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Sample records for adequate antimicrobial therapy

  1. Seven hours to adequate antimicrobial therapy in urosepsis using isothermal microcalorimetry.

    PubMed

    Braissant, Olivier; Müller, Georg; Egli, Adrian; Widmer, Andreas; Frei, Reno; Halla, Armin; Wirz, Dieter; Gasser, Thomas C; Bachmann, Alexander; Wagenlehner, Florian; Bonkat, Gernot

    2014-02-01

    Urosepsis can progress toward severe sepsis, septic shock, and, ultimately, death. Rapid antimicrobial susceptibility testing is crucial to decrease mortality and morbidity. This report shows that isothermal microcalorimetry can provide an antibiogram within 7 h with a sensitivity of 95% and specificity of 91% using Vitek-2 system as a reference.

  2. General principles of antimicrobial therapy.

    PubMed

    Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

    2011-02-01

    Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.

  3. Antimicrobial therapy for skin infections.

    PubMed

    Hirschmann, Jan V

    2007-06-01

    The most common skin infections are caused by Staphylococcus aureus, group A streptococci (Streptococcus pyogenes), or the normal skin flora. An antistaphylococcal oral antibiotic is the preferred treatment for nonbullous and bullous impetigo, and a therapeutic agent that is effective against both S aureus and streptococci is appropriate for most cases of cellulitis. For furuncles, carbuncles, cutaneous abscesses, and inflamed epidermal cysts, the most important therapy is incision and drainage, and in most cases there is no need for antimicrobial therapy. Patients with venous ulcers and atopic eczema do not benefit from systemic antimicrobial therapy unless obvious infection is present, as indicated by clinical features such as fever, cellulitis, and lymphangitis.

  4. Antimicrobial therapy of pulmonary tuberculosis*

    PubMed Central

    McDermott, Walsh

    1960-01-01

    The discovery, some nine years ago, of the highly specific antituberculous drug, isoniazid, marked an important advance in the antimicrobial therapy of tuberculosis, first practised successfully with streptomycin and p-aminosalicylic acid (PAS) in the late 'forties. Isoniazid is relatively non-toxic and, unlike streptomycin, can be administered orally, so that it is eminently suitable for use, either alone or in combination with PAS, in the domiciliary treatment of tuberculous patients. The wisdom of employing it on a large scale in home-treatment programmes, however, has been questioned on the ground that such wide-spread use might result in a spread of tubercle bacilli resistant to the drug. This controversial subject is discussed in some detail in this general review of the chemotherapy of tuberculosis. The author is convinced that, so far, the benefits of isoniazid therapy have outweighed the disadvantages and, though well aware of the possible consequences in terms of isoniazid-resistance, sees no reason at the present time for not making full use of this valuable weapon in the antituberculosis armamentarium. PMID:20604078

  5. Prostate cancer between prognosis and adequate/proper therapy

    PubMed Central

    Grozescu, T; Popa, F

    2017-01-01

    Knowing the indolent, non-invasive nature of most types of prostate cancer, as well as the simple fact that the disease seems more likely to be associated with age rather than with other factors (50% of men at the age of 50 and 80% at the age of 80 have it [1], with or without presenting any symptom), the big challenge of this clinical entity was to determine severity indicators (so far insufficient) to guide the physician towards an adequate attitude in the clinical setting. The risk of over-diagnosing and over-treating many prostate cancer cases (indicated by all the major European and American studies) is real and poses many question marks. The present paper was meant to deliver new research data and to reset the clinical approach in prostate cancer cases. PMID:28255369

  6. Optimizing antimicrobial therapy in critically ill patients

    PubMed Central

    Vitrat, Virginie; Hautefeuille, Serge; Janssen, Cécile; Bougon, David; Sirodot, Michel; Pagani, Leonardo

    2014-01-01

    Critically ill patients with infection in the intensive care unit (ICU) would certainly benefit from timely bacterial identification and effective antimicrobial treatment. Diagnostic techniques have clearly improved in the last years and allow earlier identification of bacterial strains in some cases, but these techniques are still quite expensive and not readily available in all institutions. Moreover, the ever increasing rates of resistance to antimicrobials, especially in Gram-negative pathogens, are threatening the outcome for such patients because of the lack of effective medical treatment; ICU physicians are therefore resorting to combination therapies to overcome resistance, with the direct consequence of promoting further resistance. A more appropriate use of available antimicrobials in the ICU should be pursued, and adjustments in doses and dosing through pharmacokinetics and pharmacodynamics have recently shown promising results in improving outcomes and reducing antimicrobial resistance. The aim of multidisciplinary antimicrobial stewardship programs is to improve antimicrobial prescription, and in this review we analyze the available experiences of such programs carried out in ICUs, with emphasis on results, challenges, and pitfalls. Any effective intervention aimed at improving antibiotic usage in ICUs must be brought about at the present time; otherwise, we will face the challenge of intractable infections in critically ill patients in the near future. PMID:25349478

  7. Antimicrobial therapies for Q fever

    PubMed Central

    Kersh, Gilbert J.

    2015-01-01

    Summary Q fever is caused by the bacterium Coxiella burnetii and has both acute and chronic forms. The acute disease is a febrile illness often with headache and myalgia that can be self-limiting whereas the chronic disease typically presents as endocarditis and can be life threatening. The normal therapy for the acute disease is a two week course of doxycycline, whereas chronic disease requires 18-24 months of doxycycline in combination with hydroxychloroquine. Alternative treatments are used for pregnant women, young children, and those who cannot tolerate doxycycline. Doxycycline resistance is rare but has been reported. Co-trimoxazole is a currently recommended alternative treatment, but quinolones, rifampin, and newer macrolides may also provide some benefit. PMID:24073941

  8. Antimicrobial therapy for gastrointestinal, pancreatic, and hepatic disorders.

    PubMed

    Davenport, D

    1990-06-01

    Antimicrobials are a common part of a symptomatic approach to the treatment of gastrointestinal disorders. Without an etiologic diagnosis, antimicrobial therapy is likely to be of little value and, in the worst case, may harm the patient either by altering normal gastrointestinal flora or by producing direct toxicity. This review is a systematic appraisal of antimicrobial therapy for gastrointestinal disease, beginning with the oral cavity, proceeding through the gastrointestinal tract and concluding with pancreatic and hepatic disorders. The intent is to highlight specific etiologies which form the basis for rational therapeutic choices. Controversies concerning the need for antimicrobial therapy or therapeutic alternatives are also explored. The review concludes with a discussion of adverse gastrointestinal effects of antimicrobial therapy.

  9. Anaerobic Antimicrobial Therapy After Necrotizing Enterocolitis in VLBW Infants

    PubMed Central

    Autmizguine, Julie; Hornik, Christoph P.; Benjamin, Daniel K.; Laughon, Matthew M.; Clark, Reese H.; Cotten, C. Michael; Cohen-Wolkowiez, Michael; Benjamin, Daniel K.

    2015-01-01

    OBJECTIVE: To evaluate the effect of anaerobic antimicrobial therapy for necrotizing enterocolitis (NEC) on clinical outcomes in very low birth weight (≤1500 g) infants. METHODS: We identified very low birth weight infants with NEC from 348 US NICUs from 1997 to 2012. Anaerobic antimicrobial therapy was defined by antibiotic exposure on the first day of NEC. We matched (1:1) infants exposed to anaerobic antimicrobial therapy with infants who were not exposed by using a propensity score stratified by NEC severity (medical and surgical). The primary composite outcome was in-hospital death or intestinal stricture. We assessed the relationship between anaerobic antimicrobial therapy and outcome by using a conditional logistic regression on the matched cohort. RESULTS: A total of 1390 infants exposed to anaerobic antimicrobial therapy were matched with 1390 infants not exposed. Mean gestational age and birth weight were 27 weeks and 946 g, respectively, and were similar in both groups. We found no significant difference in the combined outcome of death or strictures, but strictures as a single outcome were more common in the anaerobic antimicrobial therapy group (odds ratio 1.73; 95% confidence interval, 1.11–2.72). Among infants with surgical NEC, mortality was less common with anaerobic antimicrobial therapy (odds ratio 0.71; 95% confidence interval, 0.52–0.95). CONCLUSIONS: Anaerobic antimicrobial therapy was not associated with the composite outcome of death or strictures but was associated with an increase in intestinal strictures. This higher incidence of intestinal strictures may be explained by the fact that death is a competing outcome for intestinal strictures, and mortality was slightly lower in the anaerobic cohort. Infants with surgical NEC who received anaerobic antimicrobial therapy had lower mortality. PMID:25511117

  10. Duration of Pulmonary Tuberculosis Infectiousness under Adequate Therapy, as Assessed Using Induced Sputum Samples

    PubMed Central

    Ko, Yousang; Shin, Jeong Hwan; Lee, Hyun-Kyung; Lee, Young Seok; Lee, Suh-Young; Park, So Young; Mo, Eun-Kyung; Kim, Changhwan

    2017-01-01

    Background A sputum culture is the most reliable indicator of the infectiousness of pulmonary tuberculosis (PTB); however, a spontaneous sputum specimen may not be suitable. The aim of this study was to evaluate the infectious period in patients with non–drug-resistant (DR) PTB receiving adequate standard chemotherapy, using induced sputum (IS) specimens. Methods We evaluated the duration of infectiousness of PTB using a retrospective cohort design. Results Among the 35 patients with PTB, 22 were smear-positive. The rates of IS culture positivity from baseline to the sixth week of anti-tuberculosis medication in the smear-positive PTB group were 100%, 100%, 91%, 73%, 36%, and 18%, respectively. For smear-positive PTB cases, the median time of conversion to culture negativity was 35.0 days (range, 28.0–42.0 days). In the smear-negative PTB group (n=13), the weekly rates of positive IS culture were 100%, 77%, 39%, 8%, 0%, and 0%, respectively, and the median time to conversion to culture-negative was 21.0 days (range, 17.5–28.0 days). Conclusion The infectiousness of PTB, under adequate therapy, may persist longer than previously reported, even in patients with non-DR PTB. PMID:28119744

  11. Ipragliflozin effectively reduced visceral fat in Japanese patients with type 2 diabetes under adequate diet therapy.

    PubMed

    Yamamoto, Chiho; Miyoshi, Hideaki; Ono, Kota; Sugawara, Hajime; Kameda, Reina; Ichiyama, Mei; Yamamoto, Kohei; Nomoto, Hiroshi; Nakamura, Akinobu; Atsumi, Tatsuya

    2016-06-30

    To investigate if ipragliflozin, a novel sodium-glucose co-transporter 2 inhibitor, alters body composition and to identify variables associated with reductions in visceral adipose tissue in Japanese patients with type 2 diabetes mellitus. This prospective observational study enrolled Japanese participants with type 2 diabetes mellitus. Subjects were administered ipragliflozin (50 mg/day) once daily for 16 weeks. Body composition, visceral adipose tissue volume and plasma variables were measured at 0, 8, and 16-weeks. The subjects' lifestyle habits including diet and exercise were evaluated at baseline and 16 weeks. The primary endpoint was defined as the decrease of visceral adipose tissue mass. Twenty-four of 26 enrolled participants completed the study. The visceral adipose tissue decreased significantly (110 ± 33 to 101 ± 36 cm(2), p = 0.005) as well as other parameters for metabolic insufficiency including hemoglobin A1c. Seventy-one % of the total body weight reduction (-2.49 kg) was estimated by a decrease in fat mass (-1.77 kg), and the remaining reduction (22%) by water volume (-0.55 kg). A minor but significant reduction in the skeletal muscle index was also observed. Correlation analyses were performed to identify variables associated with changes in visceral adipose tissue and the only significant variable identified was diet therapy (Spearman's r = -0.416, p = 0.043). Ipragliflozin significantly decreased visceral adipose tissue, and improved parametres for metabolic dysfunction. Adequate diet therapy would be necessary to induce and enhance the therapeutic merit.

  12. Important cellular targets for antimicrobial photodynamic therapy.

    PubMed

    Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

    2016-09-01

    The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets.

  13. Ertapenem: a new opportunity for outpatient parenteral antimicrobial therapy.

    PubMed

    Tice, Alan D

    2004-06-01

    Ertapenem is a parenteral carbapenem antimicrobial with pharmacological properties that allow it to be given once daily. This makes it a consideration for outpatient parenteral antimicrobial therapy (OPAT). In comparison with information from the OPAT Outcomes Registry, ertapenem seems well suited for the types of infections and bacteria that are commonly treated with OPAT, plus it has additional activity against anaerobic bacteria. This added spectrum makes it possible to treat complicated skin/skin-structure, complicated intra-abdominal and pelvic infections with a single antibiotic instead of the multiple agents that have usually been required. Ertapenem is also comparable to other OPAT antimicrobials in terms of adverse effects and clinical outcomes. This antimicrobial can be given with any delivery model, although its stability when mixed is such that daily preparation or self-mixing systems need to be considered. Ertapenem should be added to the growing list of once-daily parenteral antibiotics that can be given to outpatients.

  14. Current Concepts in Laboratory Testing to Guide Antimicrobial Therapy

    PubMed Central

    Jenkins, Stephen G.; Schuetz, Audrey N.

    2012-01-01

    Antimicrobial susceptibility testing (AST) is indicated for pathogens contributing to an infectious process that warrants antimicrobial therapy if susceptibility to antimicrobials cannot be predicted reliably based on knowledge of their identity. Such tests are most frequently used when the etiologic agents are members of species capable of demonstrating resistance to commonly prescribed antibiotics. Some organisms have predictable susceptibility to antimicrobial agents (ie, Streptococcus pyogenes to penicillin), and empirical therapy for these organisms is typically used. Therefore, AST for such pathogens is seldom required or performed. In addition, AST is valuable in evaluating the activity of new and experimental compounds and investigating the epidemiology of antimicrobial resistant pathogens. Several laboratory methods are available to characterize the in vitro susceptibility of bacteria to antimicrobial agents. When the nature of the infection is unclear and the culture yields mixed growth or usual microbiota (wherein the isolates usually bear little relationship to the actual infectious process), AST is usually unnecessary and results may, in fact, be dangerously misleading. Phenotypic methods for detection of specific antimicrobial resistance mechanisms are increasingly being used to complement AST (ie, inducible clindamycin resistance among several gram-positive bacteria) and to provide clinicians with preliminary direction for antibiotic selection pending results generated from standardized AST (ie, β-lactamase tests). In addition, molecular methods are being developed and incorporated by microbiology laboratories into resistance detection algorithms for rapid, sensitive assessment of carriage states of epidemiologically and clinically important pathogens, often directly from clinical specimens (ie, presence of vancomycin-resistant enterococci in fecal specimens). PMID:22386185

  15. Nontyphoid salmonella infection: microbiology, clinical features, and antimicrobial therapy.

    PubMed

    Chen, Hung-Ming; Wang, Yue; Su, Lin-Hui; Chiu, Cheng-Hsun

    2013-06-01

    Nontyphoid Salmonella is the most common bacterial pathogen causing gastrointestinal infection worldwide. Most nontyphoid Salmonella infection is limited to uncomplicated gastroenteritis that seldom requires antimicrobial treatment. Nevertheless, invasive infections, such as bacteremia, osteomyelitis, and meningitis, may occur and require antimicrobial therapy. Continuous genetic and genomic evolution in Salmonella leading to increased virulence and resistance to multiple drugs are of significant public health concern. Two major changes in the epidemiology of nontyphoid salmonellosis in Europe and in the USA occurred in the second half of the 20(th) century: the emergence of foodborne human infections caused by Salmonella enterica serotype Enteriditis and by multidrug-resistant strains of Salmonella enterica serotype Typhimurium. In the 21(st) century, a worsening situation is the increasing resistance to fluoroquinolones and third-generation cephalosporins in nontyphoid Salmonella. Clinical isolates showing carbapenem resistance also have been identified. Although antimicrobial therapy is usually not indicated for uncomplicated Salmonella gastroenteritis, recent studies indicated that a short-course ceftriaxone therapy (3-5 days) for patients with severe gastroenteritis would lead to a faster clinical recovery. Continuous surveillance of Salmonella in both humans and animals is mandatory. A better understanding of the mechanisms that lead to the emergence of antimicrobial resistance in Salmonella may help in the devising of better interventional strategies to reduce the spread of resistant Salmonella between humans and reservoirs along the food chain.

  16. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    SciTech Connect

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Woo, Shiao; Mohan, Radhe; Yepes, Pablo

    2009-03-10

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

  17. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    NASA Astrophysics Data System (ADS)

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

    2009-03-01

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

  18. Levofloxacin and indolicidin for combination antimicrobial therapy.

    PubMed

    Ghaffar, Khairunnisa Abdul; Hussein, Waleed M; Khalil, Zeinab G; Capon, Robert J; Skwarczynski, Mariusz; Toth, Istvan

    2015-01-01

    Despite the increasing need for antibiotics to fight infectious diseases, fewer new antibiotics are available on the market. Unfortunately, developing a new class of antibiotics is associated with high commercial risk. Therefore, modification or combination of existing antibiotics to improve their efficacy is a promising strategy. Herein, we conjugated the antibiotic, levofloxacin, with two peptides, i.e. an antimicrobial peptide indolicidin and a cell penetrating peptide (TAT). Glycolic acid and glycine linkers were used between levofloxacin and peptides. We developed an optimized condition for coupling of levofloxacin via its carboxylic group to glycolic acid using solid phase peptide synthesis (SPPS). Antibacterial and haemolytic assays were carried out on the conjugates and only the levofloxacin-indolicidin conjugate demonstrated moderate antibacterial activity. Interestingly, physical mixture of levofloxacin and indolicidin showed improvement in the activity against Gram-positive bacteria.

  19. Evaluation of Outpatient Parenteral Antimicrobial Therapy at a Veterans Affairs Hospital.

    PubMed

    Spivak, Emily Sydnor; Kendall, Brian; Orlando, Patricia; Perez, Christian; De Amorim, Marina; Samore, Matthew; Pavia, Andrew T; Hersh, Adam L

    2015-09-01

    We reviewed outpatient parenteral antimicrobial therapy at a Veterans Affairs Medical Center to identify opportunities for antimicrobial stewardship intervention. A definite or possible modification would have been recommended in 60% of courses. Forty-one percent of outpatient parenteral antimicrobial therapy courses were potentially avoidable, including 22% involving infectious diseases consultation.

  20. Optimizing antimicrobial therapy of sepsis and septic shock: focus on antibiotic combination therapy.

    PubMed

    Vazquez-Grande, Gloria; Kumar, Anand

    2015-02-01

    There has been little improvement in septic shock mortality in the past 70 years, despite ever more broad-spectrum and potent antimicrobials. In the past, resuscitative elements have been the primary area of clinical septic shock management and research. The question of the optimal use of antimicrobial therapy was relatively ignored in recent decades. This review explores the pathophysiology of sepsis in an attempt to produce a better understanding and define key determinants of antimicrobial therapy response in septic shock. Optimizing existing antimicrobials delivery can drive significant improvements in the outcome of sepsis and septic shock. Inappropriate antimicrobial selection and dosing or delays in the administration substantially increase mortality and morbidity in life-threatening infections. Definitive combination therapy (where a pathogen known to be susceptible to a given agent is additionally covered by another agent) remains controversial. Although some in vitro studies, animal models, and clinical studies of infection including endocarditis, gram-negative bacteremia, and neutropenic infections have supported combination therapy, the potential clinical benefit in other severe infections has been questioned. Several meta-analyses have failed to demonstrate improvement of outcome with combination therapy in immunocompetent patients with sepsis and/or gram-negative bacteremia. These meta-analyses did not undertake subgroup analyses of the septic shock population. This article reviews the existing evidence supporting combination therapy for severe infections, sepsis, and septic shock.

  1. Changes in vaginal microbiota following antimicrobial and probiotic therapy

    PubMed Central

    Macklaim, Jean M.; Clemente, Jose C.; Knight, Rob; Gloor, Gregory B.; Reid, Gregor

    2015-01-01

    Background The composition of the vaginal microbiota is known to be important for health. When infections occur, antimicrobial therapy is often poorly efficacious. Objective and design We used 16S rRNA gene sequencing to characterize changes in the bacterial microbiota following oral antimicrobial and probiotic interventions. Results While the bacterial vaginal profiles of women with vulvovaginal candidiasis were dominated by lactobacilli as in healthy women, and unchanged by therapy, Gardnerella vaginalis, Prevotella, Atopobium, Sneathia, and Megasphaera dominated the vagina of women with bacterial vaginosis (BV), and treatment with tinidazole plus Lactobacillus reuteri RC-14+L. rhamnosus GR-1 resulted in an increased relative abundance of indigenous L. iners or L. crispatus. Conclusions The ability to restore homeostasis provides a rationale for conjoint use of probiotics with antibiotic treatment of BV. PMID:26282697

  2. Nanoparticle-based endodontic antimicrobial photodynamic therapy

    PubMed Central

    Pagonis, Tom C.; Chen, Judy; Fontana, Carla Raquel; Devalapally, Harikrishna; Ruggiero, Karriann; Song, Xiaoqing; Foschi, Federico; Dunham, Joshua; Skobe, Ziedonis; Yamazaki, Hajime; Kent, Ralph; Tanner, Anne C.R.; Amiji, Mansoor M.; Soukos, Nikolaos S.

    2009-01-01

    Objective To study the in vitro effects of poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the photosensitizer methylene blue (MB) and light against Enterococcus faecalis (ATCC 29212). Materials and Methods The uptake and distribution of nanoparticles in E. faecalis in suspension was investigated by transmission electron microscopy (TEM) after incubation with PLGA complexed with colloidal gold particles for 2.5, 5 and 10 minutes. E. faecalis species were sensitized in planktonic phase and in experimentally infected root canals of human extracted teeth with MB-loaded nanoparticles for 10 minutes followed by exposure to red light at 665 nm. Results The nanoparticles were found to be concentrated mainly on the cell walls of microorganisms at all three time points. The synergism of light and MB-loaded nanoparticles led to approximately 2 and 1 log10 reduction of colony-forming units in planktonic phase and root canals, respectively. In both cases, mean log10 CFU levels were significantly lower than controls and MB-loaded nanoparticles without light. Conclusion The utilization of PLGA nanoparticles encapsulated with photoactive drugs may be a promising adjunct in antimicrobial endodontic treatment. PMID:20113801

  3. Early and adequate antibiotic therapy in the treatment of severe sepsis and septic shock.

    PubMed

    Dickinson, John D; Kollef, Marin H

    2011-10-01

    Severe sepsis and septic shock are conditions that pose difficult challenges to physicians and the health care system. In the past 10 years, a number of retrospective and prospective observational studies have shed light on the importance of a rapid and systematic approach to treatment of these conditions. A key component is early and appropriate use of antibiotics. Delay of even 6 h can dramatically increase hospital mortality. In addition, multivariate analyses have demonstrated that inappropriate initial antibiotics lead to worse outcomes. The treating physician can rapidly identify risk factors for initial inappropriate antibiotics at the bedside, such as recent antibiotic therapy or recent hospitalization. Organized antibiotic order sets have been shown to significantly improve timely appropriate antibiotic administration in septic patients. Finally, emerging laboratory data suggest that early in the course of septic shock, the pharmacokinetics of common broad spectrum antibiotics may be significantly altered due to increased volumes of distribution having dosing implications for antibiotics in septic shock.

  4. Synergistic combination dry powders for inhaled antimicrobial therapy

    NASA Astrophysics Data System (ADS)

    Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

    2013-06-01

    Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

  5. Biomarkers as a guide for antimicrobial therapy.

    PubMed

    Reinhart, Konrad; Hartog, Christiane S

    2010-12-01

    The use of biomarkers might help to avoid antibiotic misuse and overuse and to curb the rising incidence of microbial resistance. Amongst >100 biomarkers proposed for use as infection/sepsis markers, procalcitonin is the most frequently evaluated. It has been tested in 11 randomised controlled trials with more than 3500 patients and resulted in a considerable 35-70% reduction in antibiotic use without an apparent negative impact on patient outcome. Testing was carried out in hospital, Intensive Care Unit, emergency and primary care settings; most of the patients had lower respiratory tract infections and only smaller studies exist in surgical patients with infectious complications, immunocompromised patients and patients with sepsis. There are, however, concerns - trials designed to show non-inferiority of procalcitonin to standard management allowed rather large differences for mortality rates, in the range of 7.5-10%, thus clinically relevant excess mortality by procalcitonin-guided antibiotic therapy cannot be completely ruled out. Marker panels derived from transcriptomic or proteomic profiling hold promise in overcoming the limitations of procalcitonin for differentiating non-infectious from infection-associated inflammation. However, the utility of these novel diagnostic tools in the clinical setting remains to be proven.

  6. Antimicrobial Photodynamic Therapy for Methicillin-Resistant Staphylococcus aureus Infection

    PubMed Central

    Fu, Xiu-jun; Fang, Yong; Yao, Min

    2013-01-01

    Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug resistant bacteria both in hospitals and in the community. In the last two decades, there has been growing concern about the increasing resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection poses a serious problem for physicians and their patients. Photosensitizer-mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and innovative approach for treating multidrug resistant infection. In spite of encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large in vitro studies, there are only few in vivo studies. Therefore, applying PDT in the clinic for MRSA infection is still a long way off. PMID:23555074

  7. Cationic porphycenes as potential photosensitizers for antimicrobial photodynamic therapy

    PubMed Central

    Ragàs, Xavier; Sánchez-García, David; Ruiz-González, Rubén; Dai, Tianhong; Agut, Montserrat; Hamblin, Michael R.; Nonell, Santi

    2010-01-01

    Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines and phenothiazinium salts, with cationic charges at physiological pH values. However derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse 3rd degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log10 reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J·cm-2 of red light. PMID:20936792

  8. Antimicrobial therapy of acute diarrhoea: a clinical review.

    PubMed

    Lübbert, Christoph

    2016-01-01

    Diarrhoea is one of the most commonly occurring diseases. This article presents a review of the current state of the treatment of acute infectious diarrhoea, as well as of the most important pathogens. The general principles of the therapy of diarrhoea are exemplified, followed by a description of the targeted antimicrobial therapy of the most important bacterial gastrointestinal infections, including salmonellosis, shigellosis and Campylobacter infections, as well as infections with pathogenic Escherichia coli strains, yersiniosis and cholera. Diarrhoea caused by toxigenic Clostridium difficile strains has increased in incidence and in severity. These infections will therefore be described in detail, including important new aspects of treatment. Symptomatic therapy is still the most important component of the treatment of infectious diarrhoea. However, empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhoea, underlying immune deficiency, advanced age or significant comorbidities. Increasing resistance, in particular against fluoroquinolones, must be taken into consideration. Therapy with motility inhibitors is not recommended for Shiga toxin-producing Escherichia coli (STEC) infections, Clostridium difficile infections (CDI), and severe colitis. The macrocyclic antibiotic fidaxomicin can reduce the rate of recurrent disease in CDI. Furthermore, evidence for the benefits of faecal microbiota transplantation as a treatment option for multiple recurrences of CDI is increasing. In conclusion, the treatment of acute diarrhoea is still primarily supportive. General empirical antibiotic therapy for acute diarrhoea is not evidence-based.

  9. Physical and mathematical modeling of antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Bürgermeister, Lisa; López, Fernando Romero; Schulz, Wolfgang

    2014-07-01

    Antimicrobial photodynamic therapy (aPDT) is a promising method to treat local bacterial infections. The therapy is painless and does not cause bacterial resistances. However, there are gaps in understanding the dynamics of the processes, especially in periodontal treatment. This work describes the advances in fundamental physical and mathematical modeling of aPDT used for interpretation of experimental evidence. The result is a two-dimensional model of aPDT in a dental pocket phantom model. In this model, the propagation of laser light and the kinetics of the chemical reactions are described as coupled processes. The laser light induces the chemical processes depending on its intensity. As a consequence of the chemical processes, the local optical properties and distribution of laser light change as well as the reaction rates. The mathematical description of these coupled processes will help to develop treatment protocols and is the first step toward an inline feedback system for aPDT users.

  10. Predicting response to antimicrobial therapy in children with acute sinusitis

    PubMed Central

    Shaikh, Nader; Wald, Ellen R.; Jeong, Jong H.; Kurs-Lasky, Marcia; Bowen, A’Delbert; Flom, Lynda L.; Hoberman, Alejandro

    2014-01-01

    Objective To determine prognostic factors that independently predict response to antimicrobial therapy in children with acute sinusitis. Study design 206 children meeting a priori clinical criteria for acute sinusitis who were given antimicrobial therapy by their primary care provider were included. The severity of symptoms in the 8 to 12 days after treatment was initiated was followed using a validated scale. We examined the univariate and multivariate association between factors present at the time of diagnosis (symptoms, signs, nasopharyngeal culture result, radiograph results) and time to resolution of symptoms. This study was conducted 8 to 10 years after 7-valent pneumococcal conjugate vaccination was introduced, but before introduction of the 13-valent pneumococcal conjugate vaccination. Results Children with proven nasopharyngeal colonization with Streptococcus pneumoniae improved more rapidly (6.5 vs. 8.5 median days to symptom resolution) than those who were not colonized with S. pneumoniae. Age and radiograph findings did not predict time to symptom resolution. Conclusions In children with acute sinusitis, proven nasopharyngeal colonization with S. pneumoniae at presentation independently predicted time to symptom resolution. Future randomized, placebo-controlled trials could investigate the usefulness of testing for the presence of nasopharyngeal pathogens as a predictor of response to treatment. PMID:24367985

  11. Practical Considerations in the Use of Outpatient Antimicrobial Therapy for Musculoskeletal Infections

    PubMed Central

    Marculescu, Camelia E.; Berbari, Elie F.; Cantey, J. Robert; Osmon, Douglas R.

    2012-01-01

    Successful treatment of many musculoskeletal infections often requires an extended course of outpatient antimicrobial therapy, much of which is administered parenterally outside the hospital under the guidance of an infectious disease specialist. Delivery of outpatient parenteral antimicrobial therapy (OPAT) may occur in physicians' offices, ambulatory infusion centers, or hospital clinics but most frequently is done in patients' homes, often by the patients themselves. In this article, we outline the essential elements of outpatient antimicrobial therapy for musculoskeletal infections with particular emphasis on OPAT, including patient selection and evaluation; antimicrobial administration, including the route, duration, and complications of central venous access; and clinical and laboratory monitoring of antimicrobial therapy. We believe that primary care physicians, orthopedists, and infectious disease specialists caring for patients with musculoskeletal infections should become familiar with the use of, indications for, and complications of OPAT. PMID:22212975

  12. Enhancing antibiofilm efficacy in antimicrobial photodynamic therapy: effect of microbubbles

    NASA Astrophysics Data System (ADS)

    Kishen, Anil; George, Saji

    2013-02-01

    In this study, we tested the hypothesis that a microbubble containing photosensitizer when activated with light would enable comprehensive disinfection of bacterial biofilms in infected root dentin by antimicrobial photodynamic therapy (APDT). Experiments were conducted in two stages. In the stage-1, microbubble containing photosensitizing formulation was tested for its photochemical properties. In the stage-2, the efficacy of microbubble containing photosensitizing formulation was tested on in vitro infected root canal model, developed with monospecies biofilm models of Enterococcus faecalis on root dentin substrate. The findings from this study showed that the microbubble containing photosensitizing formulation was overall the most effective formulation for photooxidation, generation of singlet oxygen, and in disinfecting the biofilm bacteria in the infected root canal model. This modified photosensitizing formulation will have potential advantages in eliminating bacterial biofilms from infected root dentin.

  13. Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria

    PubMed Central

    Sperandio, Felipe F; Huang, Ying-Ying; Hamblin, Michael R

    2013-01-01

    Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photostimulation. ROS are formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall. This review covers significant peer-reviewed articles together with US and World patents that were filed within the past few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing agents such as EDTA, PMNP and CaCl2. The present review also covers the different laboratory animal models normally used to treat Gram-negative bacterial infections with antimicrobial PDT. PMID

  14. Antimicrobial photodynamic therapy to kill Gram-negative bacteria.

    PubMed

    Sperandio, Felipe F; Huang, Ying-Ying; Hamblin, Michael R

    2013-08-01

    Antimicrobial photodynamic therapy (PDT) or photodynamic inactivation (PDI) is a new promising strategy to eradicate pathogenic microorganisms such as Gram-positive and Gram-negative bacteria, yeasts and fungi. The search for new approaches that can kill bacteria but do not induce the appearance of undesired drug-resistant strains suggests that PDT may have advantages over traditional antibiotic therapy. PDT is a non-thermal photochemical reaction that involves the simultaneous presence of visible light, oxygen and a dye or photosensitizer (PS). Several PS have been studied for their ability to bind to bacteria and efficiently generate reactive oxygen species (ROS) upon photo-stimulation. ROS are formed through type I or II mechanisms and may inactivate several classes of microbial cells including Gram-negative bacteria such as Pseudomonas aeruginosa, which are typically characterized by an impermeable outer cell membrane that contains endotoxins and blocks antibiotics, dyes, and detergents, protecting the sensitive inner membrane and cell wall. This review covers significant peer-reviewed articles together with US and World patents that were filed within the past few years and that relate to the eradication of Gram-negative bacteria via PDI or PDT. It is organized mainly according to the nature of the PS involved and includes natural or synthetic food dyes; cationic dyes such as methylene blue and toluidine blue; tetrapyrrole derivatives such as phthalocyanines, chlorins, porphyrins, chlorophyll and bacteriochlorophyll derivatives; functionalized fullerenes; nanoparticles combined with different PS; other formulations designed to target PS to bacteria; photoactive materials and surfaces; conjugates between PS and polycationic polymers or antibodies; and permeabilizing agents such as EDTA, PMNP and CaCl₂. The present review also covers the different laboratory animal models normally used to treat Gram-negative bacterial infections with antimicrobial PDT.

  15. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality

    PubMed Central

    2012-01-01

    Introduction Although early institution of adequate antimicrobial therapy is lifesaving in sepsis patients, optimal antimicrobial strategy has not been established. Moreover, the benefit of combination therapy over monotherapy remains to be determined. Our aims are to describe patterns of empiric antimicrobial therapy in severe sepsis, assessing the impact of combination therapy, including antimicrobials with different mechanisms of action, on mortality. Methods This is a Spanish national multicenter study, analyzing all patients admitted to ICUs who received antibiotics within the first 6 hours of diagnosis of severe sepsis or septic shock. Antibiotic-prescription patterns in community-acquired infections and nosocomial infections were analyzed separately and compared. We compared the impact on mortality of empiric antibiotic treatment, including antibiotics with different mechanisms of action, termed different-class combination therapy (DCCT), with that of monotherapy and any other combination therapy possibilities (non-DCCT). Results We included 1,372 patients, 1,022 (74.5%) of whom had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), whereas non-DCCT was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCTs than in those who were administered non-DCCTs (34% versus 40%; P = 0.042). The variables independently associated with mortality were age, male sex, APACHE II score, and community origin of the infection. DCCT was a protective factor against in-hospital mortality (odds ratio (OR), 0.699; 95% confidence interval (CI), 0.522 to 0.936; P = 0.016), as was urologic focus of infection (OR, 0.241; 95% CI, 0.102 to 0.569; P = 0.001). Conclusions β-Lactams, including carbapenems, are the most frequently prescribed antibiotics in empiric

  16. Evaluation of the effect of appropriate antimicrobial therapy on mortality associated with Acinetobacter nosocomialis bacteraemia.

    PubMed

    Kuo, Shu-Chen; Lee, Yi-Tzu; Yang, Su-Pen; Chiang, Mei-Chun; Lin, Yi-Tsung; Tseng, Fan-Chen; Chen, Te-Li; Fung, Chang-Phone

    2013-07-01

    Appropriate antimicrobial therapy is effective for severe infections caused by Acinetobacter baumannii, but efficacy for other Acinetobacter species remains to be established. The current study was designed to determine whether appropriate antimicrobial therapy reduces the mortality of patients with Acinetobacter nosocomialis bacteraemia. A 9-year retrospective study of 266 patients with monomicrobial A. nosocomialis bacteraemia was conducted at a large teaching hospital in Taiwan. Multivariable analysis was performed to evaluate the impact on 14-day mortality according to clinical characteristics, severity of disease and use of appropriate antimicrobial therapy. The influence of APACHE II score on the impact of appropriate antimicrobial therapy was analysed by including an interaction term. The overall 14-day mortality was 9.4%. Multivariable analysis revealed that APACHE II score was the only factor significantly associated with mortality (odds ratio, 1.18; 95% confidence interval, 1.11-1.25; p <0.001). Appropriate antimicrobial therapy was not associated with reduced mortality regardless of disease severity. In the subgroup analyses in patients with different clinical conditions, APACHE II score was consistently an independent factor for 14-day mortality, and appropriate antimicrobial therapy did not affect the mortality in any group. In conclusion, severity of disease, based on the APACHE II score, was the independent risk factor for 14-day mortality for patients with monomicrobial A. nosocomialis bacteraemia, even in different clinical conditions. In contrast, appropriate antimicrobial therapy did not reduce the 14-day mortality. The result highlighted a different effect of appropriate antimicrobial therapy on infections caused by two phenotypically undifferentiated Acinetobacter.

  17. Antimicrobial therapy of selected diseases in turkeys, laying hens, and minor poultry species in Canada

    PubMed Central

    Agunos, Agnes; Carson, Carolee; Léger, Dave

    2013-01-01

    This paper identifies common poultry diseases requiring antimicrobial therapy, antimicrobials deemed efficacious to treat these diseases, and antimicrobial resistance (AMR) in these commodity-pathogen combinations, and describes current residue issues and minor use minor species (MUMS) guidelines. Veterinarians with turkey/layer expertise and diagnosticians were surveyed to determine the bacterial and protozoal diseases diagnosed in the last 5 years. Avian pathogenic Escherichia coli, Staphylococcus aureus, and Ornithobacterium rhinotracheale were the 3 most frequently diagnosed pathogens of turkeys. In layers, E. coli-peritonitis, and Clostridium perfringens/Eimeria spp. infections were the most common diagnoses. A literature review identified 32 antimicrobials as efficacious and/or recommended for treating these diseases. Surveillance and monitoring indicate the presence of enteric resistant organisms from some of these avian species (including resistance to antimicrobials of very high importance to human medicine). This paper highlights the need for surveillance of pathogen frequency, antimicrobial use (AMU), and AMR particularly in turkeys. PMID:24179239

  18. Mycoplasma Removal from Cell Culture Using Antimicrobial Photodynamic Therapy

    PubMed Central

    Hasebe, Akira; Ishikawa, Isao; Shamsul, Haque M.; Ohtani, Makoto; Segawa, Taku; Saeki, Ayumi; Tanizume, Naoho; Oouchi, Manabu; Okagami, Yoshihide; Okano, Teruo

    2013-01-01

    Abstract Objective: The objective of this research was to determine the effectiveness of antimicrobial photodynamic therapy (aPDT) in the removal of mycoplasmas from contaminated cells. Background data: Mycoplasmas often contaminate cell cultures. The cell-contaminating mycoplasmas are removed by antibiotics, but the use of antibiotics usually induces antibiotic-resistant bacteria. aPDT is expected to be a possible alternative to antibiotic treatments for suppressing infections. Materials and Methods: Mycoplasma salivarium (Ms)-infected human embryonic kidney (HEK) 293 cells were irradiated using a red light-emitting diode (LED) in the presence of methylene blue (MB) as a photosensitizer. The Ms viable count was determined using culture on agar plates or using a mycoplasma detection kit. Results: aPDT performed using red LED irradiation was effective in decreasing live Ms in the presence of MB without damaging the HEK293 cells. aPDT removed live Ms from the infected cells after washing the cells with sterilized phosphate-buffered saline (PBS) to decrease the initial number of live Ms before aPDT. Conclusions: This study suggests that aPDT could remove mycoplasmas from contaminated cells. PMID:23402393

  19. Outpatient parenteral antimicrobial therapy in osteoarticular infections in children.

    PubMed

    Maraqa, Nizar F; Gomez, Margarita M; Rathore, Mobeen H

    2002-01-01

    There are few data on the use of outpatient parenteral antimicrobial therapy (OPAT) in the management of osteoarticular infections (OAIs) in childhood. The objective of this study was to determine if OPAT is safe and effective in the management of OAIs. Using their OPAT database, the authors evaluated the use of OPAT in children younger than 18 years old treated for OAIs between January 1, 1995, and December 31, 1999. One hundred eighty-four OAIs were treated in 179 patients over 5 years. OPAT involved central venous lines (CVLs) in 110 (59.8%), peripherally inserted central catheters (PICCs) in 71 (38.6%), and peripheral cannulas in 3 (1.6%). One hundred eighteen (64%) OPAT courses were completed without interruption. Rehospitalization occurred in 48 (26.1%) courses and occurred earlier with PICC. OPAT complications were catheter-related in 58 (30%) courses, not catheter-related in 60 (32%), and unknown in 10 (5.3%). The mechanical complication rate was 6.3 per 1,000 catheter-days (CVL 4.2, PICC 10.6), and the rate of infectious complications was 2.7 per 1,000 catheter-days (CVL 2.8, PICC 2.4). One hundred sixty-eight (98%) of 172 evaluable OAIs were cured. Four (2.2%) patients failed treatment: one had recurrence and three had persistent infection. The authors conclude that OPAT can be safely used to manage OAIs in children without compromising outcome. Mechanical complications are more common with PICCs.

  20. Clinical Impact of MALDI-TOF MS Identification and Rapid Susceptibility Testing on Adequate Antimicrobial Treatment in Sepsis with Positive Blood Cultures

    PubMed Central

    Verroken, Alexia; Defourny, Lydwine; le Polain de Waroux, Olivier; Belkhir, Leïla; Laterre, Pierre-François; Delmée, Michel; Glupczynski, Youri

    2016-01-01

    Shortening the turn-around time (TAT) of positive blood culture (BC) identification (ID) and susceptibility results is essential to optimize antimicrobial treatment in patients with sepsis. We aimed to evaluate the impact on antimicrobial prescription of a modified workflow of positive BCs providing ID and partial susceptibility results for Enterobacteriaceae (EB), Pseudomonas aeruginosa and Staphylococcus aureus on the day of BC positivity detection. This study was divided into a pre-intervention period (P0) with a standard BC workflow followed by 2 intervention periods (P1, P2) with an identical modified workflow. ID was performed with MALDI-TOF MS from blood, on early or on overnight subcultures. According to ID results, rapid phenotypic assays were realized to detect third generation cephalosporin resistant EB/P. aeruginosa or methicillin resistant S. aureus. Results were transmitted to the antimicrobial stewardship team for patient’s treatment revision. Times to ID, to susceptibility results and to optimal antimicrobial treatment (OAT) were compared across the three study periods. Overall, 134, 112 and 154 positive BC episodes in P0, P1 and P2 respectively were included in the analysis. Mean time to ID (28.3 hours in P0) was reduced by 65.3% in P1 (10.2 hours) and 61.8% in P2 (10.8 hours). Mean time to complete susceptibility results was reduced by 27.5% in P1 and 27% in P2, with results obtained after 32.4 and 32.6 hours compared to 44.7 hours in P0. Rapid tests allowed partial susceptibility results to be obtained after a mean time of 11.8 hours in P1 and 11.7 hours in P2. Mean time to OAT was decreased to 21.6 hours in P1 and to 17.9 hours in P2 compared to 36.1 hours in P0. Reducing TAT of positive BC with MALDI-TOF MS ID and rapid susceptibility testing accelerated prescription of targeted antimicrobial treatment thereby potentially improving the patients’ clinical outcome. PMID:27228001

  1. Clinical Impact of MALDI-TOF MS Identification and Rapid Susceptibility Testing on Adequate Antimicrobial Treatment in Sepsis with Positive Blood Cultures.

    PubMed

    Verroken, Alexia; Defourny, Lydwine; le Polain de Waroux, Olivier; Belkhir, Leïla; Laterre, Pierre-François; Delmée, Michel; Glupczynski, Youri

    2016-01-01

    Shortening the turn-around time (TAT) of positive blood culture (BC) identification (ID) and susceptibility results is essential to optimize antimicrobial treatment in patients with sepsis. We aimed to evaluate the impact on antimicrobial prescription of a modified workflow of positive BCs providing ID and partial susceptibility results for Enterobacteriaceae (EB), Pseudomonas aeruginosa and Staphylococcus aureus on the day of BC positivity detection. This study was divided into a pre-intervention period (P0) with a standard BC workflow followed by 2 intervention periods (P1, P2) with an identical modified workflow. ID was performed with MALDI-TOF MS from blood, on early or on overnight subcultures. According to ID results, rapid phenotypic assays were realized to detect third generation cephalosporin resistant EB/P. aeruginosa or methicillin resistant S. aureus. Results were transmitted to the antimicrobial stewardship team for patient's treatment revision. Times to ID, to susceptibility results and to optimal antimicrobial treatment (OAT) were compared across the three study periods. Overall, 134, 112 and 154 positive BC episodes in P0, P1 and P2 respectively were included in the analysis. Mean time to ID (28.3 hours in P0) was reduced by 65.3% in P1 (10.2 hours) and 61.8% in P2 (10.8 hours). Mean time to complete susceptibility results was reduced by 27.5% in P1 and 27% in P2, with results obtained after 32.4 and 32.6 hours compared to 44.7 hours in P0. Rapid tests allowed partial susceptibility results to be obtained after a mean time of 11.8 hours in P1 and 11.7 hours in P2. Mean time to OAT was decreased to 21.6 hours in P1 and to 17.9 hours in P2 compared to 36.1 hours in P0. Reducing TAT of positive BC with MALDI-TOF MS ID and rapid susceptibility testing accelerated prescription of targeted antimicrobial treatment thereby potentially improving the patients' clinical outcome.

  2. Antimicrobial potential of bacteriocins: in therapy, agriculture and food preservation.

    PubMed

    Ahmad, Varish; Khan, Mohd Sajid; Jamal, Qazi Mohammad Sajid; Alzohairy, Mohammad A; Al Karaawi, Mohammad A; Siddiqui, Mughees Uddin

    2017-01-01

    Due to the appearance of antibiotic resistance and the toxicity associated with currently used antibiotics, peptide antibiotics are the need of the hour. Thus, demand for new antimicrobial agents has brought great interest in new technologies to enhance safety. One such antimicrobial molecule is bacteriocin, synthesised by various micro-organisms. Bacteriocins are widely used in agriculture, veterinary medicine as a therapeutic, and as a food preservative agent to control various infectious and food-borne pathogens. In this review, we highlight the potential therapeutic and food preservative applications of bacteriocin.

  3. Outpatient parenteral antimicrobial therapy for orthopedic infections - a successful public healthcare experience in Brazil.

    PubMed

    Oliveira, Priscila Rosalba; Felix, Cassia da Silva; Carvalho, Vladimir Cordeiro de; Giovani, Arlete Mazzini; Reis, Rosangela Suarti Dos; Beraldo, Marisa; Albuquerque, Edmir Peralta; Ferreira, Walter Cintra; Silva, Jorge Dos Santos; Lima, Ana Lucia Lei

    2016-01-01

    Treatment of orthopedic infections usually requires prolonged antimicrobial therapy, ranging from 14 days up to 6 months. Nowadays, rising levels of antimicrobial resistance demands parenteral therapy for many patients. Outpatient parenteral antimicrobial therapy (OPAT) is a modality that allows treatment out of hospital in these situations. In Brazil, where a public universal healthcare system allows full coverage for all citizens, implantation and dissemination of OPAT programs would be beneficial for patients and for the system, because it would allow a better allocation of health resources. The Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da USP (IOT) started, in July 2013, a partnership with municipal health authorities in Sao Paulo, Brazil, in order to initiate an OPAT program in which patients discharged from that hospital would be able to continue antimicrobial therapy at primary care facilities. When necessary, patients could also receive their therapy at the day-hospital located at IOT. Primary care nursing and physician staff were trained about antimicrobial infusion and peripherally inserted central catheter manipulation. An OPAT specific antimicrobial protocol was designed and a special reference and counter-reference organized. As a result, 450 primary healthcare professionals were trained. In the first year of this program, 116 patients were discharged for OPAT. Chronic and acute osteomyelitis were most frequent diagnosis. Teicoplanin, ertapenem and tigecycline were the most used drugs. Duration of treatment varied from 10 to 180 days (average 101, median 42). Total sum of days in OPAT regimen was 11,698. Only 3 patients presented adverse effects. Partnership between services of different levels of complexity allowed implantation of a safe and effective public healthcare OPAT program for treatment of orthopedic infections. This program can serve as a model for developing similar strategies in other regions

  4. Pseudomonas aeruginosa: arsenal of resistance mechanisms, decades of changing resistance profiles, and future antimicrobial therapies.

    PubMed

    El Zowalaty, Mohamed E; Al Thani, Asmaa A; Webster, Thomas J; El Zowalaty, Ahmed E; Schweizer, Herbert P; Nasrallah, Gheyath K; Marei, Hany E; Ashour, Hossam M

    2015-01-01

    Antimicrobial resistance is one of the most serious public health issues facing humans since the discovery of antimicrobial agents. The frequent, prolonged, and uncontrolled use of antimicrobial agents are major factors in the emergence of antimicrobial-resistant bacterial strains, including multidrug-resistant variants. Pseudomonas aeruginosa is a leading cause of nosocomial infections. The abundant data on the increased resistance to antipseudomonal agents support the need for global action. There is a paucity of new classes of antibiotics active against P. aeruginosa. Here, we discuss recent antibacterial resistance profiles and mechanisms of resistance by P. aeruginosa. We also review future potential methods for controlling antibiotic-resistant bacteria, such as phage therapy, nanotechnology and antipseudomonal vaccines.

  5. Origins of Combination Therapy for Tuberculosis: Lessons for Future Antimicrobial Development and Application

    PubMed Central

    Kerantzas, Christopher A.

    2017-01-01

    ABSTRACT Tuberculosis is a global health problem that causes the death of approximately 1.5 million people worldwide each year (WHO, p. 1–126, Global Tuberculosis Report, 2015). Treatment of drug-susceptible tuberculosis requires combination antimicrobial therapy with a minimum of four antimicrobial agents applied over the course of 6 months. The first instance of combination antimicrobial therapy applied to tuberculosis was the joint use of streptomycin and para-aminosalicylic acid as documented by the Medical Research Council of the United Kingdom in 1950. These antimicrobial drugs were the product of many decades of investigation into both organism-derived antibiotics and synthetic chemotherapy and were the first agents in those respective categories to show substantial clinical efficacy and widespread use for tuberculosis. The events leading to the discovery and application of these two agents demonstrate that investments in all aspects of research, from basic science to clinical application, are necessary for the continued success of science in finding treatments for human disease. This observation is especially worth considering given the expanded role that combination therapy may play in combating the current rise in resistance to antimicrobial drugs. PMID:28292983

  6. Antimicrobial effect of silver-impregnated cellulose: potential for antimicrobial therapy

    PubMed Central

    2009-01-01

    Background Silver has long been known to have antimicrobial activity. To incorporate this property into multiple applications, a silver-impregnated cellulose (SIC) with low cytotoxicity to human cells was developed. SIC differs from other silver treatment methods in that the leaching of silver particles is non-existent and the release of ionic silver is highly controlled. Results Candida albicans, Micrococcus luteu, Pseudomonas putida, and Escherichia coli were used for antimicrobial testing. No microbial cells were able to grow in the presence of SIC at concentrations above 0.0035 Ag w/v %. Even at a concentration of 0.00035 Ag w/v %, P. putida and M. luteu failed to grow, and C. albicans and E. coli exhibited diminished growth. To determine the cytotoxic effect of silver on human cells, five different concentrations of SIC were tested on human fibroblasts. In SIC concentrations of 0.035 Ag w/v % and below, no cytotoxicity was observed. Conclusion The optimal concentration of SIC for a broad range of anti-microbial activity and low or negligible cytotoxicity was 0.0035 Ag w/v %. Although the highly controlled releasing characteristics of SIC would prove a substantial improvement over current technologies, further investigation for genotoxicity and other biocompatibility test will be required. PMID:19961601

  7. Clinical and in vitro evidence for the antimicrobial therapy in Burkholderia cepacia complex infections.

    PubMed

    Gautam, Vikas; Shafiq, Nusrat; Singh, Meenu; Ray, Pallab; Singhal, Lipika; Jaiswal, Nishant P; Prasad, Amber; Singh, Shaunik; Agarwal, Amit

    2015-05-01

    Treatment of infections caused by Burkholderia cepacia complex (Bcc) in cystic fibrosis (CF) patients poses a complex problem. Bcc is multidrug-resistant due to innate and acquired mechanisms of resistance. As CF patients receive multiple courses of antibiotics, susceptibility patterns of strains from CF patients may differ from those noted in strains from non-CF patients. Thus, there was a need for assessing in vitro and clinical data to guide antimicrobial therapy in these patients. A systematic search of literature, followed by extraction and analysis of available information from human and in vitro studies was done. The results of the analysis are used to address various aspects like use of antimicrobials for pulmonary and non-pulmonary infections, use of combination versus monotherapy, early eradication, duration of therapy, route of administration, management of biofilms, development of resistance during therapy, pharmacokinetics-pharmacodynamics correlations, therapy in post-transplant patients and newer drugs in Bcc-infected CF patients.

  8. Antimicrobial Photodynamic Therapy to treat chemotherapy-induced oral lesions: Report of three cases.

    PubMed

    Rocha, Breno Amaral; Melo Filho, Mário Rodrigues; Simões, Alyne

    2016-03-01

    The development of Angular Cheilitis and the reactivation of Herpes Simplex Virus, could be related to a decrease in the resistance of the immune system in the infected host, being common in cancer patients receiving antineoplastic chemotherapy. The objective of the present manuscript is to report Antimicrobial Photodynamic Therapy as a treatment of infected oral lesions of patients submitted to chemotherapy.

  9. Antimicrobial therapy of experimental Legionella micdadei pneumonia in guinea pigs.

    PubMed Central

    Pasculle, A W; Dowling, J N; Frola, F N; McDevitt, D A; Levi, M A

    1985-01-01

    Several antimicrobial agents were evaluated for activity against experimental Legionella micdadei pneumonia in guinea pigs. Erythromycin, rifampin, doxycycline, and sulfamethoxazole-trimethoprim produced significant reductions in mortality. Penicillin, cefazolin, cefoxitin, chloramphenicol, and gentamicin were not efficacious even though, at the doses administered, the peak concentrations of these agents in serum substantially exceeded their MICs for the test strain. It is suggested that the poor performance of the latter group of agents resulted from poor penetration into cells in which L. micdadei was multiplying. PMID:3878688

  10. Multidrug-Resistant Enterococcal Infections: New Compounds, Novel Antimicrobial Therapies?

    PubMed

    van Harten, Roel M; Willems, Rob J L; Martin, Nathaniel I; Hendrickx, Antoni P A

    2017-02-13

    Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting.

