Line Antibiotics Research Articles

Improving Antibiotic Prescribing for UTIs in Renal Impairment

Background: Urinary Tract Infections (UTIs) are the most common bacterial infections in the elderly. First line antibiotic therapy includes Trimethoprim and Nitrofurantoin, both of which should be used with caution in renal impairment. The project aim was to improve antibiotic prescribing in UTIs for patients with renal impairment. Methods: Initially an online questionnaire was sent to prescribers working in Forth Valley Hospital to ascertain their knowledge of antibiotic prescribing in renal failure. Quantitative data was obtained reviewing Trimethoprim and Nitrofurantoin prescriptions over 1 month (19/02/19-19/03/19) using HEPMA electronic prescribing system. These results were cross matched with patients renal function collected from SciStore database. Results: Despite 95% of medical staff having experience of prescribing in renal failure, 35% of those still did not feel confident in prescribing the correct antibiotic dosage with 90% of the opinion that prescribing guidance was necessary. Quantitative data showed that 12.9% (28/217) of patients treated with either trimethoprim or nitrofurantoin had renal impairment. Of these 79% had an Acute Kidney Injury and 71% a degree of Chronic Kidney Injury. 78% of the patients on Trimthoprim had an AKI and 38% of these developed hyperkalaemia. Those prescribed Nitrofurantoin 100% of this group had a concurrent Acute on Chronic Kidney Disease. Conclusion: 79% of patients prescribed Trimthoprim or Nitrofurantoin had a degree of renal impairment leading to potential undertreatment or renal damage in the patient. As a result NHS Forth Valley has now updated prescribing guidelines regarding UTI treatment in patients with renal impairment advising alternative antibiotic therapy.

Attenuated total reflection: Fourier transform infrared spectroscopy for detection of heterogeneous vancomycin-intermediate Staphylococcus aureus.

Staphylococcus aureus strains resistant to the last line antibiotic, vancomycin, have been of clinical concern. These include heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA. The hVISA phenotype cannot be detected by routine laboratory methods. Characterization of hVISA/VISA by new technologies is necessary to differentiate them rapidly from the vancomycin-susceptible isolates (VSSA). In this study, we developed a model for discrimination of hVISA from VSSA by using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy combined with multivariate data analysis, displaying a phenotypic signature of the bacteria. ATR-FTIR spectra were acquired from a total of 59 clinical methicillin-resistant S. aureus (MRSA) isolates comprising 28 hVISA and 31 VSSA strains. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were used to analyze 351 spectra of 39 isolates and develop a discrimination model for identifying hVISA and VSSA. The classification model, which was used for blind testing of 90 spectra from each of 10 hVISA, and 10 VSSA isolates, provided 100% sensitivity and specificity. The modeling revealed that the major discrimination between hVISA and VSSA phenotypes involved bands related to cell wall content (1087 and 1057cm-1). This study showed that ATR-FTIR technique may be an alternative method for rapid detection of low-level vancomycin-resistant S. aureus.

Neonatal Sepsis: Treatment of Neonatal Sepsis in Multidrug-Resistant (MDR) Infections: Part 2.

Sepsis is one of the major causes of neonatal deaths in India and worldwide. Pathogens encountered in neonatal sepsis vary worldwide; reports from developing countries more commonly show Gram negative organisms, most common being Acinetobacter spp., Klebsiella spp. and Escherichia coli. Recent studies show that the incidence of antimicrobial resistance, to third generation cephalosporins and carbapenems, has been on a rise. Because of widespread antimicrobial resistance, 'Higher' or 'Reserve' antibiotics are increasingly being used as first/second line antibiotics. In the past decade, there has been a resurgence in the use of colistin as a result of Extended-spectrum β-lactamase (ESBL)- producing Enterobacteriaceae and carbapenem resistant Enterobacteriaceae (CRE), which retain susceptibility only to colistin. The increasing burden of drug resistant Gram negative organisms, particularly Acinetobacter spp., Klebsiella spp., and E. coli might pose a formidable threat in coming years.

