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Antibiotic Sensitivity Pattern of Blood Isolates of Acinetobacter Species in a Tertiary Care Hospital: A Retrospective Analysis

Problem statement: Multi-drug resistant Acinetobacter bacterium is one of the major causes of sepsis in ICUs in tertiary care hospitals in India. In this report we describe the antibiotic sensitivity patterns of Acinetobacter species isolated from blood over a one year period at a tertiary care hospital. Approach: We retrospectively analyzed the sensitivity pattern of Acinetobacter species isolated from blood during the period 1/6/2010 to 31/5/2011. Isolation and identification were performed using the best alert system and VITEK2 respectively. Sensitivities were determined by Kirby Bauer disc diffusion and broth dilution using VITEK2 -AST cards. Results: The total number of Acinetobacter species isolated during the study period was 72, out of which 57 (79%) were A. baumanii, 7 (9.7%) were A. Iwofii and 3 (5.2%) were A. Junii. One each from A. calcoaceticus, A. ursingii and A. denitrificans were isolated. All of the baumanii isolates were sensitive to polymyxin B and 61.4% were sensitive to tigecycline. Only 25% of the isolates in baumanii group were sensitive to meropenem and imipenem. In the non-baumanii group however, 73% were sensitive to carbapenems. Conclusion: There is a very high incidence of resistance to most antibiotics, including carbapenems. All of the Acinetobacter isolates tested are sensitive to polymyxin B. Tigecycline is the only other drug with reasonable susceptibilities, but this drug is not recommended for primary bacteriemias. If Acinetobacter sepsis is suspected, empiric therapy with polymyxins, followed by de-escalation after sensitivity results are back, is advisable.

Urine Turbidity and Microhaematuria as Rapid Assessment Indicators for Schistosoma haematobium Infection among School Children in Endemic Areas

Problem statement: Urinary schistosomiasis is highly endemic in Nigeria and for effective control measure, an efficient, quick and yet cheap diagnosis should be integrated. This will ensure the proper management of infection due to Schistosoma haematobium in low resource communities of Nigeria. Approach: This cross-sectional study recruited a total of 456 (252 males, 204 females) school children aged 3-20 years between November 2010 and June 2011. Urine samples were examined macroscopically for turbidity and subsequently screened for microhaematuria using diagnostic reagent strips. The microscopic examination of urine samples for schistosome eggs was used as the standard for diagnosis. Results: The prevalence of S. haematobium and geometric mean intensity of infection were 54.8% and 13.9 � 0.67 eggs/10 mL of urine respectively. The age and sex prevalence of urinary schistosomiasis showed no significant differences (p>0.05). The prevalences of urine turbidity and microhaematuria were 37.1 and 53.9% respectively and these varied significantly across age groups (p<0.05). The sensitivities of urine turbidity and microhaematuria used for the indirect diagnosis of urinary schistosomiasis were 54.8 and 59.3 (p>0.05) with their corresponding specificities 80.2 and 65.8% respectively. Intensity of infection was significantly correlated with the indirect diagnostic methods, urine turbidity (r = 0.203, p<0.01) and microhaematuria (r = 0.487, p<0.01). Conclusion: The possible use of urine turbidity as an indicator for rapid diagnosis of urinary schistosomiasis in low resource communities is implied.

Development of Curcumin Based Ophthalmic Formulation

Problem statement: Ophthalmic drug delivery system has been a major challenge due to the distinctive and unique anatomy of the eye. The use of phytochemicals for the application in ocular disease has not been investigated much, due to poor pharmacokinetics of phytochemical and hence poor therapeutic efficacy. Approach: Curcumin is one such phytochemical known for its medicinal properties, but its usage has been limited due to its poor bioavailability. Therapeutic ocular application of curcumin for indications such as allergic conjunctivitis and use of nanotechnology based delivery system for increasing its bioavailability haven�t been explored much. Thus the objective of current study was to develop a nanoemulsification based formulation for curcumin with enhanced bioavailability and efficacy for ophthalmic therapeutic application. Different surfactants and oils were screened based on its ability to solubilize hydrophobic curcumin for developing formulation. Ultrasonication was used for dispersion of curcumin in surfactants and nanoemulsification. Charecterization of the selected formulation was done based on particle size, Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM) analysis and tested for different physiochemcial properties. Results: A novel formulation was developed through nanoemulsification technology by ultrasonication using carefully selected nonionic surafactants. Acconon and Tween 80 were chosen after thorough screening studies. The ratio of curcumin: Acconon: Tween80: water (0.12:1:7:1) was found to be optimum for the formulation. Particle size analysis showed that the nano droplets are in the range of 8-22 nm. Further the TEM and SEM studies also confirmed that the nanodroplets are in spherical shape. Formulation was found to be stable as ascertained by phase separation and observational studies. Conclusion: The studies ensured the stability and formation of characteristic nanodroplets with curcumin entrapment as a result of the developed formulation. The so developed formulation is expected to have higher ophthalmic bioavailability, which further needs to be confirmed through in vitro and in vivo studies.

Antimicrobial-Impregnated Discs for Prevention of Intravenous Catheter-Related Infections

Problem statement: Healthcare-associated infections are the 5th leading cause of death in the United States. Catheter-Related Bloodstream Infections (CRBSIs) comprise 14% of all healthcare-associated infections and contribute to increased mortality and financial costs. Antimicrobial-impregnated sponge discs to be used surrounding the catheter insertion site are a newer addition to the options available for the prevention of catheter-related infections. Approach: This review critically appraises the literature regarding the utility of antimicrobial-impregnated discs. We performed a literature search using the MEDLINE (1948-November 2011) database. Only controlled clinical trials were included and the electronic database search was performed using the following MeSH and keyword search terms: (�Biopatch� or �chlorhexidine�) and (�dressing� or �sponge�) and (�catheter�). Results: Our search yielded eight trials. Chlorhexidine-impregnated discs are effective in preventing catheter colonization in hospitalized patients and outpatients; however, effectiveness in preventing CRBSIs may be limited to hospitalized, critically ill patients. Although many studies have evaluated the effectiveness of several pharmaceutical agents for the prevention of catheter-related infections, there are still significant gaps in the literature regarding these infections, including the effectiveness of Polyhexamethylene Biguanide (PHMB)-impregnated discs and the cost-effectiveness of PHMB-impregnated discs compared to chlorhexidine-impregnated discs. It is also unclear if antimicrobial-impregnated discs are effective in specific populations, like in outpatients, patients at high risk compared to low risk patients and patients with long-term catheters. Conclusion: Chlorhexidine-impregnated discs should be utilized for the duration of catheterization in high risk, critically ill patients and in hospitals where catheter-related infection rates are persistently high despite other preventative strategies. Futher investigation of the effectiveness of these discs in other populations and of other antimicrobial-impregnated discs is needed.

Molecular Medicine-Prospects and Challenges

Drug discovery and development is a process that rationally leads to instigation of compound or formulation for the treatment of particular disease/diseased condition by acting on its specific target (s). Most of the drugs identified by conventional drug discovery process were as a result of unsystematic, random and serendipitous approach. Enhancement of knowledge in the field of biotechnology, molecular biology and medicinal chemistry improved the basic understanding of disease mechanism, mechanism of drug action resulting in a paradigm shift in drug discovery approach towards development of targeted drug discovery. Currently, molecular medicine encompassing elucidation of the genetic basis of disease, diagnosis of the disease and the design of an appropriate approach to disease management or therapy, promises to be an effective strategy for modern drug discovery. The change in approach resulted in improvement in target innovation, however doesn�t impact the rate of NMEs approved. The challenges limiting the drug discovery and prospects offered by molecular medicine and reverse pharmacology for its improvement were discussed in this review.

In Silico, In Vitro and In Vivo Assessment of Safety and Anti-inflammatory Activity of Curcumin

