Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects.

The ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all experiments (5 Escherichia coli, 2 Klebsiella pneumoniae, and 1 Proteus mirabilis). MICs were performed via agar dilution. Urinary bactericidal titers (UBTs) were performed via modified Schlichter test using participant's drug-free urine as the diluent. Urinary time-kill analyses were performed on pooled 24-h urine aliquots from days 1 and 5. All experiments were performed in triplicate with and without the addition of 25 mg/liter of glucose-6-phosphate (G6P). Mean 24-h urine concentrations of fosfomycin ranged from 324.7 to 434.6 mg/liter regardless of study day or dosing regimen. The urinary antibacterial activity of fosfomycin was also similar across study days and dosing regimens. UBT values did not correlate with MICs determined in the presence of G6P. Fosfomycin was reliably bactericidal in urine only against the 5 E. coli strains, regardless of genotype or MIC value. Together, these data do not support the use of oral fosfomycin tromethamine for pathogens other than E. coli or at a dosing frequency higher than QOD. Fosfomycin MICs determined in the presence of G6P may not accurately reflect the in vivo activity given the lack of G6P in human urine. (This study has been registered at ClinicalTrials.gov under identifier NCT02570074.).

Relationship between vancomycin exposure and outcomes among patients with MRSA bloodstream infections with vancomycin Etest® MIC values of 1.5mg/L: A pilot study.

Data suggest that vancomycin is less effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) with vancomycin Etest® MIC (MICEtest) ≥1.5 mg/L. No published studies have evaluated the relationship between vancomycin exposure and outcomes among patients with MRSA BSIs vancomycin MICEtest ≥1.5 mg/L. This study was a retrospective cohort of 71 hospitalized, adult, non-dialysis patients with MRSA BSIs treated with vancomycin. All but three patients had a vancomycin MICEtest of 1.5 mg/L. Achievement of CART-derived AUC24-48h of at least 550 mg*h/L (AUC24-48h/MIC of 366 mg*h/L) was associated with a lower incidence of treatment failure. In multivariate analyses, the risk ratio was 0.45 for the CART-derived AUC24-48h threshold, indicating that achievement of the CART-derived AUC24-48h threshold of 550 was associated with a 2-fold decrease in treatment failure. These findings suggest a potential association between vancomycin exposure and outcomes in patients with MRSA BSIs with MICEtest ≥1.5 mg/L. As this study was retrospective, these findings provide the basis for a future large-scale, multi-center prospective study.

The practice orientations of physicians and patients: the effect of doctor-patient congruence on satisfaction.

This study investigated the extent to which the individual orientations of physicians and patients and the congruence between them are associated with patient satisfaction. A survey was mailed to 400 physicians and 1020 of their patients. All respondents filled out the Patient-Practitioner Orientation Scale, which measures the roles that doctors and patients believe each should play in the course of their interaction. Patients also rated their satisfaction with their doctors. Among patients, we found that females and those who were younger, more educated, and healthier were significantly more patient-centered. However, none of these variables were significantly related to satisfaction. Among physicians, females were more patient-centered, and years in practice was related to satisfaction and orientation in a non-linear fashion. The congruence data indicated that patients were highly satisfied when their physicians either had a matching orientation or were more patient-centered. However, patients whose doctors were not as patient-centered were significantly less satisfied.

Clinical quality measurement. Comparing chart review and automated methodologies.

OBJECTIVES: This study investigates the use of data from automated systems within a large managed care plan to create indicators of clinical quality. METHODS: Measures from the first year of Health Plan Employer Data and Information Set, HEDIS 2.0, are used to compare chart review and automated analysis methodologies. The contributions of various data systems in creating clinical quality measures are evaluated. RESULTS: Chart review data usually are better for creating clinical quality indicators, although the level of agreement between the two methodologies often is quite high. Computerized patient record systems are found to be the most reliable automated data source, and automated claims are found to be the least reliable. This study's findings suggest that automated encounter systems may provide relatively reliable data. CONCLUSIONS: Managed care plans may not want to rely on automated data alone for clinical quality measurement. The results reported here support the use of combined methodologies such as the "hybrid" method, which utilizes both automated and chart-review data.

Promotion of high school blood donations: testing the efficacy of a videotaped intervention.

"Life to Life," an 11-minute videotape based on social learning principles, was used by 10 blood centers in presentations to 4970 high school students one week before school blood drives. At each school, some students saw the videotape and others attended a blood center's customary presentation. Students also completed a brief questionnaire assessing donation attitudes, donation history, and intent to donate. The videotape accounted for a relative increase of 18.7 percent in donations even when other factors were not controlled for. Results were analyzed with logistic models and showed a consistently positive effect over all models used. For students who had never donated, the estimated odds ratio for actual donation (videotape:control) was 1.528. When the model included both type of presentation and ethnicity, the relative increase in donation over that after the blood centers' usual presentation was 69.8 percent for first-time donors. Among previous donors considered alone, the effect on donation was not significant. Whatever their donor history, students who viewed the videotape showed significantly more positive attitudes toward donation and had greater intention to donate than students who saw the blood centers' standard presentations. These results suggest that this videotape is a useful tool for recruitment of high school blood donors.

