skin and wound, changes that may contribute to the overall alterations in carbohydrate metabolism during burn trauma.

Animals

Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue: a study of 15 patients.

Extranodal low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type occurs in the gastrointestinal tract, salivary gland, thyroid, orbit, lung, and breast. We report 15 patients with MALT-type lymphomas involving skin and subcutaneous tissue. All patients had tumors with histologic features of low-grade B-cell lymphoma of MALT type, including marginal zone cells (15 of 15 cases), plasmacytic differentiation (10 of 15 cases), Dutcher bodies (three of 15 cases), and reactive germinal centers (10 of 15 cases). All expressed pan B-cell antigens and monotypic immunoglobulin. Seven patients (five women, two men) aged 29 to 86 years (median, 53 years) had primary MALT-type lymphoma of skin (6) or subcutaneous tissue (1). One patient had persistent disease, and four patients had relapses involving skin, subcutaneous tissue, breast, orbit, and lymph node. At last follow-up (11-121 months; median, 36 months), one patient was alive with disease, and six patients had no evidence of disease. Three patients (two women, one man) aged 36 to 67 years (median, 57 years) had concurrent MALT-type lymphoma involving both subcutaneous tissue and extracutaneous sites at primary diagnosis, including lung, breast, orbit, lymph node, and bone marrow. One patient responded to treatment but relapsed with lymphoma of the skin and breast. The other two patients had persistent disease despite treatment. One patient died of disease at 25 months, and, at last follow-up (7 and 46 months), two patients were alive with disease. Five patients (four women and one man) aged 29 to 72 years (median, 63 years) had secondary skin or subcutaneous involvement by MALT-type lymphoma with primary tumors of ocular adnexa (3) or parotid gland (2). All five patients had relapses, which involved skin or subcutaneous tissue, parotid gland, lacrimal gland, breast, and lymph node. At last follow-up (61-137 months), two patients were alive with disease and three were alive with no evidence of disease. Low-grade B-cell lymphomas of MALT type may arise in or secondarily involve the skin and subcutaneous tissue and have a tendency to affect middle-aged to older women. These tumors are characterized by multiple extranodal relapses and are associated with long patient survival. Patients with primary MALT-type lymphoma of skin or subcutaneous tissue without extracutaneous involvement at diagnosis were more likely to experience prolonged disease-free survival than patients with extracutaneous spread at presentation (p < 0.03).

Adult

A practical look at the clinical usefulness of the beta-lactam/beta-lactamase inhibitor combinations.

OBJECTIVE: To aid clinicians in developing an approach to the use of intravenous beta-lactam/beta-lactamase inhibitors on a patient-specific basis. To achieve this, the pharmacology, in vitro activity, and clinical use of the intravenous beta-lactam/beta-lactamase inhibitor combinations in the treatment of selected infections seen in hospitalized patients are discussed. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1987-1995); Index Medicus (1987-1995); program and abstracts of the 32nd (1992), 33rd (1993), 34th (1994), and 35th (1995) Interscience Conference on Antimicrobial Agents and Chemotherapy; bibliographic reviews of review articles; and package inserts. STUDY SELECTION: In vitro and in vivo studies on the pharmacokinetics, microbiology, pharmacology, and clinical effectiveness of ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam were evaluated. DATA SYNTHESIS: Many properties of the beta-lactam/beta-lactamase inhibitor combinations are similar. Differences in dosing, susceptibilities, and clinical applications are important considerations for clinicians. Potential roles for these agents in the clinical setting include pneumonia, intraabdominal infections, and soft tissue infections. A short discussion on susceptibility data interpretation is also presented. CONCLUSIONS: There are important differences among the available beta-lactam/beta-lactamase inhibitor combinations, such as spectra of activity, which need to be considered in choosing an agent for a patient-specific case. These products can be useful alternatives to conventional two- to three-drug regimens in mixed infections such as foot infections in patients with diabetes and hospital-acquired intraabdominal infections.

