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1. Ealuation Of Empitical Antibiotic Therapy In Intensive Care Unit Patients Treated For Nosocomial Lower Respiratory Tract

by Sarwat Ali Raja | Prof.Dr.Muhammad Ashraf | Dr. Aftab | Dr. Aqeel Javeed.

Material type: book Book; Format: print ; Literary form: not fiction Publisher: 2011Dissertation note: This study was designed to check the effectiveness of current empirical therapy in the treatment of a nosocomial lower respiratory tract infection in patients on mechanical ventilation caIled Ventilator associated pneumonia (YAP). To evaluate the empirical therapy, antibiotic susceptibility testing and pattern of resistance by YAP isolates in patients suspected to be suffering from YAP was determined. This was a prospective study involving 58 patients on mechanical ventilation with suspected VA.P in a tertiary care hospital. The method involved pathogen identification, Antibiotic Sensitivity testing, hepatic, renal and hematological profiles and monitoring of Arterial blood gases of the patient. Pathogens from tracheal aspirates of the patients were subjected to comrnonly used antibiotics for their antibiograms. The prescribed antibiotics were evaluated by routine culture/sensitivity testing of tracheal aspirates and each patient was followed up to be assessed for the treatment progress. Effect of Antibiotic was evaluated for seven days by recording the parameters of patients such as Temperature of the patient, Pa02, effect on leukocyte count, and from evaluation of LFTs and RFTs of the patient and the disease status of the patient. Other outcomes were the mortality in these patients and the impact of inadequate empirical therapy on patient mortality. Also to study the contribution of various risk factors upon VAP prognosis. It was inferred from the study that most of the patients remained febrile. Changes were observed in the level of liver functional enzymes and less in the values of renal functional tests. Leucocytes count in most of the patients remained either less than 4000 or greater than I 1000 indicating persistence of infection. High mortality was observed in patients suspected for YAP. Major factor that caused patients mortality was the treatment failure due to inadequate amttibiotics. Cross contamination, unhygienic practices by health personnel and lack of adequate guidelines for antibiotic utilization in the ICU were the important contributors for development ofVAP and other lower respiratory tract nosocomial infections. Methicillin sensitive Staphylococcus aureus and E.coli were found to be the most common pathogens involved. Empirical antibiotic therapy was found inappropriate in 53.4% of cases. It was inferred from the study that significant results were obtained for correlation of patient's age with treatment progress. With increase in age chances of treatment failure also increased. The risk factor showing significant result for increased treatment failure was the prior exposure to antibiotics. High patient mortality was contributed by increased treatment failure. The two most significant factors that contributed to treatment failure were either inadequate antim.icrobial therapy or use of already resistant antibiotics. It was concluded in the study, there was a high incidence of infection with resistant bacteria and inappropriate initial antibiotic therapy. Treatment failure due to inadequate antibiotics caused most mortality. Organ deterioration was also found to contribute to overall mortality in mechanically ventilated patients. Availability: Items available for loan: UVAS Library [Call number: 1324,T] (1).

2. Proteomic And Genomic Analysis Of Methicillin-Resistant Staphylococcus Aureus And Efficacy Of Indigenous Medicinal Plants Essential Oils

by Sarwat Ali Raja | Prof. Dr. Muhammad Ashraf | Dr. Tayyaba Ijaz | Dr. Aqeel Javeed | Prof. Dr. Aftab Ahmed Anjum.