  11. The Antimicrobial Photodynamic Therapy in the Treatment of Peri-Implantitis

    PubMed Central

    Libotte, Fabrizio; Sabatini, Silvia; Grassi, Felice Roberto

    2016-01-01

    Introduction. The aim of this study is to demonstrate the effectiveness of addition of the antimicrobial photodynamic therapy to the conventional approach in the treatment of peri-implantitis. Materials and Methods. Forty patients were randomly assigned to test or control groups. Patients were assessed at baseline and at six (T1), twelve (T2), and twenty-four (T3) weeks recording plaque index (PlI), probing pocket depth (PPD), and bleeding on probing (BOP); control group received conventional periodontal therapy, while test group received photodynamic therapy in addition to it. Result. Test group showed a 70% reduction in the plaque index values and a 60% reduction in PD values compared to the baseline. BOP and suppuration were not detectable. Control group showed a significative reduction in plaque index and PD. Discussion. Laser therapy has some advantages in comparison to traditional therapy, with faster and greater healing of the wound. Conclusion. Test group showed after 24 weeks a better value in terms of PPD, BOP, and PlI, with an average pocket depth value of 2 mm, if compared with control group (3 mm). Our results suggest that antimicrobial photodynamic therapy with diode laser and phenothiazine chloride represents a reliable adjunctive treatment to conventional therapy. Photodynamic therapy should, however, be considered a coadjuvant in the treatment of peri-implantitis associated with mechanical (scaling) and surgical (grafts) treatments. PMID:27429618

  12. Antimicrobial Photodynamic Therapy and Dental Plaque: A Systematic Review of the Literature

    PubMed Central

    Santin, G. C.; Oliveira, D. S. B.; Galo, R.; Borsatto, M. C.; Corona, S. A. M.

    2014-01-01

    Background. The aim of this study was to perform a systematic review of the literature on the efficacy of antimicrobial photodynamic therapy (PDTa) on cariogenic dental biofilm. Types of Studies Reviewed. Studies in vivo, in vitro, and in situ were included. Articles that did not address PDTa, those that did not involve cariogenic biofilm, those that used microorganisms in the plankton phase, and reviews were excluded. Data extraction and quality assessments were performed independently by two raters using a scale. Results. Two hundred forty articles were retrieved; only seventeen of them met the eligibility criteria and were analyzed in the present review. Considerable variability was found regarding the methodologies and application protocols for antimicrobial PDTa. Two articles reported unfavorable results. Practical Implications. The present systematic review does not allow drawing any concrete conclusions regarding the efficacy of antimicrobial PDTa, although this method seems to be a promising option. PMID:25379545

  13. In vitro evaluation of wound healing and antimicrobial potential of ozone therapy.

    PubMed

    Borges, Gabriel Álvares; Elias, Silvia Taveira; da Silva, Sandra Márcia Mazutti; Magalhães, Pérola Oliveira; Macedo, Sergio Bruzadelli; Ribeiro, Ana Paula Dias; Guerra, Eliete Neves Silva

    2017-03-01

    Although ozone therapy is extensively applied when wound repair and antimicrobial effect are necessary, little is known about cellular mechanisms regarding this process. Thus, this study aimed to evaluate ozone cytotoxicity in fibroblasts (L929) and keratinocytes (HaCaT) cell lines, its effects on cell migration and its antimicrobial activity. Cells were treated with ozonated phosphate-buffered saline (8, 4, 2, 1, 0.5 and 0.25 μg/mL ozone), chlorhexidine 0.2% or buffered-solution, and cell viability was determined through MTT assay. The effect of ozone on cell migration was evaluated through scratch wound healing and transwell migration assays. The minimum inhibitory concentrations for Candida albicans and Staphylococcus aureus were determined. Ozone showed no cytotoxicity for the cell lines, while chlorhexidine markedly reduced cell viability. Although no significant difference between control and ozone-treated cells was observed in the scratch assay, a considerable increase in fibroblasts migration was noticed on cells treated with 8 μg/mL ozonated solution. Ozone alone did not inhibit growth of microorganisms; however, its association with chlorhexidine resulted in antimicrobial activity. This study confirms the wound healing and antimicrobial potential of ozone therapy and presents the need for studies to elucidate the molecular mechanisms through which it exerts such biological effects.

  14. Treatment of oral fungal infections using antimicrobial photodynamic therapy: a systematic review of currently available evidence.

    PubMed

    Javed, Fawad; Samaranayake, Lakshman P; Romanos, Georgios E

    2014-05-01

    The aim was to review the efficacy of antimicrobial photodynamic therapy (PDT) in the treatment of oral fungal infections. To address the focused question "Should PDT be considered a possible treatment regimen for oral fungal infections?" PubMed/Medline and Google-Scholar databases were searched from 1997 up to March 2014 using various combinations of the following key words: "Candida albicans"; "Candidiasis"; "Candidosis"; "denture stomatitis"; "oral" and "photodynamic therapy". Original studies, experimental studies and articles published solely in English language were sought. Letters to the editor, historic reviews and unpublished data were excluded. Pattern of the present literature review was customized to mainly summarize the pertinent information. Fifteen studies (3 clinical and 12 experimental) were included. All studies reported antimicrobial PDT to be an effective antifungal treatment strategy. One study reported PDT and azole therapy to be equally effective in the treatment of oral fungal infections. Methylene blue, toluidine blue and porphyrin derivative were the most commonly used photosensitizers. The laser wavelengths and power output ranged between ∼455 nm-660 nm and 30 mW-400 mW. The energy fluence ranged between 26-245 J cm(-2) and the duration or irradiation ranged between 10 seconds and 26 minutes. Clinical effectiveness of antimicrobial PDT as a potent therapeutic strategy for oral fungal infections requires further investigations.

  15. Effectiveness of antimicrobial photodynamic therapy on staphylococcus aureus using phenothiazinium dye with red laser

    NASA Astrophysics Data System (ADS)

    Monteiro, Juliana S. C.; de Oliveira, Susana C. P. S.; Pires-Santos, Gustavo M.; Sampaio, Fernando José P.; Zanin, Fátima Antônia A.; Pinheiro, Antônio L. B.

    2015-03-01

    The aim of this study was to evaluate in vitro the bactericidal effect of Antimicrobial Photodynamic Therapy - AmPDT using a phenothiazinium compound (toluidine blue O and methylene blue, 12.5 μg/mL) on Staphylococcus aureus (ATCC 23529) irradiated or not with the red laser (λ 660 nm, 12J/cm2). All tests were performed in triplicate and samples distributed into the following groups: Negative control, Laser, Photosensitizer, and AmPDT. Bactericidal effect of the Antimicrobial Photodynamic Therapy was assessed by counting of colony-forming units and analyzed statistically (ANOVA, Tukey test, p<0.05). The results showed, comparing the Laser group with Negative control, a statistically significant increase of counting on the Laser group (p = 0.003). The use of the photosensitizer alone reduced the mean number of CFU (64.8%) and its association with the Laser light resulted in 84.2% of inhibition. The results are indicative that the use of Antimicrobial Photodynamic Therapy presented in vitro bactericidal effect on Staphylococcus aureus.

  16. Engineered killer mimotopes: new synthetic peptides for antimicrobial therapy.

    PubMed

    Magliani, W; Conti, S; Salati, A; Arseni, S; Ravanetti, L; Frazzi, R; Polonelli, L

    2004-07-01

    This review deals with a novel approach to produce synthetic antibiotic peptides (killer mimotopes), similar to those described for the conversion of epitopes into peptide mimotopes, allowing their use as surrogate vaccines. Synthetic peptides pertaining to the complementary determining regions (CDRs) of a recombinant antiidiotypic antibody (PaKTscFv), which mimic the wide spectrum of microbicidal activity of a killer toxin produced by the yeast Pichia anomala (PaKT), have proven to act as structural or functional mimotopes of PaKT. This activity appeared to be mediated by interaction with specific cell wall killer toxin receptors (KTRs), mainly constituted by beta glucans. Killer mimotopes have shown in vitro an impressive microbicidal activity against Candida albicans. They were adopted as a model of PaKT- and PaKTscFv-susceptible microorganisms. Optimization through alanine scanning led to the generation of an engineered decapeptide (KP) of a CDR-L1 pertaining antibody fragment with an enhanced in vitro microbicidal activity. It had a potent therapeutic effect against experimental vaginal and systemic candidiasis in normal and immunodeficient mice caused by flucanozole susceptible and resistant yeast isolates. KP exerted a microbicidal activity in vitro against multidrug-resistant eukaryotic and prokaryotic pathogenic microorganisms, which was neutralized by interaction with laminarin (beta 1,3-glucan). To our knowledge, KP represents the prototype of an engineered peptide fragment derived from a microbicidal recombinant antiidiotypic antibody. It is capable of exerting antimicrobial activity in vitro and a therapeutic effect in vivo presumably acting through interaction with the beta glucan KTR component in the cell walls of pathogenic microorganisms.

  17. Rickettsial infection of the central nervous system: the role of prompt antimicrobial therapy.

    PubMed

    Shaked, Y

    1991-04-01

    Rickettsial diseases of man, which are prevalent in all the continents (except Antartica) continue to be a major health problem in tropical and temperate parts of the world. Rickettsioses must be considered in every traveller seeking medical attention soon after returning from endemic areas, since the disease can be associated with significant morbidity. When a definite diagnosis has been made by specific serological tests, prompt antimicrobial therapy is indicated. A tetracycline should be regarded as the drug of choice due to its high efficacy, low toxicity, superior in vitro activity and the possibility of relapse which can follow chloramphenicol therapy.

  18. A novel approach to the antimicrobial activity of maggot debridement therapy

    PubMed Central

    Andersen, Anders S.; Sandvang, Dorthe; Schnorr, Kirk M.; Kruse, Thomas; Neve, Søren; Joergensen, Bo; Karlsmark, Tonny; Krogfelt, Karen A.

    2010-01-01

    Objectives Commercially produced sterile green bottle fly Lucilia sericata maggots are successfully employed by practitioners worldwide to clean a multitude of chronic necrotic wounds and reduce wound bacterial burdens during maggot debridement therapy (MDT). Secretions from the maggots exhibit antimicrobial activity along with other activities beneficial for wound healing. With the rise of multidrug-resistant bacteria, new approaches to identifying the active compounds responsible for the antimicrobial activity within this treatment are imperative. Therefore, the aim of this study was to use a novel approach to investigate the output of secreted proteins from the maggots under conditions mimicking clinical treatments. Methods cDNA libraries constructed from microdissected salivary glands and whole maggots, respectively, were treated with transposon-assisted signal trapping (TAST), a technique selecting for the identification of secreted proteins. Several putative secreted components of insect immunity were identified, including a defensin named lucifensin, which was produced recombinantly as a Trx-fusion protein in Escherichia coli, purified using immobilized metal affinity chromatography and reverse-phase HPLC, and tested in vitro against Gram-positive and Gram-negative bacterial strains. Results Lucifensin was active against Staphylococcus carnosus, Streptococcus pyogenes and Streptococcus pneumoniae (MIC 2 mg/L), as well as Staphylococcus aureus (MIC 16 mg/L). The peptide did not show antimicrobial activity towards Gram-negative bacteria. The MIC of lucifensin for the methicillin-resistant S. aureus and glycopeptide-intermediate S. aureus isolates tested ranged from 8 to >128 mg/L. Conclusions The TAST results did not reveal any highly secreted compounds with putative antimicrobial activity, implying an alternative antimicrobial activity of MDT. Lucifensin showed antimicrobial activities comparable to other defensins and could have potential as a future drug

  19. Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships

    PubMed Central

    Mizuno, Kazue; Zhiyentayev, Timur; Huang, Liyi; Khalil, Sarwat; Nasim, Faria; Tegos, George P; Gali, Hariprasad; Jahnke, Ashlee; Wharton, Tim; Hamblin, Michael R

    2011-01-01

    Photosensitive dyes or photo sensitizers (PS) in combination with visible light and oxygen produce reactive oxygen species that kill cells in the process known as photodynamic therapy (PDT). Antimicrobial PDT employs PS that is selective for microbial cells and is a new treatment for infections. Most antimicrobial PS is based on tetrapyrrole or phenothiazinium structures that have been synthesized to carry quaternary cationic charges or basic amino groups. However we recently showed that cationic-substituted fullerene derivative were highly effective in killing a broad spectrum of microbial cells after illumination with white light. In the present report we compared a new group of synthetic fullerene derivatives that possessed either basic or quaternary amino groups as antimicrobial PS against Gram-positive (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli) and fungi (Candida albicans). Quantitative structure-function relationships were derived with LogP and hydrophilic lipophilic balance parameters. Compounds with non-quaternary amino groups tended to form nanoaggregates in water and were only effective against S. aureus. The most important determinant of effectiveness was an increased number of quaternary cationic groups that were widely dispersed around the fullerene cage to minimize aggregation. S. aureus was most susceptible; E. coli was intermediate, while C. albicans was the most resistant species tested. The high effectiveness of antimicrobial PDT with quaternized fullerenes suggest they may have applications in treatment of superficial infections (for instance in wounds and burns) where light penetration into tissue is not problematic. PMID:21743839

  20. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice

    PubMed Central

    Elliott, Thomas B.; Bolduc, David L.; Ledney, G. David; Kiang, Juliann G.; Fatanmi, Oluseyi O.; Wise, Stephen Y.; Romaine, Patricia L. P.; Newman, Victoria L.; Singh, Vijay K.

    2015-01-01

    Purpose: A combination therapy for combined injury (CI) using a non-specific immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine production. Materials and methods: Female B6D2F1/J mice received 9.75 Gy cobalt-60 gamma-radiation and wound. Bacteria were isolated and identified in three tissues. Incidence of bacteria and cytokines were compared between treatment groups. Results: Results demonstrated that the lethal dose for 50% at 30 days (LD50/30) of B6D2F1/J mice was 9.42 Gy. Antimicrobial therapy increased survival in radiation-injured (RI) mice. Combination therapy increased survival after RI and extended survival time but did not increase survival after CI. Sepsis began five days earlier in CI mice than RI mice with Gram-negative species predominating early and Gram-positive species increasing later. LVX plus AMX eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria in CI and most RI mice but not Gram-negative. Treatments significantly modulated 12 cytokines tested, which pertain to wound healing or elimination of infection. Conclusions: Combination therapy eliminates infection and prolongs survival time but does not assure CI mouse survival, suggesting that additional treatment for proliferative-cell recovery is required. PMID:25994812

  1. Photodynamic therapy: a new antimicrobial approach to infectious disease?

    PubMed Central

    Hasan, Tayyaba

    2011-01-01

    Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(−) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(+) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(−) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naïve strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin. PMID:15122361

  2. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    PubMed Central

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  3. The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review

    NASA Astrophysics Data System (ADS)

    Carrera, E. T.; Dias, H. B.; Corbi, S. C. T.; Marcantonio, R. A. C.; Bernardi, A. C. A.; Bagnato, V. S.; Hamblin, M. R.; Rastelli, A. N. S.

    2016-12-01

    In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications.

  4. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy

    PubMed Central

    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P.; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24–48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  5. Empiric antimicrobial therapy in severe sepsis and septic shock: optimizing pathogen clearance.

    PubMed

    Liang, Stephen Y; Kumar, Anand

    2015-07-01

    Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy.

  6. Empiric Antimicrobial Therapy in Severe Sepsis and Septic Shock: Optimizing Pathogen Clearance

    PubMed Central

    Liang, Stephen Y.

    2015-01-01

    Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy. PMID:26031965

  7. Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond

    PubMed Central

    Vatansever, Fatma; de Melo, Wanessa C.M.A.; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

    2013-01-01

    Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction of molecular oxygen. Four major ROS are recognized comprising: superoxide (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen (1O2), but they display very different kinetics and levels of activity. The effects of O2•− and H2O2 are less acute than those of •OH and 1O2, since the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and non-enzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or 1O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics, and non-pharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma and medicinal honey. A brief final section covers, reactive nitrogen species, and related therapeutics, such as acidified nitrite and nitric oxide releasing nanoparticles. PMID:23802986

  8. Assessment of an intervention aimed at early discontinuation of intravenous antimicrobial therapy in a Brazilian University hospital.

    PubMed

    Bonella, Gislaine Ferraresi; Fontes, Astrídia Marília de Souza; Jorge, Miguel Tanús; Silveira, Alexandre Barcelos Morais da

    2016-01-01

    Many interventions demonstrate success in adapting the duration of intravenous antibiotic therapy, but few studies have been conducted in developing countries. The aim of this study was to evaluate the effectiveness of an intervention in the induction of early discontinuation of intravenous antimicrobial therapy and/or its switch to oral therapy. The study employed a before-after intervention design that consisted of displaying a message in the computerized prescription on the third day and suspension of the prescription on the fifth day of intravenous antimicrobial therapy. A total of 465 patients were followed during the control period (CP) and 440 in the intervention period (IP). The intravenous therapy was switched to oral therapy for 11 (2.4%) patients during the CP and 25 (5.7%) in the IP (p=0.011), and was discontinued for 82 (17.6%) patients during the CP and 106 (24.1%) in the IP (p=0.017). During the IP there was a significant increase of patients who had their antimicrobial treatment discontinued before the seventh day of intravenous treatment, 37.40% (49/131) in the IP and 16.13% (15/93) in the CP (p=0.0005). The duration of intravenous antimicrobial therapy decreased by one day, but it was not significant (p=0.136). It is concluded that the proposed intervention is effective in promoting the early discontinuation of antimicrobial treatment and/or switch to oral therapy. As long as a computerized system for prescription already exists, it is easy and inexpensive to be implemented, especially in hospitals in developing countries.

  9. Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment.

    PubMed

    Gjini, Erida; Brito, Patricia H

    2016-04-01

    Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes.

  10. Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

    PubMed Central

    Gjini, Erida; Brito, Patricia H.

    2016-01-01

    Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes. PMID:27078624

  11. Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris.

    PubMed

    Borovaya, Alena; Dombrowski, Yvonne; Zwicker, Stephanie; Olisova, Olga; Ruzicka, Thomas; Wolf, Ronald; Schauber, Jürgen; Sárdy, Miklós

    2014-10-01

    In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.

  12. Antimicrobial therapy for the treatment of opportunistic infections in HIV/AIDS patients: a critical appraisal

    PubMed Central

    Seddon, Jo; Bhagani, Sanjay

    2011-01-01

    The widespread use of antiretroviral therapy (ART) has entirely changed the management of human immunodeficiency virus (HIV) infection and dramatically reduced the rates of opportunistic infections (OI). However, OI continue to cause significant morbidity and mortality in both developed countries, where presentation with advanced HIV infection is common, and also in developing countries where ART is less widely available. Evidence to direct OI guidelines is partly limited by the fact that many large-scale studies date from the pre-ART era and more recent studies are sometimes poorly powered due to the falling rates of OI. Treatment of OI is now known to be as much about antimicrobials as about immune reconstitution with ART, and recent studies help guide the timing of initiation of ART in different infections. OI have also become complicated by the immune reconstitution inflammatory syndrome phenomenon which may occur once successful immune recovery begins. Trimethoprim-sulfamethoxazole has long been one of the most important antibiotics in the treatment and prevention of OI and remains paramount. It has a broad spectrum of activity against Pneumocystis jiroveci, toxoplasmosis, and bacterial infections and has an important role to play in preventing life-threatening OI. New advances in treating OI are coming from a variety of quarters: in cytomegalovirus eye disease, the use of oral rather than intravenous drugs is changing the face of therapy; in cryptococcal meningitis, improved drug formulations and combination therapy is improving clearance rates and reducing drug toxicities; and in gut disease, the possibility of rapid immune restitution with ART is replacing the need for antimicrobials against cryptosporidia and microsporidia. PMID:22096404

  13. Antimicrobial photodynamic therapy for inactivation of biofilms formed by oral key pathogens

    PubMed Central

    Cieplik, Fabian; Tabenski, Laura; Buchalla, Wolfgang; Maisch, Tim

    2014-01-01

    With increasing numbers of antibiotic-resistant pathogens all over the world there is a pressing need for strategies that are capable of inactivating biofilm-state pathogens with less potential of developing resistances in pathogens. Antimicrobial strategies of that kind are especially needed in dentistry in order to avoid the usage of antibiotics for treatment of periodontal, endodontic or mucosal topical infections caused by bacterial or yeast biofilms. One possible option could be the antimicrobial photodynamic therapy (aPDT), whereby the lethal effect of aPDT is based on the principle that visible light activates a photosensitizer (PS), leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induce phototoxicity immediately during illumination. Many compounds have been described as potential PS for aPDT against bacterial and yeast biofilms so far, but conflicting results have been reported. Therefore, the aim of the present review is to outline the actual state of the art regarding the potential of aPDT for inactivation of biofilms formed in vitro with a main focus on those formed by oral key pathogens and structured regarding the distinct types of PS. PMID:25161649

  14. Synthesis and characterization of magnetite/silver/antibiotic nanocomposites for targeted antimicrobial therapy.

    PubMed

    Ivashchenko, Olena; Lewandowski, Mikołaj; Peplińska, Barbara; Jarek, Marcin; Nowaczyk, Grzegorz; Wiesner, Maciej; Załęski, Karol; Babutina, Tetyana; Warowicka, Alicja; Jurga, Stefan

    2015-10-01

    The article is devoted to preparation and characterization of magnetite/silver/antibiotic nanocomposites for targeted antimicrobial therapy. Magnetite nanopowder was produced by thermochemical technique; silver was deposited on the magnetite nanoparticles in the form of silver clusters. Magnetite/silver nanocomposite was investigated by XRD, SEM, TEM, AFM, XPS, EDX techniques. Adsorptivity of magnetite/silver nanocomposite towards seven antibiotics from five different groups was investigated. It was shown that rifampicin, doxycycline, ceftriaxone, cefotaxime and doxycycline may be attached by physical adsorption to magnetite/silver nanocomposite. Electrostatic surfaces of antibiotics were modeled and possible mechanism of antibiotic attachment is considered in this article. Raman spectra of magnetite, magnetite/silver and magnetite/silver/antibiotic were collected. It was found that it is difficult to detect the bands related to antibiotics in the magnetite/silver/antibiotic nanocomposite spectra due to their overlap by the broad carbon bands of magnetite nanopowder. Magnetic measurements revealed that magnetic saturation of the magnetite/silver/antibiotic nanocomposites decreased on 6-19 % in comparison with initial magnetite nanopowder. Pilot study of antimicrobial properties of the magnetite/silver/antibiotic nanocomposites were performed towards Bacillus pumilus.

  15. Action of antimicrobial photodynamic therapy on heterotypic biofilm: Candida albicans and Bacillus atrophaeus.

    PubMed

    Silva, Michelle Peneluppi; dos Santos, Thais Alves; de Barros, Patrícia Pimentel; de Camargo Ribeiro, Felipe; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2016-05-01

    The increase in survival and resistance of microorganisms organized in biofilms demonstrates the need for new studies to develop therapies able to break this barrier, such as photodynamic therapy, which is characterized as an alternative, effective, and non-invasive treatment. The objective was to evaluate in vitro the effect of antimicrobial photodynamic therapy on heterotypic biofilms of Candida albicans and Bacillus atrophaeus using rose bengal (12.5 μM) and light-emitting diode (LED) (532 nm and 16.2 J). We used standard strains of B. atrophaeus (ATCC 9372) and C. albicans (ATCC 18804). The biofilm was formed in the bottom of the plate for 48 h. For the photodynamic therapy (PDT) experimental groups, we added 100 μL of rose bengal with LED (P+L+), 100 μL of rose bengal without LED (P+L-), 100 μL of NaCl 0.9 % solution with LED (P-L+), and a control group without photosensitizer or LED (P-L-). The plates remained in agitation for 5 min (pre-irradiation) and were irradiated with LED for 3 min, and the biofilm was detached using an ultrasonic homogenizer for 30 s. Serial dilutions were plated in BHI agar and HiChrom agar and incubated at 37 °C/48 h. There was a reduction of 33.92 and 29.31 % of colony-forming units per milliliter (CFU/mL) for C. albicans and B. atrophaeus, respectively, from the control group to the group subjected to PDT. However, statistically significant differences were not observed among the P+L+, P+L-, P-L+, and P-L- groups. These results suggest that antimicrobial photodynamic therapy using rose bengal (12.5 μM) with a pre-irradiation period of 5 min and LED for 3 min was not enough to cause a significant reduction in the heterotypic biofilms of C. albicans and B. atrophaeus.

  16. Gene therapy based in antimicrobial peptides and proinflammatory cytokine prevents reactivation of experimental latent tuberculosis.

    PubMed

    Ramos-Espinosa, Octavio; Hernández-Bazán, Sujhey; Francisco-Cruz, Alejandro; Mata-Espinosa, Dulce; Barrios-Payán, Jorge; Marquina-Castillo, Brenda; López-Casillas, Fernando; Carretero, Marta; Del Río, Marcela; Hernández-Pando, Rogelio

    2016-10-01

    Mycobacterium tuberculosis (Mtb) latent infection can lead to reactivation. The design of new strategies to prevent it is an important subject. B6D2F1 mice were infected intratracheally with a low dose of Mtb H37Rv to induce chronic infection. After 7 months, mice were treated with one dose of recombinant adenoviruses encoding TNFα, β defensin-3 and LL37. Immunosupression was induced 1 month later with corticosterone. In comparison with the control group, mice treated with adenoviruses showed significantly less bacterial load and pneumonia, the adenoviruses encoding TNFα and LL37 being the most efficient. Gene therapy based in a proinflammatory cytokine or antimicrobial peptides is a potentially useful system to prevent reactivation of latent tuberculosis.

  17. In Vitro Osteoblast Model for Bone Wound Infections and Antimicrobial Therapy

    DTIC Science & Technology

    2012-10-01

    DynCorp (UK). The company stopped its  production  of  HA discs, and a suitable replacement was not found.  Therefore, the collagen  scaffold model was...repair.    For the proposed work, the collagen scaffolds were to be purchased by Beckton  Dickinson, but the  product  was not available and was uncertain... bactericidal  activities against all 3  pathogens.     Milestone 2: Therapy with antimicrobial peptides  The second stage of the proposed study was to

  18. Modeling laser irradiation conditions for mucosal tissues in antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zalesskaya, G. A.; Astaf'eva, L. G.; Plavskii, V. Yu.

    2012-05-01

    We use computer modeling to analzye empirically selected conditions for antimicrobial photodynamic therapy of mucosal tissues. We calculate the optical and thermal fields for experimental conditions for low-intensity (cold) laser irradiation used in treatment of lesions in mucosal tissues stained by methylene blue: λ = 670 nm, power density 150-300 mW/cm2, doses 9-18 J/cm2; λ = 632.8 nm, 15 mW/cm2, dose 4.5 J/cm2. For numerical estimates, we used the optical characteristics of methylene blue and three layers of mucosal tissues at the laser radiation wavelengths, and also the thermal characteristics of the tissues. The experimental conditions were optimized using the ratio of the tissue penetration depth for the absorbed optical energy and the penetration depth of methylene blue into the lesion, while maintaining safe tissue heating temperatures.

  19. Use of empiric antimicrobial therapy in neutropenic fever. Australian Consensus Guidelines 2011 Steering Committee.

    PubMed

    Tam, C S; O'Reilly, M; Andresen, D; Lingaratnam, S; Kelly, A; Burbury, K; Turnidge, J; Slavin, M A; Worth, L J; Dawson, L; Thursky, K A

    2011-01-01

    Administration of empiric antimicrobial therapy is standard practice in the management of neutropenic fever, but there remains considerable debate about the selection of an optimal regimen. In view of emerging evidence regarding efficacy and toxicity differences between empiric treatment regimens, and strong evidence of heterogeneity in clinical practice, the current guidelines were developed to provide Australian clinicians with comprehensive guidance for selecting an appropriate empiric strategy in the setting of neutropenic fever. Beta-lactam monotherapy is presented as the treatment of choice for all clinically stable patients while early treatment with combination antibiotic therapy is considered for patients at higher risk. Due consideration is given to the appropriate use of glycopeptides in this setting. Several clinical caveats, accounting for institution- and patient-specific risk factors, are provided to help guide the judicious use of the agents described. Detailed recommendations are also provided regarding time to first dose, timing of blood cultures, selection of a first-line antibiotic regimen, subsequent modification of antibiotic choice and cessation of therapy.

  20. The impact of antimicrobial photodynamic therapy on Streptococcus mutans in an artificial biofilm model

    NASA Astrophysics Data System (ADS)

    Schneider, Martin; Kirfel, Gregor; Krause, Felix; Berthold, Michael; Brede, Olivier; Frentzen, Matthias; Braun, Andreas

    2010-02-01

    The aim of the study was to assess the impact of laser induced antimicrobial photodynamic therapy on the viability of Streptococcus mutans cells employing an aritificial biofilm model. Employing sterile chambered coverglasses, a salivary pellicle layer formation was induced in 19 chambers. Streptococcus mutans cells were inoculated in a sterile culture medium. Using a live/dead bacterial viability kit, bacteria with intact cell membranes stain fluorescent green. Test chambers containing each the pellicle layer and 0.5 ml of the bacterial culture were analyzed using a confocal laser scan microscope within a layer of 10 μm at intervals of 1 μm from the pellicle layer. A photosensitizer was added to the test chambers and irradiated with a diode laser (wavelength: 660 nm, output power: 100 mW, Helbo) for 2 min each. Comparing the baseline fluorescence (median: 13.8 [U], min: 3.7, max: 26.2) with the values after adding the photosensitizer (median: 3.7, min: 1.1, max: 9), a dilution caused decrease of fluorescence could be observed (p<0.05). After irradiation of the samples with a diode laser, an additional 48 percent decrease of fluorescence became evident (median: 2.2, min: 0.4, max: 3.4) (p<0.05). Comparing the samples with added photosensitizer but without laser irradiation at different times, no decrease of fluorescence could be measured (p>0.05). The present study indicates that antimicrobial photodynamic therapy can reduce living bacteria within a layer of 10 μm in an artificial biofilm model. Further studies have to evaluate the maximum biofilm thickness that still allows a toxic effect on microorganisms.

  1. Application of benzo[a]phenoxazinium chlorides in Antimicrobial Photodynamic Therapy of Candida albicans biofilms.

    PubMed

    Lopes, Marisa; Alves, Carlos Tiago; Rama Raju, B; Gonçalves, M Sameiro T; Coutinho, Paulo J G; Henriques, Mariana; Belo, Isabel

    2014-12-01

    The use of Antimicrobial Photodynamic Therapy (APDT) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. The aim of this study was to verify the efficacy of photodynamic therapy using two new benzo[a]phenoxazinium photosensitizers against Candida albicans biofilms: N-(5-(3-hydroxypropylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSc) and N-(5-(11-hydroxyundecylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSd). The photodynamic activity of dyes against C. albicans biofilms was evaluated by incubating biofilms with dyes in the range of 100-300 μM for 3 or 18 h followed by illumination at 12 or 36 J cm(-2), using a xenon arc lamp (600 ± 2 nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300 μM of FSc with 18 h of incubation, followed by illumination at 36 J cm(-2). Contrarily, FSd had insignificant effect on biofilms inactivation by APDT. The higher uptake of FSc than FSd dye by biofilms during the dark incubation may explain the greater photodynamic effectiveness achieved with FSc. The results obtained stresses out the FSc-mediated APDT potential use to treat C. albicans infections.

  2. Adjunctive Application of Antimicrobial Photodynamic Therapy in Nonsurgical Periodontal Treatment: A Review of Literature

    PubMed Central

    Kikuchi, Takeshi; Mogi, Makio; Okabe, Iichiro; Okada, Kosuke; Goto, Hisashi; Sasaki, Yasuyuki; Fujimura, Takeki; Fukuda, Mitsuo; Mitani, Akio

    2015-01-01

    Periodontal disease is caused by dental plaque biofilms, and the removal of these biofilms from the root surface of teeth plays a central part in its treatment. The conventional treatment for periodontal disease fails to remove periodontal infection in a subset of cases, such as those with complicated root morphology. Adjunctive antimicrobial photodynamic therapy (aPDT) has been proposed as an additional treatment for this infectious disease. Many periodontal pathogenic bacteria are susceptible to low-power lasers in the presence of dyes, such as methylene blue, toluidine blue O, malachite green, and indocyanine green. aPDT uses these light-activated photosensitizer that is incorporated selectively by bacteria and absorbs a low-power laser/light with an appropriate wavelength to induce singlet oxygen and free radicals, which are toxic to bacteria. While this technique has been evaluated by many clinical studies, some systematic reviews and meta-analyses have reported controversial results about the benefits of aPDT for periodontal treatment. In the light of these previous reports, the aim of this review is to provide comprehensive information about aPDT and help extend knowledge of advanced laser therapy. PMID:26473843

  3. Antimicrobial blue light therapy for Candida albicans burn infection in mice

    NASA Astrophysics Data System (ADS)

    Zhang, Yunsong; Wang, Yucheng; Murray, Clinton K.; Hamblin, Michael R.; Gu, Ying; Dai, Tianhong

    2015-05-01

    In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans infection in acutely burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal infection in mouse burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse burns infected with C. albicans in comparison to infected mouse burns without blue light therapy (P=0.015).

  4. Evaluation of the effect of photodynamic antimicrobial therapy in dentin caries: a pilot in vivo study

    NASA Astrophysics Data System (ADS)

    Borges, F. M. C.; de-Melo, M. A. S.; Lima, J. M. P.; Zanin, I. C. J.; Rodrigues, L. K. A.; Nobre-dos-Santos, M.

    2010-02-01

    In vitro and in situ studies have demonstrated that the photodynamic antimicrobial therapy (PACT) is effective in reducing Streptococcus mutans population in artificially carious dentin. This pilot in vivo study evaluated the antimicrobial effect of PACT using toluidine blue O (TBO) and a light-emitting diode (LED) in carious dentin lesions. Five healthy adult volunteers (19-36 yr), with at least 4 active carious cavities each, participated in this study. Teeth of each volunteer were randomly divided into four groups: (1) without TBO and without light (Control); (2) with TBO alone (TBO); (3) with LED at 94/J cm2 alone (LED); and (4) with TBO plus LED at 94 J/cm2 (PACT). Each cavity was divided into two halves. The baseline carious dentin sample was collected from half of each cavity. Following, the treatments were performed using a random distribution of tooth into treatments. Then, the second collection of carious dentin samples was performed. Before and after treatments, dentin samples were analyzed with regard to the counts of total viable microorganisms, total streptococci, mutans streptococci, and lactobacilli. The data were statistically analyzed by Kruskal-Wallis and Student-Newman-Keuls tests (α=5%). Log reductions ranged from -0.12 to 2.68 and significant reductions were observed for PACT (group 4) when compared to the other groups (1, 2, and 3) for total streptococci and mutans streptococci. Concluding, PACT was effective in killing oral microorganisms present in in vivo carious dentin lesions and may be a promising technique for eliminating bacteria from dentin before restoration.

  5. Antimicrobial photodynamic therapy in a mouse model of Acinetobacter baumannii burn infection

    NASA Astrophysics Data System (ADS)

    Dai, Tianhong; Tegos, George P.; Lu, Zongshun; Zhiyentayev, Timur; Huang, Liyi; Franklin, Michael J.; Baer, David G.; Hamblin, Michael R.

    2009-06-01

    Multi-drug resistant Acinetobacter baumanii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment using traditional antibiotics can be extremely difficult and new antimicrobial approaches are being investigated. One of these antimicrobial alternatives could be the combination of non-toxic photosensitizers (PS) and visible light known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by covalent conjugation chlorin(e6) to polyethylenimine followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-second burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted on average 22 days characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after applying bacteria gave over three logs of loss of bacterial luminescence in a light exposure dependent manner, while PDT carried out on day 1 and day 2 gave approximately a 1.7-log reduction. Application of PS dissolved in 10% or 20% DMSO without light gave only modest reduction in bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multi-drug resistant localized A. baumannii infections.

  6. Effect of selective antimicrobial therapy on plaque and gingivitis in the dog.

    PubMed

    Heijl, L; Lindhe, J

    1980-12-01

    The present investigation was performed to assess the effect of selective antibiotic therapy on developing plaque and gingivitis in dogs, which at the start of the study had normal gingiva. Fifteen beagle dogs were used. Throughout the entire observation period the animals were fed a diet which favored plaque accumulation. A baseline examination involved assessments of plaque, gingivitis and gingival exudate. The subgingival bacterial flora was assessed by dark-field microscopy. Subsequently the teeth of the right jaws were allowed to accumulate plaque. A careful tooth-cleaning program was maintained in the left jaws. Plaque and gingivitis assessments were repeated and subgingival plaque sampled in the right jaws after 14 and 28 days. On experimental day 28 the second part of the study was initiated. The dogs were randomly distributed into three groups of five animals each. A new baseline examination was performed in the left jaws, after which all tooth cleanings were terminated. During the subsequent 28 days each group of dogs was treated with one of three antimicrobial compounds (vancomycin, metronidazole or clindamycin). Examinations were repeated after 14 and 28 days. The results demonstrated that systemic administration of antimicrobial substances can reduce the rate of plaque formation, change the composition of the developing subgingival microbiota and prevent (or retard) the onset of gingivitis. A comparison of the ability of the three compounds to prevent the formation of a "gingivitis-inducing" plaque revealed that metronidazole and clindamycin were markedly more effective than vancomycin. In fact, in dogs receiving metronidazole and clindamycin treatment, the initiation of gingivitis was almost entirely prevented during the 28 days of treatment.

  7. Assessing appropriateness of antimicrobial therapy: in the eye of the interpreter.

    PubMed

    DePestel, Daryl D; Eiland, Edward H; Lusardi, Katherine; Destache, Christopher J; Mercier, Renée-Claude; McDaneld, Patrick M; Lamp, Kenneth C; Chung, Thomas J; Hermsen, Elizabeth D

    2014-10-15

    To address the increase of drug-resistant bacteria and widespread inappropriate use of antimicrobials, many healthcare institutions have implemented antimicrobial stewardship programs to promote appropriate use of antimicrobials and optimize patient outcomes. However, a consensus definition of appropriate use is lacking. We conducted a multicenter observational study to compare 4 definitions of appropriateness--a study site-specific definition, use supported by susceptibility data, use supported by electronic drug information resources (Clinical Pharmacology/Micromedex), or study site principal investigator (PI) opinion-among patients receiving 1 or more of 13 identified antimicrobials. Data were collected for 262 patients. Overall, appropriateness with the 4 definitions ranged from 79% based on PI opinion to 94% based on susceptibility data. No single definition resulted in consistently high appropriate use for all target antimicrobials. For individual antimicrobials, the definitions with the highest rate of appropriate use were Clinical Pharmacology/Micromedex support (6 of 7 antimicrobials) and susceptibility data (5 of 7 antimicrobials). For specific indications, support from susceptibility data resulted in the highest rate of appropriate use (4 of 7 indications). Overall comparisons showed that appropriateness assessed by PI opinion differed significantly compared with other definitions when stratified by either target antimicrobial or indication. The significant variability in the rate of appropriate use highlights the difficulty in developing a standardized definition that can be used to benchmark judicious antimicrobial use.

  8. A Stewardship Approach To Optimize Antimicrobial Therapy through Use of a Rapid Microarray Assay on Blood Cultures Positive for Gram-Negative Bacteria.

    PubMed

    Sothoron, Conner; Ferreira, Jason; Guzman, Nilmarie; Aldridge, Petra; McCarter, Yvette S; Jankowski, Christopher A

    2015-11-01

    A Gram-negative (GN) blood culture microarray assay with an antimicrobial stewardship program (ASP) intervention was evaluated in 126 patients with GN bacteremia. The median time to optimal therapy was shorter in the postintervention group than in the preintervention group (49.3 h versus 38.5 h, respectively; P = 0.0199). ASP can utilize microarray technology to decrease the time to optimal antimicrobial therapy.

  9. Antimicrobial photodynamic therapy: an effective alternative approach to control fungal infections

    PubMed Central

    Baltazar, Ludmila M.; Ray, Anjana; Santos, Daniel A.; Cisalpino, Patrícia S.; Friedman, Adam J.; Nosanchuk, Joshua D.

    2015-01-01

    Skin mycoses are caused mainly by dermatophytes, which are fungal species that primarily infect areas rich in keratin such as hair, nails, and skin. Significantly, there are increasing rates of antimicrobial resistance among dermatophytes, especially for Trichophyton rubrum, the most frequent etiologic agent worldwide. Hence, investigators have been developing new therapeutic approaches, including photodynamic treatment. Photodynamic therapy (PDT) utilizes a photosensitive substance activated by a light source of a specific wavelength. The photoactivation induces cascades of photochemicals and photobiological events that cause irreversible changes in the exposed cells. Although photodynamic approaches are well established experimentally for the treatment of certain cutaneous infections, there is limited information about its mechanism of action for specific pathogens as well as the risks to healthy tissues. In this work, we have conducted a comprehensive review of the current knowledge of PDT as it specifically applies to fungal diseases. The data to date suggests that photodynamic treatment approaches hold great promise for combating certain fungal pathogens, particularly dermatophytes. PMID:25821448

  10. Singlet oxygen in antimicrobial photodynamic therapy: photosensitizer-dependent production and decay in E. coli.

    PubMed

    Ragàs, Xavier; He, Xin; Agut, Montserrat; Roxo-Rosa, Mónica; Gonsalves, António Rocha; Serra, Arménio C; Nonell, Santi

    2013-02-28

    Several families of photosensitizers are currently being scrutinized for antimicrobial photodynamic therapy applications. Differences in physical and photochemical properties can lead to different localization patterns as well as differences in singlet oxygen production and decay when the photosensitizers are taken up by bacterial cells. We have examined the production and fate of singlet oxygen in Escherichia coli upon photosensitization with three structurally-different cationic photosensitizers, namely New Methylene Blue N (NMB), a member of the phenothiazine family, ACS268, a hydrophobic porphyrin with a single cationic alkyl chain, and zinc(II)-tetramethyltetrapyridinoporphyrazinium salt, a phthalocyanine-like photosensitizer with four positive charges on the macrocycle core. The kinetics of singlet oxygen production and decay indicate different localization for the three photosensitizers, whereby NMB appears to localize in an aqueous-like microenvironment, whereas ACS268 localizes in an oxygen-shielded site, highly reactive towards singlet oxygen. The tetracationic zinc(II) tetrapyridinoporphyrazine is extensively aggregated in the bacteria and fails to produce any detectable singlet oxygen.

  11. Antimicrobial photodynamic therapy minimizes the deleterious effect of nicotine in female rats with induced periodontitis.

    PubMed

    Gualberto, Erivan Clementino; Theodoro, Letícia Helena; Longo, Mariellén; Novaes, Vivian Cristina Noronha; Nagata, Maria José Hitomi; Ervolino, Edilson; Garcia, Valdir Gouveia

    2016-01-01

    The aim of this study was to compare the use of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) in the treatment of experimentally induced periodontitis in female rats that were systemically treated with or without nicotine. Female rats (n = 180) were divided into two groups: vehicle administration (Veh) and nicotine administration (Nic). Mini-pumps containing either vehicle or nicotine were implanted in the rats 30 days before the induction of experimental periodontitis (EP). EP was induced by placing a cotton ligature around the left mandibular first molar. After 7 days, the ligature was removed, and the rats were randomly divided into three treatment subgroups: SRP (only SRP), DL (SRP plus diode laser), and aPDT (SRP plus aPDT). The aPDT consisted of phenothiazine photosensitizer deposition followed by diode laser irradiation. Ten rats from each subgroup were euthanized at 7, 15, and 30 days after treatment. Alveolar bone loss (ABL) in the furcation region was evaluated using histological, histometric, and immunohistochemical analyses. The rats that were treated with nicotine showed more ABL compared to those treated with vehicle. In both the Veh and Nic groups, SRP plus aPDT treatment resulted in reduced ABL, smaller numbers of both TRAP- and RANKL-positive cells, and higher numbers of PCNA-positive cells compared to SRP treatment alone. aPDT was an effective adjunctive therapy for the treatment of periodontitis in female rats regardless of whether they received nicotine.

  12. Antimicrobial peptide isolated from Bacillus amyloliquefaciens K14 revitalizes its use in combinatorial drug therapy.

    PubMed

    Regmi, Sudip; Choi, Yun Hee; Choi, Yoon Seok; Kim, Mi Ri; Yoo, Jin Cheol

    2017-03-01

    The present study was performed to evaluate the antibacterial activities of an antimicrobial peptide (CSpK14) and the synergies thereof with β-lactams against vancomycin-resistant Staphylococcus aureus (VRSA) and Enterococci (VRE). Our strain was isolated from fermented food (kimchi), which is 99.79 % homologous with Bacillus amyloliquefaciens subsp. plantarum FZB42(T). CSpK14 was purified to homogeneity by diammonium sulfate precipitation, concentration, dialysis, and followed by two-stage chromatographic separation, i.e., Sepharose Cl-6B and Sephadex G-25 chromatography, and had a molar mass of ~4.6 kDa via Tricine SDS-PAGE and in situ examination. It was stable at pH 6.0-11.5 and temperature up to 80 °C. In addition, it was also stable with various metal ions, solvents, and proteases. The N-terminal amino acid sequence was H-Y-D-P-G-D-D-S-G-N-T-G and did not show any significant homology with reported peptides. However, it shows some degrees of identity with alpha-2-macroglobulin and ligand-gated channel protein from different microorganisms. CSpK14 significantly reduced the minimum inhibitory concentrations (MICs) of β-lactams and had no effect on non-β-lactams against VRSA and VRE. MICs of CSpK14/oxacillin and CSpK14/ampicillin were reduced by 8- to 64-fold and 2- to 16-fold, respectively. The time killing assay between CSpK14/oxacillin (2.29-2.37 Δlog10CFU/mL at 24 h) and CSpK14/ampicillin (2.30-2.38 Δlog10CFU/mL at 24 h) being >2-fold and fractional inhibitory concentration index ˂0.5 revealed synergy. Furthermore, the biofilms formed by VRSA and VRE were reduced completely. CSpK14 was simple to purify, had low molecular mass, was stable over a wide pH range or tested chemicals, had broad inhibitory spectrum, and possessed potent synergistic antimicrobial-antibiofilm properties. CSpK14 synergistically enhanced the efficacy of β-lactams and is therefore suitable for combination therapy.

  13. Antimicrobial and anti-inflammatory activity of chitosan-alginate nanoparticles: a targeted therapy for cutaneous pathogens

    PubMed Central

    Friedman, Adam J; Phan, Jenny; Schairer, David; Champer, Jackson; Qin, Min; Pirouz, Aslan; Blecher, Karin; Oren, Ami; Liu, Phil; Modlin, Robert L; Kim, Jenny

    2012-01-01

    Advances in nanotechnology have demonstrated potential application of nanoparticles for effective and targeted drug delivery. Here, we investigated the antimicrobial and immunological properties and the feasibility of using nanoparticles to deliver antimicrobial agents to treat a cutaneous pathogen. Nanoparticles synthesized with chitosan and alginate demonstrated a direct antimicrobial activity in vitro against Propionibacterium acnes, the bacterium linked to the pathogenesis of acne. By electron microscopy imaging, chitosan-alginate nanoparticles were found to induce disruption of the P. acnes cell membrane, providing a mechanism for the bactericidal effect. The chitosan-alginate nanoparticles also exhibited anti-inflammatory properties as they inhibited P. acnes induced inflammatory cytokine production in human monocytes and keratinocytes. Furthermore, benzoyl peroxide, a commonly used anti-acne drug, was effectively encapsulated in the chitosan-alginate nanoparticles and demonstrated superior antimicrobial activity against P. acnes compared to benzoyl peroxide alone while demonstrating less toxicity to eukaryotic cells. Together, these data suggest the potential utility of topical delivery of chitosan-alginate nanoparticle encapsulated drug therapy for the treatment of dermatologic conditions with infectious and inflammatory components. PMID:23190896

  14. Review of antimicrobial therapy of selected bacterial diseases in broiler chickens in Canada

    PubMed Central

    Agunos, Agnes; Léger, Dave; Carson, Carolee

    2012-01-01

    This paper reviews common therapeutic applications of antimicrobials in broiler chicken production in relation to Canadian guidelines, surveillance data, and emerging public health concerns about antimicrobial use (AMU). Escherichia coli, Clostridium perfringens, and Staphylococcus spp., were reviewed because of their animal health and economic significance. Enterococcus cecorum and Salmonella were included because of their importance in antimicrobial resistance (AMR) surveillance. This review identified that i) antimicrobials are available in Canada to treat infections by these agents, but may be through over the counter or extra-label use, ii) prevalence rates for these diseases are unknown, iii) antimicrobial use estimates in broilers are lacking, and iv) AMR has emerged in clinical isolates, though data are very sparse. This review highlights the need for surveillance of AMU and AMR in broiler chickens in Canada. PMID:23729827

  15. Current State of Topical Antimicrobial Therapy in Management of Early Childhood Caries

    PubMed Central

    Jayabal, JayaBaarathi; Mahesh, Ramakrishnan

    2014-01-01

    The treatment of early childhood caries can have a significant economical burden and treatment relapses are frequent. Effective intervention by means of topical antimicrobial agents can reduce the burden of early childhood caries. The main aim in prevention and treatment should focus on inhibition of the growth of oral bacteria. This is a comprehensive review of the literature on the various antimicrobial agents which are proven to be effective in management of this carious progression. The review identified that there is a significant data to suggest use of antimicrobial agents in management of early childhood caries. Antimicrobial agents aid in better management of patients with early carious lesion. The relapse rates are less, when the treatment is combined with the use of antimicrobial agent. PMID:24701354

  16. Antimicrobial photodynamic therapy as an adjunct for treatment of deep carious lesions-a systematic review.

    PubMed

    Cieplik, Fabian; Buchalla, Wolfgang; Hellwig, Elmar; Al-Ahmad, Ali; Hiller, Karl-Anton; Maisch, Tim; Karygianni, Lamprini

    2017-01-15

    For deep carious lesions, a more conservative treatment modality ("selective caries removal") has been proposed, where only the heavily contaminated dentine is removed. In this regard, effective adjuncts for cavity disinfection such as the antimicrobial photodynamic therapy (aPDT) can be valuable clinically prior to definitive restoration. Therefore, the aim of this study was to systematically assess clinical studies on the effectiveness of aPDT as a supplementary tool in the treatment of deep caries lesions. Searches were performed in four databases (PubMed, EMBASE, ISI Web of Science, ClinicalTrials.gov) from 1st January, 2011 until 21st June, 2016 for search terms relevant to the observed parameters, pathological condition, intervention and anatomic entity. The pooled information was evaluated according to PRISMA guidelines. At first, 1,651 articles were recovered, of which 1,249 full-text articles were evaluated, 270 articles thereof were reviewed for eligibility and finally 6 articles met all inclusion criteria. The aPDT protocols involved Methylene Blue, Toluidine Blue and aluminium-chloride-phthalocyanine as photosensitizers and diode lasers, light-emitting diodes and halogen light-sources. The data from five reports, utilizing both culture-dependent and -independent methods, disclosed significant reduction of cariogenic bacterial load after mechanical caries removal with adjunct aPDT. As these studies exhibit some methodological limitations, e.g. lack of positive controls, this systematic review can support the application of aPDT to a limited extent only in terms of reducing the microbial load in deep carious lesions before restorative treatment.

  17. Efficacy of antimicrobial photodynamic therapy as an adjuvant in periodontal treatment in Down syndrome patients.

    PubMed

    Martins, Fabiana; Simões, Alyne; Oliveira, Marcio; Luiz, Ana Claudia; Gallottini, Marina; Pannuti, Claudio

    2016-12-01

    Down syndrome (DS) has characteristics that include mental retardation, a characteristic phenotype, congenital heart defects, immune disorders, and increased risk of periodontal disease (PD). Antimicrobial photodynamic therapy (aPDT) is the combined use of photosensitizers associated with low-level laser (LLL) and oxygen, leading to singlet oxygen formation, which contributes to the antibacterial activity of the phagocytes, killing bacteria. The objective of this study was to evaluate the efficacy of aPDT as an adjuvant to conventional periodontal treatment of PD in DS patients. A double-blinded, controlled, randomized, split-mouth study was conducted. A total of 13 DS subjects who were 18 years or older and who presented at least one tooth in each quadrant of the mouth with probing pocket depth (PPD) equal to or greater than 5 mm were included. The patients were evaluated at three different times: at the baseline, PPD were obtained. After 1 week, conventional scaling and root planing (SRP) was performed, and two randomly selected quadrants also received aPDT. One month after SRP, all the patients were reevaluated. Periodontal conditions were improved among all the participants. The PDT-with-SRP group presented a nonsignificant reduction in PPD (mean = 1.27 mm, median = 1.17 mm) relative to that of the SRP group (mean = 1.00 mm, median = 0.95 mm). Changes over time were compared using the Wilcoxon test. A significant reduction in median PPD was observed in both groups (p = 0.001). Both types of periodontal treatment, with and without PDT, were similarly effective and were associated with good clinical response.

  18. Conjugation of photosensitisers to antimicrobial peptides increases the efficiency of photodynamic therapy in cancer cells.

    PubMed

    Moret, Francesca; Gobbo, Marina; Reddi, Elena

    2015-07-01

    Some antimicrobial peptides (AMPs) have the ability to penetrate and kill not only pathogenic microorganisms but also cancer cells, while they are less active toward normal eukaryotic cells. Here we have investigated the potential of three AMPs, namely apidaecin 1b (Api), magainin 2 (Mag) and buforin II (Buf), as carriers of drugs for cancer cells by using the hydrophobic photosensitiser 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (cTPP) as the drug model, conjugated to the N-terminus of the peptides. Flow cytometry measurements demonstrated that conjugation of cTPP increased its rate and efficiency of uptake in A549 human lung adenocarcinoma cells in the order Mag > Buf > Api. In vitro photodynamic therapy (PDT) experiments showed that the increased uptake of the conjugated cTPP determined 100% cell killing at concentrations in the nanomolar range while micromolar concentrations were required for the same killing effect with unconjugated cTPP. Serum proteins interacted with cTPP conjugated to Buf and Api and slightly interfered with the cellular uptake of these conjugates but not with that of Mag. The data suggest electrostatic interactions of the conjugates with sialic acid and ganglioside rich domains, as lipid rafts of the plasma membrane, followed by cell internalization via non-caveolar dynamin-dependent endocytosis as indicated by the effects of inhibitors of specific endocytic pathways. Our study demonstrated that the three AMPs investigated, Mag in particular, have the ability to carry a hydrophobic cargo inside cancer cells and may therefore represent useful carriers of anticancer drugs, especially those with a poor capacity to penetrate inside the target cells.

