Comparative in-vitro activities of trimethoprimsulfamethoxazole and the new fluoroquinolones against confirmed extended spectrum beta-lactamase producing Stenotrophomonas maltophilia in Nkonkobe Municipality, Eastern Cape environment
- Adeyemi, Oluwatosin Oluwakemi
- Authors: Adeyemi, Oluwatosin Oluwakemi
- Date: 2012
- Subjects: Antibiotics , Microbial sensitivity tests , Drug resistance in microorganisms , Pathogenic microorganisms , Gram-negative bacterial infections
- Language: English
- Type: Thesis , Masters , MSc (Microbiology)
- Identifier: vital:11275 , http://hdl.handle.net/10353/d1007576 , Antibiotics , Microbial sensitivity tests , Drug resistance in microorganisms , Pathogenic microorganisms , Gram-negative bacterial infections
- Description: Stenotrophomonas maltophilia is increasingly emerging as an opportunistic pathogen of global concern. Due to its inherent resistance to several classes of antibiotics including carbapenems and its ability to acquire mobile resistance elements, treatment of infections caused by S. maltophilia is a constant challenge for clinicians. Trimethoprim-sulphamethoxazole (TMP-SMX) is the generally accepted antibiotic of choice for the treatment of infections caused by this organism, but resistance to the drug is increasingly being reported; hence, the need for alternative therapeutic options. In this study, the antimicrobial susceptibility profile of 110 commensal S. maltophilia isolates obtained from Nkonkobe municipality, Eastern Cape Province, Republic of South Africa was investigated. Twenty-one antibiotics including TMP-SMX and the newer fluoroquinolones; levofloxacin, gatifloxacin and moxifloxacin were included in the antibiotic panel. About 63.4 percent of the isolates were susceptible to TMP-SMX with a resistance rate of 28.2 percent. The fluoroquinolones were more effective with susceptibilities ranging from 76 percent to 94.7 percent. Resistance to the fluoroquinolones ranged from 1.3 percent to 2.7 percent. Levofloxacin was the most effective fluoroquinolone tested. Phenotypic dectection of extended spectrum β-lactamases (ESBLs) showed double disc synergy test (DDST) positivity in 59.5 percent of the isolates. Cefepime was the most sensitive indicator cephalosporin in the DDST with 77.3 percent of suspected ESBL-producing isolates showing cefepime-clavulanic acid synergy. Isolates exhibited nine different ESBL phenotypes, however, PCR amplification of the bla genes revealed four isolates that possessed genes belonging to the CTX-M group (CTX-M-1 and CTX-M-8 groups). ESBL genes are usually carried on mobile elements such as plasmids and transposons which may also bear genes that mediate resistance to aminoglycosides, tetracyclines, TMP-SMX and fluoroquinolones. ESBL positive isolates appeared more susceptible to the fluoroquinolones compared to TMP-SMX but there was no significant relationship between ESBL production and susceptibility to these drugs (p > 0.05). The newer fluoroquinolones are a possible alternative treatment option for S. maltophilia infections in this environment but further studies and clinical investigations are needed to determine the in vivo efficacy of these drugs.
- Full Text:
- Date Issued: 2012
- Authors: Adeyemi, Oluwatosin Oluwakemi
- Date: 2012
- Subjects: Antibiotics , Microbial sensitivity tests , Drug resistance in microorganisms , Pathogenic microorganisms , Gram-negative bacterial infections
- Language: English
- Type: Thesis , Masters , MSc (Microbiology)
- Identifier: vital:11275 , http://hdl.handle.net/10353/d1007576 , Antibiotics , Microbial sensitivity tests , Drug resistance in microorganisms , Pathogenic microorganisms , Gram-negative bacterial infections
- Description: Stenotrophomonas maltophilia is increasingly emerging as an opportunistic pathogen of global concern. Due to its inherent resistance to several classes of antibiotics including carbapenems and its ability to acquire mobile resistance elements, treatment of infections caused by S. maltophilia is a constant challenge for clinicians. Trimethoprim-sulphamethoxazole (TMP-SMX) is the generally accepted antibiotic of choice for the treatment of infections caused by this organism, but resistance to the drug is increasingly being reported; hence, the need for alternative therapeutic options. In this study, the antimicrobial susceptibility profile of 110 commensal S. maltophilia isolates obtained from Nkonkobe municipality, Eastern Cape Province, Republic of South Africa was investigated. Twenty-one antibiotics including TMP-SMX and the newer fluoroquinolones; levofloxacin, gatifloxacin and moxifloxacin were included in the antibiotic panel. About 63.4 percent of the isolates were susceptible to TMP-SMX with a resistance rate of 28.2 percent. The fluoroquinolones were more effective with susceptibilities ranging from 76 percent to 94.7 percent. Resistance to the fluoroquinolones ranged from 1.3 percent to 2.7 percent. Levofloxacin was the most effective fluoroquinolone tested. Phenotypic dectection of extended spectrum β-lactamases (ESBLs) showed double disc synergy test (DDST) positivity in 59.5 percent of the isolates. Cefepime was the most sensitive indicator cephalosporin in the DDST with 77.3 percent of suspected ESBL-producing isolates showing cefepime-clavulanic acid synergy. Isolates exhibited nine different ESBL phenotypes, however, PCR amplification of the bla genes revealed four isolates that possessed genes belonging to the CTX-M group (CTX-M-1 and CTX-M-8 groups). ESBL genes are usually carried on mobile elements such as plasmids and transposons which may also bear genes that mediate resistance to aminoglycosides, tetracyclines, TMP-SMX and fluoroquinolones. ESBL positive isolates appeared more susceptible to the fluoroquinolones compared to TMP-SMX but there was no significant relationship between ESBL production and susceptibility to these drugs (p > 0.05). The newer fluoroquinolones are a possible alternative treatment option for S. maltophilia infections in this environment but further studies and clinical investigations are needed to determine the in vivo efficacy of these drugs.
- Full Text:
- Date Issued: 2012
Inhibitory potential of honey on the enzymatic activity of Helicobacter pylori urease
- Authors: Matongo, Fredrick
- Date: 2012
- Subjects: Honey , Helicobacter pylori infections , Enzyme inhibitors , Traditional medicine , Antifungal agents
- Language: English
- Type: Thesis , Masters , MSc (Biochemistry)
- Identifier: vital:11253 , http://hdl.handle.net/10353/431 , Honey , Helicobacter pylori infections , Enzyme inhibitors , Traditional medicine , Antifungal agents
- Description: Urease of Helicobacter pylori is an important virulence factor implicated in the pathogenesis of many clinical conditions, such as chronic gastritis, peptic ulceration, and gastric cancer. Many urease inhibitors have been discovered, like phosphorodiamidates, hydroxamic acid derivatives, and imidazoles. Despite good activities at the enzyme level and excellent kinetic properties most of them have not been used as therapeutic agents in vivo because of their side effects, toxicity and instability. This has led to much attention to focus on exploring the novel urease inhibitory activities of natural products because of their low toxicity and good bioavailability. Honey, a natural product has been used in folk medicine due to its antitumor, antioxidant, antimicrobial and anti-inflammatory properties. The aims of this study were to isolate, characterise, purify urease produced by H. pylori and investigate the inhibitory effects of solvent honey extracts on its enzymatic activity. Urease was found to be both surface-associated and cytoplasmic. Maximum cytoplasmic urease activity was found to occur after 72 hr whereas maximum extracellular urease activities were found to occur after 96 hr. Characterization of the crude cytoplasmic urease revealed optimal activity at a pH of 7.5 and temperature of 40°C. The kinetic parameters Vmax and Km were 45.32 U ml-1 and 61.11 mM respectively.The honey extracts inhibited the activity of the crude urease in a concentration dependent manner. The Lineweaver-Burk plots indicated a non-competitive type of inhibition against H. pylori urease. The two honey extracts gave promising inhibitory activities against urease of H. pylori. Thus the results of this study delineates that inhibition of urease can ease development in therapeutic and preventative approaches based on the enzymatic activity of this Helicobacter protein.
- Full Text:
- Date Issued: 2012
- Authors: Matongo, Fredrick
- Date: 2012
- Subjects: Honey , Helicobacter pylori infections , Enzyme inhibitors , Traditional medicine , Antifungal agents
- Language: English
- Type: Thesis , Masters , MSc (Biochemistry)
- Identifier: vital:11253 , http://hdl.handle.net/10353/431 , Honey , Helicobacter pylori infections , Enzyme inhibitors , Traditional medicine , Antifungal agents
- Description: Urease of Helicobacter pylori is an important virulence factor implicated in the pathogenesis of many clinical conditions, such as chronic gastritis, peptic ulceration, and gastric cancer. Many urease inhibitors have been discovered, like phosphorodiamidates, hydroxamic acid derivatives, and imidazoles. Despite good activities at the enzyme level and excellent kinetic properties most of them have not been used as therapeutic agents in vivo because of their side effects, toxicity and instability. This has led to much attention to focus on exploring the novel urease inhibitory activities of natural products because of their low toxicity and good bioavailability. Honey, a natural product has been used in folk medicine due to its antitumor, antioxidant, antimicrobial and anti-inflammatory properties. The aims of this study were to isolate, characterise, purify urease produced by H. pylori and investigate the inhibitory effects of solvent honey extracts on its enzymatic activity. Urease was found to be both surface-associated and cytoplasmic. Maximum cytoplasmic urease activity was found to occur after 72 hr whereas maximum extracellular urease activities were found to occur after 96 hr. Characterization of the crude cytoplasmic urease revealed optimal activity at a pH of 7.5 and temperature of 40°C. The kinetic parameters Vmax and Km were 45.32 U ml-1 and 61.11 mM respectively.The honey extracts inhibited the activity of the crude urease in a concentration dependent manner. The Lineweaver-Burk plots indicated a non-competitive type of inhibition against H. pylori urease. The two honey extracts gave promising inhibitory activities against urease of H. pylori. Thus the results of this study delineates that inhibition of urease can ease development in therapeutic and preventative approaches based on the enzymatic activity of this Helicobacter protein.
- Full Text:
- Date Issued: 2012
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