Class of 2015 Abstract / Objectives: To (1) characterize loading doses of vancomycin administered to patients with sepsis and (2) evaluate the relative impact of loading dose on clinical outcomes between patients who received a 1 gram loading dose or any other amount. Methods: Retrospective, observational chart review of adult patients who received vancomycin for treatment of sepsis through emergency department triage. Data from November 2013 through March 2014 were obtained for timing and administration of vancomycin as well as clinical outcomes: survival; length of hospitalization and intensive care unit (ICU) stay; need for mechanical ventilation. Results: Sepsis-related hospital encounters were identified for 123 patients, of which 114 charts were fully able to be evaluated. The majority of patients (84.21%) received a 1 gram loading dose as opposed to any other amount (p=0.001); few patients (1.75%) received a dose within 25-30 mg/kg. No significant differences in trends for timing of administration, inpatient survival, duration of hospital stay, or need for mechanical ventilation were identified between patients who received 1 gram doses or any other amount. Greater effective vancomycin loading doses were associated, albeit not significantly, with shorter durations of hospitalization, ICU admissions, and mechanical ventilation. Conclusions: Despite weight-based loading dose recommendations, vancomycin was frequently administered as a fixed 1 gram loading dose to patients with sepsis. However, there was little distinguishable impact on clinical outcomes in this preliminary study.

Class of 2005 Abstract / Objectives: Doses of vancomycin are frequently estimated using various predictor formulas aiming for trough concentrations between 5 and 15 mg/L and peak concentrations between 25 and 40 mg/L.1 There is however, some controversy about the relationship between vancomycin concentrations and therapeutic response. This project compares the ability of several methods to estimate serum concentrations of vancomycin. Methods: This project was a retrospective look at 243 patient records, the patients were given vancomycin and later had at least one concentration measured. Data collected while the patient was being treated was used in the nine predictor models to determine which model would best predict actual concentrations. The methods compared were Moellering, Matzke, Lake-Peterson, Rodvold, Abbott, Birt, Burton, Ambrose, and Bauer. Results: There were 188 patients included in the analysis, 97 males and 91 women. The method with the least bias (+ 1.0) was the Rodvold method using the actual body weight. None of the models were very precise, with most around 10 (high of 12.83, and a low of 9.35). The r- values for all the models were also low, none of the models had an r- value greater than 0.5. The Lake-Peterson method predicted within 20% and 50% the most often; the Ambrose method the least often within 50%, and both Ambrose and Bauer the least often within 20%. The Lake-Peterson method predicted concentrations within plus or minus 2.5 and 5.0 mg/L of measured concentrations most frequently. The Ambrose method predicted concentrations within plus or minus 2.5 mg/L of measured the least often; Burton and Rodvold the least often within 5.0 mg/L of measured. Implications: With the best model only accurate (defined as ± 20%) less than 25 percent of the time, there is too much error to make a good decision on dose and interval without the feedback of measured serum concentrations. The models may be a good starting point as which dose and interval to choose, but they are not a substitute for measuring steady state concentrations.

Indiana University-Purdue University Indianapolis (IUPUI) / This study was undertaken to investigate histologically the effect of a combination of an antibiotic and an anti-inflammatory enzyme when used as a medication in direct pulp therapy. The pulps of 56 teeth in two Macaca Speciosa monkeys, exposed and left open to the oral environment for 24 hours to insure contamination, received direct treatment with one of four experimental medications: (1) vancomycin, starch, and hyaluronidase; (2) vancomycin, starch, and water; (3) starch and water; and (4) starch and hyaluronidase. At 30 days the teeth were removed from one animal and at 90 days•from the other for histologic interpretation. A satisfactory response was observed in 92.9 per cent of the teeth treated with vancomycin, starch, and hyaluronidase; in 71.5 per cent of the teeth treated with vancomycin, starch, and water; and in 42.9 per cent of the teeth treated with both starch and water and starch and hyaluronidase. None of the teeth treated with vancomycin, starch, and water and vancomycin, starch, and hyaluronidase became necrotic,while 35.7 per cent of the teeth treated with starch and water or starch and hyaluronidase became necrotic. Under the conditions of this investigation, vancomycin containing pulp capping agents are effective in controlling infection and in promoting reparative dentin formation in monkeys. The benefit of hyaluronidase when used in combination with vancomycin was questionable.