  19. Antimicrobial photodynamic therapy for the decolonization of methicillin-resistant Staphylococcus aureus from the anterior nares

    NASA Astrophysics Data System (ADS)

    Street, Cale N.; Pedigo, Lisa; Gibbs, Aaron; Loebel, Nicolas G.

    2009-06-01

    The nosocomial infection rate has increased dramatically due to emergence of antibiotic resistant bacterial strains such as methicillin resistant Staphylococcus aureus (MRSA). The primary anatomical site of MRSA colonization is the anterior nares, and this reservoir represents a primary vector of transmission from non-infected carriers to susceptible individuals. Antimicrobial photodynamic therapy (aPDT) has been used successfully for topical disinfection in the oral cavity. The aim of this study was to evaluate the utility of aPDT for nasal MRSA decolonization at the preclinical and clinical level. The nasal aPDT system consists of a 670 nm diode laser fibre-optically coupled to a disposable light diffusing tip, used to activate a methylene blue based photosensitizer formulation. Preclinical testing was done both in a custom nasal reservoir model and on human skin cultures colonized on the epithelial surface with MRSA. Human clinical testing was performed by clinicians in regions in which the system is approved by the regulatory authority. In vitro testing demonstrated that aPDT eradicated planktonic MRSA in an energy and photosensitizer concentration dependent manner. Furthermore, aPDT eliminated sustained colonization of MRSA on cultured human epithelial surfaces, an effect that was sustained over multiple days post-treatment. In preliminary human testing, aPDT eradicated MRSA completely from the nose with total treatment times <10 minutes. aPDT is effective against MRSA when used topically in the nose. Energy dose and photosensitizer parameters have been optimized for the nasal environment. Controlled clinical studies are currently underway to further evaluate safety and efficacy.

  20. Antibiotic-free nanotherapeutics: hypericin nanoparticles thereof for improved in vitro and in vivo antimicrobial photodynamic therapy and wound healing.

    PubMed

    Nafee, Noha; Youssef, Alaa; El-Gowelli, Hanan; Asem, Heba; Kandil, Sherif

    2013-09-15

    Hypericin (HY) is a naturally-occurring, potent photosensitizer. However, its lipophilicity limits its therapeutic applications. Our attempt is, thus, to develop a biodegradable nanocarrier for hypericin capable of preserving its antibacterial photoactivity. Amphiphilic block copolymers were synthesized to prepare hypericin-laden nanoparticles (HY-NPs). The antimicrobial photoactivity of HY-NPs was assessed; in vitro against biofilm and planktonic cells of methicillin resistant Staphylococcus aureus (MRSA) clinical isolates and in vivo on infected wounds in rats. Nanoparticles of 45 nm in diameter ensured higher amounts of reactive oxygen species upon irradiation. HY-NPs demonstrated superior inhibition of biofilm over planktonic cells. In vivo wound healing studies in rats revealed faster healing, better epithelialization, keratinization and development of collagen fibers when HY-NPs were applied. Determination of growth factors and inflammatory mediators in the wound area confirmed superior healing potential of nanoencapsulated hypericin suggesting that hypericin can join the era of antibiotic-free antimicrobial therapy.

  1. MALDI-TOF alone versus MALDI-TOF combined with real-time antimicrobial stewardship interventions on time to optimal antimicrobial therapy in patients with positive blood cultures.

    PubMed

    Beganovic, Maya; Costello, Michael; Wieczorkiewicz, Sarah M

    2017-02-22

    Introduction: Matrix-assisted laser desorption ionization time of flight (MALDI-TOF) decreases time to organism identification and improves clinical and financial outcomes. The purpose of this study was to evaluate the impact of MALDI-TOF alone vs MALDI-TOF combined with real-time, pharmacist-driven, antimicrobial stewardship (AMS) intervention on patient outcomes.Methods: This single-center, pre-post quasi-experimental study evaluated hospitalized patients with positive blood cultures identified via MALDI-TOF combined with prospective AMS intervention, compared to a control cohort with MALDI-TOF identification without AMS intervention. AMS intervention included: real-time MALDI-TOF pharmacist notification, and prospective AMS provider feedback. The primary outcome was time to optimal antimicrobial therapy (TTOT).Results: A total of 252 blood cultures were included for final analysis: 126 in each group. MALDI-TOF + AMS intervention significantly reduced overall TTOT (75.17 vs 43.06 h, p <0.001), Gram + contaminant TTOT (48.21 vs 11.75 h, p <0.001), Gram - infection (GNI) TTOT (71.83 vs 35.98 h, p <0.001), and reduced overall hospital LOS (15.03 vs 9.02 days, p 0.021). TTOT for Gram + infection (GPI) was improved (64.04 vs 41.61 h, p 0.082). For GPI: reduced hospital LOS (14.64 vs 10.31 days, p 0.002) and length of antimicrobial therapy 24.30 vs 18.97 days, p 0.018). For GNI: reduced time to microbiologic clearance (51.13 vs 34.51 h, p <0.001), hospital LOS (15.40 vs 7.90 days, p 0.027), and ICU LOS (5.55 vs 1.19 days, p 0.035).Conclusion: In order to achieve optimal outcomes, rapid identification with MALDI-TOF combined with real-time AMS interventions is more impactful than MALDI-TOF alone.

  2. Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections

    NASA Astrophysics Data System (ADS)

    Ottosson, H.; Nylén, F.; Sarker, P.; Miraglia, E.; Bergman, P.; Gudmundsson, G. H.; Raqib, R.; Agerberth, B.; Strömberg, R.

    2016-11-01

    A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD’s are promising candidates for treatment of infections.

  3. Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections

    PubMed Central

    Ottosson, H.; Nylén, F.; Sarker, P.; Miraglia, E.; Bergman, P.; Gudmundsson, G. H.; Raqib, R.; Agerberth, B.; Strömberg, R.

    2016-01-01

    A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD’s are promising candidates for treatment of infections. PMID:27827460

  4. Potency of parenteral antimicrobials including ceftolozane/tazobactam against nosocomial respiratory tract pathogens: considerations for empiric and directed therapy

    PubMed Central

    Sutherland, Christina A.

    2017-01-01

    Background Empiric therapy decisions are predicated on knowledge of both the epidemiology and antimicrobial susceptibility of the probable infecting pathogen(s). The objective of this study was to evaluate the microbial distribution and phenotypic profiles of nosocomial respiratory isolates collected from multiple US hospitals and assess the clinical utility of various monotherapy and combination regimens. Methods Hospitals provided consecutive non-duplicate adult inpatients Gram-negative nosocomial respiratory isolates from cultures received ≥48 h after hospital admission. Minimum inhibitory concentrations (MICs) for 12 antimicrobials were determined using broth microdilution methods. An antibiogram was constructed for monotherapy regimens as well as combinations inclusive of either tobramycin (TOB) or ciprofloxacin (CIP). Results Six hospitals provided 518 nosocomial respiratory isolates. P. aeruginosa (PSA) comprised 28% of the population followed by Klebsiella pneumoniae (13%), Enterobacter spp. (13%), S. maltophilia (9%), S. marcesens (6%), A. baumannii (6%), and others (18%). When considering monotherapy for the Enterobacteriaceae & PSA ceftolozane/tazobactam (C/T) provided the highest (87%) percent susceptibility (%S) followed by meropenem (MEM), CIP, cefepime (FEP), ceftazidime (CAZ) and piperacillin-tazobactam (TZP) at 71–85%S. The addition of TOB > CIP improved the probability that the antimicrobial combination would provide ≥1 active agent. Conclusions PSA was the predominant nosocomial respiratory pathogen; however, the Enterobacteriaceae comprised an additional 53% in this survey. When considering empiric β-lactam monotherapy therapy for the entire spectrum of pathogens C/T provided the highest (78%) %S followed by MEM, FEP and TZP. The addition of either TOB > CIP to these β-lactams enhances the likelihood that an active agent would be selected when considering empirical therapy choices for nosocomial respiratory tract infections. PMID

  5. Role of Combination Antimicrobial Therapy for Vancomycin-Resistant Enterococcus faecium Infections: Review of the Current Evidence.

    PubMed

    Yim, Juwon; Smith, Jordan R; Rybak, Michael J

    2017-03-08

    Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including β-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed. This article is protected by copyright. All rights reserved.

  6. Indocyanine green (ICG) as a new adjuvant for the antimicrobial photo-dynamic therapy (aPDT) in dentistry

    NASA Astrophysics Data System (ADS)

    Meister, Joerg; Hopp, Michael; Schäfers, Johannes; Verbeek, Jonas; Kraus, Dominik; Frentzen, Matthias

    2014-02-01

    Clinical surveys show a continuous increase of antimicrobial resistance related to the frequency of the administrated medication. The antimicrobial photodynamic therapy (aPDT) is an effective adjuvant to reduce the need of antibiotics in dentistry, especially in periodontics. The antimicrobial effect of lightactivated photosensitizers in periodontics is demonstrated in clinical studies and case reports. Indocyanine green (ICG) as a new adjuvant shows the high potential of antiphlogistic and antimicrobial effects in combination with laser-light activation. In trying to answer the question of just how far the influence of temperature is acting on bacteria, this study was carried out. The influences of ICG at different concentrations (0.01 up to 1 mg/ml) in combination with a culture medium (brain-heart-infusion) and a bacteria culture (Streptococcus salivarius) at different optical densities (OD600 0.5 and 0.1) were investigated under laser-light activation. Laser activation was carried out with diode laser at 810 nm and two different power settings (100 mW/300 mW). The pulse repetition rate was 2 kHz. Taking account of the fiber diameter, distance and spot size on the sample surface, the applicated intensities were 6.2 and 18.7 W/cm2. Total irradiation time was 20 s for all meaurements. Transmitted laser power and temperature increase in the culture medium as well as in the bacteria culture were determined. Additionally the influence of ICG regarding bacterial growth and bactericidal effect was investigated in the bacteria culture without laser irradiation. Without laser, no bactericidal effect of ICG was observed. Only a bacteriostatic effect could be proved. In dependence of the ICG concentration and the applied intensities a temperature increase of ΔT up to 80°C was measured.

  7. Effect of different scenarios for selective dry-cow therapy on udder health, antimicrobial usage, and economics.

    PubMed

    Scherpenzeel, C G M; den Uijl, I E M; van Schaik, G; Riekerink, R G M Olde; Hogeveen, H; Lam, T J G M

    2016-05-01

    The goal of dry-cow therapy (DCT) is to reduce the prevalence of intramammary infections (IMI) by eliminating existing IMI at drying off and preventing new IMI from occurring during the dry period. Due to public health concerns, however, preventive use of antimicrobials has become questionable. In this study, we evaluated the effects of 8 scenarios for selecting animals for DCT, taking into account variation in parity and cow-level somatic cell count (SCC) at drying off. The aim of this study was to evaluate udder health, antimicrobial usage, and economics at the herd level when using different scenarios for selecting cows for DCT. To enable calculation and comparison of the effects of different scenarios to select cows for DCT in an "average" herd, we created an example herd, with a virtual herd size of 100 dairy cows to be calving during a year. Udder health, antimicrobial usage, and economics were evaluated during the dry period and the first 100 d in lactation, the period during which the greatest effect of DCT is expected. This leads to an estimated 13,551 cow-days at risk during a year in a 100-cow dairy herd. In addition to a blanket DCT (BDCT) scenario, we developed 7 scenarios to select cows for DCT based on SCC. The scenarios covered a range of possible approaches to select low-SCC cows for DCT, all based on cow-level SCC thresholds on the last milk recording before drying off. The incidence rate of clinical mastitis in the example herd varied from 11.6 to 14.5 cases of clinical mastitis per 10,000 cow-days at risk in the different scenarios, and the prevalence of subclinical mastitis varied from 38.8% in scenario 1 (BDCT) to 48.3% in scenario 8. Total antimicrobial usage for DCT and clinical mastitis treatment varied over the scenarios from 1.27 (scenario 8) to 3.15 animal daily dosages (BDCT), leading to a maximum reduction in antimicrobial usage of 60% for scenario 8 compared with BDCT. The total costs for each of the scenarios showed little variation

  8. Catheter-associated and nosocomial urinary tract infections: antibiotic resistance and influence on commonly used antimicrobial therapy.

    PubMed

    Milan, Potic B; Ivan, Ignjatovic M

    2009-01-01

    The objective is to evaluate resistance between community-acquired urinary tract infections (CAUTI), nosocomialy-acquired urinary tract infections (NAUTI), and empirical therapy adequacy. E. coli is the predominant pathogen of both CAUTI and NAUTI, followed by Klebsiella spp. in NAUTI and Pseudomonas spp. in catheter-associated urinary tract infections. The highest level of general resistance was found among isolates of NAUTI and catheter-associated UTI followed by CAUTI isolates. Absolute or high level resistance for commonly used empirical antimicrobial therapy was found in catheter-associated UTI and NAUTI while resistance among CAUTI was respectable. Patients with NAUTI as well as patients with catheter-associated urinary tract infections have similar resistance and similar microorganisms isolated as a causative agents, and should not be empirically treated unless the clinical emergency requests.

  9. Antimicrobial Susceptibility Testing, Drug Resistance Mechanisms, and Therapy of Infections with Nontuberculous Mycobacteria

    PubMed Central

    Nash, Kevin A.; Wallace, Richard J.

    2012-01-01

    Summary: Within the past 10 years, treatment and diagnostic guidelines for nontuberculous mycobacteria have been recommended by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA). Moreover, the Clinical and Laboratory Standards Institute (CLSI) has published and recently (in 2011) updated recommendations including suggested antimicrobial and susceptibility breakpoints. The CLSI has also recommended the broth microdilution method as the gold standard for laboratories performing antimicrobial susceptibility testing of nontuberculous mycobacteria. This article reviews the laboratory, diagnostic, and treatment guidelines together with established and probable drug resistance mechanisms of the nontuberculous mycobacteria. PMID:22763637

  10. Noninvasive In Vivo Imaging to Evaluate Immune Responses and Antimicrobial Therapy against Staphylococcus aureus and USA300 MRSA Skin Infections

    PubMed Central

    Cho, John S.; Zussman, Jamie; Donegan, Niles P.; Irene Ramos, Romela; Garcia, Nairy C.; Uslan, Daniel Z.; Iwakura, Yoichiro; Simon, Scott I.; Cheung, Ambrose L.; Modlin, Robert L.; Kim, Jenny; Miller, Lloyd S.

    2011-01-01

    Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies. PMID:21191403

  11. Successful treatment of Corynebacterium urealyticum encrusting cystitis with systemic and intravesical antimicrobial therapy

    PubMed Central

    Raab, Oriana; Béraud, Romain; Tefft, Karen M.; Muckle, C. Anne

    2015-01-01

    A 6-year-old Saint Bernard dog was diagnosed with encrusting cystitis caused by Corynebacterium urealyticum. The infection persisted despite the prolonged use of antimicrobials and surgical debridement of the urinary bladder. Resolution occurred following intravenous vancomycin, urine acidification, and intravesical gentamicin. The challenges involved in the treatment of encrusting cystitis are described. PMID:25969578

  12. In vitro and in vivo antimicrobial activity of combined therapy of silver nanoparticles and visible blue light against Pseudomonas aeruginosa.

    PubMed

    Nour El Din, Suzanne; El-Tayeb, Tarek A; Abou-Aisha, Khaled; El-Azizi, Mohamed

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as potential antimicrobial agents against resistant pathogens. We investigated the possible therapeutic use of AgNPs in combination with visible blue light against a multidrug resistant clinical isolate of Pseudomonas aeruginosa in vitro and in vivo. The antibacterial activity of AgNPs against P. aeruginosa (1×10(5) colony forming unit/mL) was investigated at its minimal inhibitory concentration (MIC) and sub-MIC, alone and in combination with blue light at 460 nm and 250 mW for 2 hours. The effect of this combined therapy on the treated bacteria was then visualized using transmission electron microscope. The therapy was also assessed in the prevention of biofilm formation by P. aeruginosa on AgNP-impregnated gelatin biopolymer discs. Further, in vivo investigations were performed to evaluate the efficacy of the combined therapy to prevent burn-wound colonization and sepsis in mice and, finally, to treat a real infected horse with antibiotic-unresponsive chronic wound. The antimicrobial activity of AgNPs and visible blue light was significantly enhanced (P<0.001) when both agents were combined compared to each agent alone when AgNPs were tested at MIC, 1/2, or 1/4 MIC. Transmission electron microscope showed significant damage to the cells that were treated with the combined therapy compared to other cells that received either the AgNPs or blue light. In addition, the combined treatment significantly (P<0.001) inhibited biofilm formation by P. aeruginosa on gelatin discs compared to each agent individually. Finally, the combined therapy effectively treated a horse suffering from a chronic wound caused by mixed infection, where signs of improvement were observed after 1 week, and the wound completely healed after 4 weeks. To our knowledge, this combinatorial therapy has not been investigated before. It was proved efficient and promising in managing infections caused by multidrug resistant bacteria and could be used as an

  13. In vitro and in vivo antimicrobial activity of combined therapy of silver nanoparticles and visible blue light against Pseudomonas aeruginosa

    PubMed Central

    Nour El Din, Suzanne; El-Tayeb, Tarek A; Abou-Aisha, Khaled; El-Azizi, Mohamed

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as potential antimicrobial agents against resistant pathogens. We investigated the possible therapeutic use of AgNPs in combination with visible blue light against a multidrug resistant clinical isolate of Pseudomonas aeruginosa in vitro and in vivo. The antibacterial activity of AgNPs against P. aeruginosa (1×105 colony forming unit/mL) was investigated at its minimal inhibitory concentration (MIC) and sub-MIC, alone and in combination with blue light at 460 nm and 250 mW for 2 hours. The effect of this combined therapy on the treated bacteria was then visualized using transmission electron microscope. The therapy was also assessed in the prevention of biofilm formation by P. aeruginosa on AgNP-impregnated gelatin biopolymer discs. Further, in vivo investigations were performed to evaluate the efficacy of the combined therapy to prevent burn-wound colonization and sepsis in mice and, finally, to treat a real infected horse with antibiotic-unresponsive chronic wound. The antimicrobial activity of AgNPs and visible blue light was significantly enhanced (P<0.001) when both agents were combined compared to each agent alone when AgNPs were tested at MIC, 1/2, or 1/4 MIC. Transmission electron microscope showed significant damage to the cells that were treated with the combined therapy compared to other cells that received either the AgNPs or blue light. In addition, the combined treatment significantly (P<0.001) inhibited biofilm formation by P. aeruginosa on gelatin discs compared to each agent individually. Finally, the combined therapy effectively treated a horse suffering from a chronic wound caused by mixed infection, where signs of improvement were observed after 1 week, and the wound completely healed after 4 weeks. To our knowledge, this combinatorial therapy has not been investigated before. It was proved efficient and promising in managing infections caused by multidrug resistant bacteria and could be used as an

  14. Antimicrobial resistance: a global response.

    PubMed Central

    Smith, Richard D.; Coast, Joanna

    2002-01-01

    Resistance to antimicrobial therapies reduces the effectiveness of these drugs, leading to increased morbidity, mortality, and health care expenditure. Because globalization increases the vulnerability of any country to diseases occurring in other countries, resistance presents a major threat to global public health, and no country acting on its own can adequately protect the health of its population against it. International collective action is therefore essential. Nevertheless, responsibility for health remains predominantly national. Consequently, there is a potentially significant disparity between the problems and solutions related to antimicrobial resistance and the institutions and mechanisms that are available to deal with them. This paper considers the capacity of national and international institutions and mechanisms to generate a collective response to antimicrobial resistance. Strategies for containing resistance are outlined, with particular reference to globally coordinated activities of countries. The adequacy of national and international responses to resistance is assessed, and the actions that international bodies could take to solve difficulties associated with present responses are highlighted. Approaches are suggested for securing international collective action for the containment of antimicrobial resistance. PMID:11953791

  15. A novel dextran polymer hydrogel local antimicrobial therapy in dogs: A pilot study

    PubMed Central

    Reed, Travis P.; Thomas, Leslie A.; Weeren, F. Robert; Ruth, Jeffrey D.; Anders, Brendan B.

    2016-01-01

    Our purpose was to evaluate physical, laboratory, and/or radiographic abnormalities associated with a novel dextran polymer hydrogel local antimicrobial agent impregnated with amikacin and clindamycin in dogs having tibial plateau leveling osteotomy implants removed due to suspected surgical site infection. A total of 28 client-owned dogs were enrolled and 20 completed the study. Routine plate explantation and bacterial cultures were performed and the polymer hydrogel was applied to the surgery site. No systemic antimicrobials were used after surgery. Serum biochemistry, hematology, urinalysis, physical examinations, and radiographs were monitored before surgery and up to 12 wk after surgery. Sixteen of the 20 dogs (80%) had a positive bacterial culture, 44% of which were methicillin resistant. There were no significant alterations of laboratory values, physical examination, or radiographs to indicate adverse reactions to the polymer hydrogel. There were no signs of inflammation or infection in any patient at the 12-week postoperative recheck. PMID:26834272

  16. A novel dextran polymer hydrogel local antimicrobial therapy in dogs: A pilot study.

    PubMed

    Reed, Travis P; Thomas, Leslie A; Weeren, F Robert; Ruth, Jeffrey D; Anders, Brendan B

    2016-02-01

    Our purpose was to evaluate physical, laboratory, and/or radiographic abnormalities associated with a novel dextran polymer hydrogel local antimicrobial agent impregnated with amikacin and clindamycin in dogs having tibial plateau leveling osteotomy implants removed due to suspected surgical site infection. A total of 28 client-owned dogs were enrolled and 20 completed the study. Routine plate explantation and bacterial cultures were performed and the polymer hydrogel was applied to the surgery site. No systemic antimicrobials were used after surgery. Serum biochemistry, hematology, urinalysis, physical examinations, and radiographs were monitored before surgery and up to 12 wk after surgery. Sixteen of the 20 dogs (80%) had a positive bacterial culture, 44% of which were methicillin resistant. There were no significant alterations of laboratory values, physical examination, or radiographs to indicate adverse reactions to the polymer hydrogel. There were no signs of inflammation or infection in any patient at the 12-week postoperative recheck.

  17. The effect of subgingival antimicrobial therapy on the levels of stromelysin and tissue inhibitor of metalloproteinases in gingival crevicular fluid.

    PubMed

    Pourtaghi, N; Radvar, M; Mooney, J; Kinane, D F

    1996-09-01

    Recent investigations imply that a key mechanism in the pathogenesis of periodontal disease may be the ability of oral microorganisms to induce production and/or activation of matrix metalloproteinases (MMPs) in the host tissues. It has been suggested that the pharmacologic inhibition of MMP activity could play an important role in achieving a desirable outcome in periodontal therapy. The efficacy of locally delivered antibiotics on the level of gingival crevicular fluid (GCF) stromelysin (SL) and tissue inhibitor of metalloproteinases (TIMP) on sites with a history of a poor response to mechanical treatment was studied. Fifty-two patients with 4 periodontal pockets > or = 5 mm and bleeding on probing were randomized into four groups of 13 patients. One group received scaling and root planing alone and the other three groups received scaling and root planing plus a locally delivered antimicrobial system. These included 25% tetracycline fiber, 2% minocycline gel, and 25% metronidazole gel. The GCF samples taken at baseline and 6 weeks after treatments were analyzed using an enzyme linked immunosorbent assay (ELISA). GCF SL levels significantly decreased after adjunctive tetracycline fiber (paired t-test, P = 0.020) and minocycline gel (paired t-test, P = 0.023) treatments whereas it remained almost unchanged in the other two groups. While the GCF TIMP level did not change significantly in the scaling and root planing alone group, it significantly increased for all three adjunctive antimicrobial treatments (for tetracycline fiber P < 0.001, minocycline gel P = 0.005, metronidazole gel P < 0.001). The use of adjunctive locally delivered antimicrobial systems, particularly the tetracycline family, may offer an advantage in changing the metalloproteinase profile of the GCF to one more compatible with periodontal health.

  18. Antimicrobials from Cnidarians. A New Perspective for Anti-Infective Therapy?

    PubMed Central

    Mariottini, Gian Luigi; Grice, Irwin Darren

    2016-01-01

    The ability of microbes to counter the scientific and therapeutic advancements achieved during the second half of the twentieth century to provide effective disease treatments is currently a significant challenge for researchers in biology and medicine. The discovery of antibiotics, and the subsequent development of synthetic antimicrobial compounds, altered our therapeutic approach towards infectious diseases, and improved the quality and length of life for humans and other organisms. The current alarming rise in cases of antibiotic-resistance has forced biomedical researchers to explore new ways to recognize and/or produce new antimicrobials or to find other approaches for existing therapeutics. Aquatic organisms are known to be a source of compounds having the potential to play a role in fighting the battle against pathogenic microbes. In this connection, cnidarians occupy a pre-eminent role. Over the past few decades several studies have explored the antimicrobial/antibiotic properties of cnidarian extracts with the aim of isolating compounds possessing useful therapeutic features. This paper aims to review the existing data on this subject, taking into account the possible utilization of identified compounds. PMID:27005633

  19. Antimicrobial photodynamic therapy with decacationic monoadducts and bisadducts of [70]fullerene: in vitro and in vivo studies

    PubMed Central

    Huang, Liyi; Wang, Min; Dai, Tianhong; Sperandio, Felipe F; Huang, Ying-Ying; Xuan, Yi; Chiang, Long Y; Hamblin, Michael R

    2013-01-01

    Background Antimicrobial photodynamic therapy uses photosensitizers designed to bind to microorganisms and generate reactive oxygen species when illuminated with visible light. Materials & method We synthesized a highly water-soluble [70]fullerene monoadduct, C70[>M(C3N6+C3)2]-(I−)10 (LC17), and bisadduct, C70[>M(C3N6+C3)2][>M(C3N6C3)2] (LC18), both with a well-defined decacationic quaternary ammonium iodide moiety with ten positive charges per C70 to give water solubility and bacterial binding. We determined the antimicrobial effects against human pathogens, Gram-positive (Staphylococcus aureus) and Gramnegative species (Escherichia coli and Acinetobacter baumannii) when activated by UVA or white light. Results White light was more effective with LC17, while UVA light was more effective with LC18. Both compounds were effective in a mouse model of Gram-negative third-degree burn infections determined by bioluminescence imaging. Discussion & conclusion We propose that the attachment of an additional deca(tertiary-ethylenylamino)malonate arm to C70 allowed the moiety to act as a potent electron donor and increased the generation yield of hydroxyl radicals under UVA illumination. PMID:23738632

  20. [Physicians referent for antimicrobial therapy in French hospitals. Origins and expectations. A French infectious diseases society survey].

    PubMed

    Alfandari, S

    2006-10-01

    The French Infectious Diseases Society (SPILF) conducted a web-based survey of physicians' referent for antimicrobial therapy (ABT). The 106 respondents came mostly from public (95%) big (median 815 beds) hospitals. A referent according to health ministry requirements was identified in 88 hospitals. In, 18 others, a physician performed the job without identification per se. This activity had a specific financing in only 12% of cases. Two thirds of the referents were infectious diseases physicians, the others had for training a university degree in ABT. Expectations about SPILF were mostly implementation of good practices of ABT (73%), organization of CME sessions (61%), a referent dedicated session during the annual SPILF meeting (58%), a SPILF driven certification (58%) and the creation of regional networks of referents (55%). Implementing a training and evaluation program for ABT referents becomes a priority for the SPILF.

  1. Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement.

    PubMed

    Chapman, Ann L N; Seaton, R Andrew; Cooper, Mike A; Hedderwick, Sara; Goodall, Vicky; Reed, Corienne; Sanderson, Frances; Nathwani, Dilip

    2012-05-01

    These good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) are an update to a previous consensus statement on OPAT in the UK published in 1998. They are based on previous national and international guidelines, but have been further developed through an extensive consultation process, and are underpinned by evidence from published literature on OPAT. They provide pragmatic guidance on the development and delivery of OPAT services, looking at all aspects of service design, care delivery, outcome monitoring and quality assurance, with the aim of ensuring that OPAT services provide high-quality, low-risk care, whatever the healthcare setting. They will provide a useful resource for teams developing new services, as well as a practical set of quality indicators for existing services.

  2. Efficacy of Appropriate Antimicrobial Therapy on the Survival of Patients With Carbapenem Nonsusceptible Klebsiella Pneumoniae Infection: A Multicenter Study in Taiwan.

    PubMed

    Lin, Yi-Tsung; Chuang, Chien; Su, Chin-Fang; Chan, Yu-Jiun; Wang, Lih-Shinn; Huang, Ching-Tai; Chuang, Yin-Ching; Siu, L Kristopher; Fung, Chang-Phone

    2015-08-01

    The impact of antimicrobial treatment on the outcome of carbapenem nonsusceptible Klebsiella pneumoniae (CnsKP) infections needs to be elucidated. This nationwide, multicenter study was conducted to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality among patients with CnsKP infection in Taiwan.Patients with CnsKP infections from 11 medical centers and 4 regional hospitals in Taiwan were enrolled in 2013. Carbapenem nonsusceptibility was defined as a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. Predictors of 14-day mortality were determined using the Cox proportional regression model. The influence of infection severity on the impact of appropriate use of antimicrobials on 14-day mortality was determined using the Acute Physiology and Chronic Health Evaluation (APACHE) II score.Overall 14-day mortality was 31.8% (49/154). Unadjusted mortality for appropriate antimicrobial therapy was 23.1% (18/78 patients). Appropriate therapy was independently associated with reduced mortality (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.80; P = 0.007). A subgroup analysis revealed that the benefit of appropriate therapy was limited to patients with higher APACHE II scores (HR for patients with scores >15 and ≤35, 0.46; 95% CI 0.23-0.92; and for those with scores >35, 0.14; 95% CI, 0.02-0.99).In conclusion, appropriate antimicrobial therapy significantly reduces 14-day mortality for CnsKP infections. Survival benefit is more notable among more severely ill patients.

  3. Genomic Expression Analysis Reveals Strategies of Burkholderia cenocepacia to Adapt to Cystic Fibrosis Patients' Airways and Antimicrobial Therapy

    PubMed Central

    Mira, Nuno P.; Madeira, Andreia; Moreira, Ana Sílvia; Coutinho, Carla P.; Sá-Correia, Isabel

    2011-01-01

    Pulmonary colonization of cystic fibrosis (CF) patients with Burkholderia cenocepacia or other bacteria of the Burkholderia cepacia complex (Bcc) is associated with worse prognosis and increased risk of death. During colonization, the bacteria may evolve under the stressing selection pressures exerted in the CF lung, in particular, those resulting from challenges of the host immune defenses, antimicrobial therapy, nutrient availability and oxygen limitation. Understanding the adaptive mechanisms that promote successful colonization and long-term survival of B. cenocepacia in the CF lung is essential for an improved therapeutic outcome of chronic infections. To get mechanistic insights into these adaptive strategies a transcriptomic analysis, based on DNA microarrays, was explored in this study. The genomic expression levels in two clonal variants isolated during long-term colonization of a CF patient who died from the cepacia syndrome were compared. One of the isolates examined, IST439, is the first B. cenocepacia isolate retrieved from the patient and the other isolate, IST4113, was obtained three years later and is more resistant to different classes of antimicrobials. Approximately 1000 genes were found to be differently expressed in the two clonal variants reflecting a marked reprogramming of genomic expression. The up-regulated genes in IST4113 include those involved in translation, iron uptake (in particular, in ornibactin biosynthesis), efflux of drugs and in adhesion to epithelial lung tissue and to mucin. Alterations related with adaptation to the nutritional environment of the CF lung and to an oxygen-limited environment are also suggested to be a key feature of transcriptional reprogramming occurring during long-term colonization, antibiotic therapy and the progression of the disease. PMID:22216120

  4. Effectiveness of antimicrobial photodynamic therapy (AmPDT) on Staphylococcus aureus using phenothiazine compound with red laser.

    PubMed

    Monteiro, Juliana S C; de Oliveira, Susana C P S; Pires Santos, Gustavo M; Pires Sampaio, Fernando José; Pinheiro Soares, Luiz Guilherme; Pinheiro, Antônio L B

    2017-01-01

    The aim of this study was to evaluate, in vitro, the bactericidal effect of antimicrobial photodynamic therapy (AmPDT) using phenothiazinium dyes (Toluidine Blue O and methylene blue, 1:1) using different concentrations (100, 50, 25, 12.5, and 6.25 μg/mL) associated to red laser with different energy densities (2.4, 4.8, 7.2, 9.6, and 12 J/cm(2)) on a strain of Staphylococcus aureus (ATCC 23529). On this study, tests were performed in triplicate and the samples were distributed into 36 test groups: Control and bacterial suspensions were irradiated with the different energy densities, respectively, in the absence of photosensitizer, bacterial suspensions were irradiated with the laser in the different concentrations of the photosensitizer, and finally bacterial suspensions only in the presence of phenothiazinium dye. The pre-irradiation time was 5 min. Therefore, we analyzed the potential of the AmPDT by counting colony-forming units. The logarithm of CFU/mL (log10 CFU/mL) was calculated and the data was analyzed statistically (ANOVA, Tukey's test, p < 0.05). The results showed that the association 50 and 100 μg/mL with 12 J/cm(2) showed the highest percentage of inhibition (100 %). Based upon the present results, it may be concluded that the AmPDT was able to enhance the antimicrobial effect of phenothiazines and both concentration of the compound and energy density are important factors for greater effectiveness of therapy.

  5. New insight on antimicrobial therapy adjustment strategies for gram-negative bacterial infection

    PubMed Central

    Du, Wei; Chen, Hong; Xiao, Shuzhen; Tang, Wei; Shi, Guochao

    2017-01-01

    Abstract Gram-negative bacterial infections, especially multidrug-resistant (MDR) bacterial infection, are becoming a serious threat to public health. Although it is widely accepted that both appropriate initial empirical therapy and targeted therapy are important, but for patients needing therapy adjustment, few studies have explored whether adjustment strategy based on microbiologic susceptibility test (MST) brings better outcome compared with empirical adjustment. A total of 320 patients with gram-negative bacterial infection (airway, blood, or pleural effusion) were selected and a prospective cohort study was conducted. Baseline characteristics and outcomes (microbiologic, clinical, and economic) were documented during follow-up. MDR and nosocomial infections were common among subjects. Initial therapies consistent with MST could result in reduced in-hospital mortality, treatment failure rate, infection-related death, percentages of patients needing therapy adjustment, and daily hospitalization cost with increased successful treatment rate compared with inconsistent with MST, and microbiologic outcomes were also better with appropriate therapies. For patients needing therapy adjustment, relying on MST gained no significant benefit on mortality, clinical, or microbiologic outcomes compared with depending on clinical experience. But for patients with MDR infection, adjustment relying on MST gained more benefit than non-MDR infection. Appropriate initial therapy significantly improved the prognosis of patients with gram-negative bacterial infections, but improvement was not that obvious for patients needing therapy adjustment which was based on MST compared with clinical experience, and more beneficial effects of adjustment relying on MST were obtained for patients with MDR bacterial infection. PMID:28353572

  6. Metaphylactic antimicrobial therapy for bovine respiratory disease in stocker and feedlot cattle.

    PubMed

    Nickell, Jason S; White, Brad J

    2010-07-01

    This article provides an overview of implementing metaphylactic antimicrobial protocols to certain classes of cattle on arrival to stocker and feedlot production systems. The goal of this management practice is to reduce the negative health and performance effects induced by bovine respiratory disease (BRD). This article emphasizes the multiple factors that influence the decision for mass medication, including weight (age) of the cattle, distance traveled, environmental conditions, previous health history, visual inspection of the cattle at arrival, and prediction of the risk of disease. Current data suggest that metaphylactic programs significantly reduce negative health effects and improve feed performance that can be observed in cattle stricken with BRD.

  7. Assessing Health-Related Quality of Life with Antimicrobial Photodynamic Therapy (APDT) and Low Level Laser Therapy (LLLT) after Third Molar Removal

    PubMed Central

    Batinjan, Goran; Filipović Zore, Irina; Rupić, Ivana; Bago Jurič, Ivona; Zore, Zvonimir; Gabrić Pandurić, Dragana

    2013-01-01

    Introduction: The purpose of this study was to evaluate the antimicrobial photodynamic therapy (APDT) and low level laser therapy (LLLT) on wound healing, pain intensity, swelling problems, halitosis and the postoperative usage of analgesics after surgical removal of lower third molars. Methods: One hundred and fifty patients, randomly divided into three groups were selected (50 per each group). The P1 group received the APDT after a third molar surgery, the P2 group received the LLLT and the C group (control group) was without any additional therapy after surgery. A photoactive substance was applied in the APDT study group before suturing. After 60 seconds the photosensitive substance was thoroughly washed with saline water and the laser light was applied in two intervals (30 seconds each). The irradiation power was 50 mW while the wavelength was 660 nm. The laser therapy in P2 group was performed before suturing and the laser light was applied also in two intervals (90 seconds each), the irradiation power was 90 mW while the wavelength was the same as in the first group – 660 nm. Postoperative follow-ups were scheduled on the third and the seventh day in patients who received laser therapy. Results: The results of the postoperative evaluation showed that there was a statistically significant difference in the postoperative wound healing, pain intensity, swelling problems, halitosis and analgesics intake between patients in all three groups (p<0.001). The patients that were subjected to APDT (P1) had the least postoperative problems. After the laser therapy (P1 and P2) wound healing was without any complications, opposite from the patients from the C group (p<0.001). Postoperative application of a laser therapy significantly reduced patient’s use of analgesics over the observed period of time (p<0.001). Conclusion: Both modalities of laser therapy significantly reduced postoperative problems after surgical removal of third lower molars with the best results in

  8. [Adequate antimicrobial drug use in a third level pediatric hospital].

    PubMed

    Duarte-Raya, Fidencia; Rodríguez-Lechuga, Manuel; De Anda-Gómez, Manuel Alberto; Granados-Ramírez, Martha Patricia; Vargas-Rodríguez, Alexia Gisselle

    2015-01-01

    Introducción: el uso inadecuado de antimicrobianos contribuye al desarrollo de la resistencia bacteriana, reduce la efectividad de los tratamientos establecidos e incrementa los gastos y la mortalidad por enfermedades infecciosas. El objetivo de este artículo es evaluar si el uso de antimicrobianos en pacientes pediátricos hospitalizados se realiza de forma adecuada. Métodos: estudio epidemiológico observacional, transversal en la UMAE No. 48 de León, Guanajuato. Muestra no probabilística, con un 60 % de tratamientos adecuados esperados, desviación estándar 4. Se utilizó la técnica estadística de análisis de distribución de frecuencias por calificación final de tratamiento administrado: profiláctico, terapéutico, restringido, justificado y adecuado. Se realiza chi cuadrada para comparación de porcentajes. Resultados: se evalúan 283 prescripciones antimicrobianas en 217 pacientes, hombres (53 %) y mujeres (47 %). De los cuales fueron tratamientos adecuados: general 51.2 %, justificado 66 %, terapéutico 53.4 %, restringido 40.8 % y profiláctico 48 %. Comparación de porcentajes con chi cuadrada, asociación estadística significativa de tratamiento adecuado en neonatos (chi cuadrada 8.287; p 0.004) y tratamiento inadecuado en prematuros (chi cuadrada 4.853; p 0.028) con p < 0.05. Los antibióticos más usados fueron: penicilinas 43.7 % y aminoglucósidos 37.1 %. Conclusión: solo la mitad de los tratamientos antimicrobianos se prescriben de forma adecuada.

  9. Clinical outcomes associated with chronic antimicrobial suppression therapy in patients with continuous-flow left ventricular assist devices.

    PubMed

    Jennings, Douglas L; Chopra, Anuvrat; Chambers, Rachel; Morgan, Jeffrey A

    2014-10-01

    This retrospective cohort study evaluates the effect of chronic antimicrobial suppression (CAS) therapy on clinical outcomes in patients with continuous-flow left ventricular assist devices (CF-LVADs) and a history of device-related infection. Patients with CF-LVAD implantation between January 2008 and August 2011 who received systemic CAS after index antibiotic treatment of a device-related infection were included. Chronic suppression was defined as continuation of antibiotics for longer than 6 weeks after the index infection. Standard International Society for Heart and Lung Transplantation definitions were used. The primary outcome is failure of CAS, defined as a clinical deterioration resulting in the need for transition from oral to intravenous (IV) therapy or a need to change to a different IV antibiotic, elevation to status 1A on the transplant list as a result of ongoing infection, or device/driveline exchange. Of 140 patients screened, 16 patients were included (69% male, 63% African American, median age 52 years). The driveline was the most common site of infection (69%). Organisms isolated included Gram-positive cocci (n = 7), Gram-negative bacilli (n = 10), and Candida (n = 1). Oral trimethoprim/sulfamethoxazole treatment was most commonly used for suppression (37.5%). Failure of CAS occurred in 5/16 (31%) patients after a mean time of 175 days on therapy (range 10-598). The majority of failures (60%) required device exchanges. Side effects of nausea, vomiting, or diarrhea were reported in three patients; all required changes in oral suppression regimen. Clostridium difficile infection was noted in two patients. These results, which must be confirmed by a larger analysis, suggest that one-third of CF-LVAD patients may develop recurrent infections while on CAS therapy.

  10. Medication-Related Osteonecrosis of Jaws: A Low-Level Laser Therapy and Antimicrobial Photodynamic Therapy Case Approach

    PubMed Central

    Minamisako, Mariana Comparotto; Lisboa, Mariáh Luz; Mariela Rodríguez Cordeiro, Mabel; Grando, Liliane Janete

    2016-01-01

    Medication-related osteonecrosis of the jaws (MRONJ) can be considered an inability of the alveolar bone to respond to an injury, which frequently leads to severe local and systemic complications. Once the problem is installed, dentist must use all therapeutic approaches recommended. This manuscript reports a successful management of MRONJ handled with antibiotics, conservative debridement, low-level laser therapy (LLLT), and photodynamic therapy (PDT) up to 12 months. As healing of MRONJ may be very slow, combined therapeutic approaches are required. Besides the recommended conventional treatment protocol, LLLT and PDT are important tools to contribute to healing and improvement of patient's quality of life. PMID:27668100

  11. Antimicrobial photodynamic therapy in chronic osteomyelitis induced by Staphylococcus aureus: An in vitro and in vivo study

    NASA Astrophysics Data System (ADS)

    dos Reis Júnior, João Alves; de Assis, Patrícia Nascimento; Paraguassú, Gardênia Matos; de Vieira de Castro, Isabele Cardoso; Trindade, Renan Ferreira; Marques, Aparecida Maria Cordeiro; Almeida, Paulo Fernando; Pinheiro, Antônio Luiz Barbosa

    2012-09-01

    Osteomyelitis it is an acute or chronic inflammation in the marrow spaces in the superficial or cortical bone, and associated to bacterial infection. Chronic osteomyelitis represents a major health problem due to its difficult treatment and increased morbidity. Antimicrobial photodynamic therapy (APT) by laser is a treatment based on a cytotoxic photochemical reaction in which, a bright light produced by a laser system and an active photosensitizer absorbed by cells leads an activation that induces a series of metabolic reactions that culminates a bacterial killing. The aim of this study was to assess, both in vitro and in vivo, the effect of lethal laser photosensitization on osteomyelitis. On the in vitro study a diode laser (λ660nm; 40mW; o/ = 0.4 cm2; 5 or 10 J/cm2) and 5, 10 and 15μg/mL toluidine blue (TB) were tested and the best parameter chosen for the in vivo study. The concentration of 5μg/mL was selected to perform the decontamination of infected by Staphylococcus aureus tibial bone defects in rats. The results were performed by ANOVA test. On the in vitro studies all PDTs groups in the different concentrations reduced significantly (p<0,001) the amount of bacteria. On the in vivo study PDT group presented a bacterial reduction of 97,4% (P<0,001). The photodynamic therapy using toluidine blue was effective in reducing the staphiloccocus aureus in both in vitro and in vivo studies.

  12. Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies

    PubMed Central

    Zhu, Hong; Kochevar, Irene E.; Behlau, Irmgard; Zhao, Jie; Wang, Fenghua; Wang, Yucheng; Sun, Xiaodong; Hamblin, Michael R.; Dai, Tianhong

    2017-01-01

    Purpose To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. Methods We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Results Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Conclusions Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted. PMID:28129422

  13. The Impact of an Infectious Diseases Transition Service on the Care of Outpatients on Parenteral Antimicrobial Therapy

    PubMed Central

    Keller, Sara C.; Ciuffetelli, Danielle; Bilker, Warren; Norris, Anne; Timko, Daniel; Rosen, Alex; Myers, Jennifer S.; Hines, Janet; Metlay, Joshua

    2014-01-01

    Background Many hospitalized patients with complicated infections are discharged on outpatient parenteral antimicrobial therapy (OPAT). However, little is known about how to improve the postdischarge care of OPAT patients. Objective The impact of an infectious diseases transitions service (IDTS) on OPAT patient readmissions, as well as on processes of care, was evaluated. Methods We performed a controlled, quasi-experimental evaluation over 15 months in an academic medical center. Intervention-arm patients, before and after the introduction of an IDTS, were seen by the general infectious diseases consult teams, while control-arm patients (discharged on OPAT after hospitalization with bacteremia) were not. The IDTS prospectively tracked all OPAT patients and coordinated follow-up. The impact of the IDTS was calculated using a differences-in-differences approach where the interaction between time (before vs after the IDTS intervention) and study arm (intervention vs control arm) was the variable of interest. The control arm was used only in primary outcome analyses (readmissions and emergency department visits). Secondary outcomes included process of care measures and non-readmission clinical outcomes. Results Of 488 consecutive patients requiring OPAT, 362 were in the intervention arm (215 pre-intervention and 147 post-intervention) and 126 in the control arm (70 pre-intervention and 56 post-intervention). Compared to the control arm, the IDTS was not associated with changes in 60-day readmissions and/or emergency department visits (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI] = 0.13–1.79). In the intervention arm, implementation of the IDTS was associated with fewer antimicrobial therapy errors (OR = 0.062; 95% CI = 0.015–0.262), increased laboratory test receipt (OR = 27.85; 95% CI = 12.93–59.99), and improved outpatient follow-up (OR = 2.44; 95% CI = 1.50–3.97). Conclusions In a controlled evaluation, the IDTS did not affect readmissions

  14. Hot topics in reactive oxygen therapy: Antimicrobial and immunological mechanisms, safety and clinical applications.

    PubMed

    Dryden, Matthew; Cooke, Jonathan; Salib, Rami; Holding, Rebecca; Pender, Sylvia L F; Brooks, Jill

    2017-02-17

    Reactive oxygen species (ROS), when combined with various delivery mechanisms, has the potential to become a powerful novel therapeutic agent against difficult-to-treat infections, especially those involving biofilm. It is important in the context of the global antibiotic resistance crisis. ROS is rapidly active in vitro against all Gram-positive and Gram-negative bacteria tested. ROS also has antifungal and antiviral properties. ROS prevents the formation of biofilms caused by a range of bacterial species in wounds and respiratory epithelium. ROS has been successfully used in infection prevention, eradication of multiresistant organisms, prevention of surgical site infection, and intravascular line care. This antimicrobial mechanism has great potential for the control of bioburden and biofilm at many sites, thus providing an alternative to systemic antibiotics on epithelial/mucosal surfaces, for wound and cavity infection, chronic respiratory infections and possibly recurrent urinary infections as well as local delivery to deeper structures and prosthetic devices. Its simplicity and stability lend itself to use in developing economies as well.

  15. Antimicrobial Drugs in Fighting against Antimicrobial Resistance

    PubMed Central

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i.e., mutation and horizontal gene transfer of resistance determinants), the community level resistance (i.e., bilofilms and persisters) is also an issue causing antimicrobial therapy difficulties. Therefore, anti-resistance and antibiofilm strategies have currently become research hotspot to combat antimicrobial resistance. Although metallic nanoparticles can both kill bacteria and inhibit biofilm formation, the toxicity is still a big challenge for their clinical applications. In conclusion, rational use of the existing antimicrobials and combinational use of new strategies fighting against antimicrobial resistance are powerful warranties to preserve potent antimicrobial drugs for both humans and animals. PMID:27092125

  16. Photodynamic antimicrobial therapy to inhibit pseudomonas aeruginosa of corneal isolates (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Durkee, Heather A.; Relhan, Nidhi; Arboleda, Alejandro; Halili, Francisco; De Freitas, Carolina; Alawa, Karam; Aguilar, Mariela C.; Amescua, Guillermo; Miller, Darlene; Parel, Jean-Marie

    2016-03-01

    Keratitis associated with Pseudomonas aeruginosa is difficult to manage. Treatment includes antibiotic eye drops, however, some strains of Pseudomonas aeruginosa are resistant. Current research efforts are focused on finding alternative and adjunct therapies to treat multi-drug resistant bacteria. One promising alternate technique is photodynamic therapy (PDT). The purpose of this study was to evaluate the effect of riboflavin- and rose bengal-mediated PDT on Pseudomonas aeruginosa keratitis isolates in vitro. Two isolates (S+U- and S-U+) of Pseudomonas aeruginosa were derived from keratitis patients and exposed to five experimental groups: (1) Control (dark, UV-A irradiation, 525nm irradiation); (2) 0.1% riboflavin (dark, UV-A irradiation); and (3) 0.1% rose bengal, (4) 0.05% rose bengal and (5) 0.01% rose bengal (dark, 525nm irradiation). Three days after treatment, in dark conditions of all concentration of riboflavin and rose bengal showed no inhibition in both S+U- and S-U+ strains of Pseudomonas aeruginosa. In 0.1% and 0.05% rose bengal irradiated groups, for both S+U- and S-U+ strains, there was complete inhibition of bacterial growth in the central 50mm zone corresponding to the diameter of the green light source. These in vitro results suggest that rose bengal photodynamic therapy may be an effective adjunct treatment for Pseudomonas aeruginosa keratitis.

  17. Reducing Vibrio load in Artemia nauplii using antimicrobial photodynamic therapy: a promising strategy to reduce antibiotic application in shrimp larviculture.

    PubMed

    Asok, Aparna; Arshad, Esha; Jasmin, C; Pai, S Somnath; Singh, I S Bright; Mohandas, A; Anas, Abdulaziz

    2012-01-01

    We propose antimicrobial photodynamic therapy (aPDT) as an alternative strategy to reduce the use of antibiotics in shrimp larviculture systems. The growth of a multiple antibiotic resistant Vibrio harveyi strain was effectively controlled by treating the cells with Rose Bengal and photosensitizing for 30 min using a halogen lamp. This resulted in the death of >50% of the cells within the first 10 min of exposure and the 50% reduction in the cell wall integrity after 30 min could be attributed to the destruction of outer membrane protein of V. harveyi by reactive oxygen intermediates produced during the photosensitization. Further, mesocosm experiments with V. harveyi and Artemia nauplii demonstrated that in 30 min, the aPDT could kill 78.9% and 91.2% of heterotrophic bacterial and Vibrio population respectively. In conclusion, the study demonstrated that aPDT with its rapid action and as yet unreported resistance development possibilities could be a propitious strategy to reduce the use of antibiotics in shrimp larviculture systems and thereby, avoid their hazardous effects on human health and the ecosystem at large.

  18. Shigellosis in Subjects with Traveler's Diarrhea versus Domestically Acquired Diarrhea: Implications for Antimicrobial Therapy and Human Immunodeficiency Virus Surveillance

    PubMed Central

    Toro, Carlos; Sarria, Ana Arroyo, Ana; Iglesias, Nuria; Enríquez, Ana; Baquero, Margarita; de Guevara, Concepción Ladrón

    2015-01-01

    An increase of sexually transmitted shigellosis is currently being reported in developed countries. In addition, travel-related shigellosis can introduce resistant strains that could be disseminated within this new scenario. Epidemiological features and antimicrobial susceptibility of shigellosis depending on where infection was acquired were investigated. From 2008 to 2013, subjects with shigellosis were studied. Patients were classified according to acquisition of Shigella as traveler's diarrhea (TD) or domestically acquired diarrhea (DAD). Ninety cases of shigellosis were identified: 76 corresponding to the TD group and 14 to the DAD group. In the DAD group, most of patients were human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), being shigellosis associated to male sex (P = 0.007) and HIV infection (P < 0.0001). S. sonnei (47.8%) and S. flexneri (42.2%) were the predominant species. The highest resistance was detected for trimethoprim/sulfamethoxazole (SXT) (81.8%), followed by ampicillin (AMP) (37.8%) and ciprofloxacin (CIP) (23.3%). Resistant Shigella strains were more frequent in subjects with TD than those with DAD, although only for CIP the difference was significant (P = 0.034). Continuous monitoring of patients with shigellosis is necessary to control the spread of resistant Shigella strains and for effective therapy. Men with shigellosis who have not traveled to an endemic area should be screened for HIV infection. PMID:26195465

  19. Effect of the antimicrobial photodynamic therapy on microorganism reduction in deep caries lesions: a systematic review and meta-analysis

    NASA Astrophysics Data System (ADS)

    Ornellas, Pâmela Oliveira; Antunes, Leonardo Santos; Fontes, Karla Bianca Fernandes da Costa; Póvoa, Helvécio Cardoso Corrêa; Küchler, Erika Calvano; Iorio, Natalia Lopes Pontes; Antunes, Lívia Azeredo Alves

    2016-09-01

    This study aimed to perform a systematic review to assess the effectiveness of antimicrobial photodynamic therapy (aPDT) in the reduction of microorganisms in deep carious lesions. An electronic search was conducted in Pubmed, Web of Science, Scopus, Lilacs, and Cochrane Library, followed by a manual search. The MeSH terms, MeSH synonyms, related terms, and free terms were used in the search. As eligibility criteria, only clinical studies were included. Initially, 227 articles were identified in the electronic search, and 152 studies remained after analysis and exclusion of the duplicated studies; 6 remained after application of the eligibility criteria; and 3 additional studies were found in the manual search. After access to the full articles, three were excluded, leaving six for evaluation by the criteria of the Cochrane Collaboration's tool for assessing risk of bias. Of these, five had some risk of punctuated bias. All results from the selected studies showed a significant reduction of microorganisms in deep carious lesions for both primary and permanent teeth. The meta-analysis demonstrated a significant reduction in microorganism counts in all analyses (p<0.00001). Based on these findings, there is scientific evidence emphasizing the effectiveness of aPDT in reducing microorganisms in deep carious lesions.

  20. Shigellosis in Subjects with Traveler's Diarrhea Versus Domestically Acquired Diarrhea: Implications for Antimicrobial Therapy and Human Immunodeficiency Virus Surveillance.

