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Sample records for generation cephalosporin antibiotic

  1. Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin

    PubMed Central

    Ray, Partha; Zhang, Tong; Pruden, Amy; Strickland, Michael; Knowlton, Katharine

    2015-01-01

    Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs) to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. ?-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3) relative to control cows (n = 3). However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with “phages, prophages, transposable elements, and plasmids”, suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle), along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria). This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored. PMID:26258869

  2. CEPHALOSPORIN RESISTANCE AMONG BOVINE SALMONELLA ENTERICA SEROTYPES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Extended-spectrum *-lactamases (ESBLs) are important resistance mechanisms which affect *-lactam antibiotics, including cephalosporins. Extended-spectrum 3rd generation cephalosporins are considered drugs of choice for serious Salmonella infections. The emergence of ESBL-producing orga...

  3. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis

    PubMed Central

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I.; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    Introduction: Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. Materials and Methods: This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Results: Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Conclusion: Our findings have major implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes. PMID:25729741

  4. In vitro activity, pharmacokinetics, clinical efficacy, safety and pharmacoeconomics of ceftriaxone compared with third and fourth generation cephalosporins: review.

    PubMed

    Bijie, H; Kulpradist, S; Manalaysay, M; Soebandrio, A

    2005-02-01

    Due to their wide spectrum of activity, good pharmacokinetics, established clinical efficacy and high tolerability, cephalosporins are among the most widely used antibiotics worldwide. The third and fourth generation cephalosporins are predominantly parenteral agents, administered two or three times daily, used in the treatment of a wide range of moderate to severe infections. Ceftriaxone, a third generation cephalosporin, is unique in exhibiting an unusually long elimination half-life that allows for once-daily administration. Among third generation cephalosporins, ceftazidime and cefoperazone are unusual among cephalosporins in possessing activity, albeit moderate, against Pseudomonas aeruginosa. However, both of these agents also exhibit marked loss of activity against Gram-negative organisms producing high levels of Class A or C beta-lactamases. Sulperazone, a 1:1 combination of cefoperazone and the beta-lactamase inhibitor sulbactam, is more resistant to attack by Class A beta-lactamases but remains vulnerable to isolates producing Class C beta-lactamases. Ceftriaxone exhibits the widest antibacterial spectrum of third generation cephalosporins and this is reflected in clinical responses. Cefoperazone and sulperazone exhibit the poorest clinical responses. Although the fourth generation cephalosporins cefpirome and cefepime exhibit enhanced stability to bacterial beta-lactamases and marginally enhanced in vitro antibacterial activity over ceftriaxone, there is no clinical advantage in terms of clinical or bacteriological success. The cephalosporins are well tolerated, with few and generally transient adverse effects; the major exception being haematological abnormalities including blood coagulation disorders associated with cefoperazone. Several pharmacoeconomic studies indicate that the once-daily dosing regimen required for ceftriaxone is the major factor responsible for its cost-effectiveness over third and fourth generation cephalosporins. PMID:15828439

  5. Ceftriaxone, an FDA-approved cephalosporin antibiotic, suppresses lung cancer growth by targeting Aurora B

    PubMed Central

    Li, Xiang; Li, Haitao; Li, Shengqing; Zhu, Feng; Dong, Zigang

    2012-01-01

    Ceftriaxone, an FDA-approved third-generation cephalosporin antibiotic, has antimicrobial activity against both gram-positive and gram-negative organisms. Generally, ceftriaxone is used for a variety of infections such as community-acquired pneumonia, meningitis and gonorrhea. Its primary molecular targets are the penicillin-binding proteins. However, other activities of ceftriaxone remain unknown. Herein, we report for the first time that ceftriaxone has antitumor activity in vitro and in vivo. Kinase profiling results predicted that Aurora B might be a potential ‘off’ target of ceftriaxone. Pull-down assay data confirmed that ceftriaxone could bind with Aurora B in vitro and in A549 cells. Furthermore, ceftriaxone (500 µM) suppressed anchorage-independent cell growth by targeting Aurora B in A549, H520 and H1650 lung cancer cells. Importantly, in vivo xenograft animal model results showed that ceftriaxone effectively suppressed A549 and H520 lung tumor growth by inhibiting Aurora B. These data suggest the anticancer efficacy of ceftriaxone for the treatment of lung cancers through its inhibition of Aurora B. PMID:22962305

  6. Phototransformation of cephalosporin antibiotics in an aqueous environment results in higher toxicity.

    PubMed

    Wang, Xiao-Huan; Lin, Angela Yu-Chen

    2012-11-20

    Photodegradation may be the most important elimination process for cephalosporin antibiotics in surface water. Cefazolin (CFZ) and cephapirin (CFP) underwent mainly direct photolysis (t(1/2) = 0.7, 3.9 h), while cephalexin (CFX) and cephradine (CFD) were mainly transformed by indirect photolysis, which during the process a bicarbonate-enhanced nitrate system contributed most to the loss rate of CFX, CFD, and cefotaxime (CTX) (t(1/2) = 4.5, 5.3, and 1.3 h, respectively). Laboratory data suggested that bicarbonate enhanced the phototransformation of CFD and CFX in natural water environments. When used together, NO(3)(-), HCO(3)(-), and DOM closely simulated the photolysis behavior in the Jingmei River and were the strongest determinants in the fate of cephalosporins. TOC and byproducts were investigated and identified. Direct photolysis led to decarboxylation of CFD, CFX, and CFP. Transformation only (no mineralization) of all cephalosporins was observed through direct photolysis; byproducts were found to be even less photolabile and more toxic (via the Microtox test). CFZ exhibited the strongest acute toxicity after just a few hours, which may be largely attributed to its 5-methyl-1,3,4-thiadiazole-2-thiol moiety. Many pharmaceuticals were previously known to undergo direct sunlight photolysis and transformation in surface waters; however, the synergistic increase in toxicity caused by this cocktail (via pharmaceutical photobyproducts) cannot be ignored and warrants future research attention. PMID:23062112

  7. Comparison of Second- and Third-Generation Cephalosporin as Initial Therapy for Women with Community-Onset Uncomplicated Acute Pyelonephritis

    PubMed Central

    Chang, U-Im; Kim, Hyung Wook

    2015-01-01

    Purpose This study examined the clinical effectiveness of parenteral cefuroxime and cefotaxime as empirical antibiotics for treating hospitalized women with uncomplicated acute pyelonephritis (APN). Materials and Methods This study was based on the clinical and microbiologic data of 255 hospitalized women with APN. Of these 255 women, 144 patients received cefuroxime and 111 received cefotaxime. Results There were no marked differences in the demographic features, clinical characteristics, and treatment duration between the populations of the cefuroxime and cefotaxime groups. The rates of defervescence showed no significant differences in the two groups at 48, 72, 96, and 120 hours. The clinical cure rates observed at the follow-up visit 4 to 14 days after the completion of antimicrobial therapy were not statistically different between the cefuroxime and cefotaxime groups [94.9% (129 of 136) versus 98.0% (100 of 102), respectively; p=0.307], and the microbiological cure rates were also not significantly different [88.3% (91 of 103) versus 95.0% (76 of 80), respectively; p=0.186]. The median hospitalization periods in the cefuroxime and cefotaxime groups were 7 (6-8) and 7 (6-8) days (p=0.157), respectively. Microbiological success rates after 72-96 hours of initial antimicrobial therapy were also not statistically different in the cefuroxime and cefotaxime groups, 89.4% (110 of 123) versus 94.9% (93 of 98; p=0.140). Conclusion Cefuroxime, a second-generation cephalosporin, is an appropriate antibiotic option for the initial treatment of uncomplicated APN and its efficacy does not differ from cefotaxime, a third-generation cephalosporin, in the initial parenteral therapy for community-onset APN. PMID:26256969

  8. Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.

    PubMed

    Dickson, Scott D; Salazar, Kimberly C

    2013-08-01

    Cephalosporins are one of the most commonly prescribed classes of antibiotics. Immediate IgE-mediated hypersensitivity reactions have been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other ?-lactam antibiotics, namely, penicillin. Historically, frequent reports of anaphylaxis following administration of first- and second-generation cephalosporins to patients with a history of penicillin allergy led to the belief of a high degree of allergic cross-reactivity. More recent evidence reveals a significantly lower risk of cross-reactivity between penicillins and the newer-generation cephalosporins. The current thought is that a shared side chain, rather than the ?-lactam ring structure, is the determining factor in immunologic cross-reactivity. Understanding the chemical structure of these agents has allowed us to identify the allergenic determinants for penicillin; however, the exact allergenic determinants of cephalosporins are less well understood. For this reason, standardized diagnostic skin testing is not available for cephalosporins as it is for penicillin. Nevertheless, skin testing to the cephalosporin in question, using a nonirritating concentration, provides additional information, which can further guide the work-up of a patient suspected of having an allergy to that drug. Together, the history and the skin test results can assist the allergist in the decision to recommend continued drug avoidance or to perform a graded challenge versus an induction of tolerance procedure. PMID:23546989

  9. Evaluation of the ?Lacta Test, a Rapid Test Detecting Resistance to Third-Generation Cephalosporins in Clinical Strains of Enterobacteriaceae

    PubMed Central

    Renvoisé, Aurélie; Decré, Dominique; Amarsy-Guerle, Rishma; Huang, Te-Din; Jost, Christelle; Podglajen, Isabelle; Raskine, Laurent; Genel, Nathalie; Bogaerts, Pierre; Jarlier, Vincent

    2013-01-01

    For decades, third-generation cephalosporins (3GC) have been major drugs used to treat infections due to Enterobacteriaceae; growing resistance to these antibiotics makes the rapid detection of such resistance important. The ?Lacta test is a chromogenic test developed for detecting 3GC-resistant isolates from cultures on solid media within 15 min. A multicenter prospective study conducted in 5 French and Belgian hospitals evaluated the performance of this test on clinical isolates. Based on antibiotic susceptibility testing, strains resistant or intermediate to cefotaxime or ceftazidime were classified as 3GC resistant, and molecular characterization of this resistance was performed. The rates of 3GC resistance were 13.9% (332/2,387) globally, 9.4% in Escherichia coli (132/1,403), 25.6% in Klebsiella pneumoniae (84/328), 30.3% in species naturally producing inducible AmpC beta-lactamases (109/360), and 5.6% in Klebsiella oxytoca and Citrobacter koseri (7/124). The sensitivities and specificities of the ?Lacta test were, respectively, 87.7% and 99.6% overall, 96% and 100% for E. coli and K. pneumoniae, and 67.4% and 99.6% for species naturally producing inducible AmpC beta-lactamase. False-negative results were mainly related to 3GC-resistant strains producing AmpC beta-lactamase. Interestingly, the test was positive for all 3GC-resistant extended-spectrum beta-lactamase-producing isolates (n = 241). The positive predictive value was 97% and remained at ?96% for prevalences of 3GC resistance ranging between 10 and 30%. The negative predictive values were 99% for E. coli and K. pneumoniae and 89% for the species producing inducible AmpC beta-lactamase. In conclusion, the ?Lacta test was found to be easy to use and efficient for the prediction of resistance to third-generation cephalosporins, particularly in extended-spectrum beta-lactamase-producing strains. PMID:24068012

  10. Microbial production of 7-amino-cephalosporanic acid and new generation cephalosporins (cephalothin) by different processing strategies.

    PubMed

    Gaurav, Kumar; Kundu, Kanika; Kundu, Subir

    2007-01-01

    The development of beta-lactam antibiotics has been a continuous battle of the design of new compounds to withstand inactivation by the ever-increasing diversity of beta-lactamases. Semisynthetic cephalosporins like cephalothin were synthesized from 7-amino-cephalosporanic acid (7-ACA), and thiophene-2-acetic acid using cephalosporin-C acylase enzyme was studied. The production of cephalosporin-C acylase by Pseudomonas diminuta was used and the growth kinetics studied. The optimum condition of enzyme activity was determined by using response surface methodology. A 2(3) full-factorial composite design was employed for experimental design and the result analyzed. The pH value and temperature for optimum activity were 6.5 and 32 degrees C, respectively. The structural analog compound similar to the side-chain of semisynthetic cephalosporins, e.g., thiophene-2-acetic acid, was added. HPLC data analysis indicate that the concentration of cephalothin was 1.6 mg/mL. PMID:17701482

  11. A fluorogenic substrate of beta-lactamases and its potential as a probe to detect the bacteria resistant to the third-generation oxyimino-cephalosporins.

    PubMed

    Thai, Hien Bao Dieu; Yu, Jin Kyung; Park, Byung Sun; Park, Yeon-Joon; Min, Sun-Joon; Ahn, Dae-Ro

    2016-03-15

    We devised and synthesized a fluorogenic substrate of ?-lactamases as a probe to detect the activity of the enzymes. Fluorescence of the probe emitted upon treatment of a ?-lactamase and increased proportionally to the concentration of the enzyme, demonstrating its sensing property for the activity of the enzyme. We also showed that the probe could be utilized to assay the enzyme and to determine kinetic parameters of the enzyme. Moreover, the probe was able to detect resistance to the third-generation oxyimino-cephalosporin-derived antibiotics such as cefotaxime and ceftazidime. In particular, the probe could identify the ceftazidime-resistance in bacteria that was not detectable using conventional pH-sensing materials, indicating the practical utility of the probe. PMID:26547430

  12. Improved antibacterial activity of cephalosporins loaded in magnetic chitosan microspheres.

    PubMed

    Chifiriuc, Carmen Mariana; Grumezescu, Alexandru Mihai; Saviuc, Crina; Croitoru, Cristina; Mihaiescu, Dan Eduard; Lazar, Veronica

    2012-10-15

    During the present study, we have evaluated magnetic chitosan as a potential drug delivery device, by specifically determining if chitosan could elute antibiotics in an active form that would be efficacious in inhibiting Staphylococcus aureus and Escherichia coli growth. We have demonstrated that the incorporation of cephalosporins of second, third and fourth generation into magnetic chitosan microspheres can possibly lead to an improved delivery of antibiotics in active forms, probably due to the inherent properties of chitosan. PMID:22732671

  13. Association of Veterinary Third-Generation Cephalosporin Use with the Risk of Emergence of Extended-Spectrum-Cephalosporin Resistance in Escherichia coli from Dairy Cattle in Japan

    PubMed Central

    Sato, Toyotaka; Okubo, Torahiko; Usui, Masaru; Yokota, Shin-ichi; Izumiyama, Satoshi; Tamura, Yutaka

    2014-01-01

    The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum ?-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporin–resistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n?=?20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporin–resistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporin–resistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporin–resistant isolates possessed plasmid-mediated ?-lactamase genes, including blaCTX-M-2 (9 isolates), blaCTX-M-14 (8 isolates), or blaCMY-2 (1 isolate); isolates possessing blaCTX-M-2 and blaCTX-M-14 were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporin–resistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporin–resistant ?-lactamase-expressing E. coli clones PMID:24755996

  14. Assessment of human exposure to 3rd generation cephalosporin resistant E. coli (CREC) through consumption of broiler meat in Belgium.

    PubMed

    Depoorter, P; Persoons, D; Uyttendaele, M; Butaye, P; De Zutter, L; Dierick, K; Herman, L; Imberechts, H; Van Huffel, X; Dewulf, J

    2012-09-17

    Acquired resistance of Escherichia coli to 3rd generation cephalosporin antimicrobials is a relevant issue in intensive broiler farming. In Belgium, about 35% of the E. coli strains isolated from live broilers are resistant to 3rd generation cephalosporins while over 60% of the broilers are found to be carrier of these 3rd generation cephalosporin resistant E. coli (CREC) after selective isolation. A model aimed at estimating the exposure of the consumer to CREC by consumption of broiler meat was elaborated. This model consists of different modules that simulate the farm to fork chain starting from primary production, over slaughter, processing and distribution to storage, preparation and consumption of broiler meat. Input data were obtained from the Belgian Food Safety agencies' annual monitoring plan and results from dedicated research programs or surveys. The outcome of the model using the available baseline data estimates that the probability of exposure to 1000 colony forming units (cfu) of CREC or more during consumption of a meal containing chicken meat is ca. 1.5%, the majority of exposure being caused by cross contamination in the kitchen. The proportion of CREC (within the total number of E. coli) at primary production and the overall contamination of broiler carcasses or broiler parts with E. coli are dominant factors in the consumer exposure to CREC. The risk of this exposure for human health cannot be estimated at this stage given a lack of understanding of the factors influencing the transfer of cephalosporin antimicrobial resistance genes from these E. coli to the human intestinal bacteria and data on the further consequences of the presence of CREC on human health. PMID:22938836

  15. National Prevalence of Resistance to Third-Generation Cephalosporins in Escherichia coli Isolates from Layer Flocks in France

    PubMed Central

    Chauvin, Claire; Le Devendec, Laetitia; Jouy, Eric; Le Cornec, Maena; Francart, Sylvie; Marois-Créhan, Corinne

    2013-01-01

    Resistance of Escherichia coli to third-generation cephalosporin (3GC) in fecal samples representative of French egg production was studied. The susceptibility to cefotaxime of E. coli isolates obtained by culture on nonselective media was determined. Twenty-two nonsusceptible isolates were obtained (7.51%; 95% confidence interval, 4.49 to 10.54%), the majority of which came from young birds. Most isolates carried a blaCTX-M-1 group gene, and a few carried a blaCMY-2-like gene. Control of 3GC resistance in laying hens is needed. PMID:24041899

  16. Comparison of resistance to third-generation cephalosporins in Shigella between Europe-America and Asia-Africa from 1998 to 2012.

    PubMed

    Gu, B; Zhou, M; Ke, X; Pan, S; Cao, Y; Huang, Y; Zhuang, L; Liu, G; Tong, M

    2015-10-01

    We conducted a systematic review to compare resistance to third-generation cephalosporins (TGCs) in Shigella strains between Europe-America and Asia-Africa from 1998 to 2012 based on a literature search of computerized databases. In Asia-Africa, the prevalence of resistance of total and different subtypes to ceftriaxone, cefotaxime and ceftazidime increased markedly, with a total prevalence of resistance up to 14·2% [95% confidence interval (CI) 3·9-29·4], 22·6% (95% CI 4·8-48·6) and 6·2% (95% CI 3·8-9·1) during 2010-2012, respectively. By contrast, resistance rates to these TGCs in Europe-America remained relatively low--less than 1·0% during the 15 years. A noticeable finding was that certain countries both in Europe-America and Asia-Africa, had a rapid rising trend in the prevalence of resistance of S. sonnei, which even outnumbered S. flexneri in some periods. Moreover, comparison between countries showed that currently the most serious problem concerning resistance to these TGCs appeared in Vietnam, especially for ceftriaxone, China, especially for cefotaxime and Iran, especially for ceftazidime. These data suggest that monitoring of the drug resistance of Shigella strains should be strengthened and that rational use of antibiotics is required. PMID:25553947

  17. Prevalence of lactose fermenting coliforms resistant to third generation cephalosporins in cattle feedlot throughout a production cycle and molecular characterization of resistant isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Increases in incidence of human infections caused by Enterobacteriaceae resistant to 3rd generation cephalosporins (3GC) have become a public health concern. The 3GC ceftiofur is commonly used for the therapeutic treatment of feedlot cattle but the impact this practice has on public h...

  18. Characterization of Third-Generation-Cephalosporin-Resistant Shiga Toxin-Producing Strains of Escherichia coli O157:H7 in Japan.

    PubMed

    Kawahara, Ryuji; Seto, Kazuko; Taguchi, Masumi; Nakajima, Chie; Kumeda, Yuko; Suzuki, Yasuhiko

    2015-09-01

    We isolated Shiga toxin-producing Escherichia coli O157:H7 strains resistant to third-generation cephalosporins. The resistant strains harbored blaCMY-2, a plasmid-mediated AmpC ?-lactamase. Genotyping of isolates revealed the possible spread of this problematic bacterium. Results suggested the importance of the investigation and surveillance of enterobacteria with plasmids harboring blaCMY-2. PMID:26135870

  19. Enzymatic Deprotection of the Cephalosporin 3? Acetoxy Group Using Candida antarctica Lipase B

    PubMed Central

    Patterson, Leslie D.; Miller, Marvin J.

    2010-01-01

    Cephalosporins remain one of the most important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3?-hydroxymethyl position. While 3?-acetoxymethyl substituted cephalosporins are readily available, deacetylation to access the free 3?-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or t-butyl esters, and on the corresponding sulfoxide and sulfone of the t-butyl ester. PMID:20099862

  20. In Vitro Synergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea

    PubMed Central

    Sasidharan, Nishanth Kumar; Sreekala, Sreerag Ravikumar; Jacob, Jubi; Nambisan, Bala

    2014-01-01

    Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000??g/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria in in vitro condition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria. PMID:24949457

  1. Production of Cephalosporin C by Paecilomyces persicinus P-10

    PubMed Central

    Pisano, M. A.; Vellozzi, E. M.

    1974-01-01

    After the growth of Paecilomyces persicinus P-10 in a glucose-peptone medium, filtrates were collected and analyzed for antibiotic antivity. Activities against Salmonella gallinarum ATCC 3030 and Alcaligenes faecalis ATCC 8750 (penicillin N-resistant strain) were obtained. Part of the former activity was readily inactivated by penicillinase. The fraction active against A. faecalis was isolated by passage through Amberlite XAD-2 and Amberlite IRA-68. The powder eventually obtained was subjected to paper chromatography followed by bioautography, and the activity obtained corresponded to that of a sample of cephalosporin C. Thin-layer chromatography was also employed to verify the presence of cephalosporin C in the P-10 powder. The active solids were further purified by means of paper chromatography in a solvent system consisting of n-butanol-acetic acid-water (60:15:25, vol/vol). The material obtained from this procedure yielded an infrared absorption spectrum identical to that of cephalosporin C. Similarly, the ultraviolet absorption of the purified preparation coincided with that of cephalosporin C. Exposure of the purified solids to cephalosporinase resulted in rapid inactivation of the antibiotic. In addition to penicillin N and cephalosporin C, filtrates of P. persicinus P-10 also contained deacetylcephalosporin C, deacetoxycephalosporin C, and cephalosporin P. PMID:4157343

  2. Antibiotics.

    PubMed

    Hariprasad, Seenu M; Mieler, William F

    2016-01-01

    The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However, since the completion of the EVS, numerous unresolved issues remain. The use of oral antibiotics has important implications for the ophthalmologist, particularly in the prophylaxis and/or management of postoperative, posttraumatic, or bleb-associated bacterial endophthalmitis. One can reasonably conclude that significant intraocular penetration of an antibiotic after oral administration may be a property unique to the newer-generation fluoroquinolones. Prophylactic use of mupirocin nasal ointment resulted in significant reduction of conjunctival flora with or without preoperative topical 5% povidone-iodine preparation. Ocular fungal infections have traditionally been very difficult to treat due to limited therapeutic options both systemically and intravitreally. Because of its broad spectrum of coverage, low MIC90 levels for the organisms of concern, good tolerability, and excellent bioavailability, voriconazole through various routes of administration may be useful to the ophthalmologist in the primary treatment of or as an adjunct to the current management of ocular fungal infections. PMID:26501865

  3. An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants

    PubMed Central

    Phetsang, Wanida; Blaskovich, Mark A.T.; Butler, Mark S.; Huang, Johnny X.; Zuegg, Johannes; Mamidyala, Sreeman K.; Ramu, Soumya; Kavanagh, Angela M.; Cooper, Matthew A.

    2014-01-01

    An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile ‘click’ chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure–activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy. PMID:25023540

  4. An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants.

    PubMed

    Phetsang, Wanida; Blaskovich, Mark A T; Butler, Mark S; Huang, Johnny X; Zuegg, Johannes; Mamidyala, Sreeman K; Ramu, Soumya; Kavanagh, Angela M; Cooper, Matthew A

    2014-08-15

    An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location in a sample in real time. Modelling of the structures bound to the cognate 50S ribosome target demonstrates binding to the same site as linezolid is possible. The fluorescent probes were successfully used to image Gram-positive bacteria using confocal microscopy. PMID:25023540

  5. Degradation kinetics and mechanism of antibiotic ceftiofur in recycled water derived from beef farm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ceftiofur is a third-generation cephalosporin antibiotic that has been widely used to treat bacterial infections in concentrated animal feeding operations (CAFOs). Land application of CAFO waste may lead to the loading of ceftiofur residues and its metabolites to the environment. To mitigate the pot...

  6. Antibiotics

    MedlinePLUS

    ... better. If you stop treatment too soon, some bacteria may survive and re-infect you. Do not save antibiotics for later or use someone else's prescription. Centers for Disease Control and Prevention

  7. Third-Generation-Cephalosporin-Resistant Klebsiella pneumoniae Isolates from Humans and Companion Animals in Switzerland: Spread of a DHA-Producing Sequence Type 11 Clone in a Veterinary Setting

    PubMed Central

    Wohlwend, Nadia; Francey, Thierry

    2015-01-01

    Characterization of third-generation-cephalosporin-resistant Klebsiella pneumoniae isolates originating mainly from one human hospital (n = 22) and one companion animal hospital (n = 25) in Bern (Switzerland) revealed the absence of epidemiological links between human and animal isolates. Human infections were not associated with the spread of any specific clone, while the majority of animal infections were due to K. pneumoniae sequence type 11 isolates producing plasmidic DHA AmpC. This clonal dissemination within the veterinary hospital emphasizes the need for effective infection control practices. PMID:25733505

  8. Cephalosporin Induced Disulfiram-Like Reaction: A Retrospective Review of 78 Cases

    PubMed Central

    Ren, Shiyan; Cao, Yuxia; Zhang, Xiuwei; Jiao, Shichen; Qian, Songyi; Liu, Peng

    2014-01-01

    Concomitant ingestion of alcohol and cephalosporin may cause a disulfiram-like reaction; however its fatal outcomes are not commonly known. We retrospectively reviewed 78 patients who had cephalosporin induced disulfiram-like reaction (CIDLR). The patients who had a negative skin test to cephalosporin prior to intravenous antibiotics were included, and those who were allergic to either alcohol or antibiotics were excluded. The average age of 78 patients was 37.8±12.2 (21–60) years. Of the 78 patients, 93.58% of the patients were males, 70.51% of the patients consumed alcohol after use of antibiotics, and 29.49% patients consumed alcohol initially, followed by intravenous antibiotics; however, no significant difference of morbidity was observed in these two groups. All patients were administered antibiotics intravenously. Five of 78 patients (6.41%) developed severe CIDLR too urgently to be rescued successfully. In conclusion, it is important for clinicians to educate patients that no alcohol should be used if one is taking cephalosporin. Also, clinicians should keep in mind that cephalosporin should not be prescribed for any alcoholics. PMID:24670024

  9. Do antibiotic residues in soils play a role in amplification and transmission of antibiotic resistant bacteria in cattle populations?

    PubMed Central

    Call, Douglas R.; Matthews, Louise; Subbiah, Murugan; Liu, Jinxin

    2013-01-01

    When we consider factors that contribute to the emergence, amplification, and persistence of antibiotic resistant bacteria, the conventional assumption is that antibiotic use is the primary driver in these processes and that selection occurs primarily in the patient or animal. Evidence suggests that this may not always be the case. Experimental trials show that parenteral administration of a third-generation cephalosporin (ceftiofur) in cattle has limited or short-term effects on the prevalence of ceftiofur-resistant bacteria in the gastrointestinal tract. While this response may be sufficient to explain a pattern of widespread resistance to cephalosporins, approximately two-thirds of ceftiofur metabolites are excreted in the urine raising the possibility that environmental selection plays an important additive role in the amplification and maintenance of antibiotic resistant E. coli on farms. Consequently, we present a rationale for an environmental selection hypothesis whereby excreted antibiotic residues such as ceftiofur are a significant contributor to the proliferation of antibiotic resistant bacteria in food animal systems. We also present a mathematical model of our hypothesized system as a guide for designing experiments to test this hypothesis. If supported for antibiotics such as ceftiofur, then there may be new approaches to combat the proliferation of antibiotic resistance beyond the prudent use mantra. PMID:23874327

  10. Oxidative Stress Enhances Cephalosporin Resistance of Enterococcus faecalis through Activation of a Two-Component Signaling System

    PubMed Central

    Djori?, Dušanka

    2014-01-01

    Enterococcus faecalis is a low-GC Gram-positive bacterium, a normal resident of the gastrointestinal (GI) tract, and an important hospital-acquired pathogen. An important risk factor for hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporins, antibiotics that impair cell wall biosynthesis by inhibiting peptidoglycan cross-linking. Enterococci are intrinsically resistant to cephalosporins; however, environmental factors that modulate cephalosporin resistance have not been described. While searching for the genetic determinants of cephalosporin resistance in E. faecalis, we unexpectedly discovered that oxidative stress, whether from external sources or derived from endogenous metabolism, drives enhanced intrinsic resistance to cephalosporins. A particular source of oxidative stress, H2O2, activates signaling through the CroR-CroS two-component signaling system, a known determinant of cephalosporin resistance in E. faecalis. We find that CroR-CroS is required for adaptation to H2O2 stress and that H2O2 potentiates the activities of cephalosporins against E. faecalis when the CroR-CroS signaling system is nonfunctional. Rather than directly detecting H2O2, our data suggest that the CroR-CroS system responds to cell envelope damage caused by H2O2 exposure in order to promote cell envelope repair and enhanced cephalosporin resistance. PMID:25331701

  11. [Immune response to antibiotics in patients with secondary immunodeficiencies].