Amyloidosis in pigtailed macaques (Macaca nemestrina): epidemiologic aspects.

A retrospective study of amyloidosis in pigtailed macaques (Macaca nemestrina) at the Washington Regional Primate Research Center (WRPRC) was conducted. Between 1971 and 1985, 248 of 1,952 (13%) necropsies revealed amyloidosis in pigtailed macaques. The influence of demographic factors, diseases and experimental interventions on amyloidosis was examined. Univariate analyses, using two controls for each case, indicated that age, sex, birthplace and residence were related to amyloidosis. After adjusting for age, females were not at greater risk. However, monkeys born at the WRPRC were at greater risk and monkeys 0 to 5 years old residing at the breeding colony were at greater risk than monkeys at the research center. After adjustment for age, monkeys were at greater risk of developing amyloidosis if they had a history of episodes of diarrhea, respiratory disease or trauma. As the number of episodes increased, the risk increased. Monkeys with retroperitoneal fibromatosis, a manifestation of simian D retrovirus infection, were also at greater risk. Using logistic regression and controlling for age, sex, birthplace and residence, monkeys with diarrhea remained at an elevated risk for amyloidosis. Compared with a model combining diarrhea, respiratory disease, septicemia, surgery, trauma and retroperitoneal fibromatosis, a model with diarrhea alone accounted for most of the increased risk.

Epidemiology and etiology of diarrhea in colony-born Macaca nemestrina.

The epidemiology of diarrhea in colony-born M. nemestrina was studied in 205 neonates and infants in an Infant Primate Research Laboratory (IPRL), and in 248 neonates, juveniles and adolescents up to 4 years of age at a separate breeding and holding facility (Primate Field Station, PFS). Computerized medical records of individual animals over a 5-year period were analyzed to determine the incidence of diarrhea; age, duration and number of episodes; mortality and etiology. The incidence of diarrhea at the IPRL was highest in infants at less than 1 month of age (18.6 cases per 1000 animal days) and at 1-6 months olds (2.0 cases per 1000 animals days). Many infants had multiple episodes. All episodes were less than 10 days in duration. Mortality was low. At the PFS, the highest incidence occurred in infants at 6-12 months of age (1.36 cases per 1000 animal days). Multiple episodes were less common. Duration was variable. The infectious agents diagnosed at both facilities were Shigella, Campylobacter and Cryptosporidium. No pathogens were identified in many episodes. Shigella was more common at PFS than at the IPRL. Chronic diarrhea occurred in approximately 10% of animals at PFS. Intestinal amyloidosis and retroperitoneal fibromatosis were found in 13 animals with chronic diarrhea. Further studies are needed to determine the pathogenesis of chronic diarrhea, the etiologic significance of Campylobacter, and the causes of diarrhea when no pathogens are isolated.

Retroperitoneal fibromatosis and acquired immunodeficiency syndrome in macaques: epidemiologic studies.

At the University of Washington Regional Primate Research Center, a simian acquired immunodeficiency syndrome (SAIDS) associated with retroperitoneal fibromatosis (RF) has been observed in 82 macaques since 1976, including 77 pigtailed macaques (Macaca nemestrina), two long-tailed macaques (M. fascicularis), one Japanese macaque (M. fuscata) and two rhesus macaques (M. mulatta). The syndrome is characterized by immunodeficiency accompanied by a fibroproliferative lesion, primarily affects young monkeys (1-3 years) and has a high case fatality rate. Based on the occurrence of RF in colony-born and non-colony-born monkeys, the minimum incubation period for natural exposure is believed to be about 9 months. The incidence of RF was 0.9% in M. nemestrina, 0.1% in M. fascicularis, 1.0% in M. fuscata and 0.4% in M. mulatta. There were no significant differences in the incidence of RF by sex or seasonality. Epidemiologic studies were focused on 42 juvenile M. nemestrina that developed RF between January 1980 and June 1983, and the results were compared with 42 age- and sex-matched controls. The incidence of RF was 5.7% in monkeys 12-24 months old and 3.4% in monkeys 24-36 months old, but less than 1.0% in age groups of under 1 year and over 3 years. No significant associations were found for housing history, parentage, generations or ancestral origins. Epidemiologic information and preliminary viral studies suggest a type D retrovirus may be the causative agent in RF and SAIDS. RF associated with SAIDS appears to be an excellent model for Kaposi's sarcoma associated with human AIDS.