Development of a nystatin-loaded micellar system for oral mucoadhesion
- Authors: Sarpong, Nancy Owusu Akyere
- Date: 2019
- Subjects: Medical microbiology , HIV infections -- Treatment Clinical pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/43556 , vital:36918
- Description: Oropharyngeal Candidiasis (OPC) is an opportunistic fungal infection that affects mostly infants and immunocompromised patients. In recent years, the disease has been on the rise due to an increased life span, the HIV pandemic and the increased use of broad spectrum antibiotics. OPC may be treated using a nystatin suspension, which is not as effective as it could be due to the mechanism by which the suspension is applied to the affected tissue. This research aims to improve the effectiveness of nystatin, for the treatment of OPC, by proposing a nystatin loaded micellar system incorporated into a mucoadhesive system for drug delivery. This will ensure that nystatin is gradually released from the film, thus increasing retention time of nystatin at the affected area. In this study, a mixture design was developed, which was used to determine the most appropriate solvent system for nystatin solubilization. Optimisation of the micelle formulation was achieved by using the central composite rational design (CCRD). The two factors that were taken into consideration were the temperature of the hydration medium (water) and the length of time the micellar solution was exposed to the temperature environment of the rotary evaporator. The responses that were investigated were the mean particle size, mean polydispersity index (PDI), mean zeta potential, change in mean particle size and change in mean PDI. The optimal micelle formulation was characterised for size, stability, morphology and drug encapsulation efficiency. The micelles were found to be spherical and stable with an acceptable size range. However, their drug encapsulation efficiency was low. The mucoadhesive film was formulated and characterised for physical characteristics, pliability, percentage swelling index and drug release profile. The film was found to be highly pliable and evenly distributed with a smooth surface; no bumps or bubbles were visible. The film was able to swell to up to 550 %. In vitro studies showed that nystatin was gradually released from the film.
- Full Text:
- Date Issued: 2019
- Authors: Sarpong, Nancy Owusu Akyere
- Date: 2019
- Subjects: Medical microbiology , HIV infections -- Treatment Clinical pharmacology
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/43556 , vital:36918
- Description: Oropharyngeal Candidiasis (OPC) is an opportunistic fungal infection that affects mostly infants and immunocompromised patients. In recent years, the disease has been on the rise due to an increased life span, the HIV pandemic and the increased use of broad spectrum antibiotics. OPC may be treated using a nystatin suspension, which is not as effective as it could be due to the mechanism by which the suspension is applied to the affected tissue. This research aims to improve the effectiveness of nystatin, for the treatment of OPC, by proposing a nystatin loaded micellar system incorporated into a mucoadhesive system for drug delivery. This will ensure that nystatin is gradually released from the film, thus increasing retention time of nystatin at the affected area. In this study, a mixture design was developed, which was used to determine the most appropriate solvent system for nystatin solubilization. Optimisation of the micelle formulation was achieved by using the central composite rational design (CCRD). The two factors that were taken into consideration were the temperature of the hydration medium (water) and the length of time the micellar solution was exposed to the temperature environment of the rotary evaporator. The responses that were investigated were the mean particle size, mean polydispersity index (PDI), mean zeta potential, change in mean particle size and change in mean PDI. The optimal micelle formulation was characterised for size, stability, morphology and drug encapsulation efficiency. The micelles were found to be spherical and stable with an acceptable size range. However, their drug encapsulation efficiency was low. The mucoadhesive film was formulated and characterised for physical characteristics, pliability, percentage swelling index and drug release profile. The film was found to be highly pliable and evenly distributed with a smooth surface; no bumps or bubbles were visible. The film was able to swell to up to 550 %. In vitro studies showed that nystatin was gradually released from the film.