    PubMed

    Meroni, P L

    1994-08-01

    A biological response modifier (BRM) has been defined as an agent able to modulate effector mechanisms or mediators of host defence. Some antibiotic molecules have been shown to display a BRM like activity, being able to enhance immune responses (certain cephalosporins), to synergize with the immune effectors (macrolides, quinolones) or alternatively, to depress immune functions (tetracyclines or antimycotic drugs). The BRM-like activity of different antibiotic molecules has been widely reported in in vitro studies as well as ex vivo in experimental animal models. Only recently some Authors have approached the problem by investigating whether the in vivo administration of antibiotic was able to affect different immune effector functions, either in healthy subjects or in patients. The main question in the field is the possible clinical impact of the connections between antibiotics and the immune system, particularly in subjects with acquired immunodeficiency in whom the impairment of the immune responses leads to increased susceptibility to infectious processes. Ex vivo data seem to suggest that cefodizime, one of the newest third-generation cephalosporins, is able to enhance phagocyte and mononuclear cell functions in healthy volunteers, thus confirming the possibility of combining an antibacterial efficacy with the ability to restore or enhance immune responses. Comparable data in studies investigating the effect of cefodizime on immune functions in immunocompromised patients such as elderly subjects, hemodialyzed or diabetic patients, BPCO subjects, patients undergoing surgical stress and patients with multiple myeloma are more important from a practical clinical point of view.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7861203

  12. Trends of Antibiotic Consumption in Korea According to National Reimbursement Data (2008–2012)

    PubMed Central

    Yoon, Young Kyung; Park, Gi Chan; An, Hyonggin; Chun, Byung Chul; Sohn, Jang Wook; Kim, Min Ja

    2015-01-01

    Abstract This study determined the trends in the quantities and patterns of nationwide antibiotic consumption in the Republic of Korea (ROK). This nationwide descriptive epidemiological study was conducted in the ROK between 2008 and 2012. The quantities and patterns of total systemic antibiotic prescriptions were analyzed using National Health Insurance claims data collected through the Health Insurance Review and Assessment service. Data concerning systemic antibiotics were collected using measurement units of the defined daily dose (DDD) per 1000 people per day according to the Anatomical Therapeutic Chemical classification. Over the 5-year study period, the annual consumption of systemic antibiotics ranged from 21.68 to 23.12 DDD per 1000 people per day. Outpatient antibiotic use accounted for 80.9% of total consumption. A regression model with autoregressive errors showed significant increased consumption of major antibiotic subgroups, including 3rd-generation cephalosporins, carbapenems, and glycopeptides (P?antibiotic use of 1st- (P?=?0.003), 2nd- (P?=?0.004), and 3rd-generation (P?=?0.018) cephalosporins among patients who underwent surgery under monitoring by the antimicrobial stewardship programs for perioperative prescription was significantly lower than in those who underwent surgery without monitoring programs. In time-series analysis, total antibiotic consumption demonstrated significant seasonality (P?antibiotics was noted to have increased in the ROK from 2008 to 2012, providing a possible explanation for the changing epidemiology of multidrug resistance. Larger prospective studies are needed to investigate the impact on public health of monitoring programs of perioperative antibiotic usage. PMID:26579825

  13. ?-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis

    PubMed Central

    Gaudelli, Nicole M.; Long, Darcie H.; Townsend, Craig A.

    2014-01-01

    Non-ribosomal peptide synthetases (NRPSs) are giant enzymes comprised of modules that house repeated sets of functional domains, which select, activate and couple amino acids drawn from a pool of nearly 500 potential building blocks.1 The structurally and stereochemically diverse peptides generated in this manner underlie the biosynthesis of a large sector of natural products. Many of their derived metabolites are bioactive such as the antibiotics vancomycin, bacitracin, daptomycin and the ?-lactam-containing penicillins, cephalosporins and nocardicins. Although penicillins and cephalosporins are synthesised from a classically derived NRPS tripeptide (from ACVS, ?-(L-?-aminoadipyl)–L-cysteinyl–D-valine synthetase)2, we now report an unprecedented NRPS activity to both assemble a serine-containing peptide and mediate its cyclisation to the critical ?-lactam ring of the nocardicin family of antibiotics. A histidine-rich condensation (C) domain, which typically carries out peptide bond formation during product assembly, was found to also synthesise the embedded 4-membered ring. Here, a mechanism is proposed and supporting experiments are described, which is distinct from the pathways that have evolved to the three other ?-lactam antibiotic families: penicillin/cephalosporins, clavams and carbapenems. These findings raise the possibility that ?-lactam rings can be regio- and stereospecifically integrated into engineered peptides for application as, for example, targeted protease inactivators.3,4 PMID:25624104

  14. Decreased permeation of cephalosporins through the outer membrane of Escherichia coli grown in salicylates.

    PubMed Central

    Foulds, J; Murray, D M; Chai, T; Rosner, J L

    1989-01-01

    Escherichia coli K-12 cells grown in 1 to 5 mM sodium salicylate (SAL) or acetylsalicylate show increased phenotypic resistance to various antibiotics (J. L. Rosner, Proc. Natl. Acad. Sci. USA 82:8771-8774, 1985), including cephalosporins (this study). To determine whether these effects are caused by a decreased uptake of the antibiotics, the permeation of several cephalosporins through the outer membrane was measured. For E. coli K-12 grown in LB broth containing 5 mM SAL or acetylsalicylate, permeation of the outer membrane by the five cephalosporins tested decreased three- to fivefold compared with that in cells not grown in salicylates. Permeation of the outer membrane by cephaloridine decreased within 15 min of the addition of SAL to cells grown in broth and reached a minimum in 1 to 2 h. When cells were transferred from broth with SAL to broth without SAL, their permeability to cephaloridine increased slowly for the first 45 min and more rapidly over the next 1.5 h; the permeability then attained normal levels by 3 h. The permeability changes that occurred after media shifts, either to or from SAL, were prevented by concentrations of chloramphenicol that inhibited protein synthesis. These effects of SAL on outer membrane permeability are fully consistent with their effects on antibiotic resistance and with the report (T. Sawai, S. Hirano, and A. Yamaguchi, FEMS Microbiol. Lett. 40:233-237, 1987) that the outer membranes of SAL-treated cells are deficient in certain porins. Permeation of cephaloridine through the outer membrane also decreased when a virulent strain of E. coli K1 was grown in the presence of as little as 1 to 2 mM SAL. This raises the concern that high levels of salicylates in patients night interfere with cephalosporin or other antibiotic therapies. Images PMID:2658790

  15. Cephalosporin-Induced Toxic Epidermal Necrolysis Treated with Intravenous Immunoglobulin

    PubMed Central

    Li, Li; Riina, Louis; Ahmed, Shadab

    2015-01-01

    Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous reaction to various medications, including antipsychotics and antibiotics. While cephalosporin-induced TEN is very rare, we present a case of cefepime-induced TEN. There are several commonly used therapies for TEN, including immunosuppressive agents and intravenous immunoglobulin (IVIG), but their true efficacy has not been proven. In this case, the patient was treated with IVIG. The role of IVIG as therapy for TEN is currently being investigated. Prior observational studies suggest IVIG infers clinic benefit; however, recent meta-analyses have not shown any benefit. Our patient initially showed clinical improvement with IVIG therapy but, unfortunately, later succumbed to sepsis. We will provide a brief review of the current research of the pathological mechanism of Stevens-Johnson syndrome (SJS)/TEN and the mechanism of action of IVIG specifically in TEN/SJS.

  16. Reported antibiotic use in 90 swine farms in Alberta

    PubMed Central

    Reid-Smith, Richard; Deckert, Anne E.; Dewey, Catherine E.; McEwen, Scott A.

    2006-01-01

    Abstract Antibiotic use was described using a convenience sample of 90 Alberta swine farms representing approximately 25% of the Alberta market swine production. Data on the use of antibiotics were collected through an on-farm interview questionnaire. The vast majority of antibiotics were used in feed. The chlortetracycline/sulfamethazine/penicillin combination and tylosin were the most frequently used in-feed antibiotics in weaners and growers/finishers, respectively. The use of antibiotics through water was reported mostly occasionally in all categories. The use of injectable antibiotics was reported mostly in sick pigs. Penicillin was the most common in-water and injectable antibiotic in all categories. The apparent low frequency of critically important antimicrobials for use in humans (quinolones and 3rd generation cephalosporins) is an encouraging finding from a public health perspective. The widespread and frequently reported use of penicillin and tetracycline are of public health concern considering that both antimicrobials are also used for therapeutic purposes in human medicine. PMID:16734370

  17. Antibiotic therapy for acute uncomplicated pyelonephritis in women. Take resistance into account.

    PubMed

    2014-12-01

    Acute uncomplicated pyelonephritis is a bacterial infection of the renal parenchyma, common in women. The bacterium responsible is usually Escherichia coli. Empirical antibiotic therapy should be initiated promptly to prevent serious complications. As of 2014, which empirical antibiotic regimen should be offered to non-pregnant adult women with acute uncomplicated pyelonephritis, while awaiting the results of antimicrobial susceptibility testing? We reviewed the available evidence using the standard Prescrire methodology. Certain oral fluoroquinolones were effective in a few clinical trials in the 2000s and 2010s: ciprofloxacin and levofloxacin, an isomer of ofloxacin. Symptoms resolved within 5 to 7 days in about 96% of the women. In France, in 2011, about 10% of E. coli isolated in community laboratories from outpatients with urinary tract infections were resistant to ciprofloxacin. Resistance is mainly a problem in patients treated with a quinolone during the preceding months and in recently hospitalised patients. In hospital laboratories, the fluoroquinolone resistance rate was about 18% in 2012 in France, and even higher in some other European countries. The main harms of fluoroquinolones are neuropsychiatric disorders, photosensitivity, tendon disorders, arrhythmia and cardiac conduction disorders, and Clostridium difficile infection. Injectable "third-generation" cephalosporins, such as ceftriaxone, are often effective against enterobacteria, in particular E. coli, and have good kidney penetration. The prevalence of E. coli resistance to third-generation cephalosporins is rising rapidly in France, particularly in hospitals: 1% in 2005 versus 10% in 2012. The main harms of cephalosporins are hypersensitivity reactions and C. difficile infection. Monotherapy with an aminoglycoside is an alternative that has not been evaluated in this clinical situation. Due to the serious irreversible adverse effects of aminoglycosides (nephrotoxicity, ototoxicity), they should only be used when the other options are unacceptable. In practice, as of 2014, the first-choice empirical antibiotic treatment for acute uncomplicated pyelonephritis remains an oral fluoroquinolone (ciprofloxacin or ofloxacin) or, in certain cases, the injectable third-generation cephalosporin ceftriaxone. Given the rapid development of bacterial resistance, broader-spectrum antibiotics should not be used as empirical therapy, to preserve their efficacy in serious infections. The empirical treatment should be adjusted as soon as the results of antimicrobial susceptibility testing are known. Whenever possible, it is preferable to avoid the use of fluoroquinolones and third-generation cephalosporins in non-serious infections such as cystitis. PMID:25629148

  18. Antibiotic Susceptibilities of Bacteria Isolated within the Oral Flora of Florida Blacktip Sharks: Guidance for Empiric Antibiotic Therapy

    PubMed Central

    Unger, Nathan R.; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O.

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

  19. Urine from Treated Cattle Drives Selection for Cephalosporin Resistant Escherichia coli in Soil

    PubMed Central

    Subbiah, Murugan; Shah, Devendra H.; Besser, Thomas E.; Ullman, Jeffrey L.; Call, Douglas R.

    2012-01-01

    The U.S. Food and Drug Administration recently issued new rules for using ceftiofur in food animals in part because of an increasing prevalence of enteric bacteria that are resistant to 3rd-generation cephalosporins. Parenteral ceftiofur treatment, however, has limited effects on enteric bacteria so we tested the hypothesis that excreted ceftiofur metabolites exert significant selection pressure for ceftiofur-resistant Escherichia coli in soil. Test matrices were prepared by mixing soil with bovine feces and adding urine containing ceftiofur metabolites (CFM) (0 ppm, ?50 ppm and ?100 ppm). Matrices were incubated at 23°C or 4°C for variable periods of time after which residual CFM was quantified using a bioassay. BlaCMY-2 plasmid-bearing ceftiofur resistant (cefR) E. coli and one-month old calves were used to study the selection effects of CFM and transmission of cefR bacteria from the environment back to animals. Our studies showed that urinary CFM (?13 ppm final concentration) is biologically degraded in soil within 2.7 days at 23°C, but persists up to 23.3 days at 4°C. Even short-term persistence in soil provides a >1 log10 advantage to resistant E. coli populations, resulting in significantly prolonged persistence of these bacteria in the soil (?two months). We further show that resistant strains readily colonize calves by contact with contaminated bedding and without antibiotic selection pressure. Ceftiofur metabolites in urine amplify resistant E. coli populations and, if applicable to field conditions, this effect is far more compelling than reported selection in vivo after parenteral administration of ceftiofur. Because ceftiofur degradation is temperature dependent, these compounds may accumulate during colder months and this could further enhance selection as seasonal temperatures increase. If cost-effective engineered solutions can be developed to limit ex vivo selection, this may limit proliferation for ceftiofur resistant enteric bacteria while preserving the ability to use this important antibiotic in food animal production. PMID:23145021

  20. Study of the Electrophoretic Behavior of Cephalosporins by Capillary Zone Electrophoresis

    PubMed Central

    Hancu, Gabriel; Sasebe?i, Adina; Rusu, Aura; Kelemen, Hajnal; Ciurba, Adriana

    2015-01-01

    Purpose: The aim of the study was the characterization of the electrophoretic behavior of cephalosporins from different generation having different structural characteristics in order to develop a rapid, simple and efficient capillary electrophoretic method for their identification and simultaneous separation from complex mixtures. Methods: Ten cephalosporin derivatives (cefaclor, cefadroxil, cefalexin, cefazolin, cefoxitin, cefuroxime, cefoperazone, cefotaxime, ceftazidime, ceftriaxone) were analyzed by capillary zone electrophoresis using different background electrolyte solutions at different pH values. Electrophoretic mobilities of the analytes were calculated, the influence of the electrophoretic parameteres on the separation was established and the analytical conditions were optimized. Results: Taking into consideration their structural and chemical properties cephalosporins can be detected over a pH range between 6 and 10. The best results were obtained using a buffer solution containing 25 mM disodium hydrogenophosphate - 25 mM sodium dihydrogenophosphate, at a pH – 7.00, + 25 kV voltage at a temperature of 25 °C, UV detection at 210 nm. Using the optimized analytical conditions we achieved the simultaneous baseline separation for seven cephalosporins in less then 10 minutes. Conclusion: Using the described optimized electrophoretic procedures, capillary electrophoresis can be used for the identification and determination of cephalosporins in formulated pharmaceutical products and for their separation from complex mixtures. PMID:26236661

  1. [Structure peculiarities of cell walls of Acremonium chrysogenum--an autotroph of cephalosporin C].

    PubMed

    Kelebina, T S; Seliakh, I O; Gorkovski?, A A; Bezsonov, E E; El'darov, M A; Novak, M I; Domracheva, A G; Bartoshevich, Iu E

    2010-01-01

    Alterations of cell walls of Acremonium chrysogenum occurring at intensive synthesis of cephalosporin C has been studied. It is shown, using electron microscopy, that the cell wall of the cells ofATCC 11550 strain ("wild" type) became looser and thicker during growth. The cell wall of the cells of strain 26/8 (hyperautotroph of cephalosporin C) considerably degraded by the end of the stationary phase. Biochemical analysis has shown that these alterations entailed decrease of the proteins' content covalently or noncovalently linked with the polysaccharides of cell walls of both strains. An increase of sensitivity of cell walls of the strain-superproducer to an activity of lytic enzymes of chitinase, laminarinase, proteinase K, and lyticase preparation has been observed during the growth, but this increase has not been found in the case of "wild" type strain. The obtained results evidence to the structure failure of the cell wall of A. chrysogenum entailing the intensive creation of antibiotic. PMID:21261077

  2. Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action

    PubMed Central

    2012-01-01

    Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs. PMID:22958833

  3. Magnetic separation of antibiotics by electrochemical magnetic seeding

    NASA Astrophysics Data System (ADS)

    Ihara, I.; Toyoda, K.; Beneragama, N.; Umetsu, K.

    2009-03-01

    Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

  4. Multiresistant bacterial infections in liver cirrhosis: Clinical impact and new empirical antibiotic treatment policies

    PubMed Central

    Acevedo, Juan

    2015-01-01

    Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, including the United States and South Korea. The classic empirical antibiotic treatment (third-generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin-clavulanic acid) is still effective in infections acquired in the community, but its failure rate in hospital acquired infections and in some health-care associated infections is high enough to ban its use in these settings. The current editorial focuses on the different epidemiology of bacterial infections in cirrhosis across countries and on its therapeutic implications. PMID:25954474

  5. Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae

    PubMed Central

    Qin, Xuan; Oron, Assaf P.; Adler, Amanda L.; Wolter, Daniel J.; Berry, Jessica E.; Hoffman, Lucas; Weissman, Scott J.

    2014-01-01

    The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae, but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred. PMID:24798269

  6. Ceftaroline fosamil: A super-cephalosporin?

    PubMed

    Ghamrawi, Riane J; Neuner, Elizabeth; Rehm, Susan J

    2015-07-01

    Ceftaroline is a broad-spectrum cephalosporin used to treat infections caused by a variety of microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. However, it is not active against Pseudomonas aeruginosa, Bacteroides fragilis, and carbapenem-resistant Enterobacteriaceae. Its approved indications include community-acquired bacterial pneumonia and bacterial infections of skin and skin structures. It has also been used off-label to treat osteomyelitis, endocarditis, and meningitis caused by ceftaroline-susceptible organisms. PMID:26185943

  7. Prospective Randomized Study for Antibiotic Prophylaxis in Spine Surgery: Choice of Drug, Dosage, and Timing

    PubMed Central

    Kailash, Kannan Karthick; Vijayraghavan, P.V.

    2013-01-01

    Study Design Prospective randomized study of antibiotic prophylaxis in elective spine surgery. Purpose The aim of this study was to compare the rate of postoperative surgical site infection for a single dose of two different generations of cephalosporin with different dosage and timing of the antibiotics. Overview of Literature Current recommendation for prophylaxis in elective spine surgery is up to 60 minutes prior to incision. No study has investigated between different generation of cephalosporin for prophylaxis in elective spine surgery with respect to choice, dosage and timing. Methods This study was a prospective randomized study of 90 patients, assessed for the occurrence of surgical site infection (defined by the Centers for Disease Control and Prevention criteria) and other infections for up to 6 months after surgery. Demographic, surgical and further data were collected on subsequent operations, including hardware removal. Results Mean age in our group was 47 years (range, 19-71 years). The male to female ratio was 49:41 and the average timing of administration of antibiotics was 77 minutes (range, 30-120 minutes). The average blood loss was 626 mL (range, 150-3,000 mL) with a mean duration of surgery for 3.2 hours (range, 1.5-6 hours). One case of superficial infection and one case of deep infection met the exclusion criteria. Conclusions Our results support the use of a single preoperative dose of antibiotics in instrumented and non-instrumented elective spine surgery up to one hour prior to incision. There was no difference in terms of occurrence of surgical site infection with respect to dosage, choice and timing of antibiotics. PMID:24066215

  8. Synergism between aminoglycosides and cephalosporins with antipseudomonal activity: interaction index and killing curve method.

    PubMed Central

    Hallander, H O; Dornbusch, K; Gezelius, L; Jacobson, K; Karlsson, I

    1982-01-01

    Combinations of gentamicin with cefotaxime, moxalactam, and ceftazidime were tested against 43 bacterial strains, most of them blood isolates. With an interaction index of less than or equal to 0.5 as borderline, synergism was demonstrated against 30 to 40% of the strains by the fractional inhibitory concentration index and against 50 to 70% by the fractional bactericidal concentration index. The reproducibility of the index was within +/- 0.2 for two-thirds of 40 repetitive assays and within +/- 0.4 to 0.5 for all of these assays. Similar results were obtained when netilmicin was substituted for gentamicin. The killing curve system for studying antibiotic synergism was standardized to give results comparable to those obtained with the interaction index. This was achieved when one-half of a previously determined minimum bactericidal concentration was used for single drugs and the amount of antibiotic was at least halved again when drugs were used in combination. An initial bacterial concentration of 10(5) to 10(6) colony-forming units per ml is recommended. Given these conditions, synergism could be defined as a 2-log 10 or more decrease in viable count given by both drugs together, as compared with the more active of the pair after 24 h. Prediction of killing curve results could then be obtained with the fractional bactericidal concentration index. When cephalosporins and gentamicin were combined from the start, the beta-lactam antibiotics were less susceptible to inactivation, as demonstrated in time-killing assays. If one of the antibiotics were added after 24 h, synergism was not demonstrable. The results indicate that the new cephalosporins may be advantageously combined with aminoglycosides. PMID:7181485

  9. “Affect of anaerobiosis on the antibiotic susceptibility of H. influenzae”

    PubMed Central

    2013-01-01

    Background Haemophilus influenzae is a human-restricted facultative anaerobe which resides mostly in the oropharynx. The majority of isolates recovered from the throat are unencapsulated commensals (NTHi), but depending on host susceptibility they cause bronchitis, otitis media and on occasion bacteremia and meningitis. Because of the variable oxygen availability in the various niche permitting bacterium replication, the organism must thrive in well oxygenated surfaces, such as pharyngeal epithelium to anoxic environments like the bottom of a Biofilm and in airway mucus. Other reports indicate that H. influenzae use aerobic respiration, anaerobic respiration and fermentation to generate ATP. To gain insight in to the activity of several classes of antibiotics against five well-characterized unencapsulated H. influenzae in room air, in 5% CO2 and under strict anaerobiosis. We also tested for the role of oxidative killing by all cidal antibiotics. Results In comparison to room air, testing in 5% CO2 had minimal effects on the susceptibility to aminoglycosides, cephalosporins, tetracycline and chloramphenicol: the MIC of rifampin and ciprofloxacin increased eight fold with certain strains in 5% CO2. All antibiotics, except trimethoprim were cidal under both growth conditions. Aminoglycosides remained bactericidal in a strict anaerobic environment, while a reliable MBC was obtained with trimethoprim only under anaerobic conditions. Kinetic analysis of the cidal action of spectinomycin and tetracycline indicated slower killing anaerobically. An oxidative mechanism for aerobic killing could not be demonstrated. Conclusions We conclude that ?-lactams, cephalosporins, macrolides, tetracycline’s, aminoglycosides, chloramphenicol, rifampin and ciprofloxacin are bactericidal against five well-characterizes H. influenzae in an aerobic and anaerobic environment. The activity of trimethoprim was increased in anaerobic conditions. PMID:23803418

  10. The eradication of bacterial persisters with antibiotic-generated hydroxyl radical

    E-print Network

    Haseley, Nathan Scott

    During Mycobacterium tuberculosis infection, a population of bacteria likely becomes refractory to antibiotic killing in the absence of genotypic resistance, making treatment challenging. We describe an in vitro model ...

  11. Purification and characterization of a cephalosporin esterase from Rhodosporidium toruloides.

    PubMed Central

    Politino, M; Tonzi, S M; Burnett, W V; Romancik, G; Usher, J J

    1997-01-01

    A novel cephalosporin esterase (EC 3.1.1.41) from Rhodosporidium toruloides was purified to gel electrophoretic homogeneity. The enzyme is a glycoprotein with a molecular mass of 80 kDa. Upon deglycosylation, several forms of the enzyme were observed with a molecular mass range between 60 and 66 kDa. The isoelectric point of the enzyme is approximately 5.6, with the pH optimum for activity occurring at 6.0. The optimal activity of the enzyme occurred at 25 degrees C, with the enzyme rapidly losing activity at temperatures above 25 degrees C. The enzyme deacetylated a variety of cephalosporin derivatives, including cephalosporin C; the Km for this substrate is 51.8 mM, and the Vmax is 7.9 mumol/min/mg. In addition to cephalosporins, the enzyme hydrolyzed short-chain p-nitrophenyl esters, with the activity decreasing with increasing ester chain length. The enzyme also has the ability to acetylate desacetyl cephalosporins in high yields under mild conditions in the presence of various acetyl donors. A comparison of the physical properties of the esterase with those of other well-characterized cephalosporin esterases indicates that the enzyme is unique in this class. PMID:9406399

  12. Safety of cefepime: a new extended-spectrum parenteral cephalosporin.

    PubMed

    Neu, H C

    1996-06-24

    The purpose of this study was to compare the safety profile of cefepime, a new extended-spectrum, fourth-generation cephalosporin used to treat mild-to-severe bacterial infections, with that of ceftazidime. A total of 2,032 patients enrolled in North American and European cefepime trials were analyzed. The study population spanned adolescence to the elderly (15-100 years); the median age was 62 years. Cefepime was compared with ceftazidime (1,456 patients), a third-generation cephalosporin. Cefepime dosing was 1-4 g/day (0.5-2.0 g twice daily) for adults; ceftazidime dosing was 1-6 g/day (0.5 g every 12 hours to 2.0 g every 8 hours). A limited number of cefepime-treated patients received 2 g every 8 hours. The median length of dosing for both cefepime and ceftazidime was 7 days. In randomized trials in which cefepime (2,032 patients) was compared with ceftazidime (1,456 patients), analysis of comparative data indicated that adverse events of probable or unknown relation to study drugs were observed in 13.8% of cefepime patients and 15.6% of ceftazidime patients. The most commonly observed adverse event for cefepime was headache (2.4%), followed by nausea (1.8%), rash (1.8%), and diarrhea (1.7%). For ceftazidime, the most commonly observed adverse event was diarrhea (3.2%), followed by headache (2.5%), nausea (2.1%), rash (1.9%), and constipation (1.5%). The incidence of positive Coombs' test was higher in high-dose cefepime recipients than in ceftazidime recipients (14.5% vs 8.7%; p = 0.043), although there was no evidence of hemolysis in either treatment group. Coadministration of analgesics, diuretics, and anticoagulants did not increase incidence of adverse events associated with study-drug therapy. Adverse renal and hematologic events, as well as anaphylaxis and death, were rare in both groups. In the comparative trials with cefepime, anaphylaxis was reported in no patients receiving cefepime and in one patient receiving ceftazidime. None of the three seizures reported in patients receiving cefepime and one of six seizures in patients receiving ceftazidime were of probable or possible relationship to the study drugs. None of the 12 cases of gastrointestinal hemorrhage reported in cefepime patients or five cases reported in ceftazidime patients were judged to be related to treatment drug. Tolerance for intravenous administration in both treatment groups was similar. Cefepime did not effect any significant or unusual allergic, hematologic, gastrointestinal, neurologic, or renal toxicity when administered to patients with mild-to-severe infections, including those receiving concomitant medications. The safety profile of cefepime is excellent and comparable to that of ceftazidime and those reported for other cephalosporins. PMID:8678100

  13. Antibiotic Prescribing among Pediatric Inpatients with Potential Infections in Two Private Sector Hospitals in Central India

    PubMed Central

    Pathak, Ashish; Stålsby Lundborg, Cecilia

    2015-01-01

    Introduction Infectious diseases are one of the major causes of child mortality in India. Pediatric patients are commonly prescribed antibiotics for non-bacterial infections. Monitoring of local antibiotic prescribing with respect to the diagnosis is necessary to improve the prescribing practices. The aim of the study was to describe antibiotic prescribing for potential infections among patients admitted in pediatric departments in two private sector hospitals; one teaching (TH) and one non-teaching (NTH) in Central India. Methods Data from all patients admitted at the pediatric departments of both study hospitals was collected manually, for 3 years (2008–2011) using a customized form. Data from inpatients aged 0–18 years, diagnosed with; acute gastroenteritis (AGE), respiratory tract infections, enteric fever, viral fever or unspecified fever were focused for analysis. Antibiotic prescriptions were analysed using the WHO Anatomical Therapeutic Chemical (ATC) classification system and defined daily doses (DDDs). Adherence to the Indian Academy of Pediatrics list of essential medicines (IAP-LEM) was investigated. P-values <0.05 were considered significant. Results Oftotal6, 825 inpatients admitted at two pediatric departments, 510 patients from the TH and 2,479from the NTH were selected based on the assigned potential infectious diagnoses. Of these, 224 patients (44%) at the TH and 2,088 (84%) at the NTH were prescribed at least one antibiotic during hospital stay (odds ratio-0.69, 95%confidence interval-0.52 to 0.93; p<0.001). Patients with AGE, viral- and enteric fever were frequently prescribed antibiotics at both hospitals, yet higher proportion were prescribed antibiotics at the NTH compared to the TH. Broad-spectrum antibiotics were the most commonly prescribed antibiotic class in both hospitals, namely third generation cephalosporins, J01DD (69%) at the TH, and new fixed dose combinations of antibiotics J01R (FDCs, 42%) at the NTH. At the TH, 37% of the antibiotic prescriptions were comprised of antibiotics listed in the IAP-LEM, compared to 24% at the NTH (p<0.05). Conclusions Broad-spectrum antibiotics were prescribed frequently in both hospitals also for the un-indicated conditions such as viral fever and enteric fever. At the NTH, new FDCs were more frequently prescribed and adherence to the IAP-LEM was substantially lower at the NTH compared to the TH. The results demonstrate need to develop diagnosis-specific prescribing guidelines to facilitate rational use of antibiotics and implement antibiotic stewardship program. PMID:26540104