Evaluation of antibiotics use in a tertiary care pediatric intensive care and high-dependency unit

Objectives: Widespread antimicrobial use, both appropriate and inappropriate is prevalent in intensive care units (ICU) leading to antimicrobial resistance. Literature from adult ICUs revealed that 68% to 80% of patients receive antibiotics. Although less documented in pediatric intensive care units (PICU) results are similar; 56% to 100% of patients receive antibiotics. We evaluated the antibiotic usage in our PICU.Methods: This is a retrospective study carried out in pediatric intensive care and high dependency unit from September 2014 to February 2017. All case records of admitted children were analysed for antibiotic usage and categorized into no antibiotic group, 1st line antibiotic group and 2nd line antibiotic group. Rational antibiotic usage was assessed in those who received antibiotics. Antibiotic usage in major disease subgroups was assessed. All the positive cultures along with their sensitivity patterns were collected and reported. Results: Out of 1760 children no, 1st line and 2nd line antibiotics were prescribed in 882(50.1%), 794(45.1) and 84(4.78%) respectively. Most commonly used antibiotics were ceftriaxone, amoxicillin-clavulanic acid, glyopeptides and meropenem. Appropriate cultures were sent in 821(93.5%) and rational antibiotic usage was found in 825(94%). An overwhelming 63% (53/84) of patients were culture positive in 2nd line antibiotic group. A total 118 (13.4%) cultures were positive.Conclusion: We found high level of rational antibiotic usage at our centre. Strategies such as, following an evidence based antibiotic policy and empowering the designated persons for every antibiotic prescription ensures rational antibiotic usage in PICU.

Epidemiology of <i>Staphylococcus aureus</i> Infections in Kenya: Current State, Gaps and Opportunities

Staphylococcus aureus has maintained its clinical relevance as a major cause of hospital and community acquired infections globally with a high burden of antimicrobial resistance (AMR). Though reported, the burden of infection, antimicrobial resistance and molecular epidemiology of S. aureus are not well defined in Kenya. This descriptive review evaluated reported data on the detection and characterization of S. aureus infections in Kenya. Published data between 2000 and 2020 were evaluated. S. aureus isolation frequencies varied from 1% in blood specimens to 52.6% among skin and soft tissues infections while MRSA rates ranged from 1% to 84.1%. While penicillin resistance has consistently been high, last line and recent antibiotics such as vancomycin, linezolid, teicoplanin and daptomycin have retained their efficacy. Data on MRSA carriage in the community, among HCWs and inpatients is limited. Global clones (CC1, CC5, CC8, CC22, CC30, CC45 and CC239) alongside a few novel MRSA strains have been reported with staphylococcal protein A (spa) sequence based clustering yielding four major clusters (spa CC359, spa CC005, spa CC121 and spa CC021) in circulation. MRSA strain ST239/241 (t037) seems predominant in the country. Despite a clear paucity of data, the present analysis points to a high infection and AMR burden in S. aureus with global MRSA clones in circulation. Standardized national surveillance and reporting incorporating molecular tools for identification and characterization will help fill existing gaps in the understanding of the evolving epidemiology of MRSA infections.

Antibotics Which Distrbuted in the Hospital of Al Wahda (Derna, Libya) by Medical Supply Ward for 3 Months and Their Relations With Number of Patients Admitted and Compare These Antibiotics With Bacterial Culture Results Done by Laboratory

