The use of antibiotics as prophylaxis against postsurgical infection has been propagated. However, in the field of oral implant dentistry, the use of systemic antibiotics remains a controversial issue, with various antibiotic regimens being advocated. The aims of this multi-center randomized clinical trial were to determine the effect of various systemic antibiotic prophylaxis regimens on patient-centered outcomes and perceptions, postsurgical complications in patients undergoing standard oral implant therapy. In this preliminary study, 107 medically healthy adults who were consecutively admitted to 5 study centers for standard oral implant therapy were randomly assigned to one of the 4 groups (3 test and 1 control groups). Pre-operative antibiotics of 2 g amoxicillin 1 hour prior to standard implant placement were prescribed to test group 1 (positive control), post-operative antibiotics of 2g amoxicillin following implant placement for test group 2, and pre-operative antibiotics of 2g amoxicillin 1 hour prior to standard implant placement and 500mg three times daily on days 2 through 3 after standard implant placement for test group 3. The control group was given a placebo tablet of 2g 1 hour prior to standard implant placement without any antibiotics. Subjects were examined clinically by blinded examiners at 1 week, 2 weeks, 4 weeks and 8 weeks from implant installation for post-operative complications. In addition, Visual Analogue Scales (VAS) on pain, swelling, bruising and bleeding were obtained from the patients from Day 1 through Day 7 and 14. From the results of this preliminary study, in standard single implant placement with non-submerged healing, the postoperative complications (Flap closure, Swelling, Pain, Suppuration and Implant stability) and patient-centered outcomes (VAS of bleeding, pain, swelling and bruising) will neither be affected by using antibiotics prophylaxis in different regimens nor not using antibiotics prophylaxis. It should be reiterated that dental practitioners should be cautious when using antibiotics as a prevention of postoperative infection in dental implant therapy. The indiscriminate use of antibiotics will eventually lead to more serious consequences including allergy and the development of resistance strains. / published_or_final_version / Dental Surgery / Master / Master of Dental Surgery

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment of the requirements for the degree of Masters of Science in Medicine in Emergency Medicine. Johannesburg, 2013 / To determine the types of uropathogens encountered in patients presenting to a busy private emergency department in Johannesburg and compare sensitivity patterns of the bacteria identified with current antimicrobial prescribing patterns.

Even though it has been decades since antibiotics were put into widespread use, bacterial infections are a worsening source of morbidity and mortality worldwide. This is partially due to the formation of biofilms. Biofilms are populations of microbial cells embedded in self-produced matrices and their formation can enhance survival of the pathogen in the host. Pseudomonas aeruginosa is a major cause of acute and chronic infections and an excellent model for the study of opportunistic, biofilm-based infections. It produces a plethora of virulence factors and we do not fully understand how it harms the host. This thesis investigates the synthesis and characteristics of the Refractile-body (R-body), a newly identified P. aeruginosa virulence factor and potential roles of this virulence factor during host colonization. R-bodies are large proteinaceous polymers that are produced as a coiled ribbon but can extend to form a spear-like structure that is longer than a bacterial cell. Further, the R-body is produced stochastically and the producing minority is thought to contribute to success of the population through altruistic suicide. The purpose of this thesis is to characterize yet another virulence factor in the arsenal of the notorious pathogen P. aeruginosa. Further, the capacity for R-body production is present in diverse bacteria, and characterization of its function could be pertinent for our understanding of other bacteria with roles in medicine, agriculture, and industry. In Chapter 1, I introduce concepts from the fields of bacterial infectious disease, population biology and gene expression to provide context for my research findings on the R-body. In Chapter 2, I describe the discovery of R-body polymers in the P. aeruginosa PA14 biofilm. Using mass spectrometry analysis, I identified a novel P. aeruginosa R-body protein absent in the Caedibacter taeniospiralis and Azorhizobium caulinodans genomes, two bacteria for which R-body production had previously been described. Further, results in the chapter elucidate the role of R-bodies in P. aeruginosa PA14 colonization in the plant and virulence in the nematode hosts. The work described in Chapter 3 focuses on the transcription factor RcgA, which is required for R-body production. The gene encoding RcgA lies in a cluster and is co-expressed with R-body structural genes. Using established genetic tools, I asked the question, “what signal does RcgA sense?” I found that RcgA binding to a cyclic nucleotide is necessary for its function in turning on R-body genes. I present data in Chapter 3 and 4 that sheds light on the regulatory logic of R-body production in P. aeruginosa. Specifically, using single-cell resolution methods, I have been able to characterize the impact of various genes on stochasticity of R-body production in the population. Data presented in these chapters are another example of the importance of studying heterogeneity and stochasticity of virulence factor expression in the population. Taken together, the work in this thesis provides an expanded and multifaceted understanding of a fascinating virulence factor found across bacterial phylogeny. The R-body produced by P. aeruginosa, a notorious human pathogen, is unique in its makeup and should be further characterized. This work also underscores the necessity of studying bacterial pathogenicity in the context of the biofilm lifestyle.

published_or_final_version / Dentistry / Master / Master of Dental Surgery

Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Antibiotic effectiveness, forests, and climate stability are three of the most endangered public and common goods of the twenty-first century. All three are threatened by individuals ignoring the negative consequences of their actions on society: spreading antibiotic resistance, increasing forest degradation, and accelerating climate change. All these effects are likely to have long-lasting impacts on global health and economic development. This dissertation seeks to understand these human–environment interactions better while evaluating policies promoting sustainable behaviors or improving economic resilience. The first chapter considers the trade-off in prescribing antibiotics: they cure bacterial infections, but they spur antibiotic resistance. I estimate two essential parameters to calibrate any model of antibiotic resistance: the causal impact of prescriptions on antibiotic resistance and the elasticity of demand for an antibiotic. After developing and calibrating a dynamic bio-economic model of the issue, I show that it can be welfare-improving to increase out-of-pocket expenditure on antibiotics used to tackle spreading infections. The second chapter calculates the geographical distribution of people at risk of falling into poverty in the aftermath of droughts and floods in Malawi. Its methods can be expanded to identify the beneficiaries of scalable social safety nets or ex-ante climate insurance. Such programs would increase the resilience of the poor to climate change. The third chapter investigates the potential double dividend of internal migration in terms of poverty alleviation and forest regeneration in Central India. It relies on an innovative index of forest degradation created from high-resolution remote sensing imagery and unique data on internal migration and forest pressure based on a survey of 5,000 households.