  14. Bacteriology and antibiotic resistance pattern in community acquired urinary tract infection.

    PubMed

    Sharan, Rajiv; Kumar, Dhananjay; Mukherjee, B

    2013-07-01

    Extensive use of antibiotics have resulted in development of resistance among most commonly used drugs in community acquired urinary tract infection (UTI). This study was conducted to identify the resistance pattern in community acquired UTI .We collected urine for routine examination and culture from suprapubic urine in all the cases to avoid any contamination. E. Coli was the most common organism identified. Among oral antibiotics, there was high degree of resistance to penicillin group and cephalosporin groups. Among parentral antibiotics, all the cephalosporins were variably resistant except cephaperazone-salbactum. PMID:23942441

  15. Gentamicin Nephrotoxicity: Failure of Three Cephalosporins to Potentiate Injury in Rats

    PubMed Central

    Harrison, William O.; Silverblatt, Fredric J.; Turck, Marvin

    1975-01-01

    The possibility that gentamicin and cephalosporin antibiotics may act synergistically to produce nephrotoxicity was evaluated in an experimental model. Necrosis of the proximal tubules occurred when rats were treated with 60 to 120 mg/kg of gentamicin for 5 days but not when 15 to 20 mg/kg per day was given for up to 4 weeks. In all gentamicin-treated animals lysosomes of proximal tubules were increased in size and number and the lumens of many tubules contained a granular deposit. Examination by electron microscopy revealed that the abnormal lysosomes contained membranous whorls. The luminal deposits consisted of similar material; identical bodies were also present in the urinary sediment. To determine whether concurrent administration of a cephalosporin would augment the nephrotoxic potential of gentamicin, additional rats were treated for 4 weeks with daily injections of gentamicin (20 mg/kg) and either cephaloridine, cephalothin, or cefazolin (500 mg/kg). None of the combination regimens produced any more injury than did gentamicin alone. Images PMID:1180545

  16. The role of prophylactic antibiotics on surgical site infection in elective laparoscopic cholecystectomy

    PubMed Central

    Chong, Jae Uk; Lim, Jin Hong; Kim, Jee Ye; Kim, Sung Hoon

    2015-01-01

    Backgrounds/Aims Although laparoscopic cholecystectomy is a common and widely accepted technique, the use of prophylactic antibiotics in elective laparoscopic cholecystectomy still remains controversial. The aim of this study is to determine whether prophylactic antibiotics could prevent surgical site infection after elective laparoscopic cholecystectomy and to identify any risk factors for surgical site infection. Methods This study included 471 patients undergoing laparoscopic cholecystectomy between January 2009 and May 2012. Period 1 patients (279) received second generation cephalosporin 1 g intravenously after induction of anesthesia, and Period 2 patients (192) were not given prophylactic antibiotics. The characteristics and surgical site infections of the patients were compared and analyzed. Results The overall rate of surgical site infection was 1.69% for the total of 471 patients. The incidence of surgical site infection was similar for the two Periods: 5 of 279 patients (1.79%) in Period 1, 3 of 192 patients (1.56%) in Period 2 (p=0.973). All of the patients with surgical site infections were well treated under conservative treatments without any sequelae. The preoperative albumin level (p=0.023) contributed to surgical site infection. Conclusions Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy but patients in poor nutritional state with low albumin level should consider prophylactic antibiotics. PMID:26693239

  17. Salmonella bacteraemia in Pokhara: emergence of antibiotic resistance.

    PubMed

    Guha, Simantee; Jalan, Basavaraj Yogitha; Dey, Sangeeta; Easow, Joshy Maducolil; Wilson, Godwin; Shivananda, Padavagadu Ganapati

    2005-06-01

    We undertook a retrospective hospital based study of 2,354 blood culture specimens from June 2000 to May 2003 in order to determine the isolation rates of Salmonella species and their antibiotic susceptibility patterns in western Nepal. Blood samples were cultured and identification of Salmonella species. and their antibiotic susceptibility testing were done as per standard protocol. Of the total 114 (4.8 %) yielded Salmonella species. Of them 76 (66.7%) Salmonella typhi and 38 (33.3%) S. paratyphi A. S. typhi was found to be the predominant species each year. Higher proportion of Salmonella bacteraemia was seen in adults, with a clearcut male to female preponderance (1.8:1). Monsoons enhanced the risk of acquiring enteric fever. There is also a rise in the number of multi-drug resistant strains in and around Pokhara Valley, with 40.7% S. typhi and 5.2% S. paratyphi A showing resistance to two or more antibiotics. These isolates were primarily resistant to the first line drugs namely Ampicillin, Chloramphenicol and Cotrimoxazole but susceptible to third generation Cephalosporins. Appearance of multi drug resistance poses considerable threat of increased morbidity and mortality in this region. This emphasizes the need for prudent use of antimicrobials. PMID:16295716

  18. Determination of cephalosporins in solid binary mixtures by polarized IR- and Raman spectroscopy.

    PubMed

    Koleva, Bojidarka B; Kolev, Tsonko M; Spiteller, Michael

    2008-09-10

    Quantitative IR- and Raman spectroscopic determinations of four cephalosporin antibiotics in six solid binary mixtures have been conducted. This is a new approach for spectroscopic determination of these antibiotics, since the corresponding quantitative analysis in solution only has been reported so far. The correlation coefficient r2 was found to be in the confidence intervals within 99.32-99.88% and 99.90-95.54% for the systems under study by using the absorption ratios of the characteristic bands at 800 cm(-1) and 721 cm(-1) present in the IR- and Raman spectra of the antibiotic compounds cephalexin, cephalotin, cephaloglycin and cephamandole, respectively. Solid-state linear dichroic infrared (IR-LD) spectral analysis of the solid mixtures was carried out in order to obtain experimental IR-spectroscopic assignment of the compounds studied. Independent high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis was performed for the validation of the vibrational spectroscopic data. The application of this instrumental analytical tool for the analysis of 10 tablets of the commercial products Cefamandole and Cefalotin (Actavis) was also studied. PMID:18602240

  19. Expedient antibiotics production: Final report

    SciTech Connect

    Bienkowski, P.R.; Byers, C.H.; Lee, D.D.

    1988-05-01

    The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented. This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.

  20. [First and second line antibiotic therapy for bacterial meningitis in infants and children].

    PubMed

    Sarlangue, J; Castella, C; Lehours, P

    2009-01-01

    The potential severity of meningitis in infants and children requires an optimized initial empirical therapy, mainly based on direct cerebro spinal fluid (CSF) examination, and rapid therapeutic adaptation according to bacterial identification and susceptibility. Combination treatment including cefotaxim (300 mg/kg per day) or ceftriaxone (100mg/kg per day) and vancomycine (60 mg/kg per day) remains the standard first line if pneumococcal meningitis cannot be ruled out. A simple treatment with third generation cephalosporin can be used for Neisseria meningitidis or Haemophilus influenzae meningitis, aminoglycosides must be added in case of Enterobacteriacae, mainly before 3 months of age. Second line antibiotic therapy is adapted according to the clinical and bacteriological response on Day 2. When the minimal inhibitory concentration (MIC) of pneumococcal strain is less than 0.5mg/L, third generation cephalosporin should be continued alone for a total of 10 days. In other cases, a second lumbar puncture is necessary and the initial regimen, with or without rifampicin combination, should be used for 14 days. Amoxicillin during 3 weeks, associated with gentamycin or cotrimoxazole is recommended for listeriosis. PMID:19409744

  1. Short-duration, single-agent antibiotic prophylaxis for meningitis in trans-sphenoidal surgery.

    PubMed

    Little, Andrew S; White, William L

    2011-12-01

    Perioperative bacterial meningitis after trans-sphenoidal surgery for pituitary and parasellar lesions is an uncommon but serious complication. Little evidence guides the choice of chemoprophylaxis in this setting. To begin to address this deficiency, we investigated the incidence of perioperative meningitis in 442 patients who underwent trans-sphenoidal surgery and received a short chemoprophylaxis regimen with a single agent and did not require lumbar drainage. In 2005 we instituted a standardized antibiotic prophylaxis protocol for trans-sphenoidal surgery that utilized intravenous cefuroxime, a second-generation cephalosporin with broad coverage and excellent spinal fluid penetration, administered 30 min before surgery and 8 h later. The primary endpoint was the incidence of perioperative (within 30 days of surgery) bacterial meningitis. Data from The Barrow Pituitary Outcomes Project, a prospectively maintained patient research database, were supplemented with review of medical records and hospital discharge codes. There were no cases of perioperative meningitis. Three patients developed delayed meningitis associated with persistent or recurrent spinal fluid leakage 2-8 months after surgery. Perioperatively, seven patients received additional antibiotics for urinary tract infections. A single-agent, short-duration chemoprophylaxis regimen for trans-sphenoidal surgery is effective at preventing perioperative meningitis in patients who do not require lumbar drainage after surgery. The results of this regimen compare favorably to historical rates achieved with longer regimens that use two antibiotics. Future studies will investigate the role prophylactic antibiotics play in nasal mucosa healing and sinusitis. PMID:21347665

  2. Non-heme iron oxygenases generate natural structural diversity in carbapenem antibiotics.

    PubMed

    Bodner, Micah J; Phelan, Ryan M; Freeman, Michael F; Li, Rongfeng; Townsend, Craig A

    2010-01-13

    Carbapenems are a clinically important antibiotic family. More than 50 naturally occurring carbapenam/ems are known and are distinguished primarily by their C-2/C-6 side chains where many are only differentiated by the oxidation states of these substituents. With a limited palette of variations the carbapenem family comprises a natural combinatorial library, and C-2/C-6 oxidation is associated with increased efficacy. We demonstrate that ThnG and ThnQ encoded by the thienamycin gene cluster in Streptomyces cattleya oxidize the C-2 and C-6 moieties of carbapenems, respectively. ThnQ stereospecifically hydroxylates PS-5 (5) giving N-acetyl thienamycin (2). ThnG catalyzes sequential desaturation and sulfoxidation of PS-5 (5), giving PS-7 (7) and its sulfoxide (9). The enzymes are relatively substrate selective but are proposed to give rise to the oxidative diversity of carbapenems produced by S. cattleya, and orthologues likely function similarly in allied streptomyces. Elucidating the roles of ThnG and ThnQ will focus further investigations of carbapenem antibiotic biosynthesis. PMID:20017478

  3. Antibiotic Safety

    MedlinePLUS

    ... Copyright © 2005 by The Association for Professionals in Infection Control and Epidemiology (APIC). www.apic.org Antibiotic Safety What are Antibiotics? Antibiotics are powerful medicines that help stop bacterial infections. They are used to kill germs that cause ...

  4. Influence of hybrid inorganic/organic mesoporous and nanostructured materials on the cephalosporins' efficacy on different bacterial strains.

    PubMed

    Carmen Chifiriuc, M; Mihaiescu, D; Ilinca, E; Marutescu, L; Mihaescu, G; Mihai Grumezescu, A

    2012-12-01

    The aim of this study was to investigate the effect of different hybrid inorganic-organic micro- and nanomaterials (Fe(3)O(4)/PEG(600), Fe(3)O(4)/C(12), ZSM-5) on the antibacterial activity of different cephalosporins against Gram-positive and Gram-negative bacterial strains. The synergic effect of the studied materials was demonstrated by the increase in the growth inhibition zones diameter. All tested hybrid micro- and nanomaterials increased the activity of cefotaxime against Staphylococcus aureus. ZSM-5 increased the activity of cefotaxime and ceftriaxone and Fe(3)O(4)/C(12) that of ceftriaxone against Pseudomonas aeruginosa and S. aureus. The anti-Pseudomonas, anti-Klebsiella pneumoniae and anti-Bacillus subtilis activity of cefoperazone was increased by Fe(3)O(4)/C(12) nanoparticles, while the ZSM-5 improved its anti-Escherichia coli, K. pneumoniae, S. aureus and B. subtilis activity, whereas Fe(3)O(4)/PEG(600) against K. pneumoniae. The anti-K. pneumoniae activity of cefepime was increased by all tested nanoparticles, whereas its anti-B. subtilis and anti-E. coli activity was improved by Fe(3)O(4)/C(12) and Fe(3)O(4)/PEG(600) nanoparticles. In conclusion, both magnetic Fe(3)O(4) nanoparticles, charged outside as extra-shell with the antibiotic as well as ZSM-5 microparticles carrying the antibiotic inside the pores, significantly and specifically improved cephalosporin efficacy. A probable explanation for the increase in the antibiotic efficiency is the better penetration through the cellular wall of the antibiotic charged nanoparticles. PMID:23101869

  5. Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes methicillin-resistant Staphylococcus aureus (MRSA) to ?-lactam antibiotics

    PubMed Central

    Podoll, Jessica D.; Liu, Yongxiang; Chang, Le; Walls, Shane; Wang, Wei; Wang, Xiang

    2013-01-01

    The continuous emergence of resistant bacteria has become a major worldwide health threat. The current development of new antibacterials has lagged far behind. To discover reagents to fight against resistant bacteria, we initiated a chemical approach by synthesizing and screening a small molecule library, reminiscent of the polycyclic indole alkaloids. Indole alkaloids are a class of structurally diverse natural products, many of which were isolated from plants that have been used as traditional medicine for millennia. Specifically, we adapted an evolutionarily conserved biosynthetic strategy and developed a concise and unified diversity synthesis pathway. Using this pathway, we synthesized 120 polycyclic indolines that contain 26 distinct skeletons and a wide variety of functional groups. A tricyclic indoline, Of1, was discovered to selectively potentiate the activity of ?-lactam antibiotics in multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA), but not in methicillin-sensitive S. aureus. In addition, we found that Of1 itself does not have antiproliferative activity but can resensitize several MRSA strains to the ?-lactam antibiotics that are widely used in the clinic, such as an extended-spectrum ?-lactam antibiotic amoxicillin/clavulanic acid and a first-generation cephalosporin cefazolin. These data suggest that Of1 is a unique selective resistance-modifying agent for ?-lactam antibiotics, and it may be further developed to fight against resistant bacteria in the clinic. PMID:24019472

  6. Mass spectrometry of beta-lactam antibiotics with special reference to ionization by fast atom bombardment (FAB).

    PubMed

    Casy, A F; Cryer, C; Ominde, E M

    1989-01-01

    The mass spectral characteristics of the majority of penicillin and cephalosporin beta-lactam antibiotics in world-wide clinical use are presented and reviewed. Special attention is given to the spectra recorded under fast atom bombardment (FAB) conditions and novel data on many penicillins and cephalosporins are included. Mass spectrometry features of common degradation products of benzylpenicillin and of some synthetic intermediates are also presented. The data illustrate the value of FAB mass spectrometry in identifying members of this closely related group of antibiotics without need for derivatization. PMID:2490371

  7. Minimum requirements of hydrophobic and hydrophilic features in cationic peptide antibiotics (CPAs): pharmacophore generation and validation with cationic steroid antibiotics (CSAs).

    PubMed

    Sundriyal, Sandeep; Sharma, Rohit K; Jain, Rahul; Bharatam, Prasad V

    2008-04-01

    Cationic peptide antibiotics (CPAs) are known to possess amphiphilic structure, by virtue of which they display lytic activity against bacterial cell membranes. Naturally occurring antimicrobial peptides contain a large number of amino acid residues, which limits their clinical applicability. Recent studies indicate that it is possible to decrease the chain-length of these peptides without loss of activity, and suggest that a minimum of two positive ionizable (hydrophilic) and two bulky groups (hydrophobic) are required for antimicrobial activity. By employing the HipHop module of the software package CATALYST, we have translated these experimental findings into 3-D pharmacophore models by finding common features among active peptides. Positively ionizable (PI) and hydrophobic (HYD) features are the important characteristics of compounds used for pharmacophore model development. Based on the highest score and the presence of amphiphilic structure, two separate hypothesis, Ec-2 and Sa-6 for Escherichia coli and Staphylococcus aureus, respectively, were selected for mapping analysis of active and inactive peptides against these organisms. The resulting models not only provided information on the minimum requirement of PI and HYD features but also indicated the importance of their relative arrangement in space. The minimum requirement for PI features was two in both cases but the number of HYD features required in the case of E. coli was four while for S. aureus it was found to be three. These hypotheses were able to differentiate between active and inactive CPAs against both organisms and were able to explain the experimental results. The hypotheses were further validated using cationic steroid antibiotics (CSAs), a different class of facial amphiphiles with same mechanism of antimicrobial action as that of CPAs. The results showed that CSAs also require similar minimum features to be active against both E. coli and S. aureus. These studies also indicate that the minimum feature requirements may be conserved for different strains of the same organism. Figure shows the mapping of an active cationic peptide antibiotic (CPA) mapped to the most acceptable hypothesis Sa6 against S. aureus. PMID:18270757

  8. Ceftolozane/Tazobactam: A Novel Cephalosporin/?-Lactamase Inhibitor Combination.

    PubMed

    Cho, Jonathan C; Fiorenza, Mallory A; Estrada, Sandy J

    2015-07-01

    Ceftolozane/tazobactam is a novel antipseudomonal ?-lactam/?-lactamase inhibitor combination that is currently approved by the United States Food and Drug Administration for the treatment of complicated intraabdominal infections (cIAI) and complicated urinary tract infections (cUTI). It exhibits bactericidal properties through inhibition of bacterial cell wall biosynthesis, which is mediated through penicillin-binding proteins (PBPs). Ceftolozane is a potent PBP3 inhibitor and has a higher affinity for PBP1b compared with other ?-lactam agents. Ceftolozane/tazobactam differs from other cephalosporins due to its increased activity against some AmpC ?-lactamases and Pseudomonas aeruginosa. The addition of tazobactam provides enhanced activity against extended-spectrum ?-lactamase (ESBL)-producing Enterobacteriaceae and certain anaerobic organisms. Population pharmacokinetic studies for ceftolozane and ceftolozane/tazobactam are best described by a two-compartment model with zero-order input and linear elimination. Similar to other cephalosporins, the best pharmacodynamic property to predict efficacy for ceftolozane/tazobactam is a concentration that remains above the minimum inhibitory concentration (MIC) for 40-50% of the dosing interval. For Enterobacteriaceae and P. aeruginosa strains, the time above the MIC (T > MIC) needed to produce bactericidal activity was much less with ceftolozane than other cephalosporins, with T > MIC requirements of approximately 30%. For currently approved indications, the dose of ceftolozane/tazobactam is 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) intravenously every 8 hours given as a 1-hour infusion. Ceftolozane has low plasma protein binding (20%) and is predominantly excreted unchanged in the urine (? 92%). Dosage adjustments are required for moderate-to-severe renal impairment and in patients receiving hemodialysis. Based on data from clinical trials, adverse effects due to ceftolozane/tazobactam do not differ considerably from other cephalosporins, with the most common being nausea, diarrhea, headache, and pyrexia. Ceftolozane/tazobactam is a promising new agent for the treatment of cIAI and cUTI, including those caused by multidrug-resistant gram-negative organisms. PMID:26133315

  9. Cephalosporins to carbapenems: 1-oxygenated carbapenems and carbapenams.

    PubMed

    Rosati, R L; Kapili, L V; Morrissey, P; Retsema, J A

    1990-01-01

    The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corresponding carbapenem. The resulting 1-oxocarbapenems (2) were selectively transformed through reduction into 1-oxygenated carbapenems and carbapenams (3 and 4, respectively). On microbiological screening, a carbapenem (3c) was found to possess a broad spectrum of activity. An interesting antibacterial profile was discovered for a carbapenam (26). PMID:2404120

  10. New spectrofluorimetric method for determination of cephalosporins in pharmaceutical formulations.

    PubMed

    Ali Ahmed, Shazalia M; Elbashir, Abdalla A; Suliman, Fakhr Eldin O; Aboul-Enein, Hassan Y

    2013-01-01

    A simple, accurate, precise spectrofluorimetric method has been proposed for the determination of three cephalosporins, namely, cefixime (cefi), cephalexine (ceph), and cefotaxime sodium (cefo) in pharmaceutical formulations. This method is based on a reaction between cephalosporins with 8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt (HPTS) in alkaline medium, at pH 12.0 for cefi and 13.0 for ceph and cefo to give highly fluorescent derivatives extracted with chloroform and subsequent measurements of the formed fluorescent products at 520, 500 and 510?nm after excitation at 480, 470 and 480?nm for cefi, ceph and cefo respectively. The optimum experimental conditions have been studied. Beer's law is obeyed over concentrations of 10-60?ng/mL, 5-35?ng/mL and 10-60?ng/mL for cefi, ceph and cefo, respectively. The detection limits were 4.20?ng/mL, 2.54?ng/mL and 4.09?ng/mL for cefi, ceph and cefo, respectively, with a linear regression correlation coefficient of 0.99783, 0.99705 and 0.9978 and recoveries in ranges 96.96-105.77, 96.13-102.55 and 95.45-105.39% for cefi, ceph and cefo, respectively. This method is simple and can be applied for the determination of cefi, ceph and cefo in pharmaceutical formulations in quality control laboratories. PMID:22991324

  11. Antibiotics Quiz

    MedlinePLUS

    ... Adult Treatment Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving ...

  12. Assessment of copper and zinc salts as selectors of antibiotic resistance in Gram-negative bacteria.

    PubMed

    Becerra-Castro, Cristina; Machado, Rita A; Vaz-Moreira, Ivone; Manaia, Célia M

    2015-10-15

    Some metals are nowadays considered environmental pollutants. Although some, like Cu and Zn, are essential for microorganisms, at high concentrations they can be toxic or exert selective pressures on bacteria. This study aimed to assess the potential of Cu or Zn as selectors of specific bacterial populations thriving in wastewater. Populations of Escherichia coli recovered on metal-free and metal-supplemented culture medium were compared based on antibiotic resistance phenotype and other traits. In addition, the bacterial groups enriched after successive transfers in metal-supplemented culture medium were identified. At a concentration of 1mM, Zn produced a stronger inhibitory effect than Cu on the culturability of Enterobacteriaceae. It was suggested that Zn selected populations with increased resistance prevalence to sulfamethoxazole or ciprofloxacin. In non-selective culture media, Zn or Cu selected for mono-species populations of ubiquitous Betaproteobacteria and Flavobacteriia, such as Ralstonia pickettii or Elizabethkingia anophelis, yielding multidrug resistance profiles including resistance against carbapenems and third generation cephalosporins, confirming the potential of Cu or Zn as selectors of antibiotic resistant bacteria. PMID:26057541

  13. Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital

    PubMed Central

    Niwa, T; Shinoda, Y; Suzuki, A; Ohmori, T; Yasuda, M; Ohta, H; Fukao, A; Kitaichi, K; Matsuura, K; Sugiyama, T; Murakami, N; Itoh, Y

    2012-01-01

    Background Antimicrobial stewardship has not always prevailed in a wide variety of medical institutions in Japan. Methods The infection control team was involved in the review of individual use of antibiotics in all inpatients (6348 and 6507 patients/year during the first and second annual interventions, respectively) receiving intravenous antibiotics, according to the published guidelines, consultation with physicians before prescription of antimicrobial agents and organisation of education programme on infection control for all medical staff. The outcomes of extensive implementation of antimicrobial stewardship were evaluated from the standpoint of antimicrobial use density, treatment duration, duration of hospital stay, occurrence of antimicrobial-resistant bacteria and medical expenses. Results Prolonged use of antibiotics over 2 weeks was significantly reduced after active implementation of antimicrobial stewardship (2.9% vs. 5.2%, p < 0.001). Significant reduction in the antimicrobial consumption was observed in the second-generation cephalosporins (p = 0.03), carbapenems (p = 0.003), aminoglycosides (p < 0.001), leading to a reduction in the cost of antibiotics by 11.7%. The appearance of methicillin-resistant Staphylococcus aureus and the proportion of Serratia marcescens to Gram-negative bacteria decreased significantly from 47.6% to 39.5% (p = 0.026) and from 3.7% to 2.0% (p = 0.026), respectively. Moreover, the mean hospital stay was shortened by 2.9 days after active implementation of antimicrobial stewardship. Conclusion Extensive implementation of antimicrobial stewardship led to a decrease in the inappropriate use of antibiotics, saving in medical expenses, reduction in the development of antimicrobial resistance and shortening of hospital stay. PMID:22846073

  14. Retrospective analysis of antibiotic resistance pattern to urinary pathogens in a Tertiary Care Hospital in South India

    PubMed Central

    Somashekara, Saligrama Chikkannasetty; Deepalaxmi, Salmani; Jagannath, Narumalla; Ramesh, Bannaravuri; Laveesh, Madathil Ravindran; Govindadas, Damodaram

    2014-01-01

    Context: The distribution of uropathogens and their susceptibility pattern to antibiotics vary regionally and even in the same region, they change over time. Therefore, the knowledge on the frequency of the causative microorganisms and their susceptibility to various antibiotics are necessary for a better therapeutic outcome. Aim: The aim was to study the frequency and distribution of uropathogens and their resistance pattern to antibiotics in a tertiary care hospital. Settings and Design: Retrospective study for a period of 1 year from January 2011 to December 2011 in a tertiary care hospital. Materials and Methods: The culture and sensitivity data of the uropathogens from suspected cases of UTI were collected from the records of Microbiology Department for study period. Midstream urine samples were processed for microscopy and culture, and the organisms were identified by standard methods. Antibiotic susceptibility was carried out by Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute guidelines. Descriptive statistics were used to analyze the data. Results: Of 896 urine samples, 348 (38.84%) samples were positive for urine culture. Escherichia coli (52.59%) was the most common organism followed by Klebsiella. E. coli was least resistant to imipenem (8%) and amikacin (16%) and was highly resistant to co-trimoxazole (69%) and ampicillin (86%). Klebsiella species were least resistant to amikacin (26%) and were highly resistant to ampicillin (92%). The overall resistance pattern of antibiotics to uropathogens was the highest to nalidixic acid (79%) followed by co-trimoxazole (75%) and ampicillin (72%). Good susceptibility was seen with imipenem and cephalosporins. Conclusion: E. coli is still the most common uropathogen. Nalidixic acid, ampicillin, co-trimoxazole, and first-generation fluoroquinolones have limited value for the treatment of UTI. Sensitivity to imipenem and amikacin are still retained and may be prescribed for complicated UTI. Routine monitoring of drug resistance pattern will help to identify the resistance trends regionally. This will help in the empirical treatment of UTIs to the clinicians. PMID:25316990

  15. Antibiotic Resistance

    MedlinePLUS

    ... better. If you stop treatment too soon, some bacteria may survive and re-infect you. Don't save antibiotics for later or use someone else's prescription. Centers for Disease Control and Prevention

  16. Antibiotic Resistance

    MedlinePLUS

    ... of germs. They cause most illness. Antibiotics can kill bacteria, but they do not work against viruses. Viruses cause: Colds Coughs Sore throats Flu Sinus problems Bronchitis Ear infections Bacteria live in drinking water, food, and soil. They live ...

  17. Thin Layer Chromatographic Analysis of Beta-Lactam Antibiotics

    PubMed Central

    Hancu, Gabriel; Simon, Brigitta; Kelemen, Hajnal; Rusu, Aura; Mircia, Eleonora; Gyéresi, Árpád

    2013-01-01

    Purpose: The paper describes some thin layer chromatographic procedures that allow simple and rapid separation and identification of penicillins and cephalosporins from complex mixtures. Methods: Using silicagel GF254 as stationary phase and selecting different mobile phases we succeeded in the separation of the studied beta-lactamins. Our aim was not only to develop a simple, rapid and efficient method for their separation but also the optimization of the analytical conditions. Results: No system will separate all the beta-lactams, but they could be identified when supplementary information is used from color reactions and/or by using additional chromatographic systems. Conclusion: The right combination of solvent system and detection method allows the identification of the studied penicillins and cephalosporins and can be successfully used in the preliminary analysis beta-lactam antibiotics. PMID:24312862

  18. SK&F 75073, New Parenteral Broad-Spectrum Cephalosporin with High and Prolonged Serum Levels

    PubMed Central

    Actor, Paul; Uri, Joseph V.; Zajac, Ihor; Guarini, Joseph R.; Phillips, Lillian; Pitkin, Donald H.; Berges, David A.; Dunn, George L.; Hoover, John R. E.; Weisbach, Jerry A.