Antimicrobial resistance (and particularly antibiotic resistance) is spreading now, and there are few prospects for the development of new classes of antibiotics in the short term. However, there is today considerable awareness of the need for, and political support for, action to combat Antimicrobial resistance1. Surveillance of antimicrobial use tracks how and why antimicrobials are being used and misused by patients and healthcare providers. Monitoring antimicrobial prescription and consumption behavior provides insights and tools needed to inform therapy decisions, to assess the public health consequences of antimicrobial misuse, and to evaluate the impact resistance containment interventions2. And all reports from WHO tell us about post antibiotics era that will be start if we don’t work quickly on antibiotics resistance by all efforts and due to situations of my country in Libya now need a lot of studies to decrease corruption in budgets put for health sector. Experimental methods: Study made by pilot method and we depend on data collected from dispensing papers of medical supply ward in Al Wahda hospital. *medical statistics office of Al Wahda hospital *Al Wahda hospital laboratory. *data collected to 3 months and 477 in- patient of wahda hospital. Results and discussion: After collect data from dispensing paper that based on treatment chart, we covered 477 patients for 3 months by 2169 ceftri-702 gent-1360 aug-547 cefot-23amik. And we notice percentage of higher antibiotics use was ceftriaxone equal to 45.18 % of totality and use of broad antibiotics rather than narrow antibiotics by 84.9% ,and in all principles of clinical pharmacology direct to use narrow firstly plus first line antibiotics therapy as shown in figure 1,2 respectively. And the percentage of patients those received antibiotics that Available in hospital from all patients was 25.3% ,we found that the most higher antibiotic sensitive to bacteria was CIPRO and others appear as shown in table below where Ceftriaxone in lower rank by 2.3% as shown in figure no :3 and we found percentage of cultures done to inpatient was 28.09% to all patients’ take antibiotics and others take its blindly and we note the higher bacteria strain diagnosed was staph .c. aur and we found 70 culture tests from 134 show no bacterial growth which is shows mistake in medical requests. As shown in fig:no 4 ,then. we found the higher ward using antibiotics from all wards is FMW and this ward less one request

Comparing methods to estimate incremental inpatient costs and length of stay due to methicillin-resistant Staphylococcus aureus in Alberta, Canada

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic bacterial organism resistant to first line antibiotics. Acquisition of MRSA is often classified as either healthcare-associated or community-acquired. It has been shown that both healthcare-associated and community-acquired infections contribute to the spread of MRSA within healthcare facilities. The objective of this study was to estimate the incremental inpatient cost and length of stay for individuals colonized or infected with MRSA. Common analytical methods were compared to ensure the quality of the estimate generated. This study was performed at Alberta Ministry of Health (Edmonton, Alberta), with access to clinical MRSA data collected at two Edmonton hospitals, and ministerial administrative data holdings.MethodsA retrospective cohort study of patients with MRSA was identified using a provincial infection prevention and control database. A coarsened exact matching algorithm, and two regression models (semilogarithmic ordinary least squares model and log linked generalized linear model) were evaluated. A MRSA-free cohort from the same facilities and care units was identified for the matched method; all records were used for the regression models. Records span from January 1, 2011 to December 31, 2015, for individuals 18 or older at discharge.ResultsOf the models evaluated, the generalized linear model was found to perform the best. Based on this model, the incremental inpatient costs associated with hospital-acquired cases were the most costly at $31,686 (14,169 – 60,158) and $47,016 (23,125 – 86,332) for colonization and infection, respectively. Community-acquired MRSA cases also represent a significant burden, with incremental inpatient costs of $7397 (2924 – 13,180) and $14,847 (8445 – 23,207) for colonization and infection, respectively. All costs are adjusted to 2016 Canadian dollars. Incremental length of stay followed a similar pattern, where hospital-acquired infections had the longest incremental stays of 35.2 (16.3–69.5) days and community-acquired colonization had the shortest incremental stays of 3.0 (0.6–6.3) days.ConclusionsMRSA, and in particular, hospital-acquired MRSA, places a significant but preventable cost burden on the Alberta healthcare system. Estimates of cost and length of stay varied by the method of analysis and source of infection, highlighting the importance of selecting the most appropriate method.

160. Could Reducing Time to Bacterial Identification From Positive Blood Cultures Improve Outcomes in Bacteremic Patients?