Orientador: Daniela Ponce / Resumo: Introdução: A vancomicina é um antibiótico estratégico no tratamento de infecções por bactérias gram-positivas. Controvérsias quanto a sua posologia e monitorização se revestem de importância devido ao risco de nefrotoxicidade e à emergência de cepas resistentes. Objetivos: Caracterizar a população, descrever padrões de prescrição da vancomicina para pacientes adultos, observar a administração da vancomicina, a coleta da vancocinemia e o momento do posterior ajuste da dose da vancomicina, além de avaliar a conformidade entre prescrição, administração e monitorização da vancomicina em Hospital Universitário (HU) e assim, a confiabilidade do prontuário eletrônico. Metodologia: Para a caracterização dos sujeitos, avaliação de dados de prescrição e administração, coleta da vancocinemia e ajuste de dose realizou-se um estudo transversal, enquanto para a determinação dos desfechos realizou-se um estudo longitudinal e retrospectivo. Foram incluídos pacientes adultos internados em quatro enfermarias clínicas e cirúrgicas e em duas alas do serviço de terapia intensiva (SETI) em uso de vancomicina. Foram realizadas seis visitas às enfermarias de Clínica Médica, Neurologia e Ortopedia e cinco visitas a enfermaria de Cirurgia Vascular e aos SETIs, nos quais foram avaliados 67 pacientes e 989 prescrições, coletados dados do prontuário e observadas as rotinas de enfermagem e médica quanto a administração da vancomicina, coleta da vancocinemia e ajuste do antibiótico. Resultados: Não houve ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Vancomycin is a strategic antibiotic in the treatment of gram-positive bacterial infections. Controversies regarding dosage and monitoring are important because of the risk of nephrotoxicity and the emergence of resistant strains. Objectives: To characterize the population, to describe vancomycin prescribing standards for adult patients, to observe the administration of vancomycin, collect serum vancomycin and the vancomycin dose adjust, and to evaluate the compliance between vancomycin prescription, administration and monitoring in the University Hospital (HU) and thus, the reliability of the electronic medical record. Methodology: A cross-sectional study was carried out to description of the subjects, evaluation of prescription and administration data, collection of vancocinemia and dose adjustment, while a longitudinal and retrospective study was performed to determination of outcomes. Were included adult patients hospitalized in four clinical and surgical wards and two intensive care unit’s wards (ICU) using vancomycin. Six visits to the General practice, Neurology and Orthopedic wards were carried out, and five visits to the Vascular Surgery ward and to the ICUs were carried out, in which 67 patients and 989 prescriptions were collected, data from the medical record and nursing and medical routines were observed for administration of vancomycin, collection of serum vancomycin and adjustment of antibiotic. Results: There were no differences between the units... (Complete abstract click electronic access below) / Mestre

Student Number : 0418251N - MSc research report - School of Molecular and Cell Biology - Faculty of Science / Rifampicin is a chemotherapeutic agent used to combat mycobacterial and nocardial infections. Four enzymatic inactivation mechanisms have been identified which are partially responsible for the increasing number of rifampicin resistant strains. These are ADP-ribosylation, phosphorylation, decomposition and glucosylation. The gene encoding the latter, rgt, has been cloned and characterized from the opportunistic pathogen Nocardia brasiliensis. However, as of yet nothing is known of these inactivation enzymes. Thus in order to study the properties of the mechanism it is necessary to observe structure-function relationships through the characterization of mutants. Furthermore, the rgt gene confers a small yet reproducible increase to the vancomycin MIC. This has indicated that there may be other enzymatic mechanisms which are involved in the inactivation of vancomycin. Vancomycin is an important antibiotic as it is used to treat gram-positive infections by multi-drug resistant strains. Hitherto, no mechanisms of enzymatic inactivation have been identified for vancomycin. Thus in order to identify regions of DNA which may play a role in the high level resistance to vancomycin as observed in N. brasiliensis it was necessary to screen a genomic library of this organism. This was performed in a gram-positive background. No clones were identified in this study that had an increased resistance to vancomycin, indicating that the DNA involved in the phenotype is greater than that of the average insert size of the library, 1.9 kb. Future work will thus involve the generation of a genomic library with larger fragments and the subsequent screening of this. Additionally, performing a mutational analysis on the rgt gene may provide further insight into the specifics of the inactivation enzymes and thus will contribute to combating infection by opportunistic and other pathogens.