    1978-01-01

    SK&F 75073, a new parenteral cephalosporin, was found to have broad in vitro and in vivo antibacterial activity including isolates usually resistant to cephalothin and cefazolin. This activity included indole-positive Proteus and Enterobacter species and some Serratia isolates. Proteus mirabilis strains were particularly susceptible, as were Haemophilus influenzae and Neisseria species. The activity of SK&F 75073 against gram-positive bacteria was poorer than that of the control cephalosporins. This cephalosporin is highly bound to serum proteins, and a loss in in vitro activity was observed in the presence of serum. Parenteral administration of SK&F 75073 to experimental animals (mice, dogs, squirrel monkeys) resulted in high and prolonged serum levels when compared with cefazolin and other injectable cephalosporins. This favorable serum profile was reflected in the excellent protection observed in mice infected with pathogenic bacteria. PMID:96734

  19. Irrational antibiotic prescribing: a local issue or global concern?

    PubMed Central

    Hashemi, Shiva; Nasrollah, Azadeh; Rajabi, Mehdi

    2013-01-01

    Resistance to antibiotics is a major public-health concern and antibiotic use is being ever more recognized as the main discriminatory pressure driving this resistance. The aim was to assess the outpatient usage of antibiotics in teaching hospitals in various parts of capital city of Iran, Tehran and its association with resistance. 600 outpatient antibiotic prescriptions between December 2011 and May 2012 were reviewed in our teaching hospitals. All prescriptions were scrutinized in order to evaluate the antibiotic prescribing. The medical doctors from all grades were asked to note the chief complaints and the most possible diagnosis on each prescription. Clinical data, patient demographic and ultimately the total quantities of antibiotics were recorded. Our data was then compared against the major antibiotic guidelines and similar studies in other countries. The most common prescribed antibiotics are Penicillins (Penicillin, Co-Amoxiclav and Amoxicillin) (40 %), Cephalosporins (Cefixime, Cephalexin and Ceftriaxone) (24.5 %) and Macrolides (particularly Azithromycin) (15.3 %). In total, 18.2 % of cases were combinational antibacterial therapies (? 2). The most common diagnosis was upper respiratory tract infections as common cold (29.2 %) and sore throat (11.8 %). Directions (instructions for use) of 58 % of selected antibiotics were acceptable. Parenteral administration remains the common route of administration with 22 % of all reviewed prescriptions. Based on Cochrane reviews the antibiotic prescribing was unjustified in 42.7 % of the cases. The prescribing habit, correct diagnosis and the use of antibiotics need instant consideration. These data can provide useful information for assessing public-health policy that aims to reduce the antibiotic use and resistance levels.

  20. Comparative in vitro activity and the inoculum effect of ertapenem against Enterobacteriaceae resistant to extended-spectrum cephalosporins.

    PubMed

    Betriu, Carmen; Salso, Santiago; Sánchez, Aida; Culebras, Esther; Gómez, María; Rodríguez-Avial, Iciar; Picazo, Juan J

    2006-07-01

    The in vitro activity and the inoculum effect of ertapenem were evaluated against a total of 70 Enterobacteriaceae isolates resistant to extended-spectrum cephalosporins. The extended-spectrum beta-lactamase phenotypic confirmatory disk diffusion test was performed and AmpC-inducible species were detected using cefoxitin/cefotaxime disk antagonism tests. beta-Lactamases were characterised by isoelectric focusing and TEM-specific polymerase chain reaction. Minimum inhibitory concentrations (MICs) were determined by the National Committee for Clinical Laboratory Standards agar dilution method. Ertapenem showed excellent activity against almost all isolates tested, with MIC(50) and MIC(90) values of 0.03 mg/L and 0.12 mg/L, respectively. When the inoculum was increased 100-fold, susceptibility decreased from 98.6% to 65.7% for cefepime and from 75.7% to 54.3% for piperacillin/tazobactam, without changing for ertapenem. The data from this study suggest that this new carbapenem may be useful for treating mixed infections involving Enterobacteriaceae isolates resistant to third-generation cephalosporins. PMID:16769202

  1. Aerosolized Antibiotics.

    PubMed

    Restrepo, Marcos I; Keyt, Holly; Reyes, Luis F

    2015-06-01

    Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP. PMID:26070573

  2. A questionnaire-based survey to ascertain the views of clinicians regarding rational use of antibiotics in teaching hospitals of Kolkata

    PubMed Central

    Chatterjee, Dattatreyo; Sen, Sukanta; Begum, Sabnam Ara; Adhikari, Anjan; Hazra, Avijit; Das, Anup Kumar

    2015-01-01

    Objectives: The objective was to assess the views of clinicians in teaching hospitals of Kolkata regarding the use of antibiotics in their own hospitals, focusing on perceived misuse, reasons behind such misuse and feasible remedial measures. Materials and Methods: A total of 200 clinicians from core clinical disciplines was approached in six teaching hospitals of Kolkata through purposive sampling. A structured, validated questionnaire adopted from published studies and modified to suit the responding population was completed by consenting respondents through face-to-face interaction with a single interviewer. Respondents were free to leave out questions they did not wish to answer. Results: Among 130 participating clinicians (65% of approached), all felt that antibiotic misuse occurs in various hospital settings; 72 (55.4% of the respondents) felt it was a frequent occurrence and needed major rectification. Cough and cold (78.5%), fever (65.4%), and diarrhea (62.3%) were perceived to be the commonest conditions of antibiotic misuse. About half (50.76%) felt that oral preparations were more misused compared to injectable or topical ones. Among oral antibiotics, co-amoxiclav (66.9%) and cefpodoxime (63.07%) whereas among parenteral ones, ceftriaxone and other third generation cephalosporins (74.6%) followed by piperacillin-tazobactam (61.5%) were selected as the most misused ones. Deficient training in rational use of medicines (70.7%) and absence of institutional antibiotic policy (67.7%) were listed as the two most important predisposing factors. Training of medical students and interns in rational antibiotic use (78.5%), implementation of antibiotic policy (76.9%), improvement in microbiology support (70.7%), and regular surveillance on this issue (64.6%) were cited as the principal remedial measures. Conclusions: Clinicians acknowledge that the misuse of antibiotics is an important problem in their hospitals. A system of clinical audit of antibiotic usage, improved microbiology support and implementation of antibiotic policy can help to promote rational use of antimicrobial agents. PMID:25821321

  3. The effect of antibiotic exposure on eicosanoid generation from arachidonic acid and gene expression in a primitive chordate, Branchiostoma belcheri

    PubMed Central

    Yuan, Dongjuan; Pan, Minming; Zou, Qiuqiong; Chen, Chengyong; Chen, Shangwu; Xu, Anlong

    2015-01-01

    Chloramphenicol (Chl) is an effective antimicrobial agent widely used in veterinary medicine and commonly used in fish. Its use is restricted in the clinic because of adverse effects on the immune system and oxidative stress in mammals. However, the effects of Chl treatment on invertebrates remain unclear. Amphioxus, a basal chordate, is an ideal model to study the origin and evolution of the vertebrate immune system as it has a primary vertebrate-like arachidonic acid (AA) metabolic system. Here, we combined transcriptomic and lipidomic approaches to investigate the immune system and observe the oxygenated metabolites of AA to address the antibiotic effects on amphioxus. Tissue necrosis of the gill slits occurred in the Chl-treated amphioxus, but fewer epithelial cells were lost when treated with both Chl and ampicillin (Amp). The immune related pathways were dysregulated in both of the antibiotic treatment groups. The Chl alone treatment resulted in immunosuppression with down-regulation of the innate immune genes. In contrast, the Chl + Amp treatment resulted in immunostimulation to some extent, as shown by KEGG clustering. Furthermore, Chl induced a 3-fold reduction in the level of the eicosanoids, while the Chl + Amp treatment resulted in 1.7-fold increase of eicosanoid level. Thus in amphioxus, Amp might relieve the effects of the Chl-induced immune suppression and increase the level of eicosanoids from AA. Finally, the oxygenated metabolites from AA might be crucial to evaluate the effects of Chl treatment in animals. PMID:26288743

  4. A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing

    PubMed Central

    Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang

    2014-01-01

    In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge. PMID:24905407

  5. The effect of antibiotic exposure on eicosanoid generation from arachidonic acid and gene expression in a primitive chordate, Branchiostoma belcheri.

    PubMed

    Yuan, Dongjuan; Pan, Minming; Zou, Qiuqiong; Chen, Chengyong; Chen, Shangwu; Xu, Anlong

    2015-01-01

    Chloramphenicol (Chl) is an effective antimicrobial agent widely used in veterinary medicine and commonly used in fish. Its use is restricted in the clinic because of adverse effects on the immune system and oxidative stress in mammals. However, the effects of Chl treatment on invertebrates remain unclear. Amphioxus, a basal chordate, is an ideal model to study the origin and evolution of the vertebrate immune system as it has a primary vertebrate-like arachidonic acid (AA) metabolic system. Here, we combined transcriptomic and lipidomic approaches to investigate the immune system and observe the oxygenated metabolites of AA to address the antibiotic effects on amphioxus. Tissue necrosis of the gill slits occurred in the Chl-treated amphioxus, but fewer epithelial cells were lost when treated with both Chl and ampicillin (Amp). The immune related pathways were dysregulated in both of the antibiotic treatment groups. The Chl alone treatment resulted in immunosuppression with down-regulation of the innate immune genes. In contrast, the Chl + Amp treatment resulted in immunostimulation to some extent, as shown by KEGG clustering. Furthermore, Chl induced a 3-fold reduction in the level of the eicosanoids, while the Chl + Amp treatment resulted in 1.7-fold increase of eicosanoid level. Thus in amphioxus, Amp might relieve the effects of the Chl-induced immune suppression and increase the level of eicosanoids from AA. Finally, the oxygenated metabolites from AA might be crucial to evaluate the effects of Chl treatment in animals. PMID:26288743

  6. Degradation kinetics and mechanism of antibiotic ceftiofur in recycled water derived from a beef farm.

    PubMed

    Li, Xiaolin; Zheng, Wei; Machesky, Michael L; Yates, Scott R; Katterhenry, Michael

    2011-09-28

    Ceftiofur is a third-generation cephalosporin antibiotic that has been widely used to treat bacterial infections in concentrated animal feeding operations (CAFOs). Land application of CAFO waste may lead to the loading of ceftiofur residues and its metabolites to the environment. To understand the potential contamination of the antibiotic in the environment, the degradation kinetics and mechanisms of ceftiofur in solutions blended with and without the recycled water derived from a beef farm were investigated. The transformation of ceftiofur in aqueous solutions in the presence of the CAFO recycled water was the combined process of hydrolysis and biodegradation. The total degradation rates of ceftiofur at 15 °C, 25 °C, 35 °C, and 45 °C varied from 0.4-2.8×10(-3), 1.4-4.4×10(-3), 6.3-11×10(-3), and 11-17×10(-3) h(-1), respectively, in aqueous solutions blended with 1 to 5% CAFO recycled water. Hydrolysis of ceftiofur increased with incubation temperature from 15 to 45 °C. The biodegradation rates of ceftiofur were also temperature-dependent and increased with the application amounts of the recycled CAFO water. Cef-aldehyde and desfuroylceftiofur (DFC) were identified as the main biodegradation and hydrolysis products, respectively. This result suggests that the primary biodegradation mechanism of ceftiofur was the cleavage of the ?-lactam ring, while hydrolytic cleavage occurred at the thioester bond. Unlike DFC and ceftiofur, cef-aldehyde does not contain a ?-lactam ring and has less antimicrobial activity, indicating that the biodegradation of ceftiofur in animal wastewater may mitigate the potentially adverse impact of the antibiotic to the environment. PMID:21863813

  7. Antibiotic-Resistant Fecal Bacteria, Antibiotics, and Mercury in Surface Waters of Oakland County, Michigan, 2005-2006

    USGS Publications Warehouse

    Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

    2007-01-01

    Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony-forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic-resistance genes (class I integrons) were detected in several samples, indicating that the resistance carried by these organisms may be transferable to other bacteria, including disease-causing bacteria.

  8. Antibiotic prescription behaviours in Lao People's Democratic Republic: a knowledge, attitude and practice survey

    PubMed Central

    Quet, Fabrice; Leyer, Caroline; Buisson, Yves; Newton, Paul N; Naphayvong, Philaysak; Keoluangkhot, Valy; Chomarat, Monique; Longuet, Christophe; Steenkeste, Nicolas; Jacobs, Jan

    2015-01-01

    Abstract Objective To assess the antibiotic prescribing practices of doctors working in the Lao People's Democratic Republic and their knowledge of local antibiotic resistance patterns. Methods Doctors attending morning meetings in 25 public hospitals in four provinces were asked to complete a knowledge, attitude and practice survey. The questionnaire contained 43 multiple choice questions that the doctor answered at the time of the meeting. Findings The response rate was 83.4% (386/463). Two hundred and seventy doctors (59.8%) declared that they had insufficient information about antibiotics. Only 14.0% (54/386) recognized the possibility of cephalosporin cross-resistance in methicillin-resistant Staphylococcus aureus. Most participants had no information about local antibiotic resistance for Salmonella Typhi (211/385, 54.8%) and hospital-acquired pneumonia (253/384, 65.9%). Unnecessary antibiotic prescriptions were considered as harmless by 115 participants and 148 considered locally-available generic antibiotics to be of poor quality. Nearly three-quarters (280/386) of participants agreed that it was difficult to select the correct antibiotics. Most participants (373/386) welcomed educational programmes on antibiotic prescribing and 65.0% (249/383) preferred local over international antibiotic guidelines. Conclusion Doctors in the Lao People's Democratic Republic seem to favour antibiotic prescribing interventions. Health authorities should consider a capacity building programme that incorporates antibiotic prescribing and hospital infection control. PMID:26229186

  9. Effect of loading rate and HRT on the removal of cephalosporin and their intermediates during the operation of a membrane bioreactor treating pharmaceutical wastewater.

    PubMed

    Sundararaman, S; Saravanane, R

    2010-01-01

    The viability of treating high-concentration antibiotic wastewater by a membrane bioreactor (MBR) was studied using submerged flat sheet membrane. The major problems for these modules are concentration polarization and subsequent fouling. By using gas-liquid two-phase flow, these problems can be ameliorated. A case study has been identified and the current issues in one of the major pharmaceutical industry (manufacturing cephalosporin drugs) located in Chennai, India, has been discussed for the possible removal of anaerobically transformed intermediates of antibiotic pharmaceutical wastewater. The objective of the study was to determine the effect of organic loading rate and hydraulic retention time on the removal of cephalosporin derivative, viz., cephalexin (C(16)H(17)N(3)O(4)S.H(2)O) and the intermediates [7-amino-3-deacetoxycephalosporanic acid (7-ADCA) and acyl group (Phenyl acetic acid)] in the MBR with enhanced biodegradation using bioaugmentation technique. Based on the critical examination of results, the industry is looking for the alternatives of either direct disposal of 7-ADCA and phenyl acetic acid or for further degradation and disposal, which will essentially require additional cost and maintenance. The present regulatory standard implemented at a global level, (meaning the intermediates which are transformed during its course of travel within the industry and in the treatments plants, i.e., in the present study it is, 7-ADCA and phenyl acetic acid are not allowed to discharge on water bodies), does not envisage such disposal alternatives and hence the present study was aimed at the complete removal of intermediates (7-ADCA) and phenyl acetic acid prior to discharge. PMID:20371950

  10. Total Synthesis of the Antitumor Antibiotic (±)-Streptonigrin: First- and Second-Generation Routes for de Novo Pyridine Formation Using Ring-Closing Metathesis

    PubMed Central

    2013-01-01

    The total synthesis of (±)-streptonigrin, a potent tetracyclic aminoquinoline-5,8-dione antitumor antibiotic that reached phase II clinical trials in the 1970s, is described. Two routes to construct a key pentasubstituted pyridine fragment are depicted, both relying on ring-closing metathesis but differing in the substitution and complexity of the precursor to cyclization. Both routes are short and high yielding, with the second-generation approach ultimately furnishing (±)-streptonigrin in 14 linear steps and 11% overall yield from inexpensive ethyl glyoxalate. This synthesis will allow for the design and creation of druglike late-stage natural product analogues to address pharmacological limitations. Furthermore, assessment of a number of chiral ligands in a challenging asymmetric Suzuki–Miyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time. PMID:24328139

  11. Single-step conversion of cephalosporin-C to 7-aminocephalosporanic acid by free and immobilized cells of Pseudomonas diminuta.

    PubMed

    Nigam, V K; Kundu, S; Ghosh, P

    2005-07-01

    7-Aminocephalosporanic acid (7-ACA), the starting material for the production of a number of clinically used semisynthetic cephalosporins, is produced by deacylation of cephalosporin-C. The production of 7-ACA was studied in various modes, at the optimal conditions using free and immobilized whole cells of Pseudomonas diminuta. PMID:16014995

  12. Five-year assessment of causative agents and antibiotic resistances in urinary tract infections

    PubMed Central

    Çoban, Bayram; Ülkü, Nesrin; Kaplan, Halit; Topal, Burhan; Erdo?an, Haluk; Bask?n, Esra

    2014-01-01

    Aim: To show the distribution and changes of causative agents of urinary tract infections in children and resistance rates by years and select the most appropriate antibiotics. Material and Methods: In this study, the Ba?kent University Alanya Research and Application Hospital automation system microbiology recording book was screened retrospectively. Growth of a single microorganism above 105 colonies (cfu/mL) was included in the assessment. Throughout the study, 10 691 urinary cultures were studies and growth was found in 392 (3.7%). Results: Three hundred and nine (78.8%) of the samples with growth belonged to girls. Growth was found in the neonatal period in 32 patients (8.2%). The most commonly isolated microorganism was Escherichia coli (E. coli) which was found in 68.4% of the patients. Klebsiella spp. were found with a rate of 12.0%; Enterobacter spp. were found with a rate of 10.7% and proteus spp. were found with a rate of 5.1%. Resistance to cefalotin (62.1%), trimethoprim-sulfamethoxasole (43.1%), amoxycillin-clavulanate (34.8%), ampicillin (30.4%), cefixim (26.3%) and nitrofurantoin (3.6%) was found in E. coli species. The antibiotic which had the highest resistance rate was ampicillin with a rate of 93.2% for klebsiella and 83.4% for enterobacter. Klebsiella spp. were the most commonly grown pathogens in newborns (40.6%). In a follow-up period of 5 years, the resistance of E. coli to amoxycillin-clavulanate regressed from 40.3% to 31.3%, while the resistance to trimethoprim-sulfamethoxasole (TMP-SMX) regressed from 45.6% to 34.7%. Conclusions: A high resistance against first-generation cephalosporins, ampicillin, amoxycillin-clavulanate and TMP-SMX which are the first-line antibiotics in childhood urinary tract infections was found. Carbapenem (meropenem, imipenem) resistance was not found in our center. Nitrofurantoin, aminoglycosides and cefixime can be recommended for empirical treatment in our hospital because of low resistance. Antibiotic treatment should be redecided according to in vitro antibiotic sensitivity results. PMID:26078647

  13. Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters.

    PubMed

    Leonard, Anne F C; Zhang, Lihong; Balfour, Andrew J; Garside, Ruth; Gaze, William H

    2015-09-01

    Infections caused by antibiotic resistant bacteria (ARB) are associated with poor health outcomes and are recognised globally as a serious health problem. Much research has been conducted on the transmission of ARB to humans. Yet the role the natural environment plays in the spread of ARB and antibiotic resistance genes is not well understood. Antibiotic resistant bacteria have been detected in natural aquatic environments, and ingestion of seawater during water sports is one route by which many people could be directly exposed. The aim was to estimate the prevalence of resistance to one clinically important class of antibiotics (third-generation cephalosporins (3GCs)) amongst Escherichia coli in coastal surface waters in England and Wales. Prevalence data was used to quantify ingestion of 3GC-resistant E. coli (3GCREC) by people participating in water sports in designated coastal bathing waters. A further aim was to use this value to derive a population-level estimate of exposure to these bacteria during recreational use of coastal waters in 2012. The prevalence of 3GC-resistance amongst E. coli isolated from coastal surface waters was estimated using culture-based methods. This was combined with the density of E. coli reported in designated coastal bathing waters along with estimations of the volumes of water ingested during various water sports reported in the literature to calculate the mean number of 3GCREC ingested during different water sports. 0.12% of E. coli isolated from surface waters were resistant to 3GCs. This value was used to estimate that in England and Wales over 6.3 million water sport sessions occurred in 2012 that resulted in the ingestion of at least one 3GCREC. Despite the low prevalence of resistance to 3GCs amongst E. coli in surface waters, there is an identifiable human exposure risk for water users, which varies with the type of water sport undertaken. The relative importance of this exposure is likely to be greater in areas where a large proportion of the population enjoys water sports. Millions of water sport sessions occurred in 2012 that were likely to have resulted in people ingesting E. coli resistant to a single class of antibiotics (3GCs). However, this is expected to be a significant underestimate of recreational exposure to all ARB in seawater. This is the first study to use volumes of water ingested during different water sports to estimate human exposure to ARB. Further work needs to be done to elucidate the health implications and clinical relevance of exposure to ARB in both marine and fresh waters in order to fully understand the risk to public health. PMID:25832996

  14. Non-Phenotypic Tests to Detect and Characterize Antibiotic Resistance Mechanisms in Enterobacteriaceae

    PubMed Central

    Lupo, Agnese; Papp-Wallace, Krisztina M.; Sendi, Parham; Bonomo, Robert A.; Endimiani, Andrea

    2014-01-01

    In the past two decades, we have observed a rapid increase of infections due to multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes encoding for extended-spectrum ?-lactamases (e.g., blaCTX-M, blaTEM, blaSHV) or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last-generation cephalosporins. Furthermore, other resistance traits against quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also frequently co-associated. Even more concerning is the rapid increase of Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g., blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our antibiotic options. Unfortunately, standard microbiological procedures require several days to isolate the responsible pathogen and to provide correct antimicrobial susceptibility test results. This delay impacts the rapid implementation of adequate antimicrobial treatment and infection control countermeasures. Thus, there is emerging interest in the early and more sensitive detection of resistance mechanisms. Modern non-phenotypic tests are promising in this respect, and hence, can influence both clinical outcome and healthcare costs. In this review, we present a summary of the most advanced methods (e.g., next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays, MALDITOF MS, and PCR/ESI MS) presently available for the rapid detection of antibiotic resistance genes in Enterobacteriaceae. Taking into account speed, manageability, accuracy, versatility, and costs, the possible settings of application (research, clinic, and epidemiology) of these methods and their superiority against standard phenotypic methods are discussed. PMID:24091103

  15. Inhaled antibiotics: dry or wet?

    PubMed

    Tiddens, Harm A W M; Bos, Aukje C; Mouton, Johan W; Devadason, Sunalene; Janssens, Hettie M

    2014-11-01

    Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment of Pseudomonas aeruginosa in cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser. The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching. In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics. The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed. PMID:25323242

  16. Impact of the New Delhi metallo-beta-lactamase on beta-lactam antibiotics

    PubMed Central

    Zmarlicka, Monika T; Nailor, Michael D; Nicolau, David P

    2015-01-01

    Since the first New Delhi metallo-beta-lactamase (NDM) report in 2009, NDM has spread globally causing various types of infections. NDM-positive organisms produce in vitro resistance phenotypes to carbapenems and many other antimicrobials. It is thus surprising that the literature examining clinical experiences with NDM does not report corresponding poor clinical outcomes. There are many instances where good clinical outcomes are described, despite a mismatch between administered antimicrobials and resistant in vitro susceptibilities. Available in vitro data for either monotherapy or combination therapy does not provide an explanation for these observations. However, animal studies do begin to shed more light on this phenomenon. They imply that the in vivo expression of NDM may not confer clinical resistance to all cephalosporin and carbapenem antibiotics as predicted by in vitro testing but other resistance mechanisms need to be present to generate a resistant phenotype. As such, previously abandoned therapies, particularly carbapenems and beta-lactamase inhibitor combinations, may retain utility against infections caused by NDM producers. PMID:26345624

  17. Antibiotic resistance: An ethical challenge.

    PubMed

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper. PMID:26242553

  18. Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada

    PubMed Central

    Sawatzky, P.; Liu, G.; Allen, V; Lefebvre, B.; Hoang, L.; Drews, S.; Horsman, G.; Wylie, J.; Haldane, D.; Garceau, R.; Ratnam, S.; Wong, T.; Archibald, C.; Mulvey, M.R.

    2016-01-01

    Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010–2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines. PMID:26689114

  19. 77 FR 735 - New Animal Drugs; Cephalosporin Drugs; Extralabel Animal Drug Use; Order of Prohibition

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-06

    ...cephalosporin by [beta]-lactamases. These enzymes can be both innate and acquired (Ref...important classes of [beta]-lactamase enzymes are the AmpC cephalosporinases and the...ESBL). CMY-2 (a type of AmpC) enzymes are found on the chromosome of most...

  20. In vitro antibiotic susceptibilities of Yersinia pestis determined by broth microdilution following CLSI methods.

    PubMed

    Heine, Henry S; Hershfield, Jeremy; Marchand, Charles; Miller, Lynda; Halasohoris, Stephanie; Purcell, Bret K; Worsham, Patricia L

    2015-04-01

    In vitro susceptibilities to 45 antibiotics were determined for 30 genetically and geographically diverse strains of Yersinia pestis by the broth microdilution method at two temperatures, 28°C and 35°C, following Clinical and Laboratory Standards Institute (CLSI) methods. The Y. pestis strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, ?-lactams, cephalosporins, and carbapenems. Only a 1-well shift was observed for the majority of antibiotics between the two temperatures. Establishing and comparing antibiotic susceptibilities of a diverse but specific set of Y. pestis strains by standardized methods and establishing population ranges and MIC50 and MIC90 values provide reference information for assessing new antibiotic agents and also provide a baseline for use in monitoring any future emergence of resistance. PMID:25583720

  1. Evaluation of separation and purification processes in the antibiotic industry

    SciTech Connect

    Bienkowski, P.R.; Lee, D.D.; Byers, C.H.

    1987-05-01

    The different separation and purification processes for three major types of antibiotics, Penicillins, Cephalosporins and Tetracyclines will be discussed. All antibiotic, processing plants contain two majors sections, a relatively small and highly specialized fermentation section and a very large (60-80% of the plant) separation and purification section. The fermentation sections for the different antibiotics are essentially identical, except for differences in growth media and operating variables, but there are vast differences in the separation and purification sections. Several different separation methods are used including filtration, ultrafiltration, centrifugation, precipitation, extraction, chromatography and various membrane methods. Variables affecting the specific separation and purification configurations include final fermentation broth concentration, by-product formed during fermentation, the physical properties and molecular structure of the various antibiotics and special purification requirements. Necessary reductions in the separation and purification processes required for rebuilding the antibiotic industry after a national emergency are discussed along with several relatively new separation/purification methods that hold great promise for effecting these reductions, chromatography, supercritical fluid extraction (SCF), and membranes. 35 refs., 10 figs., 2 tabs.

  2. Antibiotics: opportunities for genetic manipulation.

    PubMed

    Hopwood, D A

    1989-08-31

    New antibiotics can still be discovered by the development of novel screening procedures. Notable successes over the last few years include the monobactams, beta-lactamase inhibitors (clavulanic acid) and new glycopeptides in the antibacterial field; antiparasitic agents such as avermectins; and herbicidal antibiotics like bialaphos. In the future we can expect the engineering of genes from 'difficult' pathogens, including mycobacteria and fungi, and cancer cells, to provide increasingly useful in vitro targets for the screening of antibiotics that can kill pathogens and tumours. There will also be a greater awareness of the need to reveal the full potential for antibiotic production on the part of microorganisms by the physiological and/or genetic awakening of 'silent' genes. Nevertheless, the supply of natural antibiotics for direct use or chemical modification is not infinite and there will be increasing scope for widening the range of available antibiotics by genetic engineering. 'Hybrid' antibiotics have been shown to be generated by the transfer of genes on suitable vectors between strains producing chemically related compounds. More exciting is the possibility of generating novelty by the genetic engineering of the synthases that determine the basic structure of antibiotics belonging to such classes as the beta-lactams and polyketides. Research in this area will certainly yield knowledge of considerable scientific interest and probably also of potential applicability. In the improvement of antibiotic titre in actinomycetes, protoplast fusion between divergent selection lines has taken a place alongside random mutation and screening. In some cases the cloning of genes controlling metabolic 'bottlenecks' in fungi and actinomycetes will give an immediate benefit in the conversion of accumulated biosynthetic intermediates to the desired end product. However, the main impact of genetic engineering in titre improvement will probably come only after a further use of this technology to understand and manipulate the regulation of antibiotic biosynthesis as a facet of the general challenge of understanding differential gene expression. Streptomyces offers a particularly fertile field for such research, following the isolation of DNA segments that carry groups of closely linked operons for the biosynthesis of and resistance to particular antibiotics, and of genes with pleiotropic effects on morphological differentiation and secondary metabolite formation. PMID:2573090

  3. Ceftobiprole: a review of a broad-spectrum and anti-MRSA cephalosporin.

    PubMed

    Zhanel, George G; Lam, Ashley; Schweizer, Frank; Thomson, Kristjan; Walkty, Andrew; Rubinstein, Ethan; Gin, Alfred S; Hoban, Daryl J; Noreddin, Ayman M; Karlowsky, James A

    2008-01-01

    Ceftobiprole, an investigational cephalosporin, is currently in phase III clinical development. Ceftobiprole is a broad-spectrum cephalosporin with demonstrated in vitro activity against Gram-positive cocci, including meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant S. epidermidis, penicillin-resistant S. pneumoniae, Enterococcus faecalis, Gram-negative bacilli including AmpC-producing Escherichia coli and Pseudomonas aeruginosa, but excluding extended-spectrum beta-lactamase-producing strains. Like cefotaxime, ceftriaxone, ceftazidime, and cefepime, ceftobiprole demonstrates limited activity against anaerobes such as Bacteroides fragilis and non-fragilis Bacteroides spp. In single-step and serial passage in vitro resistance development studies, ceftobiprole demonstrated a low propensity to select for resistant subpopulations. Ceftobiprole, like cefepime, is a weak inducer and a poor substrate for AmpC beta-lactamases.Ceftobiprole medocaril, the prodrug of ceftobiprole, is converted by plasma esterases to ceftobiprole in <30 minutes. Peak serum concentrations of ceftobiprole observed at the end of a single 30-minute infusion were 35.5 mug/mL for a 500-mg dose and 59.6 mug/mL for a 750-mg dose. The volume of distribution of ceftobiprole is 0.26 L/kg ( approximately 18 L), protein binding is 16%, and its serum half-life is approximately 3.5 hours. Ceftobiprole is renally excreted ( approximately 70% in the active form) and systemic clearance correlates with creatinine clearance, meaning that dosage adjustment is required in patients with renal dysfunction. Ceftobiprole has a modest post-antibiotic effect (PAE) of approximately 0.5 hours for MRSA and a longer PAE of approximately 2 hours for penicillin-resistant pneumococci. Ceftobiprole, when administered intravenously at 500 mg once every 8 hours (2-hour infusion), has a >90% probability of achieving f T(>MIC) (free drug concentration exceeds the minimum inhibitory concentration [MIC]) for 40% and 60%, respectively, of the dosing interval for isolates with ceftobiprole MIC < or =4 and < or =2 mg/L, respectively.Currently, only limited clinical trial data are published for ceftobiprole. In a phase III trial, 784 patients with Gram-positive skin infections were randomized to treatment with either ceftobiprole 500 mg or vancomycin 1 g, each administered twice daily for 7-14 days; 93.3% of patients were clinically cured with ceftobiprole compared with 93.5% receiving vancomycin, and the eradication rate for MRSA infections was 91.8% for ceftobiprole compared with 90% for vancomycin. A phase III, randomized, double-blind, multicenter trial compared ceftobiprole 500 mg every 8 hours with vancomycin 1 g every 12 hours plus ceftazidime 1 g every 8 hours in patients with complicated skin and skin structure infections. Of the 828 patients enrolled, 31% had diabetic foot infections, 30% had abscesses, and 22% had wounds. No difference in clinical cure was reported in the clinically evaluable, intent-to-treat and microbiologically evaluable populations with cure rates of 90.5%, 81.9%, and 90.8%, respectively, in the ceftobiprole-treated patients and 90.2%, 80.8%, and 90.5%, respectively, in the vancomycin plus ceftazidime-treated group. Microbiologic eradication of Gram-positive cocci meticillin-susceptible S. aureus (MSSA) [ceftobiprole 91% vs vancomycin plus ceftazidime 92%] and MRSA (ceftobiprole 87% vs vancomycin plus ceftazidime 80%), as well as Gram-negative bacilli, E. coli (ceftobiprole 89% vs vancomycin plus ceftazidime 92%), and P. aeruginosa (ceftobiprole 87% vs vancomycin plus ceftazidime 100%), was not significantly different between groups. Similar cures rates in the microbiologically evaluable population occurred in both groups for Panton-Valentine leukocidin (PVL)-positive MSSA and PVL-positive MRSA.Currently, ceftobiprole has completed phase III trials for complicated skin and skin structure infections due to MRSA and nosocomial pneumonia due to suspected or proven MRSA; phase III trials are also ongoing in community-acquired

  4. Efficacy of single-dose ceftriaxone in experimental otitis media induced by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.