BackgroundSurvival of patients with septic shock is dependent on the timing of effective antibiotic administration. The initial notification by the microbiology lab of a positive blood culture is a key factor in improving patient outcomes. It can take >24 hours to definitively identify bacteria from positive blood cultures. Accordingly, we employed rapid organism identification and studied the impact of this on patient management from a quality improvement perspective.MethodsRapid organism identification was performed for bacteremic patients admitted to an ICU at St. Michael’s Hospital in Toronto, ON, by creating a pellet from positive blood culture bottles using a lysis centrifugation technique. MALDI-TOF was then used to obtain an organism identification. The microbiology lab verbally notified the ward clerk of the identification and surveys were conducted with treating physicians within 24–48 hours to evaluate the downstream impact of the rapid identification including changes to antibiotics, diagnostic testing, central line management and requests for specialty consultations.ResultsBetween January 28 and April 28, 2019, 17 rapid blood culture results were included for study. When asked how physicians received the result, in 7 cases the physician did not remember; other responses included microbiology report (2), nurse (2), pharmacist (1), antimicrobial stewardship or lab (1), on-call team (1) and residents (1). Antibiotics were adjusted in 13 patients; 3 of which may have changed antibiotics for reasons other than the organism identification. Reasons for not changing therapy include: appropriate empiric treatment, likely contaminants, or physician not being notified of the result. In 5 cases, all antibiotics were discontinued, in another 2 cases the antibiotics were broadened and a further 5 narrowed to cover the organism; the remaining 5 continued the same empiric therapy. Repeat blood cultures were obtained for 5 cases, follow-up imaging in 5 cases and lines were changed/removed in 5 cases. Consultation was requested for 7 cases.ConclusionBased on preliminary data, rapid organism identification shows promise of improved patient management with line removal and antibiotics adjustments occurring 1 day sooner with rapid results.Disclosures All authors: No reported disclosures.

Current Susceptibility Trend of Antibiotics in a Tertiary Care Hospital - Need to Emphasize on Alternate Therapeutic Agents

Introduction: In the light of changing anti-microbial resistance pattern, the understanding of the local antibiogram is essential in the antibiotic selection procedures and preparation of hospital antibiotic policy.
 Aim: This retrospective study was aimed to analyze the antibacterial susceptibility pattern of major isolates from ICU and IPD.
 Materials and Methods: Antimicrobial susceptibility testing was done for a total of 565 Gram-negative isolates including E. coli, K. pnuemoniae, A. baumannnii and P. aeruginosa from ICU and IPD patients enrolled between July 2016 to December 2016.
 Results: The majority of the isolates were reported from urine samples (52%) in IPD and sputum (59%) in ICU. The susceptibility to BL/BLI was 50-75% in IPD patients and Carbapenem susceptibility was reported in more than 75% except P. aeruginosa. In ICU patients, the beta-lactam/beta-lactam inhibitor (BL/BLI) susceptibility ranged between 20-60% and the carbapenem susceptibility was around 40%-75%. The susceptibility of CSE-1034 (Ceftriaxone + Sulbactam + EDTA) was almost similar to minocycline and amikacin ranging from 50-90% against different species. Compared to carbapenems, the CSE-1034 performed overall better than carbapenems against P. aeruginosa and A. baumannii and was comparable to carbapenems against Enterobacteriaceae. The susceptibility of colistin ranged from 92-97% in both IPD and ICU isolates.
 Conclusion: Considering the value of carbapenems and colistin as the last option for multi-drug resistant (MDR) bacterial infections, irrational prescription of these drugs should be stopped. The use of ampicillin-sulbactam, cefepime and gentamicin from 1st line antibiotics in ICU patients can help to reduce the load on 2nd line antibiotics. Among 2nd line drugs, CSE-1034 along with amikacin should be an empirical choice of treatment for bacterial infections where the 1st line drugs are suspected to fail and the need of carbapenems arises.

Elucidating the Efficacy of the Bacille Calmette-Guérin Vaccination in Conjunction with First Line Antibiotics and Liposomal Glutathione.

Mycobacterium tuberculosis (M. tb) is the etiological agent that is responsible for causing tuberculosis (TB). Although every year M. tb infection affects millions of people worldwide, the only vaccine that is currently available is the Bacille Calmette–Guérin (BCG) vaccine. However, the BCG vaccine has varying efficacy. Additionally, the first line antibiotics administered to patients with active TB often cause severe complications and side effects. To improve upon the host response mechanism in containing M. tb infection, our lab has previously shown that the addition of the biological antioxidant glutathione (GSH) has profound antimycobacterial effects. The aim of this study is to understand the additive effects of BCG vaccination and ex-vivo GSH enhancement in improving the immune responses against M. tb in both groups; specifically, their ability to mount an effective immune response against M. tb infection, maintain CD4+ and CD8+ T cells in the granulomas, their response to liposomal glutathione (L-GSH), with varying suboptimal levels of the first line antibiotics isoniazid (INH) and pyrazinamide (PZA), the expressions of programmed death receptor 1 (PD-1), and their ability to induce autophagy. Our results revealed that BCG vaccination, along with GSH enhancement, can prevent the loss of CD4+ and CD8+ T cells in the granulomas and improve the control of M. tb infection by decreasing the expressions of PD-1 and increasing autophagy and production of the cytokines interferon gamma IFN-γ and tumor necrosis factor-α (TNF-α).