    PubMed

    Toro, Carlos; Arroyo, Ana; Sarria, Ana; Iglesias, Nuria; Enríquez, Ana; Baquero, Margarita; de Guevara, Concepción Ladrón

    2015-09-01

    An increase of sexually transmitted shigellosis is currently being reported in developed countries. In addition, travel-related shigellosis can introduce resistant strains that could be disseminated within this new scenario. Epidemiological features and antimicrobial susceptibility of shigellosis depending on where infection was acquired were investigated. From 2008 to 2013, subjects with shigellosis were studied. Patients were classified according to acquisition of Shigella as traveler's diarrhea (TD) or domestically acquired diarrhea (DAD). Ninety cases of shigellosis were identified: 76 corresponding to the TD group and 14 to the DAD group. In the DAD group, most of patients were human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), being shigellosis associated to male sex (P = 0.007) and HIV infection (P < 0.0001). S. sonnei (47.8%) and S. flexneri (42.2%) were the predominant species. The highest resistance was detected for trimethoprim/sulfamethoxazole (SXT) (81.8%), followed by ampicillin (AMP) (37.8%) and ciprofloxacin (CIP) (23.3%). Resistant Shigella strains were more frequent in subjects with TD than those with DAD, although only for CIP the difference was significant (P = 0.034). Continuous monitoring of patients with shigellosis is necessary to control the spread of resistant Shigella strains and for effective therapy. Men with shigellosis who have not traveled to an endemic area should be screened for HIV infection.

  1. The Effect of Antimicrobial Photodynamic Therapy with Radachlorin and Toluidine Blue on Streptococcus Mutans: An in Vitro Study

    PubMed Central

    Vahabi, S.; Fekrazad, R.; Ayremlou, S.; Taheri, S.; Zangeneh, N.

    2011-01-01

    Objectives: Dental caries and periodontal diseases are caused by infection of teeth and supporting tissues due to complex aggregate of bacteria known as biofilm, firstly colonized by streptococci. The main purpose of this in vitro study was to evaluate the antimicrobial effects of toluidine blue O (TBO) and Radachlorin® in combination with a diode laser on the viability of Streptococcus mutans. Materials and Methods: Bacterial suspensions of Streptococcus mutans were exposed to either 0.1% TBO associated with (20 mW, 633 nm diode laser, continuous mode, 150 s) or 0.1% Radachlorin® and laser irradiation (100 mW, 662 nm diode laser, continuous mode, 120 s). Those in control groups were subjected to laser irradiation alone or TBO/Radachlorin® alone or received neither TBO/Radachlorin® nor laser exposure. The suspensions were then spread over specific agar plates and incubated aerobically at 37°C. Finally, the bactericidal effects were evaluated based on colony formation. Results: Potential bacterial cell killing was only observed following photosensitization with TBO and 3 j/cm2 laser exposure (p<0.05), whereas Radachlorin® showed significant reduction in dark condition compared to laser exposure (p<0.05). Conclusion: TBO-mediated photodynamic therapy seems to be more efficient than Radachlorin® in significantly reducing the viability of Streptococcus mutans in vitro. PMID:21998808

  2. Antimicrobial photodynamic therapy with two photosensitizers on two oral streptococci: an in vitro study

    NASA Astrophysics Data System (ADS)

    Vahabi, S.; Fekrazad, R.; Ayremlou, S.; Taheri, S.; Lizarelli, R. F. Z.; Kalhori, K. A. M.

    2011-12-01

    Periodontal diseases are caused by infection of tissues supporting the teeth due to complex aggregate of bacteria known as biofilm and firstly colonized by streptococci. The aim of this in vitro study was to evaluate the effect of Radachlorin® and Toluidine Blue O (TBO)-mediated photodynamic therapy (PDT) on the viability of two oral streptococci. Bacterial suspensions of Streptococcus mutans and Streptococcus sanguis were subjected to either TBO or Radachlorin®, Then exposed to two different diode laser light at energy densities of 3, 6 J/cm2 at 633 nm and 6, 12 J/cm2 at 662 nm, respectively. The control groups were subjected to laser light alone, photosensitizer alone or received neither photosensitizer nor light exposure. The suspensions were then spread over specific agar mediums and viable microorganisms were counted after overnight incubation aerobically at 37°C, 5% CO2 and then reported as colony forming unit. The results indicated that photosensitization by the energy density of 6 J/cm2 with Radachlorin® and both 3 and 6 J/cm2 with TBO caused significant reduction in bacterial colony formation ( p < 0.05). Radachlorin® and TBO-mediated photodynamic therapy seem to show excellent potential in significantly killing of two oral streptococci in vitro.

  3. Antimicrobial Peptides

    PubMed Central

    Bahar, Ali Adem; Ren, Dacheng

    2013-01-01

    The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs), a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes) and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics). PMID:24287494

  4. [Antimicrobial therapy in severe infections with multidrug-resistant Gram-negative bacterias].

    PubMed

    Duszyńska, Wiesława

    2010-01-01

    Multidrug-resistant Gram-negative bacteria pose a serious and rapidly emerging threat to patients in healthcare settings, and are especially prevalent and problematic in intensive therapy units. Recently, the emergence of pandrug-resistance in Gram-negative bacteria poses additional concerns. This review examines the clinical impact and epidemiology of multidrug-resistant Gram-negative bacteria as a cause of increased morbidity and mortality among ITU patients. Beta-lactamases, cephalosporinases and carbapenemases play the most important role in resistance to antibiotics. Despite the tendency to increased resistance, carbapenems administered by continuous infusion remain the most effective drugs in severe sepsis. Drug concentration monitoring, albeit rarely used in practice, is necessary to ensure an effective therapeutic effect.

  5. European recommendations for antimicrobial resistance surveillance.

    PubMed

    Cornaglia, G; Hryniewicz, W; Jarlier, V; Kahlmeter, G; Mittermayer, H; Stratchounski, L; Baquero, F

    2004-04-01

    The problem of antimicrobial resistance surveillance in Europe has been debated extensively in many excellent documents issued by national committees that often assume the value of national guidelines. However, a comprehensive document addressing the whole matter from a European perspective, as well as reviewing its present status and drafting future perspectives, has been lacking. The present recommendations have been produced by the ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS) through a consensus process involving all members of the Study Group. The recommendations focus on the detection of bacterial resistance and its reporting to clinicians, public health officers and a wider-and ever-increasing-audience. The leading concept is that the basis for resistance monitoring is microbiological diagnostics. The prerequisites for resistance monitoring are findings of adequate quality and quantity, which have been recorded properly and evaluated correctly. Different types of surveillance studies should fulfil different requirements with regard to data collection and reporting, the expected use of data, and the prerequisites for networking such activities. To generate relevant indicators, bacterial resistance data should be reported using adequate denominators and stratification. Reporting of antimicrobial resistance data is necessary for selection of empirical therapy at the local level, for assessing the scale of the resistance problem at the local, national or international levels, for monitoring changes in resistance rates, and for detecting the emergence and spread of new resistances types. Any type of surveillance study should conclude, where appropriate, with a proposal for intervention based on the data obtained.

  6. Antimicrobial Doses in Continuous Renal Replacement Therapy: A Comparison of Dosing Strategies

    PubMed Central

    Kempke, Anna P.; Daneshvar, Farzad

    2016-01-01

    Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population. PMID:27433357

  7. Antimicrobial Doses in Continuous Renal Replacement Therapy: A Comparison of Dosing Strategies.

    PubMed

    Kempke, Anna P; Leino, Abbie S; Daneshvar, Farzad; Lee, John Andrew; Mueller, Bruce A

    2016-01-01

    Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population.

  8. Thiocyanate potentiates antimicrobial photodynamic therapy: In situ generation of the sulfur trioxide radical anion by singlet oxygen

    PubMed Central

    St Denis, Tyler G.; Vecchio, Daniela; Zadlo, Andrzej; Rineh, Ardeshir; Sadasivam, Magesh; Avci, Pinar; Huang, Liyi; Kozinska, Anna; Chandran, Rakkiyappan; Sarna, Tadeusz; Hamblin, Michael R.

    2013-01-01

    Antimicrobial photodynamic therapy (PDT) is used for the eradication of pathogenic microbial cells and involves the light excitation of dyes in the presence of O2, yielding reactive oxygen species including the hydroxyl radical (•OH) and singlet oxygen (1O2). In order to chemically enhance PDT by the formation of longer-lived radical species, we asked whether thiocyanate (SCN−) could potentiate the methylene blue (MB) and light-mediated killing of the gram-positive Staphylococcus aureus and the gram-negative Escherichia coli. SCN− enhanced PDT (10 μM MB, 5J/cm2 660 nm hv) killing in a concentration-dependent manner of S. aureus by 2.5 log10 to a maximum of 4.2 log10 at 10 mM (P < 0.001) and increased killing of E. coli by 3.6 log10 to a maximum of 5.0 log10 at 10 mM (P < 0.01). We determined that SCN− rapidly depleted O2 from an irradiated MB system, reacting exclusively with 1O2, without quenching the MB excited triplet state. SCN− reacted with 1O2, producing a sulfur trioxide radical anion (a sulfur-centered radical demonstrated by EPR spin trapping). We found that MB-PDT of SCN− in solution produced both sulfite and cyanide anions, and that addition of each of these salts separately enhanced MB-PDT killing of bacteria. We were unable to detect EPR signals of •OH, which, together with kinetic data, strongly suggests that MB, known to produce •OH and 1O2, may, under the conditions used, preferentially form 1O2. PMID:23969112

  9. Self-administered outpatient parenteral antimicrobial therapy (S-OPAT) for infective endocarditis: a safe and effective model.

    PubMed

    Pajarón, Marcos; Fernández-Miera, Manuel F; Allende, Iciar; Arnaiz, Ana M; Gutiérrez-Cuadra, Manuel; Cobo-Belaustegui, Manuel; Armiñanzas, Carlos; de Berrazueta, Jose R; Fariñas, Maria C; Sanroma, Pedro

    2015-03-01

    The safety and efficacy of treatment of infectious endocarditis (IE) was evaluated within a program of hospital-in-home (HIH) based on self-administered outpatient parenteral antimicrobial therapy (S-OPAT). IE episodes (n=48 in 45 patients; 71% middle-aged males) were recruited into the HIH program between 1998 and 2012. Following treatment stabilization at the hospital they returned home for HIH in which a physician and/or a nurse supervised the S-OPAT. Safety and efficacy were evaluated as mortality, re-occurrence, and unexpected re-admission to hospital. Of the episodes of IE, 83.3% had comorbidities with a mean score of 2.3 on the Charlson index and 1.5 on the Profund index; 60.4% had pre-existing valve disease (58.6% having had surgical intervention); 8.3% of patients had suffered a previous IE episode; 62.5% of all episodes affected a native valve; 45.8% being mitral; 70.8% of infection derived from the community. In 75% of the episodes there was micro-organism growth, of which 83.3% were Gram positive. Overall duration of antibiotic treatment was 4.8 weeks; 60.4% of this time corresponding to HIH. Re-admission occurred in 12.5% of episodes of which 33.3% returned to HIH to complete the S-OPAT. No deaths occurred during HIH. One year after discharge, 2 patients had recurrence and 5 patients died, in 2 of whom previous IE as cause-of-death could not be excluded. In conclusion, the S-OPAT schedule of hospital-in-home is safe and efficacious in selected patients with IE.

  10. Poly(carboxylic acid)-Cyclodextrin/Anionic Porphyrin Finished Fabrics as Photosensitizer Releasers for Antimicrobial Photodynamic Therapy.

    PubMed

    Castriciano, Maria Angela; Zagami, Roberto; Casaletto, Maria Pia; Martel, Bernard; Trapani, Mariachiara; Romeo, Andrea; Villari, Valentina; Sciortino, Maria Teresa; Grasso, Laura; Guglielmino, Salvatore; Scolaro, Luigi Monsù; Mazzaglia, Antonino

    2017-03-20

    In the development of new antibacterial therapeutic approaches to fight multidrug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) represents a well-known alternative to treat local infections caused by different microorganisms. Here we present a polypropylene (PP) fabric finished with citrate-hydroxypropyl-βCD polymer (PP-CD) entrapping the tetra-anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine (TPPS) as photosensitizer-eluting scaffold (PP-CD/TPPS) for aPDT. The concept is based on host-guest complexation of porphyrin in the cavities of CDs immobilized on the PP fibers, followed by its sustained and controlled delivery in release medium and simultaneous photoinactivation of microorganisms. Morphology of fabric was characterized by optical (OM) and scanning electron microscopies (SEM). Optical properties were investigated by UV-vis absorption, steady- and time-resolved fluorescence emission spectroscopy. X-ray photoelectron spectroscopy (XPS) and FT-IR revealed the surface chemical composition and the distribution map of the molecular components on the fabric, respectively. Direct (1)O2 determination allowed to assess the potential photodynamic activity of the fabric. Release kinetics of TPPS in physiological conditions pointed out the role of the CD cavity to control the TPPS elution. Photoantimicrobial activity of the porphyrin-loaded textile was investigated against both Gram-positive Staphylococcus aureus ATCC 29213 (S. aureus) and Gram-negative Pseudomonas aeruginosa ATCC 27853 (P. aeruginosa). Optical microscopy coupled with UV-vis extinction and fluorescence spectra aim to ascertain the uptake of TPPS to S. aureus bacterial cells. Finally, PP-CD/TPPS fabric-treated S. aureus cells were photokilled of 99.98%. Moreover, low adhesion of S. aureus cells on textile was established. Conversely, no photodamage of fabric-treated P. aeruginosa cells was observed, together with their satisfying adhesion.

  11. Improved antimicrobial therapy with cationic tetra- and octa-substituted phthalocyanines

    NASA Astrophysics Data System (ADS)

    Angelov, I.; Mantareva, V.; Kussovski, V.; Woehrle, D.; Borisova, E.; Avramov, L.

    2008-12-01

    Photodynamic therapy (PDT) today is an innovative and not yet widespread light-drug initiated treatment that is based on the photoactive compound irradiated with proper light to produce oxygen species that are toxic to the pathogenic biological objects- bacteria, viruses, tumor cells. The obstacles that limited the efficacy of PDT concern to the selectivity and multi-drug resistance prolong time for cellular release and side effects of skin photosensitivity for commercial porphyrin originated photosensitizers (PS). Now there are very intensive investigations for introducing in practice a new, with a least side effects PSs for PDT. The usefulness of the more extended macromolecules structured with proper substituents refers not only to the improved optical properties like far-red and with intensive absorption and emission capacity, but mainly to the ability for selective delivery and adhesion to the target cells, such as bacteria or other pathogens. The present study focuses on the charge effect of photodynamic agent on the uptake capacity toward gram-negative bacteria cells and their further photoinactivation. The multi-drug resistant microorganism Aeromanas hydrophilla, which is causing diseases to fishes and humans, is treated. The new octa-cationic phthalocyanines are designed to compare PDT efficacy to the efficacy of tetra-substituted derivatives with the same functional peripheral substituents. The higher cellular accumulation to the bacteria cells as a result of the high number of positive charges of photosensitizer, leading to the better adhesion to the cellular membranes and improved photoinactivation of bacteria causing superficial and intraorgan infections. These results set a base of a rationale design of covalently octa-substituted phthalocyanines with positive charge for a successful treatment of microorganisms.

  12. A randomized trial of open lung biopsy versus empiric antimicrobial therapy in cancer patients with diffuse pulmonary infiltrates.

    PubMed

    Browne, M J; Potter, D; Gress, J; Cotton, D; Hiemenz, J; Thaler, M; Hathorn, J; Brower, S; Gill, V; Glatstein, E

    1990-02-01

    Twenty-four cancer patients with diffuse interstitial pneumonitis (DIP) were randomized to undergo an open lung biopsy (OLB) within 8 hours of presentation (12 patients) or to receive empiric antimicrobial therapy (ET) with trimethoprim-sulfamethoxazole (TMP-SMX) erythromycin for a minimum of 4 days (12 patients). Patients whose condition deteriorated underwent an OLB on day 4. Eight of 12 patients (67%) having OLB survived versus 10 of 12 (83%) receiving ET (P = .64). Morbidity occurred in nine of 12 (75%) having OLB versus eight of 12 (67%) receiving ET (P = 1.0). Concurrently, there were 14 additional cancer patients with DIP who were not randomized (nine refused, three had a coagulopathy contraindicating surgery, two were excluded by primary care physicians) and who were comparable demographically to the randomized group. Two received OLB and 12 ET. Combining the randomized and nonrandomized groups, eight of 14 (57%) having an initial OLB survived versus 18 of 24 (75%) of ET-treated patients (P2 = .19). Results of the OLB were seven Pneumocystis carinii pneumonia (PCP), five nonspecific pneumonitis (NSP), one cytomegalovirus, and one lymphoma. Results of OLB led to discontinuation of antibiotics in three patients. Of the 24 ET patients, eight failed to improve by day 4 and had an OLB. Results were two NSP, two PCP, two cancer, one blastomycosis, and one Candida pneumonia. Complications were seen in 10 of 14 (72%) initial OLB patients versus 14 of 24 (58%) patients on the ET arm (P = .65). When the complication rate between patients receiving only empiric antibiotics was compared with all patients having an OLB (initially or on day 4), the difference was greater in patients undergoing OLB (37% v 72%, respectively) (P2 = .14). ET with TMP-SMX plus erythromycin and broad spectrum antibiotics in granulocytopenic patients appeared to be as successful and potentially less toxic than an OLB in this study. Although the number of patients in this study was small, these

  13. Bloodstream Infections Due to Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae: Risk Factors for Mortality and Treatment Outcome, with Special Emphasis on Antimicrobial Therapy

    PubMed Central

    Kang, Cheol-In; Kim, Sung-Han; Park, Wan Beom; Lee, Ki-Deok; Kim, Hong-Bin; Kim, Eui-Chong; Oh, Myoung-Don; Choe, Kang-Won

    2004-01-01

    This study was conducted to evaluate risk factors for mortality and treatment outcome of bloodstream infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK). ESBL production in stored K. pneumoniae and E. coli blood isolates from Jan 1998 to Dec 2002 was phenotypically determined according to NCCLS guidelines and/or the double-disk synergy test. A total of 133 patients with ESBL-EK bacteremia, including 66 patients with ESBL-producing K. pneumoniae and 67 with ESBL-producing E. coli, were enrolled. The overall 30-day mortality rate was 25.6% (34 of 133). Independent risk factors for mortality were severe sepsis, peritonitis, neutropenia, increasing Acute Physiology and Chronic Health Evaluation II score, and administration of broad-spectrum cephalosporin as definitive antimicrobial therapy (P < 0.05 for each of these risk factors). In 117 of the 133 patients, excluding 16 patients who died within 3 days after blood culture sample acquisition, the 30-day mortality rates according to definitive antibiotics were as follows: carbapenem, 12.9% (8 of 62); ciprofloxacin, 10.3% (3 of 29); and others, such as cephalosporin or an aminoglycoside, 26.9% (7 of 26). When patients who received appropriate definitive antibiotics, such as carbapenem or ciprofloxacin, were evaluated, mortality in patients receiving inappropriate empirical antimicrobial therapy was found not to be significantly higher than mortality in those receiving appropriate empirical antimicrobial therapy (18.9 versus 15.5%; P = 0.666). Carbapenem and ciprofloxacin were the most effective antibiotics in antimicrobial therapy for ESBL-EK bacteremia. A delay in appropriate definitive antimicrobial therapy was not associated with higher mortality if antimicrobial therapy was adjusted appropriately according to the susceptibility results. Our data suggest that more prudent use of carbapenem as empirical antibiotic may be reasonable. PMID:15561828

  14. [Outpatient Parenteral Antimicrobial Therapy (OPAT) with Elastomeric Pumps in Collaboration with Home-visit Nursing Services in Japan: Experience of the First 10 Patients].

    PubMed

    Hase, Ryota; Uno, Shunsuke; Miyoshi, Kazuyasu; Fujita, Koji; Suzuki, Hiroyuki; Suzuki, Daisuke; Mikawa, Takahiro; Muranaka, Kiyoharu; Hosokawa, Naoto

    2015-09-01

    In 2014, we reported the first trial based on outpatient parenteral antimicrobial therapy (OPAT) with continuous infusions in Japan. Following this, we found many patients who were eligible for OPAT but could not undertake it owing to difficulties in accessing the clinic daily. To overcome this problem, we created a model in collaboration with visiting nursing stations and started providing OPAT with the services. We report herein on a summary of the investigation of the first 10 patients treated under this model. We collected data pertaining to diseases, organisms, antimicrobials, treatment duration, bed days saved, outcome, readmission rate, and cost reductions associated with these patients. The most commonly targeted disease was osteomyelitis, followed by infective endocarditis. The condition of nine of the patients was complicated by bacteremia. The most commonly targeted organism was Staphylococcus aureus. Cefazolin was the most frequently prescribed antimicrobial, followed by Penicillin G. The median duration for OPAT was 12 days (range: 5-23 days). The total number of bed days saved was 129. All patients completed the planned OPAT. Eight patients were cured and two showed improvement. Only one patient was readmitted within a month after the completion of therapy. The estimated medical cost reduction was 496,540 yen, which is approximately 4,200 US dollars. Collaboration with visiting nursing stations provided OPAT to the patients who had difficulties in accessing the clinic daily. Our study shows that OPAT administered by continuous infusion in collaboration with home-visit nursing services would be a safe and feasible practice for efficient bed utilization and medical cost saving.

  15. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  16. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  17. Antimicrobial Peptides in 2014

    PubMed Central

    Wang, Guangshun; Mishra, Biswajit; Lau, Kyle; Lushnikova, Tamara; Golla, Radha; Wang, Xiuqing

    2015-01-01

    This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms. PMID:25806720

  18. Antimicrobial Stewardship

    PubMed Central

    Doron, Shira; Davidson, Lisa E.

    2011-01-01

    Antimicrobial resistance is increasing; however, antimicrobial drug development is slowing. Now more than ever before, antimicrobial stewardship is of the utmost importance as a way to optimize the use of antimicrobials to prevent the development of resistance and improve patient outcomes. This review describes the why, what, who, how, when, and where of antimicrobial stewardship. Techniques of stewardship are summarized, and a plan for implementation of a stewardship program is outlined. PMID:22033257

  19. ACVIM consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance.

    PubMed

    Weese, J S; Giguère, S; Guardabassi, L; Morley, P S; Papich, M; Ricciuto, D R; Sykes, J E

    2015-01-01

    The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.

  20. Prevention of combat-related infections: antimicrobial therapy in battlefield and barrier measures in French military medical treatment facilities.

    PubMed

    Mérens, Audrey; Rapp, Christophe; Delaune, Deborah; Danis, Julien; Berger, Franck; Michel, Remy

    2014-01-01

    Infection is a major complication associated with combat-related injuries. Beside immobilization, wound irrigation, surgical debridement and delayed coverage, post-injury antimicrobials contribute to reduce combat-related infections, particularly those caused by bacteria of the early contamination flora. In modern warfare, bacteria involved in combat-related infections are mainly Gram-negative bacteria belonging to the late contamination flora. These bacteria are frequently resistant or multiresistant to antibiotics and spread through the deployed chain of care. This article exposes the principles of war wounds antimicrobial prophylaxis recommended in the French Armed Forces and highlights the need for high compliance to hygiene standard precautions, adapted contact precautions and judicious use of antibiotics in French deployed military medical treatment facilities (MTF).

  1. The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy

    PubMed Central

    Hsieh, I-Ni; Hartshorn, Kevan L.

    2016-01-01

    Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins), and proteins more recently discovered to have AMP-like activity (histones and Alzheimer’s associated β-amyloid). We will discuss the interactions between AMPs and other host defense proteins. Major emphasis will be placed on novel synthetic AMPs derived from modification of natural proteins, and on potential methods of increasing expression of endogenous AMPs, since these approaches may lead to novel antiviral therapeutics. PMID:27608030

  2. 5 CFR 919.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Adequate evidence. 919.900 Section 919.900 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 919.900 Adequate...

  3. Antimicrobial Pesticides

    MedlinePlus

    Jump to main content US EPA United States Environmental Protection Agency Search Search Pesticides Share Facebook Twitter Google+ ... of antimicrobial pesticides (Part 158W) Antimicrobials play an important role in public health and safety. While providing ...

  4. Antimicrobials Treatment

    NASA Astrophysics Data System (ADS)

    Drosinos, Eleftherios H.; Skandamis, Panagiotis N.; Mataragas, Marios

    The use of antimicrobials is a common practice for preservation of foods. Incorporation, in a food recipe, of chemical antimicrobials towards inhibition of spoilage and pathogenic micro-organisms results in the compositional modification of food. This treatment is nowadays undesirable for the consumer, who likes natural products. Scientific community reflecting consumers demand for natural antimicrobials has made efforts to investigate the possibility to use natural antimicrobials such us bacteriocins and essential oils of plant origin to inhibit microbial growth.

  5. Antimicrobial stewardship.

    PubMed

    Allerberger, F; Mittermayer, H

    2008-03-01

    The aim of antimicrobial management or stewardship programmes is to ensure proper use of antimicrobial agents in order to provide the best treatment outcomes, to lessen the risk of adverse effects (including antimicrobial resistance), and to promote cost-effectiveness. Increasingly, long-term sustainability is found to be the major focus of antimicrobial stewardship. Implementing structural measures in healthcare institutions is therefore a major, but not the sole, focus of attention in promoting prudent use of antibiotics. The problem of antimicrobial resistance requires common strategies at all levels--for the prescribers and at ward, departmental, hospital, national and international levels.

  6. Evaluation of the efficacy of photodynamic antimicrobial therapy using a phenothiazine compound and LED (red-orange) on the interface: macrophage vs S. aureus

    NASA Astrophysics Data System (ADS)

    Sampaio, Fernando José P.; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Pires-Santos, Gustavo M.; Gesteira, Maria F. M.; Pinheiro, Antônio L. B.

    2015-03-01

    Antimicrobial Photodynamic therapy is a technique in which microorganisms are exposed to a photosensitizing drug and then irradiated with low-intensity visible light of the appropriate wavelength. The resulting photochemical reaction generates cytotoxic reactive oxygen species, such as singlet oxygen and free radicals, which are able to exert bactericidal effect. Much is already known about the photodynamic inactivation of microorganisms: both antibiotic-sensitive and - resistant strains can be successfully photo inactivated, and there is the additional advantage that repeated photosensitization of bacterial cells does not induce a selection of resistant strains. Recently, a series of studies have shown that it is possible to kill bacteria with a light source after the microorganisms have been sensitized with low concentration of dye, such as phenothiazines. The aim of this study was to evaluate the phagocytic function of macrophages J774 against S. aureus in the presence and absence of AmPDT with phenothiazine compound (12.5 μg/mL) and red-orange LED. Experimental groups: Control Group (L-F-), Phenothiazine group (L-F+) LED group (L+F-), Photodynamic therapy group (L+F+). The tests presented in this study were carried out in triplicate. This study demonstrated that AmPDT is able to increase about twice the phagocytic ability of macrophages; however, the bactericidal capacity of these cells did not show a substantial improvement, probably because the oxidative burst was less intense.

  7. [Phenomenology of craving: from differentiation to adequate therapy].

    PubMed

    Mendelevich, V D

    2010-01-01

    The author analyzes a phenomenon of addiction from the psychological/psychiatric position and differentiates it from psychopathological disorders, including parabulia, hyperbulia, paraphylia, commonly used for the definition of drive disorders. It has been concluded that addition is a specific complex of clinical symptoms which is not similar to other drive disorders. To avoid diagnostic and therapeutic errors, the author suggests to revise definitions by assigning the biological sense to the conception of addiction within psychoactive substance dependence and sexual addiction, some forms of eating dependence and to use the definition of paraaddictive drives in cases of over-valued drives (gambling, Internet dependence, fanaticism etc).

  8. Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy.

    PubMed

    Yuan, Yu-Guo; Peng, Qiu-Ling; Gurunathan, Sangiliyandi

    2017-03-06

    Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance (MDR) has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative, cost-effective, and efficient antimicrobial agents that overcome antimicrobial resistance. Here, AgNPs synthesized using the bio-molecule quercetin were characterized using various analytical techniques. The synthesized AgNPs were highly spherical in shape and had an average size of 11 nm. We evaluated the efficacy of synthesized AgNPs against two MDR pathogenic bacteria, namely, Pseudomonas aeruginosa and Staphylococcus aureus, which were isolated from milk samples produced by mastitis-infected goats. The minimum inhibitory concentrations (MICs) of AgNPs against P. aeruginosa and S. aureus were found to be 1 and 2 μg/mL, respectively. Our findings suggest that AgNPs exert antibacterial effects in a dose- and time-dependent manner. Results from the present study demonstrate that the antibacterial activity of AgNPs is due to the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and leakage of proteins and sugars in bacterial cells. Results of the present study showed that AgNP-treated bacteria had significantly lower lactate dehydrogenase activity (LDH) and lower adenosine triphosphate (ATP) levels compared to the control. Furthermore, AgNP-treated bacteria

  9. Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy

    PubMed Central

    Yuan, Yu-Guo; Peng, Qiu-Ling; Gurunathan, Sangiliyandi

    2017-01-01

    Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance (MDR) has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative, cost-effective, and efficient antimicrobial agents that overcome antimicrobial resistance. Here, AgNPs synthesized using the bio-molecule quercetin were characterized using various analytical techniques. The synthesized AgNPs were highly spherical in shape and had an average size of 11 nm. We evaluated the efficacy of synthesized AgNPs against two MDR pathogenic bacteria, namely, Pseudomonas aeruginosa and Staphylococcus aureus, which were isolated from milk samples produced by mastitis-infected goats. The minimum inhibitory concentrations (MICs) of AgNPs against P. aeruginosa and S. aureus were found to be 1 and 2 μg/mL, respectively. Our findings suggest that AgNPs exert antibacterial effects in a dose- and time-dependent manner. Results from the present study demonstrate that the antibacterial activity of AgNPs is due to the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and leakage of proteins and sugars in bacterial cells. Results of the present study showed that AgNP-treated bacteria had significantly lower lactate dehydrogenase activity (LDH) and lower adenosine triphosphate (ATP) levels compared to the control. Furthermore, AgNP-treated bacteria

  10. Antimicrobial Activity.

    PubMed

    2016-01-01

    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  11. Asbestos/NESHAP adequately wet guidance

    SciTech Connect

    Shafer, R.; Throwe, S.; Salgado, O.; Garlow, C.; Hoerath, E.

    1990-12-01

    The Asbestos NESHAP requires facility owners and/or operators involved in demolition and renovation activities to control emissions of particulate asbestos to the outside air because no safe concentration of airborne asbestos has ever been established. The primary method used to control asbestos emissions is to adequately wet the Asbestos Containing Material (ACM) with a wetting agent prior to, during and after demolition/renovation activities. The purpose of the document is to provide guidance to asbestos inspectors and the regulated community on how to determine if friable ACM is adequately wet as required by the Asbestos NESHAP.

  12. Antimicrobial drug resistance.

    PubMed

    Martinez, Marilyn; Silley, Peter

    2010-01-01

    This chapter provides an overview of our current understanding of the mechanisms associated with the development of antimicrobial drug resistance, international differences in definitions of resistance, ongoing efforts to track shifts in drug susceptibility, and factors that can influence the selection of therapeutic intervention. The latter presents a matrix of complex variables that includes the mechanism of drug action, the pharmacokinetics (PK) of the antimicrobial agent in the targeted patient population, the pharmacodynamics (PD) of the bacterial response to the antimicrobial agent, the PK/PD relationship that will influence dose selection, and the integrity of the host immune system. Finally, the differences between bacterial tolerance and bacterial resistance are considered, and the potential for non-traditional anti-infective therapies is discussed.

  13. Polyphenols as antimicrobial agents.

    PubMed

    Daglia, Maria

    2012-04-01

    Polyphenols are secondary metabolites produced by higher plants, which play multiple essential roles in plant physiology and have potential healthy properties on human organism, mainly as antioxidants, anti-allergic, anti-inflammatory, anticancer, antihypertensive, and antimicrobial agents. In the present review the antibacterial, antiviral, and antifungal activities of the most active polyphenol classes are reported, highlighting, where investigated, the mechanisms of action and the structure-activity relationship. Moreover, considering that the microbial resistance has become an increasing global problem, and there is a compulsory need to find out new potent antimicrobial agents as accessories to antibiotic therapy, the synergistic effect of polyphenols in combination with conventional antimicrobial agents against clinical multidrug-resistant microorganisms is discussed.

  14. Antimicrobial (Drug) Resistance Prevention

    MedlinePlus

    ... Visitor Information Contact Us Research > NIAID's Role in Research > Antimicrobial (Drug) Resistance > Understanding share with facebook share with twitter ... Prevention, Antimicrobial (Drug) Resistance Antimicrobial (Drug) Resistance Antimicrobial ... To prevent antimicrobial resistance, you and your healthcare ...

  15. Funding the Formula Adequately in Oklahoma

    ERIC Educational Resources Information Center

    Hancock, Kenneth

    2015-01-01

    This report is a longevity, simulational study that looks at how the ratio of state support to local support effects the number of school districts that breaks the common school's funding formula which in turns effects the equity of distribution to the common schools. After nearly two decades of adequately supporting the funding formula, Oklahoma…

  16. How to fight antimicrobial resistance.

    PubMed

    Foucault, Cédric; Brouqui, Philippe

    2007-03-01

    Antimicrobial misuse results in the development of resistance and superbugs. Over recent decades, resistance has been increasing despite continuing efforts to control it, resulting in increased mortality and cost. Many authorities have proposed local, regional and national guidelines to fight against this phenomenon, and the usefulness of these programmes has been evaluated. Multifaceted intervention seems to be the most efficient method to control antimicrobial resistance. Monitoring of bacterial resistance and antibiotic use is essential, and the methodology has now been homogenized. The implementation of guidelines and infection control measures does not control antimicrobial resistance and needs to be reinforced by associated measures. Educational programmes and rotation policies have not been evaluated sufficiently in the literature. Combination antimicrobial therapy is inefficient in controlling antimicrobial resistance.

  17. Effect of a Salmonella Group H1 R Factor on Virulence and Response of Infections to Antimicrobial Therapy

    PubMed Central

    Butler, Thomas; Shuster, C. W.; Franco, Amalia

    1979-01-01

    A group H1 R factor encoding resistance to chloramphenicol, streptomycin, sulfonamide, and tetracycline was transferred into Salmonella typhimurium LT-2. The virulence of LT-2 for mice, as assessed by intraperitoneal 50% lethal dose and the number of organisms in the spleen, was not affected by the R factor. On the other hand, the R factor conferred resistance in mouse infections to therapy with chloramphenicol and trimethoprim plus sulfamethoxazole. PMID:380460

  18. Nanoemulsion Therapy for Burn Wounds is Effective as a Topical Antimicrobial Against Gram Negative and Gram Positive Bacteria

    PubMed Central

    Dolgachev, Vladislav A.; Ciotti, Susan M.; Eisma, Rone; Gracon, Stephen; Wilkinson, J. Erby; Baker, James R.; Hemmila, Mark R.

    2014-01-01

    Objective The aim of this study is to investigate the antimicrobial efficacy of two different nanoemulsion formulations against Gram positive and Gram negative bacteria in an in vivo rodent scald burn model. Methods Male Sprague-Dawley rats were anesthetized and received a partial-thickness scald burn. Eight hours following burn injury the wound was inoculated with 1x108 colony forming units of Pseudomonas aeruginosa or Staphylococcus aureus. Treatment groups consisted of two different nanoemulsion formulations (NB-201, NB-402), nanoemulsion vehicle (NE vehicle), or saline. Topical application of the treatment was performed at 16 and 24 hours after burn injury. Animals were euthanized 32 hours after burn injury and skin samples obtained for quantitative wound culture and determination of dermal inflammation markers. In a separate set of experiments, burn wound progression was measured histologically after 72 hours of treatment. Results Both nanoemulsion formulations (NB-201, NB 402) significantly reduced burn wound infections with either Pseudomonas aeruginosa or Staphylococcus aureus, and decreased median bacterial counts at least 3 logs as compared to animals with saline applications (p<0.0001). NB-201 and NB-402 also decreased dermal neutrophil recruitment and sequestration into the wound as measured by myeloperoxidase assay and histopathology (p<0.05). In addition, there was a reduction in the pro-inflammatory dermal cytokines (IL-1β, IL-6 and TNF-α) and the neutrophil chemoattractants CXCL1 and CXCL2. By histology examination, both NB-201 and NB-402 appeared to suppress burn wound progression 72 hours after injury. Conclusions Topically applied NB-201 and NB-402 are effective in decreasing Gram positive and negative bacteria growth in burn wounds, reducing inflammation and abrogating burn wound progression. PMID:26182074

  19. Nanoemulsion Therapy for Burn Wounds Is Effective as a Topical Antimicrobial Against Gram-Negative and Gram-Positive Bacteria.

    PubMed

    Dolgachev, Vladislav A; Ciotti, Susan M; Eisma, Rone; Gracon, Stephen; Wilkinson, J Erby; Baker, James R; Hemmila, Mark R

    2016-01-01

    The aim of this study is to investigate the antimicrobial efficacy of two different nanoemulsion (NE) formulations against Gram-positive and Gram-negative bacteria in an in vivo rodent scald burn model. Male Sprague-Dawley rats were anesthetized and received a partial-thickness scald burn. Eight hours after burn injury, the wound was inoculated with 1 × 10(8) colony-forming units of Pseudomonas aeruginosa or Staphylococcus aureus. Treatment groups consisted of two different NE formulations (NB-201 and NB-402), NE vehicle, or saline. Topical application of the treatment was performed at 16 and 24 hours after burn injury. Animals were killed 32 hours after burn injury, and skin samples were obtained for quantitative wound culture and determination of dermal inflammation markers. In a separate set of experiments, burn wound progression was measured histologically after 72 hours of treatment. Both NE formulations (NB-201 and NB-402) significantly reduced burn wound infections with either P. aeruginosa or S. aureus and decreased median bacterial counts at least three logs when compared with animals with saline applications (p < .0001). NB-201 and NB-402 also decreased dermal neutrophil recruitment and sequestration into the wound as measured by myeloperoxidase (MPO) assay and histopathology (p < .05). In addition, there was a decrease in the proinflammatory dermal cytokines (interleukin 1-beta [IL-1β], IL-6, and tumor necrosis factor alpha [TNF-α]) and the neutrophil chemoattractants CXCL1 and CXCL2. Using histologic examination, it was found that both NB-201 and NB-402 appeared to suppress burn wound progression 72 hours after injury. Topically applied NB-201 and NB-402 are effective in decreasing Gram-positive and Gram-negative bacteria growth in burn wounds, reducing inflammation, and abrogating burn wound progression.

  20. Antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model: implications for prophylaxis and treatment of combat-related wound infections.

    PubMed

    Zhang, Yunsong; Zhu, Yingbo; Gupta, Asheesh; Huang, Yingying; Murray, Clinton K; Vrahas, Mark S; Sherwood, Margaret E; Baer, David G; Hamblin, Michael R; Dai, Tianhong

    2014-06-15

    In this study, we investigated the utility of antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model. A bioluminescent clinical isolate of multidrug-resistant A. baumannii was obtained. The susceptibility of A. baumannii to blue light (415 nm)-inactivation was compared in vitro to that of human keratinocytes. Repeated cycles of sublethal inactivation of bacterial by blue light were performed to investigate the potential resistance development of A. baumannii to blue light. A mouse model of third degree burn infected with A. baumannii was developed. A single exposure of blue light was initiated 30 minutes after bacterial inoculation to inactivate A. baumannii in mouse burns. It was found that the multidrug-resistant A. baumannii strain was significantly more susceptible than keratinocytes to blue light inactivation. Transmission electron microscopy revealed blue light-induced ultrastructural damage in A. baumannii cells. Fluorescence spectroscopy suggested that endogenous porphyrins exist in A. baumannii cells. Blue light at an exposure of 55.8 J/cm(2) significantly reduced the bacterial burden in mouse burns. No resistance development to blue light inactivation was observed in A. baumannii after 10 cycles of sublethal inactivation of bacteria. No significant DNA damage was detected in mouse skin by means of a skin TUNEL assay after a blue light exposure of 195 J/cm(2).

  1. [Antimicrobial susceptibility in Chile 2012].

    PubMed

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  2. Antimicrobial Polymer

    DOEpatents

    McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

    2004-09-28

    A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The polymeric composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from metals, metal alloys, metal salts, metal complexes and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one example embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl; and the metallic antimicrobial agent is selected from chelated silver ions, silver metal, chelated copper ions, copper metal, chelated zinc ions, zinc metal and mixtures thereof.

  3. Clinical, biochemical and histological study of the effect of antimicrobial photodynamic therapy on oral mucositis induced by 5-fluorouracil in hamsters.

    PubMed

    Cruz, Érika de Paula da; Campos, Luana; Pereira, Filipi da Silva; Magliano, Gabriela Campos; Benites, Bernar Monteiro; Arana-Chavez, Victor Elias; Ballester, Rafael Yagüe; Simões, Alyne

    2015-06-01

    Oral mucositis (OM) is a debilitating side effect of chemotherapy, which can be relieved by phototherapy. Antimicrobial photodynamic therapy (aPDT) may be used for the treatment of OM, when infection is present. However, there are no studies showing that aPDT affects tissue repair process when used in the treatment of lesions caused by OM. This work aims to evaluate the effect of aPDT in healing OM induced by 5-Fluorouracil (5-FU). Two hundred forty-five hamsters were divided into two groups, control (C) and experimental, which were subdivided into 4 subgroups (Ch, ChP, ChL, aPDT). C group received only the vehicle of chemotherapy and anesthesia, whereas all animals of the experimental groups received anesthesia and chemotherapy agent 5-FU to induce OM. Ch group received no OM treatment; ChP group received an application of methylene blue (MB) 0.01%; ChL received irradiation with low-power-laser (LPL-660 nm/120 J /cm(2)/40 mW/4.4 J per point); and aPDT received MB and LPL irradiation. OM Clinical severity were daily assessed by a blinded examiner. The animals were sacrificed after 5, 7 and 10 days of experiment and their oral mucosa were removed for biochemical (enzymatic activity of SOD and catalase) and histological analyzes (light microscopy). After statistical analysis was performed, results showed that aPDT reduced the severity of OM on the tenth day of the experiment, when compared to the initial OM score (p < 0.05), as well as increased keratinization with organized collagen deposition in the lamina propria. In conclusion, aPDT can be safely used in animals with infected OM because it does not affect lesion-repairing processes.

  4. Efficacy of Antimicrobial Photodynamic Therapy as an Adjunctive to Mechanical Debridement in the Treatment of Peri-implant Diseases: A Randomized Controlled Clinical Trial

    PubMed Central

    Karimi, Mohammad Reza; Hasani, Ali; Khosroshahian, Salva

    2016-01-01

    Introduction: The purpose of the present study was to assess the clinical effects of anti-microbial photodynamic therapy (PDT) after closed surface scaling in the treatment of peri-implant diseases. Methods: Ten patients with a total of 15 pairs of dental implants, showing clinical and radiographic signs of peri-implant diseases, were included in this study. In each patient, one implant randomly served as control implant and the other served as test implant. The control implants were treated with closed surface scaling only and the test implants received additionally PDT, using light with a wavelength of 630 nm and intensity of 2000 mw/cm2 for 120 seconds after application of photosensitizer in peri-implant sulcus. Clinical parameters were evaluated before and 1.5 and 3 months after treatment. Results: Statistical analysis showed significant differences in probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and gingival index (GI) at each time point between the two groups. There were no statistically significant changes with respect to any of the parameters in the control group. Complete resolution of BOP at 3 months was achieved in 100% of test implants. At 1.5 and 3 months, there were significant differences in the mean probing depth and CAL gain measurements at implants in the test group. Conclusion: The present study revealed that adjunctive use of PDT following closed surface scaling could lead to clinical improvement of peri-implant diseases. Further studies are necessary to confirm our results. PMID:28144432

  5. Local adjunct effect of antimicrobial photodynamic therapy for the treatment of chronic periodontitis in type 2 diabetics: split-mouth double-blind randomized controlled clinical trial.

    PubMed

    Castro Dos Santos, Nídia Cristina; Andere, Naira Maria Rebelatto Bechara; Araujo, Cássia Fernandes; de Marco, Andrea Carvalho; Dos Santos, Lúcio Murilo; Jardini, Maria Aparecida Neves; Santamaria, Mauro Pedrine

    2016-11-01

    Diabetes has become a global epidemic. Its complications can have a significant impact on quality of life, longevity, and public health costs. The presence of diabetes might impair the prognosis of periodontal treatments due to its negative influence on wound healing. Antimicrobial photodynamic therapy (aPDT) is a local approach that can promote bacterial decontamination in periodontal pockets. The aim of this study was to investigate the local effect of adjunct aPDT to ultrasonic periodontal debridement (UPD) and compare it to UD only for the treatment of chronic periodontitis in type 2 diabetic patients. Twenty type 2 diabetic patients with moderate to severe generalized chronic periodontitis were selected. Two periodontal pockets with probing depth (PD) and clinical attachment level (CAL) ≥5 mm received UPD only (UPD group) or UPD plus adjunct aPDT (UPD + aPDT group). Periodontal clinical measures were collected and compared at baseline and 30, 90, and 180 days. After 180 days of follow-up, there were statistically significant reductions in PD from 5.75 ± 0.91 to 3.47 ± 0.97 mm in the UPD group and from 6.15 ± 1.27 to 3.71 ± 1.63 mm in the UPD + aPDT group. However, intergroup analysis did not reveal statistically significant differences in any of the evaluated clinical parameters (p > 0.05). The adjunct application of aPDT to UPD did not present additional benefits for the treatment of chronic periodontitis in type 2 diabetic patients. The ClinicalTrials.gov identifier of the present study is NCT02627534.

  6. [Comparative study of the efficacy of larva therapy for debridement and control of bacterial burden compared to surgical debridement and topical application of an antimicrobial].

    PubMed

    Contreras-Ruiz, José; Fuentes-Suárez, Adán; Arroyo-Escalante, Sara; Moncada-Barron, David; Sosa-de-Martínez, María Cristina; Maravilla-Franco, Ernesto; Domínguez-Cherit, Judith Guadalupe

    2016-10-01

    Maggot debridement therapy (MDT) is the use of medical grade maggots of the fly Lucilia sericata for wound debridement. Recent observations show that MDT decreases bacterial burden as well. Venous ulcers are the most commonly seen in wound clinics and require, besides adequate treatment of venous hypertension, proper wound bed preparation with debri dement of necrotic tissue and control of potential infections. To evaluate the efficacy of MDT in venous ulcers a randomized controlled trial was designed to compare MDT to surgical debridement and topical application of silver sulfadiazine (SSD) in 19 patients for 4 weeks. The study variables were area reduction, wound bed characteristics, pain, odor, anxiety and bacterial burden using quantitative tissue biopsies. MDT was effective as surgical debridement associated with topical SDD in the debridement of the wound and in reducing its size. A significant difference was observed in the reduction of bacterial burden in favor of the MDT group. Odor and anxiety increased in the MDT group without any difference in the pain intensity between groups. In conclusion, this study suggests that MDT is as effective as surgical debridement for the debridement of necrotic tissue and promote wound healing in venous ulcers and better at reducing bacterial burden.

  7. Outpatient Parenteral Antibiotic Therapy in an Academic Practice in Rhode Island

    PubMed Central

    Touzard Romo, F; Resnick, B; Perez-Cioe, M; Flanigan, TP; Kojic, E; Beckwith, CG

    2015-01-01

    Outpatient parenteral antimicrobial therapy (OPAT) is an increasingly utilized treatment modality that has been proven to be safe and cost-effective for treating infections that require prolonged antimicrobial treatment. Adequate patient selection, a structured OPAT team with an effective communication system, and routine clinical monitoring are key elements to establish a successful OPAT program. The Infectious Diseases and Immunology Center at The Miriam Hospital offers a multidisciplinary OPAT model coordinated by infectious diseases specialists and serves as a major referral center in Rhode Island. PMID:25562060

  8. Serum thyroglobulin reference intervals in regions with adequate and more than adequate iodine intake.

    PubMed

    Wang, Zhaojun; Zhang, Hanyi; Zhang, Xiaowen; Sun, Jie; Han, Cheng; Li, Chenyan; Li, Yongze; Teng, Xiaochun; Fan, Chenling; Liu, Aihua; Shan, Zhongyan; Liu, Chao; Weng, Jianping; Teng, Weiping

    2016-11-01

    The purpose of this study was to establish normal thyroglobulin (Tg) reference intervals (RIs) in regions with adequate and more than adequate iodine intake according to the National Academy of Clinical Biochemistry (NACB) guidelines and to investigate the relationships between Tg and other factors.A total of 1317 thyroid disease-free adult subjects (578 men, 739 nonpregnant women) from 2 cities (Guangzhou and Nanjing) were enrolled in this retrospective, observational study. Each subject completed a questionnaire and underwent physical and ultrasonic examination. Serum Tg, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), Tg antibody (TgAb), and urinary iodine concentration (UIC) were measured. Reference groups were established on the basis of TSH levels: 0.5 to 2.0 and 0.27 to 4.2 mIU/L.The Tg RIs for Guangzhou and Nanjing were 1.6 to 30.0 and 1.9 to 25.8 ng/mL, respectively. No significant differences in Tg were found between genders or among different reference groups. Stepwise linear regression analyses showed that TgAb, thyroid volume, goiter, gender, age, and TSH levels were correlated with Tg.In adults from regions with adequate and more than adequate iodine intake, we found that Tg may be a suitable marker of iodine status; gender-specific Tg RI was unnecessary; there was no difference between Tg RIs in regions with adequate and more than adequate iodine intake; and the TSH criterion for selecting the Tg reference population could follow the local TSH reference rather than 0.5 to 2.0 mIU/L.

  9. Serum thyroglobulin reference intervals in regions with adequate and more than adequate iodine intake

    PubMed Central

    Wang, Zhaojun; Zhang, Hanyi; Zhang, Xiaowen; Sun, Jie; Han, Cheng; Li, Chenyan; Li, Yongze; Teng, Xiaochun; Fan, Chenling; Liu, Aihua; Shan, Zhongyan; Liu, Chao; Weng, Jianping; Teng, Weiping

    2016-01-01

    Abstract The purpose of this study was to establish normal thyroglobulin (Tg) reference intervals (RIs) in regions with adequate and more than adequate iodine intake according to the National Academy of Clinical Biochemistry (NACB) guidelines and to investigate the relationships between Tg and other factors. A total of 1317 thyroid disease-free adult subjects (578 men, 739 nonpregnant women) from 2 cities (Guangzhou and Nanjing) were enrolled in this retrospective, observational study. Each subject completed a questionnaire and underwent physical and ultrasonic examination. Serum Tg, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), Tg antibody (TgAb), and urinary iodine concentration (UIC) were measured. Reference groups were established on the basis of TSH levels: 0.5 to 2.0 and 0.27 to 4.2 mIU/L. The Tg RIs for Guangzhou and Nanjing were 1.6 to 30.0 and 1.9 to 25.8 ng/mL, respectively. No significant differences in Tg were found between genders or among different reference groups. Stepwise linear regression analyses showed that TgAb, thyroid volume, goiter, gender, age, and TSH levels were correlated with Tg. In adults from regions with adequate and more than adequate iodine intake, we found that Tg may be a suitable marker of iodine status; gender-specific Tg RI was unnecessary; there was no difference between Tg RIs in regions with adequate and more than adequate iodine intake; and the TSH criterion for selecting the Tg reference population could follow the local TSH reference rather than 0.5 to 2.0 mIU/L. PMID:27902589

  10. Quantifying Antimicrobial Exposure: Hazards in Populations With End-Stage Renal Disease.

    PubMed

    Snyder, Graham M; McCoy, Christopher; D'Agata, Erika M C

    2017-03-01

    Using a rigorously collected data set of antimicrobial use among patients receiving chronic hemodialysis, antimicrobial use was calculated using 3 different methodologies: daily defined dose, days of therapy, and start-stop days. Estimates of antimicrobial use varied by as much as 10-fold, depending on the type of antimicrobial. Infect Control Hosp Epidemiol 2017;38:360-363.

  11. Adipose Tissue - Adequate, Accessible Regenerative Material

    PubMed Central

    Kolaparthy, Lakshmi Kanth.; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-01-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  12. Failure of standard antimicrobial therapy in children aged 3-59 months with mild or asymptomatic HIV infection and severe pneumonia.

    PubMed Central

    Jeena, Prakash; Thea, Donald M.; MacLeod, William B.; Chisaka, Noel; Fox, Matthew P.; Coovadia, H. M.; Qazi, Shamim

    2006-01-01

    OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1. PMID:16628299

  13. Antimicrobial Stewardship and Urinary Tract Infections

    PubMed Central

    Abbo, Lilian M.; Hooton, Thomas M.

    2014-01-01

    Urinary tract infections are the most common bacterial infections encountered in ambulatory and long-term care settings in the United States. Urine samples are the largest single category of specimens received by most microbiology laboratories and many such cultures are collected from patients who have no or questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed inappropriately in such patients. Antimicrobial use, whether appropriate or inappropriate, is associated with the selection for antimicrobial-resistant organisms colonizing or infecting the urinary tract. Infections caused by antimicrobial-resistant organisms are associated with higher rates of treatment failures, prolonged hospitalizations, increased costs and mortality. Antimicrobial stewardship consists of avoidance of antimicrobials when appropriate and, when antimicrobials are indicated, use of strategies to optimize the selection, dosing, route of administration, duration and timing of antimicrobial therapy to maximize clinical cure while limiting the unintended consequences of antimicrobial use, including toxicity and selection of resistant microorganisms. This article reviews successful antimicrobial stewardship strategies in the diagnosis and treatment of urinary tract infections. PMID:27025743

  14. Antimicrobial Stewardship

    PubMed Central

    King, Sarah; Exley, Josephine; Taylor, Jirka; Kruithof, Kristy; Larkin, Jody; Pardal, Mafalda

    2016-01-01

    Abstract RAND Europe undertook a systematic review of the evidence of effectiveness and cost effectiveness on changing the public's risk related behaviour pertaining to antimicrobial use to inform the development of a NICE public health guideline aimed at delaying antimicrobial resistance (AMR). The review considered educational interventions targeting individuals, communities or the general public delivered via any mode. Specifically, it aimed to address: 1. Which educational interventions are effective and cost-effective in changing the public's behaviour to ensure they only ask for antimicrobials when appropriate and use them correctly? 2. Which educational interventions are effective and cost-effective in changing the public's behaviour to prevent infection and reduce the spread of antimicrobial resistance? Overall, 60 studies met the inclusion criteria; 29 related to research question 1, and 36 related to research question 2 (five studies were applicable to both). The key findings are summarised in “Evidence Statements” in accordance with NICE guidelines. Evidence Statements provide a high level overview of the key features of the evidence including: the number of studies, the quality of evidence, and the direction of the estimated effect followed by a brief summary of each of the supporting studies. Studies are grouped into Evidence Statements by setting and intervention. PMID:28083399

  15. Antimicrobial polymers.

    PubMed

    Jain, Anjali; Duvvuri, L Sailaja; Farah, Shady; Beyth, Nurit; Domb, Abraham J; Khan, Wahid

    2014-12-01

    Better health is basic requirement of human being, but the rapid growth of harmful pathogens and their serious health effects pose a significant challenge to modern science. Infections by pathogenic microorganisms are of great concern in many fields such as medical devices, drugs, hospital surfaces/furniture, dental restoration, surgery equipment, health care products, and hygienic applications (e.g., water purification systems, textiles, food packaging and storage, major or domestic appliances etc.) Antimicrobial polymers are the materials having the capability to kill/inhibit the growth of microbes on their surface or surrounding environment. Recently, they gained considerable interest for both academic research and industry and were found to be better than their small molecular counterparts in terms of enhanced efficacy, reduced toxicity, minimized environmental problems, resistance, and prolonged lifetime. Hence, efforts have focused on the development of antimicrobial polymers with all desired characters for optimum activity. In this Review, an overview of different antimicrobial polymers, their mechanism of action, factors affecting antimicrobial activity, and application in various fields are given. Recent advances and the current clinical status of these polymers are also discussed.

