ETD Collection
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Item The in vitro activity of antimicrobial agents alone and in combination against clinical isolates of gram-positive bacteria.(1993) Van den Berg, AlanAnalysis of organisms involved in hospital infections has shown that Gram-positive bacteria have assumed an increasingly important role. Examples that have been recognised as important pathogens are staphylococci , enterococci, streptococci, Corynebacterium jeikeium and Leuconostoc species. Methicillin resistance in staphylococci has become a major problem in certain hospitals. Viridans streptococci continue to be the most frequent cause of native valve endocarditis. Leuconostoc species are being increasingly isolated from blood cuIture specimens. strains of Gram-positive bacteria have become resistant to specific antibiotics; e.g. staphylococci to methicillin, enterococci to ampicillin, and viridans streptococci to penicillin. JK corynebacteria are sensitive only to vancomycin and resistant to other antimicrobials normally used for treating infection caused by Gram-positive bacteria. In this study various combinations of antimicrobials against 35 clinical isolates of Gram-positive bacteria obtained from three hospitals in the Johannesburg area (Johannesburg, Hillbrow, and Baragwanath) from 1987- 1988 were investigated. The MIC / MBC results conformed to others described in worldwide studies. Results when different methodologies for determining synergy were used, varied. This emphasizes the need for standardization, especially with regard to the time-kill studies. Most antimicrobial combinations demonstrated tested against Leuconostoc species synergy using the checkerboard method, but these results were not confirmed by time-kill procedures, which showed mainly indifference. Synergy was also obtained when gentamicin plus ciprofloxacin was combined Corynebacterium jeikeium. Because of increasing resistance and the fact that Gram- positive bacteria cause serious infections, various and new combinations of antimicrobials need to be tested before treating these infections. Parts of this dissertation have been presented at the following congresses: 10th Annual Congress of the Society of Medical. Laboratory Technologists of South Africal Sun city 1989 75th Anniversary Congress of Pathology Johannesburg 1990 11th Annual Congress of the Society of Medical Laboratory Technologists of South Africa, Durban 1991Item Characterisation of plasmids conferring ampicillin resistance in South African isolates of haemophilus ducreyi(1996-03-27) Leong, May-Yong GeraldineFifty-two strains of Haemophilus ducreyi from various geographic regions of southern Africa (Botswana, Lesotho, Namibia, Gauteng, Natal and Transkei) isolated between 1988 to 1994 were tested for susceptibilities to five antimicrobial agents and characterized according to their plasmid content and ampicillin- resistance genes.Item The composition, geographical variation and antimicrobial activity of Lippia javanica ( Verbenaceae ) leaf essential oils(2003) Subramoney, SivanasenLippia javanica is a widely spread woody shrub and the major traditional use is reflected in its vernacular name; fever tea ' koorsbossie '. An infusion of the leaves is also used as a decongestant for colds and coughs. Infusions may also be used topically to treat scabies and lice A preliminary study indicated that the essential oil chemistry varies dramatically both within and between natural plant populations.Item The antimicrobial activity and Phytochemistry of leaf essential oils of selected rutaceae species(2002-07) Khusal, PristishThe Retuceae is an aromatic family of plants confined to the Fynbos biome in South Africa. This family is represented by a number of genera e.g. Agasthosma, Adenandra, Coleonema, Vepris etc. all containing a number of species which have been used for centuries in traditional healing. Although many of these species have been used for centuries in local healing rites the biological activity and phytochemistry are poorly recorded.Item The antimicrobial activity and phytochemistry of african wormwood ( artemisia )(2003-06-13) Gwebu, Lehlohonolo, TebogoArtemisia afra Jacq. wild also known as African wormwood, " umhlonyane" ( Xhosa and Zulu ) "lengana" ( Sotho And Tswana ) and "wildeals" ( Afrikaans 0 is an aromatic shrub belonging to the Asteraceace. It is widespread in South Africa extending from the mountainous regions of South Western cape, along the eastern coast to the Northern Province ( van Wyk et. al;1997 ) Due to the popular use of A. afra. The aerial part of sixteen samples from four natural populations were hydrodistilled and the essential oil analysed by GC_MS and tested for antimicrobial activity on anumber of bacteria and fungi.Item The composition and antimicrobial activity of leaf essential oils of selected agathosma species ( rutaceae )(2003-11-14) Fourie, CarlaThis project was conducted to investigate properties and to record the essential oil profiles of a selection of species belonging to the genus agasthosma. Plants have been used for many years by the local South African to treat various infections and illnesses. This knowledge has largely been untapped. Buchu is one of the plant species that are used extensively by the San and Khoi people. It is remarkable that of the ca. 150 agathosma species indigenous to South Africa only two species ( Agasthosma crenulata and agathosma betulina ) have been investigated for biological activity. The genus Agasthosma is traditionally used for the following conditions ; stomach