Anti-Bacterial Agents

Assessment of the mitogenic potential of the alkaloids produced by endophyte (Acremonium coenophialum)-infected tall fescue (Festuca arundinacea) on bovine vascular smooth muscle in vitro.

The objective of these experiments was to test the hypothesis that the major alkaloid classes found in endophyte-infected tall fescue could act as growth promoters for vascular smooth muscle. Bovine vascular smooth muscle cells (VSMC) from the dorsal metatarsal artery were grown in vitro and exposed to five concentrations (10(-6), 10(-8), 10(-9), 10(-11) and 0 M) of ergonovine, alpha-ergocryptine, ergovaline, and N-acetyl loline for 48 h. The mitogenic potential of the alkaloids was tested on both actively growing cells (serum fed, 10% fetal bovine serum) and quiescent cells (serum starved, 0.1% serum) to assess the need for serum constituents for alkaloid induced growth or toxicity. Ergonovine stimulated (P < .07) VSMC growth at 10(-6) M concentration in growing and quiescent culturs and at 10(-8) M concentration in quiescent cultures. alpha-Ergocryptine stimulated (P < .01) growth at 10(-6) M concentration in growing cultures and at 10(-8) and 10(-9) M concentrations in quiescent cultures. Ergovaline exhibited a dual activity on the growth of VSMC in culture, stimulating (P = .06) growth of quiescent cells at 10(-9) M concentration but inhibiting (P < .05) growth of growing cultures at concentrations of 10(-6) and 10(-9) M. This duality of activity was also noted for N-acetyl loline: N-acetyl loline stimulated (P < .05) growth of quiescent cultures at concentrations of 10(-8), 10(-9), and 10(-11) M but inhibited (P < .05) growth of growing cultures at concentrations of 10(-8) and 10(-9) M. The growth effects of the alkaloids in vitro on VSMC support in part the hypothesis that the alkaloids may contribute to the vascular complications noted in cattle grazing endophyte-infected tall fescue through hyperplasia of the intima. This would result in a decreased luminal diameter of the blood vessels and a resultant decrease in blood flow to the afflicted tissues. The diminished blood flow to tissues would result in tissue death and reduced ability to dissipate heat.

Acremonium

Mescalbean (Sophora secundiflora) toxicity in a dog.

Mescalbean (Sophora secundiflora) toxicity is reported in a dog. Mescalbean toxicity causes intolerance to exercise, muscle rigidity and collapse upon exercise, with a rapid recovery upon resting in dogs. Mescalbean toxicity is a rare cause of the periodic weakness/syncope class of diseases in dogs in areas of the habitat of Sophora secundiflora.

Animals

Immune globulin use at a multihospital medical center.

Use of i.v. immune globulin (IVIG) at four hospitals was audited to evaluate the need for therapeutic protocols and identify strategies for reducing drug expenditures. Charts and nursing notes for patients who received IVIG over a six-month period were reviewed retrospectively to obtain the following data: patient demographics, indication for IVIG use, product used, amount administered, and adverse reactions. Indications were categorized as to whether they are included in FDA-approved labeling, recognized in national guidelines, documented in published studies, or not documented. Expenditures were calculated from acquisition costs. At the first hospital (which offers oncology and other specialty services for adult patients), 71 patients received IVIG for 15 indications, with 89.5% of the orders for unlabeled uses. Of all grams reconstituted, 17.8% were wasted. The rate of documented adverse reactions was 11.3%. At the second, a pediatric hospital, 34 patients received IVIG for six indications, with 65% of the orders for unlabeled uses. Of all grams reconstituted, 13% were wasted. At the third hospital (which specializes in emergency trauma and critical care medicine), two patients received IVIG for a labeled indication. At the fourth (a maternity hospital), no patients received IVIG. Three of four hospitals used IVIG during a six-month audit period. In most instances, the drug was used for indications not included in FDA-approved labeling. Audit information may be useful in creating guidelines for appropriate use of IVIG.