  16. Adequate mathematical modelling of environmental processes

    NASA Astrophysics Data System (ADS)

    Chashechkin, Yu. D.

    2012-04-01

    In environmental observations and laboratory visualization both large scale flow components like currents, jets, vortices, waves and a fine structure are registered (different examples are given). The conventional mathematical modeling both analytical and numerical is directed mostly on description of energetically important flow components. The role of a fine structures is still remains obscured. A variety of existing models makes it difficult to choose the most adequate and to estimate mutual assessment of their degree of correspondence. The goal of the talk is to give scrutiny analysis of kinematics and dynamics of flows. A difference between the concept of "motion" as transformation of vector space into itself with a distance conservation and the concept of "flow" as displacement and rotation of deformable "fluid particles" is underlined. Basic physical quantities of the flow that are density, momentum, energy (entropy) and admixture concentration are selected as physical parameters defined by the fundamental set which includes differential D'Alembert, Navier-Stokes, Fourier's and/or Fick's equations and closing equation of state. All of them are observable and independent. Calculations of continuous Lie groups shown that only the fundamental set is characterized by the ten-parametric Galilelian groups reflecting based principles of mechanics. Presented analysis demonstrates that conventionally used approximations dramatically change the symmetries of the governing equations sets which leads to their incompatibility or even degeneration. The fundamental set is analyzed taking into account condition of compatibility. A high order of the set indicated on complex structure of complete solutions corresponding to physical structure of real flows. Analytical solutions of a number problems including flows induced by diffusion on topography, generation of the periodic internal waves a compact sources in week-dissipative media as well as numerical solutions of the same

  17. [Use of trovafloxacin therapy in community-acquired pneumonia].

    PubMed

    Luna, C M; Gené, R J

    1999-01-01

    In community-acquired pneumonia (CAP) the pathogenic microorganism is unknown at the time of diagnosis. For that reason the antimicrobial therapy is empirical, based in the clinical picture and the presumptive causal microorganisms. Hospitalization is one of the most important decisions in patients with CAP. Clinical criteria appropriate to identifying those patients requiring hospital admission for antimicrobial administration and clinical control must be defined. The stratification of patients according to the presence of risk factors such as age and co-morbidities permit to predict which are the potential pathogenic microorganisms and their adequate therapy. Trovafloxacin covers all the presumed bacterial spectrum, pharmacokinetics, easiness to be administered and to pass to the oral route, advantageous for all the groups under consideration. Patients older than 65 years of age or with co-morbidities and those that need to be hospitalized receive clear benefits from this antibiotic.

  18. Antimicrobial Resistance of Urinary Tract Isolates in Acute Uncomplicated Cystitis among College-Aged Women: Choosing a First-Line Therapy

    ERIC Educational Resources Information Center

    Hames, Leesa; Rice, Craig E.

    2007-01-01

    Objective and Participants: The authors of this retrospective case study focused on antimicrobial susceptibility of urinary tract isolates in cases of acute uncomplicated cystitis in college-aged women, aged 18 to 24 years, diagnosed at a major south-central university student health center. Methods: The authors obtained pertinent data from…

  19. Nonsurgical periodontal therapy.

    PubMed

    Drisko, C H

    2001-01-01

    Regular home care by the patient in addition to professional removal of subgingival plaque is generally very effective in controlling most inflammatory periodontal diseases. When disease does recur, despite frequent recall, it can usually be attributed to lack of sufficient supragingival and subgingival plaque control or to other risk factors that influence host response, such as diabetes or smoking. Causative factors contributing to recurrent disease include deep inaccessible pockets, overhangs, poor crown margins and plaque-retentive calculus. In most cases, simply performing a thorough periodontal debridement under local anesthesia will stop disease progression and result in improvement in the clinical signs and symptoms of active disease. If however, clinical signs of disease activity persist following thorough mechanical therapy, such as increased pocket depths, loss of attachment and bleeding on probing, other pharmacotherapeutic therapies should be considered. Augmenting scaling and root planing or maintenance visits with adjunctive chemotherapeutic agents for controlling plaque and gingivitis could be as simple as placing the patient on an antimicrobial mouthrinse and/or toothpaste with agents such as fluorides, chlorhexidine or triclosan, to name a few. Since supragingival plaque reappears within hours or days after its removal, it is important that patients have access to effective alternative chemotherapeutic products that could help them achieve adequate supragingival plaque control. Recent studies, for example, have documented the positive effect of triclosan toothpaste on the long-term maintenance of both gingivitis and periodontitis patients. Daily irrigation with a powered irrigation device, with or without an antimicrobial agent, is also useful for decreasing the inflammation associated with gingivitis and periodontitis. Clinically significant changes in probing depths and attachment levels are not usually expected with irrigation alone. Recent

  20. Synthetic biology platform technologies for antimicrobial applications.

    PubMed

    Braff, Dana; Shis, David; Collins, James J

    2016-10-01

    The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels.

  1. Addressing Antimicrobial Resistance: An Overview of Priority Actions to Prevent Suboptimal Antimicrobial Use in Food-Animal Production

    PubMed Central

    Lhermie, Guillaume; Gröhn, Yrjö T.; Raboisson, Didier

    2017-01-01

    The growing concern regarding emergence of bacteria resistant to antimicrobials and their potential for transmission to humans via animal production has led various authorities worldwide to implement measures to decrease antimicrobial use (AMU) in livestock production. These measures are influenced by those implemented in human medicine, and emphasize the importance of antimicrobial stewardship, surveillance, infection prevention and control and research. In food producing animals, unlike human medicine, antimicrobials are used to control diseases which cause economic losses. This major difference may explain the failure of the public policies implemented to control antimicrobial usage. Here we first review the specific factors influencing AMU across the farm animal sector and highlighting the farmers’ decision-making process of AMU. We then discuss the efficiency of existing regulations implemented by policy makers, and assess the need for alternative strategies, such as substitution between antimicrobials and other measures for infectious disease control. We also discuss the interests of regulating antimicrobial prices. Finally, we emphasize the value of optimizing antimicrobial regimens, and developing veterinary precision medicine to achieve clinical efficacy in animals while limiting negative impacts on public health. The fight against antimicrobial resistance requires both a reduction and an optimization of antimicrobial consumption. The set of actions currently implemented by policy makers does not adequately address the economic interests of farmers’ use of antimicrobials. PMID:28111568

  2. Addressing Antimicrobial Resistance: An Overview of Priority Actions to Prevent Suboptimal Antimicrobial Use in Food-Animal Production.

    PubMed

    Lhermie, Guillaume; Gröhn, Yrjö T; Raboisson, Didier

    2016-01-01

    The growing concern regarding emergence of bacteria resistant to antimicrobials and their potential for transmission to humans via animal production has led various authorities worldwide to implement measures to decrease antimicrobial use (AMU) in livestock production. These measures are influenced by those implemented in human medicine, and emphasize the importance of antimicrobial stewardship, surveillance, infection prevention and control and research. In food producing animals, unlike human medicine, antimicrobials are used to control diseases which cause economic losses. This major difference may explain the failure of the public policies implemented to control antimicrobial usage. Here we first review the specific factors influencing AMU across the farm animal sector and highlighting the farmers' decision-making process of AMU. We then discuss the efficiency of existing regulations implemented by policy makers, and assess the need for alternative strategies, such as substitution between antimicrobials and other measures for infectious disease control. We also discuss the interests of regulating antimicrobial prices. Finally, we emphasize the value of optimizing antimicrobial regimens, and developing veterinary precision medicine to achieve clinical efficacy in animals while limiting negative impacts on public health. The fight against antimicrobial resistance requires both a reduction and an optimization of antimicrobial consumption. The set of actions currently implemented by policy makers does not adequately address the economic interests of farmers' use of antimicrobials.

  3. Cationic Antimicrobial Polymers and Their Assemblies

    PubMed Central

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2013-01-01

    Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

  4. Food Antimicrobials Nanocarriers

    PubMed Central

    Blanco-Padilla, Adriana; Soto, Karen M.; Hernández Iturriaga, Montserrat

    2014-01-01

    Natural food antimicrobials are bioactive compounds that inhibit the growth of microorganisms involved in food spoilage or food-borne illness. However, stability issues result in degradation and loss of antimicrobial activity. Nanoencapsulation allows protection of antimicrobial food agents from unfavorable environmental conditions and incompatibilities. Encapsulation of food antimicrobials control delivery increasing the concentration of the antimicrobials in specific areas and the improvement of passive cellular absorption mechanisms resulted in higher antimicrobial activity. This paper reviews the present state of the art of the nanostructures used as food antimicrobial carriers including nanoemulsions, nanoliposomes, nanoparticles, and nanofibers. PMID:24995363

  5. Antimicrobial AApeptides

    PubMed Central

    Sang, Peng; Shi, Yan; Teng, Peng; Cao, Annie; Xu, Hai; Li, Qi; Cai, Jianfeng

    2017-01-01

    Antibiotic resistance is one of the biggest public concerns in the 21st century. Host-defense peptides (HDPs) can potentially mitigate the problem through bacterial membrane disruption; however, they suffer from moderate activity and low stability. We recently developed a new class of peptidomimetics termed “AApeptides”. This class of peptidomimetics can mimic the mechanism of action of HDPs, and effectively arrest the growth of multidrug resistant Gram-positive and Gram-negative bacteria. As they are built on unnatural backbone, they are resistant to proteolytic degradation. In this review, we summarize the development of this class of antimicrobial peptidomimetics, and discuss the future perspective on how they can move forward on combating antibiotic resistance. PMID:27758686

  6. Evaluation of the efficacy of photodynamic antimicrobial therapy using a phenothiazine compound and Laser (λ=660ηm) on the interface: macrophage vs S. aureus

    NASA Astrophysics Data System (ADS)

    de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Pires-Santos, Gustavo M.; Sampaio, Fernando José P.; Zanin, Fátima Antônia A.; Pinheiro, Antônio L. B.

    2015-03-01

    Nowadays photodynamic inactivation has been proposed as an alternative treatment for localized bacterial infections as a response to the problem of antibiotic resistance. Much is already known about the photodynamic inactivation of microorganisms: both antibiotic-sensitive and -resistant strains can be successfully photoinactivated and there is the additional advantage that repeated photosensitization of bacterial cells does not induce a selection of resistant strains. Staphylococcus spp. are opportunistic microorganisms known for their capacity to develop resistance against antimicrobial agents. The emergence of resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) poses a major challenge to healthcare. MRSA is a major cause of hospital-acquired infection throughout the world and is now also prevalent in the community as well as nursing and residential homes. The aim of this study was to evaluate the phagocytic function of macrophages J774 against S. aureus in the presence and absence of AmPDT with phenothiazine compound (12.5 μg/mL) and low level laser (λ=660nm, 12 J/cm²). Experimental groups: Control group (L-P-), Phenothiazine group (L-P+) Laser group (L+P-), AmPDT group (L+P+).The tests presented in this study were performed in triplicate. This study showed that AmPDT induced bacterial death in about 80% as well as increasing phagocytic capacity of macrophages by approximately 20% and enhanced the antimicrobial activity by approximately 50% compared to the control group and enabling more intense oxidative burst.

  7. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Adequate file search. 716.25 Section 716.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of...

  8. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Adequate file search. 716.25 Section 716.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of...

  9. "Something Adequate"? In Memoriam Seamus Heaney, Sister Quinlan, Nirbhaya

    ERIC Educational Resources Information Center

    Parker, Jan

    2014-01-01

    Seamus Heaney talked of poetry's responsibility to represent the "bloody miracle", the "terrible beauty" of atrocity; to create "something adequate". This article asks, what is adequate to the burning and eating of a nun and the murderous gang rape and evisceration of a medical student? It considers Njabulo Ndebele's…

  10. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  11. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  12. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  13. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  14. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 2 2011-07-01 2011-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  15. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  16. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  17. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  18. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  19. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  20. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  1. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  2. Molecular Detection of Antimicrobial Resistance

    PubMed Central

    Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

    2001-01-01

    The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

  3. The role of poverty in antimicrobial resistance.

    PubMed

    Planta, Margaret B

    2007-01-01

    Antimicrobial resistance is a worldwide problem that has deleterious long-term effects as the development of drug resistance outpaces the development of new drugs. Poverty has been cited by the World Health Organization as a major force driving the development of antimicrobial resistance. In developing countries, factors such as inadequate access to effective drugs, unregulated dispensing and manufacture of antimicrobials, and truncated antimicrobial therapy because of cost are contributing to the development of multidrug-resistant organisms. Within the United States, poverty-driven practices such as medication-sharing, use of "leftover" antibiotics, and the purchase and use of foreign-made drugs of questionable quality are likely contributing to antimicrobial resistance. However, there is currently a dearth of studies in the United States analyzing the socioeconomic and behavioral factors behind antimicrobial resistance in United States communities. Further studies of these factors, with an emphasis on poverty-driven practices, need to be undertaken in order to fully understand the problem of antimicrobial resistance in the United States and to develop effective intervention to combat this problem.

  4. Clinical and Antibiofilm Efficacy of Antimicrobial Hydrogels

    PubMed Central

    Finnegan, Simon; Percival, Steven L.

    2015-01-01

    Significance: Hydrogels have been shown to have a significant role to play in wound healing. Hydrogels are used to assist in the management of dry, sloughy, or necrotic wounds. However, recent scientific evidence has shown that biofilms delay wound healing and increase a wound propensity to infection. It is therefore essential that hydrogels incorporating antimicrobials demonstrate efficacy on biofilms. Consequently, it is the aim of this article to review the efficacy of hydrogels, incorporating antimicrobials, on wounds with specific reference to their efficacy on biofilms. Recent Advances: Technologies being developed for the management of wounds are rapidly expanding. In particularly next-generation hydrogels, incorporating copolymers, have been reported to enable the smart release of antimicrobials. This has led to the development of a more tailored patient-specific antimicrobial hydrogel therapy. Critical Issues: Evidence relating to the efficacy of hydrogels, incorporating antimicrobials, on biofilms within both the in vitro and in vivo environments is lacking. Future Direction: Studies that investigate the efficacy of antimicrobial hydrogel wound dressings on both in vivo and in vitro biofilms are important. However, there is a significant need for better and more reproducible in vivo biofilm models. Until this is possible, data generated from appropriate and representative in vitro models will help to assist researchers and clinicians in evaluating antimicrobial and antibiofilm hydrogel technology for the extrapolation of efficacy data relevant to biofilms present in the in vivo environment. PMID:26155382

  5. Clinical and Antibiofilm Efficacy of Antimicrobial Hydrogels.

    PubMed

    Finnegan, Simon; Percival, Steven L

    2015-07-01

    Significance: Hydrogels have been shown to have a significant role to play in wound healing. Hydrogels are used to assist in the management of dry, sloughy, or necrotic wounds. However, recent scientific evidence has shown that biofilms delay wound healing and increase a wound propensity to infection. It is therefore essential that hydrogels incorporating antimicrobials demonstrate efficacy on biofilms. Consequently, it is the aim of this article to review the efficacy of hydrogels, incorporating antimicrobials, on wounds with specific reference to their efficacy on biofilms. Recent Advances: Technologies being developed for the management of wounds are rapidly expanding. In particularly next-generation hydrogels, incorporating copolymers, have been reported to enable the smart release of antimicrobials. This has led to the development of a more tailored patient-specific antimicrobial hydrogel therapy. Critical Issues: Evidence relating to the efficacy of hydrogels, incorporating antimicrobials, on biofilms within both the in vitro and in vivo environments is lacking. Future Direction: Studies that investigate the efficacy of antimicrobial hydrogel wound dressings on both in vivo and in vitro biofilms are important. However, there is a significant need for better and more reproducible in vivo biofilm models. Until this is possible, data generated from appropriate and representative in vitro models will help to assist researchers and clinicians in evaluating antimicrobial and antibiofilm hydrogel technology for the extrapolation of efficacy data relevant to biofilms present in the in vivo environment.

  6. Usefulness of gram-stained sputum obtained just after administration of antimicrobial agents as the earliest therapeutic indicator for evaluating the effectiveness of empiric therapy in community-acquired pneumonia caused by pneumococcus or Moraxella catarrhalis.

    PubMed

    Fujisaki, Ryuichi; Yamaoka, Toshimori; Yamamura, Michiko; Kawakami, Sayoko; Ono, Yasuo; Miyazawa, Yukihisa; Teramoto, Tamio; Nishiya, Hajime

    2013-06-01

    We present here three cases in which morphological changes and/or a decreased number of Streptococcus pneumoniae or Moraxella catarrhalis could be observed in gram-stained sputum obtained just after the first administration of an antimicrobial agent. Case 1 was a 53-year-old man with pneumonia caused by gram-positive diplococcus, identified as S. pneumoniae, who was administered 2 g of ampicillin over a period of 1 h. Gram-stained sputum showed smaller or gram-negative pneumococci at the completion of administration of the agent, a decreased number of cocci at 1 h after administration, and almost no cocci at 12 h after the completion of administration. Case 2 was a 72-year-old woman with pneumonia caused by diplococcus, identified as S. pneumoniae, who was administered 2 g of ampicillin over a period of 1 h. Gram-stained sputum showed weakly stained, small cocci at the completion of administration of the agent and few cocci at 1 h after the completion of administration. Case 3 was a 58-year-old woman with pneumonia caused by a gram-negative diplococcus, identified as Moraxella catarrhalis, who was administered 1 g of cefotaxime over a period of 30 min. Gram-stained sputum showed few extracellular cocci and some intracellular cocci inside neutrophils 1 h after administration and no cocci 2 h after the completion of administration. These three cases showed that gram-stained sputum obtained just after and/or 1 h after administration of the first antimicrobial agent were suitable as the quickest therapeutic indicator of the effectiveness of empiric therapy, with the effectiveness of the agent being shown much earlier than with markers such as the white blood cell count and C-reactive protein level.

  7. Diverse antimicrobial activity from Enterococcus faecium NRRL B-30746 bacteriocin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic therapy to resolve bacterial disease has been compromised by the increased prevalence and magnitude of bacterial antibiotic resistance. In our efforts to identify new effective antimicrobials, bacteria isolated from poultry intestinal contents were screened for bacteriocin synthesis again...

  8. Biofilm disruption with rotating microrods enhances antimicrobial efficacy

    NASA Astrophysics Data System (ADS)

    Mair, Lamar O.; Nacev, Aleksandar; Hilaman, Ryan; Stepanov, Pavel Y.; Chowdhury, Sagar; Jafari, Sahar; Hausfeld, Jeffrey; Karlsson, Amy J.; Shirtliff, Mark E.; Shapiro, Benjamin; Weinberg, Irving N.

    2017-04-01

    Biofilms are a common and persistent cause of numerous illnesses. Compared to planktonic microbes, biofilm residing cells often demonstrate significant resistance to antimicrobial agents. Thus, methods for dislodging cells from the biofilm may increase the antimicrobial susceptibility of such cells, and serve as a mechanical means of increasing antimicrobial efficacy. Using Aspergillus fumigatus as a model microbe, we magnetically rotate microrods in and around biofilm. We show that such rods can improve the efficacy of antimicrobial Amphotericin B treatments in vitro. This work represents a first step in using kinetic magnetic particle therapy for disrupting fungal biofilms.

  9. [Update of antimicrobial resistance in Gram-positive microorganisms].

    PubMed

    Cercenado, Emilia

    2010-12-01

    In the last few decades, resistance among Gram-positive microorganisms to classical antimicrobials as well as the emergence of resistance to new antimicrobials has been observed in our environment. Methicillin resistance among Staphylococcus aureus and coagulase-negative staphylococci seems to have stabilized at around 30% and 70%, respectively, however, multiresistance of these species to other antimicrobials, emergence of linezolid resistance, and decreased susceptibility to glycopeptides is a cause of concern. Daptomycin has good antimicrobial activity, although some strains with slightly increased MICs have been detected. Among enterococci, vancomycin resistance is less than 5%, but multiresistance among these microorganisms, emerging linezolid resistance and reports of some isolates with decreased susceptibility to daptomycin are worrying. Adequate use of antimicrobials could help to prevent the increase in resistance and dissemination of these pathogens and will allow their efficacy to be guaranteed in the future.

  10. Antimicrobial Treatments and Efficacy

    EPA Science Inventory

    To limit exposure to indoor biological contamination a risk-management approach which employs various antimicrobial treatments can effectively control contaminants and reduce exposure. Antimicrobial treatment of biological contaminants, especially mold in buildings, it is often n...

  11. Region 9: Arizona Adequate Letter (10/14/2003)

    EPA Pesticide Factsheets

    This is a letter from Jack P. Broadben,. Director, to Nancy Wrona and Dennis Smith informing them that Maricopa County's motor vehicle emissions budgets in the 2003 MAGCO Maintenance Plan are adequate for transportation conformity purposes.

  12. Region 6: Texas Adequate Letter (4/16/2010)

    EPA Pesticide Factsheets

    This letter from EPA to Texas Commission on Environmental Quality determined 2021 motor vehicle emission budgets for nitrogen oxides (NOx) and volatile organic compounds (VOCs) for Beaumont/Port Arthur area adequate for transportation conformity purposes

  13. Region 2: New Jersey Adequate Letter (5/23/2002)

    EPA Pesticide Factsheets

    This April 22, 2002 letter from EPA to the New Jersey Department of Environmental Protection determined 2007 and 2014 Carbon Monoxide (CO) Mobile Source Emissions Budgets adequate for transportation conformity purposes and will be announced in the Federal

  14. Region 8: Colorado Adequate Letter (10/29/2001)

    EPA Pesticide Factsheets

    This letter from EPA to Colorado Department of Public Health and Environment determined Denvers' particulate matter (PM10) maintenance plan for Motor Vehicle Emissions Budgets adequate for transportation conformity purposes.

  15. Region 1: New Hampshire Adequate Letter (8/12/2008)

    EPA Pesticide Factsheets

    This July 9, 2008 letter from EPA to the New Hampshire Department of Environmental Services, determined the 2009 Motor Vehicle Emissions Budgets (MVEBs) are adequate for transportation conformity purposes and will be announced in the Federal Register (FR).

  16. Region 8: Colorado Adequate Letter (1/20/2004)

    EPA Pesticide Factsheets

    This letter from EPA to Colorado Department of Public Health and Environment determined Greeleys' Carbon Monoxide (CO) maintenance plan for Motor Vehicle Emissions Budgets adequate for transportation conformity purposes and will be announced in the FR.

  17. Region 8: Utah Adequate Letter (6/10/2005)

    EPA Pesticide Factsheets

    This letter from EPA to Utah Department of Environmental Quality determined Salt Lake Citys' and Ogdens' Carbon Monoxide (CO) maintenance plan for Motor Vehicle Emissions Budgets adequate for transportation conformity purposes.

  18. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  19. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  20. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  1. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  2. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must...

  3. Region 6: New Mexico Adequate Letter (8/21/2003)

    EPA Pesticide Factsheets

    This is a letter from Carl Edlund, Director, to Alfredo Santistevan regarding MVEB's contained in the latest revision to the Albuquerque Carbon Monoxide State Implementation Plan (SIP) are adequate for transportation conformity purposes.

  4. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  5. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... require access to and use of records contained in a system of records are adequately trained to protect... with the appropriate security software, in accordance with regulations of the Archivist of the...

  6. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  7. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... require access to and use of records contained in a system of records are adequately trained to protect... with the appropriate security software, in accordance with regulations of the Archivist of the...

  8. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  9. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... contained in a system of records are adequately trained to protect the security and privacy of such records..., by degaussing or by overwriting with the appropriate security software, in accordance...

  10. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... require access to and use of records contained in a system of records are adequately trained to protect... with the appropriate security software, in accordance with regulations of the Archivist of the...

  11. Region 9: Nevada Adequate Letter (3/30/2006)

    EPA Pesticide Factsheets

    This is a letter from Deborah Jordan, Director, to Leo M. Drozdoff regarding Nevada's motor vehicle emissions budgets in the 2005 Truckee Meadows CO Redesignation Request and Maintenance Plan are adequate for transportation conformity decisions.

  12. De Novo Design of Potent Antimicrobial Peptides

    PubMed Central

    Frecer, V.; Ho, B.; Ding, J. L.

    2004-01-01

    Lipopolysaccharide (LPS), shed by gram-negative bacteria during infection and antimicrobial therapy, may lead to lethal endotoxic shock syndrome. A rational design strategy based on the presumed mechanism of antibacterial effect was adopted to design cationic antimicrobial peptides capable of binding to LPS through tandemly repeated sequences of alternating cationic and nonpolar residues. The peptides were designed to achieve enhanced antimicrobial potency due to initial bacterial membrane binding with a reduced risk of endotoxic shock. The peptides designed displayed binding affinities to LPS and lipid A (LA) in the low micromolar range and by molecular modeling were predicted to form amphipathic β-hairpin-like structures when they bind to LPS or LA. They also exhibited strong effects against gram-negative bacteria, with MICs in the nanomolar range, and low cytotoxic and hemolytic activities at concentrations significantly exceeding their MICs. Quantitative structure-activity relationship (QSAR) analysis of peptide sequences and their antimicrobial, cytotoxic, and hemolytic activities revealed that site-directed substitutions of residues in the hydrophobic face of the amphipathic peptides with less lipophilic residues selectively decrease the hemolytic effect without significantly affecting the antimicrobial or cytotoxic activity. On the other hand, the antimicrobial effect can be enhanced by substitutions in the polar face with more polar residues, which increase the amphipathicity of the peptide. On the basis of the QSARs, new analogs that have strong antimicrobial effects but that lack hemolytic activity can be proposed. The findings highlight the importance of peptide amphipathicity and allow a rational method that can be used to dissociate the antimicrobial and hemolytic effects of cationic peptides, which have potent antimicrobial properties, to be proposed. PMID:15328096

  13. In Vitro Approach for Identification of the Most Effective Agents for Antimicrobial Lock Therapy in the Treatment of Intravascular Catheter-Related Infections Caused by Staphylococcus aureus

    PubMed Central

    Hogan, S.; Zapotoczna, M.; Stevens, N. T.; Humphreys, H.; O'Gara, J. P.

    2016-01-01

    Infection of intravascular catheters by Staphylococcus aureus is a significant risk factor within the health care setting. To treat these infections and attempt salvage of an intravascular catheter, antimicrobial lock solutions (ALSs) are being increasingly used. However, the most effective ALSs against these biofilm-mediated infections have yet to be determined, and clinical practice varies greatly. The purpose of this study was to evaluate and compare the efficacies of antibiotics and antiseptics in current clinical use against biofilms produced by reference and clinical isolates of S. aureus. Static and flow biofilm assays were developed using newly described in vivo-relevant conditions to examine the effect of each agent on S. aureus within the biofilm matrix. The antibiotics daptomycin, tigecycline, and rifampin and the antiseptics ethanol and Taurolock inactivated established S. aureus biofilms, while other commonly used antistaphylococcal antibiotics and antiseptic agents were less effective. These findings were confirmed by live/dead staining of S. aureus biofilms formed and treated within a flow cell model. The results from this study demonstrate the most effective clinically used agents and their concentrations which should be used within an ALS to treat S. aureus-mediated intravascular catheter-related infections. PMID:26926633

  14. Klebsiella pneumoniae: Development of Carbapenem Resistance due to Acquisition of blaNDM-1 During Antimicrobial Therapy in Twin Infants with Pneumonia

    PubMed Central

    Zhu, Junying; Ding, Baixing; Xu, Xiaogang; Zhu, Demei; Yang, Fan; Zhang, Hong; Hu, Fupin

    2015-01-01

    Objectives: To identify the mechanism of in vivo development of carbapenem resistance in Klebsiella pneumoniae.Methods: Seven sequential isolates of K. pneumoniae were obtained from twin infants with pneumonia. Antimicrobial susceptibility testing was performed by agar dilution method. Carbapenemases including KPC and MβL were initially screened using phenotypic methods, and carbapenemase-encoding genes were identified by polymerase chain reaction and amplicon sequencing. Plasmids of all clinical isolates and the conjugants of resistant isolates were estimated by S1 pulsed-field gel electrophoresis (PFGE). Molecular typing were conducted by PFGE of XbaI-digested genomic DNA and multilocus sequence typing.Results: For old brother, the first and third isolates were susceptible to meropenem, whereas the second and fourth isolates were resistant (MICs 16 mg/L). The first and second isolates from the young brother were susceptible to meropenem whereas the third isolate was resistant. All the resistant isolates produced NDM-1 metallo-β-lactamase. PFGE of XbaI-digested DNA revealed almost identical patterns with similarity indices of above 92% for all the seven isolates. All the isolates had the same sequence type named sequence type 37 (ST37).Conclusion: To our knowledge, this is the first documented case of development of carbapenem resistance in vivo mediated by NDM-1 metallo-β-lactamase in K. pneumoniae during treatment of pneumonia with meropenem. PMID:26733952

  15. In Vivo Monitoring of Staphylococcus aureus Biofilm Infections and Antimicrobial Therapy by [18F]Fluoro-Deoxyglucose–MicroPET in a Mouse Model

    PubMed Central

    Garrido, Victoria; Collantes, María; Barberán, Montserrat; Peñuelas, Iván; Arbizu, Javier; Amorena, Beatriz

    2014-01-01

    A mouse model was developed for in vivo monitoring of infection and the effect of antimicrobial treatment against Staphylococcus aureus biofilms, using the [18F]fluoro-deoxyglucose–MicroPET ([18F]FDG-MicroPET) image technique. In the model, sealed Vialon catheters were briefly precolonized with S. aureus strains ATCC 15981 or V329, which differ in cytotoxic properties and biofilm matrix composition. After subcutaneous implantation of catheters in mice, the S. aureus strain differences found in bacterial counts and the inflammatory reaction triggered were detected by the regular bacteriological and histological procedures and also by [18F]FDG-MicroPET image signal intensity determinations in the infection area and regional lymph node. Moreover, [18F]FDG-MicroPET imaging allowed the monitoring of the rifampin treatment effect, identifying the periods of controlled infection and those of reactivated infection due to the appearance of bacteria naturally resistant to rifampin. Overall, the mouse model developed may be useful for noninvasive in vivo determinations in studies on S. aureus biofilm infections and assessment of new therapeutic approaches. PMID:25155589

  16. Marriage or Family Therapy.

    ERIC Educational Resources Information Center

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  17. MRI can determine the adequate area for debridement in the case of Fournier's gangrene.

    PubMed

    Yoneda, Akira; Fujita, Fumihiko; Tokai, Hirotaka; Ito, Yuichiro; Haraguchi, Masashi; Tajima, Yoshitsugu; Kanematsu, Takashi

    2010-01-01

    A 57-year-old man was transferred to our hospital because of gluteal pain. His right buttock had flare and swelling. Complete blood count showed leukocytosis, and renal failure was evident. Pelvic computed tomography (CT) revealed that the abscess, including gas, was widespread into the hypodermal tissue of the right buttock. Fournier's gangrene had been suspected, and immediate drainage was performed on the right buttock. The symptom and the condition improved rapidly, but on the day after the operation, the patient became drowsy and fell into endotoxic shock. Magnetic resonance imaging (MRI) revealed strong inflammation along the entire fascia of the right femur and necrotizing fasciitis. MRI was very useful for identification of the necrotic range. Immediately, an emergency operation was performed; 3 wide incisions were made on the right thigh and crus for drainage. The patient was cared for intensively under a sedated condition, and irrigation and debridement were repeated every day. Culture of the pus revealed mixed infection of Escherichia coli and anaerobic bacteria, and a large quantity of antimicrobial drug was used. The inflammatory reaction decreased, and the patient's general condition tentatively improved. With Fournier's gangrene, initiating adequate surgical and medical treatment is essential. Therefore, MRI should be used in the early exact diagnosis of this disease to obtain knowledge of the extent of necrosis and to determine the adequate area for debridement.

  18. Anti-antimicrobial Peptides

    PubMed Central

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  19. [Antimicrobial prophylaxis in surgery].

    PubMed

    Cisneros, José Miguel; Rodríguez-Baño, Jesús; Mensa, José; Trilla, Antoni; Cainzos, Miguel

    2002-01-01

    Antimicrobial prophylaxis in surgery refers to a very brief course of an antimicrobial agent initiated just before the start of the procedure. The efficacy of antimicrobials to prevent postoperative infection at the site of surgery (incisional superficial, incisional deep, or organ/space infection) has been demonstrated for many surgical procedures. Nevertheless, the majority of studies centering on the quality of preoperative prophylaxis have found that a high percentage of the antimicrobials used are inappropriate for this purpose. This work discusses the scientific basis for antimicrobial prophylaxis, provides general recommendations for its correct use and specific recommendations for various types of surgery. The guidelines for surgical antimicrobial prophylaxis are based on results from well-designed studies, whenever possible. These guidelines are focussed on reducing the incidence of infection at the surgical site while minimizing the contribution of preoperative administration of antimicrobials to the development of bacterial resistance.

  20. The antimicrobial possibilities of green tea

    PubMed Central

    Reygaert, Wanda C.

    2014-01-01

    Green tea is a popular drink, especially in Asian countries, although its popularity continues to spread across the globe. The health benefits of green tea, derived from the leaves of the Camellia sinensis plant, have been studied for many years. Fairly recently, researchers have begun to look at the possibility of using green tea in antimicrobial therapy, and the potential prevention of infections. The particular properties of catechins found in the tea have shown promise for having antimicrobial effects. There are four main catechins (polyphenols) found in green tea: (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG). Three of these, ECG, EGC, and EGCG have been shown to have antimicrobial effects against a variety of organisms. These catechins have exhibited a variety of antimicrobial mechanisms. The results of studies on the antimicrobial effects of green tea have shown that the potential for preventive and therapeutic purposes is present. Further data collection on studies performed with human consumption during the course of infections, and studies on the occurrence of infections in populations that consume regular amounts of green tea will be necessary to complete the picture of its antimicrobial possibilities. PMID:25191312

  1. Antimicrobial stewardship: application in the intensive care unit.

    PubMed

    Owens, Robert C

    2009-09-01

    Critical-care units can be barometers for appropriate antimicrobial use. There, life and death hang on empirical antimicrobial therapy for treatment of infectious diseases. With increasing therapeutic empiricism, triple-drug, broad-spectrum regimens are often necessary, but cannot be continued without fear of the double-edged sword: a life-saving intervention or loss of life following Clostridium difficile infection, infection from a resistant organism, nephrotoxicity, cardiac toxicity, and so on. While broadened initial empirical therapy is considered a standard, it must be necessary, dosed according to pharmacokinetic-pharmacodynamic principles, and stopped when no longer needed. Antimicrobial stewardship interventions shepherd these considerations in antimicrobial therapy. With pharmacists and physicians trained in infectious disease and critical care, clear-cut interventions can be focused on beginning or growing a stewardship program, or proposing future studies.

  2. Regulatory requirements for providing adequate veterinary care to research animals.

    PubMed

    Pinson, David M

    2013-09-01

    Provision of adequate veterinary care is a required component of animal care and use programs in the United States. Program participants other than veterinarians, including non-medically trained research personnel and technicians, also provide veterinary care to animals, and administrators are responsible for assuring compliance with federal mandates regarding adequate veterinary care. All program participants therefore should understand the regulatory requirements for providing such care. The author provides a training primer on the US regulatory requirements for the provision of veterinary care to research animals. Understanding the legal basis and conditions of a program of veterinary care will help program participants to meet the requirements advanced in the laws and policies.

  3. High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila

    PubMed Central

    Chiaraviglio, Lucius

    2015-01-01

    Legionella pneumophila is a Gram-negative opportunistic human pathogen that causes a severe pneumonia known as Legionnaires' disease. Notably, in the human host, the organism is believed to replicate solely within an intracellular compartment, predominantly within pulmonary macrophages. Consequently, successful therapy is predicated on antimicrobials penetrating into this intracellular growth niche. However, standard antimicrobial susceptibility testing methods test solely for extracellular growth inhibition. Here, we make use of a high-throughput assay to characterize intracellular growth inhibition activity of known antimicrobials. For select antimicrobials, high-resolution dose-response analysis was then performed to characterize and compare activity levels in both macrophage infection and axenic growth assays. Results support the superiority of several classes of nonpolar antimicrobials in abrogating intracellular growth. Importantly, our assay results show excellent correlations with prior clinical observations of antimicrobial efficacy. Furthermore, we also show the applicability of high-throughput automation to two- and three-dimensional synergy testing. High-resolution isocontour isobolograms provide in vitro support for specific combination antimicrobial therapy. Taken together, findings suggest that high-throughput screening technology may be successfully applied to identify and characterize antimicrobials that target bacterial pathogens that make use of an intracellular growth niche. PMID:26392509

  4. Comparability and Reliability Considerations of Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Maier, Kimberly S.; Maiti, Tapabrata; Dass, Sarat C.; Lim, Chae Young

    2012-01-01

    The purpose of this study is to develop an estimate of Adequate Yearly Progress (AYP) that will allow for reliable and valid comparisons among student subgroups, schools, and districts. A shrinkage-type estimator of AYP using the Bayesian framework is described. Using simulated data, the performance of the Bayes estimator will be compared to…

  5. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... operate actively in accordance with your Articles and within the context of your business plan, as... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL...

  6. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... operate actively in accordance with your Articles and within the context of your business plan, as... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL...

  7. Is the Stock of VET Skills Adequate? Assessment Methodologies.

    ERIC Educational Resources Information Center

    Blandy, Richard; Freeland, Brett

    In Australia and elsewhere, four approaches have been used to determine whether stocks of vocational education and training (VET) skills are adequate to meet industry needs. The four methods are as follows: (1) the manpower requirements approach; (2) the international, national, and industry comparisons approach; (3) the labor market analysis…

  8. Do Beginning Teachers Receive Adequate Support from Their Headteachers?

    ERIC Educational Resources Information Center

    Menon, Maria Eliophotou

    2012-01-01

    The article examines the problems faced by beginning teachers in Cyprus and the extent to which headteachers are considered to provide adequate guidance and support to them. Data were collected through interviews with 25 school teachers in Cyprus, who had recently entered teaching (within 1-5 years) in public primary schools. According to the…

  9. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  10. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  11. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  12. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  13. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Companies. 108.200 Section 108.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order...

  14. Understanding Your Adequate Yearly Progress (AYP), 2011-2012

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2011

    2011-01-01

    The "No Child Left Behind Act (NCLB) of 2001" requires all schools, districts/local education agencies (LEAs) and states to show that students are making Adequate Yearly Progress (AYP). NCLB requires states to establish targets in the following ways: (1) Annual Proficiency Target; (2) Attendance/Graduation Rates; and (3) Participation…

  15. 34 CFR 200.13 - Adequate yearly progress in general.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Adequate yearly progress in general. 200.13 Section 200.13 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE...

  16. 34 CFR 200.13 - Adequate yearly progress in general.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Adequate yearly progress in general. 200.13 Section 200.13 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE...

  17. Region 9: Arizona Adequate Letter (11/1/2001)

    EPA Pesticide Factsheets

    This is a letter from Jack P. Broadbent, Director, Air Division to Nancy Wrona and James Bourney informing them of the adequacy of Revised MAG 1999 Serious Area Carbon Monoxide Plan and that the MAG CO Plan is adequate for Maricopa County.

  18. Antimicrobials in beekeeping.

    PubMed

    Reybroeck, Wim; Daeseleire, Els; De Brabander, Hubert F; Herman, Lieve

    2012-07-06

    The bee diseases American and European foulbrood and nosemosis can be treated with anti-infectious agents. However, in the EU and the USA the use of these agents in beekeeping is strictly regulated due to the lack of tolerance (e.g. Maximum Residue Limit) for residues of antibiotics and chemotherapeutics in honey. This article reviews the literature dealing with antimicrobials of interest in apiculture, stability of these antimicrobials in honey, and disposition of the antimicrobials in honeybee hives.

  19. Appropriate Antibiotic Therapy.

    PubMed

    Allison, Michael G; Heil, Emily L; Hayes, Bryan D

    2017-02-01

    Prescribing antibiotics is an essential component of initial therapy in sepsis. Early antibiotics are an important component of therapy, but speed of administration should not overshadow the patient-specific characteristics that determine the optimal breadth of antimicrobial therapy. Cultures should be drawn before antibiotic therapy if it does not significantly delay administration. Combination antibiotic therapy against gram-negative infections is not routinely required, and combination therapy involving vancomycin and piperacillin/tazobactam is associated with an increase in acute kidney injury. Emergency practitioners should be aware of special considerations in the administration and dosing of antibiotics in order to deliver optimal care to septic patients.

  20. How to educate prescribers in antimicrobial stewardship practices

    PubMed Central

    Pulcini, Céline; Gyssens, Inge C.

    2013-01-01

    Widespread antimicrobial use has compromised its value, leading to a crisis of antimicrobial resistance. A major cause of misuse is insufficient knowledge of prescribing of antimicrobials in many categories of professionals. An important principle of antimicrobial stewardship is avoiding selection pressure in the patient, both on pathogen and commensal by avoiding unnecessary use, choosing the least broad-spectrum antibiotic, adequate doses, a good timing and the shortest possible duration. Up to now, most educational efforts have been targeted at professionals (mostly medical doctors) after their training and at the adult public. In the past few years, progress has been made in educating children. It is now crucial that academia and ministries of Health and Education jointly focus on an adapted undergraduate medical/professional curriculum that teaches all necessary principles of microbiology, infectious diseases and clinical pharmacology, with emphasis on the principles of prudent prescribing. PMID:23361336

  1. Impact of formulary restriction with prior authorization by an antimicrobial stewardship program

    PubMed Central

    Reed, Erica E.; Stevenson, Kurt B.; West, Jessica E.; Bauer, Karri A.; Goff, Debra A.

    2013-01-01

    In an era of increasing antimicrobial resistance and few antimicrobials in the developmental pipeline, many institutions have developed antimicrobial stewardship programs (ASPs) to help implement evidence-based (EB) strategies for ensuring appropriate utilization of these agents. EB strategies for accomplishing this include formulary restriction with prior authorization. Potential limitations to this particular strategy include delays in therapy, prescriber pushback, and unintended increases in use of un-restricted antimicrobials; however, our ASP found that implementing prior authorization for select antimicrobials along with making a significant effort to educate clinicians on criteria for use ensured more appropriate prescribing of these agents, hopefully helping to preserve their utility for years to come. PMID:23154323

  2. Efficacy of the photodynamic antimicrobial therapy (PACT) with the use of methylene blue associated with the λ660nm laser in Leishmania (Leishmania) amazonesis: in vitro study

    NASA Astrophysics Data System (ADS)

    Pires-Santos, Gustavo M.; Marques, Aparecida M. C.; Alves, Eliomara S. S.; Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Rosa, Cristiane B.; Colombo, Fabio; Pinheiro, Antônio L. B.; Vannier-Santos, Marcos A.

    2012-03-01

    The present studied evaluated the in vitro effects of PDT on Leishmania (Leishmania) amazonensis promastigotes. For this examination L. amazonensis promastigotes, stain Josefa, were used and maintained in Warren media supplement with fetal bovine serum at 26°C for 96 hours. A viability curve was accomplished using different concentrations of methylene blue photosensitizer associated to red laser light in order to obtain the most effective interaction to inhibit the parasite's growth. Two pre-irradiation periods, 5 and 30 minutes, were evaluated and the promastigotes were counted by colorimetry. On fluorescence microscopy the autophagic processes and reactive oxygen species were detected. Promastigotes treated with Photodynamic Therapy (PDT) by concentrations of 5 and 0,315ug/mL, presented cellular proliferation inhibition when compared to the control. In the first condition, the cells had structural alterations such as truncated cells, cells with two flagella, bleb formation and cells body deformation, while none of these modifications could be visualized in the control group. When analyzed through fluorescence microscopy, the promastigotes treated were positives for free radicals immediately after light application and also 1 hour after treatment presenting signs of autophagia. PDT on L. (L.) amazonensis is effective causing alterations that can help elucidate the mechanisms of the parasite's death when treated with methilene

  3. Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model

    PubMed Central

    Drago, Lorenzo; Bottagisio, Marta; Bongio, Matilde; Ferrario, Marzia; Perego, Silvia; Sansoni, Veronica; De Vecchi, Elena; Romanò, Carlo L.

    2016-01-01

    S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics. PMID:27478310

  4. Army General Fund Adjustments Not Adequately Documented or Supported

    DTIC Science & Technology

    2016-07-26

    statements were unreliable and lacked an adequate audit trail. Furthermore, DoD and Army managers could not rely on the data in their accounting...risk that AGF financial statements will be materially misstated and the Army will not achieve audit readiness by the congressionally mandated...and $6.5 trillion in yearend adjustments made to Army General Fund data during FY 2015 financial statement compilation. We conducted this audit in

  5. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  6. Alternative Antimicrobial Approach: Nano-Antimicrobial Materials

    PubMed Central

    Beyth, Nurit; Houri-Haddad, Yael; Domb, Avi; Khan, Wahid; Hazan, Ronen

    2015-01-01

    Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail. PMID:25861355

  7. Topical Antimicrobials for Burn Wound Infections

    PubMed Central

    Dai, Tianhong; Huang, Ying-Ying; Sharma, Sulbha K.; Hashmi, Javad T.; Kurup, Divya B.; Hamblin, Michael R.

    2010-01-01

    Throughout most of history, serious burns occupying a large percentage of body surface area were an almost certain death sentence because of subsequent infection. A number of factors such as disruption of the skin barrier, ready availability of bacterial nutrients in the burn milieu, destruction of the vascular supply to the burned skin, and systemic disturbances lead to immunosuppression combined together to make burns particularly susceptible to infection. In the 20th century the introduction of antibiotic and antifungal drugs, the use of topical antimicrobials that could be applied to burns, and widespread adoption of early excision and grafting all helped to dramatically increase survival. However the relentless increase in microbial resistance to antibiotics and other antimicrobials has led to a renewed search for alternative approaches to prevent and combat burn infections. This review will cover patented strategies that have been issued or filed with regard to new topical agents, preparations, and methods of combating burn infections. Animal models that are used in preclinical studies are discussed. Various silver preparations (nanocrystalline and slow release) are the mainstay of many approaches but antimicrobial peptides, topical photodynamic therapy, chitosan preparations, new iodine delivery formulations, phage therapy and natural products such as honey and essential oils have all been tested. This active area of research will continue to provide new topical antimicrobials for burns that will battle against growing multi-drug resistance. PMID:20429870

  8. Antimicrobial prophylaxis in adults.

    PubMed

    Enzler, Mark J; Berbari, Elie; Osmon, Douglas R

    2011-07-01

    Antimicrobial prophylaxis is commonly used by clinicians for the prevention of numerous infectious diseases, including herpes simplex infection, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, infective endocarditis, pertussis, and acute necrotizing pancreatitis, as well as infections associated with open fractures, recent prosthetic joint placement, and bite wounds. Perioperative antimicrobial prophylaxis is recommended for various surgical procedures to prevent surgical site infections. Optimal antimicrobial agents for prophylaxis should be bactericidal, nontoxic, inexpensive, and active against the typical pathogens that can cause surgical site infection postoperatively. To maximize its effectiveness, intravenous perioperative prophylaxis should be administered within 30 to 60 minutes before the surgical incision. Antimicrobial prophylaxis should be of short duration to decrease toxicity and antimicrobial resistance and to reduce cost.

  9. The Use of Antimicrobial Drugs in Office Practice

    PubMed Central

    Achong, Michael R.

    1982-01-01

    Antimicrobial drugs are used extensively, but not well. Widespread and indiscriminate use of these drugs encourages the development of antibiotic resistance. Before prescribing an antimicrobial drug, physicians should ask themselves whether prophylactic or empirical therapy is justified, what is (are) the most likely micro-organism(s) involved, what is the best antimicrobial drug for this patient, and what is the optimal dosage and duration of treatment. The penicillins, erythromycin, tetracycline, cephalosporins, sulfonamides, cotrimoxazole and trimethoprim are discussed in the light of these questions. PMID:20469389

  10. Genetic modification of preimplantation embryos: toward adequate human research policies.

    PubMed

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo modification proposals might not receive adequate scientific and ethical scrutiny. This article describes current policy shortcomings and recommends policy actions designed to ensure that the investigational genetic modification of embryos meets accepted standards for research on human subjects.

  11. Elements for adequate informed consent in the surgical context.

    PubMed

    Abaunza, Hernando; Romero, Klaus

    2014-07-01

    Given a history of atrocities and violations of ethical principles, several documents and regulations have been issued by a wide variety of organizations. They aim at ensuring that health care and clinical research adhere to defined ethical principles. A fundamental component was devised to ensure that the individual has been provided the necessary information to make an informed decision regarding health care or participation in clinical research. This article summarizes the history and regulations for informed consent and discusses suggested components for adequate consent forms for daily clinical practice in surgery as well as clinical research.

  12. Antimicrobial drugs for treating cholera

    PubMed Central

    Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

    2014-01-01

    Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. Objectives To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Selection criteria Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Data collection and analysis Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Main results Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43

  13. Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis

    PubMed Central

    Arabi, Yaseen M; Dara, Saqib I; Memish, Ziad; Al Abdulkareem, Abdulmajeed; Tamim, Hani M; Al-Shirawi, Nehad; Parrillo, Joseph E; Dodek, Peter; Lapinsky, Stephen; Feinstein, Daniel; Wood, Gordon; Dial, Sandra; Zanotti, Sergio; Kumar, Anand

    2012-01-01

    It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315) PMID:22753144

  14. Clinical outcomes of antimicrobial lock solutions used in a treatment modality: a retrospective case series analysis

    PubMed Central

    Bookstaver, P Brandon; Gerrald, Katherine R; Moran, Robert R

    2010-01-01

    Background Antimicrobial lock therapy (ALT) may be considered as adjunctive therapy in the treatment of catheter-related bloodstream infections (CRBSI) when catheter removal is not a favorable option. Objective To evaluate the outcomes associated with ALT as adjunctive treatment of CRBSI. Methods This was a 24-month retrospective case series analysis evaluating patients treated for more than 24 hours with ALT. The primary outcome was blood culture sterilization for 30 days posttherapy. The impact of ALT duration and time to initiation on central venous catheter (CVC) salvage were evaluated. Logistic regression modeled the association between ALT and sterilization rates, with a prespecified level of significance (α) of 0.1. Results Twenty-six cases were included in data analysis. Patients included ranged from 5 months to 82 years of age; 77% of patients were receiving total parenteral nutrition or chemotherapy. The majority of patients received vancomycin, daptomycin, or gentamicin combined with heparin in a lock solution. Blood culture sterilization was achieved in 69.2% of cases, and sterilization plus CVC retention was achieved in 11 cases (42.3%). Longer durations of ALT (≥9 days) were significantly correlated with blood culture sterilization (odds ratio = 1.367, P = 0.077). Conclusion ALT used as an adjunct to systemic therapy for adequate duration in CRBSI can achieve CVC sterilization and retainment without subsequent infectious complications. PMID:22291495

  15. Quantifying dose to the reconstructed breast: Can we adequately treat?

    SciTech Connect

    Chung, Eugene; Marsh, Robin B.; Griffith, Kent A.; Moran, Jean M.; Pierce, Lori J.

    2013-04-01

    To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V{sub 20}. Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.

  16. Is Antimicrobial Resistance a Slowly Emerging Disaster?

    PubMed Central

    Viens, A. M.

    2015-01-01

    The problem of antimicrobial resistance is so dire that people are predicting that the era of antibiotics may be coming to an end, ushering in a ‘post-antibiotic’ era. A comprehensive policy response is therefore urgently needed. A part of this response will require framing the problem in such a way that adequately reflects its nature as well as encompassing an approach that has the best prospect of success. This paper considers framing the problem as a slowly emerging disaster, including its potential benefits and difficulties, from a conceptual and policy perspective. PMID:26566396

  17. Recommendations for the Empirical Treatment of Complicated Urinary Tract Infections Using Surveillance Data on Antimicrobial Resistance in the Netherlands

    PubMed Central

    Koningstein, Maike; van der Bij, Akke K.; de Kraker, Marlieke E. A.; Monen, Jos C.; Muilwijk, Jan; de Greeff, Sabine C.; Geerlings, Suzanne E.; van Hall, Maurine A. Leverstein-

    2014-01-01

    Background Complicated urinary tract infections (c-UTIs) are among the most common nosocomial infections and a substantial part of the antimicrobial agents used in hospitals is for the treatment of c-UTIs. Data from surveillance can be used to guide the empirical treatment choices of clinicians when treating c-UTIs. We therefore used nation-wide surveillance data to evaluate antimicrobial coverage of agents for the treatment of c-UTI in the Netherlands. Methods We included the first isolate per patient of urine samples of hospitalised patients collected by the Infectious Disease Surveillance Information System for Antibiotic Resistance (ISIS-AR) in 2012, and determined the probability of inadequate coverage for antimicrobial agents based on species distribution and susceptibility. Analyses were repeated for various patient groups and hospital settings. Results The most prevalent bacteria in 27,922 isolates of 23,357 patients were Escherichia coli (47%), Enterococcus spp. (14%), Proteus mirabilis (8%), and Klebsiella pneumoniae (7%). For all species combined, the probability of inadequate coverage was <5% for amoxicillin or amoxicillin-clavulanic acid combined with gentamicin and the carbapenems. When including gram-negative bacteria only, the probability of inadequate coverage was 4.0%, 2.7%, 2.3% and 1.7%, respectively, for amoxicillin, amoxicillin-clavulanic acid, a second or a third generation cephalosporin in combination with gentamicin, and the carbapenems (0.4%). There were only small variations in results among different patient groups and hospital settings. Conclusions When excluding Enterococcus spp., considered as less virulent, and the carbapenems, considered as last-resort drugs, empirical treatment for c-UTI with the best chance of adequate coverage are one of the studied beta-lactam-gentamicin combinations. This study demonstrates the applicability of routine surveillance data for up-to-date clinical practice guidelines on empirical antimicrobial

  18. ['In vitro' activity of different antimicrobial agents on Gram-negative nonfermentative bacilli, excluding Pseudomonas aeruginosa and Acinetobacter spp].