Developing treatments for antibiotic resistant bacterial infections is among the highest priority public health challenges worldwide. Tetracyclines, one of the most important classes of antibiotics, have fallen prey to antibiotic resistance, necessitating the generation of new analogs. Many tetracycline analogs have been accessed through both total synthesis and semisynthesis, but key A- and C-ring tetracycline analogs remain inaccessible. New methods are needed to unlock access to these analogs, and heterologous biosynthesis in a tractable host such as Saccharomyces cerevisiae is a candidate method. C-ring analog biosynthesis can mimic nature’s biosynthesis of tetracyclines from anhydrotetracyclines, but challenges exist, including the absence of the unique cofactor F420 in common heterologous hosts. Chapter 1 provides background on antibiotics, and the tetracycline class in particular, and the metabolic engineering and directed evolution techniques available to us for heterologous expression of enzymes in yeasts. In Chapter 2, we describe the biosynthesis of tetracycline from anhydrotetracycline in S. cerevisiae heterologously expressing three enzymes from three bacterial hosts. Further, in Chapter 3, we highlight our Tang Laboratory collaborators’ work, where they reported the heterologous biosynthesis of a non-antibiotic fungal anhydrotetracycline derivative, TAN-1612, in S. cerevisiae from Aspergillus niger. We have built upon this system, allowing for the high-titer production of TAN-1612 in yeasts. Finally, in Chapter 4, we outline our efforts to convert TAN-1612 into a high titer tetracycline- and analog-producer by modifying the 2-, 4-, and 6-positions, proven critical for antibiotic activity. By hijacking biosynthetic hydroxylating and reducing enzymes, we attempted to modify the 6α-position, dearomatizing the C-ring. We also expressed heterologous enzymes within the TAN-1612 pathway that could furnish the 2-position with a carboxamido group instead of its natural hydrogen groups. By taking advantage of yeast’s natural biosynthetic pathways, we will create inexpensive, single-dose antibiotics, setting the stage to pursue yeast as a novel therapeutic. These state-of-the-art synthetic biology technologies will create entirely new paradigms, leading the charge against infections and diseases.

Thesis (PhD (Microbiology))--University of Stellenbosch, 2009. / Multidrug resistant strains of Staphylococcus aureus is presenting an increasing threat, especially immune compromised individuals. Many of these strains have developed resistance to newly approved drugs such as quinupristin-dalfopristin, linezolid and daptomycin. The search for alternative treatment, including bacteriocins (ribosomally synthesized antimicrobial peptides) of lactic acid bacteria is increasing . Lactococcus lactis subsp. lactis F10, isolated from freshwater catfish, produced a new nisin variant active against clinical strains of S. aureus. The operon encoding nisin F is located on a plasmid and the structural gene has been sequenced. The lantibiotic is closely related to nisin Z, except at position 30 where valine replaced isoleucine. The antimicrobial activity of nisin F against S. aureus was tested in the respiratory tract of Wistar rats. Non-immunosuppressed and immunosuppressed rats were intranasally infected with S. aureus K and then treated with either nisin F or sterile physiological saline. Nisin F protected immunosuppressed rats against S. aureus, as symptoms of an infection were only detected in the trachea and lungs of immunosuppressed rats treated with saline. The safety of intranasally administered nisin F was also evaluated and proved to have no adverse side effects. The potential of nisin F as an antimicrobial agent to treat subcutaneous skin infections was evaluated by infecting C57BL/6 mice with a bioluminescent strain of S. aureus (Xen 36). Immunosuppressed mice were treated with either nisin F or sterile physiological saline 24 h and 48 h after infection with subcutaneously injected S. aureus Xen 36. Histology and bioluminescence flux measurements revealed that nisin F was ineffective in the treatment of deep dermal staphylococcal infections. Non-infected and infected mice treated with nisin F had an influx of polymorphonuclear cells in the deep stroma of the skin tissue. This suggested that nisin F, when injected subcutaneously, may have modulated the immune system. Nisin F proved an effective antimicrobial agent against S. aureus-related infections in the respiratory tract, but not against subcutaneous infections. The outcome of nisin F treatment thus depends on the route of administration and site of infection.

L’ostéomyélite chronique est une infection chronique du tissu osseux et de la moelle. C’est une infection grave du fait de sa localisation au sein d’un tissu profond, de la complexité de sa prise en charge thérapeutique et de la mise en jeu du pronostic fonctionnel. L’incidence de l’ostéomyélite chronique est accrue sur certains terrains (drépanocytose, diabète, et polyarthrite rhumatoïde entre autres). Son traitement classique repose sur un curettage chirurgical associé à une antibiothérapie par voie générale durant au moins 6 semaines. Ce traitement est marqué le plus souvent par des échecs du fait de la difficulté de faire parvenir des antibiotiques à doses efficaces et de manière prolongée ou continue au niveau de l'os infecté.<p>\ / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished