Prevalence Of Antibiotic Resistant Strains Research Articles

In silico identification of novel antimicrobial peptides from the venom gland transcriptome of the spider Argiope bruennichi (Scopoli, 1772).

As the emergence and prevalence of antibiotic-resistant strains have resulted in a global crisis, there is an urgent need for new antimicrobial agents. Antimicrobial peptides (AMPs) exhibit inhibitory activity against a wide spectrum of pathogens and can be utilized as an alternative to conventional antibiotics. In this study, two novel AMPs were identified from the venom transcriptome of the spider Argiope bruennichi (Scopoli, 1772) using in silico methods, and their antimicrobial activity was experimentally validated. Aranetoxin-Ab2a (AATX-Ab2a) and Aranetoxin-Ab3a (AATX-Ab3a) were identified by homology analysis and were predicted to have high levels of antimicrobial activity based on in silico analysis. Both peptides were found to have antibacterial effect against Gram-positive and -negative strains, and, in particular, showed significant inhibitory activity against multidrug-resistant Pseudomonas aeruginosa isolates. In addition, AATX-Ab2a and AATX-Ab3a inhibited animal and vegetable fungal strains, while showing low toxicity to normal human cells. The antimicrobial activity of the peptides was attributed to the increased permeability of microbial membranes. The study described the discovery of novel antibiotic candidates, AATX-Ab2a and AATX-Ab3a, using the spider venom gland transcriptome, and validated an in silico-based method for identifying functional substances from biological resources.

Modelling of AgrA inhibitors to combat anti-microbial resistance in Staphylococcus aureus

Staphylococcus aureus is a Gram-positive bacterium found on human skin that causes skin and soft tissue infections, as well as pneumonia, osteomyelitis, and endocarditis. The prevalence of antibiotic resistant strains has made the treatments less effective. An efficient alternate method for battling these contagious diseases is anti-virulence strategy. The AgrA protein, a key activator of Accessory Gene Regulator system in S. aureus, is vital to the virulence of the organism and, consequently, its pathogenesis. Using a Machine Learning algorithm, the Support Vector Machine (SVM), and a ligand-based pharmacophore modelling method, prediction models of AgrA inhibitors were developed. The metrics of the SVM model were inadequate, hence it was not used for virtual screening. For ligand-based pharmacophore modelling, 14 of 29 compounds were removed from the active set due to a lack of shared pharmacophore properties, and 504 compounds were designated as decoys. A 3D pharmacophore model was created using LigandScout 4.4.5, with a fit score of 57.48, including a positive ionizable group, one hydrogen bond donor, and three hydrogen bond acceptors. The model after further validation was used to virtually screen an external database which resulted in six hits. These compounds were docked with the AgrA domain crystal structure to determine the inhibitor activity. Further, each docked complex was subjected to a 100 ns molecular dynamics simulation. CID238 and CID20510252 demonstrated potent inhibitory binding interactions and hence can be used to develop AgrA inhibitors in future after proper validation. Communicated by Ramaswamy H. Sarma

Antibiotic Resistance and Genetic Variability of Acinetobacter spp. from Wastewater Treatment Plant in Kokšov-Bakša (Košice, Slovakia).

This study investigated the genetic variability and antibiotic resistance of Acinetobacter community depending on the stage of wastewater treatment in Kokšov-Bakša for the city of Košice (Slovakia). After cultivation, bacterial isolates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and their sensitivity to ampicillin, kanamycin, tetracycline, chloramphenicol and ciprofloxacin was examined. Acinetobacter spp. and Aeromonas spp. dominated bacterial populations in all wastewater samples. We identified 12 different groups based on protein profiling, 14 genotypes by amplified ribosomal DNA restriction analysis and 11 Acinetobacter species using 16S rDNA sequence analysis within Acinetobacter community, which showed significant variability in their spatial distribution. While Acinetobacter population structure changed during the wastewater treatment, the prevalence of antibiotic-resistant strains did not significantly vary depending on the stage of wastewater treatment. The study highlights the role of a highly genetically diverse Acinetobacter community surviving in wastewater treatment plants as an important environmental reservoir assisting in the further dissemination of antibiotic resistance in aquatic systems.

Clinico-bacteriological profile and antibiotic resistance pattern in patients with acute exacerbation of COPD

BackgroundRepeated attacks of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have been attributed to bacterial infections. However, sputum microbiology for identifying the bacteriological profile is not performed usually and remains controversial. Thus, we performed a prospective, cross-sectional study to assess the clinico-bacteriological profile of the patients with AECOPD and antibiotic resistance pattern of bacteria isolated from sputum samples. The study involved 104 consecutive hospitalized patients, of either gender, aged 40–90 years, and diagnosed with AECOPD. Before initiating an empirical antibiotic therapy, the sputum samples of all the patients were collected and subjected to Gram staining, bacterial culture, and antibiotic sensitivity.ResultsThe most common bacterial isolates were P. aeruginosa (30.7%) followed by K. pneumoniae (20.3%) and S. pneumoniae (8.6%). Both Gram-positive and Gram-negative bacteria were most sensitive to Meropenem (91%) followed by Amoxicillin-clavulanic acid (83%). However, these bacteria were most resistant to Cefoperazone-sulbactam (43%) followed by Levofloxacin (41%). P. aeruginosa and K. pneumoniae were most resistant to Cefoperazone-sulbactam (23%) followed by Fluoroquinolones (23–35%), while S. pneumoniae was most resistant to Ciprofloxacin (44%) followed by Amoxicillin-clavulanic acid (33%).ConclusionsIsolation of P. aeruginosa, as the most common agent, further confirms its roles in severe attacks of AECOPD. The regularly used antibiotics were found to be resistant to most isolates, thereby suggesting that severity of AECOPD may be attributed to the prevalence of antibiotic-resistant strains.

PECULIARITIES OF DISTRIBUTION OF ANTIBIOTIC RESISTANT STRAINS OF E. COLI - E. FAECALIS ASSOCIATION IN THE UROGENITAL TRACT OF PREGNANT WOMEN

The aim: To investigate the prevalence of antibiotic-resistant strains from the association of E. coli - E. faecalis in the urogenital tract of pregnant women. Materials and methods: Used bacteriological method of sectoral culture of urine on nutrient media and identification of strains to the species. The susceptibility of strains to antibiotics was determined by disk-diffusion method, the interpretation of results - according to current EUCAST recommendations. Statistical processing was performed in MS Excel (Analysis of variance (ANOVA)). Results: The number of resistant to cefuroxime, cephalexin, nitrofurantoin, norfloxacin and trimethoprim uropathogenic strains of Escherichia coli does not change depending on the monostrain and associated strain of E. coli from the urine of pregnant women in Dnipro. It was found that the differences in the number of fosfomycin-resistant uropathogenic strains of E. coli depending on the type of culture - the number of fosfomycintolerant urostrains E. coli is 2 times higher among the associated strains, compared with monostains of the studied microorganism. The number of uropathogenic strains of E. faecalis resistant to ampicillin, trimethoprim, nitrofurantoin and norfloxacin does not change depending on the type of culture isolated from the urine of pregnant women in Dnipro. Conclusions: The symbiotic type of existence of two representatives of the normal intestinal flora on the uroepithelium of pregnant women may be associated with the development of Escherichia coli antibiotic resistance only to fosfomycin compared with monoinfection caused by each of these microorganisms.

Characterization and Inhibition of 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase: A Promising Drug Target in Acinetobacter baumannii and Klebsiella pneumoniae.

The ESKAPE pathogens comprise a group of multidrug-resistant bacteria that are the leading cause of nosocomial infections worldwide. The prevalence of antibiotic resistant strains and the relative ease by which bacteria acquire resistance genes highlight the continual need for the development of novel antibiotics against new drug targets. The methylerythritol phosphate (MEP) pathway is an attractive target for the development of new antibiotics. The MEP pathway governs the synthesis of isoprenoids, which are key lipid precursors for vital cell components such as ubiquinone and bacterial hopanoids. Additionally, the MEP pathway is entirely distinct from the corresponding mammalian pathway, the mevalonic acid (MVA) pathway, making the first committed enzyme of the MEP pathway, 1-deoxy-d-xylulose 5-phosphate reductoisomerase (IspC), an attractive target for antibiotic development. To facilitate drug development against two of the ESKAPE pathogens, Acinetobacter baumannii and Klebsiella pneumoniae, we cloned, expressed, purified, and characterized IspC from these two Gram-negative bacteria. Enzyme inhibition assays using IspC from these two pathogens, and compounds fosmidomycin and FR900098, indicate IC50 values ranging from 19.5–45.5 nM. Antimicrobial susceptibility tests with these inhibitors reveal that A. baumannii is susceptible to FR900098, whereas K. pneumoniae is susceptible to both compounds. Finally, to facilitate structure-based drug design of inhibitors targeting A. baumannii IspC, we determined the 2.5 Å crystal structure of IspC from A. baumannii in complex with inhibitor FR900098, and cofactors NADPH and magnesium.

Antimicrobial susceptibility of Salmonella spp.isolated from raw meats at traditional markets in Ho Chi Minh city

The study’s results on a total of 380 fresh samples of raw meat (pork, beef, chicken) randomly collected at conventional markets of districts in Ho Chi Minh city showed that the prevalence of Salmonella spp. is 42.37%. The prevalence of Salmonella in pork, chicken, and beef were 50.00%, 49.62%, and 26.83%, respectively. The proportion of Salmonella strains that resisted at least 1 antibiotic was 37.89%, from 2 to 5 antibiotics was 22.98%, and from 6 to 11 antibiotics occupied 8.70%, mainly for β-lactams, Tetracyclin, Chloramphenicol, Streptomycin, and Sulfamethoxazole/Trimethoprim antibiotics. In particular, up to 83.72% of the Salmonellastrains carry antibiotic resistance genes (mainly isolated from pork). In antibiotic-resistant Salmonella strains, the sul1, cmlA, tetA, sul2, cmlB genes were detected with the rates of 27.90, 23.26, 21.74, 9.30, and 5.59%, respectively. Salmonella strains carrying genes encoding ESBL in the TEM group were 58.14% and 9.30% in the CTX group. This data provided more direct evidence of Salmonellacontamination in food and the prevalence of antibiotic-resistant strains in Ho Chi Minh city. Therefore, there is an urgent need to establish programs to monitor and control Salmonella and the use of antibiotics in Vietnam to protect the health of consumers.

A Biological Inventory of Prophages in A. baumannii Genomes Reveal Distinct Distributions in Classes, Length, and Genomic Positions.

Acinetobacter baumannii is of major clinical importance as the bacterial pathogen often causes hospital acquired infections, further complicated by the high prevalence of antibiotic resistant strains. Aside from natural tolerance to certain antibiotic classes, resistance is often acquired by the exchange of genetic information via conjugation but also by the high natural competence exhibited by A. baumannii. In addition, bacteriophages are able to introduce resistance genes but also toxins and virulence factors via phage mediated transduction. In this work, we analyzed the complete genomes of 177 A. baumannii strains for the occurrence of prophages, and analyzed their taxonomy, size and positions of insertion. Among all the prophages that were detected, Siphoviridae and Myoviridae were the two most commonly found families, while the average genome size was determined to be approximately 4 Mbp. Our data shows the wide variation in the number of prophages in A. baumannii genomes and the prevalence of certain prophages within strains that are most “successful” or potentially beneficial to the host. Our study also revealed that only two specific sites of insertion within the genome of the host bacterium are being used, with few exceptions only. Lastly, we analyzed the existence of genes that are encoded in the prophages, which may confer antimicrobial resistance (AMR). Several phages carry AMR genes, including OXA-23 and NDM-1, illustrating the importance of lysogenic phages in the acquisition of resistance genes.

Bacterial Membrane Selective Antimicrobial Peptide-Mimetic Polyurethanes: Structure-Property Correlations and Mechanisms of Action.

The rise in prevalence of antibiotic resistant strains of bacteria is a very significant challenge for treating life-threatening infections worldwide. A source of novel therapeutics that has shown great promise is a class of biomolecules known as antimicrobial peptides. Previously, within our laboratories, we developed a new family of water-soluble antimicrobial polyurethanes that mimic antimicrobial peptides. Within this current investigation, studies were carried out to gain a greater understanding of the structure/property relationships of the polyurethanes. This was achieved by synthesizing a variety of pendant group functionalized polyurethanes and testing their effectiveness as an antimicrobial by carrying out minimum inhibitory concentration testing and determining their compatibility with blood cells. Additionally, insight into the mode of action of the polyurethanes was obtained through experiments using dye encapsulated phospholipids and assays of bacterial cells that indicated the ability of the polyurethanes to penetrate and disrupt membranes. Collectively, the results indicate that the addition of hydrophobic, uncharged polar, and anionic moieties do not have a strong influence on the antimicrobial activity; yet, the addition of hydrophobic groups enhances cytoplasmic membrane disruption, a larger proportion of cationic pendant groups promotes greater outer membrane disruption of Gram negative bacteria, and uncharged polar groups and anionic groups improve compatibility of the polyurethanes with mammalian cells.

Prevalence of antibiotic resistant mastitis pathogens in dairy cows in Egypt and potential biological control agents produced from plant endophytic actinobacteria.

Dairy production is threatened by antibiotic resistant pathogens worldwide, and alternative solutions to treat mastitis are not available. The prevalence of antibiotic resistant strains is not well known in less developed countries. The prevalence of pathogenic bacteria and their resistance to 21 commercial antibiotics were studied in milk samples taken from 122 dairy cows suffering from the symptoms of mastitis in Egypt. The bacterial species were identified with molecular methods, and antibiotic resistance was studied with disc diffusion method. The prevalence of Streptococcus aureus, Escherichia coli and Pseudomonas aeruginosa were 30%, 17% and 3.5%, respectively. Most (90%) of the S. aureus strains showed resistance to penicillin whereas only 10% of the strains were resistant to oxacillin. Nearly half (40%) of E. coli strains showed resistance to streptomycin. Six P. aeruginosa strains showed resistance to several antibiotics, including ceftriaxone, enrofloxacin and levofloxacin. This points out that despite P. aeruginosa was not common, it should be followed up carefully. Potential biocontrol agents against antibiotic resistant mastitis bacteria were searched among 30 endophytic actinobacterial strains derived from wild medicinal plants. Three plants, namely Mentha longifolia, Malva parviflora and Pulicaria undulata were chosen for a more detailed study; their endophytic actinobacteria were used to prepare metabolic extracts. The crude metabolites of the actinobacteria were extracted with ethyl acetate. All metabolic extracts inhibited the growth of S. aureus, methicillin-resistant Staphylococcus aureus (MRSA), E. coli and P. aeruginosa in vitro. The 16S rRNA sequence analysis revealed that the most efficient actinobacterial strains were two Micromonospora sp. and one Actinobacteria bacterium. We conclude that the combination of the metabolites of several endophytic actinobacteria derived from several medicinal plants would be the most efficient against pathogens. Different metabolite cocktails should be studied further in order to develop novel biocontrol agents to treat antibiotic resistant mastitis bacteria in dairy cows.

Comparative Genomics and Phenotypic Investigations Into Antibiotic, Heavy Metal, and Disinfectant Susceptibilities of Salmonella enterica Strains Isolated in Australia.

Salmonella enterica is recognized as a major contributor of gastrointestinal illness worldwide. Concerns have been raised over the increasing prevalence of antibiotic resistant strains of Salmonella isolated from animals and food, and the role of antibiotics and other antimicrobial agents such as biocides and heavy metals in the selection and dissemination of antibiotic resistant bacteria to human hosts. In this study the antibiotic, heavy metal and disinfectant resistance genotypes and phenotypes of 19 S. enterica isolates from food-producing animals were established using whole genome sequence analysis, disc diffusion, as well as broth or agar dilution methods. This study also investigated the genomic environment of resistance genes on mobile genetic elements and chromosomal DNA. An ampicillin and streptomycin resistant S. Infantis isolate in this study harbored a β-lactamase (blaTEM–1), and two streptomycin resistance conferring genes (strA and strB) on a class 1 integron mobilized on a large conjugative plasmid. This plasmid also harbored two arsenic resistance gene cassettes. The arsenic resistance cassette, arsRCDAB, was also observed in two S. Singapore isolates with high tolerance to arsenate. A nalidixic acid resistant S. Typhimurium isolate was found to possess a mutation in gyrA resulting in amino acid change Asp87Gly and tetracycline resistant S. Typhimurium isolate was found to harbor efflux pump gene, tetA. No resistance (genotypic or phenotypic) was recorded to the disinfectants screened in this study. Taken together, results of this study showed a good correlation between predicted and measured resistances when comparing genotypic and phenotypic data, respectively. The findings of this study do not suggest resistance to clinically relevant antibiotics are widespread among Salmonella isolated from Australian food-producing animals.

Neonatal sepsis due to ESBL producing Klebsiella

Neonatal sepsis due to ESBL producing Klebsiella - IJMR- Print ISSN No: - 2394-546X Online ISSN No:- 2394-5478 Article DOI No:- 10.18231/j.ijmr.2019.024, Indian Journal of Microbiology Research-Indian J Microbiol Res

Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics.

Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Due to the prevalence of antibiotic resistance, and the current limitations on antibiotic development, an active and highly promising avenue of research has been to develop strategies to specifically inhibit the activity of virulence factors produced S. aureus as an alternative means to treat disease. In this review we specifically highlight several major virulence factors produced by S. aureus for which recent advances in antivirulence approaches may hold promise as an alternative means to treating diseases caused by this pathogen. Strategies to inhibit virulence factors can range from small molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence proteins. The major prevalence of antibiotic resistant strains of S. aureus combined with the lack of new antibiotic discoveries highlight the need for vigorous research into alternative strategies to combat diseases caused by this highly successful pathogen. Current efforts to develop specific antivirulence strategies, vaccine approaches, and alternative therapies for treating severe disease caused by S. aureus have the potential to stem the tide against the limitations that we face in the post-antibiotic era.

EPIDEMIOLOGICAL ASSESSMENT OF RISK FACTORS FOR PREVALENCE OF ANTIBIOTIC-RESISTANT STRAINS OF UPPER AIRWAYS AND ENT-ORGANS INFECTIOUS PATHOGENS IN CHILDREN

Aim. To give epidemiological assessment of potential risk factors for prevalence of antibiotic resistant strains of upper airways and ENT-organs infectious pathogens in children. Materials and methods. The study included children (165 persons) aged 1 to 17years, who asked for ambulatory-polyclinic medical care in connection with upper airways and ENT-organs diseases and formed the group of “cases” (75 persons) - patients, colonized by Streptococcus spp. and Staphylococcus aureus strains with antibiotic resistance not less than one of three classes (beta-lactams, macrolides, lincosamides) and the control group (90 persons) - patients without the facts of colonization by antibiotic-resistant strains of the studied microorganisms. During doctor’s reception, parents of all patients were surveyed. Results. According to the results of a survey carried out, there was estimated connection of 18 potential risk factors with carriage of antibiotic-resistant strains. Pneumococcal vaccination in the investigated population was a factor, rendering preventive effect on the colonization rate of antibiotic-resistant strains Streptococcus spp. and Staphylococcus aureus ( OR = 0,40 [95 %DI 0,19-0,86]). At the same time, no ties between colonization by antibiotic-resistant microorganisms and risk factors, connected with previous use of antibiotics, especially without doctor’s administration, was noted. Conclusions. Vaccination with pneumococcal vaccines in the studied population is a factor, controlling prevalence of resistance to antimicrobial drugs

Binary mixture of Satureja hortensis and Origanum vulgare subsp. hirtum essential oils: in vivo therapeutic efficiency against Helicobacter pylori infection.

Helicobacter pylori can cause many gastrointestinal and also extra-gastrointestinal disorders and is a major risk factor for gastric carcinoma and MALT lymphoma. Currently, numerous antibiotic-based therapies are available; however, these therapies have numerous drawbacks, mainly due to increasing prevalence of antibiotic resistant strains. Thus, there is an urgent need to develop novel therapeutic agents against H.pylori infections. In this study, the anti-H.pylori activity of 2:1 mixture of Satureja hortensis and Origanum vulgare subsp. hirtum essential oils (2MIX) was investigated in vivo. After screening in vitro cytotoxicity of 2MIX on mammalian cell lines, the therapeutic efficiency was studied in a mouse model, where changes in H.pylori colonization were detected by PCR and histology of gastric samples. The immune reaction of mice was tested based on cytokine and chemokine production, and the in vivo toxicity of 2MIX was also investigated by measuring ALT and AST enzyme activities and Cyp3a11 and HO-1 mRNA levels in livers of mice. 2MIX had not shown in vitro cytotoxicity against cell lines, only the highest concentration caused significant decrease in their survival rates. In the in vivo experiments, 2MIX successfully eradicated the pathogen in 70% of the mice. We could not detect toxicity or altered cytokine and chemokine balance after in vivo treatments in mice. These results show that 2MIX is effective in reducing H.pylori colonization suggesting that this essential oil mixture has great potential as a new, effective, and safe therapeutic agent against H.pylori.

Characterization of Enterococcus faecium bacteriophage IME-EFm5 and its endolysin LysEFm5

Due to the worldwide prevalence of antibiotic resistant strains, phages therapy has been revitalized recently. In this study, an Enterococcus faecium phage named IME-EFm5 was isolated from hospital sewage. Whole genomic sequence analysis demonstrated that IME-EFm5 belong to the Siphoviridae family, and has a double-stranded genome of 42,265bp (with a 35.51% G+C content) which contains 70 putative coding sequences. LysEFm5, the endolysin of IME-EFm5, contains an amidase domain in its N-terminal and has a wider bactericidal spectrum than its parental phage IME-EFm5, including 7 strains of vancomycin-resistant E. faecium. The mutagenesis analysis revealed that the zinc ion binding residues (H27, H132, and C140), E90, and T138 are required for the catalysis of LysEFm5. However, the antibacterial activity of LysEFm5 is zinc ion independent, which is inconsistent with most of other amidase members. The phage lysin LysEFm5 might be an alternative treatment strategy for infections caused by multidrug-resistant E. faecium.

Heterologous expression and purification of biologically active domains 3 and 4 of human polymeric immunoglobulin receptor and its interaction with choline binding protein A of Streptococcus pneumoniae

Streptococcus pneumoniae, one of the common causes of pneumonia, colonises the epithelium via the interaction between a choline binding protein of S. pneumoniae and the human polymeric immunoglobulin receptor (pIgR). One of the functions of pIgR is to mediate the transcytosis of polymeric immunoglobulins from the basolateral to the apical surface of epithelial cells. S. pneumoniae invades human epithelial cells by exploiting the transcytosis machinery. Due to an increase in the prevalence of antibiotic resistant strains of S. pneumoniae, and the limitations and expense of the vaccines available, extensive research may provide insights into the potential of new therapeutic regimes. This study investigated the potential of pIgR domains as an alternative non-antibiotic immune therapy for treating pneumonia. The aim was to determine the binding affinity of recombinant D3D4 protein, the domains of pIgR responsible for binding S. pneumoniae, to recombinant R1R2 repeat domains of choline binding protein A of S. pneumoniae. Biologically active recombinant D3D4 was produced in Escherichia coli using a gel filtration chromatography refolding method, a novel approach for the refolding of pIgR domains, after the purification of inclusion bodies using nickel affinity chromatography. Surface Plasmon resonance (SPR) spectroscopy showed that purified recombinant D3D4 binds recombinant R1R2 with an equilibrium dissociation constant (KD) of 3.36×10−7M.

Prevalence of antibiotic resistant strains in fecal surveillance cultures of patients from a new tertiary care cancer center in eastern part of India.

e20686 Background: Drug resistant organisms are a very common cause of infections in critically ill patients in India. Surveillance Cultures is part of a multi-factorial approach to control MDRO[Multi-Drug Resistant Organisms]. Colonization surveillance may have the potential to improve empiric antimicrobial treatment in a critical care setting. Methods: Design: Retrospective. Setting: Newly started Comprehensive Cancer Center in Eastern part of India. Period: Dec 2011 - Jan 2013. Review of fecal surveillance cultures of patients undergoing intensive chemotherapy for hematological cancers or haemopoietic stem cell transplant. Fecal Surveillance cultures were done prior to Intensive Chemotherapy using a method based on Landman D et al (J Clin Microbiol 2005). Results: 48 patients [35 male,13 female] admitted with diagnoses of AML(22), ALL(6), APL(1), Acute Mixed Lineage Leukemia(1), MDS(1), Hodgkin Lymphoma(1), DLBCL(1), Fanconi Anemia(1), Multiple Myeloma(4), and Myeloproliferative Disorder(1) had information on Fecal Surveillance Cultures. Mean age: 35yrs [range; Male: 6-67yrs, Female:10-59yrs]. Total Samples collected: 67. Median sample per pateint: 1(range 1-4). All samples excepting one, grew MDRO isolates (98.5%). No. of Isolates:136 [95 gram negative bacilli (GNB), 41 gram positive cocci (GPC)]. Among GPC isolates, resistance to Ampicillin, Vancomycin, High level Gentamycin, and Linezolid were 86.5% (32/37), 7.3%(3/41), 60.9%(25/41) and nil(0/41) respectively. Among GNB isolates, resistance to Cefotaxime, Ciprofloxacin, Co-Amoxiclav, Gentamycin, Amikacin, Piperacillin-Tazobactum, Meropenem and Colistin were respectively 90.8%(79/87), 67.4%(60/89), 67.4%(60/89), 45.2%(43/95), 23.4%(22/94), 39.7%(37/93), 25.8%(24/93) and 6.4%(5/78). In the coliform group, the prevalence of ESBL/Amp-C producing isolates was 91.7%. Carbapenamase production was noted in 25.8% of GNB isolates. Conclusions: There is a very high prevalence of background antimicrobial resistance in the enteric flora of patients receiving intensive chemotherapy at our center. The causes of widespread MDRO in our setting needs further studies.

Francisella tularensis 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase: kinetic characterization and phosphoregulation.

Deliberate and natural outbreaks of infectious disease, the prevalence of antibiotic resistant strains, and the ease by which antibiotic resistant bacteria can be intentionally engineered all underscore the necessity of effective vaccines and continued development of novel antimicrobial/antiviral therapeutics. Isoprenes, a group of molecules fundamentally involved in a variety of crucial biological functions, are derived from either the mevalonic acid (MVA) or methylerythritol phosphate (MEP) pathway. While mammals utilize the MVA pathway, many bacteria utilize the MEP pathway, highlighting the latter as an attractive target for antibiotic development. In this report we describe the cloning and characterization of Francisella tularensis MEP cytidylyltransferase, a MEP pathway enzyme and potential target for antibiotic development. Size exclusion chromatography indicates the protein exists as a dimer in solution. Enzyme assays produced an apparent , , , , and a . The enzyme exhibits a strict preference for Mg+2 as a divalent cation and CTP as the nucleotide. Titanium dioxide chromatography-tandem mass spectrometry identified Thr141 as a site of phosphorylation. T141D and T141E site-directed mutants are catalytically inactive, suggesting a mechanism for post-translational control of metabolic flux through the F. tularensis MEP pathway. Overall, our study suggests that MEP cytidylyltransferase is an excellent target for the development of novel antibiotics against F. tularensis.

Shape-Memory Nitinol Tympanostomy Tube and All-in-One Introducer Device for Treatment of Otitis Media

Otitis media is the most common bacterial illness in children, resulting in millions of office visits, antibiotic prescriptions, and surgical procedures annually in the United States. Antibiotics are commonly prescribed and has resulted in increased prevalence of antibiotic resistant strains of organisms. Additionally, patients with otitis media are candidates for tympanocentesis, myringotomy, and tympanostomy tube placement procedures. The ability to safely and efficiently perform these procedures to accurately diagnose, identify the bacterial organism, and treat otitis media with point of care therapy is needed. A shape-memory nitinol tympanostomy tube and an all-in-one introducer device (OtoStent tympanostomy device) currently under development will allow clinicians to safely and efficiently perform myringotomy, tympanocentesis, and tympanostomy tube placement with a single disposable device.