Material type: book Book; Literary form: not fiction Publisher: 2015Dissertation note: A Cohort study (prospective and observational) was performed to study the prevalence of Methicillin resistant Staphylococcus aureus from the healthy individuals of community, hospitalized patients and associated health-care workers and indigenous plants essential oils were screened as new, improved & potent antibacterial/s against resistant strains of MRSA. The method involved isolation and identification of MRSA from surgical wounds of hospitalized patients & associated health care workers in a tertiary care hospital in Lahore and healthy volunteers from the community. Plant essentials oils & extracts were evaluated for their antibacterial activity against selected MRSA isolates. Oils were recovered by steam distillation using an all-glass distillation assembly. Then in vitro sensitivity and MICs of plant essential oils were determined using vancomycin and linezolid as commercial standards. The essential oils were screened further for the active constituents by column chromatography using various solvents and identification of compounds were performed by GC/MS analysis and the fractions which showed prompt results were evaluated for antimicrobial activity against the MRSA isolates in quest to find new therapeutic options. Finally effective essential oils and their active fractions were studied for their toxicity using in vitro Genotoxic assays such as Ames and Comet assays. To further ensure their beneficial effects antimutagenic effect of the essential oils were also studied. Prevalence of S. aureus among patients was 52.9%, in HCWs 86.5% and in community 74% with an overall percentage of 72.6%. Among S. aureus those declared as MRSA were 91.8% from patients, 50.6% from HCWs and 59.5% from community with an overall percentage of 62.2% MRSA. Among the isolated MRSA overall 90.6% were Coagulase positive and 75.2% were biofilm positive. SUMMARY 211 The pattern of MRSA resistance against current antibiotics have shown an overall increase in the resistance with maximum shown for lincomycin followed by tetracycline, ampicillin, fusidic acid, amoxicillin and piperacillin with tazobactam. The most effective options among current regime were tigecyclin, amikacin and meropenem showing an overall least resistance. Resistance against linezolid was observed with an overall percentage of 25.6 % and vancomycin 33.3% by disc diffusion method. The MRSA isolates resistant to one or more groups of antibiotics were declared as MDRs. Among patients and health-care workers all were declared as MDRs where as in community 93.1% isolates were MDRs. Upon Protein profiling using whole cell proteins 44 bands of the polypeptides were produced with molecular size 10-200kDa from the three sampling groups and were categorized into 5 clusters showing an overall significance correlation with each other explaining an interesting fact that all these strains were interlinked establishing the fact of flow of hospital acquired MRSA in the community and vice versa. This analysis also gave an insight in explaining the fact of horizontal transmission of infection within the hospital. Keeping in view the raise in resistance among current available antibiotics indigenous medicinal plants essential oils were screened for active constituents exhibiting anti-bacterial effects against MRSA isolates. Maximum yield was obtained from Carum copticum followed by Cuminum cyminum and minimum yield was obtained in case of Zingiber officinale. Upon qualitative analysis of all five essential oils Carum copticum essential oil showed zones of inhibition greater than the standards vancomycin and linezolid followed Cuminum cyminum and Zingiber officinale in all three SUMMARY 212 sampling groups. Anethum sowa and Myristica fragrans essential oils showed no activity against MRSA. Minimum inhibitory concentration of the three essential oils determined by micro broth dilution method indicated that Carum copticum showed least value in all three types of MRSA isolates followed by Zingiber officinale and Cuminum cyminum. Effective essential oils were further fractioned using silica gel gravity columns. All the fractions obtained were screened for the anti-bacterial activity against all three types of MRSA isolates. Only fraction F1 of Carum copticum showed activity greater than pure essential oil and the two commercial standards of vancomycin and linezolid. For the identification of active constituents GC/MS analysis was performed on all three essential oils and their respective fractions. In case of fraction F1 the most dominant constituents were Carvacrol, p-Cymene, Ʈ-Terpinene and Apiol. In other two plants none of the fractions were effective. Therefore it was concluded to use pure essential oils in case of Zingiber officinale and Cuminum cyminum rather than their individual fractions and incase of Carum copticum Fraction F1 has shown superior activity. Finally these essential oils were tested for possible mutagenic effect using bacterial reversion mutation assay and Comet assay. No mutagenic effects were observed at MIC and above doses. These effective essential oils were also evaluated for possible antimutagenic effect. Both Carum copticum and Zingiber officinale essential oils showed strong antimutagenic effects and weak antimutagenic effect by Cuminum cyminum. Upon analysis of nuclear damage none of the plants essential oils and fraction F1 of Carum copticum showed genotoxic effects and indicated to be safe. Thus from the study it was concluded that Carum copticum essential oil and its fraction F1 were the most effective to be further investigated as an alternative treatment for MRSA infections. Availability: Items available for loan: UVAS Library [Call number: 2410-T] (1).



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