    PubMed

    Vay, C A; Almuzara, M N; Rodríguez, C H; Pugliese, M L; Lorenzo Barba, F; Mattera, J C; Famiglietti, A M R

    2005-01-01

    Gram-negative nonfermentative bacilli (NFB) are widely spread in the environment. Besides of difficulties for identification, they often have a marked multiresistance to antimicrobial agents, including those active against Pseudomonas aeruginosa. The objective of this study was to evaluate the 'in vitro' activity of different antimicrobial agents on 177 gram-negative nonfermentative bacilli isolates (excluding Pseudomonas aeruginosa and Acinetobacter spp.) isolated from clinical specimens. Minimum inhibitory concentrations (MIC) were determined according to the Mueller Hinton agar dilution method against the following antibacterial agents: ampicillin, piperacillin, piperacillin-tazobactam, sulbactam, cefoperazone, cefoperazone-sulbactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, colistin, gentamicin, amikacin, trimethoprim-sulfamethoxazole, chloramphenicol, erythromycin, rifampin, norfloxacin, ciprofloxacin and minocycline. Seven isolates: Sphingobacterium multivorum (2), Sphingobacteriumspiritivorum (1), Empedobacterbrevis (1), Weeksella virosa (1), Bergeyella zoohelcum (1) and Oligella urethralis (1), were tested for amoxicillin-clavulanic acid and ampicillin-sulbactam susceptibility, and susceptibility to cefoperazone or sulbactam was not determined. Multiresistance was generally found in Stenotrophomonas maltophilia, Burkholderia cepacia, Chryseobacterium spp., Myroides spp., Achromobacter xylosoxidans, and Ochrobactrum anthropi isolates. On the other hand, Pseudomonas stutzeri, Shewanella putrefaciens-algae, Sphingomonas paucimobilis, and Pseudomonas oryzihabitans, Bergeyella zoohelcum, Weeksella virosa and Oligella urethralis were widely susceptible to the antibacterial agents tested. As a result of the wide variation in antimicrobial susceptibility shown by different species, a test on susceptibility to different antibacterial agents is essential in order to select an adequate therapy. The marked multiresistance evidenced by some species

  19. Selection of empiric therapy in patients with catheter-related infections.

    PubMed

    Rodríguez-Baño, J

    2002-05-01

    Catheter-related infections (CRI) are frequent and manifest in a wide range of clinical situations. A rational approach is necessary for the adequate management of these infections. Whenever a CRI is suspected, two main questions have to be addressed: whether to remove the catheter and whether to initiate empiric antimicrobial treatment. As the clinical diagnosis of CRI has a low specificity, the catheter should be removed only in circumstances such as severe or ongoing sepsis, persistent bacteremia, pulmonary or peripheral embolization, endocarditis, signs of tunnel infection, when the catheters or when the CRI is caused by fungi, Staphylococcus aureus or Pseudomonas aeruginosa are easy to replace among others. Exchanging the catheter through a guidewire is a frequent practice but is not recommended by some authors. Empiric antimicrobial treatment should be administered in any of the following situations: when the catheter is not removed, in the case of central venous or surgically implanted catheters and prosthetic implants, in the presence of severe sepsis, neutropenia or other immunodepressed status, suppurative phlebitis, embolization and acute endocarditis. Empriic antimicrobial treatment should include a glycopeptide (vancomycin or teicoplanin) as staphylococci are the most frequent cause of CRI. Adding an antipseudomonal agent, such as amikacin, aztreonam, ceftazidime, cefepime, piperacillin/tazobactam, or a carbapenem (depending on the local antimicrobial susceptibility data or antibiotic policy) is necessary in cases of neutropenia, burn patients, severe sepsis, or suspicion of contaminated infusate. Empiric treatment against Candida is not initially necessary in most cases. Empiric treatment should be replaced by specific therapy whenever possible.

  20. Antimicrobial Peptides in Reptiles

    PubMed Central

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  1. Inhalation Therapy in Horses.

    PubMed

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials.

  2. Fast disinfecting antimicrobial surfaces.

    PubMed

    Madkour, Ahmad E; Dabkowski, Jeffery M; Nusslein, Klaus; Tew, Gregory N

    2009-01-20

    Silicon wafers and glass surfaces were functionalized with facially amphiphilic antimicrobial copolymers using the "grafting from" technique. Surface-initiated atom transfer radical polymerization (ATRP) was used to grow poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces. Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S. aureus and E. coli 100% in less than 5 min. The molecular weight and grafting density of the polymer were controlled by varying the polymerization time and initiator surface density. Antimicrobial studies showed that the killing efficiency of these surfaces was independent of polymer layer thickness or grafting density within the range of surfaces studied.

  3. Fast Disinfecting Antimicrobial Surfaces

    PubMed Central

    Madkour, Ahmad E.; Dabkowski, Jeffery M.; Nüsslein, Klaus; Tew, Gregory N.

    2013-01-01

    Silicon wafers and glass surfaces were functionalized with facially amphiphilic antimicrobial copolymers using the “grafting from” technique. Surface initiated atom transfer radical polymerization (ATRP) was used to grow poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces. Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S. aureus and E. coli 100% in less than 5 min. The molecular weight and grafting density of the polymer were controlled by varying the polymerization time and initiator surface density. Antimicrobial studies showed that the killing efficiency of these surfaces was independent of polymer layer thickness or grafting density within the range of surfaces studied. PMID:19177651

  4. New Approaches to Antibiotic Use and Review of Recently Approved Antimicrobial Agents.

    PubMed

    Hahn, Andrew W; Jain, Rupali; Spach, David H

    2016-07-01

    Antimicrobial drug-resistance continues to force adaptation in our clinical practice. We explore new evidence regarding adjunctive antibiotic therapy for skin and soft tissue abscesses as well as duration of therapy for intra-abdominal abscesses. As new evidence refines optimal practice, it is essential to support clinicians in adopting practice patterns concordant with evidence-based guidelines. We review a simple approach that can 'nudge' clinicians towards concordant practices. Finally, the use of novel antimicrobials will play an increasingly important role in contemporary therapy. We review five new antimicrobials recently FDA-approved for use in drug-resistant infections: dalbavancin, oritavancin, ceftaroline, ceftolozane-tazobactam, and ceftazidime-avibactam.

  5. Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection

    PubMed Central

    Melvin, Jeffrey A.; Lashua, Lauren P.; Kiedrowski, Megan R.; Yang, Guanyi; Deslouches, Berthony; Montelaro, Ronald C.

    2016-01-01

    ABSTRACT Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents. Here, we tested the ability of an eCAP, WLBU2, to disrupt recalcitrant Pseudomonas aeruginosa biofilms. WLBU2 was capable of significantly reducing biomass and viability of P. aeruginosa biofilms formed on airway epithelium and maintained activity during viral coinfection, a condition that confers extraordinary levels of antibiotic resistance. Biofilm disruption was achieved in short treatment times by permeabilization of bacterial membranes. Additionally, we observed simultaneous reduction of infectivity of the viral pathogen respiratory syncytial virus (RSV). WLBU2 is notable for its ability to maintain activity across a broad range of physiological conditions and showed negligible toxicity toward the airway epithelium, expanding its potential applications as an antimicrobial therapeutic. IMPORTANCE Antimicrobial-resistant infections are an urgent public health threat, making development of novel antimicrobials able to effectively treat these infections extremely important. Chronic and polymicrobial infections further complicate antimicrobial therapy, often through the development of microbial biofilms. Here, we describe the ability of an engineered antimicrobial peptide to disrupt biofilms

  6. The cerebellopontine angle: does the translabyrinthine approach give adequate access?

    PubMed

    Fagan, P A; Sheehy, J P; Chang, P; Doust, B D; Coakley, D; Atlas, M D

    1998-05-01

    A long-standing but unfounded criticism of the translabyrinthine approach is the misperception that this approach does not give adequate access to the cerebellopontine angle. Because of what is perceived as limited visualization and operating space within the cerebellopontine angle, some surgeons still believe that the translabyrinthine approach is inappropriate for large acoustic tumors. In this study, the surgical access to the cerebellopontine angle by virtue of the translabyrinthine approach is measured and analyzed. The parameters are compared with those measured for the retrosigmoid approach. This series objectively confirms that the translabyrinthine approach offers the neurotologic surgeon a shorter operative depth to the tumor, via a similar-sized craniotomy. This permits superior visualization by virtue of a wider angle of surgical access. Such access is achieved with the merit of minimal cerebellar retraction.

  7. Public health risk of antimicrobial resistance transfer from companion animals.

    PubMed

    Pomba, Constança; Rantala, Merja; Greko, Christina; Baptiste, Keith Edward; Catry, Boudewijn; van Duijkeren, Engeline; Mateus, Ana; Moreno, Miguel A; Pyörälä, Satu; Ružauskas, Modestas; Sanders, Pascal; Teale, Christopher; Threlfall, E John; Kunsagi, Zoltan; Torren-Edo, Jordi; Jukes, Helen; Törneke, Karolina

    2017-04-01

    Antimicrobials are important tools for the therapy of infectious bacterial diseases in companion animals. Loss of efficacy of antimicrobial substances can seriously compromise animal health and welfare. A need for the development of new antimicrobials for the therapy of multiresistant infections, particularly those caused by Gram-negative bacteria, has been acknowledged in human medicine and a future corresponding need in veterinary medicine is expected. A unique aspect related to antimicrobial resistance and risk of resistance transfer in companion animals is their close contact with humans. This creates opportunities for interspecies transmission of resistant bacteria. Yet, the current knowledge of this field is limited and no risk assessment is performed when approving new veterinary antimicrobials. The objective of this review is to summarize the current knowledge on the use and indications for antimicrobials in companion animals, drug-resistant bacteria of concern among companion animals, risk factors for colonization of companion animals with resistant bacteria and transmission of antimicrobial resistance (bacteria and/or resistance determinants) between animals and humans. The major antimicrobial resistance microbiological hazards originating from companion animals that directly or indirectly may cause adverse health effects in humans are MRSA, methicillin-resistant Staphylococcus pseudintermedius, VRE, ESBL- or carbapenemase-producing Enterobacteriaceae and Gram-negative bacteria. In the face of the previously recognized microbiological hazards, a risk assessment tool could be applied in applications for marketing authorization for medicinal products for companion animals. This would allow the approval of new veterinary medicinal antimicrobials for which risk levels are estimated as acceptable for public health.

  8. Barriers to adequate prenatal care utilization in American Samoa

    PubMed Central

    Hawley, Nicola L; Brown, Carolyn; Nu’usolia, Ofeira; Ah-Ching, John; Muasau-Howard, Bethel; McGarvey, Stephen T

    2013-01-01

    Objective To describe the utilization of prenatal care in American Samoan women and to identify socio-demographic predictors of inadequate prenatal care utilization. Methods Using data from prenatal clinic records, women (n=692) were categorized according to the Adequacy of Prenatal Care Utilization Index as having received adequate plus, adequate, intermediate or inadequate prenatal care during their pregnancy. Categorical socio-demographic predictors of the timing of initiation of prenatal care (week of gestation) and the adequacy of received services were identified using one way Analysis of Variance (ANOVA) and independent samples t-tests. Results Between 2001 and 2008 85.4% of women received inadequate prenatal care. Parity (P=0.02), maternal unemployment (P=0.03), and both parents being unemployed (P=0.03) were negatively associated with the timing of prenatal care initation. Giving birth in 2007–2008, after a prenatal care incentive scheme had been introduced in the major hospital, was associated with earlier initiation of prenatal care (20.75 versus 25.12 weeks; P<0.01) and improved adequacy of received services (95.04% versus 83.8%; P=0.02). Conclusion The poor prenatal care utilization in American Samoa is a major concern. Improving healthcare accessibility will be key in encouraging women to attend prenatal care. The significant improvements in the adequacy of prenatal care seen in 2007–2008 suggest that the prenatal care incentive program implemented in 2006 may be a very positive step toward addressing issues of prenatal care utilization in this population. PMID:24045912

  9. Non-tuberculous mycobacterial infection of the musculoskeletal system: pattern of infection and efficacy of combined surgical/antimicrobial treatment.

    PubMed

    Park, J W; Kim, Y S; Yoon, J O; Kim, J S; Chang, J S; Kim, J M; Chun, J M; Jeon, I H

    2014-11-01

    Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a rare disease. An early and accurate diagnosis is often difficult because of the indolent clinical course and difficulty of isolating pathogens. Our goal was to determine the clinical features of musculoskeletal NTM infection and to present the treatment outcomes. A total of 29 patients (nine females, 20 males between 34 and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the musculoskeletal system between 1998 to 2011 were identified and their treatment retrospectively analysed. Microbiological studies demonstrated NTM in 29 patients: the isolates were Mycobacterium intracellulare in six patients, M. fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining patients we failed to identify the species. The involved sites were the hand/wrist in nine patients the knee in five patients, spine in four patients, foot in two patients, elbow in two patients, shoulder in one, ankle in two patients, leg in three patients and multiple in one patient. The mean interval between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180). All patients underwent surgical treatment and antimicrobial medication according to our protocol for chronic musculoskeletal infection: 20 patients had NTM-specific medication and nine had conventional antimicrobial therapy. At the final follow-up 22 patients were cured, three failed to respond to treatment and four were lost to follow-up. Identifying these diseases due the initial non-specific presentation can be difficult. Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes.

  10. What are Antimicrobial Pesticides?

    EPA Pesticide Factsheets

    Antimicrobial pesticides are substances or mixtures of substances used to destroy or suppress the growth of harmful microorganisms such as bacteria, viruses, or fungi on inanimate objects and surfaces.

  11. Pharmacogenomics of antimicrobial agents

    PubMed Central

    Aung, Ar Kar; Haas, David W; Hulgan, Todd; Phillips, Elizabeth J

    2015-01-01

    Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use. PMID:25495412

  12. Novel antimicrobial textiles

    NASA Astrophysics Data System (ADS)

    Cho, Unchin

    2003-10-01

    Many microorganisms can survive, and perhaps proliferate on textiles, generating adverse effects such as: disease transmission, odor generation, pH changes, staining, discoloration and loss of performance. These adverse effects may threaten users' health, deteriorate textile properties and degrade service quality. It may, therefore, be desirable to incorporate antimicrobials on textiles for controlling the growth of microorganisms. This dissertation focuses on the development of antimicrobial fibers and fabrics by integration of antimicrobials with these textiles. The applications of hydantoin-based halamines were mainly investigated in the research. The typical process is that hydantoin containing compounds are grafted onto textiles and transformed to halamine by chlorination. Hydantoin-based halamines are usually chloramines that release chlorine (Cl+) via cleavage of the -NCl functional group which attacks and kills microbes. The antimicrobial behavior is rechargeable many times by rinsing the fiber or fabric with chlorine-containing solution. Some quaternary ammonium type antimicrobials were also investigated in this research. The choice of integrating techniques is dependant on both the textile and antimicrobial compounds. In this dissertation, the nine approaches were studied for incorporating antimicrobial with various textiles: (1) co-extrusion of fibers with halamine precursor additive; (2) grafting of the quaternary ammonium compounds onto ethylene-co-acrylic acid fiber for creating quaternary ammonium type antimicrobial fiber; (3) entrapment of the additives in thermally bonded bicomponent nonwoven fabrics; (4) attaching antimicrobial additives to surfaces with latex adhesive coating; (5) grafting of antimicrobial compounds onto rubber latex via UV exposure; (6) reaction of halamine with needle-punched melamine formaldehyde nonwoven fabric and laminates; (7) coating melamine resin onto tent fabrics and laminates; (8) synthesis of super absorbent polymer

  13. How many patients complete an adequate trial of donepezil?

    PubMed

    Roe, Catherine M; Anderson, Michael J; Spivack, Barney

    2002-01-01

    Pharmacy claims data were used to evaluate medication adherence among 59 new users of donepezil aged 65 to 94 years. The probability (+/- 95% confidence interval) of a new user continuing donepezil at 90 days was.797 +/-.103 and at 180 days was.627 +/-.124. Additionally, 13.9% of those who continued therapy for at least 180 days showed gaps in treatment of six weeks or more. These results suggest that adherence with donepezil could be improved in clinical practice.

  14. Antimicrobial Compounds in Tears

    PubMed Central

    McDermott, Alison M.

    2013-01-01

    The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here. PMID:23880529

  15. Suggested guidelines for using systemic antimicrobials in bacterial skin infections: part 2— antimicrobial choice, treatment regimens and compliance

    PubMed Central

    Beco, L.; Guaguère, E.; Méndez, C. Lorente; Noli, C.; Nuttall, T.; Vroom, M.

    2013-01-01

    Systemic antimicrobials are critically important in veterinary healthcare, and resistance is a major concern. Antimicrobial stewardship will be important in maintaining clinical efficacy by reducing the development and spread of antimicrobial resistance. Bacterial skin infections are one of the most common reasons for using systemic antimicrobials in dogs and cats. Appropriate management of these infections is, therefore, crucial in any policy for responsible antimicrobial use. The goals of therapy are to confirm that an infection is present, identify the causative bacteria, select the most appropriate antimicrobial, ensure that the infection is treated correctly, and to identify and manage any underlying conditions. This is the second of two articles that provide evidence-led guidelines to help practitioners address these issues. Part 1 discussed the use of clinical signs, cytology and culture in diagnosis. This article will cover the rationale for topical and systemic antimicrobial therapy, including choice of first-, second- and third-line drugs, the dose, duration of therapy, compliance and identification of underlying predisposing conditions. In addition, there is guidance on cases of therapeutic failure and environmental hygiene. These guidelines will help veterinarians avoid the development and propagation of antimicrobial-resistant bacterial strains. PMID:23292948

  16. Recommended Initial Antimicrobial Therapy for Emphysematous Pyelonephritis

    PubMed Central

    Lu, Yu-Chuan; Hong, Jian-Hua; Chiang, Bing-Juin; Pong, Yuan-Hung; Hsueh, Po-Ren; Huang, Chao-Yuan; Pu, Yeong-Shiau

    2016-01-01

    Abstract The aim of this study was to investigate the profiles of pathogens and patterns of antibiotic resistance of emphysematous pyelonephritis (EPN), offering recommendations for initial antibiotic treatment. Between January, 2001, and November, 2014, demographic data, presenting clinical features, management strategies, and treatment outcomes of 51 patients with EPN were retrospectively reviewed, analyzing microbiological characteristics of causative pathogens and patterns of antibiotic resistance. Overall survival rate was 90.2% (46/51). Pathogens isolated most frequently were Escherichia coli (49.0%), Klebsiella pneumoniae (19.6%), and Proteus mirabilis (17.7%). Approximately 24% of E coli isolates and 22% K pneumoniae isolates were resistant to fluoroquinolones. Improper empiric antibiotic use (P = 0.02) and third-generation cephalosporin-resistant pathogens (G3CRP) (P = 0.01) were significantly more common in cases of patient fatality. Prior hospitalization and antibiotic use within past year (P = 0.03), need for emergency hemodialysis (P = 0.03), and development of disseminated intravascular coagulation (DIC) (P = 0.03) were factors correlating significantly with microbial resistance to third-generation cephalosporins. The area under the receiver operating characteristic curve was 0.91. The cut-off point determined by the maximum Youden index for 2 of these 3 factors yielded a sensitivity of 0.8 and specificity of 0.93. Third-generation cephalosporins are recommended as initial treatment of EPN. In patients with histories of prior hospitalization and antibiotic use and in those needing emergency hemodialysis or developing DIC, carbapenem is the empiric antibiotic of choice. Patients presenting with 2 or more factors carry the highest risk of G3CRP involvement. Fluoroquinolone and gentamicin should be avoided. PMID:27227920

  17. [Antimicrobial therapy in pregnancy (author's transl)].

    PubMed

    Reinlein, J M; Garcia, F S

    1979-12-14

    At the present time there is no medicament completely harmless to the embryo or fetus. Passage through the placenta probably occurs by simple diffusion. Substances with a molecular weight under 600, low protein binding, a low degree of ionization and good solubility in lipids cross the placenta most easily. The harmful effects of the different groups of medicaments are describedand the substances classified into those not particularly toxic, those which can only be used in certain conditions and those only to be used in exceptional cases. The treatment of the most common infections in pregnancy is dealth with in detail. Infections of the maternal urinary tract and amnionitis raise most problems. For the treatment of amnionitis, direct instillation of the medicament into the amniotic sac is recommended.

  18. Principles of Antimicrobial Therapy in Older Adults.

    PubMed

    Bradley, Suzanne F

    2016-08-01

    Antibiotic use is common in older adults, and much of it is deemed unnecessary. Complications of antibiotic use may occur as a consequence of changes in age-related physiology and dosing with resulting drug toxicity and secondary infection. Knowing when it is appropriate to initiate antibiotics may help reduce unnecessary antibiotic use and prevent adverse drug events. Careful attention to antibiotic selection, dosing adjustments, and drug-drug interactions may also help prevent antibiotic-related adverse events.

  19. Antimicrobials, susceptibility testing, and minimum inhibitory concentrations (MIC) in veterinary infection treatment.

    PubMed

    Papich, Mark G

    2013-09-01

    Veterinarians are quick to attribute an unsuccessful antimicrobial treatment to a failure of the culture and susceptibility test. There are many reasons why antimicrobial treatment fails. When evaluating a patient that has failed to respond to therapy, one must consider any of the many factors that contribute to antibiotic failure.

  20. Opportunities to improve antimicrobial use in paediatric intensive care units: a nationwide survey in Spain.

    PubMed

    Paño-Pardo, J R; Schüffelmann-Gutiérrez, C; Escosa-García, L; Laplaza-González, M; Moreno-Ramos, F; Gómez-Gil, R; López, J D; Jordán, I; Téllez, C; de la Oliva, P

    2016-02-01

    Improving antimicrobial use is a complex process that requires an accurate assessment of ongoing problems and barriers. Paediatric intensive care units (PICU) have seldom been assessed from this perspective. Two Internet-based, self-administered surveys were conducted nationwide in Spain between January and February 2014. The first survey aimed to assess those characteristics of Spanish PICUs that could influence antimicrobial prescribing or antimicrobial stewardship. The second survey targeted Spanish PICU physicians and pursued to assess their attitudes and perceptions regarding antimicrobial resistance and antimicrobial use. Information about 29/39 contacted PICUs was obtained. A total of 114/206 (55.3%) paediatric intensivists responded. PICUs were heterogeneous regarding years since foundation, number of beds, type of patients admitted and staffing. Only 11 (37.9%) PICUs had available e-prescribing systems. Procalcitonin was available in 24 (89.1%) PICUs, but there were no procalcitonin-based protocols in 14 (60.9%) of them. Half of surveyed PICUs had implemented antimicrobial stewardship activities. Ninety-eight of the 114 PICU physicians (86%) who participated considered that antimicrobial resistance was a significantly relevant problem for their daily and that improving antimicrobial use in their PICU should be a priority (103; 90.4%). The main perceived problems regarding antimicrobial use were the excessive use of antimicrobials in patients with nonconfirmed infections and excessive use of broad-spectrum antimicrobials. The most valued antimicrobial stewardship interventions were the implementation of protocols to guide antimicrobial therapy. Spanish PICU doctors are aware of the relevance of the problem of antimicrobial resistance and the need to improve antimicrobial use. Targeted interventions should take into account their difficulties and preferences when feasible.

  1. Systemic Crisis of Civilization: In Search for Adequate Solution

    NASA Astrophysics Data System (ADS)

    Khozin, Grigori

    In December 1972 a jumbo jet crashed in the Florida Everglades with the loss of 101 lives. The pilot, distracted by a minor malfunction, failed to note until too late the warning signal that - correctly - indicated an impending disaster. His sudden, astonished cry of Hey, what happening here? were his last words 1. Three decades after this tragic episode, as the Humankind approaches the threshold of the third Millennium, the problem of adequate reaction to warning signals of different nature and of distinguishing minor malfunctions in everyday life of society, in economy and technology as well as in evolution of biosphere from grave threats to the world community and the phenomenon of life on our planet remains crucial to human survival and the future of Civilization. Rational use of knowledge and technology available to the world community remains in this context the corner stone of discussions on the destiny of the intelligent life both on the planet Earth and in the Universe (the fact of intelligent life in the Universe is to be detected by the Humankind)…

  2. ENSURING ADEQUATE SAFETY WHEN USING HYDROGEN AS A FUEL

    SciTech Connect

    Coutts, D

    2007-01-22

    Demonstration projects using hydrogen as a fuel are becoming very common. Often these projects rely on project-specific risk evaluations to support project safety decisions. This is necessary because regulations, codes, and standards (hereafter referred to as standards) are just being developed. This paper will review some of the approaches being used in these evolving standards, and techniques which demonstration projects can implement to bridge the gap between current requirements and stakeholder desires. Many of the evolving standards for hydrogen-fuel use performance-based language, which establishes minimum performance and safety objectives, as compared with prescriptive-based language that prescribes specific design solutions. This is being done for several reasons including: (1) concern that establishing specific design solutions too early will stifle invention, (2) sparse performance data necessary to support selection of design approaches, and (3) a risk-adverse public which is unwilling to accept losses that were incurred in developing previous prescriptive design standards. The evolving standards often contain words such as: ''The manufacturer shall implement the measures and provide the information necessary to minimize the risk of endangering a person's safety or health''. This typically implies that the manufacturer or project manager must produce and document an acceptable level of risk. If accomplished using comprehensive and systematic process the demonstration project risk assessment can ease the transition to widespread commercialization. An approach to adequately evaluate and document the safety risk will be presented.

  3. DARHT -- an adequate EIS: A NEPA case study

    SciTech Connect

    Webb, M.D.

    1997-08-01

    In April 1996 the US District Court in Albuquerque ruled that the Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility Environmental Impact Statement (EIS), prepared by the Los Alamos Area Office, US Department of Energy (DOE), was adequate. The DARHT EIS had been prepared in the face of a lawsuit in only 10 months, a third of the time usually allotted for a DOE EIS, and for only a small fraction of the cost of a typical DOE EIS, and for only a small fraction of the cost of a typical DOE EIS. It subject was the first major facility to be built in decades for the DOE nuclear weapons stockpile stewardship program. It was the first EIS to be prepared for a proposal at DOE`s Los Alamos National Laboratory since 1979, and the first ever prepared by the Los Alamos Area Office. Much of the subject matter was classified. The facility had been specially designed to minimize impacts to a nearby prehistoric Native American ruin, and extensive consultation with American Indian Pueblos was required. The week that the draft EIS was published Laboratory biologists identified a previously unknown pair of Mexican spotted owls in the immediate vicinity of the project, bringing into play the consultation requirements of the Endangered Species Act. In spite of these obstacles, the resultant DARHT EIS was reviewed by the court and found to meet all statutory and regulatory requirements; the court praised the treatment of the classified material which served as a basis for the environmental analysis.

  4. Dose Limits for Man do not Adequately Protect the Ecosystem

    SciTech Connect

    Higley, Kathryn A.; Alexakhin, Rudolf M.; McDonald, Joseph C.

    2004-08-01

    It has been known for quite some time that different organisms display differing degrees of sensitivity to the effects of ionizing radiations. Some microorganisms such as the bacterium Micrococcus radiodurans, along with many species of invertebrates, are extremely radio-resistant. Humans might be categorized as being relatively sensitive to radiation, and are a bit more resistant than some pine trees. Therefore, it could be argued that maintaining the dose limits necessary to protect humans will also result in the protection of most other species of flora and fauna. This concept is usually referred to as the anthropocentric approach. In other words, if man is protected then the environment is also adequately protected. The ecocentric approach might be stated as; the health of humans is effectively protected only when the environment is not unduly exposed to radiation. The ICRP is working on new recommendations dealing with the protection of the environment, and this debate should help to highlight a number of relevant issues concerning that topic.

  5. Antimicrobial applications of water-dispersible magnetic nanoparticles in biomedicine.

    PubMed

    Huang, Keng-Shiang; Shieh, Dar-Bin; Yeh, Chen-Sheng; Wu, Ping-Ching; Cheng, Fong-Yu

    2014-01-01

    The increasing morbidity and mortality of infectious diseases is an increasing concern. Despite the continuous development and synthesis of new antimicrobial drugs, microbial pathogens are exhibiting increased multi-drug resistance. Nanomaterials display unique and well-defined physical and chemical properties including a very high surface area to volume ratio, and new approaches for antimicrobial therapies have attempted to combine nanomaterials and current antimicrobial drugs. Magnetic nanoparticles (MNPs) are characterized by biocompatibility, biodegradation, and safety for human ingestion. Iron oxide nanoparticles have been approved for human use by the US Food and Drug Administration (FDA). For biomedicine applications, MNPs require surface modification to become water-soluble and be stable enough to resist the effects of proteins and salts in the physiological environment. MNPs can combine various substrata, such as biomolecules and nanomaterials to generate new antimicrobial agents which combine antibacterial, antiviral, and antifungal properties. This can be accomplished through a series of surface modification methods. Because MNPs have unique superparamagnetic characteristics, they can be controlled and recycled by an external magnetic field.In addition, the antimicrobial activity of MNPs-based nanocomposites is superior to that of metallic nanoparticles. This paper reviews the recent literature on the use of MNP-based nanomaterials in antimicrobial applications in biomedicine. Antimicrobial applications mainly focus on inhibiting and killing bacteria and fungi and viruses inactivation. The synthesis, surface modification, and characteristics related to MNPs will also be briefly addressed.

  6. Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori.

    PubMed

    Cosme, A; Montes, M; Martos, M; Gil, I; Mendarte, U; Salicio, Y; Piñeiro, L; Recasens, M T; Ibarra, B; Sarasqueta, C; Bujanda, L

    2013-04-01

    The rate of eradication of Helicobacter pylori with standard triple therapy using omeprazole, amoxicillin and clarithromycin (OAC) is unacceptable in populations with high rates of clarithromycin resistance (15-20%). The aim of this study was to compare the efficacy of 10-day OAC therapy as the first-line treatment in patients diagnosed by culture with antimicrobial susceptibility or diagnosed by a (13) C-labelled urea breath test (UBT) without antimicrobial susceptibility in an area where the clarithromycin resistance rate was 15-20%. This was a retrospective cohort study of 266 patients, recruited consecutively throughout 2008. A total of 247 H. pylori-infected patients received antibiotic therapy (221 received the 10-day OAC therapy and 26 received other regimens) of which 134 patients were diagnosed by culture of gastric samples followed by antimicrobial susceptibility testing and 113 were diagnosed by UBT. In all patients, the eradication of H. pylori was checked by UBT. The cost of eradication by 10-day OAC treatment was assessed in each patient. The success rate of 10-day OAC therapy in patients diagnosed by culture and by UBT was 88% (103/117) and 49% (51/104), respectively (p <0.0005). The treatment was also more cost-effective in the former of these two groups (€571 versus €666). To perform culture and antimicrobial susceptibility of the H. pylori isolates was a more successful and cost effective strategy than empirical 10-day OAC treatment in populations with high rates of resistance to clarithromycin.

  7. The antimicrobial resistance crisis: management through gene monitoring

    PubMed Central

    2016-01-01

    Antimicrobial resistance (AMR) is an acknowledged crisis for humanity. Its genetic origins and dire potential outcomes are increasingly well understood. However, diagnostic techniques for monitoring the crisis are currently largely limited to enumerating the increasing incidence of resistant pathogens. Being the end-stage of the evolutionary process that produces antimicrobial resistant pathogens, these measurements, while diagnostic, are not prognostic, and so are not optimal in managing this crisis. A better test is required. Here, using insights from an understanding of evolutionary processes ruling the changing abundance of genes under selective pressure, we suggest a predictive framework for the AMR crisis. We then discuss the likely progression of resistance for both existing and prospective antimicrobial therapies. Finally, we suggest that by the environmental monitoring of resistance gene frequency, resistance may be detected and tracked presumptively, and how this tool may be used to guide decision-making in the local and global use of antimicrobials. PMID:27831476

  8. Mycoplasma bovis: Mechanisms of Resistance and Trends in Antimicrobial Susceptibility

    PubMed Central

    Lysnyansky, Inna; Ayling, Roger D.

    2016-01-01

    Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC) for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired. PMID:27199926

  9. Antimicrobial Treatment Improves Mycobacterial Survival in Nonpermissive Growth Conditions

    PubMed Central

    Turapov, Obolbek; Waddell, Simon J.; Burke, Bernard; Glenn, Sarah; Sarybaeva, Asel A.; Tudo, Griselda; Labesse, Gilles; Young, Danielle I.; Young, Michael; Andrew, Peter W.; Butcher, Philip D.; Cohen-Gonsaud, Martin

    2014-01-01

    Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis. PMID:24590482

  10. Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus pneumoniae.

    PubMed

    de Gracia Retamosa, María; Díez-Martínez, Roberto; Maestro, Beatriz; García-Fernández, Esther; de Waal, Bas; Meijer, E W; García, Pedro; Sanz, Jesús M

    2015-11-09

    A double approach was followed in the search of novel inhibitors of the surface choline-binding proteins (CBPs) of Streptococcus pneumoniae (pneumococcus) with antimicrobial properties. First, a library of 49 rationally-designed esters of alkyl amines was screened for their specific binding to CBPs. The best binders, being esters of bicyclic amines (EBAs), were then tested for their in vitro effect on pneumococcal growth and morphology. Second, the efficiency of EBA-induced CBP inhibition was enhanced about 45,000-fold by multivalency effects upon synthesizing a poly(propylene imine) dendrimer containing eight copies of an atropine derivative. Both approaches led to compounds that arrest bacterial growth, dramatically decrease cell viability, and exhibit a protection effect in animal disease models, demonstrating that the pneumococcal CBPs are adequate targets for the discovery of novel antimicrobials that overcome the currently increasing antimicrobial resistance issues.

  11. The antimicrobial assessment of some Nigerian herbal soap.

    PubMed

    Igbeneghu, O A

    2013-01-01

    Twenty samples of herbal soaps were evaluated for their antimicrobial activity against bacteria and yeast of significance in skin infections with the aim to provide some justification for the continued use of the soaps in the management of superficial skin infections. All the soaps were found to possess antimicrobial activity in a concentration and organism dependent manner. The soaps were more active against the gram positive organisms than the Gram negative organisms while none of the soaps had activity against the tested yeasts. Only 35% of the soaps were appropriately packaged with adequate directions for use and storage. The study showed that the tested soaps possessed antimicrobial properties and they can contribute to the treatment and management of skin infections caused by bacteria if well prepared with the appropriate plant materials to target specific causative organisms and packaged with appropriate directions for use and storage.

  12. On Adequate Comparisons of Antenna Phase Center Variations

    NASA Astrophysics Data System (ADS)

    Schoen, S.; Kersten, T.

    2013-12-01

    One important part for ensuring the high quality of the International GNSS Service's (IGS) products is the collection and publication of receiver - and satellite antenna phase center variations (PCV). The PCV are crucial for global and regional networks, since they introduce a global scale factor of up to 16ppb or changes in the height component with an amount of up to 10cm, respectively. Furthermore, antenna phase center variations are also important for precise orbit determination, navigation and positioning of mobile platforms, like e.g. the GOCE and GRACE gravity missions, or for the accurate Precise Point Positioning (PPP) processing. Using the EUREF Permanent Network (EPN), Baire et al. (2012) showed that individual PCV values have a significant impact on the geodetic positioning. The statements are further supported by studies of Steigenberger et al. (2013) where the impact of PCV for local-ties are analysed. Currently, there are five calibration institutions including the Institut für Erdmessung (IfE) contributing to the IGS PCV file. Different approaches like field calibrations and anechoic chamber measurements are in use. Additionally, the computation and parameterization of the PCV are completely different within the methods. Therefore, every new approach has to pass a benchmark test in order to ensure that variations of PCV values of an identical antenna obtained from different methods are as consistent as possible. Since the number of approaches to obtain these PCV values rises with the number of calibration institutions, there is the necessity for an adequate comparison concept, taking into account not only the numerical values but also stochastic information and computational issues of the determined PCVs. This is of special importance, since the majority of calibrated receiver antennas published by the IGS origin from absolute field calibrations based on the Hannover Concept, Wübbena et al. (2000). In this contribution, a concept for the adequate

  13. Are Vancomycin Trough Concentrations Adequate for Optimal Dosing?

    PubMed Central

    Youn, Gilmer; Jones, Brenda; Jelliffe, Roger W.; Drusano, George L.; Rodvold, Keith A.; Lodise, Thomas P.

    2014-01-01

    The current vancomycin therapeutic guidelines recommend the use of only trough concentrations to manage the dosing of adults with Staphylococcus aureus infections. Both vancomycin efficacy and toxicity are likely to be related to the area under the plasma concentration-time curve (AUC). We assembled richly sampled vancomycin pharmacokinetic data from three studies comprising 47 adults with various levels of renal function. With Pmetrics, the nonparametric population modeling package for R, we compared AUCs estimated from models derived from trough-only and peak-trough depleted versions of the full data set and characterized the relationship between the vancomycin trough concentration and AUC. The trough-only and peak-trough depleted data sets underestimated the true AUCs compared to the full model by a mean (95% confidence interval) of 23% (11 to 33%; P = 0.0001) and 14% (7 to 19%; P < 0.0001), respectively. In contrast, using the full model as a Bayesian prior with trough-only data allowed 97% (93 to 102%; P = 0.23) accurate AUC estimation. On the basis of 5,000 profiles simulated from the full model, among adults with normal renal function and a therapeutic AUC of ≥400 mg · h/liter for an organism for which the vancomycin MIC is 1 mg/liter, approximately 60% are expected to have a trough concentration below the suggested minimum target of 15 mg/liter for serious infections, which could result in needlessly increased doses and a risk of toxicity. Our data indicate that adjustment of vancomycin doses on the basis of trough concentrations without a Bayesian tool results in poor achievement of maximally safe and effective drug exposures in plasma and that many adults can have an adequate vancomycin AUC with a trough concentration of <15 mg/liter. PMID:24165176

  14. Is clinical measurement of anatomic axis of the femur adequate?

    PubMed

    Wu, Chi-Chuan

    2017-03-23

    Background and purpose - The accuracy of using clinical measurement from the anterior superior iliac spine (ASIS) to the center of the knee to determine an anatomic axis of the femur has rarely been studied. A radiographic technique with a full-length standing scanogram (FLSS) was used to assess the adequacy of the clinical measurement. Patients and methods - 100 consecutive young adult patients (mean age 34 (20-40) years) with chronic unilateral lower extremity injuries were studied. The pelvis and intact contralateral lower extremity images in the FLSS were selected for study. The angles between the tibial axis and the femoral shaft anatomic axis (S-AA), the piriformis anatomic axis (P-AA), the clinical anatomic axis (C-AA), and the mechanical axis (MA) were compared between sexes. Results - Only the S-AA and C-AA angles were statistically significantly different in the 100 patients (3.6° vs. 2.8°; p = 0.03). There was a strong correlation between S-AA, P-AA, and C-AA angles (r > 0.9). The average intersecting angle between MA and S-AA in the femur in the 100 patients was 5.5°, and it was 4.8° between MA and C-AA. Interpretation - Clinical measurement of an anatomic axis from the ASIS to the center of the knee may be an adequate and acceptable method to determine lower extremity alignment. The optimal inlet for antegrade femoral intramedullary nailing may be the lateral edge of the piriformis fossa.

  15. Design and Application of Antimicrobial Peptide Conjugates

    PubMed Central

    Reinhardt, Andre; Neundorf, Ines

    2016-01-01

    Antimicrobial peptides (AMPs) are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT) or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry. PMID:27187357

  16. Therapeutic antimicrobial peptides may compromise natural immunity

    PubMed Central

    Habets, Michelle G. J. L.; Brockhurst, Michael A.

    2012-01-01

    Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that Staphylococcus aureus rapidly evolved resistance to pexiganan, a drug-candidate for diabetic leg ulcer infections. Evolved resistance was costly in terms of impaired growth rate, but costs-of-resistance were completely ameliorated by compensatory adaptation. Crucially, we show that, in some populations, experimentally evolved resistance to pexiganan provided S. aureus with cross-resistance to human-neutrophil-defensin-1, a key component of the innate immune response to infection. This unintended consequence of therapeutic use could drastically undermine our innate immune system's ability to control and clear microbial infections. Our results therefore highlight grave potential risks of AMP therapies, with implications for their development. PMID:22279153

  17. Peptide Antimicrobial Agents

    PubMed Central

    Jenssen, Håvard; Hamill, Pamela; Hancock, Robert E. W.

    2006-01-01

    Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents. PMID:16847082

  18. [Antimicrobial susceptibility cumulative reports].

    PubMed

    Canut-Blasco, Andrés; Calvo, Jorge; Rodríguez-Díaz, Juan Carlos; Martínez-Martínez, Luis

    2016-10-01

    Cumulative reports on antimicrobial susceptibility tests data are important for selecting empirical treatments, as an educational tool in programs on antimicrobial use, and for establishing breakpoints defining clinical categories. These reports should be based on data validated by clinical microbiologists using diagnostic samples (not surveillance samples). In order to avoid a bias derived from including several isolates obtained from the same patient, it is recommended that, for a defined period, only the first isolate is counted. A minimal number of isolates per species should be presented: a figure of >=30 isolates is statistically acceptable. The report is usually presented in a table format where, for each cell, information on clinically relevant microorganisms-antimicrobial agents is presented. Depending on particular needs, multiple tables showing data related to patients, samples, services or special pathogens can be prepared.

  19. Antimicrobial Peptides from Fish

    PubMed Central

    Masso-Silva, Jorge A.; Diamond, Gill

    2014-01-01

    Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

  20. Antimicrobial activity of spices.

    PubMed

    Arora, D S; Kaur, J

    1999-08-01

    Spices have been shown to possess medicinal value, in particular, antimicrobial activity. This study compares the sensitivity of some human pathogenic bacteria and yeasts to various spice extracts and commonly employed chemotherapeutic substances. Of the different spices tested only garlic and clove were found to possess antimicrobial activity. The bactericidal effect of garlic extract was apparent within 1 h of incubation and 93% killing of Staphylococcus epidermidis and Salmonella typhi was achieved within 3 h. Yeasts were totally killed in 1 h by garlic extract but in 5 h with clove. Some bacteria showing resistance to certain antibiotics were sensitive to extracts of both garlic and clove. Greater anti-candidal activity was shown by garlic than by nystatin. Spices might have a great potential to be used as antimicrobial agents.

  1. Antimicrobial resistance: addressing the global threat through greater awareness and transformative action.

    PubMed

    Keown, Oliver P; Warburton, Will; Davies, Sally C; Darzi, Ara

    2014-09-01

    Antimicrobial therapies have played an unquestionably important role in advancing modern medical and surgical care, treating animals, reducing the global burden of communicable disease, and prolonging human life expectancy. These transformational benefits are threatened because of the rapidly advancing phenomenon of antimicrobial resistance. As a result of complex factors across many sectors and international actors, the global impact of antimicrobial resistance is an escalating economic and health crisis. This article draws on the collective expertise and summit report of the Antimicrobial Resistance Working Group from the 2013 World Innovation Summit for Health, in Doha, Qatar. It defines a framework of principles and tasks for key policy makers to raise international awareness of antimicrobial resistance and lead transformative action through policy-driven improvements in sanitation, antimicrobial conservation, agricultural practices, and research and development.

  2. Antimicrobial resistance challenged with metal-based antimicrobial macromolecules.

    PubMed

    Abd-El-Aziz, Alaa S; Agatemor, Christian; Etkin, Nola

    2017-02-01

    Antimicrobial resistance threatens the achievements of science and medicine, as it deactivates conventional antimicrobial therapeutics. Scientists respond to the threat by developing new antimicrobial platforms to prevent and treat infections from these resistant strains. Metal-based antimicrobial macromolecules are emerging as an alternative to conventional platforms because they combine multiple mechanisms of action into one platform due to the distinctive properties of metals. For example, metals interact with intracellular proteins and enzymes, and catalyse various intracellular processes. The macromolecular architecture offers a means to enhance antimicrobial activity since several antimicrobial moieties can be conjugated to the scaffold. Further, these macromolecules can be fabricated into antimicrobial materials for contact-killing medical implants, fabrics, and devices. As volatilization or leaching out of the antimicrobial moieties from the macromolecular scaffold is reduced, these medical implants, fabrics, and devices can retain their antimicrobial activity over an extended period. Recent advances demonstrate the potential of metal-based antimicrobial macromolecules as effective platforms that prevent and treat infections from resistant strains. In this review these advances are thoroughly discussed within the context of examples of metal-based antimicrobial macromolecules, their mechanisms of action and biocompatibility.

  3. Antimicrobial use metrics and benchmarking to improve stewardship outcomes: methodology, opportunities, and challenges.

    PubMed

    Ibrahim, Omar M; Polk, Ron E

    2014-06-01

    Measurement of antimicrobial use before and after an intervention and the associated outcomes are key activities of antimicrobial stewardship programs. In the United States, the recommended metric for aggregate antibiotic use is days of therapy/1000 patient-days. Clinical outcomes, including response to therapy and bacterial resistance, are critical measures but are more difficult to document than economic outcomes. Interhospital benchmarking of risk adjusted antimicrobial use is possible, although several obstacles remain before it can have an impact on patient care. Many challenges for stewardship programs remain, but the methods and science to support their efforts are rapidly evolving.

  4. Development of quality indicators for antimicrobial treatment in adults with sepsis

    PubMed Central

    2014-01-01

    Background Outcomes in patients with sepsis are better if initial empirical antimicrobial use is appropriate. Several studies have shown that adherence to guidelines dictating appropriate antimicrobial use positively influences clinical outcome, shortens length of hospital stay and contributes to the containment of antibiotic resistance. Quality indicators (QIs) can be systematically developed from these guidelines to define and measure appropriate antimicrobial use. We describe the development of a concise set of QIs to assess the appropriateness of antimicrobial use in adult patients with sepsis on a general medical ward or Intensive Care Unit (ICU). Methods A RAND-modified, five step Delphi procedure was used. A multidisciplinary panel of 14 experts appraised and prioritized 40 key recommendations from within the Dutch national guideline on antimicrobial use for adult hospitalized patients with sepsis (http://www.swab.nl/guidelines). A procedure to select QIs relevant to clinical outcome, antimicrobial resistance and costs was performed using two rounds of questionnaires with a face-to-face consensus meeting between the rounds over a period of three months. Results The procedure resulted in the selection of a final set of five QIs, namely: obtain cultures; prescribe empirical antimicrobial therapy according to the national guideline; start intravenous drug therapy; start antimicrobial treatment within one hour; and streamline antimicrobial therapy. Conclusion This systematic, stepwise method, which combined evidence and expert opinion, led to a concise and therefore feasible set of QIs for optimal antimicrobial use in hospitalized adult patients with sepsis. The next step will entail subjecting these quality indicators to an applicability test for their clinimetric properties and ultimately, using these QIs in quality-improvement projects. This information is crucial for antimicrobial stewardship teams to help set priorities and to focus improvement. PMID

  5. Antimicrobial Peptides in Human Sepsis

    PubMed Central

    Martin, Lukas; van Meegern, Anne; Doemming, Sabine; Schuerholz, Tobias

    2015-01-01

    Nearly 100 years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1–3 and human beta-defensins (HBDs) 1–3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1–3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1–3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1–11 (hLF 1–11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections

  6. Antimicrobial Photodynamic Therapy as an Adjunct to Nonsurgical Periodontal Therapy.

    PubMed

    Bowen, Denise M

    2015-12-01

    The purpose of Linking Research to Clinical Practice is to present evidence based information to clinical dental hygienists so that they can make informed decisions regarding patient treatment and recommendations. Each issue will feature a different topic area of importance to clinical dental hygienists with A BOTTOM LINE to translate the research findings into clinical application.

  7. Antimicrobial Resistance in Agriculture.

    PubMed

    Thanner, Sophie; Drissner, David; Walsh, Fiona

    2016-04-19

    In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans.

  8. Pediatric Antimicrobial Stewardship Programs

    PubMed Central

    Nichols, Kristen; Stoffella, Sylvia; Meyers, Rachel; Girotto, Jennifer

    2017-01-01

    The frequent use of antimicrobials in pediatric patients has led to a significant increase in multidrug-resistant bacterial infections among children. Antimicrobial stewardship programs have been created in many hospitals in an effort to curtail and optimize the use of antibiotics. Pediatric-focused programs are necessary because of the differences in antimicrobial need and use among this patient population, unique considerations and dosing, vulnerability for resistance due to a lifetime of antibiotic exposure, and the increased risk of adverse events. This paper serves as a position statement of the Pediatric Pharmacy Advocacy Group (PPAG) who supports the implementation of antimicrobial stewardship programs for all pediatric patients. PPAG also believes that a pediatric pharmacy specialist should be included as part of that program and that services be covered by managed care organizations and government insurance entities. PPAG also recommends that states create legislation similar to that in existence in California and Missouri and that a federal Task Force for Combating Antibiotic-Resistant Bacteria be permanently established. PPAG also supports post-doctoral pharmacy training programs in antibiotic stewardship.

  9. Triclosan antimicrobial polymers

    PubMed Central

    Petersen, Richard C.

    2016-01-01

    Triclosan antimicrobial molecular fluctuating energies of nonbonding electron pairs for the oxygen atom by ether bond rotations are reviewed with conformational computational chemistry analyses. Subsequent understanding of triclosan alternating ether bond rotations is able to help explain several material properties in Polymer Science. Unique bond rotation entanglements between triclosan and the polymer chains increase both the mechanical properties of polymer toughness and strength that are enhanced even better through secondary bonding relationships. Further, polymer blend compatibilization is considered due to similar molecular relationships and polarities. With compatibilization of triclosan in polymers a more uniform stability for nonpolar triclosan in the polymer solid state is retained by the antimicrobial for extremely low release with minimum solubility into aqueous solution. As a result, triclosan is projected for long extended lifetimes as an antimicrobial polymer additive. Further, triclosan rapid alternating ether bond rotations disrupt secondary bonding between chain monomers in the resin state to reduce viscosity and enhance polymer blending. Thus, triclosan is considered for a polymer additive with multiple properties to be an antimicrobial with additional benefits as a nonpolar toughening agent and a hydrophobic wetting agent. The triclosan material relationships with alternating ether bond rotations are described through a complete different form of medium by comparisons with known antimicrobial properties that upset bacterial cell membranes through rapid fluctuating mechanomolecular energies. Also, triclosan bond entanglements with secondary bonding can produce structural defects in weak bacterial lipid membranes requiring pliability that can then interfere with cell division. Regarding applications with polymers, triclosan can be incorporated by mixing into a resin system before cure, melt mixed with thermoplastic polymers that set on cooling

  10. Antimicrobial stewardship and Clostridium difficile-associated diarrhea.

    PubMed

    Piacenti, Frank J; Leuthner, Kimberly D

    2013-10-01

    Antimicrobial stewardship programs are essential to health care institutions to promote the appropriate use of antibiotics not only to decrease antimicrobial resistance but to prevent the spread and infection of Clostridium difficile. Clostridium difficile-associated diarrhea is increasing rapidly in the United States and is now considered a major public health problem that poses an immediate threat to the health of patients prescribed antibiotics, more so than antimicrobial resistance. Clostridium difficile-associated disease is the result of collateral damage to the normal bacterial flora of the human body, which is an inevitable consequence of any antibiotic use. Antimicrobial stewardship programs such as audit with feedback and antibiotic restriction are designed to help limit Clostridium difficile infections and other hospital-associated organisms by optimizing antimicrobial selection, dosing, de-escalation, and duration of therapy. These programs also incorporate implementation of hospital-wide guidelines, staff education, enforcement of infection-control policies, and the use of electronic medical records when possible to help control antibiotic use. This article reviews the literature on how antimicrobial stewardship programs impact Clostridium difficile rates and discusses experiences in designing, implementing, monitoring, and follow-through of such programs.

  11. Community intravenous therapy provision.

    PubMed

    O'Hanlon, Sue; McGrail, Pam; Hodgkins, Paul

    2017-03-08

    Many healthcare services that were once only available in acute settings are now common in the community. Intravenous (IV) therapy is increasingly available as a community service. Given the option, most patients would choose to receive their treatment in a community setting, rather than in hospital. This article describes several outpatient parenteral antimicrobial therapy services, including their advantages and disadvantages. It explores the ways one community NHS trust has developed its community IV therapy service over the past ten years and examines issues pertinent to effective service delivery.

  12. Antianaerobic Antimicrobials: Spectrum and Susceptibility Testing

    PubMed Central

    Wexler, Hannah M.; Goldstein, Ellie J. C.

    2013-01-01

    SUMMARY Susceptibility testing of anaerobic bacteria recovered from selected cases can influence the choice of antimicrobial therapy. The Clinical and Laboratory Standards Institute (CLSI) has standardized many laboratory procedures, including anaerobic susceptibility testing (AST), and has published documents for AST. The standardization of testing methods by the CLSI allows comparisons of resistance trends among various laboratories. Susceptibility testing should be performed on organisms recovered from sterile body sites, those that are isolated in pure culture, or those that are clinically important and have variable or unique susceptibility patterns. Organisms that should be considered for individual isolate testing include highly virulent pathogens for which susceptibility cannot be predicted, such as Bacteroides, Prevotella, Fusobacterium, and Clostridium spp.; Bilophila wadsworthia; and Sutterella wadsworthensis. This review describes the current methods for AST in research and reference laboratories. These methods include the use of agar dilution, broth microdilution, Etest, and the spiral gradient endpoint system. The antimicrobials potentially effective against anaerobic bacteria include beta-lactams, combinations of beta-lactams and beta-lactamase inhibitors, metronidazole, chloramphenicol, clindamycin, macrolides, tetracyclines, and fluoroquinolones. The spectrum of efficacy, antimicrobial resistance mechanisms, and resistance patterns against these agents are described. PMID:23824372

  13. Antimicrobial activity of preparation Bioaron C.

    PubMed

    Gawron-Gzella, Anne; Michalak, Anna; Kędzia, Anna

    2014-01-01

    The antimicrobial activity of sirupus Bioaron C, a preparation, whose main ingredient is an extract from the leaves of Aloe arborescens, was tested against different microorganisms isolated from patients with upper respiratory tract infections. The experiments were performed on 40 strains: 20 strains of anaerobic bacteria, 13 strains of aerobic bacteria and 7 strains of yeast-like fungi from the genus Candida and on 18 reference strains (ATCC). The antimicrobial activity of Bioaron C (MBC and MFC) was determined at undiluted concentration. Bioaron C proved to be very effective against the microorganisms causing infections. At the concentration recommended by the producer, the preparation showed biocidal activity (MBC, MFC) against the strains of the pathogenic microorganisms, which cause respiratory infections most frequently, including, among others, Peptostreptococcus anaerobius, Parvimonas micra, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus anginosus, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa and Candida albicans, already after 15 min. The MIC of Bioaron C against most of the tested microorganisms was 5 to 100 times lower than the usually applied concentration. The great antimicrobial activity means that the preparation may be used in the prevention and treatment of infections of the upper respiratory tract. Bioaron C may be an alternative or complement to classical therapy, especially in children.

