Diarrhea is a global concern that the United Nations Children’s Fund (UNICEF) and the World Health Organization (WHO), have confirmed to be the second major cause of death in children under the age of five. Major bacterial pathogens that cause diarrhea include Escherichia coli, Salmonella species, Shigella species and Staphylococcus aureus. Antibiotic therapy is recommended depending on the severity and presentation of the disease; however, the appearance of antibiotic-resistant bacteria is an emerging global threat to the ability to treat these bacterial infections. This situation could be overcome by the discovery of new natural antibiotics. Plants have been a source of medicine for centuries and have been used to treat diseases including diarrhea. This makes plants a natural potential target to study for their antibiotic properties. The objective of this study was to determine the antibiotic properties of medicinal plants against known pathogens that cause bacterial diarrhea. Three medicinal plants, Cassia abbreviata, Kigelia africana, and Geranium incanum were investigated for their antimicrobial properties against these strains of microorganisms: American Type Culture Collection (ATTC) and Clinical Strains (CS). The plant materials were ground into powder, which was then dissolved in methanol, acetone and distilled water to extract the active compounds. The plant extracts were then used to (i) determine their antibiotic activity, (ii) determine the minimum inhibitory concentration (MICs), (iii) analyze the thin layer chromatography (TLC) fingerprints, and (iv) analyze the autobiography assay. The results obtained in this study met the aim and objectives of this study. The antimicrobial activities of the selected plants were obtained as discussed in Chapter 2 and 3. These results indicated that the traditional plants could be used as antimicrobials. In the screening assays, the test microorganisms were inhibited by the plant extracts, when they were subjected to plant extracts. This was performed on Mueller Hinton agar as sensitivity testing, which revealed clear zones of inhibition. The MIC values for each plant extract were established which ranged from 0.101 to 13.3 mg/dl. The TLC analysis revealed the spots which contained the active compounds which inhibited the bacterial growth. A bioautography assay was performed on the TLC plates, which exposed the exact spots containing the active compound inhibiting the bacteria. These results are clearly consistent with what former scientists have observed. Detailed explanations on the results are in Chapter 3 and 4 of this paper. It is important to note that all the procedures performed in this study were in vitro assays. Some effective in vitro assay activity may not always result in the same effective in vivo activity, because some active compounds may be metabolized and degraded into inactive metabolites. For this reason, the in vitro results obtained in this study, may not reflect the true effectiveness of the compounds in in vivo trials. It is therefore advised that future scientists should take a step further in analyzing the plant extracts through in vivo assays. Further testing and study on these plants at an advanced molecular level will be beneficial in the medical fields in the search for new antibiotics to treat infectious diseases. Purification and further analysis of their products can be helpful in the production of pure natural medicines. This will discover the active ingredients and compounds responsible for inhibition of the microorganisms. This will make the compounds potential candidates for a scientific validation and analysis for future scientists to bring a new dawn in the fight against infectious diseases.