N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity.

Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram - Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4-8 μg/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC50 = 15 μg/mL; compound 15 IC50 = 65 μg/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design.

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records.

The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management.

Vanillin mediated green synthesis and application of gold nanoparticles for reversal of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates

Antimicrobial resistance (AMR) is a serious concern in pathogenic bacteria. As a new approach to addressing AMR, we report here the green synthesis of vanillin capped gold nanoparticles (VAuNPs) using the popular flavouring molecule vanillin (C8H8O3) as a reducing and capping agent. Physicochemical characterization revealed that the synthesised VAuNPs were stable and crystalline in nature. VAuNPs were non-bactericidal even at high concentration (>2000 μg/ml). The antibiotic potentiation activity was studied in combination with seven widely used antibiotics against extremely drug resistant (XDR) Pseudomonas aeruginosa. Major reductions in minimum inhibitory concentrations (MIC, 10–14-folds) of the antibiotics meropenem (10 fold) and trimethoprim (14 fold) were observed in the presence of VAuNPs (50 μg/ml). Furthermore, it was found that VAuNPs in combination with meropenem or trimethoprim provided 1.5–3-fold better potentiation effects than that of vanillin alone. Use of an ethidium bromide agar cart wheel assay indicated that VAuNPs can block the activity of efflux pumps. High reduction in the MIC of antibiotics was therefore attributed to the efflux pump repression activity of VAuNPs. Further, RT-qPCR of clinically relevant MexAB-OprM efflux pump components showed down-regulation in mexB and OprM transcripts in VAuNPs treated P. aeruginosa clinical isolates. Our results reveal that VAuNPs impart susceptibility to the last line antibiotics meropenem, trimethoprim and few widely used antibiotics in XDR P. aeruginosa clinical isolates that display resistance to these antibiotics. Therefore, this study indicate the ability of VAuNPs and vanillin to be used as antibiotic adjuvants for inhibiting bacterial efflux pumps to potentiate antibiotics for addressing AMR problem affecting human health and environment.

Drug Repurposing to Fight Colistin and Carbapenem-Resistant Bacteria.

The emergence of new resistance mechanisms, the failure of classical antibiotics in clinic, the decrease in the development of antibiotics in the industry are all challenges that lead us to consider new strategies for the treatment of infectious diseases. Indeed, in recent years controversy has intensified over strains resistant to carbapenem and/or colistin. Various therapeutic solutions are used to overcome administration of last line antibiotics. In this context, drug repurposing, which consists of using a non-antibiotic compound to treat multi-drug resistant bacteria (MDR), is encouraged. In this review, we first report what may have led to drug repurposing. Main definitions, advantages and drawbacks are summarized. Three major methods are described: phenotypic, computational and serendipity. In a second time we will focus on the current knowledge in drug repurposing for carbapenem and colistin-resistant bacteria with different studies describing repurposed compounds tested on Gram-negative bacteria. Furthermore, we show that drug combination therapies can increase successful by drug repurposing strategy. In conclusion, we discuss the pharmaceutical industries that have little interest in reprofiling drugs due to lack of profits. We also consider what a clinician might think of the indications of these uncommon biologists to treat MDR bacterial infections and avoid therapeutic impasses.

Rare actinobacteria: a potential source of bioactive polyketides and peptides.

