Stephen A. Sonstein

Effect of low concentrations of quinolone antibiotics on bacterial virulence mechanisms.

Recent studies have shown that exposure to quinolone antibiotics at or below the minimal inhibitory concentration (MIC) results in reduction in the level of production or total elimination of certain factors that contribute to the virulence of bacteria. This study was designed to determine whether low concentrations of enoxacin, lomefloxacin, and ciprofloxacin altered the morphology or affected the production of various virulence factors in several different genera of bacteria. The factors studied were nuclease and a toxin production in Staphylococcus aureus, cell size, pili and fimbriae production, and adherence of Salmonella typhimurium, Escherichia coli, and Pseudomonas aeruginosa to urinary epithelial cells and dog bladder cells, and the major virulence factor in Yersinia pseudotuberculosis. In addition, the effect of growth in low levels of enoxacin on phagocytosis of S. aureus by human polymorphonuclear leukocytes (PMNs) was studied. Following exposure to subinhibitory levels of quinolones tested, significant reduction in activity or complete elimination was seen in all of those factors measured. Minor differences were noted in the efficiency of elimination among the three quinolones tested. At as low as 1/8 MIC there is significant enhancement of phagocytic activity by human PMNs. These data suggest that exposure to quinolones at concentrations below the MIC disrupts the regulatory mechanisms that control cell morphology, adherence as well as exocellular enzyme production and plasmid maintenance. This may mean that certain virulent organisms that survive exposure to quinolone antibiotics may be less likely to produce or maintain the disease state in susceptible hosts.

Alignment of Competencies to Address Inefficiencies in Medicines Development and Clinical Research: Need for Inter-Professional Education

The challenges faced by the biopharmaceutical industry in its key role to overcome the bottlenecks in innovative medicines development are related to addressing the technical knowledge gaps, the limitations to clinical trial testing, and the lack of clarity in the global pathways and processes to efficient outcomes. It is postulated that the lack of an adequately sized and appropriately trained multi-professional workforce, both in the industry and in the clinical research field, to enable fulfillment of the demanding aims for medicines development is a significant part of the problem. The current global status of pharmaceutical medicine’s efforts to conduct education and training is seen as patchy, inadequate, and without recognition, direction or leadership. It is therefore proposed that the movement towards competency-based education (CBE) should be harnessed, and core competency job and role profiles and competency curricula should be developed. CBE presents a means of addressing the educational and training needs within medicines development, harmonizing the workforce and the requirement for increased inter-professional teamwork. An educational environment in which aspiring and established biomedical professionals could readily learn about the competencies they need to pursue a particular career path is envisioned. Utilizing competencies provides the building blocks to align and harmonize the desired learning outcomes for effective performance amongst a multi-professional workforce. The effective implementation of training programs as described here has the potential to transform drug development procedures into an efficient and integrated process; medical product life-cycle management would result in the availability of better and safer medicines more rapidly, for the benefit of patients and society.

Moving from Compliance to Competency

Medicines development and clinical research are among the most heavily regulated activities on a global basis. As our understanding of pathophysiology and therapeutic intervention has increased, there has been a concomitant increase in the complexity of clinical trial protocol requirements[1][1] and

In vitro activity of lomefloxacin (SC 47111 or NY-198), a new quinolone antimicrobial, against clinical isolates of common pathogens

The lomefloxacin antibacterial activity was assessed against 442 clinical isolates of common bacterial pathogens and compared to the previously studied activity of ciprofloxacin, imipenem, norfloxacin, and other commonly used antibacterials. Lomefloxacin showed activity against the species of Enterobacteriaceae tested at a concentration equal to or below that of the most commonly used agents. Activity was lower against Pseudomonas species as well as most Gram-positive isolates tested with the exception of Staphylococcus aureus. Streptococcal strains were least susceptible. The results of this study support previous reports of excellent antimicrobial activity for lomefloxacin, especially against Gram-negative organisms.

Education and Training Needs Among Clinical Investigators and Medicines Development Professionals from Two Latin American Countries

There is increasing demand within the medicines development industry for sponsors and sites to improve clinical trial performance. Suggested methods include cost reduction, simplifying trial complexity, limiting patient risk, and improving trial efficiency, while at the same time increasing patient

Global Self-Assessment of Competencies, Role Relevance, and Training Needs Among Clinical Research Professionals

The Joint Task Force for Clinical Trial Competency conducted a multinational survey of clinical research professionals as a first step toward validating its previously published framework. Participants self-assessed their competence level and the relevance of specific core competencies to their current professional activities, as well as their perceived need for further training to enhance performance quality. Significant differences in the perception of competence and relevance for the role were observed among the various members of the clinical research team.

Joint Task Force for Clinical Trial Competency and Clinical Research Professional Workforce Development

Clinical research workforce development efforts have focused on both increasing the size of the workforce of investigators and professionals working in the clinical research enterprise, but also the education and training of those individuals to ensure the quality of study performance to improve the public’s health. A major contribution to these efforts has been the establishment of core competencies for clinical research professionals by the Joint Task Force for Clinical Trial Competency. This article reviews the development of the clinical research core competencies, their wide adoption and influence on job descriptions, education, training, and academic accreditation.