Methicillin-resistant S.aureus (MRSA) is a highly virulent pathogen associated with serious healthcare-associated (HCA-MRSA) and community-associated (CA-MRSA) infections. MRSA is an increasingly important cause of skin and skin-structure, bloodstream and other invasive infections including pneumonia and endocarditis. The pharmacodynamics of existing treatments and anovel cephalosporin with activity against MRSA were studied in an in vitro infection model comparing the antibacterial effects of monotherapy and combination therapy under standard and altered environmental conditions. The activity of monotherapy with vancomycin, daptomycin, linezolid and ceftobiprole against clinical MRSA isolates were tested along with combinations of vancomycin-ceftobiprole, daptomycin-ceftobiprole and linezolid-ceftobiprole. Antibacterial response under standard conditions supporting optimal bacterial growth were compared to altered conditions with acidic pH 5.5, diluted nutrient broth (1:2) and increased temperature 40°C. Two clinical isolates including one HCA-MRSA (#81655) and one CA-MRSA (#79002) were studied in an in vitro pharmacodynamic model (IPDM) over 24 hours. Clinical dosing regimens equivalent to vancomycin 1500 mg intravenously every 12 hours (peak =24.4 mg/L, trough =7.4 mg/L), daptomycin 6 mg/kg (420 mg) intravenously every 24 hours (peak =8.2 mg/L, trough =0.8 mg/L) and linezolid 600 mg intravenously every 12 hours (peak =9.2 mg/L, trough =2.8 mg/L) were tested. Ceftobiprole was administrated as a bolus dose followed by constant infusion of 10 mg/L. Antibacterial effects were quantified as initial bacterial kill rate over 4 hours (KR4) and absolute bacterial kill at 24 hours (BK24). Minimum inhibitory concentrations (MIC) were measured via E-test® methods using initial isolates and those recovered after 24 hours of therapy. The KR4 with daptomycin and vancomycin were equivalent (P=0.14), yet daptomycin was more rapid than ceftobiprole (P=0.03) and linezolid (P<0.0001). The BK24 was greatest with ceftobiprole and vancomycin which were superior to linezolid (P<0.0001, P<0.0001, respectively) and daptomycin (P=0.0001, P=0.0001, respectively). Daptomycin was associated with bacterial re-growth and increasing MICs from 0.25 mg/L to 2-4 mg/L during therapy for isolate #79002 under standard conditions. Furthermore, daptomycin activity against both isolates was significantly reduced under altered conditions (KR4, P=0.0001; BK24, P=0.04). Combination therapy with vancomycin-ceftobiprole was indifferent compared with either agent alone. Although daptomycin-ceftobiprole prevented daptomycin non-susceptibility during therapy and resulted in significantly greater BK24 compared with daptomycin alone (BK24 difference of 4.07 log10 cfu/mL, P=0.0001), the combination was indifferent from ceftobiprole alone. Finally, linezolid-ceftobiprole was similar to linezolid but significantly less active than ceftobiprole alone (BK24 difference of 1.39 log10 cfu/mL, P=0.005) raising concerns of potential antagonism with this combination. In conclusion, this study provides important data regarding antimicrobial pharmacodynamics against MRSA. Overall, monotherapy with either ceftobiprole or vancomycin was most active. Combination therapy with ceftobiprole prevented the emergence of daptomycin non-susceptibility during therapy, but demonstrated potential antagonism with linezolid.

No description available.