Critical Care

The molecular basis of canine pyruvate kinase deficiency.

Inherited hemolytic anemia due to pyruvate kinase (PK) deficiency is an autosomal recessive disease of the Basenji dog that closely resembles human PK deficiency. Characterization of transcriptional and translational expression of PK isozymes and sequencing of DNA from normal and mutant dogs were performed to identify the genetic defect in Basenji dogs. Measurement of erythrocytic PK activity by ion exchange chromatography, substrate kinetics, immunologic reactivity, and electrophoretic mobility suggests that M2-type PK is the major form of PK activity in erythrocytes of PK-deficient dogs, in contrast to normal dogs having only R-type PK activity. Both R-type and M2-type PK mRNA are detectable in reticulocytes of PK-deficient dogs, suggesting that the aberrant isozyme expression is not due to a failure in the erythroid maturational switch from M2- to R-type isozymes. Nucleotide sequence data from wild-type and mutant R-type PK cDNA identified a single nucleotide deletion, delta C433, in the mutant cDNA. The deduced amino acid sequence predicts a truncated mutant protein devoid of all residues contributing to the catalytic site of the wild-type protein. In the absence of R-type PK activity, there is anomalous compensatory expression of M2-type PK in erythroid cells of PK-deficient Basenjis. The PK-deficient Basenji dog may be valuable in somatic cell gene therapy trials involving manipulation of hematopoietic stem cells.

Amino Acid Sequence

Enterococcus, an emerging pathogen.

OBJECTIVE: To review the bacterial genus Enterococcus with respect to its epidemiology, specific infections in humans, mechanisms of resistance and tolerance, and antimicrobial treatment. DATA SOURCES: A MEDLINE search of English-language journal articles published from 1977 to 1992 was completed. Articles published prior to 1977 were identified through Index Medicus and from references appearing in the bibliographies of other journal articles. Information also was acquired from abstracts, personal communication with infectious disease specialists with active research in the area of enterococcal infection, and conference proceedings. STUDY SELECTION: In vitro data; animal models of enterococcal infection; case reports; and case-controlled, cohort, and randomized controlled trials in humans were evaluated for relevant information. DATA EXTRACTION: Studies were evaluated by their methodologic strength (e.g., randomized controlled trial), reporting of clinically relevant outcomes (e.g., clinical response to antimicrobial therapy), statistical analyses, and accountability of all patients who entered the study. DATA SYNTHESIS: The incidence of enterococcal infections has increased in recent years and enterococci are now the second most frequently reported nosocomial pathogens. Enterococcus faecalis is the pathogen responsible for most enterococcal infections seen today; it has been implicated as an important cause of endocarditis, bacteremia, urinary tract infections, and intraabdominal infections. CONCLUSIONS: Enterococcal infection is of particular concern clinically because of its resistance to several antibiotics. Controlled comparative clinical trials of antimicrobial therapy in humans are lacking for several enterococcal infections. Therefore, the recommendations for antimicrobial therapy presented in this review are guidelines that reflect our current understanding of antibiotics used for enterococcal infection.

Abdomen

The urinary light-chain ladder pattern. A product of improved methodology that may complicate the recognition of Bence Jones proteinuria.