ailments, fever, coughs, cold, flu, urinary tract, and kidney infections, haematuria, prostatitis, rheumatism, gout, bruises and for antiseptic purposes.Item Assessing the rational use of cefotaxime at Queen Elizabeth ll Hospital(2004) Maphasa, TebohoThe purpose of the study was to evaluate the use of cefotaxime with the idea of improving its use within the hospital. Improving the use of cefotaxime could result in a change in the proportion spent from the pharmacy budget. More importantly a change in prescribing patterns of this drug could also result in a reduction in resistant patterns of cefotaxime.Item Surveillance of antimicrobial susceptibility patterns among pathogens isolated in public sector hospitals associated with academic institutions in South Africa(2015) Nyasulu, Peter SuwirakwendaBackground: Antimicrobial resistance (AMR) is a global public health challenge since infection with resistant organisms may cause death, can spread across the community, and increase health care costs at individual, community and government level as more expensive antimicrobials will have to be made available for the treatment of infections caused by resistant bacteria. This calls for urgent and consolidated efforts in order to effectively curb this growing crisis, to prevent the world from slipping back to the pre-antibiotic era. The World Health Organization made a call in 2011 advocating for strengthening of surveillance and laboratory capacity as one-way of detecting and monitoring trends and patterns of emerging AMR. Knowledge of AMR guides clinical decisions regarding choice of antimicrobial therapy, during an episode of bacteraemia and forms the basis of key strategies in containing the spread of resistant bacteria. The current study focused on Staphylococcus aureus (SA), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA), as they are common hospital acquired infections which are prone to developing resistance to multiple antibiotics. Aim: The aim of this project was to assess and utilize the laboratory information system (LIS) at the National Health Laboratory Services (NHLS), as a tool for reporting AMR and monitoring resistance patterns and trends over time of clinical isolates of SA, KP and PA, cultured from the blood of patients admitted to seven tertiary public hospitals in three provinces in South Africa. Methods: A retrospective and prospective analysis was done on isolates of SA, KP, PA from blood specimens collected from patients with bacteraemia and submitted to diagnostic microbiology laboratories of the NHLS at seven tertiary public hospitals in three provinces in South Africa. These hospitals comprised the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), Chris Hani Baragwanath Hospital (CBH), Helen Joseph Hospital (HJH), Steve Biko Pretoria Academic Hospital (SBPAH), Groote Schuur Hospital (GSH), Tygerberg Hospital (TH) and the Universitas Hospital of the Free State (UH). For retrospective analysis, data submitted during the period July 2005 to December 2009 were used and for prospective analysis, data relating to AMR in SA, KP, PA, collected by the Group for Enteric, Respiratory and Meningeal disease Surveillance in South Africa, (GERMS-SA) from July 2010 to June 2011 were used. AMR in these three pathogens to commonly used antimicrobial drugs was systematically investigated. Multivariate logistic regressions models were used to assess factors associated with AMR. In addition, a systematic review of research done to date on AMR in bacterial pathogens commonly associated with hospital-acquired infections was conducted in order to understand the existing antimicrobial surveillance systems and baseline resistance patterns in South Africa. Results: A total of 9969 isolates were reported from the retrospective dataset. These were 3942 (39.5%) SA, 4466 (44.8%) KP and 1561 (15.7%) PA. From the prospective dataset, a total of 3026 isolates were reported, 1494 (49.4%) SA and 1532 (50.6%) KP isolates respectively. The proportion of invasive bacteraemia was higher in the <5 year old children. Nearly all strains of SA in South Africa were resistant to penicillin, and >30% up to as high as 80% were resistant to methicillin-related drugs among~560 invasive SA isolates over the two year period. Methicillin resistant Staphylococcus aureus (MRSA) rates significantly differed between hospitals (p=<0.001). The proportion of MRSA isolates in relation to methicillin-susceptible strains showed a declining trend from 22.2% in 2005 to 10.5% in 2009 (p=0.042). Emerging resistance was observed for vancomycin: 1 isolate was identified in 2006 and 9 isolates between July 2010-June 2011, and all except 1 were from Gauteng hospitals. The study found increasing rates of carbapenem-resisant KP of 0.4% in 2005 to 4.0% in 2011 for imipenem. The mean rate of extended spectrum beta lactamase (ESBL-KP) producing KP was 74.2%, with the lowest rate of 62.4% in SBPAH and the highest rate of 81.3% in UH, showing a significant geographical variation in rates of resistance (p=0.021). PA showed a tendency for multi-drug resistance with resistance rates of >20% to extended spectrum cephalosporins, fluoroquinolones and aminoglycosides respectively. Emerging resistance in PA isolates was observed to colistin, showing a resistance rate of 1.9% over the 5 years period. In the multivariate model, age <5 years, male gender, and hospital location were factors significantly associated with MRSA, while ESBL-KP was significantly associated with age <5 years and hospital location. Concluding remarks: The study has clearly demonstrated that AMR is relatively