    PubMed Central

    Barry, B; Muffat-Joly, M; Bauchet, J; Faurisson, F; Gehanno, P; Pocidalo, J J; Carbon, C

    1996-01-01

    We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media. PMID:8878566

  5. Potentiality of yeast Candida sp. SMN04 for degradation of cefdinir, a cephalosporin antibiotic: kinetics, enzyme analysis and biodegradation pathway.

    PubMed

    Selvi, A; Das, Devlina; Das, Nilanjana

    2015-12-01

    A new yeast strain isolated from the pharmaceutical wastewater was capable of utilizing cefdinir as a sole carbon source for their growth in mineral medium. The yeast was identified and named as Candida sp. SMN04 based on morphology and 18S-ITS-D1/D2/D3 rRNA sequence analysis. The interaction between factors pH (3.0-9.0), inoculum dosage (1-7%), time (1-11 day) and cefdinir concentration (50-450?mg/L) was studied using a Box-Behnken design. The factors were studied as a result of their effect on cell dry weight (R1; g/L), extended spectrum ?-lactamase (ESBL) assay (R2; mm), P450 activity (R3; U/mL) and degradation (R4; %). Maximum values of R1, R2, R3 and R4 were obtained at central values of all the parameters. The isolated yeast strain efficiently degraded 84% of 250?mg?L(-1) of cefdinir within 6 days with a half-life of 2.97 days and degradation rate constant of 0.2335 per day. Pseudo-first-order model efficiently described the process. Among the various enzymes tested, the order of activity at the end of Day 4 was noted to be: cytochrome P450 (1.76?±?0.03)?>?NADPH reductase (1.51?±?0.20)?>?manganese peroxidase and amylase (0.66?±?0.15; 0.66?±?0.70). Intermediates were successfully characterized by liquid chromatography-mass spectrometry. The opening of the ?-lactam ring involving ESBL activity was considered as one of the major steps in the cefdinir degradation process. Fourier transform-infrared spectroscopy analysis showed the absence of spectral vibrations between 1766 and 1519?cm(-1) confirming the complete removal of lactam ring during cefdinir degradation. The results of the present study are promising for the use of isolated yeast Candida sp. SMN04 as a potential bioremediation agent. PMID:26000889

  6. Metabolic engineering of ?-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis.

    PubMed

    Veiga, Tânia; Gombert, Andreas K; Landes, Nils; Verhoeven, Maarten D; Kiel, Jan A K W; Krikken, Arjen M; Nijland, Jeroen G; Touw, Hesselien; Luttik, Marijke A H; van der Toorn, John C; Driessen, Arnold J M; Bovenberg, Roel A L; van den Berg, Marco A; van der Klei, Ida J; Pronk, Jack T; Daran, Jean-Marc

    2012-07-01

    Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporin-related products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. chrysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via ?-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of ?-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of ?-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis. PMID:22525490

  7. Spectrophotometric complexation of cephalosporins with palladium (II) chloride in aqueous and non-aqueous solvents

    NASA Astrophysics Data System (ADS)

    Bagheri Gh., A.; Yosefi rad, A.; Rezvani, M.; Roshanzamir, S.

    2012-04-01

    The complexation reaction of cephalosporins namely cefotaxime (CTX), cefuroxime (CRX), and cefazolin (CEFAZ) with palladium (II) ions have been studied in water and DMF in 25 °C by the spectrophotometric methods. The method is based on the formation of yellow to yellowish brown complex between palladium (II) chloride and the investigated cephalosporins in the presence of sodium lauryl sulfate (SLS) as surfactant. The complexation process was optimized in terms of pH, temperature and contact time. The stoichiometry of all the complexes was found to be 2:1 (metal ion/ligand) for CTX, CRX, and 1:2 for CEFAZ. The stoichiometry of palladium (II)-cephalosporins was estimated by mole ratio and continuous variation methods and emphasized by the KINFIT program. These drugs could be determined by measuring the absorbance of each complex at its specific ?max. The results obtained are in good agreement with those obtained using the official methods. The proposed method was successfully applied for the determination of these compounds in their dosage forms.

  8. Precursor structure of cephalosporin acylase. Insights into autoproteolytic activation in a new N-terminal hydrolase family.

    PubMed

    Kim, Youngsoo; Kim, Sanggu; Earnest, Thomas N; Hol, Wim G J

    2002-01-25

    Autocatalytic proteolytic cleavage is a frequently observed post-translational modification in proteins. Cephalosporin acylase (CA) is a recently identified member of the N-terminal hydrolase family that is activated from an inactive precursor by autoproteolytic processing, generating a new N-terminal residue, which is either a Ser or a Thr. The N-terminal Ser or Thr becomes a nucleophilic catalytic center for intramolecular and intermolecular amide cleavages. The gene structure of the open reading frame of CAs generally consists of a signal peptide followed by the alpha-subunit, a spacer sequence, and the beta-subunit, which are all translated into a single polypeptide chain, the CA precursor. The precursor is post-translationally modified into an active heterodimeric enzyme with alpha- and beta-subunits, first by intramolecular cleavage and second by intermolecular cleavage. We solved the first CA precursor structure (code 1KEH) from a class I CA from Pseudomonas diminuta at a 2.5-A resolution that provides insight into the mechanism of intramolecular cleavage. A conserved water molecule, stabilized by four hydrogen bonds in unusual pseudotetrahedral geometry, plays a key role to assist the OG atom of Ser(1beta) to generate a strong nucleophile. In addition, the site of the secondary intermolecular cleavage of CA is proposed to be the carbonyl carbon of Gly(158alpha) (Kim, S., and Kim, Y., (2001) J. Biol. Chem., 276, 48376-48381), which is different from the situation in two other class I CAs. PMID:11706000

  9. Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia

    PubMed Central

    Sánchez, María B.

    2015-01-01

    Stenotrophomonas maltophilia is an environmental bacterium found in the soil, associated with plants and animals, and in aquatic environments. It is also an opportunistic pathogen now causing an increasing number of nosocomial infections. The treatment of S. maltophilia is quite difficult given its intrinsic resistance to a number of antibiotics, and because it is able to acquire new resistances via horizontal gene transfer and mutations. Certainly, strains resistant to quinolones, cotrimoxale and/or cephalosporins—antibiotics commonly used to treat S. maltophilia infections—have emerged. The increasing number of available S. maltophilia genomes has allowed the identification and annotation of a large number of antimicrobial resistance genes. Most encode inactivating enzymes and efflux pumps, but information on their role in intrinsic and acquired resistance is limited. Non-typical antibiotic resistance mechanisms that also form part of the intrinsic resistome have been identified via mutant library screening. These include non-typical antibiotic resistance genes, such as bacterial metabolism genes, and non-inheritable resistant phenotypes, such as biofilm formation and persistence. Their relationships with resistance are complex and require further study. PMID:26175724

  10. Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia.

    PubMed

    Sánchez, María B

    2015-01-01

    Stenotrophomonas maltophilia is an environmental bacterium found in the soil, associated with plants and animals, and in aquatic environments. It is also an opportunistic pathogen now causing an increasing number of nosocomial infections. The treatment of S. maltophilia is quite difficult given its intrinsic resistance to a number of antibiotics, and because it is able to acquire new resistances via horizontal gene transfer and mutations. Certainly, strains resistant to quinolones, cotrimoxale and/or cephalosporins-antibiotics commonly used to treat S. maltophilia infections-have emerged. The increasing number of available S. maltophilia genomes has allowed the identification and annotation of a large number of antimicrobial resistance genes. Most encode inactivating enzymes and efflux pumps, but information on their role in intrinsic and acquired resistance is limited. Non-typical antibiotic resistance mechanisms that also form part of the intrinsic resistome have been identified via mutant library screening. These include non-typical antibiotic resistance genes, such as bacterial metabolism genes, and non-inheritable resistant phenotypes, such as biofilm formation and persistence. Their relationships with resistance are complex and require further study. PMID:26175724

  11. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic

    PubMed Central

    Kaur, Dardi Charan; Chate, Sadhana Sanjay

    2015-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Staphylococcus aureus demonstrates a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin, until the most recent, linezolid and daptomycin. Methicillin resistant S. aureus (MRSA) has become endemic today in hospitals worldwide. Resistance to the newer antimicrobial-agents — linezolid, vancomycin, teicoplanin, and daptomycin are been reported and also the fear of pandrug-resistance. This study was carried out to know the antimicrobial resistant pattern of MRSA to newer antibiotic, to know any isolates are extensively-drug resistant (XDR)/pandrug resistant (PDR), inducible macrolide-lincosamide streptogramin B (iMLSB), and mupirocin resistance. Thirty-six MRSA isolates resistant to the routinely tested antibiotic were further tested for list of antibiotic by a group of international experts. Isolates were tested for iMLSB and mupirocin resistance by the disk diffusion method. Of 385 MRSA, 36 (9.35%) isolates of MRSA were resistant to the routinely tested antibiotic. Among these 36 MRSA isolates, none of our isolates were XDR/PDR or showed resistant to anti-MRSA cephalosporins (ceftaroline), phosphonic acids, glycopeptides, glycylcyclines, and fucidanes. Lower resistance was seen in oxazolidinones (2.78%), streptogramins (5.56%), lipopeptide (5.56%). Thirty-four (94.44%) isolates showed constitutive MLSB (cMLSB) resistance and two (5.56%) iMLSB phenotypes. High- and low-level mupirocin resistance were seen in 13 (36.11%) and six (16.67%), respectively. In our study, none of our isolates were XDR or PDR. No resistance was observed to ceftaroline, telavancin, teicoplanin, and vancomycin; but the presence of linezolid resistance (1, 2.28%) and daptomycin resistance (2, 5.56%) in our rural set-up is a cause of concern. PMID:26069428

  12. Anaerobic digestion of antibiotic residue in combination with hydrothermal pretreatment for biogas.

    PubMed

    Zhang, Guangyi; Li, Chunxing; Ma, Dachao; Zhang, Zhikai; Xu, Guangwen

    2015-09-01

    Antibiotic residues are difficult to be treated or utilized because of their high water content and residual antibiotics. This article is devoted to investigating the possibility of biogas production from cephalosporin C residue (CPCAR), one typical type of antibiotic residues, via anaerobic digestion in combination with hydrothermal pretreatment (HTPT). The results from the bench-scale experiments showed that the combination of HTPT and anaerobic digestion can provide a viable way to convert CPCAR into biogas, and the biogas and methane yields reached 290 and 200 ml(g TS)(-1), respectively. This article further evaluated the proposed technology in terms of energy balance and technical feasibility based on theoretical calculation using the data from a pilot HTPT test. It was shown that the process is totally self-sufficient in energy and its main challenging problem of ammonia inhibition can be solved via ammonia stripping. PMID:26038331

  13. Combating Antibiotic Resistance

    MedlinePLUS

    ... for infectious diseases. back to top Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used ... treat strep throat, which is caused by streptococcal bacteria, and skin infections caused by staphylococcal bacteria. Although ...

  14. Antibiotics and Resistance: Glossary

    MedlinePLUS

    ... induced by natural or human activity on the ecology and living organisms. Ecology The study of the relationships and interactions between ... antibiotics The Cost of Resistance Science of Resistance Ecology Antibiotics in Agriculture Antibacterial Agents Glossary References Web ...

  15. Antibiotic susceptibility profile of bacilli isolated from the skin of healthy humans.

    PubMed

    Tarale, Prashant; Gawande, Sonali; Jambhulkar, Vinay

    2015-12-01

    In the present work, twelve bacilli were isolated from four different regions of human skin from Bela population of Nagpur district, India. The isolated bacilli were identified by their morphological, cultural and biochemical characteristics. Seven isolates were Gram negative rods, out of which five were belong to genus Pseudomonas. Three among the five Gram positive isolates were identified as Dermabactor and the remaining two Bacillus. Their antimicrobial susceptibility profile was determined by Kirby-Bauer disc diffusion method. The isolates showed resistance to several currently used broad-spectrum antibiotics. The Dermabactor genus was resistant to vancomycin, although it was earlier reported to be susceptible. Imipenem was found to be the most effective antibiotic for Pseudomonas while nalidixic acid, ampicillin and tetracycline were ineffective. Isolates of Bacillus displayed resistance to the extended spectrum antibiotics cephalosporin and ceftazidime. Imipenem, carbenicillin and ticarcillin were found to be the most effective antibiotics as all the investigated isolates were susceptible to them. Antibiotic resistance may be due to the overuse or misuse of antibiotics during the treatment, or following constant exposure to antibiotic-containing cosmetic formulations. PMID:26691469

  16. Inpatient antibiotics pharmacology and physiological use in Hayatabad medical complex, Pakistan

    PubMed Central

    Khan, Salman; Shehzad, Adeeb; Shehzad, Omer; Al-Suhaimi, Ebtesam A

    2013-01-01

    Antibiotics are used commonly and as powerful medicines, it well known that they affect the variety and composition of the microflora which has important physiological roles, therefore and for other health complications, the aim of the current study was to evaluate and estimate the appropriateness of antimicrobial drugs use in Hayatabad Medical Complex (HMC), Peshawar, Pakistan. The present work is based on the hospitalized patient’s case studies. Individual patients were interviewed using the prepared questionnaire for the study. All hospitalized patients who received antibiotics were evaluated by a cross-sectional study. The total number of patients interviewed was 270 in medical department. According to our study in medical department, for prophylaxis 64.3% of antibiotic was used, whereas, an empirical use was 35.7%. Prodigious double regimen of antibiotics was observed throughout the study. The most prescribed antimicrobial group is penicillin and followed by tetracycline, macrolides, quinolones, and cephalosporin. Furthermore, 14.56% antibiotics were prescribed on generic name and 85.43% were prescribed on the basis of brand names. Taken together, the antibiotic use in medical department was unsatisfactory and irrational. In summary, in order to protect the physiological functions of flora microorganisms, a combination of both limitation, continuous education of physicians and elaboration of local guidelines appear to be necessary to improve rational antibiotic use. PMID:23750310

  17. Role of pleiotropy during adaptation of TEM-1 ?-lactamase to two novel antibiotics

    PubMed Central

    Schenk, Martijn F; Witte, Sariette; Salverda, Merijn L M; Koopmanschap, Bertha; Krug, Joachim; de Visser, J Arjan G M

    2015-01-01

    Pleiotropy is a key feature of the genotype–phenotype map, and its form and extent have many evolutionary implications, including for the dynamics of adaptation and the evolution of specialization. Similarly, pleiotropic effects of antibiotic resistance mutations may affect the evolution of antibiotic resistance in the simultaneous or fluctuating presence of different antibiotics. Here, we study the role of pleiotropy during the in vitro adaptation of the enzyme TEM-1 ?-lactamase to two novel antibiotics, cefotaxime (CTX) and ceftazidime (CAZ). We subject replicate lines for four rounds of evolution to selection with CTX and CAZ alone, and in their combined and fluctuating presence. Evolved alleles show positive correlated responses when selecting with single antibiotics. Nevertheless, pleiotropic constraints are apparent from the effects of single mutations and from selected alleles showing smaller correlated than direct responses and smaller responses after simultaneous and fluctuating selection with both than with single antibiotics. We speculate that these constraints result from structural changes in the oxyanion pocket surrounding the active site, where accommodation of CTX and the larger CAZ is balanced against their positioning with respect to the active site. Our findings suggest limited benefits from the combined or fluctuating application of these related cephalosporins for containing antibiotic resistance. PMID:25861383

  18. Macrolide Antibiotics and Survival in Patients With Acute Lung Injury

    PubMed Central

    Wiener, Renda S.

    2012-01-01

    Background: Animal models suggest that immunomodulatory properties of macrolide antibiotics have therapeutic value for patients with acute lung injury (ALI). We investigated the association between receipt of macrolide antibiotics and clinical outcomes in patients with ALI. Methods: Secondary analysis of multicenter, randomized controlled trial data from the Acute Respiratory Distress Syndrome Network Lisofylline and Respiratory Management of Acute Lung Injury Trial, which collected detailed data regarding antibiotic use among participants with ALI. Results: Forty-seven of 235 participants (20%) received a macrolide antibiotic within 24 h of trial enrollment. Among patients who received a macrolide, erythromycin was the most common (57%), followed by azithromycin (40%). The median duration of macrolide use after study enrollment was 4 days (interquartile range, 2-8 days). Eleven of the 47 (23%) patients who received macrolides died, compared with 67 of the 188 (36%) who did not receive a macrolide (P = .11). Participants administered macrolides were more likely to have pneumonia as an ALI risk factor, were less likely to have nonpulmonary sepsis or to be randomized to low tidal volume ventilation, and had a shorter length of stay prior to trial enrollment. After adjusting for potentially confounding covariates, use of macrolide was associated with lower 180-day mortality (hazard ratio [HR], 0.46; 95% CI, 0.23-0.92; P = .028) and shorter time to successful discontinuation of mechanical ventilation (HR, 1.93; 95% CI, 1.18-3.17; P = .009). In contrast, fluoroquinolone (n = 90) and cephalosporin antibiotics (n = 93) were not associated with improved outcomes. Conclusions: Receipt of macrolide antibiotics was associated with improved outcomes in patients with ALI. PMID:22116799

  19. Finding alternatives to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The spread of antibiotic-resistant pathogens requires new treatments. The availability of new antibiotics has severely declined, and so alternatives to antibiotics need to be considered in both animal agriculture and human medicine. Products for disease prevention are different than products for d...

  20. Effect of antibiotics on cellular stress generated in Shiga toxin-producing Escherichia coli O157:H7 and non-O157 biofilms.

    PubMed

    Angel Villegas, Natalia; Baronetti, José; Albesa, Inés; Etcheverría, Analía; Becerra, M Cecilia; Padola, Nora L; Paraje, M Gabriela

    2015-10-01

    Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, with the main virulence factor of this bacterium being its capacity to secrete Shiga toxins (Stxs). Therefore, the use of certain antibiotics for the treatment of this infection, which induces the liberation of Stxs, is controversial. Reactive oxygen and nitrogen species are also involved in the pathogenesis of different diseases. The purpose of this study was to analyze the effects of antibiotics on biofilms of STEC and the relationships between cellular stress and the release of Stx. To this end, biofilms of reference and clinical strains were treated with antibiotics (ciprofloxacin, fosfomycin and rifaximin) and the production of oxidants, the antioxidant defense system and toxin release were evaluated. Ciprofloxacin altered the prooxidant-antioxidant balance, with a decrease of oxidant metabolites and an increase of superoxide dismutase and catalase activity, being associated with high-levels of Stx production. Furthermore, inhibition of oxidative stress by exogenous antioxidants was correlated with a reduction in the liberation of Stx, indicating the participation of this phenomenon in the release of this toxin. In contrast, fosfomycin and rifaximin produced less alteration with a minimal production of Stx. Our data show that treatment of biofilm-STEC with these antibiotics induces oxidative stress-mediated release of Stx. PMID:26130220

  1. Ultrastructural Changes in Clinical and Microbiota Isolates of Klebsiella pneumoniae Carriers of Genes blaSHV, blaTEM, blaCTX-M, or blaKPC When Subject to ?-Lactam Antibiotics

    PubMed Central

    Veras, Dyana Leal; de Souza Lopes, Ana Catarina; Vaz da Silva, Grasielle; Araújo Gonçalves, Gabriel Gazzoni; de Freitas, Catarina Fernandes; de Lima, Fernanda Cristina Gomes; Vieira Maciel, Maria Amélia; Feitosa, Ana Paula Sampaio; Alves, Luiz Carlos; Brayner, Fábio André

    2015-01-01

    The aim of this study was to characterize the ultrastructural effects caused by ?-lactam antibiotics in Klebsiella pneumoniae isolates. Three K. pneumoniae clinical isolates were selected for the study with resistance profiles for third-generation cephalosporins, aztreonam, and/or imipenem and with different resistance genes for extended-spectrum ?-lactamases (ESBL) or Klebsiella pneumoniae carbapenemase (KPC). Two K. pneumoniae isolates obtained from the microbiota, which were both resistant to amoxicillin and ampicillin, were also analyzed. In accordance with the susceptibility profile, the clinical isolates were subjected to subminimum inhibitory concentrations (sub-MICs) of cefotaxime, ceftazidime, aztreonam, and imipenem and the isolates from the microbiota to ampicillin and amoxicillin, for analysis by means of scanning and transmission electron microscopy. The K. pneumoniae isolates showed different morphological and ultrastructural changes after subjection to ?-lactams tested at different concentrations, such as cell filamentation, loss of cytoplasmic material, and deformation of dividing septa. Our results demonstrate that K. pneumoniae isolates harboring different genes that encode for ?-lactamases show cell alterations when subjected to different ?-lactam antibiotics, thus suggesting that they possess residual activity in vitro, despite the phenotypic resistance presented in the isolates analyzed. PMID:26491715

  2. Antibiotics 2015, 4, 455-466; doi:10.3390/antibiotics4040455 antibiotics

    E-print Network

    Antibiotics 2015, 4, 455-466; doi:10.3390/antibiotics4040455 antibiotics ISSN 2079-6382 www.mdpi.com/journal/antibiotics prescription of antibiotic drugs. The antimicrobial susceptibility test (AST) is one of the most crucial experimental procedures, providing the baseline information for choosing effective antibiotic agents

  3. Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data

    PubMed Central

    2013-01-01

    Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporin’s decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energy’s values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps. PMID:23594763

  4. Evaluation of antibiotic prescription in the Lebanese community: a pilot study

    PubMed Central

    Saleh, Nadine; Awada, Sanaa; Awwad, Rana; Jibai, Sahar; Arfoul, Chadi; Zaiter, Liliana; Dib, Wissam; Salameh, Pascale

    2015-01-01

    Background Antibiotics are considered among the most commonly prescribed drug classes in developing countries. Inappropriate prescription of antibiotics is a major public health concern and is related to the development of antimicrobial resistance. Objective This study aimed at assessing the appropriateness of antibiotic prescription by non-infectious disease physicians in a community setting in Lebanon. Methods A pilot cross-sectional study was undertaken on community pharmacy patients presenting with antibiotic prescription. It was performed over a period of 4 months in different regions of Lebanon. Participants answered a questionnaire inquiring about socio-demographic characteristics, medical conditions, symptoms that required medical attention, the doctor's diagnosis, the prescribed antibiotic, and whether laboratory tests were ordered to identify the causative organism or not. Data were analyzed using SPSS 17. Results We studied 270 patients (49.3% males and 50.7% females). This study showed that the most-prescribed antibiotics were the cephalosporins (82%) and that almost half of the illnesses for which antibiotics were prescribed were respiratory tract infections (41%). The study also showed that the choice of the prescribed antibiotic was appropriate in 61.5% of the studied cases, while the prescribed dose and the duration of the treatment were inaccurate in 52 and 64% of the cases, respectively. In addition, fever seemed to be a factor that influenced the physician's prescriptions, since the choice of drug conformity to guidelines increased from 53.7% (1 day of fever) to 88.9% (1 week of fever), and the dose prescription compliance to guidelines was higher (55.9%) for patients suffering from fever compared to those with no fever (38.1%). Conclusion This study showed a high prevalence of inappropriate antibiotic prescriptions in Lebanon. Therefore, actions should be taken to optimize antibiotic prescription. PMID:26112266

  5. Certain attributes of the sexual ecosystem of high-risk MSM have resulted in an altered microbiome with an enhanced propensity to generate and transmit antibiotic resistance.

    PubMed

    Kenyon, C; Osbak, K

    2014-08-01

    Surveillance data from a number of countries have indicated that antibiotic resistance in Neisseriagonorrhoea is strongly associated with men who have sex with men (MSM). This manuscript advances the hypothesis that certain features of the MSM sexual ecosystem may be responsible for this association. It is argued that in comparison with heterosexuals, high-risk MSM (hrMSM) have a higher prevalence of oro-penile, oro-rectal and anal sex which facilitates an enhanced mixing of the pharyngeal, rectal and penile microbiomes. In addition, hrMSM have an increased number of sexual partners per unit time and an increased prevalence of sexual relationships overlapping in time. The increased flux of microbiomes between different body habitats between sexual partners, in combination with the increased connectivity of the sexual network, serve to create a novel high-risk MSM sexual ecosystem with important consequences for the genesis and spread of antibiotic resistance. PMID:24857261

  6. Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand.

    PubMed

    Clendennen, T E; Echeverria, P; Saengeur, S; Kees, E S; Boslego, J W; Wignall, F S

    1992-08-01

    The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending sexually transmitted disease clinics in Cholburi and Bangkok, Thailand, were determined by agar dilution. Some 28.2% of isolates produced beta-lactamase. A total of 97.9% of beta-lactamase-positive and 51% of beta-lactamase-negative isolates tested were resistant to penicillin (MICs, greater than or equal to 2 micrograms/ml), 70% of isolates tested were resistant to tetracycline (MICs, greater than or equal to 2 micrograms/ml), and 91% of isolates tested were susceptible to spectinomycin (MICs, less than or equal to 64 micrograms/ml). The MICs for 90% of isolates for the other drugs tested were 2 micrograms/ml for erythromycin, 2 micrograms/ml for cefoxitin, 1 micrograms/ml for cefuroxime, 0.125 micrograms/ml for cefpodoxime, 0.06 micrograms/ml for cefotaxime, 0.25 micrograms/ml for ceftazidime, 0.03 micrograms/ml for ceftizoxime, 0.03 micrograms/ml for ceftriaxone, 0.03 micrograms/ml for cefixime, 0.06 micrograms/ml for aztreonam, 0.008 micrograms/ml for ciprofloxacin, 0.125 micrograms/ml for norfloxacin, and 0.075 micrograms/ml for ofloxacin. Fewer than 1.5% of isolates were resistant to the extended-spectrum cephalosporins tested. Some 0.3% or fewer isolates were resistant to broad-spectrum cephalosporins, fluoroquinolones, or the monobactam aztreonam. Antibiotic resistance among N. gonorrhoeae isolates from Cholburi and Bangkok in May 1990 appeared to be primarily limited to penicillin and tetracycline, which are no longer used to control gonorrhea. Spectinomycin, which has been in general use against gonorrhea in Thailand since 1983, has dwindling utility, with resistance at a level of 8.9%. PMID:1416851

  7. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections

    PubMed Central

    Krupp, Karl; Madhivanan, Purnima

    2015-01-01

    The emergence of multi-drug resistant sexually transmitted infections (STIs) is causing a treatment crisis across the globe. While cephalosporin-resistant gonorrhea is one of the most pressing issues, extensively antibiotic resistant Chlamydia trachomatis and Mycoplasma hominis are also becoming commonplace. Experts have suggested that the failure of current treatment regimens are “largely inevitable” and have called for entirely new classes of antimicrobial agents. With the exception of several new classes of drugs primarily targeting nosocomial infections, progress has been slow. While pharmaceutical companies continue to introduce new drugs, they are based on decade-old discoveries. While there is disagreement about what constitutes new classes of antibiotics, many experts suggest that the last truly new family of antimicrobials was discovered in 1987. This review summarizes the existing literature on antibiotic resistance in common bacterial and protozoal STIs. It also briefly discusses several of the most promising alternatives to current therapies, and further examines how advances in drug delivery, formulation, concentration, and timing are improving the efficacy of existing treatments. Finally, the paper discusses the current state of pharmaceutical development for multidrug-resistant STI. PMID:26392647

  8. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections.