OBJECTIVE: --To describe the recently reported urinary light-chain "ladder" pattern and to indicate that this phenomenon, which may give rise to confusion with Bence Jones protein (BJP), may be observed during routine examination of 50-fold concentrated urine samples tested by high-resolution agarose gel electrophoresis and immunofixation. METHODS: --Urine samples that were usually submitted for examination for the presence of BJP were concentrated 50-fold. Concentrated urine samples were subjected to immunoelectrophoresis and agarose gel electrophoresis. Samples that failed to show a BJP on immunoelectrophoresis but which did show a faint banding pattern in the stained agarose gel were subjected to immunofixation. RESULTS--Samples of urine from 23 patients failed to show a distinct BJP. Nevertheless, these samples did show a kappa, with or without a lambda, light-chain banding pattern. The urine samples came from patients with serum M components associated with neoplasms of either plasma cells (n = 2) or lymphocytes (n = 2) or with M components of undetermined significance (n = 6). The remainder came from patients with infectious (n = 8), inflammatory (n = 4), or neoplastic (n = 1) processes. Some of these patients had no apparent renal disease, while others had variably altered renal function. CONCLUSIONS--The urinary light-chain ladder pattern was found by routine examination of 50-fold concentrated urine samples subjected to agarose gel electrophoresis and immunofixation. The pattern probably reflects the limited heterogeneity of normal human light chains. Detection in the urine samples of some patients may reflect increased synthesis, failure of resorption/degradation in the kidney, or the interference in proximal tubular function by substances producing transient tubular proteinuria. The presence of the light-chain ladder pattern in urine may prevent the detection of small amounts of BJP sharing the electrophoretic mobility of one of the normal light-chain bands.

Adult

In vitro pharmacodynamic effects of concentration, pH, and growth phase on serum bactericidal activities of daptomycin and vancomycin.

Clinical trials with daptomycin were halted in December 1990 because of treatment failures including two resistant Staphylococcus aureus strains. High protein binding of daptomycin (> 90%) and the lower-than-expected concentrations in serum with the dosage regimen of 3 mg/kg of body weight every 12 h may have contributed to these failures. To evaluate the effect that higher concentrations would have on bactericidal activity measured by time-kill curves, peak and trough concentrations were estimated for dosage regimens of 3, 5, and 10 mg/kg every 12 h. MICs, MBCs, and killing curves for daptomycin and vancomycin were performed by using the estimated concentrations with four S. aureus strains obtained from patients who failed daptomycin therapy for endocarditis. MICs and MBCs of daptomycin demonstrated a greater inoculum effect than those of vancomycin; MICs and MBCs of daptomycin increased three- to fourfold, but those of vancomycin increased only one- to twofold when the inoculum was increased from 5 x 10(5) to 5 x 10(7) CFU/ml. No pH-dependent effect on MICs or MBCs was seen. Strenuous experimental conditions were chosen: high inoculums (5 x 10(7) CFU/ml), extremes of pH (6.4, 7.4, and 8), and stationary and exponentially growing organisms; and all experiments completed in the presence of pooled human serum. Daptomycin exhibited concentration-dependent killing and statistically faster kill rates than vancomycin against stationary- or exponential-growth-phase organisms. A pH-dependent decrease in activity with daptomycin was also demonstrated. Daptomycin and vancomycin produced higher kill rates against exponentially growing organisms. A pH-dependent decrease in activity with daptomycin was also demonstrated. Daptomycin and vancomycin produced higher kill rates against exponentially growing organisms. The results indicate that the use of higher dosage regimens with compounds similar to daptomycin may be capable of overcoming the effects of pH, high inoculum, and protein binding.

Blood Bactericidal Activity

Pharmacodynamics of once-daily amikacin in various combinations with cefepime, aztreonam, and ceftazidime against Pseudomonas aeruginosa in an in vitro infection model.