Polyketides and peptides obtained from actinobacteria are important therapeutic compounds which include front line antibiotics and anticancer drugs. Many screening programs are directed towards isolation of bioactive compounds from these organisms but the chances of finding novel antimicrobial leads among common actinobacteria are fast dwindling. As a result, the focus has shifted to the members of less exploited genera of rare actinobacteria. Three isolates, MMS8, MMS16 and KCR3 found to be potent polyketide and peptide producers were identified by 16S rRNA gene sequencing and their sequences deposited in the GenBank under the accession numbers MG407702, MG372012 and MG430204 respectively. MMS8 identified as Micromonospora auratinigra, yielded one potent compound determined to be chloroanthraquinone with an minimum inhibitory concentration (MIC) of 8µg/ml against Bacillus subtilis and an IC50 value of 10µg/ml and 4μg/ml against HeLa and IMR cell lines respectively. This is the first report of the production of chloroanthraquinone by M. auratinigra. MMS16, identified as a member of the family Micromonosporaceae, yielded a potent compound MMS16B analyzed to be a novel bafilomycin analogue. The MIC of the compound was found to be 7μg/ml against B.subtilis and IC50 value against HeLa and IMR was observed to be 9μg/ml and 14μg/ml respectively. MMS16B was also found to exhibit anti-quorum sensing (AQS) activity at sublethal concentrations. KCR3 identified as Kocuria kristinae yielded a novel antimicrobial peptide with antibacterial, antifungal and AQS activity. To the best of our knowledge, no antimicrobial activity has ever been reported from K. kristinae.

Carbon-Electrode Dielectrophoresis to Identify Candida strains

Presented here is the use of 3D carbon microelectrodes in the separation of two different Candida strains using dielectrophoresis. The identification of Candida glabrata from Candida albicans has clinical relevance as front line antibiotics commonly used for Candida albicans, the most likely cause of candidiasis, are not effective to eradicate C. glabrata. Candidiasis occurs when a Candida species infiltrates the bloodstream. It is the most common bloodstream infection in the United States, and represents a significant challenge to the healthcare industry (1). While these yeast species are common inhabitants of the gastrointestinal tract and skin, they have the potential to cause infection in patients with compromised immune systems. These infections are problematic in hospitals, and have been estimated to have a mortality rate of up to 44% in some studies (2). Standard procedures following suspicion of candidiasis is the culturing of a sample for up to 1-2 days in agar followed by further testing to analyze spore formation before the species can be appropriately identified and treated (1). In the meantime, the patient is treated with a cocktail of antibiotics to target the most common pathogens. However, C. glabrata are resistant to commonly used antifungal drugs such as fluconazole (3). Hence, a rapid assay to detect the presence of Candida in a sample and further identifying the strain present can have a drastic impact on the treatment of candidiasis. This will enable timely treatment with the most suitable antibiotic, i.e. amphotericin B for C. glabrata, rather than treating the patient with a cocktail of antibiotics; an approach now leading to resistance in many Candida strains (3). Here we report the potential of dielectrophoresis to separate strains of Candida. Dielectrophoresis is an electrokinetic method that allows the dielectric properties of cells to be exploited for manipulation, isolation, and separation purposes. This is because targeted cells will display a specific response to a non-uniform electric field varying in frequency and magnitude (4). In our system, we implement the electric field gradient required for DEP using 3D carbon electrodes. When compared to traditional 2D electrodes, the use of 3D electrodes reduces the main distance from any cell flowing in the channel to the nearest electrode, thus resulting in better trapping throughput and efficiency (4). The use of carbon allows for a more robust device since carbon features a wider electrochemical stability than Au and Pt. Initial results show that different Candida strains feature a different DEP response at different frequencies (fig. 1). Using these methods of manipulation, our goal is to use this technique to devise a tool that uses the different response frequencies to separate the strains of Candida present in a sample. This could be useful in a clinical diagnostic setting for determining which strain is present to pinpoint certain interventions that are preferred for the different strains. Ongoing work is on determining the specific frequency at which one strain, and not the other, shows positive DEP as the basis of isolation. We will trap one strain on the electrode array while eluting the other one. This will allow for cell separation but also enrichment of the targeted species. Once enriched, the population concentration could be determined using optical or electrochemical means. Candidiasis affects thousands of people worldwide due to it’s resistant tendencies. A DEP-based assay to detect the cause of candidiasis will be an important tool in reducing its socioeconomic burden. Morrell M, Fraser VJ, Kollef MH. 2005. Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49:3640-3645. Almirante B, Rodriguez D, Park BJ, Cuenca-Estrella M, Planes AM, Almela M, Mensa J, Sanchez F, Ayats J, Gimenez M, Saballs P, Fridkin SK, Morgan J, Rodriguez-Tudela JL, Warnock DW, Pahissa A, Barcelona Candidemia Project Study Group. 2005. Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 43: 1829 –1835. https://doi.org/10.1128/JCM.43.4.1829-1835.2005Fidel PL, Jr, Vazquez JA, Sobel JD. 1999. Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev 12:80 –96.Martinez-Duarte, R., Renaud, P., & Madou, M. J. (2011). A novel approach to dielectrophoresis using carbon electrodes. Electrophoresis. doi:10.1002/elps.201100059 Figure 1