Antimicrobials are the most frequently used medications in the Neonatal Intensive Care Unit (NICU). Antimicrobial Stewardship (AMS) efforts may be used to mitigate the consequences of antimicrobial overuse while optimizing clinical outcomes through the safe, judicious use of antimicrobials. One target of AMS efforts is to reduce the incidence of necrotizing enterocolitis (NEC), a serious intestinal infection in neonates of which a necessary component is dysbiosis, the development of aberrant intestinal microbiota typically associated with prior antibiotic use. The goal of this ILE is to implement and enhance AMS efforts in the neonatal population with a focus on preventing NEC. The specific aims progress through three relevant, practical examples of AMS in a stepwise manner. Methods: In Aim 1, a systematic review of the literature evaluating the relationship between antimicrobial therapy and subsequent development of NEC and a meta-analysis including non-interventional studies was performed. Data were pooled on adjusted odds ratios (OR) and analyzed using the generic inverse variance method. All analyses were random effects models. A sensitivity analysis was performed based on a range (0-40%) of credibility ceilings. In Aim 2, institutional guidelines for early and late onset neonatal sepsis using the principles of AMS and the evidence for safe restriction of antimicrobials targeted for reduction in use in neonates by the National Healthcare Safety Network (NHSN) were created and implemented . In Aim 3, a reproducible 2-class latent variable model to extract a date-stamped diagnosis of NEC from the Pediatric Health Information System (PHIS) database was created as a tool to enhance research evaluating antibiotic use and NEC from large databases. This model was created using a subset of infants at two PHIS sites that were able to be validated. M plus software was used. Conclusions: For Aim 1, 36 studies met inclusion criteria for the systematic review, with 33 proceeding to quantitative analysis. There were 10 RCTs, the remaining being observational studies. Using the ROBINS-I or RoB 2.0 tools as appropriate, all studies including the RCTs had a least a moderate or high risk of bias respectively. The overall analysis failed to provide evidence of an association between prior antimicrobial use and NEC when all 33 studies were included, with a summary OR of 1.13, CI95 (0.88, 1.45) and significant heterogeneity, I2 = 77%. Multiple subgroup analyses were performed: “intent” of antibiotic use (prophylaxis versus not) drug delivery method (oral versus parenteral) and study type. Subgroup analysis of prophylactic enteral antibiotics showed a reduction in NEC: OR 0.2 CI95 (0.08, 0.54), I2 = 35% while prior use of parental antibiotics showed a positive association with NEC OR 1.48, CI95 (1.18, 1.86), I2 72%; for this subgroup, using a c% shows heterogeneity first reaching an estimate of 0% at a ceiling of 10% with nominal statistical significance is maintained starting at a ceiling of 10%. This shows that consideration of the biologic mechanism of the exposure-disease association, as indicated by the subgroup analyses in this study, must be considered when performing further dataset evaluations lest biased conclusions will be reached. For Aim 2, Four guidelines were created and implemented and are being validated: • The evaluation and management of infants ≥ 35 weeks gestational age at risk for early onset sepsis at Tufts Medical Center • The evaluation and management of infants ≥ 36 weeks gestational age at risk for early onset sepsis at BronxCare Hospital Center • The evaluation and management of infants < 36 weeks gestational age at risk for early onset sepsis at BronxCare Hospital Center • The evaluation and management of infants at risk for late onset sepsis at BronxCare Hospital Center For Aim 3 a model was successfully created that can be used to add an important layer of detail, time-of-event, to patient level variables in a large data set. This model can also be used to tabulate the sensitivity of a disease in the absence of a gold standard. The model is portable and could serve as a template for the PHIS or other large databases where certain important exposures may not be date stamped. The model may be adapted to not only allow for appropriate extraction of variables, but also allow the correct modelling of time-dependent co-variables.

On December 7, 1972, a hearing was held in Washington, D.C. on the use and abuse of antimicrobials. Senator Gaylor Nelson of the Sub-committee on the Monopoly of the Select Committee on Small Business stated, "Antibiotics are among the most frequently prescribed drugs in this country exceeded only by the psychoactive drugs." Dr. Charles C. Edwards, former Commissioner of the Food and Drug Administration, recognized that a problem existed and recommended the establishment of a National Task Force on the clinical use of antimicrobials (Kunin, et al., 1973). The following examples of illustrate problems the medical profession faces with antimicrobials. Of the 33 million patients discharged from general hospitals in 1972, 27% received one or more antibiotics during their hospital stay. The totals almost 9 million patients receiving antibiotics during the course of the year (McGowan, 1976). Dr. John Porterfield of JCAH recognized the Pharmacy-Therapeutics and Infection Control Committees as the formal organizational elements with the ultimate responsibility for formulating drug usage studies and overall administration of a quality assurance program. It was the opinion of Zeman et al., (1974), that in a large hospital (more than 500 beds) a separate Antibiotic Utilization Committee may more efficiently handle the volume of data and work. To implement this monitoring system, Brodie and Smith, (1976), recommended five drug utilization review principles: (1) authority, (2) operational and demographic characteristics of the delivery setting and service population, (3) knowledge of the existing pattern of utilization, (4) comparison of the later with local standards, and (5) evaluation of the impact of review on utilization patterns. Pierpaoli, et al., (1976), suggested that, conceptually a monitoring program could include utilization of retrospective and prospective chart review processes, complimented by a formal education program, and in-house controls on the use of certain antibiotics. A monitoring system could consist of evaluating antibiotics in three possible ways: (1) evaluate the usage of an antibiotic, or a family of antibiotics, in all medical-surgical cases, (2) evaluate one type of medical or surgical problem and review prophylactic and therapeutic use of all antibiotics, or (3) evaluate the usage of one antibiotic in one type of medical or surgical problem. The method of studying one antibiotic in one type of clinical condition might have some advantages since the number of variables is much smaller than either of the other two systems. I decided to use this approach and concentrate an open-heart surgery in which the cephalosporins have been used prophylactically.