The pharmacodynamics of once-daily amikacin administered as monotherapy and in combination with aztreonam, ceftazidime, and cefepime against Pseudomonas aeruginosa ATCC 27853 and clinical isolate 16690 (moderately susceptible to ceftazidime) were investigated with an in vitro model of infection over a 24-h period. Monotherapy with aztreonam, ceftazidime, and cefepime and combinations of aztreonam with cefepime or ceftazidime were also studied. MICs and MBCs were determined for viable organisms at 24 h to test for the development of resistance. Once-daily amikacin demonstrated killing activity over the initial 8 h superior to those of all other drugs administered as monotherapy against both strains tested (P < 0.01). Regrowth by 24 h was greatest for the amikacin regimen (P < 0.01) but was apparent for all monotherapy regimens against both strains. No changes in susceptibilities were observed. All combination therapies containing once-daily amikacin achieved 99.9% reductions in log10 CFU/ml by 2.0 h against both strains, with no regrowth of organisms at 24 h. Aztreonam-cefepime and -ceftazidime combinations required approximately 5 to 6 h to achieve a 99.9% reduction in log10 CFU/ml. Although there was no difference in time to the 99.9% kill between the aztreonam-cefepime and -ceftazidime regimens against either strain, the killing activity of these combinations was significantly less than those of regimens containing once-daily amikacin (P < 0.01). Minor differences in the initial susceptibilities of beta-lactams and the monobactam aztreonam against P. aeruginosa may not be important for therapeutic outcomes when used in combination with single-daily aminoglycoside therapy.

Amikacin

Pharmacokinetics and bactericidal rates of daptomycin and vancomycin in intravenous drug abusers being treated for gram-positive endocarditis and bacteremia.

The pharmacokinetics and bactericidal killing rates (BR) of daptomycin (D) and vancomycin (V) in 12 intravenous drug abusers (6 treated with daptomycin and 6 treated with vancomycin) were evaluated. Pharmacokinetic parameters were determined from multiple serum samples drawn at steady state over a 12-h dosing interval after intravenous infusions of 3 mg of D per kg of body weight and 1,000 mg of V. The BRs were determined from the 1- and 6-h serum samples by using four isolates of Staphylococcus aureus (three methicillin susceptible and one methicillin resistant) obtained from the patients enrolled in the study. Peak serum daptomycin concentrations were lower and volumes of distribution were higher than reported in healthy volunteers. Although not statistically different, D clearance was 22% higher than reported in healthy volunteers. V pharmacokinetics were similar to those reported in previous studies. Daptomycin's BRs, although comparable to those of V in patients' serum, were significantly decreased compared with those found in broth. This may be related to the high degree of protein binding of D (93% versus 50% for V). Conversely, the BRs of V in serum were significantly greater than those in broth. The BRs of D and V in broth were greater when killing curves were performed with test strains in logarithmic versus stationary-phase growth. The ability to kill organisms in stationary phase may be an important factor in determining the performance of an antibiotic in deep-seated infections such as endocarditis.3+

Adult

CI-960, a new fluoroquinolone, for therapy of experimental ciprofloxacin-susceptible and -resistant Staphylococcus aureus endocarditis.

CI-960 is a new fluoroquinolone with enhanced in vitro activity against gram-positive pathogens. The efficacy of the drug was compared with that of vancomycin by using the rabbit model of nafcillin- and ciprofloxacin-susceptible and -resistant Staphylococcus aureus endocarditis. Animals received intravenous therapy with CI-960, 20 mg/kg of body weight every 8 h, or vancomycin, 17.5 mg/kg every 6 h, for 4 days. In a comparison with the effects on untreated controls, both antimicrobial agents effectively cleared bacteremia and significantly reduced bacterial counts in vegetations and tissues of animals infected with any of the test strains. In some cases, the efficacy of CI-960 was superior to that of vancomycin. The therapeutic activity of CI-960 was reduced, but still very good, against ciprofloxacin-resistant strains. One rabbit infected with such a strain and treated with CI-960 was found to harbor a small number of vegetation-associated organisms resistant to the drug at fivefold its original MIC; this was associated with a microbiological, but not a clinical, failure of therapy. We conclude that CI-960 is as effective as vancomycin is in this model of a serious systemic S. aureus infection, including that caused by strains resistant to ciprofloxacin. Increases in CI-960 MICs may develop during therapy of infections caused by strains highly resistant to ciprofloxacin, but they appear unlikely to occur in ciprofloxacin-susceptible strains.