    PubMed

    Krupp, Karl; Madhivanan, Purnima

    2015-01-01

    The emergence of multi-drug resistant sexually transmitted infections (STIs) is causing a treatment crisis across the globe. While cephalosporin-resistant gonorrhea is one of the most pressing issues, extensively antibiotic resistant Chlamydia trachomatis and Mycoplasma hominis are also becoming commonplace. Experts have suggested that the failure of current treatment regimens are "largely inevitable" and have called for entirely new classes of antimicrobial agents. With the exception of several new classes of drugs primarily targeting nosocomial infections, progress has been slow. While pharmaceutical companies continue to introduce new drugs, they are based on decade-old discoveries. While there is disagreement about what constitutes new classes of antibiotics, many experts suggest that the last truly new family of antimicrobials was discovered in 1987. This review summarizes the existing literature on antibiotic resistance in common bacterial and protozoal STIs. It also briefly discusses several of the most promising alternatives to current therapies, and further examines how advances in drug delivery, formulation, concentration, and timing are improving the efficacy of existing treatments. Finally, the paper discusses the current state of pharmaceutical development for multidrug-resistant STI. PMID:26392647

  9. Antibiotics in the environment.

    PubMed

    Larsson, D G Joakim

    2014-05-01

    Molecules with antibiotic properties, produced by various microbes, have been around long before mankind recognized their usefulness in preventing and treating bacterial infections. Bacteria have therefore been exposed to selection pressures from antibiotics for very long times, however, generally only on a micro-scale within the immediate vicinity of the antibiotic-producing organisms. In the twentieth century we began mass-producing antibiotics, mainly synthetic derivatives of naturally produced antibiotic molecules, but also a few entirely synthetic compounds. As a consequence, entire bacterial communities became exposed to unprecedented antibiotic selection pressures, which in turn led to the rapid resistance development we are facing today among many pathogens. We are, rightly, concerned about the direct selection pressures of antibiotics on the microbial communities that reside in or on our bodies. However, other environments, outside of our bodies, may also be exposed to antibiotics through different routes, most often unintentionally. There are concerns that increased selection pressures from antibiotics in the environment can contribute to the recruitment of resistance factors from the environmental resistome to human pathogens. This paper attempts to 1) provide a brief overview of environmental exposure routes of antibiotics, 2) provide some thoughts about our current knowledge of the associated risks for humans as well as ecosystems, and 3) indicate management options to reduce risks. PMID:24646081

  10. Antibiotic resistance of Gram-negative benthic bacteria isolated from the sediments of Kardzhali Dam (Bulgaria)

    PubMed Central

    Iliev, Ivan; Marhova, Mariana; Gochev, Velizar; Tsankova, Marinela; Trifonova, Sonya

    2015-01-01

    The aim of the present study was to carry out a preliminary assessment for the occurrence of bacterial strains resistant to frequently used antibiotics in the sediments beneath the sturgeon cage farm in Kardzhali Dam (Bulgaria). Samples were taken from the top 2 cm of sediments under a fish farm and from a control station in the aquatory of the reservoir in the period July–October 2011. Surveillance of bacterial susceptibility to 16 antimicrobial agents was performed for 160 Gram-negative strains (Pseudomonas mandelii – 100 strains; Hafnia alvei – 30 strains; and Raoultella ornithinolytica – 30 strains). No significant differences in the resistance to the tested antibiotics were observed between the strains isolated from the two stations (analysis of variance, P > 0.05). Widespread resistance to penicillins and certain cephalosporin antibiotics was observed in both stations. None of the studied strains showed resistance to the aminoglycoside antibiotics gentamicin and amikacin, or to ciprofloxacin. Minimal Inhibitory Concentrations (MIC) were determined for five of the tested antimicrobial agents by the microdilution antibiotic sensitivity assay. The data indicate that amikacin, tetracycline and ciprofloxacin effectively suppress the growth of the tested micro-organisms. The isolates from genus Pseudomonas showed the highest MIC and were characterized by the highest percentage of antibiotic resistance. PMID:26019641

  11. On the use of antibiotics to reduce rhizoplane microbial populations in root physiology and ecology investigations

    NASA Technical Reports Server (NTRS)

    Smart, D. R.; Ferro, A.; Ritchie, K.; Bugbee, B. G.

    1995-01-01

    No straightforward method exists for separating the proportion of ion exchange and respiration due to rhizoplane microbial organisms from that of root ion exchange and respiration. We examined several antibiotics that might be used for the temporary elimination of rhizoplane bacteria from hydroponically grown wheat roots (Triticum aestivum cv. Veery 10). Each antibiotic was tested for herbicidal activity and plate counts were used to enumerate bacteria and evaluate antibiotic kinetics. Only lactam antibiotics (penicillins and cephalosporins) did not reduce wheat growth rates. Aminoglycosides, the pyrimidine trimethoprim, colistin and rifampicin reduced growth rates substantially. Antibiotics acted slowly, with maximum reductions in rhizoplane bacteria occurring after more than 48 h of exposure. Combinations of nonphytotoxic antibiotics reduced platable rhizoplane bacteria by as much as 98%; however, this was generally a reduction from about 10(9) to 10(6) colony forming units per gram of dry root mass, so that many viable bacteria remained on root surfaces. We present evidence which suggests that insufficient bacterial biomass exists on root surfaces of nonstressed plants grown under well-aerated conditions to quantitatively interfere with root nitrogen absorption measurements.

  12. Environmental risk assessment of antibiotics including synergistic and antagonistic combination effects.

    PubMed

    Marx, Conrad; Mühlbauer, Viktoria; Krebs, Peter; Kuehn, Volker

    2015-08-15

    The interaction-based hazard index (HIint) allows a prediction of mixture effects different from linear additivity by including information on binary mixtures between the chemicals. The aim of this study is to make a solid estimate on the possible synergistic potential of combined antibiotics and to quantify the subsequent effect for the case of the receiving river Elbe, Germany. Pieces of information on binary interactions between antibiotic groups were used from literature and from knowledge on human antibiotic combination therapy. Applying a moderate and a worst-case scenario, in terms of the interaction magnitude, resulted in 50 to 200% higher environmental risks, compared to the classical assessment approach applying simple concentration addition. A subsequent sensitivity analysis revealed that the data strength for some binary antibiotic combinations is too low to be considered for a solid estimate of synergistic effects. This led to the definition of certain preconditions in order to decide whether or not to include certain interaction information (e.g. the necessary number of interaction studies). The exclusion of information with low data strength resulted in an attenuated risk increase of 20 to 50%, based on the currently available scientific information on binary antibiotic mixtures. In order to include antibiotics with the highest share in the overall risk (macrolides, quinolones, and cephalosporins) as well as their corresponding metabolites, investigations should focus on binary interactions between them. PMID:25897732

  13. A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?

    PubMed Central

    Baietto, Lorena; Corcione, Silvia; Pacini, Giovanni; Di Perri, Giovanni; D’Avolio#†, Antonio; Giuseppe De Rosa†, Francesco

    2014-01-01

    Drug bioavailability may vary greatly amongst individuals, affecting both efficacy and toxicity: in humans, genetic variations account for a relevant proportion of such variability. In the last decade the use of pharmacogenetics in clinical practice, as a tool to individualize treatment, has shown a different degree of diffusion in various clinical fields. In the field of infectious diseases, several studies identified a great number of associations between host genetic polymor-phisms and responses to antiretroviral therapy. For example, in patients treated with abacavir the screening for HLA-B*5701 before starting treatment is routine clinical practice and standard of care for all patients; efavirenz plasma levels are influenced by single nucleotide polymorphism (SNP) CYP2B6-516G> T (rs3745274). Regarding antibiotics, many studies investigated drug transporters involved in antibiotic bioavailability, especially for fluoroquinolones, cephalosporins, and antituberculars. To date, few data are available about pharmacogenetics of recently developed antibiotics such as tigecycline, daptomycin or linezolid. Considering the effect of SNPs in gene coding for proteins involved in antibiotics bioavailability, few data have been published. Increasing knowledge in the field of antibiotic pharmacogenetics could be useful to explain the high drug inter-patients variability and to individualize therapy. In this paper we reported an overview of pharmacokinetics, pharmacodynamics, and pharmacogenetics of antibiotics to underline the importance of an integrated approach in choosing the right dosage in clinical practice. PMID:24909419

  14. Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

    PubMed

    Thornton, Christina S; Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2015-11-01

    The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone (?antibiotic resistance was to the macrolides [azithromycin (56.4?%) and erythromycin (51.6?%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome. PMID:26408040

  15. Turning the tide or riding the waves? Impacts of antibiotic stewardship and infection control on MRSA strain dynamics in a Scottish region over 16?years: non-linear time series analysis

    PubMed Central

    Lawes, Timothy; López-Lozano, José-María; Nebot, César; Macartney, Gillian; Subbarao-Sharma, Rashmi; Dare, Ceri R J; Edwards, Giles F S; Gould, Ian M

    2015-01-01

    Objectives To explore temporal associations between planned antibiotic stewardship and infection control interventions and the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). Design Retrospective ecological study and time-series analysis integrating typing data from the Scottish MRSA reference laboratory. Setting Regional hospital and primary care in a Scottish Health Board. Participants General adult (N=1?051?993) or intensive care (18?235) admissions and primary care registrations (460?000 inhabitants) between January 1997 and December 2012. Interventions Hand-hygiene campaign; MRSA admission screening; antibiotic stewardship limiting use of macrolides and ‘4Cs’ (cephalosporins, coamoxiclav, clindamycin and fluoroquinolones). Outcome measures Prevalence density of MRSA clonal complexes CC22, CC30 and CC5/Other in hospital (isolates/1000 occupied bed days, OBDs) and community (isolates/10?000 inhabitant-days). Results 67% of all clinical MRSA isolates (10?707/15?947) were typed. Regional MRSA population structure was dominated by hospital epidemic strains CC30, CC22 and CC45. Following declines in overall MRSA prevalence density, CC5 and other strains of community origin became increasingly important. Reductions in use of ‘4Cs’ and macrolides anticipated declines in sublineages with higher levels of associated resistances. In multivariate time-series models (R2=0.63–0.94) introduction of the hand-hygiene campaign, reductions in mean length of stay (when >4?days) and bed occupancy (when >74 to 78%) predicted declines in CC22 and CC30, but not CC5/other strains. Lower importation pressures, expanded MRSA admission screening, and reductions in macrolide and third generation cephalosporin use (thresholds for association: 135–141, and 48–81 defined daily doses/1000 OBDs, respectively) were followed by declines in all clonal complexes. Strain-specific associations with fluoroquinolones and clindamycin reflected resistance phenotypes of clonal complexes. Conclusions Infection control measures and changes in population antibiotic use were important predictors of MRSA strain dynamics in our region. Strategies to control MRSA should consider thresholds for effects and strain-specific impacts. PMID:25814495

  16. Novel Method for Detection of ?-Lactamases by Using a Chromogenic Cephalosporin Substrate

    PubMed Central

    O'Callaghan, Cynthia H.; Morris, A.; Kirby, Susan M.; Shingler, A. H.

    1972-01-01

    A new cephalosporin with a highly reactive ?-lactam ring was found to give an immediate color change in the presence of ?-lactamases from many bacteria, including staphylococci, Bacillus species, Enterobacteriaceae, and Pseudomonas. The reaction is confined to organisms producing ?-lactamases, but it is sufficiently sensitive to indicate the presence of this enzyme is small amounts in strains previously considered not to produce it. The compound has an unusual ultraviolet spectrum, and the color change can be followed quantitatively by measuring changes in absorption which occur in the 380- to 500-nm region, where cephalosporins normally have no absorption. The development of color is thought to be a consequence of the ?-lactam ring being unusually highly conjugated with the 3-substituent. Although in the bacteria only ?-lactamases produce this color change, it was found that serum and tissues from experimental animals also rapidly produced the colored breakdown product, which was then excreted in the urine. The mechanism of the mammalian breakdown was considered to be different from that found in bacteria. PMID:4208895

  17. Biotic acts of antibiotics

    PubMed Central

    Aminov, Rustam I.

    2013-01-01

    Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic – in particular mammalian – cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and ?-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed. PMID:23966991

  18. The Real Practice of Antibiotic Prophylaxis for Prostate Biopsy in Korea Where the Prevalence of Quinolone-Resistant Escherichia coli Is High

    PubMed Central

    Kim, Dae Hyun; Bae, Sang Rak; Choi, Woo Suk; Paick, Sung Hyun; Kim, Hyeong Gon; Loh, Yong Soo

    2014-01-01

    Purpose Transrectal ultrasonography-guided prostate biopsy (TRUS-Bx) is an essential procedure for diagnosing prostate cancer. The American Urological Association (AUA) Guideline recommends fluoroquinolone alone for 1 day during TRUS-Bx. However, this recommendation may not be appropriate in regions where the prevalence of quinolone-resistant Escherichia coli is high. We investigated the real practice of antibiotic prophylaxis for TRUS-Bx in Korea. Materials and Methods A total of 77 hospitals performing TRUS-Bx were identified and an e-mail was sent to the Urology Department of those hospitals. The questions in the e-mail included the choice of antibiotics before and after the procedure and the duration of antibiotic therapy after TRUS-Bx. Results A total of 54 hospitals (70.0%) responded to the e-mail. Before TRUS-Bx, all hospitals administered intravenous antibiotic prophylaxis. The percentage of hospitals that used quinolone, cephalosporin, and aminoglycoside alone was 48.1%, 20.4%, and 9.3%, respectively. The percentage of hospitals that used two or more antibiotics was 22.2%. After biopsy, all 54 hospitals prescribed oral antibiotics. The percentage of hospitals that prescribed quinolone alone, cephalosporin alone, or a combination of two or more antibiotics was 77.8%, 20.4%, and 1.8%, respectively. The duration of antibiotic use was more than 3 days in most hospitals (79.6%). Only four hospitals (7.4%) followed the AUA recommendation of a 1-day regimen. Conclusions The AUA recommendation was not followed by most hospitals in Korea. This clinical behavior might reflect the high quinolone resistance rate in Korea, and further studies on the most efficient prophylactic antibiotics after TRUS-Bx in Korea are warranted. PMID:25237461

  19. Antibiotic / Antimicrobial Resistance Glossary

    MedlinePLUS

    ... Adult Treatment Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving ...

  20. Facts about Antibiotic Resistance

    MedlinePLUS

    ... Adult Treatment Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving ...

  1. Prescription antibiotics for outpatients in Bangladesh: a cross-sectional health survey conducted in three cities

    PubMed Central

    2014-01-01

    Background Antibiotics prescribing by physicians have gained due importance across the globe, mainly because of an increase in antibiotic usage, prevalence of infections and drug resistances. The present study is aimed to evaluate the physicians prescribing pattern of antibiotics, their usages by outpatients and disease conditions for which the antibiotics are prescribed in three cities of Bangladesh. Methods This cross sectional health survey was carried out with a self designed standard questionnaire by manual data collection over a three months period (20.03.2013 to 20.06.2013) at three adjacent cities Jessore Sadar, Monirampur and Keshabpur upazila respectively. The data were collected from the patient’s prescription and by directly interviewing the patients who were prescribed at least one antibiotic during the study period. WHO Anatomical Therapeutic Chemical (ATC) classifications for antibiotics was used and descriptive statistics were applied to the collected data and analyzed using Microsoft Excel software. Modified Wald method was applied to calculate 95% CI. Results A total of 900 prescriptions were analyzed during the study period. It was found that the prescriber prescribed antibiotics to the patients who were suffering mainly from cold and fever, infections, diarrhea and gonorrhea. The highest prescribed antibiotic groups were cephalosporins (31.78%), macrolides (27.33%), quinolones (16.33%), penicillins (7.11%), and metronidazoles (6.78%) respectively. Two or more antibiotics were prescribed in 25.44% of prescriptions. A total of 66.89% prescriptions had complete information on dosage form, 57% had complete direction for antibiotics use and 64.22% patients completed full course of antibiotics. Although 83% prescriptions have no clinical test for using antibiotics, even though the percentages of patients’ disease recovery were 61.78% and incompliance were 38.22%. Conclusion From this research, it is observed that physicians prescribed antibiotics rationally in some cases but needs to ensure in all cases of prescription. Because irrational use leads to the spread of bacterial resistance to antibiotics and related health problems, our findings have important implications for public education and the enforcement of regulations regarding the prescription of antibiotics in Bangladesh. PMID:24755269

  2. Impact of the Use of ?-Lactam Antimicrobials on the Emergence of Escherichia coli Isolates Resistant to Cephalosporins under Standard Pig-Rearing Conditions

    PubMed Central

    Cameron-Veas, Karla; Solà-Ginés, Marc; Moreno, Miguel A.; Fraile, Lorenzo

    2014-01-01

    The aim of this study was to evaluate if the treatments with ceftiofur and amoxicillin are risk factors for the emergence of cephalosporin resistant (CR) E. coli in a pig farm during the rearing period. One hundred 7-day-old piglets were divided into two groups, a control (n = 50) group and a group parenterally treated with ceftiofur (n = 50). During the fattening period, both groups were subdivided in two. A second treatment with amoxicillin was administered in feed to two of the four groups, as follows: group 1 (untreated, n = 20), group 2 (treated with amoxicillin, n = 26), group 3 (treated with ceftiofur, n = 20), and group 4 (treated with ceftiofur and amoxicillin, n = 26). During treatment with ceftiofur, fecal samples were collected before treatment (day 0) and at days 2, 7, 14, 21, and 42 posttreatment, whereas with amoxicillin, the sampling was extended 73 days posttreatment. CR E. coli bacteria were selected on MacConkey agar with ceftriaxone (1 mg/liter). Pulsed-field gel electrophoresis (PFGE), MICs of 14 antimicrobials, the presence of cephalosporin resistance genes, and replicon typing of plasmids were analyzed. Both treatments generated an increase in the prevalence of CR E. coli, which was statistically significant in the treated groups. Resistance diminished after treatment. A total of 47 CR E. coli isolates were recovered during the study period; of these, 15 contained blaCTX-M-1, 10 contained blaCTX-M-14, 4 contained blaCTX-M-9, 2 contained blaCTX-M-15, and 5 contained blaSHV-12. The treatment with ceftiofur and amoxicillin was associated with the emergence of CR E. coli during the course of the treatment. However, by the time of finishing, CR E. coli bacteria were not recovered from the animals. PMID:25548055

  3. Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs

    SciTech Connect

    Wang, Xiaojun; Minasov, George; Shoichet, Brian K.

    2010-03-08

    Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the {beta}-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182 {yields} Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.

  4. Antibiotic-Resistant Bacteria.

    ERIC Educational Resources Information Center

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

    A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

  5. Replacement for antibiotics: Lysozyme

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics have been fed at subtherapeutic levels to swine as growth promoters for more than 60 years, and the majority of swine produced in the U.S. receive antibiotics in their feed at some point in their production cycle. These compounds benefit the producers by minimizing production losses by ...

  6. Mining the antibiotic resistome.

    PubMed

    Sello, Jason K

    2012-10-26

    Antibiotic-producing microoganisms are a reservoir of drug resistance genes. Studies of the "antibiotic resistome" can inform antimicrobial drug discovery and explain the emergence of multidrug resistant pathogens. In this issue of Chemistry & Biology, Westman and colleagues take an alternative look at the resistome and identify genes that could be used to detoxify the anticancer compound, doxorubicin. PMID:23102216

  7. Sorption Mechanisms of Antibiotic Cephapirin onto Quartz and Feldspar by Raman Spectroscopy

    SciTech Connect

    Peterson, Jonathan; Wang, Wei; Gu, Baohua

    2009-01-01

    Raman spectroscopy was used to investigate the sorption mechanisms of cephapirin (CHP), a veterinary antibiotic, onto quartz (SiO2) and feldspar (KAlSi3O8) at different pH values. Depending on the charge and surface properties of the mineral, different reaction mechanisms including electrostatic attraction, monodentate and bidentate complexation were found to be responsible for CHP sorption. The zwitterion (CHPo) adsorbs to a quartz(+) surface by electrostatic attraction of the carboxylate anion group ( COO-) at a low pH, but adsorbs to a quartz(-) surface through electrostatic attraction of the pyridinium cation and possibly COO- bridge complexes at relatively higher pH conditions. CHP- bonds to a quartz(-) surface by bidentate complexation between one oxygen of COO- and oxygen from the carbonyl (C=O) of the acetoxymethyl group. On a feldspar surface of mixed charge, CHPo forms monodentate complexes between C=O as well as COO- bridging complexes or electrostatically attached to localized edge (hydr)oxy-Al surfaces. CHP- adsorbs to feldspar(-) through monodentate C=O complexation, and similar mechanisms may operate for the sorption of other cephalosporins. This research demonstrates, for the first time, that Raman spectroscopic techniques can be effective for evaluating the sorption processes and mechanisms of cephalosporin antibiotics even at relatively low sorbed concentrations (97-120 ?mol/kg).

  8. Molecular Assay for Detection of Genetic Markers Associated with Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae

    PubMed Central

    Peterson, S. W.; Martin, I.; Demczuk, W.; Bharat, A.; Hoang, L.; Wylie, J.; Allen, V.; Lefebvre, B.; Tyrrell, G.; Horsman, G.; Haldane, D.; Garceau, R.; Wong, T.

    2015-01-01

    The incidence of antimicrobial-resistant Neisseria gonorrhoeae continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in ponA, mtrR, penA, porB, and one N. gonorrhoeae-specific marker (porA). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24 N. gonorrhoeae-negative NAAT specimens, and 34 N. gonorrhoeae-positive NAAT specimens. Twenty-four of the N. gonorrhoeae-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252 N. gonorrhoeae strains, the agreement between the DNA sequence and real-time PCR was 100% for porA, ponA, and penA, 99.6% for mtrR, and 95.2% for porB. The presence of ?2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for porB, 95.8% for ponA and mtrR, and 91.7% for penA. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in N. gonorrhoeae. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results. PMID:25878350

  9. Ultrasound-assisted matrix solid phase dispersive extraction for the simultaneous analysis of ?-lactams (four penicillins and eight cephalosporins) in milk by high performance liquid chromatography with photodiode array detection.

    PubMed

    Karageorgou, Eftichia G; Samanidou, Victoria F; Papadoyannis, Ioannis N

    2012-10-01

    The application of ultrasound-assisted matrix solid phase dispersive extraction for the confirmatory analysis of 12 ?-lactam antibiotics in milk by high performance liquid chromatography with photodiode array detection has been proposed herein. Four penicillins (cloxacillin, dicloxacillin, oxacillin, and amoxicillin) and eight cephalosporins (cefaclor, cefadroxil, ceftiofur, cefuroxime, cefoperazone, cefazolin, cephalexin, and cefotaxime) are effectively extracted using a mixed sorbent of Quick Easy Cheap Effective Rugged Safe technique and OASIS HLB providing a matrix free from any endogenous interference. Examined analytes were well resolved on an Inertsil ODS-3 analytical column with a mobile phase of CH(3)COONH(4) (0.05 M) and acetonitrile delivered under a gradient program. 1,7-Dimethyl-xanthine was used as internal standard. The method was validated meeting the European Legislation determining linearity, selectivity, stability, decision limit, detection capability, accuracy, precision, and ruggedness according to the Youden approach. Recoveries of all antibiotics rated from 85.0 to 115.7%, while RSD values were <12.7%. Finally, the method was successfully applied to milk samples purchased from local market. PMID:22941669

  10. Antibiotic Resistance Bioscene 17 Measurement of Mutation to Antibiotic

    E-print Network

    Antonovics, Janis

    Antibiotic Resistance Bioscene 17 Measurement of Mutation to Antibiotic Resistance: Ampicillin College 3026 Laclede Ave. St. Louis, MO 63103 Abstract: The public health problem of antibiotic resistance or more students. Key words: Serratia marcescens; antibiotic resistance; Luria-Delbrück fluctuation test

  11. Structure-activity relationship of carbacephalosporins and cephalosporins: antibacterial activity and interaction with the intestinal proton-dependent dipeptide transport carrier of Caco-2 cells.

    PubMed Central

    Snyder, N J; Tabas, L B; Berry, D M; Duckworth, D C; Spry, D O; Dantzig, A H

    1997-01-01

    An intestinal proton-dependent peptide transporter located on the lumenal surface of the enterocyte is responsible for the uptake of many orally absorbed beta-lactam antibiotics. Both cephalexin and loracarbef are transported by this mechanism into the human intestinal Caco-2 cell line. Forty-seven analogs of the carbacephalosporin loracarbef and the cephalosporin cephalexin were prepared to evaluate the structural features necessary for uptake by this transport carrier. Compounds were evaluated for their antibacterial activities and for their ability to inhibit 1 mM cephalexin uptake and, subsequently, uptake into Caco-2 cells. Three clinically evaluated orally absorbed carbacephems were taken up by Caco-2 cells, consistent with their excellent bioavailability in humans. Although the carrier preferred the L stereoisomer, these compounds lacked antibacterial activity and were hydrolyzed intracellularly in Caco-2 cells. Compounds modified at the 3 position of cephalexin and loracarbef with a cyclopropyl or a trifluoromethyl group inhibited cephalexin uptake. Analogs with lipophilic groups on the primary amine of the side chain inhibited cephalexin uptake, retained activity against gram-positive bacteria but lost activity against gram-negative bacteria. Substitution of the phenylglycl side chain with phenylacetyl side chains gave similar results. Compounds which lacked an aromatic ring in the side chain inhibited cephalexin uptake but lost all antibacterial activity. Thus, the phenylglycl side chain is not absolutely required for uptake. Different structural features are required for antibacterial activity and for being a substrate of the transporter. Competition studies with cephalexin indicate that human intestinal Caco-2 cells may be a useful model system for initially guiding structure-activity relationships for the rational design of new oral agents. PMID:9257735

  12. When Antibiotics Are Needed

    MedlinePLUS

    ... news item will not be available after 02/16/2016) By Robert Preidt Wednesday, November 18, 2015 ... Control and Prevention and other partners from Nov. 16-22. "All use of antibiotics leads, eventually, to ...

  13. [Antibiotic therapy in psittacines].

    PubMed

    Krautwald, M E

    1989-01-01

    The use of different antibiotics in psittacines is described. Among other aspects especially the anatomy of the bird and its consequence for the application of medicaments is taken into account. The use of antibiotics in psittacines often turns out to be difficult because of missing data about their pharmacokinetics, dosage, period of application and their compatibility. In order to deal with the increasing number of pet-birds in the veterinary practice, further examinations have to be conducted. PMID:2655172

  14. Strategies to Minimize Antibiotic Resistance

    PubMed Central

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-01-01

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

  15. Occurrences and fate of selected human antibiotics in influents and effluents of sewage treatment plant and effluent-receiving river Yamuna in Delhi (India).