  14. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  15. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  16. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  17. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  18. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  19. 78 FR 14801 - Veterinary Oversight of Antimicrobial Use in Livestock: Impact on Stakeholders; Public Meetings...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-07

    ... HUMAN SERVICES Food and Drug Administration Veterinary Oversight of Antimicrobial Use in Livestock... areas that may lack access to adequate veterinary services. The meetings are jointly sponsored by FDA...: Patricia Arnwine, Center for Veterinary Medicine (HFV-6), Food and Drug Administration, 7519 Standish...

  20. INVESTIGATION OF THE POTENTIAL ANTIMICROBIAL EFFICACY OF SEALANTS USED IN HVAC SYSTEMS

    EPA Science Inventory

    The paper gives results of an investigation of the potential antimicrobial efficacy of sealants used in heating, ventilation and air-conditioning systems. Recent experiments confirm field experience that duct cleaning alone may not provide adequate protection from regrowth of fu...

  1. Adequate antigen availability: a key issue for novel approaches to tumor vaccination and tumor immunotherapy.

    PubMed

    Accolla, Roberto S; Tosi, Giovanna

    2013-03-01

    A crucial parameter for activation of the anti-tumor immune response is an adequate antigen availability (AAA) defined here as the optimal tumor antigen dose and related antigen processing and MHC-II-restricted presentation necessary to efficiently trigger tumor-specific TH cells. We will discuss two distinct experimental systems: a) a preventive anti-tumor vaccination system; b) a therapy-induced anti-tumor vaccination approach. In the first case tumor cells are rendered constitutively MHC-II+ by transfecting them with the MHC-II transcriptional activator CIITA. Here AAA is generated by the function of tumor's newly expressed MHC-II molecules to present tumor-associated antigens to tumor-specific TH cells. In the second case, AAA is generated by treating established tumors with neovasculature-targeted TNFα. In conjuction with Melphalan, targeted TNFα delivery produces extensive areas of tumor necrosis that generate AAA capable of optimally activate tumor-specific TH cells which in turn activate CTL immune effectors. In both experimental systems tumor rejection and persistent and long-lived TH cell anti-tumor memory, responsible of defending the animals from subsequent challenges with tumor cells, are achieved. Based on these and other investigators' results we propose that AAA is a key element for triggering adaptive immune functions resulting in subversion from a pro-tumor to an anti-tumor microenvironment, tumor rejection and acquisition of anti-tumor immune memory. Hypotheses of neuro-immune networks involved in these approaches are discussed. These considerations are important also for the comprehension of how chemotherapy and/or radiation therapies may help to block and/or to eradicate the tumor and for the construction of suitable anti-tumor vaccine strategies.

  2. Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

    PubMed

    Sartelli, Massimo; Weber, Dieter G; Ruppé, Etienne; Bassetti, Matteo; Wright, Brian J; Ansaloni, Luca; Catena, Fausto; Coccolini, Federico; Abu-Zidan, Fikri M; Coimbra, Raul; Moore, Ernest E; Moore, Frederick A; Maier, Ronald V; De Waele, Jan J; Kirkpatrick, Andrew W; Griffiths, Ewen A; Eckmann, Christian; Brink, Adrian J; Mazuski, John E; May, Addison K; Sawyer, Rob G; Mertz, Dominik; Montravers, Philippe; Kumar, Anand; Roberts, Jason A; Vincent, Jean-Louis; Watkins, Richard R; Lowman, Warren; Spellberg, Brad; Abbott, Iain J; Adesunkanmi, Abdulrashid Kayode; Al-Dahir, Sara; Al-Hasan, Majdi N; Agresta, Ferdinando; Althani, Asma A; Ansari, Shamshul; Ansumana, Rashid; Augustin, Goran; Bala, Miklosh; Balogh, Zsolt J; Baraket, Oussama; Bhangu, Aneel; Beltrán, Marcelo A; Bernhard, Michael; Biffl, Walter L; Boermeester, Marja A; Brecher, Stephen M; Cherry-Bukowiec, Jill R; Buyne, Otmar R; Cainzos, Miguel A; Cairns, Kelly A; Camacho-Ortiz, Adrian; Chandy, Sujith J; Che Jusoh, Asri; Chichom-Mefire, Alain; Colijn, Caroline; Corcione, Francesco; Cui, Yunfeng; Curcio, Daniel; Delibegovic, Samir; Demetrashvili, Zaza; De Simone, Belinda; Dhingra, Sameer; Diaz, José J; Di Carlo, Isidoro; Dillip, Angel; Di Saverio, Salomone; Doyle, Michael P; Dorj, Gereltuya; Dogjani, Agron; Dupont, Hervé; Eachempati, Soumitra R; Enani, Mushira Abdulaziz; Egiev, Valery N; Elmangory, Mutasim M; Ferrada, Paula; Fitchett, Joseph R; Fraga, Gustavo P; Guessennd, Nathalie; Giamarellou, Helen; Ghnnam, Wagih; Gkiokas, George; Goldberg, Staphanie R; Gomes, Carlos Augusto; Gomi, Harumi; Guzmán-Blanco, Manuel; Haque, Mainul; Hansen, Sonja; Hecker, Andreas; Heizmann, Wolfgang R; Herzog, Torsten; Hodonou, Adrien Montcho; Hong, Suk-Kyung; Kafka-Ritsch, Reinhold; Kaplan, Lewis J; Kapoor, Garima; Karamarkovic, Aleksandar; Kees, Martin G; Kenig, Jakub; Kiguba, Ronald; Kim, Peter K; Kluger, Yoram; Khokha, Vladimir; Koike, Kaoru; Kok, Kenneth Y Y; Kong, Victory; Knox, Matthew C; Inaba, Kenji; Isik, Arda; Iskandar, Katia; Ivatury, Rao R; Labbate, Maurizio; Labricciosa, Francesco M; Laterre, Pierre-François; Latifi, Rifat; Lee, Jae Gil; Lee, Young Ran; Leone, Marc; Leppaniemi, Ari; Li, Yousheng; Liang, Stephen Y; Loho, Tonny; Maegele, Marc; Malama, Sydney; Marei, Hany E; Martin-Loeches, Ignacio; Marwah, Sanjay; Massele, Amos; McFarlane, Michael; Melo, Renato Bessa; Negoi, Ionut; Nicolau, David P; Nord, Carl Erik; Ofori-Asenso, Richard; Omari, AbdelKarim H; Ordonez, Carlos A; Ouadii, Mouaqit; Pereira Júnior, Gerson Alves; Piazza, Diego; Pupelis, Guntars; Rawson, Timothy Miles; Rems, Miran; Rizoli, Sandro; Rocha, Claudio; Sakakhushev, Boris; Sanchez-Garcia, Miguel; Sato, Norio; Segovia Lohse, Helmut A; Sganga, Gabriele; Siribumrungwong, Boonying; Shelat, Vishal G; Soreide, Kjetil; Soto, Rodolfo; Talving, Peep; Tilsed, Jonathan V; Timsit, Jean-Francois; Trueba, Gabriel; Trung, Ngo Tat; Ulrych, Jan; van Goor, Harry; Vereczkei, Andras; Vohra, Ravinder S; Wani, Imtiaz; Uhl, Waldemar; Xiao, Yonghong; Yuan, Kuo-Ching; Zachariah, Sanoop K; Zahar, Jean-Ralph; Zakrison, Tanya L; Corcione, Antonio; Melotti, Rita M; Viscoli, Claudio; Viale, Perluigi

    2016-01-01

    Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

  3. A Study of Utilization of Antimicrobial Agents in Patients on Ventilator in Intensive Care Unit (ICU) at Tertiary Care Teaching Hospital, India

    PubMed Central

    Gandhi, Anuradha M; Patel, Prakruti P

    2014-01-01

    Objective: To study the use of antimicrobial agents in patients on ventilator in ICU. Materials and Methods: Study was conducted at tertiary care teaching hospital Ahmedabad, India. Total 300 patients admitted in ICU and prescribed antimicrobial agents were included in the study. The data were recorded in preformed Case Record Form (CRF) and were analysed by Z and x2 Test. Results: Patients were divided into group A (patients on ventilator support) and group B (patients without ventilator support). In all the patients antimicrobial agents were prescribed empirically and more than two antimicrobial agents were prescribed in both groups. It was observed that above 60% antimicrobial agents were prescribed according to WHO, National and State Essential Medicine List (EML). Restricted antimicrobial agents (according to antimicrobial policy of tertiary care teaching hospital) were prescribed significantly (p<0.05) higher in group A as compared to group B. Resistance to antimicrobial agents by Pseudomonas aeruginosa and Kleibsella shown significantly (p<0.05) higher in group A as compared to group B. Change of antimicrobial therapy after Culture Sensitivity Test (CST) was significantly (p<0.05) higher in group A as compared to group B. Conclusion: Number of antimicrobial agents, antimicrobial resistance and change of antimicrobial therapy after CST were higher in patients on ventilator support. PMID:25584243

  4. Antimicrobial Resistance and Virulence Characterization among Escherichia coli Clinical Isolates Causing Severe Obstetric Infections in Pregnant Women

    PubMed Central

    Guiral, Elisabet; Sáez-López, Emma; Bosch, Jordi; Goncé, Anna; López, Marta; Sanz, Sergi; Vila, Jordi

    2015-01-01

    The virulence markers and the antimicrobial resistance profiles of 78 Escherichia coli isolates causing obstetric infections accompanied by sepsis or not were studied. Adhesion-related virulence factors were the most prevalent markers. Low rates of resistance to the antimicrobial agents used as first-line therapy suggest their correct implementation in stewardship guidelines. PMID:25740771

  5. Antimicrobial Resistance in Agriculture

    PubMed Central

    Thanner, Sophie; Drissner, David

    2016-01-01

    ABSTRACT In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans. PMID:27094336

  6. Substandard/Counterfeit Antimicrobial Drugs

    PubMed Central

    Kelesidis, Theodoros

    2015-01-01

    SUMMARY Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue. PMID:25788516

  7. Antimicrobial Peptides and Colitis

    PubMed Central

    Ho, Samantha; Pothoulakis, Charalabos; Koon, Hon Wai

    2013-01-01

    Antimicrobial peptides (AMPs) are important components of innate immunity. They are often expressed in response to colonic inflammation and infection. Over the last several years, the roles of several antimicrobial peptides have been explored. Gene expression of many AMPs (beta defensin HBD2-4 and cathelicidin) is induced in response to invasion of gut microbes into the mucosal barrier. Some AMPs are expressed in a constitutive manner (alpha defensin HD 5-6 and beta defensin HBD1), while others (defensin and bactericidal/permeability increasing protein BPI) are particularly associated with Inflammatory Bowel Disease (IBD) due to altered defensin expression or development of autoantibodies against Bactericidal/permeability increasing protein (BPI). Various AMPs have different spectrum and strength of antimicrobial effects. Some may play important roles in modulating the colitis (cathelicidin) while others (lactoferrin, hepcidin) may represent biomarkers of disease activity. The use of AMPs for therapeutic purposes is still at an early stage of development. A few natural AMPs were shown to be able to modulate colitis when delivered intravenously or intracolonically (cathelicidin, elafin and SLPI) in mouse colitis models. New AMPs (synthetic or artificial non-human peptides) are being developed and may represent new therapeutic approaches against colitis. This review discusses the latest research developments in the AMP field with emphasis in innate immunity and pathophysiology of colitis. PMID:22950497

  8. [Antimicrobial mechanisms of action].

    PubMed

    Calvo, Jorge; Martínez-Martínez, Luis

    2009-01-01

    A large number of families and groups of antimicrobial agents are of clinical interest. The mechanisms by which compounds with antibacterial activity inhibit growth or cause bacterial death are varied and depend on the affected targets. The bacterial cell wall-a unique structure in most bacteria that is absent in eukaryotic cells-can be affected in several ways: at different stages of synthesis (fosfomycin, cycloserine) or transport (bacitracin, mureidomycins) of its metabolic precursors, or by a direct action on its structural organization (beta-lactams, glycopeptides). The main drugs affecting the cytoplasmic membrane are polymyxins and daptomycin. Protein synthesis can be blocked by a large variety of compounds that affect any of the phases of this process, including activation (mupirocin), initiation (oxazolidinones, aminoglycosides), binding of the tRNA amino acid complex to ribosomes (tetracyclines, glycylcyclines) and elongation (amphenicols, lincosamides, macrolides, ketolides, streptogramins, fusidic acid). The metabolism of nucleic acids can be altered at the DNA-dependent RNA polymerase or in the process of DNA coiling (quinolones); some compounds affect DNA directly (nitroimidazoles, nitrofurans). Trimethoprim and sulfamides (often used in combination) are examples of antimicrobial agents that block bacterial metabolic pathways. Some compounds are unable to inhibit or kill bacteria in themselves, but can block bacterial mechanisms of resistance, enhancing the activity of other antimicrobials administered in combination. Among this group of agents, only certain beta-lactamase inhibitors are currently in clinical use.

  9. Photodynamic Antimicrobial Polymers for Infection Control

    PubMed Central

    McCoy, Colin P.; O’Neil, Edward J.; Cowley, John F.; Carson, Louise; De Baróid, Áine T.; Gdowski, Greg T.; Gorman, Sean P.; Jones, David S.

    2014-01-01

    Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm2 for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting. PMID:25250740

  10. Inappropriate use of antibiotics in hospitals: the complex relationship between antibiotic use and antimicrobial resistance.

    PubMed

    Cantón, Rafael; Horcajada, Juan Pablo; Oliver, Antonio; Garbajosa, Patricia Ruiz; Vila, Jordi

    2013-09-01

    Hospitals are considered an excellent compartment for the selection of resistant and multi-drug resistant (MDR) bacteria. The overuse and misuse of antimicrobial agents are considered key points fuelling this situation. Antimicrobial stewardship programs have been designed for better use of these compounds to prevent the emergence of resistant microorganisms and to diminish the upward trend in resistance. Nevertheless, the relationship between antibiotic use and antimicrobial resistance is complex, and the desired objectives are difficult to reach. Various factors affecting this relationship have been advocated including, among others, antibiotic exposure and mutant selection windows, antimicrobial pharmacodynamics, the nature of the resistance (natural or acquired, including mutational and that associated with horizontal gene transfer) and the definition of resistance. Moreover, antimicrobial policies to promote better use of these drugs should be implemented not only in the hospital setting coupled with infection control programs, but also in the community, which should also include animal and environmental compartments. Within hospitals, the restriction of antimicrobials, cycling and mixing strategies and the use of combination therapies have been used to avoid resistance. Nevertheless, the results have not always been favorable and resistant bacteria have persisted despite the theoretical benefits of these strategies. Mathematical models as well as microbiological knowledge can explain this failure, which is mainly related to the current scenario involving MDR bacteria and overcoming the fitness associated with resistance. New antimicrobials, rapid diagnostic and antimicrobial susceptibility testing and biomarkers will be useful for future antimicrobial stewardship interventions.

  11. Antimicrobial resistance in campylobacter: susceptibility testing methods and resistance trends.

    PubMed

    Ge, Beilei; Wang, Fei; Sjölund-Karlsson, Maria; McDermott, Patrick F

    2013-10-01

    Most Campylobacter infections are self-limiting but antimicrobial treatment (e.g., macrolides, fluoroquinolones) is necessary in severe or prolonged cases. Susceptibility testing continues to play a critical role in guiding therapy and epidemiological monitoring of resistance. The methods of choice for Campylobacter recommended by the Clinical and Laboratory Standards Institute (CLSI) are agar dilution and broth microdilution, while a disk diffusion method was recently standardized by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Macrolides, quinolones, and tetracyclines are among the common antimicrobials recommended for testing. Molecular determination of Campylobacter resistance via DNA sequencing or PCR-based methods has been performed. High levels of resistance to tetracycline and ciprofloxacin are frequently reported by many national surveillance programs, but resistance to erythromycin and gentamicin in Campylobacter jejuni remains low. Nonetheless, variations in susceptibility observed over time underscore the need for continued public health monitoring of Campylobacter resistance from humans, animals, and food.

  12. Antimicrobial Activity of Calcium Hydroxide in Endodontics: A Review

    PubMed Central

    Shalavi, S; Yazdizadeh, M

    2012-01-01

    The purpose of endodontic therapy is to preserve the patient's natural teeth without compromising the patient's local or systemic health. Calcium hydroxide has been included in several materials and antimicrobial formulations that are used in several treatment modalities in endodontics, such as inter-appointment intracanal medicaments. The purpose of this article was to review the antimicrobial properties of calcium hydroxide in endodontics. Calcium hydroxide has a high pH (approximately 12.5-12.8) and is classified chemically as a strong base. The lethal effects of calcium hydroxide on bacterial cells are probably due to protein denaturation and damage to DNA and cytoplasmic membranes. Calcium hydroxide has a wide range of antimicrobial activity against common endodontic pathogens but is less effective against Enterococcus faecalis and Candida albicans. Calcium hydroxide is also a valuable anti-endotoxin agent. However, its effect on microbial biofilms is controversial. PMID:23323217

  13. Antiendotoxin activity of cationic peptide antimicrobial agents.

    PubMed

    Gough, M; Hancock, R E; Kelly, N M

    1996-12-01

    The endotoxin from gram-negative bacteria consists of a molecule lipopolysaccharide (LPS) which can be shed by bacteria during antimicrobial therapy. A resulting syndrome, endotoxic shock, is a leading cause of death in the developed world. Thus, there is great interest in the development of antimicrobial agents which can reverse rather than promote sepsis, especially given the recent disappointing clinical performance of antiendotoxin therapies. We describe here two small cationic peptides, MBI-27 and MBI-28, which have both antiendotoxic and antibacterial activities in vitro and in vivo in animal models. We had previously demonstrated that these peptides bind to LPS with an affinity equivalent to that of polymyxin B. Consistent with this, the peptides blocked the ability of LPS and intact cells to induce the endotoxic shock mediator, tumor necrosis factor (TNF), upon incubation with the RAW 264.7 murine macrophage cell line. MBI-28 was equivalent to polymyxin B in its ability to block LPS induction of TNF by this cell line, even when added 60 min after the TNF stimulus. Furthermore, MBI-28 offered significant protection in a galactosamine-sensitized mouse model of lethal endotoxic shock. This protection correlated with the ability of MBI-28 to reduce LPS-induced circulating TNF by nearly 90% in this mouse model. Both MBI-27 and MBI-28 demonstrated antibacterial activity against gram-negative bacteria in vitro and in vivo against Pseudomonas aeruginosa infections in neutropenic mice.

  14. Antiendotoxin activity of cationic peptide antimicrobial agents.

    PubMed Central

    Gough, M; Hancock, R E; Kelly, N M

    1996-01-01

    The endotoxin from gram-negative bacteria consists of a molecule lipopolysaccharide (LPS) which can be shed by bacteria during antimicrobial therapy. A resulting syndrome, endotoxic shock, is a leading cause of death in the developed world. Thus, there is great interest in the development of antimicrobial agents which can reverse rather than promote sepsis, especially given the recent disappointing clinical performance of antiendotoxin therapies. We describe here two small cationic peptides, MBI-27 and MBI-28, which have both antiendotoxic and antibacterial activities in vitro and in vivo in animal models. We had previously demonstrated that these peptides bind to LPS with an affinity equivalent to that of polymyxin B. Consistent with this, the peptides blocked the ability of LPS and intact cells to induce the endotoxic shock mediator, tumor necrosis factor (TNF), upon incubation with the RAW 264.7 murine macrophage cell line. MBI-28 was equivalent to polymyxin B in its ability to block LPS induction of TNF by this cell line, even when added 60 min after the TNF stimulus. Furthermore, MBI-28 offered significant protection in a galactosamine-sensitized mouse model of lethal endotoxic shock. This protection correlated with the ability of MBI-28 to reduce LPS-induced circulating TNF by nearly 90% in this mouse model. Both MBI-27 and MBI-28 demonstrated antibacterial activity against gram-negative bacteria in vitro and in vivo against Pseudomonas aeruginosa infections in neutropenic mice. PMID:8945527

  15. Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention.

    PubMed

    Dela-Pena, Jennifer; Kerstenetzky, Luiza; Schulz, Lucas; Kendall, Ron; Lepak, Alexander; Fox, Barry

    2017-03-01

    OBJECTIVE To characterize the top 1% of inpatients who contributed to the 6-month antimicrobial budget in a tertiary, academic medical center and identify cost-effective intervention opportunities targeting high-cost antimicrobial utilization. DESIGN Retrospective cohort study. PATIENTS Top 1% of the antimicrobial budget from July 1 through December 31, 2014. METHODS Patients were identified through a pharmacy billing database. Baseline characteristics were collected through a retrospective medical chart review. Patients were presented to the antimicrobial stewardship team to determine appropriate utilization of high-cost antimicrobials and potential intervention opportunities. Appropriate use was defined as antimicrobial therapy that was effective, safe, and most cost-effective compared with alternative agents. RESULTS A total of 10,460 patients received antimicrobials in 6 months; 106 patients accounted for $889,543 (47.2%) of the antimicrobial budget with an antimicrobial cost per day of $219±$192 and antimicrobial cost per admission of $4,733±$7,614. Most patients were immunocompromised (75%) and were followed by the infectious disease consult service (80%). The most commonly prescribed antimicrobials for treatment were daptomycin, micafungin, liposomal amphotericin B, and meropenem. Posaconazole and valganciclovir accounted for most of the prophylactic therapy. Cost-effective opportunities (n=71) were present in 57 (54%) of 106 patients, which included dose optimization, de-escalation, dosage form conversion, and improvement in transitions of care. CONCLUSION Antimicrobial stewardship oversight is important in implementing cost-effective strategies, especially in complex and immunocompromised patients who require the use of high-cost antimicrobials. Infect Control Hosp Epidemiol 2017;38:259-265.

  16. Covering more Territory to Fight Resistance: Considering Nurses’ Role in Antimicrobial Stewardship

    PubMed Central

    Edwards, R; Drumright, LN; Kiernan, M; Holmes, A

    2011-01-01

    The potential contribution nurses can make to the management of antimicrobials within an in-patient setting could impact on the development of antimicrobial resistance (AMR) and healthcare associated infections (HCAIs). Current initiatives promoting prudent antimicrobial prescribing and management have generally failed to include nurses, which subsequently limits the extent to which these strategies can improve patient outcomes. For antimicrobial stewardship (AS) programmes to be successful, a sustained and seamless level of monitoring and decision making in relation to antimicrobial therapy is needed. As nurses have the most consistent presence as patient carer, they are in the ideal position to provide this level of service. However, for nurses to truly impact on AMR and HCAIs through increasing their profile in AS, barriers and facilitators to adopting this enhanced role must be contextualised in the implementation of any initiative. PMID:21532974

  17. Antimicrobial activity of biogenic silver nanoparticles, and silver chloride nanoparticles: an overview and comments.

    PubMed

    Durán, Nelson; Nakazato, Gerson; Seabra, Amedea B

    2016-08-01

    The antimicrobial impact of biogenic-synthesized silver-based nanoparticles has been the focus of increasing interest. As the antimicrobial activity of nanoparticles is highly dependent on their size and surface, the complete and adequate characterization of the nanoparticle is important. This review discusses the characterization and antimicrobial activity of biogenic synthesized silver nanoparticles and silver chloride nanoparticles. By revising the literature, there is confusion in the characterization of these two silver-based nanoparticles, which consequently affects the conclusion regarding to their antimicrobial activities. This review critically analyzes recent publications on the synthesis of biogenic silver nanoparticles and silver chloride nanoparticles by attempting to correlate the characterization of the nanoparticles with their antimicrobial activity. It was difficult to correlate the size of biogenic nanoparticles with their antimicrobial activity, since different techniques are employed for the characterization. Biogenic synthesized silver-based nanoparticles are not completely characterized, particularly the nature of capped proteins covering the nanomaterials. Moreover, the antimicrobial activity of theses nanoparticles is assayed by using different protocols and strains, which difficult the comparison among the published papers. It is important to select some bacteria as standards, by following international foundations (Pharmaceutical Microbiology Manual) and use the minimal inhibitory concentration by broth microdilution assays from Clinical and Laboratory Standards Institute, which is the most common assay used in antibiotic ones. Therefore, we conclude that to have relevant results on antimicrobial effects of biogenic silver-based nanoparticles, it is necessary to have a complete and adequate characterization of these nanostructures, followed by standard methodology in microbiology protocols.

  18. Case reports on the use of antimicrobial (silver impregnated) soft silicone foam dressing on infected diabetic foot ulcers.

    PubMed

    Tong, Jasper W K

    2009-08-01

    This article described four patients who had an episode of an infected foot ulcer, and subsequently treated with a novel antimicrobial soft silicone foam dressing together with standard off-loading and antibiotic therapy. Qualitative description of the ulcer-healing process was documented. All four ulcers showed positive wound contraction and reduction in size throughout the follow-up period ranging from 3 to 16 weeks. In addition, clinical signs of infection were absent at the end of the follow-up period. Moreover, surrounding skin maceration and trauma were absent in all wounds. Adequate moisture control was also achieved with the evidence of a healthy red granulating base, and a thin layer of clear light exudate in three out of the four cases. However, these reports had very little evidence to show the dressing's effectiveness in combating wound infection, but there might be some possible clinical efficacies of the dressing to control infection. Appropriate antibiotic therapy and off-loading are still essential components when treating diabetic foot infection.

  19. Bacillus clausii probiotic strains: antimicrobial and immunomodulatory activities.

    PubMed

    Urdaci, Maria C; Bressollier, Philippe; Pinchuk, Irina

    2004-07-01

    The clinical benefits observed with probiotic use are mainly attributed to the antimicrobial substances produced by probiotic strains and to their immunomodulatory effects. Currently, the best-documented probiotic bacteria used in human therapy are lactic acid bacteria. In contrast, studies aiming to characterize the mechanisms responsible for the probiotic beneficial effects of Bacillus are rare. The current work seeks to contribute to such characterization by evaluating the antimicrobial and immunomodulatory activities of probiotic B. clausii strains. B. clausii strains release antimicrobial substances in the medium. Moreover, the release of these antimicrobial substances was observed during stationary growth phase and coincided with sporulation. These substances were active against Gram-positive bacteria, in particular against Staphylococcus aureus, Enterococcus faecium, and Clostridium difficile. The antimicrobial activity was resistant to subtilisin, proteinase K, and chymotrypsin treatment, whereas it was sensitive to pronase treatment. The evaluation of the immunomodulatory properties of probiotic B. clausii strains was performed in vitro on Swiss and C57 Bl/6j murine cells. The authors demonstrate that these strains, in their vegetative forms, are able to induce NOS II synthetase activity, IFN-gamma production, and CD4 T-cell proliferation.

  20. Absorbent silver (I) antimicrobial fabrics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In recent years, silver in form of silver ions, has been gaining importance in the wound management as an effective broad-spectrum antimicrobial agent. Silver has a long history as an antimicrobial agent, especially in the treatment of wounds. Alginates and carboxymethyl (CM) cotton contain carboxyl...

  1. Engineering Antimicrobials Refractory to Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant superbugs are a persistent problem in modern health care, demonstrating the need for a new class of antimicrobials that can address this concern. Triple-acting peptidoglycan hydrolase fusions are a novel class of antimicrobials which have qualities well suited to avoiding resis...

  2. Use of Antimicrobials during Pregnancy

    PubMed Central

    Nicolle, L.E.

    1987-01-01

    The use of any drug during pregnancy is complicated by concerns of adverse effects, not only on the pregnant woman, but also on the fetus. This paper provides an overview of the use of antimicrobials in pregnancy, based on current knowledge of fetal development and on available documented experience. The author also discusses the use of specific antimicrobial agents during pregnancy. PMID:21263935

  3. Plant antimicrobial peptides.

    PubMed

    Nawrot, Robert; Barylski, Jakub; Nowicki, Grzegorz; Broniarczyk, Justyna; Buchwald, Waldemar; Goździcka-Józefiak, Anna

    2014-05-01

    Plant antimicrobial peptides (AMPs) are a component of barrier defense system of plants. They have been isolated from roots, seeds, flowers, stems, and leaves of a wide variety of species and have activities towards phytopathogens, as well as against bacteria pathogenic to humans. Thus, plant AMPs are considered as promising antibiotic compounds with important biotechnological applications. Plant AMPs are grouped into several families and share general features such as positive charge, the presence of disulfide bonds (which stabilize the structure), and the mechanism of action targeting outer membrane structures.

  4. Responsibilities of regulatory agencies in the marketing of antimicrobials.

    PubMed

    Grein, K

    2012-04-01

    The regulatory agencies' main responsibility regarding the marketing of veterinary medicinal products is to ensure that the products have a marketing authorisation with specific conditions of use adequate to ensure the quality, safety and efficacy of the product under consideration. In addition, control and surveillance systems are necessary to allow monitoring of the product after it has been authorised. In respectto antimicrobials, specific consideration must be given to minimising resistance development and retaining the effectiveness of these drugs for the treatment of humans and animals. Surveillance programmes should be in place to follow trends in resistance development, as well as in the consumption of veterinary antimicrobials, in order to provide for science-based policy recommendations regarding public and animal health.

  5. The Human Right to Adequate Housing: A Tool for Promoting and Protecting Individual and Community Health

    PubMed Central

    Thiele, Bret

    2002-01-01

    The human right to adequate housing is enshrined in international law. The right to adequate housing can be traced to the Universal Declaration of Human Rights, which was unanimously adopted by the world community in 1948. Since that time, the right to adequate housing has been reaffirmed on numerous occasions and further defined and elaborated. A key component of this right is habitability of housing, which should comply with health and safety standards. Therefore, the right to adequate housing provides an additional tool for advocates and others interested in promoting healthful housing and living conditions and thereby protecting individual and community health. PMID:11988432

  6. Antimicrobial dyes and mechanosensitive channels.

    PubMed

    Boulos, Ramiz A

    2013-08-01

    The search for new and effective antimicrobial agents has never been as important; however, since the discovery of antibiotics, exploring the antimicrobial activity of dyes has been forgotten. Antimicrobial dyes are an untapped resource and have the ability to potentially combat the spread of drug-resistant bacteria either alone or as antimicrobial adjuvants. The mechanosensitive ion channel of large conductance (MscL) is highly conserved and ubiquitous in bacterial species. There is evidence to suggest that at least one triphenylmethane dye acts through the highly conserved MscL channel and combining the two approaches of exploring the mechanism of action of other triphenylmethane dyes or antimicrobial dyes in general and the novel MscL target provides a new opportunity for further exploration.

  7. In-vitro activity of sparfloxacin in comparison with currently available antimicrobials against respiratory tract pathogens.

    PubMed

    Baquero, F; Cantón, R

    1996-05-01

    Bacterial resistance to antimicrobial agents is an ever-increasing problem. The in-vitro activity of sparfloxacin compared with that of currently available antimicrobial agents against pathogens implicated in respiratory tract infections is reviewed. Sparfloxacin is a fluoroquinolone active against both penicillin-susceptible and -resistant strains of Streptococcus pneumoniae. It is also active against many other respiratory tract pathogens and may be a suitable alternative for empirical therapy of community-acquired respiratory tract infections.

  8. Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile: Potential Consequences for Induction, Treatment, and Recurrence of C. difficile Infection

    PubMed Central

    Baines, Simon D.; Wilcox, Mark H.

    2015-01-01

    Clostridium difficile infection (CDI) remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments. PMID:27025625

  9. Survey of antimicrobial resistance in clinical Burkholderia pseudomallei isolates over two decades in Northeast Thailand.

    PubMed

    Wuthiekanun, Vanaporn; Amornchai, Premjit; Saiprom, Natnaree; Chantratita, Narisara; Chierakul, Wirongrong; Koh, Gavin C K W; Chaowagul, Wipada; Day, Nicholas P J; Limmathurotsakul, Direk; Peacock, Sharon J

    2011-11-01

    A 21-year survey conducted in northeast Thailand of antimicrobial resistance to parenteral antimicrobial drugs used to treat melioidosis identified 24/4,021 (0.6%) patients with one or more isolates resistant to ceftazidime (n = 8), amoxicillin-clavulanic acid (n = 4), or both drugs (n = 12). Two cases were identified at admission, and the remainder were detected a median of 15 days after starting antimicrobial therapy. Resistance to carbapenem drugs was not detected. These findings support the current prescribing recommendations for melioidosis.

  10. The Critical Role of the Staff Nurse in Antimicrobial Stewardship--Unrecognized, but Already There.

    PubMed

    Olans, Richard N; Olans, Rita D; DeMaria, Alfred

    2016-01-01

    An essential participant in antimicrobial stewardship who has been unrecognized and underutilized is the "staff nurse." Although the role of staff nurses has not formally been recognized in guidelines for implementing and operating antimicrobial stewardship programs (ASPs) or defined in the medical literature, they have always performed numerous functions that are integral to successful antimicrobial stewardship. Nurses are antibiotic first responders, central communicators, coordinators of care, as well as 24-hour monitors of patient status, safety, and response to antibiotic therapy. An operational analysis of inpatient admissions evaluates these nursing stewardship activities and analyzes the potential benefits of nurses' formal education about, and inclusion into, ASPs.

  11. Antimicrobial Mechanism of Monocaprylate

    PubMed Central

    Hyldgaard, Morten; Sutherland, Duncan S.; Sundh, Maria; Mygind, Tina

    2012-01-01

    Monoglyceride esters of fatty acids occur naturally and encompass a broad spectrum of antimicrobial activity. Monocaprylate is generally regarded as safe (GRAS) and can function both as an emulsifier and as a preservative in food. However, knowledge about its mode of action is lacking. The aim of this study was therefore to elucidate the mechanism behind monocaprylate's antimicrobial effect. The cause of cell death in Escherichia coli, Staphylococcus xylosus, and Zygosaccharomyces bailii was investigated by examining monocaprylate's effect on cell structure, membrane integrity, and its interaction with model membranes. Changes in cell structure were visible by atomic force microscopy (AFM), and propidium iodide staining showed membrane disruption, indicating the membrane as a site of action. This indication was confirmed by measuring calcein leakage from membrane vesicles exposed to monocaprylate. AFM imaging of supported lipid bilayers visualized the integration of monocaprylate into the liquid disordered, and not the solid ordered, phase of the membrane. The integration of monocaprylate was confirmed by quartz crystal microbalance measurements, showing an abrupt increase in mass and hydration of the membrane after exposure to monocaprylate above a threshold concentration. We hypothesize that monocaprylate destabilizes membranes by increasing membrane fluidity and the number of phase boundary defects. The sensitivity of cells to monocaprylate will therefore depend on the lipid composition, fluidity, and curvature of the membrane. PMID:22344642

  12. Antimicrobial mechanism of monocaprylate.

    PubMed

    Hyldgaard, Morten; Sutherland, Duncan S; Sundh, Maria; Mygind, Tina; Meyer, Rikke Louise

    2012-04-01

    Monoglyceride esters of fatty acids occur naturally and encompass a broad spectrum of antimicrobial activity. Monocaprylate is generally regarded as safe (GRAS) and can function both as an emulsifier and as a preservative in food. However, knowledge about its mode of action is lacking. The aim of this study was therefore to elucidate the mechanism behind monocaprylate's antimicrobial effect. The cause of cell death in Escherichia coli, Staphylococcus xylosus, and Zygosaccharomyces bailii was investigated by examining monocaprylate's effect on cell structure, membrane integrity, and its interaction with model membranes. Changes in cell structure were visible by atomic force microscopy (AFM), and propidium iodide staining showed membrane disruption, indicating the membrane as a site of action. This indication was confirmed by measuring calcein leakage from membrane vesicles exposed to monocaprylate. AFM imaging of supported lipid bilayers visualized the integration of monocaprylate into the liquid disordered, and not the solid ordered, phase of the membrane. The integration of monocaprylate was confirmed by quartz crystal microbalance measurements, showing an abrupt increase in mass and hydration of the membrane after exposure to monocaprylate above a threshold concentration. We hypothesize that monocaprylate destabilizes membranes by increasing membrane fluidity and the number of phase boundary defects. The sensitivity of cells to monocaprylate will therefore depend on the lipid composition, fluidity, and curvature of the membrane.

  13. Genome-Wide Identification of Antimicrobial Intrinsic Resistance Determinants in Staphylococcus aureus

    PubMed Central

    Leng, Bingfeng; Haaber, Jakob; Bojer, Martin S.; Vegge, Christina S.; Ingmer, Hanne

    2016-01-01

    The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired resistance has received considerable attention, relatively little is known of intrinsic resistance that allows bacteria to naturally withstand antimicrobials. Gene products that confer intrinsic resistance to antimicrobial agents may be explored for alternative antimicrobial therapies, by potentiating the efficacy of existing antimicrobials. In this study, we identified the intrinsic resistome to a broad spectrum of antimicrobials in the human pathogen, Staphylococcus aureus. We screened the Nebraska Transposon Mutant Library of 1920 single-gene inactivations in S. aureus strain JE2, for increased susceptibility to the anti-staphylococcal antimicrobials (ciprofloxacin, oxacillin, linezolid, fosfomycin, daptomycin, mupirocin, vancomycin, and gentamicin). Sixty-eight mutants were confirmed by E-test to display at least twofold increased susceptibility to one or more antimicrobial agents. The majority of the identified genes have not previously been associated with antimicrobial susceptibility in S. aureus. For example, inactivation of genes encoding for subunits of the ATP synthase, atpA, atpB, atpG and atpH, reduced the minimum inhibitory concentration (MIC) of gentamicin 16-fold. To elucidate the potential of the screen, we examined treatment efficacy in the Galleria mellonella infection model. Gentamicin efficacy was significantly improved, when treating larvae infected with the atpA mutant compared to wild type cells with gentamicin at a clinically relevant concentration. Our results demonstrate that many gene products contribute to the intrinsic antimicrobial resistance of S. aureus. Knowledge of these intrinsic resistance determinants provides alternative targets for compounds that may potentiate the efficacy of existing antimicrobial agents against this important pathogen. PMID:28066345

  14. Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945 to 2014 Identified Through a Systematic Literature Review.

    PubMed

    Pillai, Satish K; Huang, Eileen; Guarnizo, Julie T; Hoyle, Jamechia D; Katharios-Lanwermeyer, Stefan; Turski, Theresa K; Bower, William A; Hendricks, Katherine A; Meaney-Delman, Dana

    2015-01-01

    Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of 2 weeks, bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax, and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English-language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. A total of 149 cases of systemic anthrax were identified. Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n = 77), survival was greater for those receiving 3 or more antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe anthrax disease, particularly anthrax meningitis, in a mass casualty incident.

  15. Antimicrobial Treatment for Systemic Anthrax: Analysis of Cases from 1945–2014 Identified through Systematic Literature Review

    PubMed Central

    Pillai, Satish K.; Huang, Eileen; Guarnizo, Julie; Hoyle, Jamechia; Katharios-Lanwermeyer, Stefan; Turski, Theresa; Bower, William; Hendricks, Katherine; Meaney-Delman, Dana

    2015-01-01

    Background Systemic anthrax is associated with high mortality. Current national guidelines, developed for the individualized treatment of systemic anthrax, outline the use of combination intravenous antimicrobials for a minimum of two weeks; bactericidal and protein synthesis inhibitor antimicrobials for all cases of systemic anthrax; and at least 3 antimicrobials with good blood-brain barrier penetration for anthrax meningitis. However, in an anthrax mass casualty incident, large numbers of anthrax cases may create challenges in meeting antimicrobial needs. Methods To further inform our understanding of the role of antimicrobials in treating systemic anthrax, a systematic review of the English language literature was conducted to identify cases of systemic anthrax treated with antimicrobials for which a clinical outcome was recorded. Results A total of 149 cases of systemic anthrax were identified (cutaneous [n=59], gastrointestinal [n=28], inhalation [n=26], primary anthrax meningitis [n=19], multiple routes [n=9], and injection [n=8]). Among the identified 59 cases of cutaneous anthrax, 33 were complicated by meningitis (76% mortality), while 26 simply had evidence of the systemic inflammatory response syndrome (4% mortality); 21 of 26 (81%) of this latter group received monotherapy. Subsequent analysis regarding combination antimicrobial therapy was restricted to the remaining 123 cases of more severe anthrax (overall 67% mortality). Recipients of combination bactericidal and protein synthesis inhibitor therapy had a 45% survival versus 28% in the absence of combination therapy (p = 0.07). For meningitis cases (n=77), survival was greater for those receiving a total of ≥3 antimicrobials over the course of treatment (3 of 4; 75%), compared to receipt of 1 or 2 antimicrobials (12 of 73; 16%) (p = 0.02). Median parenteral antimicrobial duration was 14 days. Conclusion Combination bactericidal and protein synthesis inhibitor therapy may be appropriate in severe

  16. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT... and Adequate Veterinary Care § 2.40 Attending veterinarian and adequate veterinary care (dealers and... veterinary care to its animals in compliance with this section. (1) Each dealer and exhibitor shall employ...

  17. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... veterinary care. 2.33 Section 2.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... adequate veterinary care. (a) Each research facility shall have an attending veterinarian who shall provide adequate veterinary care to its animals in compliance with this section: (1) Each research facility...

  18. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Exemptions for pesticides adequately... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The...

  19. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Exemptions for pesticides adequately... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The...

  20. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Exemptions for pesticides adequately... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The...

  1. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Exemptions for pesticides adequately... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The...

  2. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Exemptions for pesticides adequately... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The...

  3. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Adequate financial records, statistical data, and....568 Adequate financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination...

  4. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Adequate financial records, statistical data, and....568 Adequate financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination...

  5. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Adequate financial records, statistical data, and....568 Adequate financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination...

  6. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Assurances of adequate capacity and services. 438... Improvement Access Standards § 438.207 Assurances of adequate capacity and services. (a) Basic rule. The State... provides supporting documentation that demonstrates that it has the capacity to serve the...

  7. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Assurances of adequate capacity and services. 438... Improvement Access Standards § 438.207 Assurances of adequate capacity and services. (a) Basic rule. The State... provides supporting documentation that demonstrates that it has the capacity to serve the...

  8. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Assurances of adequate capacity and services. 438... Improvement Access Standards § 438.207 Assurances of adequate capacity and services. (a) Basic rule. The State... provides supporting documentation that demonstrates that it has the capacity to serve the...

  9. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Assurances of adequate capacity and services. 438... Improvement Access Standards § 438.207 Assurances of adequate capacity and services. (a) Basic rule. The State... provides supporting documentation that demonstrates that it has the capacity to serve the...

  10. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian and adequate veterinary care. (a) Each research facility shall have an attending veterinarian who shall provide adequate veterinary care to its animals in compliance with this section: (1) Each research facility...

  11. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian and adequate veterinary care. (a) Each research facility shall have an attending veterinarian who shall provide adequate veterinary care to its animals in compliance with this section: (1) Each research facility...

  12. The efficacy of different anti-microbial metals at preventing the formation of, and eradicating bacterial biofilms of pathogenic indicator strains.

    PubMed

    Gugala, Natalie; Lemire, Joe A; Turner, Raymond J

    2017-02-15

    The emergence of multidrug-resistant pathogens and the prevalence of biofilm-related infections have generated a demand for alternative anti-microbial therapies. Metals have not been explored in adequate detail for their capacity to combat infectious disease. Metal compounds can now be found in textiles, medical devices and disinfectants-yet, we know little about their efficacy against specific pathogens. To help fill this knowledge gap, we report on the anti-microbial and antibiofilm activity of seven metals: silver, copper, titanium, gallium, nickel, aluminum and zinc against three bacterial strains, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. To evaluate the capacity of metal ions to prevent the growth of, and eradicate biofilms and planktonic cells, bacterial cultures were inoculated in the Calgary Biofilm Device (minimal biofilm eradication concentration) in the presence of the metal salts. Copper, gallium and titanium were capable of preventing planktonic and biofilm growth, and eradicating established biofilms of all tested strains. Further, we observed that the efficacies of the other tested metal salts displayed variable efficacy against the tested strains. Further, contrary to the enhanced resistance anticipated from bacterial biofilms, particular metal salts were observed to be more effective against biofilm communities versus planktonic cells. In this study, we have demonstrated that the identity of the bacterial strain must be considered before treatment with a particular metal ion. Consequent to the use of metal ions as anti-microbial agents to fight multidrug-resistant and biofilm-related infections increases, we must aim for more selective deployment in a given infectious setting.The Journal of Antibiotics advance online publication, 15 February 2017; doi:10.1038/ja.2017.10.

  13. 45 CFR 1159.15 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... of maintaining adequate technical, physical, and security safeguards to prevent...

  14. 45 CFR 1159.15 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... of maintaining adequate technical, physical, and security safeguards to prevent...

  15. Novel Formulations for Antimicrobial Peptides

    PubMed Central

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  16. Novel formulations for antimicrobial peptides.

    PubMed

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2014-10-09

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  17. Contemporary treatment of heart failure: is there adequate evidence to support a unique strategy for African-Americans? Con position.

    PubMed

    Ferdinand, Keith C; Serrano, Claudia C; Ferdinand, Daphne P

    2002-08-01

    Heart failure is a substantial cause of increased morbidity and mortality in the African-American population, with poorer prognosis versus white patients. Systolic heart failure is predominantly caused by poorly controlled hypertension in African-Americans. Overall, African-Americans remain underrepresented in morbidity and mortality heart failure trials, and further data are needed to confirm the potential benefit of present therapies and newer approaches to heart failure in African-Americans. Intensive blood pressure control and control of other risk factors, along with the appropriate application of evidence-based therapies including angiotensin converting enzyme (ACE) inhibitors and approved beta-blockers, are required to decrease racial disparities. Although some data suggest that contemporary treatment with ACE inhibitors and beta-blockers may be less effective in African-Americans in terms of reducing heart failure morbidity and mortality, there is not adequate evidence to support a unique strategy for this population. The use of evidence-based therapies should be equally applied to African-Americans as well as to other ethnic groups while awaiting further studies.

  18. New vessel formation in the context of cardiomyocyte regeneration--the role and importance of an adequate perfusing vasculature.

    PubMed

    Michelis, Katherine C; Boehm, Manfred; Kovacic, Jason C

    2014-11-01

    The history of revascularization for cardiac ischemia dates back to the early 1960's when the first coronary artery bypass graft procedures were performed in humans. With this 50 year history of providing a new vasculature to ischemic and hibernating myocardium, a profound depth of experience has been amassed in clinical cardiovascular medicine as to what does, and does not work in the context of cardiac revascularization, alleviating ischemia and adequacy of myocardial perfusion. These issues are of central relevance to contemporary cell-based cardiac regenerative approaches. While the cardiovascular cell therapy field is surging forward on many exciting fronts, several well accepted clinical axioms related to the cardiac arterial supply appear to be almost overlooked by some of our current basic conceptual and experimental cell therapy paradigms. We present here information drawn from five decades of the clinical revascularization experience, review relevant new data on vascular formation via cell therapy, and put forward the case that for optimal cell-based cardiac regeneration due attention must be paid to providing an adequate vascular supply.

  19. New vessel formation in the context of cardiomyocyte regeneration – the role and importance of an adequate perfusing vasculature

    PubMed Central

    Michelis, Katherine C.; Boehm, Manfred; Kovacic, Jason C.

    2014-01-01

    The history of revascularization for cardiac ischemia dates back to the early 1960's when the first coronary artery bypass graft procedures were performed in humans. With this 50 year history of providing a new vasculature to ischemic and hibernating myocardium, a profound depth of experience has been amassed in clinical cardiovascular medicine as to what does, and does not work in the context of cardiac revascularization, alleviating ischemia and adequacy of myocardial perfusion. These issues are of central relevance to contemporary cell-based cardiac regenerative approaches. While the cardiovascular cell therapy field is surging forward on many exciting fronts, several well accepted clinical axioms related to the cardiac arterial supply appear to be almost overlooked by some of our current basic conceptual and experimental cell therapy paradigms. We present here information drawn from five decades of the clinical revascularization experience, review relevant new data on vascular formation via cell therapy, and put forward the case that for optimal cell-based cardiac regeneration due attention must be paid to providing an adequate vascular supply. PMID:24841067

  20. Evaluation of the antimicrobial activity and dimensional alterations of alginate impression disinfectants.

    PubMed

    Semensato, Ana Paula Nocentini; Crosariol, Sonia Khouri; Marchini, Leonardo

    2009-09-01

    This paper offers a quantitative evaluation of the antimicrobial efficacy of eight different disinfection procedures for irreversible hydrocolloid impressions and the dimensional changes induced by them. Samples were collected immediately after impressions, after the disinfection procedures and over casts and analyzed for bacterial growth. Control, enzyme solutions, acetic acid and ultraviolet irradiation samples showed bacterial growth. Chlorhexidine and 1% sodium hypochlorite presented adequate antimicrobial activity, while 2% sodium hypochlorite solution showed the best results. Dimensional changes were similar to those of the controls in all the tested agents. The results indicated 2% hypochlorite was the most appropriate disinfectant tested.

  1. Antimicrobial peptides: therapeutic potentials.

    PubMed

    Kang, Su-Jin; Park, Sung Jean; Mishig-Ochir, Tsogbadrakh; Lee, Bong-Jin

    2014-12-01

    The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.

  2. Optimization of pharmacotherapy in chronic heart failure: is heart rate adequately addressed?

    PubMed

    Franke, Jennifer; Wolter, Jan Sebastian; Meme, Lillian; Keppler, Jeannette; Tschierschke, Ramon; Katus, Hugo A; Zugck, Christian

    2013-01-01

    bpm (p <0.01). Likewise, comparing the groups ≥75 and <75 bpm, the primary endpoint was significantly increased in the group of patients with heart rates ≥75 bpm 27 vs. 12.2 %; p < 0.01). 5-year event-free survival was significantly lower among patients with heart rates ≥70 bpm as compared to those with <70 bpm (log-rank test p < 0.05) and among patients in the ≥75 bpm group versus <75 bpm group (log-rank test p < 0.01). In conclusion, in clinical practice, 53 % of CHF patients have inadequate heart rate control (heart rates ≥75 bpm) despite concomitant beta-blocker therapy. In this non-randomized cohort, adequate heart rate control under individually optimized beta-blocker therapy was associated with improved mid- and long-term clinical outcome up to 5 years. As further up titration of beta-blockers is not achievable in many patients, the administration of a selective heart rate lowering agent, such as ivabradine adjuvant to beta-blockers may pose an opportunity to further modulate outcome.

  3. Targeted anti bacterial therapy.

    PubMed

    Yacoby, Iftach; Benhar, Itai

    2007-09-01

    The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus necessitating a strong need to develop new antimicrobial agents. These new antimicrobials should possess novel modes of action and/or different cellular targets compared with the existing antibiotics. As a result, new classes of compounds designed to avoid defined resistance mechanisms are undergoing pre clinical and clinical evaluation. Microbial and phage genomic sequencing are now being used to find previously unidentified genes and their corresponding proteins. In both traditional and newly developed antibiotics, the target selectivity lies in the drug itself, in its ability to affect a mechanism that is unique to prokaryotes. As a result, a vast number of potent agents that, due to low selectivity, in addition to the pathogen also affect the eukaryote host have been excluded from use as therapeutics. Such compounds could be re-considered for clinical use if applied as part of a targeted delivery platform where the drug selectivity is replaced by target-selectivity borne by the targeting moiety. With a large number of antibodies and antibody-drug conjugates already approved or near approval as cancer therapeutics, targeted therapy is becoming increasingly attractive and additional potential targeting moieties that are non-antibody based, such as peptides, non-antibody ligand-binding proteins and even carbohydrates are receiving increasing attention. Still, targeted therapy is mostly focused on cancer, with targeted anti bacterial therapies being suggested only very recently. This review will focus in the various methods of antimicrobial targeting, by systemic and local application of targeted antimicrobial substances.

  4. Herd-level association between antimicrobial use and antimicrobial resistance in bovine mastitis Staphylococcus aureus isolates on Canadian dairy farms.