Animals

Absence of "red man syndrome" in patients being treated with vancomycin or high-dose teicoplanin.

Twenty-five febrile patients with a history of intravenous drug use who were receiving either vancomycin (15 patients) or teicoplanin (10 patients) as part of a multicenter, double-blind, randomized, clinical efficacy trial were enrolled, upon receipt of their first dose of antibiotic, into a study to evaluate the effect of 1 g of vancomycin and high-dose teicoplanin (30 mg/kg of body weight) on histamine release and the occurrence of "red man syndrome" (RMS). In addition, 10 healthy volunteer subjects (HVS) were randomized to receive either 1 g of vancomycin intravenously or a saline infusion in a double-blind, crossover design study. Patients and HVS were observed for the presence of erythema, flushing, pruritus, and hypotension during and for up to 1 h postinfusion by a blinded investigator. Histamine concentrations in plasma were measured at baseline and during and after drug infusion. No significant differences were noted in baseline temperature between patients (vancomycin recipients, 102.3 degrees F [39.1 degrees C]; teicoplanin recipients, 102.4 degrees F [39.1 degrees C]) or incidence of bacteremia (7 of 15 vancomycin recipients; 5 of 10 teicoplanin recipients). There were no significant differences in peak vancomycin concentrations in the sera of patients (40.8 micrograms/ml) and HVS (49.9 micrograms/ml). There were no reactions consistent with RMS in any patient who received teicoplanin (0 of 10); there was a significant difference in the occurrence of RMS in patients in comparison with that in HVS (0 of 15 patients, 9 of 10 HVS; P less than 0.001) who received vancomycin. The predominant reaction was erythema and pruritus. Histamine concentrations in plasma and the area under the histamine plasma concentration-time curve were highly variable within groups and were not statistically different between patients and HVS. The incidence of RMS secondary to vancomycin or teicoplanin in our patient population appears to be low and consistent with clinical observations. Similar to previous investigations, RMS secondary to vancomycin in HVS was high (90%). However, we found no relationship between the histamine concentration in plasma or the area under the plasma histamine concentration-time curve and the severity of RMS in HVS. The reason for the discrepancy of RMS in patients versus that in HVS in unknown, but it may be related to a blunted effect of glycopeptides to produce the reaction in the presence of infection or it may be specific to our patient population.

Adult

Ofloxacin clinical pharmacokinetics.

Ofloxacin is a new fluoroquinolone with a spectrum of activity similar to other fluoroquinolones with activity which includes Chlamydia trachomatis, Mycobacterium spp., Mycoplasma spp. and Legionella pneumophila. Through its additional mechanisms of action, ofloxacin may be less susceptible to the development of resistance from Staphylococcus aureus commonly seen with currently available fluoroquinolones. The impact of these findings cannot be evaluated without further clinical experience. The pharmacokinetics of ofloxacin are characterised by almost complete bioavailability (95 to 100%), peak serum concentrations in the range of 2 to 3 mg/L after a 400mg oral dose and an average half-life of 5 to 8h. In comparison with other available quinolones, elimination is more highly dependent on renal clearance, which may lead to more frequent dosage adjustments in patients with impaired renal function. Ofloxacin appears less likely to affect the pharmacokinetics of drugs (e.g. theophylline) which commonly interact with fluoroquinolones such as ciprofloxacin and enoxacin. The properties of ofloxacin make it a therapeutic alternative to currently available fluoroquinolones.

Absorption

The effect of dietary supplements on chronic bitterweed (Hymenoxys odorata) poisoning in sheep.