    PubMed

    Mutiyar, Pravin K; Mittal, Atul K

    2014-01-01

    Antibiotics consumption has increased worldwide, and their residues are frequently reported in aquatic environments. It is believed that antibiotics reach aquatic water bodies through sewage. Medicine consumed for healthcare practices are often released into sewage, and after sewage treatment plant, it reaches the receiving water bodies of lakes or rivers. In the present study, we determined the fate of some commonly used antibiotics in a sewage treatment plant (STP) located in Delhi and the environmental concentration of these antibiotics in the Yamuna River, which receives the sewage and industrial effluent of Delhi. There are many reports on antibiotics occurrences in STP and river water worldwide, but monitoring data from the Indian subcontinent is sparse. Samples were taken from a STP and from six sampling sites on the Yamuna River. Several antibiotics were tested for using offline solid-phase extraction followed by high-performance liquid chromatography equipped with photodiode array analysis. Recoveries varied from 25.5-108.8 %. Ampicillin had the maximum concentration in wastewater influents (104.2?±?98.11 ?g l(-1)) and effluents (12.68?±?8.38 ?g l(-1)). The fluoroquinolones and cephalosporins had the lower concentrations. Treatment efficiencies varied between 55 and 99 %. Significant amounts of antibiotics were discharged in effluents and were detected in the receiving water body. The concentration of antibiotics in the Yamuna River varied from not detected to 13.75 ?g l(-1) (ampicillin) for the compounds investigated. PMID:24085621

  16. Antibiotic Prescriptions in Critically-Ill Patients: A Latin American Experience

    PubMed Central

    Curcio, D

    2013-01-01

    Background: It is widely acknowledged that the presence of infection is an important outcome determinant for intensive care unit (ICU) patients. In fact, antibiotics are one of the most common therapies administered in the ICU settings. Aim: To evaluate the current usage of antibiotics in Latin American ICUs. Subjects and Methods: A one-day p-oint prevalence study to investigate the patterns of antibiotic was undertaken in 72 Latin American (LA) ICUs. Data was analyzed using the Statistix 8 statistical software, version 2.0 (USA). Results were expressed as proportions. When applicable, two tailed hypothesis testing for difference in proportions was used (Proportion Test); a P value of <0.05 was considered significant. Results: Of 704 patients admitted, 359 received antibiotic treatment on the day of the study (51%), of which 167/359 cases (46.5%) were due to hospital-acquired infections. The most frequent infection reorted was nosocomial pneumonia (74/359, 21%). Only in 264/359 patients (73.5%), cultures before starting antibiotic treatment were performed. Thirty-eight percent of the isolated microorganisms were Enterobacteriaceae extended-spectrum ?-lactamase-producing, 11% methicillin-resistant Staphylococcus aureus and 10% carbapenems-resistant non-fermentative Gram-negatives. The antibiotics most frequently prescribed were carbapenems (125/359, 35%), alone or in combination with vancomycin or other antibiotic. There were no significant differences in the “restricted” antibiotic prescription (carbapenems, vancomycin, piperacillin–tazobactam, broad-spectrum cephalosporins, fluoroquinolones, tigecycline and linezolid) between patients with APACHE II score at the beginning of the antibiotic treatment <15 [83/114 (72.5%)] and ?15 [179/245 (73%)] (P = 0.96). Only 29% of the antibiotic treatments were cultured directed (104/359). Conclusion: Carbapenems (alone or in combination) were the most frequently prescribed antibiotics in LA ICUs. However, the problem of carbapenem resistance in LA requires that physicians improve the use of this class of antibiotics. Our findings show that our web-based method for collection of one-day point prevalence was implemented successfully. However, based on the limitations of the model used, the results of this study must be taken with caution. PMID:23919194

  17. Evaluation of Ceftaroline Activity versus Ceftriaxone against Clinical Isolates of Streptococcus pneumoniae with Various Susceptibilities to Cephalosporins in an In Vitro Pharmacokinetic/Pharmacodynamic Model

    E-print Network

    Steed, Molly E.; Vidaillac, Celine; Winterfield, Patricia; Biek, Donald; Rybak, Michael J.

    2012-05-01

    Drug resistance in Streptococcus pneumoniae, a frequent pathogen in community-acquired pneumonia, is increasing. Ceftaroline (active metabolite of ceftaroline fosamil) is a broad-spectrum intravenous cephalosporin with activity in vitro against drug...

  18. BEL-2, an extended-spectrum beta-lactamase with increased activity toward expanded-spectrum cephalosporins in Pseudomonas aeruginosa.

    PubMed

    Poirel, Laurent; Docquier, Jean-Denis; De Luca, Filomena; Verlinde, Annemie; Ide, Louis; Rossolini, Gian Maria; Nordmann, Patrice

    2010-01-01

    A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ss-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla(BEL-2) gene was identified from a P. aeruginosa isolate clonally related to another bla(BEL-1)-positive isolate. PMID:19884378

  19. BEL-2, an Extended-Spectrum ?-Lactamase with Increased Activity toward Expanded-Spectrum Cephalosporins in Pseudomonas aeruginosa?

    PubMed Central

    Poirel, Laurent; Docquier, Jean-Denis; De Luca, Filomena; Verlinde, Annemie; Ide, Louis; Rossolini, Gian Maria; Nordmann, Patrice

    2010-01-01

    A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ß-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The blaBEL-2 gene was identified from a P. aeruginosa isolate clonally related to another blaBEL-1-positive isolate. PMID:19884378

  20. Development and Evaluation of an Ontology for Guiding Appropriate Antibiotic Prescribing

    E-print Network

    Cimino, James J.

    Development and Evaluation of an Ontology for Guiding Appropriate Antibiotic Prescribing Tiffani J knowledge management tasks to maintain the ontology and for generating alerts to guide antibiotic: 1) antibiotic-microorganism mismatch alert; 2) medication-allergy alert; and 3) non

  1. Bacteriology and antibiotic sensitivity patterns of urinary tract infections in a tertiary hospital in Bangladesh.

    PubMed

    Majumder, M I; Ahmed, T; Hossain, D; Begum, S A

    2014-01-01

    Urinary tract infection (UTI) is common bacterial infection in mankind. The changing antimicrobial sensitivity in UTI demands use of appropriate antibiotics. This prospective study was performed in Comilla Medical Collage during the period of January 2011 to December 2011. Five hundred and fifty one urine specimens from clinically suspected UTI patients were examined by Semi quantitative culture method and their antimicrobial sensitivity patterns were determined by disc diffusion technique. The study was designed to isolate and identify the nature of bacteria in UTI with their sensitivity pattern to common antibiotics. Of the 551 tested sample 131 samples showed growth of pathogens among which the most prevalent were E. coli 98(75%) followed by Klebsiella pneumonia 14(10.7%) and Enterococcus 8(6%). The majority 96(73.3%) of the isolates were from female while the remaining were from male and this sex difference was statistically significant (p<0.001). Imipenem, meropenem, amikacin, nitrofurantoin, gentamycin, mecillinum and amoxyclav are found to be effective against 76-100% of the uropathogens. Most powerful antibiotics in our study were imipenem, meropenem, amikacin and nitrofurantoin which show their efficacy against 91-100% isolates. In more than 60% case shows their resistance against amoxycillin, nalidexic acid, cefixime, ciprofloxacin, cotrimoxazole and cephalosporins which raises the question regarding rationality to empirically use of these antibiotics in UTI with out culture and sensitivity reports. PMID:24584381

  2. History and epidemiology of antibiotic susceptibilities of Neisseria gonorrhoeae.

    PubMed

    Shigemura, Katsumi; Fujisawa, Masato

    2015-01-01

    Neisseria gonorrhoeae is a common causative microorganism of male urethritis. The most important problem with this infectious disease is antibiotic resistance. For instance, in the 1980's-1990's, most studies showed almost 100% susceptibility of N. gonorrhoeae to the representative cephalosporins, cefixime and cefpodoxime. By the late 1990s, the reported susceptibility decreased to 93.3-100% and further decreased to 82.9-100% in the early 2000's. However, reported susceptibility was revived to 95.8-100% in the late 2000's to 2010's. The susceptibility of N. gonorrhoeae to penicillins varied in different countries and regions. A 2002 Japanese study showed a resistance ratio of about 30% and while Laos, China and Korea showed 80-100% resistance. Fluoroquinolones have shown a dramatic change in their effect on N. gonorrhoeae. In the early 1990's, 0.3-1.3% of N. gonorrhoeae showed low susceptibility or resistance to ciprofloxacin in the US but this figure jumped to 9.5% by 1999. In Asia, N. gonorrhoeae ciprofloxacin resistance or lower susceptibility was about 80-90% in the early 2000's and this trend continues to the present day. Azithromycin is currently the possible last weapon for N. gonorrhoeae treatment per oral administration. The susceptibility of N. gonorrhoeae to azithromycin was 100% in Indonesia in 2004 and the latest study from Germany showed 6% resistance in strains from 2010-2011. This review summarizes the history and epidemiology of N. gonorrhoeae antibiotic susceptibilities, for which the most frequently used antibiotics vary between countries or regions. PMID:25410409

  3. The multifaceted roles of antibiotics and antibiotic resistance in nature

    PubMed Central

    Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

    2013-01-01

    Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host–parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics in nature. PMID:23487476

  4. Immobilization of a cephalosporin acetylesterase by containment within an ultrafiltration device.

    PubMed

    Abbott, B J; Cerimele, B; Fukuda, D S

    1976-08-01

    A cephalosporin acetylesterase produced by Bacillus subtilis catalyzes the deacetylation of 7-aminocephalosporanic acid (7-ACA). Previous reports from our laboratory described the kinetic constants that characterize the reaction: Km = 2.8 X 10(-3)M, Kia acetate = 5 X 10(-2)M, and Kid deacetyl-7-ACA = 3.6 X 10(-2)M. These constants were used to predict the time course of the reaction using the following equation for dual competitive product inhibition. (see article) where St =mg/ml 7-ACA, At =mg/ml acetate, Dt =mg/ml deacetyl-7-ACA. The predicted time course closely matched the time course measured experimentally. The equation also was solved without the inhibition terms and the solution indicated that product inhibition caused about a 30% increase in the time required for complete (greater than 97%) hydrolysis of a 24 mg/ml 7-ACA solution. The esterase was immobilized by containment within an ultrafiltration device. With this technique the enzyme was reused 20 times over an 11 day span to deacetylate 7-ACA solutions containing 4 to 24 mg/ml 7-ACA. The specific activity after the 20th use was the same as the activity prior to the first use, indicating little enzyme inactiviation occurred. PMID:953166

  5. [Effect of DQ-2556, a new cephalosporin derivative, on fecal microflora].

    PubMed

    Inagaki, Y; Chida, T; Nakaya, R; Hashimoto, S

    1992-10-01

    A new cephalosporin derivative antibacterial agent, DQ-2556, was administered intravenously to 4 healthy adult male volunteers at 2 grams per dosage 2 times a day for 5 days, and degrees of effects of drug concentrations on the fecal microflora were investigated. 1. The total viable count remained unchanged during the study period due to the minimal change in the number of members of the family Bacteroidaceae, which were the most dominant organisms. In one of the volunteers, however, the total count was remarkably reduced immediately after the end of administration of the drug. 2. Among the obligate anaerobes, most of the organisms decreased except members of the family Bacteroidaceae. A marked increase of lecithinase-positive clostridia was noted in 2 volunteers. 3. The number of aerobes, including facultative anaerobes, members of the family Enterobacteriaceae were suppressed but bacilli and yeasts showed slight increases. In many cases, increases in enterococci were also observed. 4. DQ-2556 was not detected in the feces from any of the volunteers during the study period. 5. Neither Clostridium difficile nor its toxin D-1 was detected in any of the volunteers. 6. Diarrhoea or other side-effects were not noted in any of the volunteers. PMID:1479685

  6. Antibiotic prophylaxis in otolaryngologic surgery

    PubMed Central

    Ottoline, Ana Carolina Xavier; Tomita, Shiro; Marques, Marise da Penha Costa; Felix, Felippe; Ferraiolo, Priscila Novaes; Laurindo, Roberta Silveira Santos

    2013-01-01

    Summary Aim:?Antibiotic prophylaxis aims to prevent infection of surgical sites before contamination or infection occurs. Prolonged antibiotic prophylaxis does not enhance the prevention of surgical infection and is associated with higher rates of antibiotic-resistant microorganisms. This review of the literature concerning antibiotic prophylaxis, with an emphasis on otolaryngologic surgery, aims to develop a guide for the use of antibiotic prophylaxis in otolaryngologic surgery in order to reduce the numbers of complications stemming from the indiscriminate use of antibiotics. PMID:25991999

  7. Tensions in antibiotic prescribing.

    PubMed

    Metlay, Joshua P

    2002-05-01

    Since 1999, the Agency for Healthcare Research and Quality has funded seven centers across the country to provide practical guidance to physicians and other health care professionals about the drugs they prescribe. These Centers for Education and Research on Therapeutics (CERTs) develop, translate and disseminate objective information on drugs to improve practice. The University of Pennsylvania's CERTs focuses on developing evidence for optimal treatment strategies for infectious diseases, and promoting the judicious use of antibiotics to combat the problem of antibiotic resistance. This Issue Brief explores one of the fundamental challenges physicians face in optimizing antibiotic use: the potential conflict between what is best for an individual patient, and what is best for society as a whole. PMID:12528744

  8. Antibiotic Precautions in Athletes

    PubMed Central

    Fayock, Kristopher; Voltz, Matthew; Sandella, Bradley; Close, Jeremy; Lunser, Matthew; Okon, Joshua

    2014-01-01

    Context: Antibiotics are the mainstay of treatment for bacterial infections in patients of all ages. Athletes who maximally train are at risk for illness and various infections. Routinely used antibiotics have been linked to tendon injuries, cardiac arrhythmias, diarrhea, photosensitivity, cartilage issues, and decreased performance. Evidence Acquisition: Relevant articles published from 1989 to 2012 obtained through searching MEDLINE and OVID. Also, the Food and Drug Administration website was utilized. Study Design: Clinical review. Level of Evidence: Level 3. Results: The team physician should consider alternative medications in place of the “drug of choice” when adverse drug effects are a concern for an athlete’s health or performance. If alternative medications cannot be selected, secondary preventative measures, including sunscreen or probiotics, may be needed. Conclusion: Physicians choose medications based on a variety of factors to help ensure infection resolution while limiting potential side effects. Extra precautions are indicated when treating athletes with certain antibiotics. PMID:24982704

  9. Antibiotic activity in space.

    PubMed

    Lapchine, L; Moatti, N; Gasset, G; Richoilley, G; Templier, J; Tixador, R

    1986-01-01

    Environmental factors in space exert an influence on the behaviour of bacteria, particularly on their sensitivity to antibiotics. Thus, G. Taylor and S. Zaloguev observed that bacterial samples collected on the crew during flight in the Apollo-Soyouz Test Project Mission presented higher antibiotic resistance than controls. This paper presents the results of two experiments performed in 1982 and 1985 (Cytos 2 during the French-Soviet Mission and "Antibio" in the Biorack programme of the European Space Agency). The results show an increase of antibiotic resistance in bacteria growth in flight and a modification in the structure of the cell wall. All these modifications are transitory. Two hypotheses are put forward to explain the phenomenon. PMID:3569006

  10. Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride

    SciTech Connect

    Harvey, R.A.; Alcid, D.V.; Greco, R.S.

    1982-09-01

    Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds /sup 14/C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds /sup 14/C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

  11. Application of 1H nuclear magnetic resonance spectroscopy to the analysis of beta-lactam antibiotics and their common degradation products.

    PubMed

    Branch, S K; Casy, A F; Ominde, E M

    1987-01-01

    The (1)H NMR characteristics of the majority of penicillin and cephalosporin beta-lactam antibiotics in world-wide clinical use are presented. Some of the data are novel and include several high resolution (220, 400 MHz) spectra. The influence of solvent and ionisation state upon spectral parameters is discussed and a scheme of analysis proposed for identifying an unknown beta-lactam sample. Spectral features of common degradation products of benzylpenicillin and other penicillins are provided and the use of (1)H NMR spectroscopy in monitoring the breakdown of penicillin antibiotics described. Other aspects discussed are NMR studies of the stereochemistry, association and protein binding of beta-lactam antibiotics. PMID:16867529

  12. Tackling antibiotic resistance

    PubMed Central

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.

    2014-01-01

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

  13. Antibiotic-Resistant Gonorrhea (ARG)

    MedlinePLUS

    ... please visit this page: About CDC.gov . Gonorrhea Antibiotic Resistance Basic Information Laboratory Information Resources & References Facts & Brochures ... Page Surveillance Trends and Treatment Challenges Laboratory Issues Antibiotic resistance (AR) is the ability of bacteria to resist ...

  14. Bacterial cheating limits antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

    2012-02-01

    The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

  15. Best antibiotics for buccal delivery

    E-print Network

    Goldberg, Manijeh Nazari

    2011-01-01

    The purpose of the research was to identify the clinical and commercial benefits of switching from intravenous (IV) to buccal delivery of antibiotics. then, the research continued to select 3-5 antibiotics that best met ...

  16. What Can Be Done about Antibiotic Resistance?

    MedlinePLUS

    ... antibiotics for treating human disease. (See Antibiotics in agriculture .) Is there any international action on the antibiotic ... and reducing antibiotic use in animal farming and agriculture. Experts agree that a global system for tracking ...

  17. Colds and flus - antibiotics

    MedlinePLUS

    Antibiotics - colds and flu ... treat infections that are caused by a virus. Colds and flu are caused by viruses. If you ... Hamilton A. Treatments for symptoms of the common cold. Am Fam Physician. 2013;88(3):864C-864D.

  18. Resistance-Resistant Antibiotics

    PubMed Central

    Oldfield, Eric; Feng, Xinxin

    2014-01-01

    New antibiotics are needed because as drug resistance is increasing, the introduction of new antibiotics is decreasing. Here, we discuss six possible approaches to develop ‘resistance-resistant’ antibiotics. First, multi-target inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy due to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, re-purposing existing drugs can lead to combinations of multi-target therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and in some cases suggest that sensitivity to existing antibiotics may be restored, in otherwise drug resistant organisms. PMID:25458541

  19. Antibiotics before surgery.

    PubMed

    Kaatz, B

    1996-01-01

    The antimicrobial era (along with greater surgical skill and precision) has brought us relative safety for procedures that previously were fraught with danger. Civil War amputation surgeries, for example, had an extraordinarily high incidence of infections and mortality. Staying aware of and avoiding the small, but real, risks associated with surgical antibiotic prophylaxis will help sustain the advances we enjoy today. PMID:8650524

  20. Mass flow of antibiotics in a wastewater treatment plant focusing on removal variations due to operational parameters.

    PubMed

    Marx, Conrad; Günther, Norbert; Schubert, Sara; Oertel, Reinhard; Ahnert, Markus; Krebs, Peter; Kuehn, Volker

    2015-12-15

    Wastewater treatment plants (WWTPs) are not designed to purposefully eliminate antibiotics and therefore many previous investigations have been carried out to assess their fate in biological wastewater treatment processes. In order to consolidate previous findings regarding influencing factors like the solid and hydraulic retention time an intensive monitoring was carried out in a municipal WWTP in Germany. Over a period of 12months daily samples were taken from the in- and effluent as well as diverse sludge streams. The 14 selected antibiotics and one metabolite cover the following classes: cephalosporins, diaminopyrimidines, fluoroquinolones, lincosamide, macrolides, penicillins, sulfonamides and tetracyclines. Out of the 15 investigated substances, the removal of only clindamycin and ciprofloxacin show significant correlations to SRT, temperature, HRT and nitrogen removal. The dependency of clindamycin's removal could be related to the significant negative removal (i.e. production) of clindamycin in the treatment process and was corrected using the human metabolite clindamycin-sulfoxide. The average elimination was adjusted from -225% to 3% which suggests that clindamycin can be considered as an inert substance during the wastewater treatment process. Based on the presented data, the mass flow analysis revealed that macrolides, clindamycin/clindamycin-sulfoxide and trimethoprim were mainly released with the effluent, while penicillins, cephalosporins as well as sulfamethoxazole were partly degraded in the studied WWTP. Furthermore, levofloxacin and ciprofloxacin are the only antibiotics under investigation with a significant mass fraction bound to primary, excess and digested sludge. Nevertheless, the sludge concentrations are highly inconsistent which leads to questionable results. It remains unclear whether the inconsistencies are due to insufficiencies in sampling and/or analytical determination or if the fluctuations can be considered reasonable for digesters. Hence, future investigations have to address antibiotic's temporal dynamics during the sludge treatment to decide whether or not the widely reported standard deviations of sludge concentrations reflect realistic fluctuations. PMID:26340581

  1. Reversing resistance: The next generation antibacterials

    PubMed Central

    Shah, Neel Jayesh

    2015-01-01

    Irrational antibiotic usage has led to vast spread resistance to available antibiotics, but we refuse to slide back to “preantibiotic era.” The threat is serious with the “Enterococcus, Staphylococcous, Klebsiella, Acinetobacter, Pseudomonas and Enterobacter” organisms causing nosocomial infections that are difficult to treat because of the production of extended spectrum ?-lactamases, carbapenamases and metallo-?-lactamases. Facing us is a situation where soon multidrug resistance would have spread across the globe with no antibiotics to withstand it. The infectious disease society of America and Food and Drug Administration have taken initiatives like the 10 × ‘20 where they plan to develop 10 new antibiotics by the year 2020. Existing classes of antibiotics against resistant bacteria include the carbapenems, oxazolidinones, glycopeptides, monobactams, streptogramins and daptomycin. Newer drugs in existing classes of antibiotics such as cephalosporins, aminoglycosides, tetracyclines, glycopeptides and ?-lactamase inhibitors continue to get synthesized. The situation demands newer targets against bacterial machinery. Some of them include the peptidoglycantransferase, outer membrane protein of Pseudomonas, tRNA synthase, fatty acid synthase and mycobacterial ATP synthase. To curb the irrational and excessive usage of presently available antibiotics should be a priority if they are still to be kept in usage for the future. PMID:26069360

  2. Investigating the Antibiotic Resistance Problem.

    ERIC Educational Resources Information Center

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

    Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

  3. Antibiotics acting on the translational

    E-print Network

    Yonath, Ada E.

    Antibiotics acting on the translational machinery Jörg M. Harms1,*, Heike Bartels1, Frank Schlünzen antibiotics, including vancomycin (the `last resort'), development of new antimicrobial agents has slowed during recent decades. To aid design of new antibiotics, we must develop a detailed understanding

  4. Increasing prevalence of vancomycin-resistant Enterococcus faecium, expanded-spectrum cephalosporin-resistant Klebsiella pneumoniae, and imipenem-resistant Pseudomonas aeruginosa in Korea: KONSAR study in 2001.

    PubMed

    Lee, Kyungwon; Jang, Sook-Jin; Lee, Hee-Joo; Ryoo, Namhee; Kim, Myungshin; Hong, Seong-Geun; Chong, Yunsop

    2004-02-01

    The 5th year KONSAR surveillance in 2001 was based on routine test data at 30 participating hospitals. It was of particular interest to find a trend in the resistances of enterococci to vancomycin, of Enterobacteriaceae to the 3rd generation cephalosporin and fluoroquinolone, and of Pseudomonas aeruginosa and acinetobacters to carbapenem. Resistance rates of Gram-positive cocci were: 70% of Staphylococcus aureus to oxacillin; 88% and 16% of Enterococcus faecium to ampicillin and vancomycin, respectively. Seventy-two percent of pneumococci were nonsusceptible to penicillin. The resistance rates of Enterobacteriaceae were: Escherichia coli, 28% to fluoroquinolone; Klebsiella pneumoniae, 27% to ceftazidime, and 20% to cefoxitin; and Enterobacter cloacae, > or =40% to cefotaxime and ceftazidime. The resistance rates of P. aeruginosa were 21% to ceftazidime, 17% to imipenem, and those of the acinetobacters were > or =61% to ceftazidime, aminoglycosides, fluoroquinolone and cotrimoxazole. Thirty-five percent of non-typhoidal salmonellae were ampicillin resistant, and 66% of Haemophilus influenzae were beta-lactamase producers. Notable changes over the 1997-2001 period were: increases in vancomycin-resistant E. faecium, and amikacin- and fluoroquinolone-resistant acinetobacters. With the increasing prevalence of resistant bacteria, nationwide surveillance has become more important for optimal patient management, for the control of nosocomial infection, and for the conservation of the newer antimicrobial agents. PMID:14966334

  5. Increasing Prevalence of Vancomycin-Resistant Enterococcus faecium, Expanded-Spectrum Cephalosporin-Resistant Klebsiella pneumoniae, and Imipenem-Resistant Pseudomonas aeruginosa in Korea: KONSAR Study in 2001

    PubMed Central

    Lee, Kyungwon; Jang, Sook-Jin; Lee, Hee Joo; Ryoo, Namhee; Kim, Myungshin; Hong, Seong Geun

    2004-01-01

    The 5th year KONSAR surveillance in 2001 was based on routine test data at 30 participating hospitals. It was of particular interest to find a trend in the resistances of enterococci to vancomycin, of Enterobacteriaceae to the 3rd generation cephalosporin and fluoroquinolone, and of Pseudomonas aeruginosa and acinetobacters to carbapenem. Resistance rates of Gram-positive cocci were: 70% of Staphylococcus aureus to oxacillin; 88% and 16% of Enterococcus faecium to ampicillin and vancomycin, respectively. Seventy-two percent of pneumococci were nonsusceptible to penicillin. The resistance rates of Enterobacteriaceae were: Escherichia coli, 28% to fluoroquinolone; Klebsiella pneumoniae, 27% to ceftazidime, and 20% to cefoxitin; and Enterobacter cloacae, ?40% to cefotaxime and ceftazidime. The resistance rates of P. aeruginosa were 21% to ceftazidime, 17% to imipenem, and those of the acinetobacters were ?61% to ceftazidime, aminoglycosides, fluoroquinolone and cotrimoxazole. Thirty-five percent of non-typhoidal salmonellae were ampicillin resistant, and 66% of Haemophilus influenzae were ?-lactamase producers. Notable changes over the 1997-2001 period were: increases in vancomycin-resistant E. faecium, and amikacin- and fluoroquinolone-resistant acinetobacters. With the increasing prevalence of resistant bacteria, nationwide surveillance has become more important for optimal patient management, for the control of nosocomial infection, and for the conservation of the newer antimicrobial agents. PMID:14966334

  6. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

    PubMed Central

    2014-01-01

    Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p?generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77)?=?5.82, p?antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients. PMID:24405683

  7. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed Central

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

  8. The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal

    PubMed Central

    Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

    2014-01-01

    Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level. PMID:24637798

  9. The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal.

    PubMed

    Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

    2014-01-01

    Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level. PMID:24637798

  10. Diverse antibiotic resistance genes in dairy cow manure.

    PubMed

    Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

    2014-01-01

    Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. IMPORTANCE The increasing prevalence of antibiotic resistance among bacteria is one of the most intractable challenges in 21st-century public health. The origins of resistance are complex, and a better understanding of the impacts of antibiotics used on farms would produce a more robust platform for public policy. Microbiomes of farm animals are reservoirs of antibiotic resistance genes, which may affect distribution of antibiotic resistance genes in human pathogens. Previous studies have focused on antibiotic resistance genes in manures of animals subjected to intensive antibiotic use, such as pigs and chickens. Cow manure has received less attention, although it is commonly used in crop production. Here, we report the discovery of novel and diverse antibiotic resistance genes in the cow microbiome, demonstrating that it is a significant reservoir of antibiotic resistance genes. The genomic resource presented here lays the groundwork for understanding the dispersal of antibiotic resistance from the agroecosystem to other settings. PMID:24757214

  11. The Comprehensive Antibiotic Resistance Database

    PubMed Central

    McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

    2013-01-01

    The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

  12. Current perspectives on the dynamics of antibiotic resistance in different reservoirs.

    PubMed

    Caniça, Manuela; Manageiro, Vera; Jones-Dias, Daniela; Clemente, Lurdes; Gomes-Neves, Eduarda; Poeta, Patrícia; Dias, Elsa; Ferreira, Eugénia

    2015-09-01

    Antibiotic resistance consists of a dynamic web. In this review, we describe the path by which different antibiotic residues and antibiotic resistance genes disseminate among relevant reservoirs (human, animal, and environmental settings), evaluating how these events contribute to the current scenario of antibiotic resistance. The relationship between the spread of resistance and the contribution of different genetic elements and events is revisited, exploring examples of the processes by which successful mobile resistance genes spread across different niches. The importance of classic and next generation molecular approaches, as well as action plans and policies which might aid in the fight against antibiotic resistance, are also reviewed. PMID:26247891

  13. Molecular Characteristics of Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae from Humans in the Community

    PubMed Central

    van Hoek, Angela H. A. M.; Schouls, Leo; van Santen, Marga G.; Florijn, Alice; de Greeff, Sabine C.; van Duijkeren, Engeline

    2015-01-01

    Objective To investigate the molecular characteristics of extended-spectrum cephalosporin (ESC)-resistant Enterobacteriaceae collected during a cross-sectional study examining the prevalence and risk factors for faecal carriage of extended-spectrum ?-lactamase (ESBL)-producing Enterobacteriaceae in humans living in areas with high or low broiler density. Methods ESC-resistant Enterobacteriaceae were identified by combination disc-diffusion test. ESBL/AmpC/carbapenemase genes were analysed using PCR and sequencing. For E. coli, phylogenetic groups and MLST were determined. Plasmids were characterized by transformation and PCR-based replicon typing. Subtyping of plasmids was done by plasmid multilocus sequence typing. Results 175 ESC-resistant Enterobacteriaceae were cultured from 165/1,033 individuals. The isolates were Escherichia coli(n=65), Citrobacter freundii (n=52), Enterobacter cloacae (n=38), Morganella morganii (n=5), Enterobacter aerogenes (n=4), Klebsiella pneumoniae (n=3), Hafnia alvei (n=2), Shigella spp. (n=2), Citrobacter amalonaticus (n=1), Escherichia hermannii (n=1), Kluyvera cryocrescens (n=1), and Pantoea agglomerans (n=1). The following ESBL genes were recovered in 55 isolates originating from 49 of 1,033 (4.7 %) persons: blaCTX-M-1 (n=17), blaCTX-M-15 (n=16), blaCTX-M-14 (n=9), blaCTX-M-2 (n=3), blaCTX-M-3 (n=2), blaCTX-M-24 (n=2), blaCTX-M-27 (n=1), blaCTX-M-32 (n=1), blaSHV-12 (n=2), blaSHV-65 (n=1) and blaTEM-52 (n=1). Plasmidic AmpC (pAmpC) genes were discovered in 6 out of 1,033 (0.6 %) persons. One person carried two different E. coli isolates, one with blaCTX-M-1 and the other with blaCMY-2 and therefore the prevalence of persons carrying Enterobacteriaceae harboring ESBL and/or pAmpC genes was 5.2 %. In eight E. coli isolates the AmpC phenotype was caused by mutations in the AmpC promoter region. No carbapenemase genes were identified. A large variety of E. coli genotypes was found, ST131 and ST10 being most common. Conclusions ESBL/pAmpC genes resembled those from patients in Dutch hospitals, indicating that healthy humans form a reservoir for transmission of these determinants to vulnerable people. The role of poultry in the transmission to humans in the community remains to be elucidated. PMID:26029910

  14. Degradation kinetics and mechanism of ?-lactam antibiotics by the activation of H2O2 and Na2S2O8 under UV-254nm irradiation.