common in South Africa among children <5 years. Enhancement of continued surveillance of nosocomial infections through use of routine laboratory data should be reinforced as this will facilitate effective interpretation and mapping of trends and patterns of AMR. Therefore, the LIS as a tool for gathering such data should be strengthened to provide reliable AMR data for improved understanding of the extent of the AMR, and present evidence on which future policies and practices aimed at containing AMR could be based. Key words: Laboratory information system, Trends, Patterns, Antimicrobial resistance, Bacterial pathogens, Nosocomial infections, Surveillance, Bacteraemia, Blood culture.Item Sensitivity of HIV-1 subtype C viruses to Griffithsin, cyanovirin-N and scytovirin: potential HIV-1 microbicides(2013-05-07) Alexandre, Kabamba BankolediThe majority of HIV-1 infections around the world occur via sexual intercourse and women, especially in developing countries, are disproportionately affected. Recently a number of strategies have been proposed to control the spread of HIV, among these the use of microbicides to prevent the sexual transmission of the virus. A clinical trial of 1% tenofovir gel that conferred up to 39% protection provided a proof-of-concept that an anti-HIV microbicide is feasible. Various other compounds, acting at different stages of HIV-1 life cycle, are also being investigated as potential microbicides. These include the lectins Griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN). GRFT was isolated from the red algae griffithsia sp. while CV-N and SVN were isolated from the blue green alga Nostoc ellipsosporum and the cyanobacterium Scytonema varium, respectively. These lectins bind mannose-rich glycans found on the surface of HIV-1 envelope and act as entry inhibitors. Although HIV-1 subtype C is the main cause of infections around the world, almost all studies conducted with GRFT, CV-N and SVN are based on subtype B viruses. The Chapter Two sought to establish the neutralization sensitivity of HIV-1 subtype C viruses to the three lectins, using both a cell line and primary cells, and compared this sensitivity to subtype B. This Chapter also examined mannose-rich glycans on HIV-1 that are involved in GRFT, CV-N and SVN binding. The conclusion from this study was that the neutralization of subtype C viruses by these lectins is similar to subtype B and that the 234 and 295 mannose-rich glycans were involved in their interaction with the virus. In general these data supported further studies on the use of GRFT, CV-N and SVN for prevention of HIV-1 subtype C sexual transmission. In Chapter Three, the ability of GRFT to expose the CD4 binding site (CD4bs) on HIV-1 gp120 is explored. I found that this exposure resulted in the enhancement of HIV-1 binding to plates coated with anti-CD4bs antibodies b12 and b6 or the CD4 receptor mimetic CD4-IgG2. This lectin also synergized with b12 and HIVpositive plasma containing antibodies to the CD4bs to neutralize the virus. Furthermore, the glycan at position 386, which shields the CD4bs, was shown to be involved in both GRFT enhancement of HIV-1 binding to b12 and b6 and in the synergistic interaction between the lectin and these antibodies. The importance of this study is that it investigated in details the effect of GRFT binding on HIV-1 envelope and also suggests this lectin can be used in combination with anti-HIV-1 antibodies to synergistically enhance the anti-viral activity. In Chapter Four I investigated GRFT, CV-N and SVN inhibition of the virus binding to the DC-SIGN receptor and their inhibition of the DCSIGN transfer of HIV-1 to target cells. These lectins only moderately inhibited the virus binding to the receptor while they potently inhibited its transfer to target cells. However, the inhibition of transfer was stronger when the virus bound the lectins after binding the DC-SIGN receptor compared to when it bound the lectins prior to binding the receptor. These three lectins can, therefore, inhibit the sexual transmission of HIV-1 since the DCSIGN- mediated transfer of the virus to susceptible cells is pivotal to this mode of transmission. Chapter Five is an investigation of the ability of HIV-1 subtype C to escape GRFT, CV-N and SVN, which involved growing the virus under escalating concentrations of these compounds. This was to know how this virus behaves under conditions of continuous exposure to the lectins. I found that HIV-1 subtype C became increasingly resistant to the lectins and viral envelope sequence analysis showed that this was associated with the deletion of mannose-rich glycans on gp120. Furthermore, of the 11 potential mannose-rich glycosylation sites on gp120 seven (230, 234, 241, 289, 339, 392 and 448) were involved in GRFT, CV-N and SVN resistance. Thus, the conclusion was that although these three lectins are potent inhibitors of HIV-1 infection, the virus is also able to escape their neutralization by deleting mannose-rich glycans on its envelope. However, the fact that escape to these lectins involved multiple deglycosylation and was only partial suggests that HIV-1 subtype C escape from GRFT, CV-N and SVN in a microbicide formulation may not be an easy process. We discuss the implications of these findings in Chapter Six and suggest future studies that could complement data presented in this thesis. Overall our data show that GRFT, CV-N and SVN can prevent the sexual transmission of both free and DC-SIGN associated HIV-1 particles and supports further development of these lectins as microbicides against HIV-1.