- Full Text:
- Date Issued: 2019
Incidence of bacterial infections and colonisation in patients admitted to a tuberculosis hospital
- Authors: Annear, Dale John
- Date: 2018
- Subjects: Medical microbiology , Microbiology Bacteriology Tuberculosis -- Hospitals -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/21482 , vital:29526
- Description: Patients with drug resistant tuberculosis (TB) are treated with multiple antibiotics including moxifloxacin, linezolid, and meropenem, which puts them at greater risk for colonisation by multi-drug resistant (MDR) bacteria. The objectives of this study were to: (i) assess the antimicrobial prescribing patterns practiced within the hospital by retrospective patient file review; (ii) determine the spectrum of bacterial colonisation in TB patients upon admission and during hospitalisation; (iii) identify bacterial isolates and evaluate antimicrobial susceptibility profiles; (iv) detect antimicrobial resistance genes in the bacterial isolates by PCR and DNA sequencing; and (v) investigate genetic relatedness of Klebsiella pneumoniae isolates using Multi Locus Sequence Typing. Nasal, groin and rectal swabs [for the detection of extended spectrum beta lactamases (EBSLs), carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA)] were analysed from a cohort of patients (n=37) admitted either from the community (n = 28) or from other healthcare facilities (n=9) to a TB hospital. Swab samples were collected at admission and at four week intervals thereafter during hospitalization. Identification and antimicrobial susceptibility testing of bacterial isolates (n=62) were determined at the National Health Laboratory Services (NHLS) by the VITEK-MS and Vitek 2 systems respectively. Additional antimicrobial susceptibility testing was conducted by Sensititre Gram Negative Xtra (GNFX2) MIC plates. PCR and DNA sequencing were used for detection of resistance genes. Patients (n=13/37; 35%) were colonized by MDR bacteria (ESBLs [n=11], MRSA [n=2]) on admission. Colonization rates were lower in patients admitted from the community (9/28; 32%) compared to those transferred from other healthcare facilities (4/9; 44%). All admitted patients who did not exhibit colonization at baseline and who were resident within the hospital for longer than 4 weeks (17/37; 46% of total patients) became colonised by an ESBL-producing Enterobacteriaceae species. No patients acquired MRSA during hospitalisation. Among ESBL Enterobacteriaceae, Escherichia coli (41/62; 66%) and K. pneumoniae [14/62; 23%]) predominated. Nineteen percent (7/37) of patients demised during their hospitalization. Both the Vitek system and Sensititre Gram Negative Xtra (GNFX2) MIC plates susceptibilities were similar for most antimicrobials, however there were discrepancies for tigecycline susceptibility profiles. A high number of isolates exhibited resistance to aminoglycosides and fluoroquinolones. Genes encoding for ESBLs (CTX-M-14, CTX-M-15, SHV-28, OXA-1, and OXY-2-9) were detected among ESBL Enterobacteriaceae. Two Enterobacteriaceae isolates with reduced carbapenem susceptibility did not contain carbapenemase-encoding genes. MLST revealed unique sequence types and genetic diversity among the K. pneumoniae isolates from hospitalised patients. However, the source and colonization routes of these isolates could not be determined, which requires further investigation. This study provides insight into the spectrum of bacterial pathogen colonisation in hospitalised TB patients and suggests a review of infection control programs and practices at the TB hospital.
- Full Text:
- Date Issued: 2018
- Authors: Annear, Dale John
- Date: 2018
- Subjects: Medical microbiology , Microbiology Bacteriology Tuberculosis -- Hospitals -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/21482 , vital:29526
- Description: Patients with drug resistant tuberculosis (TB) are treated with multiple antibiotics including moxifloxacin, linezolid, and meropenem, which puts them at greater risk for colonisation by multi-drug resistant (MDR) bacteria. The objectives of this study were to: (i) assess the antimicrobial prescribing patterns practiced within the hospital by retrospective patient file review; (ii) determine the spectrum of bacterial colonisation in TB patients upon admission and during hospitalisation; (iii) identify bacterial isolates and evaluate antimicrobial susceptibility profiles; (iv) detect antimicrobial resistance genes in the bacterial isolates by PCR and DNA sequencing; and (v) investigate genetic relatedness of Klebsiella pneumoniae isolates using Multi Locus Sequence Typing. Nasal, groin and rectal swabs [for the detection of extended spectrum beta lactamases (EBSLs), carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA)] were analysed from a cohort of patients (n=37) admitted either from the community (n = 28) or from other healthcare facilities (n=9) to a TB hospital. Swab samples were collected at admission and at four week intervals thereafter during hospitalization. Identification and antimicrobial susceptibility testing of bacterial isolates (n=62) were determined at the National Health Laboratory Services (NHLS) by the VITEK-MS and Vitek 2 systems respectively. Additional antimicrobial susceptibility testing was conducted by Sensititre Gram Negative Xtra (GNFX2) MIC plates. PCR and DNA sequencing were used for detection of resistance genes. Patients (n=13/37; 35%) were colonized by MDR bacteria (ESBLs [n=11], MRSA [n=2]) on admission. Colonization rates were lower in patients admitted from the community (9/28; 32%) compared to those transferred from other healthcare facilities (4/9; 44%). All admitted patients who did not exhibit colonization at baseline and who were resident within the hospital for longer than 4 weeks (17/37; 46% of total patients) became colonised by an ESBL-producing Enterobacteriaceae species. No patients acquired MRSA during hospitalisation. Among ESBL Enterobacteriaceae, Escherichia coli (41/62; 66%) and K. pneumoniae [14/62; 23%]) predominated. Nineteen percent (7/37) of patients demised during their hospitalization. Both the Vitek system and Sensititre Gram Negative Xtra (GNFX2) MIC plates susceptibilities were similar for most antimicrobials, however there were discrepancies for tigecycline susceptibility profiles. A high number of isolates exhibited resistance to aminoglycosides and fluoroquinolones. Genes encoding for ESBLs (CTX-M-14, CTX-M-15, SHV-28, OXA-1, and OXY-2-9) were detected among ESBL Enterobacteriaceae. Two Enterobacteriaceae isolates with reduced carbapenem susceptibility did not contain carbapenemase-encoding genes. MLST revealed unique sequence types and genetic diversity among the K. pneumoniae isolates from hospitalised patients. However, the source and colonization routes of these isolates could not be determined, which requires further investigation. This study provides insight into the spectrum of bacterial pathogen colonisation in hospitalised TB patients and suggests a review of infection control programs and practices at the TB hospital.
- Full Text:
- Date Issued: 2018
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