Problem statement: Curcumin the active component of turmeric is known for its wide biological actions. Extensive studies on curcumin highlighted its anti-inflammatory, anti-oxidant, anti-microbial, anti-carcinogenic and anti-coagulant activity. The anti-inflammatory activities of curcumin have been demonstrated both in vitro and in vivo. Though curcumin and its anti-inflammatory properties are well documented, the exact mechanism of action and effective in vivo dosage required for potential anti-inflammatory activity of curcumin are yet to be determined. The current work reflects in identfying the the role curcumin in the inflmmatory cascade and arriving at an optimal effective dose (ED₅₀). Approach: The objective of the current study is to understand and establish the role of curcumin in the treatment of inflammatory condition, through in-silico, in-vitro and in-vivo studies. The specificity and binding affinity of curcumin to major inflammatory mediators such as, cytokines/chemokines, signaling proteins and transcription factors were evaluated using molecular docking. Subsequently, in-vitro experiments were conducted to establish the role of curcumin in reducing the release of histamine and β-hexosaminidase form U937 human monocytes cell lines. Further, the Effective Dose (ED₅₀) of curcumin was established for its potent in vivo anti-inflammatory activity. Results: Our study confirmed a strong affinity of curcumin to various inflammatory mediators (ERK, PKC, P38 MAP Kinase, NFkB and Lipoxygenase). Curcumin when studied for its affinity towards chemokines/cytokines and TNF-α was found to be ineffective. Proportionate reduction in histamine and β-hexosaminidase release in U937 cells in vitro and inhibition of paw edema in carrageenan induced inflammation in rats affirmed the dose dependent anti-inflammatory activity of curcumin. This in vivo study elucidated the ED₅₀ value to be 570.6 mg kg^-1 body weight for curcumin, which apparently shall be the potent dose to screen its anti-inflammatory activity. Conclusion: Overall results suggest that, curcumin mediates its anti-inflammatory activity by its direct effect on multi-target inflammatory mediators while others were mediated by the downstream effects of curcumin. Curcumin can be a potent molecule in treatment of various diseases associated with inflammation, with its multi-target potency and high safety profile.

Assessment of Cardio-Metabolic Risk Factors among Young Adult Females

Problem statement: Over the past two decades there has been a striking increase in the number of people with metabolic syndrome in developing countries. The current study was thus undertaken to map the prevalence of Metabolic Syndrome (MS) and to assess the cardio-metabolic risk factors among young adult females (n = 1303) aged 18-26y from four girls hostel of the Maharaja Sayajirao University of Baroda. Approach: The anthropometric analysis showed a high prevalence of overweight/obesity (20.8%), abdominal obesity (12.7%) among the subjects. The clinical profile revealed that 12.1% were hypertensives. The prevalence of dyslipidemia revealed that no one had hypercholesterolemia and 4.1% had hypertriglyceridemia, 12.1% had elevated LDL-C and 40.3% had low levels of HDL-C. The prevalence of metabolic syndrome was 2.4 and 4.1% according to the International Diabetes Federation (IDF) and World Health Organization (WHO) criteria respectively. Lipid profile in relation to metabolic syndrome showed that VLDL-C and Triglyceride (TG) values were non-significantly higher among the young adult females and HDL-C values were significantly (p<0.001) lower among those subjects who had metabolic syndrome. The mean C-Reactive Protein (CRP) level of the study subjects was found to be in normal range, except for 10.5% who had elevated CRP levels. A high prevalence of multiple risk factors seen among the subjects like low fruits and vegetable consumption, sedentary lifestyle, hypertension, obesity. Results: The three common and predominant risk factors (>80%) identified were lower intake of fruits (81.5%), vegetables (96%) and physical inactivity (88.7%). The other risk factors which were present between 30-50% were hypertension, lower HDL-C, Body Mass Index (BMI) and Waist Circumference (WC). Among the non-modifiable factor heredity component was present in 34% of the subjects. Conclusion: The study highlights that lifestyle factors had equivalent risk for overweight and metabolic syndrome. Multiple risk factor scenario calls for lifestyle management to avert later consequences.