    PubMed

    Saini, V; McClure, J T; Scholl, D T; DeVries, T J; Barkema, H W

    2012-04-01

    Surveillance of antimicrobial use and resistance is needed to manage antimicrobial resistance in bacteria. In this study, data were collected on antimicrobial use and resistance in Staphylococcus aureus (n=562), isolated from intramammary infections and (sub)clinical mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and the Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Dairy producers were asked to deposit empty drug containers into specially provided receptacles, and antimicrobial drug use rate was calculated to quantify antimicrobial use. Minimum inhibitory concentrations were determined using the Sensititer bovine mastitis plate system (TREK Diagnostic Systems Inc., Cleveland, OH), containing antimicrobials commonly used for mastitis treatment and control. Multivariable logistic regression models were built to determine herd-level risk factors of penicillin, ampicillin, pirlimycin, penicillin-novobiocin combination, tetracycline and sulfadimethoxine resistance in Staph. aureus isolates. Intramammary administration of the penicillin-novobiocin combination for dry cow therapy was associated with penicillin and ampicillin resistance [odds ratio (OR): 2.17 and 3.10, respectively]. Systemic administration of penicillin was associated with penicillin resistance (OR: 1.63). Intramammary administration of pirlimycin for lactating cow mastitis treatment was associated with pirlimycin resistance as well (OR: 2.07). Average herd parity was associated with ampicillin and tetracycline resistance (OR: 3.88 and 0.02, respectively). Average herd size was also associated with tetracycline resistance (OR: 1.02). Dairy herds in the Maritime region had higher odds of penicillin and lower odds of ampicillin resistance than dairy herds in Québec (OR: 2.18 and 0.19, respectively). Alberta dairy herds had lower odds of ampicillin and sulfadimethoxine resistance than dairy herds in Québec (OR: 0.04 and 0.08, respectively

  5. Topical Antimicrobials for Burn Infections – An Update

    PubMed Central

    Sevgi, Mert; Toklu, Ani; Vecchio, Daniela; Hamblin, Michael R

    2014-01-01

    The relentless rise in antibiotic resistance among pathogenic bacteria and fungi, coupled with the high susceptibility of burn wounds to infection, and the difficulty of systemically administered antibiotics to reach damaged tissue, taken together have made the development of novel topical antimicrobials for burn infections a fertile area of innovation for researchers and companies. We previously covered the existing patent literature in this area in 2010, but the notable progress made since then, has highlighted the need for an update to bring the reader up to date on recent developments. New patents in the areas of topically applied antibiotics and agents that can potentiate the action of existing antibiotics may extend their useful lifetime. Developments have also been made in biofilm-disrupting agents. Antimicrobial peptides are nature’s way for many life forms to defend themselves against attack by pathogens. Silver has long been known to be a highly active antimicrobial but new inorganic metal derivatives based on bismuth, copper and gallium have emerged. Halogens such as chlorine and iodine can be delivered by novel technologies. A variety of topically applied antimicrobials include chitosan preparations, usnic acid, ceragenins and XF porphyrins. Natural product derived antimicrobials such as tannins and essential oils have also been studied. Novel techniques to deliver reactive oxygen species and nitric oxide in situ have been developed. Light-mediated techniques include photodynamic therapy, ultraviolet irradiation, blue light, low-level laser therapy and titania photocatalysis. Passive immunotherapy employs antibodies against pathogens and their virulence factors. Finally an interesting new area uses therapeutic microorganisms such as phages, probiotic bacteria and protozoa to combat infections. PMID:24215506

  6. Clinical translation of polymyxin-based combination therapy: Facts, challenges and future opportunities.

    PubMed

    Zhang, Xueli; Guo, Fengmei; Shao, Hua; Zheng, Xiao

    2017-02-01

    The emergence and spread of multidrug resistant Gram-negative bacteria has led to a resurgence in the clinical use of polymyxin antibiotics. However, the prevalence of polymyxin resistance is on the rise at an alarming rate, motivating the idea of combination therapy to sustain the revival of these "old" antibiotics. Although ample evidence in favor of combination therapy has emerged, it seems impracticable and confusing to find a promising combination from the diverse reports or gain adequate information on the efficacy and safety profile. With a stagnating discovery pipeline of novel antimicrobials, there is a clear need to fill the knowledge gaps in translating these basic research data to beneficial clinical practice. In this review, we examined the factors and ambiguities that stand as major hurdles in bringing polymyxin combination therapy to bedside care, highlighting the importance and urgency of incorporating translational research insights into areas of difficulty. We also discussed future research priorities that are essential to gather the necessary evidence and insights for promoting the best possible use of polymyxins in combination therapy.

  7. Antimicrobial Pesticide Use Site Index

    EPA Pesticide Factsheets

    This Use Site Index provides guidance to assist applicants for antimicrobial pesticide registration by helping them identify the data requirements necessary to register a pesticide or support their product registrations.

  8. Antimicrobial seafood packaging: a review.

    PubMed

    Singh, Suman; Ho Lee, Myung; Park, Lnsik; Shin, Yangjai; Lee, Youn Suk

    2016-06-01

    Microorganisms are the major cause of spoilage in most seafood products; however, only few microbes, called the specific spoilage organisms (SSOs), contribute to the offensive off-flavors associated with seafood spoilage. In food, microbial degradation manifests itself as spoilage, or changes in the sensory properties of a food product, rendering it unsuitable for human consumption. The use of antimicrobial substances can control the general microflora as well as specific microorganisms related to spoilage to provide products with higher safety and better quality. Many antimicrobial compounds have been evaluated in film structures for use in seafood, especially organic acids and their salts, enzymes, bacteriocins; some studies have considered inorganic compounds such as AgSiO2, zinc oxide, silver zeolite, and titanium oxide. The characteristics of some organic antimicrobial packaging systems for seafood and their antimicrobial efficiency in film structures are reviewed in this article.

  9. Antimicrobial peptides: properties and applicability.

    PubMed

    van 't Hof, W; Veerman, E C; Helmerhorst, E J; Amerongen, A V

    2001-04-01

    All organisms need protection against microorganisms, e. g. bacteria, viruses and fungi. For many years, attention has been focused on adaptive immunity as the main antimicrobial defense system. However, the adaptive immune system, with its network of humoral and cellular responses is only found in higher animals, while innate immunity is encountered in all living creatures. The turning point in the appreciation of the innate immunity was the discovery of antimicrobial peptides in the early eighties. In general these peptides act by disrupting the structural integrity of the microbial membranes. It has become clear that membrane-active peptides and proteins play a crucial role in both the innate and the adaptive immune system as antimicrobial agents. This review is focused on the functional and structural features of the naturally occurring antimicrobial peptides, and discusses their potential as therapeutics.

  10. Automation of antimicrobial activity screening.

    PubMed

    Forry, Samuel P; Madonna, Megan C; López-Pérez, Daneli; Lin, Nancy J; Pasco, Madeleine D

    2016-03-01

    Manual and automated methods were compared for routine screening of compounds for antimicrobial activity. Automation generally accelerated assays and required less user intervention while producing comparable results. Automated protocols were validated for planktonic, biofilm, and agar cultures of the oral microbe Streptococcus mutans that is commonly associated with tooth decay. Toxicity assays for the known antimicrobial compound cetylpyridinium chloride (CPC) were validated against planktonic, biofilm forming, and 24 h biofilm culture conditions, and several commonly reported toxicity/antimicrobial activity measures were evaluated: the 50 % inhibitory concentration (IC50), the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC). Using automated methods, three halide salts of cetylpyridinium (CPC, CPB, CPI) were rapidly screened with no detectable effect of the counter ion on antimicrobial activity.

  11. Inferential Processing among Adequate and Struggling Adolescent Comprehenders and Relations to Reading Comprehension

    PubMed Central

    Barth, Amy E.; Barnes, Marcia; Francis, David J.; Vaughn, Sharon; York, Mary

    2015-01-01

    Separate mixed model analyses of variance (ANOVA) were conducted to examine the effect of textual distance on the accuracy and speed of text consistency judgments among adequate and struggling comprehenders across grades 6–12 (n = 1203). Multiple regressions examined whether accuracy in text consistency judgments uniquely accounted for variance in comprehension. Results suggest that there is considerable growth across the middle and high school years, particularly for adequate comprehenders in those text integration processes that maintain local coherence. Accuracy in text consistency judgments accounted for significant unique variance for passage-level, but not sentence-level comprehension, particularly for adequate comprehenders. PMID:26166946

  12. Using Multitheory Model of Health Behavior Change to Predict Adequate Sleep Behavior.

    PubMed

    Knowlden, Adam P; Sharma, Manoj; Nahar, Vinayak K

    The purpose of this article was to use the multitheory model of health behavior change in predicting adequate sleep behavior in college students. A valid and reliable survey was administered in a cross-sectional design (n = 151). For initiation of adequate sleep behavior, the construct of behavioral confidence (P < .001) was found to be significant and accounted for 24.4% of the variance. For sustenance of adequate sleep behavior, changes in social environment (P < .02), emotional transformation (P < .001), and practice for change (P < .001) were significant and accounted for 34.2% of the variance.

  13. In Vitro Evaluation of Nanoscale Hydroxyapatite-Based Bone Reconstructive Materials with Antimicrobial Properties.

    PubMed

    Ajduković, Zorica R; Mihajilov-Krstev, Tatjana M; Ignjatović, Nenad L; Stojanović, Zoran; Mladenović-Antić, Snezana B; Kocić, Branislava D; Najman, Stevo; Petrović, Nenad D; Uskoković, Dragan P

    2016-02-01

    In the field of oral implantology the loss of bone tissue prevents adequate patient care, and calls for the use of synthetic biomaterials with properties that resemble natural bone. Special attention is paid to the risk of infection after the implantation of these materials. Studies have suggested that some nanocontructs containing metal ions have antimicrobial properties. The aim of this study was to examine the antimicrobial and hemolytic activity of cobalt-substituted hydroxyapatite nanoparticles, compared to hydroxyapatite and hydroxyapatite/poly-lactide-co-glycolide. The antibacterial effects of these powders were tested against two pathogenic bacterial strains: Escherichia coi (ATCC 25922) and Staphylococcus aureus (ATCC 25923), using the disc diffusion method and the quantitative antimicrobial test in a liquid medium. The quantitative antimicrobial test showed that all of the tested biomaterials have some antibacterial properties. The effects of both tests were more prominent in case of S. aureus than in E coli. A higher percentage of cobalt in the crystal structure of cobalt-substituted hydroxyapatite nanoparticles led to an increased antimicrobial activity. All of the presented biomaterial samples were found to be non-hemolytic. Having in mind that the tested of cobalt-substituted hydroxyapatite (Ca/Co-HAp) material in given concentrations shows good hemocompatibility and antimicrobial effects, along with its previously studied biological properties, the conclusion can be reached that it is a potential candidate that could substitute calcium hydroxyapatite as the material of choice for use in bone tissue engineering and clinical practices in orthopedic, oral and maxillofacial surgery.

  14. Recombinant probiotics with antimicrobial peptides: a dual strategy to improve immune response in immunocompromised patients.

    PubMed

    Mandal, Santi M; Silva, Osmar N; Franco, Octavio L

    2014-08-01

    Bacterial infectious diseases are currently a serious health problem, especially in patients compromised by illness or those receiving immune-suppressant drugs. In this context, it is not only essential to improve the understanding of infectious mechanisms and host response but also to discover novel therapies with extreme urgency. Probiotics and antimicrobial peptides are also favorably viewed as novel strategies in the control of resistant bacteria. The present review will shed some light on the use of probiotic microorganisms expressing antimicrobial peptides as a dual therapy to control bacterial infectious diseases.

  15. Antimicrobial resistance in Escherichia coli O157 and non-O157 isolated from feces of domestic farm animals in Culiacan, Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance in E. coli O157 and non-O157 strains is a matter of increasing concern, and the association with some virulence traits in the same bacteria remains unclear. Inappropriate antimicrobial use in human and animal therapy has been associated with selective pressure in enteric mi...

  16. Antimicrobial resistance in Escherichia coli O157 and non-O157 recovered from feces of domestic farm animals in Northwestern Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance in Shiga toxin-producing Escherichia coli (STEC) O157 and non-O157 is a matter of increasing concern. Inappropriate antimicrobial use in human and animal therapy has been associated with an acquired resistance in enteric microorganisms. The aim of the present study was to de...

  17. Region 8: Colorado Lamar and Steamboat Springs Adequate Letter (11/12/2002)

    EPA Pesticide Factsheets

    This letter from EPA to Colorado Department of Public Health and Environment determined Lamar and Steamboat Springs particulate matter (PM10) maintenance plan for Motor Vehicle Emissions Budgets adequate for transportation conformity purposes

  18. 75 FR 5893 - Suspension of Community Eligibility for Failure To Maintain Adequate Floodplain Management...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... To Maintain Adequate Floodplain Management Regulations AGENCY: Federal Emergency Management Agency... floodplain management regulations meeting minimum requirements under the National Flood Insurance Program... they have brought their floodplain management regulations into compliance with the NFIP...

  19. Region 9: California Adequate / Inadequate Letter Attachment (5/30/2008)

    EPA Pesticide Factsheets

    This is a document that states that it has been found adequate for transportation conformitypurposes certain 8-hour ozone and PM2.5 motor vehicleemissions budgets in the 2007 South Coast StateImplementation Plan.

  20. Planning 4-Dimensional Computed Tomography (4DCT) Cannot Adequately Represent Daily Intrafractional Motion of Abdominal Tumors

    SciTech Connect

    Ge, Jiajia; Santanam, Lakshmi; Noel, Camille; Parikh, Parag J.

    2013-03-15

    Purpose: To evaluate whether planning 4-dimensional computed tomography (4DCT) can adequately represent daily motion of abdominal tumors in regularly fractionated and stereotactic body radiation therapy (SBRT) patients. Methods and Materials: Intrafractional tumor motion of 10 patients with abdominal tumors (4 pancreas-fractionated and 6 liver-stereotactic patients) with implanted fiducials was measured based on daily orthogonal fluoroscopic movies over 38 treatment fractions. The needed internal margin for at least 90% of tumor coverage was calculated based on a 95th and fifth percentile of daily 3-dimensional tumor motion. The planning internal margin was generated by fusing 4DCT motion from all phase bins. The disagreement between needed and planning internal margin was analyzed fraction by fraction in 3 motion axes (superior-inferior [SI], anterior-posterior [AP], and left-right [LR]). The 4DCT margin was considered as an overestimation/underestimation of daily motion when disagreement exceeded at least 3 mm in the SI axis and/or 1.2 mm in the AP and LR axes (4DCT image resolution). The underlying reasons for this disagreement were evaluated based on interfractional and intrafractional breathing variation. Results: The 4DCT overestimated daily 3-dimensional motion in 39% of the fractions in 7 of 10 patients and underestimated it in 53% of the fractions in 8 of 10 patients. Median underestimation was 3.9 mm, 3.0 mm, and 1.7 mm in the SI axis, AP axis, and LR axis, respectively. The 4DCT was found to capture irregular deep breaths in 3 of 10 patients, with 4DCT motion larger than mean daily amplitude by 18 to 21 mm. The breathing pattern varied from breath to breath and day to day. The intrafractional variation of amplitude was significantly larger than intrafractional variation (2.7 mm vs 1.3 mm) in the primary motion axis (ie, SI axis). The SBRT patients showed significantly larger intrafractional amplitude variation than fractionated patients (3.0 mm vs 2

  1. Lasers in periodontal therapy.

    PubMed

    Passanezi, Euloir; Damante, Carla Andreotti; de Rezende, Maria L Rubo; Greghi, Sebastião L Aguiar

    2015-02-01

    About 50 years ago, lasers started to be used in periodontal treatment following evidence that wounds produced in animals healed more quickly after being irradiated with low-intensity lasers. Increased production of growth factors, stimulated mainly by red and infrared lasers, may participate in this process by influencing the behavior of various types of cells. High-intensity lasers have been used as an alternative to nonsurgical periodontal therapy in root biomodification and to reduce dentin hypersensivity; low-intensity lasers are frequently employed to improve tissue repair in regenerative procedures and in antimicrobial photodynamic therapy. Despite the abundance of promising data on the advantages of their use, there is still controversy regarding the real benefits of lasers and antimicrobial photodynamic therapy in periodontal and peri-implant treatment. A huge variation in the parameters of laser application among studies makes comparisons very difficult. An overview of the current concepts and findings on lasers in periodontal therapy is presented with emphasis on data collected from Latin-American researchers.

  2. Increasing antimicrobial resistance and narrowing therapeutics in typhoidal salmonellae.

    PubMed

    Kaurthe, Jaspal

    2013-03-01

    Multidrug-resistant typhoid fever (MDRTF) is a major public health problem in developing countries and is an emerging problem in the developed world. Because of the difficulties in preventing typhoid by public health measures or immunization in developing countries, great reliance is placed on antimicrobial chemotherapy. The treatment should commence as soon as the clinical diagnosis is made rather than after the results of antimicrobial susceptibility tests but the existence of MDRTF poses a serious clinical dilemma in the selection of empiric antimicrobial therapy. With the widespread emergence and spread of strains resistant to chloramphenicol, ampicillin and trimethoprim, ciprofloxacin became the drug of choice for the treatment of typhoid fever. However, of late the efficacy of fluoroquinolones too has been questioned, mainly due to increasing reports of increasing defervescence time and poor patient response. This indicates that the organism has begun to develop resistance to fluoroquinolones, and is corroborated by a steady increase in Minimum Inhibitory Concentration (MIC) of ciprofloxacin. The therapeutics of ciprofloxacin-resistant enteric fever narrows down to third- and fourth-generation cephalosporins and azithromycin. However, the emergence of extended-spectrum b-lactamases (ESBLs) in typhoidal Salmonellae poses a new challenge and would greatly limit the therapeutic options leaving only tigecycline and carbepenems as secondary antimicrobial drugs. This increasing resistance is alarming and emphasizes the need of effective preventive measures to control typhoid and to limit the unnecessary use of antibiotics.

  3. Antimicrobial activity of the metals and metal oxide nanoparticles.

    PubMed

    Dizaj, Solmaz Maleki; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad Hossein; Adibkia, Khosro

    2014-11-01

    The ever increasing resistance of pathogens towards antibiotics has caused serious health problems in the recent years. It has been shown that by combining modern technologies such as nanotechnology and material science with intrinsic antimicrobial activity of the metals, novel applications for these substances could be identified. According to the reports, metal and metal oxide nanoparticles represent a group of materials which were investigated in respect to their antimicrobial effects. In the present review, we focused on the recent research works concerning antimicrobial activity of metal and metal oxide nanoparticles together with their mechanism of action. Reviewed literature indicated that the particle size was the essential parameter which determined the antimicrobial effectiveness of the metal nanoparticles. Combination therapy with the metal nanoparticles might be one of the possible strategies to overcome the current bacterial resistance to the antibacterial agents. However, further studies should be performed to minimize the toxicity of metal and metal oxide nanoparticles to apply as proper alternatives for antibiotics and disinfectants especially in biomedical applications.

  4. Individual and contextual determinants of adequate maternal health care services in Kenya.

    PubMed

    Achia, Thomas N O; Mageto, Lillian E

    2015-01-01

    This study aimed to examine individual and community level factors associated with adequate use of maternal antenatal health services in Kenya. Individual and community level factors associated with adequate use of maternal health care (MHC) services were obtained from the 2008-09 Kenya Demographic and Health Survey data set. Multilevel partial-proportional odds logit models were fitted using STATA 13.0 to quantify the relations of the selected covariates to adequate MHC use, defined as a three-category ordinal variable. The sample consisted of 3,621 women who had at least one live birth in the five-year period preceding this survey. Only 18 percent of the women had adequate use of MHC services. Greater educational attainment by the woman or her partner, higher socioeconomic status, access to medical insurance coverage, and greater media exposure were the individual-level factors associated with adequate use of MHC services. Greater community ethnic diversity, higher community-level socioeconomic status, and greater community-level health facility deliveries were the contextual-level factors associated with adequate use of MHC. To improve the use of MHC services in Kenya, the government needs to design and implement programs that target underlying individual and community level factors, providing focused and sustained health education to promote the use of antenatal, delivery, and postnatal care.

  5. Peptides and Peptidomimetics for Antimicrobial Drug Design

    PubMed Central

    Mojsoska, Biljana; Jenssen, Håvard

    2015-01-01

    The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics. PMID:26184232

  6. Editorial of the Special Issue Antimicrobial Polymers

    PubMed Central

    Piozzi, Antonella; Francolini, Iolanda

    2013-01-01

    The special issue “Antimicrobial Polymers” includes research and review papers concerning the recent advances on preparation of antimicrobial polymers and their relevance to industrial settings and biomedical field. Antimicrobial polymers have recently emerged as promising candidates to fight microbial contamination onto surfaces thanks to their interesting properties. In this special issue, the main strategies pursued for developing antimicrobial polymers, including polymer impregnation with antimicrobial agents or synthesis of polymers bearing antimicrobial moieties, were discussed. The future application of these polymers either in industrial or healthcare settings could result in an extremely positive impact not only at the economic level but also for the improvement of quality of life. PMID:24005863

  7. Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future

    PubMed Central

    Unemo, Magnus

    2014-01-01

    SUMMARY Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection. PMID:24982323

  8. Factors associated with antimicrobial-resistant Escherichia coli in zoo animals.

    PubMed

    Ishihara, Kanako; Hosokawa, Yuko; Makita, Kohei; Noda, Jun; Ueno, Hiroshi; Muramatsu, Yasukazu; Ueno, Hiroshi; Mukai, Takeshi; Yamamoto, Hideaki; Ito, Masaki; Tamura, Yutaka

    2012-10-01

    Factors associated with the carriage of antimicrobial-resistant Escherichia coli isolates were analysed among zoo animals. An association was observed between selection of amoxicillin as the first-line therapy and a significantly higher percentage of resistance to ampicillin (54.5%) from 11 animals treated with antimicrobials, compared with isolates from 32 untreated animals (9.4%). In addition, the percentage resistance to kanamycin (36.4%), gentamicin (27.3%), trimethoprim (27.3%) and tetracycline (63.6%) from 11 treated animals was significantly higher than those from 32 untreated animals (3.1%, 3.1%, 3.1% and 25%, respectively), although these antimicrobials were rarely used. All kanamycin-, gentamicin- and trimethoprim-resistant isolates and more than half of the tetracycline-resistant isolates from treated animals were also resistant to ampicillin. Co-resistance to other antimicrobials with ampicillin was suggested to contribute to an increasing of resistance towards antimicrobials that were rarely administered. The present investigation revealed an association of antimicrobial treatment with the spread of antimicrobial-resistant bacteria among zoo animals.

  9. An overview of harms associated with β-lactam antimicrobials: where do the carbapenems fit in?

    PubMed Central

    Owens, Robert C

    2008-01-01

    The US Institute of Medicine's focus on patient safety has motivated hospital administrators to facilitate a culture of safety. As a result, subcommittees of the pharmacy and therapeutics committee have emerged in many hospitals to focus on adverse events and patient safety. Antimicrobial harms have gained the attention of practicing clinicians and hospital formulary committees, because they top the list of drugs that are associated with adverse events and because of certain serious harms that have ultimately led to the withdrawal of some antimicrobial agents. In the near future, several antimicrobials in the late phase of development will become available for clinical use (ceftobiprole, ceftaroline, and telavancin), and others (doripenem and dalbavancin) have recently joined the armamentarium. Because new antimicrobials will become part of the treatment armamentarium, it is important to discuss our current understanding of antimicrobial harms in general. Although not thought of as traditional adverse events, Clostridium difficile infection and development of resistance during therapy are adverse events that occur as a result of antimicrobial exposure and therefore are discussed. In addition, a distillation of our current understanding of β-lactam specific adverse events will be provided. Finally, new methods of administration are being evaluated that may influence peak concentration-related antimicrobial adverse events. PMID:18495060

  10. Antimicrobial anxiety: the impact of stress on antimicrobial immunity

    PubMed Central

    Radek, Katherine A.

    2010-01-01

    Leukocytes and epithelial cells are fundamental to antimicrobial immunity. Their antimicrobial responses are an evolutionarily conserved component of the innate immune system and are influenced by the host’s response to external stimuli. The efficacy of host defense via antimicrobial responses derives from the ability of AMPs to rapidly identify and eradicate foreign microbes and activate proinflammatory pathways, and from the capacity of later innate and adaptive immune responses to amplify protection through distinct biochemical mechanisms. Recent advances in neuroimmunology have identified a direct link between the neuroendocrine and immune systems, where environmental stimuli are generally believed to promote a transient effect on the immune system in response to environmental challenges and are presumably brought back to baseline levels via neuroendocrine pathways. Stress is an environmental stimulus that flares from a variety of circumstances and has become engrained in human society. Small bouts of stress are believed to enhance the host’s immune response; however, prolonged periods of stress can be detrimental through excess production of neuroendocrine-derived mediators that dampen immune responses to invasive pathogens. Elucidation of the mechanisms behind stress-induced immune modulation of antimicrobial responses will ultimately lead to the development of more effective therapeutic interventions for pathologic conditions. It is the intent of this review to broaden the existing paradigm of how stress-related molecules dampen immune responses through suppression of antimicrobial mechanisms, and to emphasize that bacteria can use these factors to enhance microbial pathogenesis during stress. PMID:20442225

  11. Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance.

    PubMed

    Maddox, T W; Clegg, P D; Williams, N J; Pinchbeck, G L

    2015-11-01

    Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin-resistant Staphylococcus aureus has been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin-resistant Staphylococcus aureus strains either to be predominantly of types associated with horses or of sequence type ST398. Antimicrobial-resistant Escherichia coli (including multidrug-resistant and extended spectrum β-lactamase-producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci, Salmonella, Acinetobacter and Pseudomonas species. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.

  12. Antimicrobial Peptides from Plants

    PubMed Central

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  13. Antimicrobial activity of flavonoids.

    PubMed

    Cushnie, T P Tim; Lamb, Andrew J

    2005-11-01

    Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (-)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2'-trihydroxy-5'-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

  14. The research agenda of the National Institute of Allergy and Infectious Diseases for antimicrobial resistance.

    PubMed

    Peters, N Kent; Dixon, Dennis M; Holland, Steven M; Fauci, Anthony S

    2008-04-15

    Antimicrobial resistance is an intrinsic and inevitable aspect of microbial survival that continually challenges human health. Research on antimicrobial resistance is central to the mission of the National Institute of Allergy and Infectious Diseases (NIAID). In fiscal year 2007, NIAID invested more than USD800 million to support basic and translational research on antimicrobials, more than USD200 million of which is devoted to understanding the causes, consequences, and treatments of antimicrobial drug resistance. The complex process that facilitates the transformation of ideas into therapies requires a pipeline that runs from bench to bedside, and NIAID has leveraged the entire spectrum of conventional and biodefense resources. NIAID works in partnership with other federal agencies, industry, foundation partners, and foreign governments. The basic and clinical research supported by NIAID will, ideally, continue to yield profound rewards in terms of the understanding, diagnosis, and treatment of infectious diseases.

  15. Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

    PubMed Central

    Bolhuis, Mathieu S.; Panday, Prashant N.; Pranger, Arianna D.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2011-01-01

    Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs. PMID:24309312

  16. Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams.

    PubMed

    Bolhuis, Mathieu S; Panday, Prashant N; Pranger, Arianna D; Kosterink, Jos G W; Alffenaar, Jan-Willem C

    2011-11-18

    Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs.

  17. Potential of medicinal plants as antimicrobial and antioxidant agents in food industry: a hypothesis.

    PubMed

    Ortega-Ramirez, Luis Alberto; Rodriguez-Garcia, Isela; Leyva, Juan Manuel; Cruz-Valenzuela, Manuel Reynaldo; Silva-Espinoza, Brenda Adriana; Gonzalez-Aguilar, Gustavo A; Siddiqui, Wasim; Ayala-Zavala, Jesus Fernando

    2014-02-01

    Many food preservation strategies can be used for the control of microbial spoilage and oxidation; however, these quality problems are not yet controlled adequately. Although synthetic antimicrobial and antioxidant agents are approved in many countries, the use of natural safe and effective preservatives is a demand of food consumers and producers. This paper proposes medicinal plants, traditionally used to treat health disorders and prevent diseases, as a source of bioactive compounds having food additive properties. Medicinal plants are rich in terpenes and phenolic compounds that present antimicrobial and antioxidant properties; in addition, the literature revealed that these bioactive compounds extracted from other plants have been effective in food systems. In this context, the present hypothesis paper states that bioactive molecules extracted from medicinal plants can be used as antimicrobial and antioxidant additives in the food industry.

  18. Why a second look might be worth it: immuno-modulatory therapies in the critically ill patient

    PubMed Central

    Siegler, Benedikt H.; Brenner, Thorsten; Uhle, Florian; Weiterer, Sebastian; Weigand, Markus A.

    2016-01-01

    Sepsis and septic shock are associated with high mortality rates and remain a serious menace for the critically ill patient. Concurrent activation of pro- and anti-inflammatory pathways and an excessive cytokine release represent initial key features in the deregulation of the humoral and cellular antimicrobial defense. Research of the last decades addressed both the ebullient inflammation as well as the resulting long-term failure of the host immunity. While the reestablishment of an adequate immune-competence is still under investigation, many promising experimental trials to limit the inflammatory response during sepsis were challenged by missing beneficial effects in clinical studies. Nevertheless, due to advanced knowledge about the complex regulation of inflammatory mediators and their overlapping involvement in other potentially life-threatening diseases, further evaluation of these approaches in relevant subgroups could help to identify critically ill patients with potential benefit from anti-inflammatory therapies. PMID:27293871

  19. Antimicrobial resistance: action to combat the rising microbial challenges.

    PubMed

    Paphitou, Niki I

    2013-06-01

    Antimicrobial therapy transformed medical practice from a merely diagnosis-focused approach 80 years ago to a treatment-focused approach, saving millions of lives in the years to follow. Today, numerous medical advances made possible by effective antibiotics are being threatened by the relentlessly rising rates of bacteria resistant to all currently available antibiotics. This phenomenon is a consequence of antibiotic misuse, which exerts undue selective pressure on micro-organisms, combined with defective infection control practices that accelerate their spread. Its impact on societies worldwide is immense, resulting in loss of human life and money. An alarming pattern of resistance involving multidrug-resistant and sometimes pandrug-resistant Gram-negative bacteria is currently emerging. In response to the global public health threat posed by antimicrobial resistance (AMR), a number of national and international actions and initiatives have been developed in recent years to address this issue. Although the optimally effective and cost-effective strategy to reduce AMR is not known, a multifaceted approach is most likely to be successful. It should include actions aiming at optimising antibiotic use, strengthening surveillance and infection control, and improving healthcare worker and public education with regard to antibiotics. Research efforts to bring new effective antibiotics to patients need to be fostered in order to negate the consequences of the current lack of antimicrobial therapy options. A holistic view of AMR as well as intersectoral collaboration between human and veterinary medicine is required to best address the problem.

  20. Antimicrobial resistance in Scandinavia after ban of antimicrobial growth promoters.

    PubMed

    Bengtsson, Björn; Wierup, Martin

    2006-01-01

    The banned use of antimicrobial growth promoters resulted in a considerably decreased use of antimicrobials in food animal production in Sweden (65%), Denmark (47%), Norway (40%) and Finland (27%). The current prevalence of antimicrobial resistance in animal bacterial populations is also considerably lower than in some other countries in the EU. In the swine production, no or limited effect was found in the finisher production (>25 to 30 kg). Temporary negative effects occurred during the post weaning period (7-30 kg). In Denmark, the cost of production from birth to slaughter per pig produced increased by approximately 1.0 euro with a high variability between pig producers. In the broiler production the termination had no significant negative effect on animal health and welfare or on production economy.

  1. Novel histone-derived antimicrobial peptides use different antimicrobial mechanisms.

    PubMed

    Pavia, Kathryn E; Spinella, Sara A; Elmore, Donald E

    2012-03-01

    The increase in multidrug resistant bacteria has sparked an interest in the development of novel antibiotics. Antimicrobial peptides that operate by crossing the cell membrane may also have the potential to deliver drugs to intracellular targets. Buforin 2 (BF2) is an antimicrobial peptide that shares sequence identity with a fragment of histone subunit H2A and whose bactericidal mechanism depends on membrane translocation and DNA binding. Previously, novel histone-derived antimicrobial peptides (HDAPs) were designed based on properties of BF2, and DesHDAP1 and DesHDAP3 showed significant antibacterial activity. In this study, their DNA binding, permeabilization, and translocation abilities were assessed independently and compared to antibacterial activity to determine whether they share a mechanism with BF2. To investigate the importance of proline in determining the peptides' mechanisms of action, proline to alanine mutants of the novel peptides were generated. DesHDAP1, which shows significant similarities to BF2 in terms of secondary structure, translocates effectively across lipid vesicle and bacterial membranes, while the DesHDAP1 proline mutant shows reduced translocation abilities and antimicrobial potency. In contrast, both DesHDAP3 and its proline mutant translocate poorly, though the DesHDAP3 proline mutant is more potent. Our findings suggest that a proline hinge can promote membrane translocation in some peptides, but that the extent of its effect on permeabilization depends on the peptide's amphipathic properties. Our results also highlight the different antimicrobial mechanisms exhibited by histone-derived peptides and suggest that histones may serve as a source of novel antimicrobial peptides with varied properties.

  2. Antimicrobial Resistance Mechanisms among Campylobacter

    PubMed Central

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  3. Antimicrobial resistance mechanisms among Campylobacter.

    PubMed

    Wieczorek, Kinga; Osek, Jacek

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

  4. Ruthenium complexes as antimicrobial agents.

    PubMed

    Li, Fangfei; Collins, J Grant; Keene, F Richard

    2015-04-21

    One of the major advances in medical science has been the development of antimicrobials; however, a consequence of their widespread use has been the emergence of drug-resistant populations of microorganisms. There is clearly a need for the development of new antimicrobials--but more importantly, there is the need for the development of new classes of antimicrobials, rather than drugs based upon analogues of known scaffolds. Due to the success of the platinum anticancer agents, there has been considerable interest in the development of therapeutic agents based upon other transition metals--and in particular ruthenium(II/III) complexes, due to their well known interaction with DNA. There have been many studies of the anticancer properties and cellular localisation of a range of ruthenium complexes in eukaryotic cells over the last decade. However, only very recently has there been significant interest in their antimicrobial properties. This review highlights the types of ruthenium complexes that have exhibited significant antimicrobial activity and discusses the relationship between chemical structure and biological processing--including site(s) of intracellular accumulation--of the ruthenium complexes in both bacterial and eukaryotic cells.

  5. Antimicrobial implications of vitamin D

    PubMed Central

    Youssef, Dima A; Miller, Christopher WT; El-Abbassi, Adel M; Cutchins, Della C; Cutchins, Coleman; Grant, William B

    2011-01-01

    Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections. PMID:22259647

  6. [In this study, it was investigated that, whether the FR-3 appliance was adequate or not in functional orthopedic therapy].

    PubMed

    Bengi, O; Uzel, I; Işimer, Y; Sağdiç, D

    1989-11-01

    Examinations were based on lateral cephalometric changes in sagittal extent. For this purpose, The FR-3 appliance was tried out on total 13 patients (5 female and 8 male) Who have skeletal Angle Class III malocclusion due to maxillary inadequacy. The changes in the sagittal direction on lateral cephalograms and the findings obtained as a result of treatment, were compared with the usual grow up and maturation values. Then, whole data were evaluated biostatistically. Consequently, all results showed that, although FR-3 appliance can be used on this type of malocclusions, good patient cooperation and knowing the individual optimal grow-up models are extremely important and necessary.

  7. Treatment practices and quantification of antimicrobial drug usage in conventional and organic dairy farms in Wisconsin.

    PubMed

    Pol, M; Ruegg, P L

    2007-01-01

    The objective of this study was to develop a method to quantify antimicrobial drug usage and treatment practices on conventional and organic dairy farms that had been recruited to represent a broad spectrum of potential exposure to antimicrobial drugs. Data on disease prevalence and treatment practices of organic (n = 20) and conventional (n = 20) farms were obtained during a farm visit using a survey instrument. A standardized estimate of antimicrobial drug usage was developed using a defined daily dose (DDD) of selected compounds. Density of antimicrobial drug usage was expressed as the number of DDD per adult cow per year. Differences in prevalence and management of selected diseases between conventional and organic farms were identified. The overall estimated prevalence of selected diseases was greater for conventional farms compared with organic farms. Organic farmers reported use of a variety of nonantimicrobial compounds for treatment and prevention of disease. Conventional farmers reported that penicillin was the compound most commonly used for dry cow therapy and cephapirin was most commonly used for treatment of clinical mastitis. On conventional farms, the estimated overall exposure to antimicrobial drugs was 5.43 DDD per cow per year composed of 3.58 and 1.85 DDD of intramammary and parenteral antimicrobial drugs, respectively. Of total intramammary antimicrobial drug usage, treatment of clinical mastitis contributed 2.02 DDD compared with 1.56 DDD attributed to the use of dry cow therapy. Of total parenteral treatments, the distribution of exposure was 0.52 (dry cow therapy), 1.43 (clinical mastitis treatment), 0.39 (treatment of foot disease), 0.14 (treatment of respiratory disease), and 0.32 (treatment of metritis) DDD. For treatments of foot infections (0.33 DDD), respiratory infections (0.07 DDD), and metritis (0.19 DDD), the mean density of ceftiofur usage was significantly greater compared with other compounds.

  8. Antimicrobial susceptibilities of Mycoplasma isolated from bovine mastitis in Japan.

    PubMed

    Kawai, Kazuhiro; Higuchi, Hidetoshi; Iwano, Hidetomo; Iwakuma, Akihiro; Onda, Ken; Sato, Reiichiro; Hayashi, Tomohito; Nagahata, Hajime; Oshida, Toshio

    2014-01-01

    Mycoplasma spp. are highly contagious pathogens and intramammary Mycoplasma infection is a serious issue for the dairy industry. As there is no effective vaccine for Mycoplasma infection, control depends on good husbandry and chemo-antibiotic therapy. In this study, antimicrobial susceptibility of Mycoplasma strains recently isolated from cases of bovine mastitis in Japan was evaluated by minimum inhibitory concentration (MIC). All Mycoplasma bovis strains were sensitive to pirlimycin, danofloxacin and enrofloxacin, but not kanamycin, oxytetracycline, tilmicosin or tylosin. M. californicum and M. bovigenitalium strains were sensitive to pirlimycin, danofloxacin, enrofloxacin, oxytetracycline, tilmicosin and tylosin, but not to kanamycin. This is the first report to describe the MIC of major antimicrobial agents for Mycoplasma species isolated from bovine mastitis in Japan.

  9. Antimicrobial effect of ozonated water on bacteria invading dentinal tubules.

    PubMed

    Nagayoshi, Masato; Kitamura, Chiaki; Fukuizumi, Takaki; Nishihara, Tatsuji; Terashita, Masamichi

    2004-11-01

    Ozone is known to act as a strong antimicrobial agent against bacteria, fungi, and viruses. In the present study, we examined the effect of ozonated water against Enterococcus faecalis and Streptcoccus mutans infections in vitro in bovine dentin. After irrigation with ozonated water, the viability of E. faecalis and S. mutans invading dentinal tubules significantly decreased. Notably, when the specimen was irrigated with sonication, ozonated water had nearly the same antimicrobial activity as 2.5% sodium hypochlorite (NaOCl). We also compared the cytotoxicity against L-929 mouse fibroblasts between ozonated water and NaOCl. The metabolic activity of fibroblasts was high when the cells were treated with ozonated water, whereas that of fibroblasts significantly decreased when the cells were treated with 2.5% NaOCl. These results suggest that ozonated water application may be useful for endodontic therapy.

  10. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  11. Antimicrobial Properties of Titanium Nanoparticles

    NASA Astrophysics Data System (ADS)

    Erdural, B. K.; Yurum, A.; Bakir, U.; Karakas, G.

    In the present study, nanostructured titania particles were synthesized using hydrothermal processing and their photocatalytic antimicrobial activities were characterized. Sol-gel synthesized TiO2 samples were treated with a two step hydrothermal treatment. The first stage treatment was the alkaline treatment with 10 M of NaOH for 48 h at 130°C, followed with the second step which applied with distilled water for 48 h at 200°C. Scanning Electron Microscope (SEM) images showed that alkaline treatment yields lamellar structure particles from the sol-gel synthesized anatase. Further treatment of nanoplates with distilled water results in crystal growth and the formation of nano structured thorn like particles. The photocatalytic antimicrobial activities of samples were determined against Escherichia coli under solar irradiation for 4 h. It was observed that the samples treated under alkaline conditions have higher antimicrobial activity than the untreated samples.

  12. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  13. Importance of adequate exercise in the detection of coronary heart disease by radionuclide ventriculography

    SciTech Connect

    Brady, T.J.; Thrall, J.H.; Lo, K.; Pitt, B.

    1980-12-01

    Rest and exercise radionuclide ventriculograms were obtained on 77 symptomatic patients without prior documented coronary artery disease (CAD). Coronary artery disease was present by angiograms in 48. Radionuclide ventriculography (RNV) was abnormal in 41 patients (overall sensitivity 85%). In 29 patients with normal coronary arteries, RNV was normal in 24 (specificity 83%). To determine if the exercise level affects sensitivity, the studies were graded for adequacy of exercise. It was considered adequate if patients developed (a) chest pain, or (b) ST segment depression of at least 1 mm, or (c) if they achieved a pressure rate product greater than 250. Among the 48 patients with coronary artery disease, 35 achieved adequate exercise. Thirty-three had an abnormal RNV (sensitivity 94%). In 13 patients who failed to achieve adequate exercise, RNV was abnormal in eight (sensitivity of only 62%). Some patients with coronary artery disease may have a normal ventricular response at inadequate levels of stress.

  14. [Prevention of ocular complications of herpes zoster ophthalmicus by adequate treatment with acyclovir].

    PubMed

    Borruat, F X; Buechi, E R; Piguet, B; Fitting, P; Zografos, L; Herbort, C P

    1991-05-01

    We compared the frequency of severe ocular complications secondary to Herpes Zoster Ophthalmicus (HZO) in 232 patients. They were divided into three groups: 1) patients without treatment (n = 164); 2) patients treated adequately (n = 48) with acyclovir (ACV; 5 x 800 mg/d orally and ophthalmic ointment 5 x /d for a minimum of 7 days, given within three days after skin eruption); and, 3) patients treated inadequately (n = 20) with ACV (only topical treatment, insufficient doses, interrupted treatment, delayed treatment). Patients with no treatment or with inadequate treatments showed the same frequency of severe ocular complications (21% (34/164) and 25% (5/20), respectively). In contrast, when adequate treatment of ACV was given complications occurred in only 4% (2/48) of cases. This study emphasizes the need for prompt (within three days after skin eruption) and adequate (5 x 800 mg/d for at least 7 days) treatment of ACV to prevent the severe complications of HZO.

  15. Uses of antimicrobial genes from microbial genome

    DOEpatents

    Sorek, Rotem; Rubin, Edward M.

    2013-08-20

    We describe a method for mining microbial genomes to discover antimicrobial genes and proteins having broad spectrum of activity. Also described are antimicrobial genes and their expression products from various microbial genomes that were found using this method. The products of such genes can be used as antimicrobial agents or as tools for molecular biology.

  16. Broadband inversion of 1J(CC) responses in 1,n-ADEQUATE spectra.

    PubMed

    Reibarkh, Mikhail; Williamson, R Thomas; Martin, Gary E; Bermel, Wolfgang

    2013-11-01

    Establishing the carbon skeleton of a molecule greatly facilitates the process of structure elucidation, both manual and computer-assisted. Recent advances in the family of ADEQUATE experiments demonstrated their potential in this regard. 1,1-ADEQUATE, which provides direct (13)C-(13)C correlation via (1)J(CC), and 1,n-ADEQUATE, which typically yields (3)J(CC) and (1)J(CC) correlations, are more sensitive and more widely applicable experiments than INADEQUATE and PANACEA. A recently reported modified pulse sequence that semi-selectively inverts (1)J(CC) correlations in 1,n-ADEQUATE spectra provided a significant improvement, allowing (1)J(CC) and (n)J(CC) correlations to be discerned in the same spectrum. However, the reported experiment requires a careful matching of the amplitude transfer function with (1)J(CC) coupling constants in order to achieve the inversion, and even then some (1)J(CC) correlations could still have positive intensity due to the oscillatory nature of the transfer function. Both shortcomings limit the practicality of the method. We now report a new, dual-optimized inverted (1)J(CC) 1,n-ADEQUATE experiment, which provides more uniform inversion of (1)J(CC) correlations across the range of 29-82 Hz. Unlike the original method, the dual optimization experiment does not require fine-tuning for the molecule's (1)J(CC) coupling constant values. Even more usefully, the dual-optimized version provides up to two-fold improvement in signal-to-noise for some long-range correlations. Using modern, cryogenically-cooled probes, the experiment can be successfully applied to samples of ~1 mg under favorable circumstances. The improvements afforded by dual optimization inverted (1)J(CC) 1,n-ADEQUATE experiment make it a useful and practical tool for NMR structure elucidation and should facilitate the implementation and utilization of the experiment.

  17. Establishing an antimicrobial stewardship program.

    PubMed

    Morris, Andrew M; Stewart, Thomas E; Shandling, Maureen; McIntaggart, Scott; Liles, W Conrad

    2010-01-01

    Hospitals are faced with increasing challenges of antibiotic-resistant organisms and rising antimicrobial costs despite widespread attention to infection prevention and control measures. Government, professional organizations and accreditation bodies are all signalling an urgent need for the establishment of programs in hospitals to address antibiotic misuse. Although variations of such "antimicrobial stewardship programs" have been functioning in Canada for some time, a formal approach using change management and quality improvement principles has largely been lacking. We describe how we have established such a program in a teaching hospital, modelled on John Kotter's eight steps of leading change.

  18. Self-reported segregation experience throughout the life course and its association with adequate health literacy.

    PubMed

    Goodman, Melody S; Gaskin, Darrell J; Si, Xuemei; Stafford, Jewel D; Lachance, Christina; Kaphingst, Kimberly A

    2012-09-01

    Residential segregation has been shown to be associated with health outcomes and health care utilization. We examined the association between racial composition of five physical environments throughout the life course and adequate health literacy among 836 community health center patients in Suffolk County, NY. Respondents who attended a mostly White junior high school or currently lived in a mostly White neighborhood were more likely to have adequate health literacy compared to those educated or living in predominantly minority or diverse environments. This association was independent of the respondent's race, ethnicity, age, education, and country of birth.

  19. Self-reported segregation experience throughout the life course and its association with adequate health literacy

    PubMed Central

    Gaskin, Darrell J.; Si, Xuemei; Stafford, Jewel D.; Lachance, Christina; Kaphingst, Kimberly A.

    2012-01-01

    Residential segregation has been shown to be associated with health outcomes and health care utilization. We examined the association between racial composition of five physical environments throughout the life course and adequate health literacy among 836 community health center patients in Suffolk County, NY. Respondents who attended a mostly White junior high school or currently lived in a mostly White neighborhood were more likely to have adequate health literacy compared to those educated or living in predominantly minority or diverse environments. This association was independent of the respondent’s race, ethnicity, age, education, and country of birth. PMID:22658579

  20. Antimicrobial drug use in Austrian pig farms: plausibility check of electronic on-farm records and estimation of consumption.

    PubMed

    Trauffler, M; Griesbacher, A; Fuchs, K; Köfer, J

    2014-10-25

    Electronic drug application records from farmers from 75 conventional pig farms were revised and checked for their plausibility. The registered drug amounts were verified by comparing the farmers' records with veterinarians' dispensary records. The antimicrobial consumption was evaluated from 2008 to 2011 and expressed in weight of active substance(s), number of used daily doses (nUDD), number of animal daily doses (nADD) and number of product-related daily doses (nPrDD). All results were referred to one year and animal bodyweight (kg biomass). The data plausibility proof revealed about 14 per cent of unrealistic drug amount entries in the farmers' records. The annual antimicrobial consumption was 33.9 mg/kg/year, 4.9 UDDkg/kg/year, 1.9 ADDkg/kg/year and 2.5 PrDDkg/kg/year (average). Most of the antimicrobials were applied orally (86 per cent) and at group-level. Main therapy indications were metaphylactic/prophylactic measures (farrow-to-finish and fattening farms) or digestive tract diseases (breeding farms). The proportion of the 'highest priority critically important antimicrobials' was low (12 per cent). After determination of a threshold value, farms with a high antimicrobial use could be detected. Statistical tests showed that the veterinarian had an influence on the dosage, the therapy indication and the active substance. Orally administered antimicrobials were mostly underdosed, parenterally administered antimicrobials rather correctly or overdosed.

  1. Study of the nanomaterials and their antimicrobial activities

    NASA Astrophysics Data System (ADS)

    Ramadi, Muntaha

    In the last decade, the world faced huge problems associated with the spread of antimicrobial resistant infections that are essentially untreatable such as methicillin resistant Staphylococcus aureus (MRSA) infection. These infections have begun to occur in both hospital and community environments. Developing new antimicrobial surface coatings can hold a great promise to minimize and control various problems that associated with the spreading of infections and biofilms formation, these coatings can be used in medicine where medical devices associated with severe infections, in construction industry and the in food packaging industry. It has been established that single-walled CNTs exhibit a strong antimicrobial activity and can pierce bacterial cell walls. Recently, nanomaterial structures that made from pure carbon such as CNTs have been seen as promising candidates for many potential applications in Biotechnology and bioscience due to the combination of their extraordinary properties that arise from surface area, light weight, strength, flexibility, unique electrical conductivity and many more novel physical and chemical properties at nanoscale level. CNTs have been used widely in biomedical field including drug delivery, gene therapy and creating new biomedical devices with novel properties. Researchers have now made a first step to add carbon nanotubes to antimicrobial agents list. There are two types of CNTs have been used in biomedical research. The first one is a single-walled carbon nanotube (SWNT) and the second is a multi-walled carbon nanotube (MWNT). Recent in vitro studies suggest that carbon nanotubes have antimicrobial activity and coating CNTs with nickel nanoparticle could enhance the antimicrobial activity of cabon nanotubes. In order to test this hypothesis, nickel nanoparticles were deposited on carbon nanotubes (CNTs) by electrochemical deposition. The carbon nanotubes used in this study were XD-CNTs, SWNTs and Ni-coated CNTs. The structure and

  2. Treatment of chronic sinusitis in a horse with systemic and intra-sinus antimicrobials.

    PubMed

    Gordon, Danielle L; Radtke, Catherine L

    2017-03-01

    A 12-year-old Norwegian Fjord gelding was diagnosed with paranasal sinusitis as a post-operative complication of tooth repulsion surgery. The infection with inspissated purulent material persisted despite sinus trephination and lavage, and systemic antimicrobial therapy. Resolution occurred following infusion of a gelatin/penicillin mixture into the right rostral and caudal maxillary sinus.

  3. Peptides with Dual Antimicrobial and Anticancer Activities

    PubMed Central

    Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

    2017-01-01

    In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting toward intracellular targets, which increases their success compartively to one-target specific drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials. PMID:28271058

  4. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)†

    PubMed Central

    Maschmeyer, G.; Carratalà, J.; Buchheidt, D.; Hamprecht, A.; Heussel, C. P.; Kahl, C.; Lorenz, J.; Neumann, S.; Rieger, C.; Ruhnke, M.; Salwender, H.; Schmidt-Hieber, M.; Azoulay, E.

    2015-01-01

    Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-d-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons. PMID:24833776

  5. 75 FR 69648 - Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... ENERGY Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers... designed to hold firmly in place. 10 CFR Part 830 imposes a requirement that a documented safety analysis... provide guidance on meeting the requirements imposed by DOE Order 5480.23, Nuclear Safety Analysis...

  6. 42 CFR 413.24 - Adequate cost data and cost finding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... Adequate data capable of being audited is consistent with good business concepts and effective and efficient management of any organization, whether it is operated for profit or on a nonprofit basis. It is a... contract for services (for example, a management contract), directly assigning the costs to the...

  7. Prenatal zinc supplementation of zinc-adequate rats adversely affects immunity in offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that zinc (Zn) supplementation of Zn-adequate dams induced immunosuppressive effects that persist in the offspring after weaning. We investigated whether the immunosuppressive effects were due to in utero exposure and/or mediated via milk using a cross-fostering design. Pregnant...

  8. Towards Defining Adequate Lithium Trials for Individuals with Mental Retardation and Mental Illness.

    ERIC Educational Resources Information Center

    Pary, Robert J.

    1991-01-01

    Use of lithium with mentally retarded individuals with psychiatric conditions and/or behavior disturbances is discussed. The paper describes components of an adequate clinical trial and reviews case studies and double-blind cases. The paper concludes that aggression is the best indicator for lithium use, and reviews treatment parameters and…

  9. ADEQUATE SHELTERS AND QUICK REACTIONS TO WARNING: A KEY TO CIVIL DEFENSE.

    PubMed

    LYNCH, F X

    1963-11-08

    Case histories collected by investigators in Japan during 1945 illustrate both the effectiveness of shelters and the dangers inherent in apathy of the population, which suffered needless casualties by ignoring air raid warnintgs. Adequate shelters and immediate response to warnings are essential to survival in nuclear attack.

  10. Perceptions of Teachers in Their First Year of School Restructuring: Failure to Make Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Moser, Sharon

    2010-01-01

    The 2007-2008 school year marked the first year Florida's Title I schools that did not made Adequate Yearly Progress (AYP) for five consecutive years entered into restructuring as mandated by the "No Child Left Behind Act" of 2001. My study examines the perceptions of teacher entering into their first year of school restructuring due to…

  11. 45 CFR 1182.15 - Institute responsibility for maintaining adequate technical, physical, and security safeguards to...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... record systems. These security safeguards shall apply to all systems in which identifiable personal data... data and automated systems shall be adequately trained in the security and privacy of personal data. (4... technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of manual...

  12. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Adequate financial records, statistical data, and... financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination of costs payable by...

  13. Effect of tranquilizers on animal resistance to the adequate stimuli of the vestibular apparatus

    NASA Technical Reports Server (NTRS)

    Maksimovich, Y. B.; Khinchikashvili, N. V.

    1980-01-01

    The effect of tranquilizers on vestibulospinal reflexes and motor activity was studied in 900 centrifuged albino mice. Actometric studies have shown that the tranquilizers have a group capacity for increasing animal resistance to the action of adequate stimuli to the vestibular apparatus.

  14. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  15. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  16. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  17. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  18. The Relationship between Parental Involvement and Adequate Yearly Progress among Urban, Suburban, and Rural Schools

    ERIC Educational Resources Information Center

    Ma, Xin; Shen, Jianping; Krenn, Huilan Y.

    2014-01-01

    Using national data from the 2007-08 School and Staffing Survey, we compared the relationships between parental involvement and school outcomes related to adequate yearly progress (AYP) in urban, suburban, and rural schools. Parent-initiated parental involvement demonstrated significantly positive relationships with both making AYP and staying off…

  19. Which Food Security Determinants Predict Adequate Vegetable Consumption among Rural Western Australian Children?

    PubMed

    Godrich, Stephanie L; Lo, Johnny; Davies, Christina R; Darby, Jill; Devine, Amanda

    2017-01-03

    Improving the suboptimal vegetable consumption among the majority of Australian children is imperative in reducing chronic disease risk. The objective of this research was to determine whether there was a relationship between food security determinants (FSD) (i.e., food availability, access, and utilisation dimensions) and adequate vegetable consumption among children living in regional and remote Western Australia (WA). Caregiver-child dyads (n = 256) living in non-metropolitan/rural WA completed cross-sectional surveys that included questions on FSD, demographics and usual vegetable intake. A total of 187 dyads were included in analyses, which included descriptive and logistic regression analyses via IBM SPSS (version 23). A total of 13.4% of children in this sample had adequate vegetable intake. FSD that met inclusion criteria (p ≤ 0.20) for multivariable regression analyses included price; promotion; quality; location of food outlets; variety of vegetable types; financial resources; and transport to outlets. After adjustment for potential demographic confounders, the FSD that predicted adequate vegetable consumption were, variety of vegetable types consumed (p = 0.007), promotion (p = 0.017), location of food outlets (p = 0.027), and price (p = 0.043). Food retail outlets should ensure that adequate varieties of vegetable types (i.e., fresh, frozen, tinned) are available, vegetable messages should be promoted through food retail outlets and in community settings, towns should include a range of vegetable purchasing options, increase their reliance on a local food supply and increase transport options to enable affordable vegetable purchasing.

  20. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... veterinary care. 2.33 Section 2.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian and adequate veterinary care. (a) Each research facility shall have an attending veterinarian who shall...