Two experiments were designed to establish a chronic bitterweed dose in sheep and to study the prevention of chronic bitterweed poisoning with dietary supplements of high protein (20% crude protein) and sodium sulfate. The first experiment consisted of 5 lambs in each of 3 groups. The low dose received up to 5.0 g bitterweed/kg/day which was equivalent to 10 mg hymenoxon/kg bw. The high dose group received a maximum bitterweed dose of 1 g/kg/day or 20 mg hymenoxon/kg. The final average weights of the low (29 kg) and the high (30 kg) dose groups were significantly different from the control (40 kg) group. The prophylactic experiment consisted of 5 groups of 4 sheep each. Each group received a different combination of bitterweed, a basal ration, soybean meal, urea, or sodium sulfate. The soybean meal and urea were used to adjust the ration to 20% crude protein, and each animal received 1.2 g bitterweed/kg/day. The high protein-sodium sulfate diet did not prevent chronic bitterweed toxicity, but soybean meal-sodium sulfate combination had the greatest effect on the reduction of bitterweed toxicity. Urea potentiated the toxic effects of bitterweed.

Animal Feed

Comparative effect of protein binding on the killing activities of teicoplanin and vancomycin.

The effect of protein binding on the activity of teicoplanin against Staphylococcus aureus was evaluated. Bactericidal rates of teicoplanin in cation-supplemented Mueller-Hinton broth (SMHB) and in a 1:1 mixture of pooled human serum and cation-supplemented Mueller-Hinton broth (PHS-SMHB) were compared with those of vancomycin. Eight concentrations of each drug ranging from 15 to 150 micrograms/ml were studied in two series which correspond to the concentrations in serum achieved with low- (6 mg/kg of body weight once daily) and high-dose (30 mg/kg once daily) teicoplanin. Overall, the bactericidal rate of teicoplanin was lower than that of vancomycin. In the presence of serum, the bactericidal rate of teicoplanin in PHS-SMHB was lower than that in SMHB, often resulting in only one log10 drop in CFU over a 24-h period. There was no statistical difference in the bactericidal rates of high- and low-concentration teicoplanin in either medium. Additionally, concentration-dependent killing in SMHB was not evident with either agent. The bactericidal rates of teicoplanin and vancomycin in a 1:1 mixture of serum ultrafiltrate and SMHB at 60 micrograms/ml were also studied. It was noted that the bactericidal rate of neither agent was affected by the presence of serum ultrafiltrate. This finding is consistent with teicoplanin's high degree of protein binding (reported to be greater than 90% in undiluted serum) and further substantiates the hypothesis that only the free drug is active against microorganisms. These data support protein binding as being a factor in teicoplanin activity against S. aureus.

Anti-Bacterial Agents

Clinical evaluation of teicoplanin fluorescence polarization immunoassay.

A teicoplanin fluorescence polarization immunoassay (FPIA) developed by International BioClinical (IBC) was evaluated by using serum samples from patients who had been receiving teicoplanin at Detroit Receiving Hospital (DRH) as part of a clinical investigation. Patient samples collected over a 1-year span were assayed at DRH and at IBC, and the results were compared with those of a standard microbiological assay performed at Merrell Dow Research Institute, Indianapolis, Ind. The FPIA has a rapid turnaround time (circa 20 min), utilizes small sample volumes (less than 100 microliters) and is sensitive and accurate in determining concentrations in the range of 5 to 100 micrograms/ml. The intra-assay and interassay coefficient of variation for controls (7, 35, and 75 micrograms/ml) was less than or equal to 13%. Concentrations greater than 100 micrograms/ml must be diluted prior to the assay, which may introduce additional error in determination. The FPIA compared well with the bioassay (r = 0.901) for 193 clinical samples. The results obtained utilizing the FPIA system were reproducible at two different sites, as illustrated by the high degree of correlation between the results at DRH and IBC (r = 0.92). There was less than 7% interference noted when teicoplanin was assayed in the presence of other antibiotics. Patient samples stored for up to 1 year retained their potency: the mean recovery rate in these samples was 107%. The FPIA should be useful for monitoring and adjusting teicoplanin dosage regimens in patients.

Anti-Bacterial Agents