Bronchoalveolar lavage for etiological diagnosis of childhood pneumonia

Background: Pneumonia is the most common cause of childhood morbidity and mortality in age group less than 5 years. Identification of causative organism is a real challenge in these children though many of them are responding to the first line antibiotics therapy. Isolation of the organism is of paramount importance those who fails to respond to first line therapy. The objective of this study was to determine the relative efficacy of Bronchoalveolar Lavage (BAL) over blood culture in finding out causative organisms of childhood non responder community acquired pneumonia and to study antibiotic-sensitivity pattern of causative organisms. Methods: BAL and blood culture was performed in 17 patients of age 2 months to 5 years with pneumonia or severe pneumonia. Lavage fluid was cultured and growth of organism 10000CFU/ml was considered positive. Blood culture was taken on the same day. Antibiotic sensitivity was tested.Results: BAL isolated the organism in 82.35% (n=14) cases out of 17 patients and in 11.76% (n=2) by blood culture (p=0.002). Streptococcus pneumoniae was the most common organism isolated (58.82% (n=10)), followed by K. pneumoniae (23.53% (n=4)). Antibiotic therapy was changed in 58.82% (n=10) cases according on culture report. Transient rise in temperature, tachycardia and tachypnea was noted after procedure but no major complication was associated with BAL.Conclusions: BAL fluid culture in childhood pneumonia has high diagnostic value and better efficacy over blood culture in isolating causative organism without increased risk of complication and decreases unwanted exposure to empiric antibiotic in children with community acquired pneumonia who did not respond to initial 1st line therapy.

Prevalence and Antibiotic Susceptibility of Salmonella Species among Food Handlers in Khartoum- State (Sudan)

Aims/Objectives: To screen the prevalence of Salmonella fecal carriage among healthy foodhandlers and to identify the common species of Salmonella among study population and its antibacterial susceptibility in Khartoum state by taking stool samples.
 Study Design: Cross-sectional study.
 Place and Duration of Study: Khartoum state, Sudan, from January 2009 to December 2009.
 Methodology: Stool samples were collected, processed and cultured on suitable bacterial culture media. Presence of colonies resembling (non-lactose fermenting) Salmonella species were further studied to identify the bacterium by using appropriate biochemical tests.Confirmation and serotyping of isolates were done by using Salmonella antisera. Antibacterial susceptibility test for common antibacterial drugs were also studied.
 Results: A total of 387 stool samples collected from apparently healthy food handlers werestudied. Salmonella fecal carriage among food handlers was 17 (4.4%) and the highest prevalence was noted in Umbada locality (5.1%). Salmonella Paratyphi B was the commonest 14 (3.6%), followed by Salmonella Typhi 2(0.5%) and Salmonella Cholerasuis 1 (0.3%). Our study revealed that 141 (36.4%) of food handlers were illiterate, 29 (7.5%) werepreschool, 134 (34.6%) were elementary school graduates 68 (17.6%) and 15 (3.9%) university graduates. Forty two (10.9%) of the studied cases mentioned that, they sometimes wash their hands by soap after defecation, while, 9 (2.3%) never washed theirhands. The study also, revealed that 3 (17.6%) of positive food handlers have had history ofprevious typhoid or gastroenteritis. The study demonstrated that Salmonella species isolated were sensitive to co-trimoxazole, ciprofloxacin, chloramphenicol, tetracycline, amoxicillin/ clavulanic acid, ceftriaxone and cefuroxime.
 Conclusion: This study demonstrated the presence of considerable number of Salmonella fecal carriage among food handlers in Khartoum state. Most of them were illiterate and had poor compliance of hand washing after toilet use. Study also revealed that isolated Salmonella species were highly susceptibility to the common first line antibiotics used in Sudan.