Nutritional Status and Quality of Life of Women with HIV/AIDS

Problem statement: HIV infection is a multisystem disorder which causes chronic infections that lead to profound immune- suppression. Women have always been a vulnerable section of the society. They are doubly vulnerable due to the HIV and malnutrition vicious cycle, which may affect their Quality Of Life (QOL). There are different literature reviews which suggest under-nutrition, wasting due to HIV but it is important to know whether this under-nutrition affects their Quality Of Life (QOL) of these vulnerable women. Approach: This cross sectional study recruited female patients on antiretroviral therapy. Weight, height, grip strength, Tricep Skin Fold (TSF) and Mid Upper Arm Circumference (MUAC) were measured. Nutrient intake was calculated by 24 h recall and food frequency questionnaire. WHO QOL-HIV BREF was used to assess QOL. Results: Among 55 patients, 32 (58.2%), 23 (41.8%) were asymptomatic and symptomatic respectively. The mean adequacies of energy and protein for all the subjects were 57.56 � 21.89, 61.27 � 28.50 percent respectively. The Body Mass Index (BMI) of the symptomatic were significantly (p = 0.009) lower than the asymptomatic subjects, the mean being 19.84 � 3.6 (kg/m�), with 27.3% having BMI < 18.5 (kg/m�). The mean TSF, MUAC, grip strength and hemoglobin level were 10.66 � 4.36 mm, 23.72 � 3.43 cm, 16.12 � 5.03 kg force and 10.8 � 1.3g/dl respectively. The scores of QOL were correlated positively with all the parameters of nutritional status. Grip strength and hemoglobin level were significantly correlated (p = 0.01) with the scores of four and five domains of QOL respectively. Conclusion: Dietary intake was inadequate, which affected the nutritional status. Conservation of muscle mass and maintenance of hemoglobin levels may improve QOL in HIV infected women. Thus there is a need for nutritional counseling and other nutritional intervention.

Study on Survival of Chlamydia trachomatis in the Presence of Antichlamydial Drugs

Problem statement: Recurrent genital Chlamydia trachomatis infections due to treatment failures may results in complex sequelae leading to reproductive complexity and morbidity. It can be resulted by the heterotypic resistance with decreased drug susceptibility characteristic of the isolate. Studies are needed to understand the treatment failures and resistance characteristic of C. trachomatis. Hence, in vitro study was conducted on C. trachomatis isolate in the presence of antichlamydial drugs. Approach: Our aim was to study ygeD gene in C. trachomatis clinical isolate having decreased drug susceptibility profile and to analyze HeLa cells phenotypically upon infection in presence of antichlamydial drugs. Sequencing was done to check any mutational change (s) in ygeD gene of C. trachomatis isolate (CT-244), mRNA expression was analyzed in presence of antichlamydial drugs by Real Time RT-PCR. Transduction study was carried out in infected HeLa cells to detect changes at cellular level in presence of antichlamydial drugs by transducing with GFP/RFP-tagged proteins and analyzed by FACS. Results: A point mutation was detected in ygeD gene of C. trachomatis isolate. Further, mRNA expression level of ygeD gene was observed to be increased at 8 hpi in presence of doxycycline while in presence of azithromycin it was increased at 24 hpi. GFP-tagged plasma membrane protein expression in infected HeLa cells found to be reduced as compare to the uninfected cells. Upon infection, the RFP-tagged actin protein expression was up-regulated in comparison to the uninfected HeLa cells. No difference in expression of plasma membrane and actin protein was observed in susceptible serovar D and CT-244 isolate. Conclusion: The present study suggest that C. trachomatis isolate with decreased drug susceptibility profile may have an active efflux strategy for its survival in the presence of antichlamydial drugs and it may not affect its host cell plasma membrane or actin organization for its survival in order to resist the antichlamydial drugs.

Comparing of Routine 2 Mercaptoethanol (2ME) and Coombs Wright Plus 2ME

Problem statement: Serologic tests like Wright, Wright containing Anti-human globulin (Coombs Wright) and 2ME are the main methods of diagnosing brucellosis. The routine method of using Wright test and then performing 2ME is not enough sensitive to diagnose brucellosis. The goal of this study is to compare the results of routine 2ME with 2ME on serum containing antihuman globulin (Coombs Wright+2ME). Approach: In this study 100 patients with brucellosis were evaluated. The serums of these patients were tested using routine 2ME and Coombs Wright with adding 2ME. Then the results of these tests were compared. Sensitivity and Specificity of these two methods were also calculated. Results: The sensitivity of routine 2ME was 52%. The sensitivity of 2ME Plus Coombs Wright was calculated as 97%. Sensitivity and Specificity of routine 2ME method against Coombs Wright plus 2ME method were respectively 53% (54-51: CI) and 75% (95-31: CI). Conclusion: According to the results, Coombs Wright plus 2ME can be used for negative 2ME test patients in order to follow up their response to treatment. In addition, it is not necessary to do Wright test and routine 2ME and instead of them, Coombs Wright plus 2ME can be used.