Methicillin-resistant S.aureus (MRSA) is a highly virulent pathogen associated with serious healthcare-associated (HCA-MRSA) and community-associated (CA-MRSA) infections. MRSA is an increasingly important cause of skin and skin-structure, bloodstream and other invasive infections including pneumonia and endocarditis. The pharmacodynamics of existing treatments and anovel cephalosporin with activity against MRSA were studied in an in vitro infection model comparing the antibacterial effects of monotherapy and combination therapy under standard and altered environmental conditions. The activity of monotherapy with vancomycin, daptomycin, linezolid and ceftobiprole against clinical MRSA isolates were tested along with combinations of vancomycin-ceftobiprole, daptomycin-ceftobiprole and linezolid-ceftobiprole. Antibacterial response under standard conditions supporting optimal bacterial growth were compared to altered conditions with acidic pH 5.5, diluted nutrient broth (1:2) and increased temperature 40°C. Two clinical isolates including one HCA-MRSA (#81655) and one CA-MRSA (#79002) were studied in an in vitro pharmacodynamic model (IPDM) over 24 hours. Clinical dosing regimens equivalent to vancomycin 1500 mg intravenously every 12 hours (peak =24.4 mg/L, trough =7.4 mg/L), daptomycin 6 mg/kg (420 mg) intravenously every 24 hours (peak =8.2 mg/L, trough =0.8 mg/L) and linezolid 600 mg intravenously every 12 hours (peak =9.2 mg/L, trough =2.8 mg/L) were tested. Ceftobiprole was administrated as a bolus dose followed by constant infusion of 10 mg/L. Antibacterial effects were quantified as initial bacterial kill rate over 4 hours (KR4) and absolute bacterial kill at 24 hours (BK24). Minimum inhibitory concentrations (MIC) were measured via E-test® methods using initial isolates and those recovered after 24 hours of therapy. The KR4 with daptomycin and vancomycin were equivalent (P=0.14), yet daptomycin was more rapid than ceftobiprole (P=0.03) and linezolid (P<0.0001). The BK24 was greatest with ceftobiprole and vancomycin which were superior to linezolid (P<0.0001, P<0.0001, respectively) and daptomycin (P=0.0001, P=0.0001, respectively). Daptomycin was associated with bacterial re-growth and increasing MICs from 0.25 mg/L to 2-4 mg/L during therapy for isolate #79002 under standard conditions. Furthermore, daptomycin activity against both isolates was significantly reduced under altered conditions (KR4, P=0.0001; BK24, P=0.04). Combination therapy with vancomycin-ceftobiprole was indifferent compared with either agent alone. Although daptomycin-ceftobiprole prevented daptomycin non-susceptibility during therapy and resulted in significantly greater BK24 compared with daptomycin alone (BK24 difference of 4.07 log10 cfu/mL, P=0.0001), the combination was indifferent from ceftobiprole alone. Finally, linezolid-ceftobiprole was similar to linezolid but significantly less active than ceftobiprole alone (BK24 difference of 1.39 log10 cfu/mL, P=0.005) raising concerns of potential antagonism with this combination. In conclusion, this study provides important data regarding antimicrobial pharmacodynamics against MRSA. Overall, monotherapy with either ceftobiprole or vancomycin was most active. Combination therapy with ceftobiprole prevented the emergence of daptomycin non-susceptibility during therapy, but demonstrated potential antagonism with linezolid.

Thesis (M.S.)--University of Wisconsin--Madison, 1984. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 99-101).

Class of 2012 Abstract / Specific Aims: The primary purpose of this study was to evaluate the time of vancomycin pre-operative surgical site infection prophylaxis administration relative to other scheduled antibiotic therapy at a tertiary care, academic medical center. The secondary purpose was to characterize the incidence of adverse events post-surgery that were associated with vancomycin therapy in patients who received both pre-operative scheduled vancomycin therapy and vancomycin for surgical site infection prophylaxis Methods: This descriptive study was a retrospective medical chart review of all patients over the age of 28 days who received vancomycin for surgical site infection prophylaxis between February 2011 and May 2011 at a tertiary care, academic medical center. This study was approved be the Institutional Review Board. The subject population included patients admitted to the hospital for at least 72 hours who received at least 48 hours of scheduled vancomycin (IV), daptomycin or linezolid therapy before index surgery and subsequently received surgical site infection prophylaxis with vancomycin. Main Results: Of the 20 subjects who meet the study inclusion criteria, 18 (90%) subjects received scheduled vancomycin doses within 48 hours prior to surgery, 5 (25%) subjects within 4 hours, and 4 (20%) subjects within 2 hours. No surgical site infections were reported. Conclusions: This was a pilot study to evaluate the timing of vancomycin surgical site infection prophylaxis doses with scheduled vancomycin, linezolid, and daptomycin. No adverse effects associated with surgical site infection prophylaxis were reported but the sample size is small and likely inadequate to detect this potential issue.