A Clinical Prediction Tool for Extended-Spectrum Cephalosporin Resistance in Community-Onset Enterobacterales Urinary Tract Infection

BackgroundBacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to increase. We sought to create a clinical prediction tool for community-onset UTIs due to extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (formerly Enterobacteriaceae, EB).MethodsA case-control study was performed. The source population included patients presenting to an emergency department (ED) or outpatient practice with an EB UTI between 2010 and 2013. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched to cases 1:1 on study year. Multivariable conditional logistic regression was performed to develop the predictive model by maximizing the area under the receiver-operating curve (AUC). Internal validation was performed via bootstrapping.ResultsA total of 302 patients with a community-onset EB UTI were included, with 151 cases and 151 controls. After multivariable analysis, we found that presentation with an ESC-R EB community-onset UTI could be predicted by the following: (1) a history of malignancy; (2) a history of diabetes; (3) recent skilled nursing facility or hospital stay; (4) recent trimethoprim-sulfamethoxazole exposure; and (5) pyelonephritis at the time of presentation (AUC 0.73, Hosmer-Lemeshow goodness-of-fit P value 0.23). With this model, each covariate confers a single point, and a patient with ≥ 2 points is considered high risk for ESC-R EB (sensitivity 80%, specificity 54%). The adjusted AUC after bootstrapping was 0.71.ConclusionsCommunity-onset ESC-R EB UTI can be predicted using the proposed scoring system, which can help guide diagnostic and therapeutic interventions.

Safety and efficacy of current gentamicin dosing schedules used in neonates in Sri Lanka

Introduction: Gentamicin is the first line antibiotic for early onset neonatal sepsis. Yet the problem with gentamicin is the low therapeutic index. It is known that high trough levels correlate with ototoxicity and nephrotoxicity while the peak levels decide the therapeutic effect. Once daily dose (ODD) and twice daily dose (TDD) schedules are practised in neonatal units in Sri Lanka. Objectives: To assess whether the ODD and TDD schedules of gentamicin used in neonates are effective in avoiding high serum trough levels and in achieving peak serum levels in the therapeutic range. Method: A prospective study was conducted from April to August 2017 in four neonatal units on term neonates less than one week old, in whom gentamicin was started (TDD regime= 2.5 mg/kg 12 hourly and ODD regime= 5mg /kg 24 hourly) during the study period. Trough and peak serum gentamicin levels (SGLs) were assessed before and after the third dose in the TDD regime and after the second dose in the ODD regime. Serum creatinine (SCr) was measured in all the neonates and neonates with high trough levels were referred for hearing assessment. Results: A total of 50 neonates of clinical maturity 37-41 weeks and birth weight 1.8-4.1 kg was included. High trough levels (>2 mg/dl) were seen in 48% of the TDD group and in 12% of the ODD group (p=0.005) Mean trough value in the ODD group was 1.15 mg/dl (SD 0.87) and in the TDD group was 2.14 mg/dl (SD 1.72). (T=-2.564, df=35, p = 0.015). Peak SGL in the therapeutic range (5-10 mg/dl) was seen in 92% of ODD regime and in 80% of the TDD regime. Mean peak values in the ODD and TDD regimes were 9.42 (SD 2.37) mg/dl and 7.12 (SD 2.18) mg/dl respectively (T= 3.56, df=48, p = 0.001). SCr and the hearing assessment were within normal limits in all neonates. Conclusions: The ODD gentamicin schedule of 5 mg/kg achieves a significantly higher peak serum gentamicin level and safer trough levels than the TDD schedule of 2.5 mg/kg.