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The essential oils of clove, thyme, black pepper, pimenta, origanum, garlic, onion, and cinnamon were evaluated for their effect on germination, outgrowth, growth, and toxin production of C. botulinum strains in microbiological media. The oils of clove, thyme, origanum, and cinnamon were studied for their mechanism of inhibition of C. botulinum 67B. The most effective oil, in combination with sodium nitrite at different levels was further tested against the growth and toxin production of C. botulinum (mixed types) in a meat model system. Among all the spice oils, origanum and pimenta were the most effective in inhibiting six strains of types A, B, and E of C. botulinum in prereduced PY medium. These oils at a concentration of 200 ppm completely inhibited C. botulinum growth. Garlic, onion and black pepper exhibited the lowest inhibitory activity towards the growth of C. botulinum strains. Strains of type A were more sensitive to the inhibitory action of the oils than those of types B and E. The inhibition of germination of C. botulinum by the eight spice oils indicated that garlic oil was the most potent inhibitor. Oils of pimenta, and clove were the least effective in inhibiting germination. The inhibitory effect of the oils was shown to be reversible. The oils appeared to have no significant effect on the outgrowth of the germinated spores. Nevertheless, the oils were highly active in inhibiting vegetative growth (cell division). Black pepper, clove, cinnamon, and origanum were the strongest inhibitors of vegetative growth. Yet, the oils had no direct effect on toxin production. The delay in toxin production caused by the oils was attributed to the effect of the oils on growth rather than on toxin production. Origanum oil acted synergistically with sodium nitrite in inhibiting the growth. of C. botulinum in a microbiological medium. In vacuum-packaged comminuted pork, origanum oil at 400 ppm, in combination with 50-100 ppm of sodium nitrite, significantly delayed the growth and toxin production of C.botulinum (mixed types). The probability of growth and toxin production of C. botulinum (p) in the vacuum packaged comminuted pork was calculated with Hauschild 's formula. The results showed that sodium nitrite significantly lowered p values, whereas origanum oil had very low effect on p values. / Ph. D.

by Mei Choi Tang. / Thesis submitted in 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references. / Abstract also in Chinese. / Chapter Chapter 1. --- Introduction --- p.1-22 / Chapter Chapter 2. --- PAE studies for antimicrobial combinations using the Fractional Maximal Effect method (FME method) --- p.23-64 / Chapter Chapter 3. --- Effect of sequential antibiotic administration on the postantibiotic effect exhibited by an antimicrobial combination: A case for the combination of rifampin and tobramycin against E.coli ATCC 25922 --- p.65-84 / Chapter Chapter 4. --- Effect of antimicrobial resistance to the components of an antimicrobial combination: A pilot study with piperacillin and gentamicin against Ps. aeruginosa --- p.85-100 / Chapter Chapter 5. --- Conclusions --- p.101-106 / Appendix I --- p.107-113 / Appendix II --- p.114-116 / Appendix III --- p.117-120 / Appendix IV --- p.121-138 / Appendix V --- p.139-153

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains viii, 33 p. : col. ill. Vita. Includes abstract. Includes bibliographical references (p. 26-31).