    PubMed

    He, Xuexiang; Mezyk, Stephen P; Michael, Irene; Fatta-Kassinos, Despo; Dionysiou, Dionysios D

    2014-08-30

    The extensive production and usage of antibiotics have led to an increasing occurrence of antibiotic residuals in various aquatic compartments, presenting a significant threat to both ecosystem and human health. This study investigated the degradation of selected ?-lactam antibiotics (penicillins: ampicillin, penicillin V, and piperacillin; cephalosporin: cephalothin) by UV-254nm activated H2O2 and S2O8(2-) photochemical processes. The UV irradiation alone resulted in various degrees of direct photolysis of the antibiotics; while the addition of the oxidants improved significantly the removal efficiency. The steady-state radical concentrations were estimated, revealing a non-negligible contribution of hydroxyl radicals in the UV/S2O8(2-) system. Mineralization of the ?-lactams could be achieved at high UV fluence, with a slow formation of SO4(2-) and a much lower elimination of total organic carbon (TOC). The transformation mechanisms were also investigated showing the main reaction pathways of hydroxylation (+16Da) at the aromatic ring and/or the sulfur atom, hydrolysis (+18Da) at the ?-lactam ring and decarboxylation (-44Da) for the three penicillins. Oxidation of amine group was also observed for ampicillin. This study suggests that UV/H2O2 and UV/S2O8(2-) advanced oxidation processes (AOPs) are capable of degrading ?-lactam antibiotics decreasing consequently the antibiotic activity of treated waters. PMID:25086235

  15. Rationalizing antibiotic use to limit antibiotic resistance in India+

    PubMed Central

    2011-01-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

  16. De novo Comparative Transcriptome Analysis of Acremonium chrysogenum: High-Yield and Wild-Type Strains of Cephalosporin C Producer

    PubMed Central

    Liu, Yan; Xie, Liping; Gong, Guihua; Zhang, Wei; Zhu, Baoquan; Hu, Youjia

    2014-01-01

    ?-lactam antibiotics are widely used in clinic. Filamentous fungus Acremonium chrysogenum is an important industrial fungus for the production of CPC, one of the major precursors of ?-lactam antibiotics. Although its fermentation yield has been bred significantly over the past decades, little is known regarding molecular changes between the industrial strain and the wild type strain. This limits the possibility to improve CPC production further by molecular breeding. Comparative transcriptome is a powerful tool to understand the molecular mechanisms of CPC industrial high yield producer compared to wild type. A total of 57 million clean sequencing reads with an average length of 100 bp were generated from Illumina sequencing platform. 22,878 sequences were assembled. Among the assembled unigenes, 9502 were annotated and 1989 annotated sequences were assigned to 121 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Furthermore, we compared the transcriptome differences between a high-yield and a wild-type strain during fermentation. A total of 4329 unigenes with significantly different transcription level were identified, among which 1737 were up-regulated and 2592 were down-regulated. 24 pathways were subsequently determined which involve glycerolipid metabolism, galactose metabolism, and pyrimidine metabolism. We also examined the transcription levels of 18 identified genes, including 11 up-regulated genes and 7 down-regulated genes using reverse transcription quantitative -PCR (RT-qPCR). The results of RT-qPCR were consistent with the Illumina sequencing. In this study, the Illumina sequencing provides the most comprehensive sequences for gene expression profile of Acremonium chrysogenum and allows de novo transcriptome assembly while lacking genome information. Comparative analysis of RNA-seq data reveals the complexity of the transcriptome in the fermentation of different yield strains. This is an important public information platform which could be used to accelerate the research to improve CPC production in Acremonium chrysogenum. PMID:25118715

  17. The erratic antibiotic susceptibility patterns of bacterial pathogens causing urinary tract infections

    PubMed Central

    Ahmed, Iftkhar; Sajed, Muhammad; Sultan, Aneesa; Murtaza, Iram; Yousaf, Sohail; Maqsood, Bushra; Vanhara, Petr; Anees, Mariam

    2015-01-01

    Increasing trend of antibiotic resistance and expression of Extended Spectrum Beta Lactamases (ESBLs) are serious threats for public health as they render the treatment ineffective. Present study was designed to elucidate the antibiotic-susceptibility patterns of ESBL and non-ESBL producing E. coli and K. pneumoniae causing urinary tract infections so that the ineffective antibiotics could be removed from the line of treatment. The bacterial isolates obtained from the urine of patients visiting a tertiary health care facility were cultured for strain identification using API20E. Antimicrobial susceptibility and ESBL detection were done by Kirby-bauer diffusion technique. Almost 53.4 % isolates of E. coli and 24.5 % isolates of K. pneumoniae were found to be ESBL producers. The ESBL producing bacteria were found to be more resistant towards various antibiotics. The most effective drugs against E. coli ESBL isolates were imipenem (99.54 %), ampicillin-sulbactam (97.48 %), piperacillin-tazobactam (96.86 %), fosfomycin (94.51 %), amikacin (92.26 %) and nitrofurantoin (90.68 %). The most effective drugs against K. pneumoniae ESBL isolates were imipenem (97.62 %), piperacillin-tazobactam (95.35 %), ampicillin-sulbactam (90.48 %) and amikacin (88.37 %). The antibiotics having the highest resistance, particularly by the ESBL producers were amoxicillin clavulanic acid, sulphamethoxalzole/ trimethoprim, cefuroxime, cefpirome, ceftriaxone and ciprofloxacin. Most of the isolates showed multi drug resistance (MDR). High frequency of ESBL producing E. coli and K. pneumoniae were observed as compared to previous data. Penicillins, cephalosporins and some representatives of fluoroquinolones were least effective against the common UTIs and are recommended to be removed from the line of treatment.

  18. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    PubMed

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. PMID:24919144

  19. Prevalence of extended-spectrum cephalosporin-resistant Escherichia coli in a farrowing farm: ST1121 clone harboring IncHI2 plasmid contributes to the dissemination of blaCMY-2

    PubMed Central

    Deng, Hui; Si, Hong-Bin; Zeng, Shu-Yi; Sun, Jian; Fang, Liang-Xing; Yang, Run-Shi; Liu, Ya-Hong; Liao, Xiao-Ping

    2015-01-01

    During a regular monitoring of antimicrobial resistance in a farrowing farm in Southern China, 117 Escherichia coli isolates were obtained from sows and piglets. Compared with the isolates from piglets, the isolates from sows exhibited higher resistance rates to the tested cephalosporins. Correspondingly, the total detection rate of the blaCMY-2/blaCTX-M genes in the sow isolates (34.2%) was also significantly higher than that of the piglet isolates (13.6%; p < 0.05). The blaCMY-2 gene had a relatively high prevalence (11.1%) in the E. coli isolates. MLST and PFGE analysis revealed the clonal spread of ST1121 E. coli in most (7/13) of the blaCMY-2-positive isolates. An indistinguishable IncHI2 plasmid harboring blaCMY-2 was also identified in each of the seven ST1121 E. coli isolates. Complete sequence analysis of this IncHI2 plasmid (pEC5207) revealed that pEC5207 may have originated through recombination of an IncHI2 plasmid with a blaCMY-2-carrying IncA/C plasmid like pCFSAN007427_01. In addition to blaCMY-2, pEC5207 also carried other resistance determinants for aminoglycosides (aacA7), sulfonamides (sul1), as well as heavy metals ions, such as Cu and Ag. The susceptibility testing showed that the pEC5207 can mediate both antibiotic and heavy metal resistance. This highlights the role of pEC5207 in co-selection of blaCMY-2-positive isolates under the selective pressure of heavy metals, cephalosporins, and other antimicrobials. In conclusion, clonal spread of an ST1121 type E. coli strain harboring an IncHI2 plasmid contributed to the dissemination of blaCMY-2 in a farrowing farm in Southern China. We also have determined the first complete sequence analysis of a blaCMY-2-carrying IncHI2 plasmid. PMID:26579110

  20. Liquid antibiotics in bone cement

    PubMed Central

    Chang, Y. H.; Tai, C. L.; Hsu, H. Y.; Hsieh, P. H.; Lee, M. S.; Ueng, S. W. N.

    2014-01-01

    Objectives The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246–51. PMID:25104836

  1. Antibiotic Resistance Questions and Answers

    MedlinePLUS

    ... Adult Treatment Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving ...

  2. [Pathways for surgical antibiotic prophylaxis].

    PubMed

    Maio, Patrizia

    2003-09-01

    Surgical site infections (SSIs) are a notable cause of hospital morbidity and mortality. Antibiotic prophylaxis has demonstrated a significant reduction in infection rate in clean-contaminated surgery and in clean surgery to a limited extent. To make antibiotic prophylaxis effective it is necessary to choose the right antibiotic, to administer it preoperatively and maintain sufficient serum and tissue levels through the operation. Open issues remain: antibiotic prophylaxis duration in prosthetic surgery, its use in hernia repair, breast surgery and mini-invasive surgery. PMID:14985643

  3. The antibiotic resistome: what's new?

    PubMed

    Perry, Julie Ann; Westman, Erin Louise; Wright, Gerard D

    2014-10-01

    The antibiotic resistome is dynamic and ever expanding, yet its foundations were laid long before the introduction of antibiotics into clinical practice. Here, we revisit our theoretical framework for the resistome concept and consider the many factors that influence the evolution of novel resistance genes, the spread of mobile resistance elements, and the ramifications of these processes for clinical practice. Observing the trends and prevalence of genes within the antibiotic resistome is key to maintaining the efficacy of antibiotics in the clinic. PMID:25280222

  4. Applications of medical informatics in antibiotic therapy.

    PubMed

    Evans, R S; Pestotnik, S L

    1994-01-01

    The Infectious Disease Society of America is concerned about the excessive and inappropriate use of antibiotics in U.S. hospitals. Applications of Medical Informatics can help improve the use of antibiotics and help improve patient care by monitoring and managing enormous amounts of patient information. Monitoring the duration of every antibiotic ordered in the hospital or keeping tract of the antibiotic susceptibilities for five years are examples of tasks better performed by computers. The impact of computers in medicine is seen by some as disappointing. The computer revolution has not had the impact in medicine experienced by other areas. The acceptance and use of computers by medicine will be evolutionary rather than revolutionary. In 1979, the MYCIN project demonstrated that the computer could aid physicians in the selection of antibiotics. However, MYCIN was never clinically used because physicians were require to enter all patient information into the computer. The development of computerized medical records is an essential step to further the development and implementation of computer-aided decision support. The science of Medical Informatics is still relatively new but is emerging as a distinct academic field. A few hospitals are now installing information systems and have determined that these systems will play an essential role in their ability to survive into the next century. The telephone and the automobile have been recognized as two of the most important tools for improving medical care during the past 100 years. People could more readily get medical care and the time to transmit medical information was greatly reduced through physician use of the telephone and automobile. The computer is a tool that can be used to help physicians manage the great amount of medical information being generated every day. The computer can also alert the physician of patient conditions that need attention. However, it is the physician who must use and apply the computer provided information. Thus, the computer will assist but not replace physicians in providing medical care. PMID:8209811

  5. Counteraction of antibiotic production and degradation stabilizes microbial communities

    PubMed Central

    Kelsic, Eric D.; Zhao, Jeffrey; Vetsigian, Kalin; Kishony, Roy

    2015-01-01

    Summary A major challenge in theoretical ecology is understanding how natural microbial communities support species diversity1-8, and in particular how antibiotic producing, sensitive and resistant species coexist9-15. While cyclic “rock-paper-scissors” interactions can stabilize communities in spatial environments9-11, coexistence in unstructured environments remains an enigma12,16. Here, using simulations and analytical models, we show that the opposing actions of antibiotic production and degradation enable coexistence even in well-mixed environments. Coexistence depends on 3-way interactions where an antibiotic degrading species attenuates the inhibitory interactions between two other species. These 3-way interactions enable coexistence that is robust to substantial differences in inherent species growth rates and to invasion by “cheating” species that cease producing or degrading antibiotics. At least two antibiotics are required for stability, with greater numbers of antibiotics enabling more complex communities and diverse dynamical behaviors ranging from stable fixed-points to limit cycles and chaos. Together, these results show how multi-species antibiotic interactions can generate ecological stability in both spatial and mixed microbial communities, suggesting strategies for engineering synthetic ecosystems and highlighting the importance of toxin production and degradation for microbial biodiversity. PMID:25992546

  6. ROTATING ANTIBIOTICS SELECTS OPTIMALLY AGAINST ANTIBIOTIC RESISTANCE, IN THEORY

    E-print Network

    Beardmore, Robert

    Is Crop Rotation of Antibiotics the Solution to a Resistant Problem in the ICU? (see [9]) states "The `crop rotation' theory of antibiotic use has suggested that if we rou- tinely vary our `go to at the start of a clinical trial, say, just as a crop rotation might only change the crop with each new season

  7. POSTDOCTORAL RESEARCH ASSOCIATE Antibiotics and Antibiotic Resistant Bacteria The USDA, Agricultural Research Service, Contaminant Fate and

    E-print Network

    Ma, Lena

    POSTDOCTORAL RESEARCH ASSOCIATE ­ Antibiotics and Antibiotic Resistant Bacteria The USDA in the environment, (b) study the interactions of antibiotics and antibiotic resistance bacteria, and (c) develop information that could be used reduce the prevalence of antibiotic chemicals and/or antibiotic resistance

  8. A call for antibiotic alternatives research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The persistence and spread of antibiotic resistance and decreased profitability of new antibiotics have created the dangerous prospect of ineffective therapies against bacterial diseases. The discovery, development, and application of effective antibiotic alternatives, especially in agriculture, sho...

  9. Danger of Antibiotic Overuse (For Parents)

    MedlinePLUS

    ... against them. This is called bacterial resistance or antibiotic resistance. Treating these resistant bacteria requires higher doses of ... to even the most powerful antibiotics available today. Antibiotic resistance is a widespread problem, and one that the ...

  10. Essential Oils, A New Horizon in Combating Bacterial Antibiotic Resistance

    PubMed Central

    Yap, Polly Soo Xi; Yiap, Beow Chin; Ping, Hu Cai; Lim, Swee Hua Erin

    2014-01-01

    For many years, the battle between humans and the multitudes of infection and disease causing pathogens continues. Emerging at the battlefield as some of the most significant challenges to human health are bacterial resistance and its rapid rise. These have become a major concern in global public health invigorating the need for new antimicrobial compounds. A rational approach to deal with antibiotic resistance problems requires detailed knowledge of the different biological and non-biological factors that affect the rate and extent of resistance development. Combination therapy combining conventional antibiotics and essential oils is currently blooming and represents a potential area for future investigations. This new generation of phytopharmaceuticals may shed light on the development of new pharmacological regimes in combating antibiotic resistance. This review consolidated and described the observed synergistic outcome between essential oils and antibiotics, and highlighted the possibilities of essential oils as the potential resistance modifying agent. PMID:24627729

  11. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  12. Antibiotic use in livestock production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic usage is a useful and commonly implemented practice in livestock and production agriculture that has progressively gained attention in recent years from consumers of animal products due to concerns about human and environmental health. Sub-therapeutic usage of antibiotics has led to a con...

  13. Characterization of extended-spectrum cephalosporin-resistant Salmonella enterica serovar Heidelberg isolated from food animals, retail meat, and humans in the United States 2009

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment and ceftriaxone, an extended-spectrum cephalosporin, is commonly used in both adults and child...

  14. Antibiotics from neglected bacterial sources.

    PubMed

    Pidot, Sacha J; Coyne, Sébastien; Kloss, Florian; Hertweck, Christian

    2014-01-01

    The current crop of antibiotics in clinical use are either natural products or their derivatives. However, the rise of a multitude of different antibiotic resistant human pathogens has meant that new antibiotics are urgently needed. Unfortunately, the search for new antibiotics from traditional bacterial sources often results in a high rediscovery rate of known compounds and a low chance of identifying truly novel chemical entities. To overcome this, previously unexplored (or under investigated) bacterial sources are being tapped for their potential to produce novel compounds with new activities. Here, we review a number of antibiotic compounds identified from bacteria of the genera Burkholderia, Clostridium, Lysobacter, Pantoea and Xenorhabdus and describe the potential of organisms and their associated metabolites in future drug discovery efforts. PMID:24120363

  15. [Antibiotic resistance: A global crisis].

    PubMed

    Alós, Juan-Ignacio

    2015-12-01

    The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics. PMID:25475657

  16. Comparative in vitro activity of the new oral cephalosporin Bay v 3522 against aerobic and anaerobic bacteria.

    PubMed

    Rylander, M; Nord, C E; Norrby, S R

    1990-10-01

    The in vitro activity of the new oral cephalosporin Bay v 3522 against 229 aerobic and 330 anaerobic clinical isolates was determined using the agar dilution technique. For comparison, amoxicillin, amoxicillin/clavulanate, cefaclor, cefadroxil, cefuroxime, cephalexin, ciprofloxacin, clindamycin, co-trimoxazole, doxycycline, erythromycin and metronidazole (only anaerobic bacteria) were tested. Bay v 3522 was found to have high activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, anaerobic cocci, Propionibacterium acnes, Clostridium perfringens and fusobacteria. When tested against a higher inoculum or using the broth dilution technique, the activity of Bay v 3522 showed little dependence on inoculum size and the bactericidal activity was similar to inhibitory activity in most bacterial groups. Bay v 3522 may be useful in the treatment of skin, soft tissue and respiratory tract infections. Clinical studies are thus warranted. PMID:2261923

  17. Determination of endotoxin in injectable antibiotic preparations by the chromogenic assay method using a Limulus reagent (Tachypleus hemocyte lysate) and a chromogenic substrate.

    PubMed Central

    Yano, S; Hotta, Y; Takahashi, S

    1986-01-01

    The effects of 50 antibiotics on the detection and determination of bacterial endotoxins by the chromogenic method using a Limulus reagent (Tachypleus hemocyte lysate) and a chromogenic substrate of p-nitroaniline derivatives were tested, and the antibiotic concentration for 50% inhibition of the chromogenic reaction in the presence of 0.5 ng of endotoxin (Escherichia coli 0111:B4) per ml was estimated. All the antibiotic preparations were depyrogenized by ultrafiltration treatment before they were subjected to the test. The reaction was conducted in the presence of a high concentration (0.5 M) of Tris buffer to constantly maintain the pH of the reaction mixture, and liberated p-nitroaniline was determined by high-pressure liquid chromatography. Several aminoglycosides (amikacin, bekanamycin, kanamycin, and streptomycin sulfate), bleomycin hydrochloride, and fosfomycin disodium showed no inhibition of the reaction up to 20 mg/ml. However, other antibiotics, including penicillins, cephalosporins, macrolides, and tetracyclines, inhibited the reaction concentration dependently. Polymyxin B sulfate was the most potent inhibitor, with less than 8 micrograms/ml for 50% inhibition. It was concluded that the chromogenic method can be applied to the detection and determination of endotoxin in most of the antibiotic preparations. An application of this method to carbenicillin disodium preparations was exemplified. PMID:3700595

  18. Trends in Expanded-Spectrum Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae among Dutch Clinical Isolates, from 2008 to 2012

    PubMed Central

    van der Steen, Matthijs; Leenstra, Tjalling; Kluytmans, Jan A. J. W.; van der Bij, Akke K.

    2015-01-01

    We investigated time trends in extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates from different patient settings in The Netherlands from 2008–2012. E. coli and K. pneumoniae isolates from blood and urine samples of patients > = 18 years were selected from the Dutch Infectious Disease Surveillance System-Antimicrobial Resistance (ISIS-AR) database. We used multivariable Poisson regression to study the rate per year of blood stream infections by susceptible and resistant isolates, and generalized estimating equation (GEE) log-binomial regression for trends in the proportion of extended-spectrum cephalosporin-resistant isolates. Susceptibility data of 197,513 E. coli and 38,244 K. pneumoniae isolates were included. The proportion of extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates from urine and blood samples increased in all patient settings, except for K. pneumoniae isolates from patients admitted to intensive care units. For K. pneumoniae, there was a different time trend between various patient groups (p<0.01), with a significantly higher increase in extended-spectrum cephalosporin-resistant isolates from patients attending a general practitioner than in isolates from hospitalized patients. For E. coli, the increasing time trends did not differ among different patient groups. This nationwide study shows a general increase in extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates. However, differences in trends between E. coli en K. pneumoniae underline the importance of E. coli as a community-pathogen and its subsequent influence on hospital resistance level, while for K. pneumoniae the level of resistance within the hospital seems less influenced by the resistance trends in the community. PMID:26381746

  19. A longitudinal field trial assesing the impact of feeding waste milk containing antibiotic residues on the prevalence of ESBL-producing Escherichia coli in calves.

    PubMed

    Brunton, L A; Reeves, H E; Snow, L C; Jones, J R

    2014-11-15

    A longitudinal field trial was carried out on a farm known to harbour cefotaximase (CTX-M)-positive Escherichia coli, in order to assess the impact of feeding waste milk containing antibiotic residues (WM+AR) on the prevalence of these bacteria in the faeces of calves. Fifty calves were alternately assigned to one of two groups at birth and fed either milk replacer (control group) or WM+AR (treatment group). Faecal samples were collected from all calves daily for the first week after enrolment, twice weekly until weaning, then weekly for a further six weeks. Environmental samples from the calf housing were collected weekly. WM+AR and powdered milk samples were examined for antibiotic residues and CTX-M-positive E. coli. Total E. coli and CTX-M-positive E. coli in faecal samples were enumerated using selective media. Regression analyses were performed on the bacterial count data using a population-averaged approach based on generalised estimating equations (GEE) to account for repeated measurements on individual calves over time. Cefquinome, a fourth generation cephalosporin, was detected in 87% of WM+AR samples at a mean concentration of 0.746 mg/l. All environmental sampling locations yielded CTX-M-positive E. coli. Significantly more pen floor samples were positive in the treatment group. Calves in the treatment group shed greater numbers of CTX-M-positive E. coli than calves in the control group throughout the study, and shedding decreased at a slower rate in the treatment group. CTX-M-positive E. coli persisted in a larger number of calves fed WM+AR compared with calves fed milk replacer where the prevalence in the treatment group declined significantly slower over time. There was no difference between calves fed WM+AR or calves fed milk replacer in the proportion of E. coli isolates that were CTX-M-positive. These findings indicate that feeding WM+AR increased the amount of resistant bacteria shed in the faeces. Shedding of CTX-M-positive E. coli persisted for longer in calves fed WM+AR, and persisted after weaning. PMID:25172121

  20. Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates with Decreased Cephalosporin Susceptibility Collected in Canada between 1989 and 2013

    PubMed Central

    Lynch, Tarah; Martin, Irene; Van Domselaar, Gary; Graham, Morag; Bharat, Amrita; Allen, Vanessa; Hoang, Linda; Lefebvre, Brigitte; Tyrrell, Greg; Horsman, Greg; Haldane, David; Garceau, Richard; Wylie, John; Wong, Tom; Mulvey, Michael R.

    2014-01-01

    A large-scale, whole-genome comparison of Canadian Neisseria gonorrhoeae isolates with high-level cephalosporin MICs was used to demonstrate a genomic epidemiology approach to investigate strain relatedness and dynamics. Although current typing methods have been very successful in tracing short-chain transmission of gonorrheal disease, investigating the temporal evolutionary relationships and geographical dissemination of highly clonal lineages requires enhanced resolution only available through whole-genome sequencing (WGS). Phylogenomic cluster analysis grouped 169 Canadian strains into 12 distinct clades. While some N. gonorrhoeae multiantigen sequence types (NG-MAST) agreed with specific phylogenomic clades or subclades, other sequence types (ST) and closely related groups of ST were widely distributed among clades. Decreased susceptibility to extended-spectrum cephalosporins (ESC-DS) emerged among a group of diverse strains in Canada during the 1990s with a variety of nonmosaic penA alleles, followed in 2000/2001 with the penA mosaic X allele and then in 2007 with ST1407 strains with the penA mosaic XXXIV allele. Five genetically distinct ESC-DS lineages were associated with penA mosaic X, XXXV, and XXXIV alleles and nonmosaic XII and XIII alleles. ESC-DS with coresistance to azithromycin was observed in 5 strains with 23S rRNA C2599T or A2143G mutations. As the costs associated with WGS decline and analysis tools are streamlined, WGS can provide a more thorough understanding of strain dynamics, facilitate epidemiological studies to better resolve social networks, and improve surveillance to optimize treatment for gonorrheal infections. PMID:25378573

  1. Antibiotic-Resistant Klebsiella pneumoniae and Escherichia coli High-Risk Clones and an IncFIIk Mosaic Plasmid Hosting Tn1 (blaTEM-4) in Isolates from 1990 to 2004

    PubMed Central

    Rodríguez, Irene; Novais, Ângela; Lira, Felipe; Valverde, Aránzazu; Curião, Tânia; Martínez, José Luis; Baquero, Fernando; Cantón, Rafael

    2015-01-01

    We describe the genetic background of blaTEM-4 and the complete sequence of pRYC11::blaTEM-4, a mosaic plasmid that is highly similar to pKpQIL-like variants, predominant among TEM-4 producers in a Spanish hospital (1990 to 2004), which belong to Klebsiella pneumoniae and Escherichia coli high-risk clones responsible for the current spread of different antibiotic resistance genes. Predominant populations of plasmids and host adapted clonal lineages seem to have greatly contributed to the spread of resistance to extended-spectrum cephalosporins. PMID:25691645

  2. Antibiotic Treatment of Hidradenitis Suppurativa.

    PubMed

    Bettoli, Vincenzo; Join-Lambert, Olivier; Nassif, Aude

    2016-01-01

    Although hidradenitis suppurativa (HS) is not primarily an infectious disease, antibiotics are widely used to treat HS. Recent microbiological data show that HS suppurating lesions are associated with a polymorphous anaerobic flora, including actinomycetes and milleri group streptococci, and can therefore be considered as polymicrobial soft tissue and skin infections. Analysis of the literature provides little information on the efficacy of antibiotics in HS but suggests a beneficial effect of certain antimicrobial treatments, depending on the clinical severity of the disease. Patients must be informed and should agree with the treatment strategy before starting antibiotic treatments. PMID:26617361

  3. Diverse Antibiotic Resistance Genes in Dairy Cow Manure

    PubMed Central

    Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

    2014-01-01

    ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

  4. In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines.

    PubMed

    Clendennen, T E; Hames, C S; Kees, E S; Price, F C; Rueppel, W J; Andrada, A B; Espinosa, G E; Kabrerra, G; Wignall, F S

    1992-02-01

    Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta-Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines. PMID:1605592

  5. Potential impacts of aquatic pollutants: sub-clinical antibiotic concentrations induce genome changes and promote antibiotic resistance

    PubMed Central

    Chow, Louise; Waldron, Liette; Gillings, Michael R.

    2015-01-01

    Antibiotics are disseminated into aquatic environments via human waste streams and agricultural run-off. Here they can persist at low, but biologically relevant, concentrations. Antibiotic pollution establishes a selection gradient for resistance and may also raise the frequency of events that generate resistance: point mutations; recombination; and lateral gene transfer. This study examined the response of bacteria to sub-inhibitory levels of antibiotics. Pseudomonas aeruginosa and Pseudomonas protegens were exposed kanamycin, tetracycline or ciprofloxacin at 1/10 the minimal inhibitory concentration (MIC) in a serial streaking experiment over 40 passages. Significant changes in rep-PCR fingerprints were noted in both species when exposed to sub-inhibitory antibiotic concentrations. These changes were observed in as few as five passages, despite the fact that the protocols used sample less than 0.3% of the genome, in turn suggesting much more widespread alterations to sequence and genome architecture. Experimental lines also displayed variant colony morphologies. The final MICs were significantly higher in some experimental lineages of P. protegens, suggesting that 1/10 the MIC induces de-novo mutation events that generate resistance phenotypes. The implications of these results are clear: exposure of the environmental microbiome to antibiotic pollution will induce similar changes, including generating newly resistant species that may be of significant concern for human health. PMID:26300869

  6. Multiscale Models of Antibiotic Probiotics

    PubMed Central

    Kaznessis, Yiannis N.

    2014-01-01

    The discovery of antibiotics is one of the most important advances in the history of humankind. For eighty years human life expectancy and standards of living improved greatly thanks to antibiotics. But bacteria have been fighting back, developing resistance to our most potent molecules. New, alternative strategies must be explored as antibiotic therapies become obsolete because of bacterial resistance. Mathematical models and simulations guide the development of complex technologies, such as aircrafts, bridges, communication systems and transportation systems. Herein, models are discussed that guide the development of new antibiotic technologies. These models span multiple molecular and cellular scales, and facilitate the development of a technology that addresses a significant societal challenge. We argue that simulations can be a creative source of knowledge. PMID:25313349

  7. The Double Life of Antibiotics

    PubMed Central

    Yap, Mee-Ngan F.

    2013-01-01

    Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response. “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant.”~Alexander Fleming PMID:24003650

  8. Heat inactivation of beta-lactam antibiotics in milk.

    PubMed

    Zorraquino, M A; Roca, M; Fernandez, N; Molina, M P; Althaus, R

    2008-06-01

    The presence of residues of antimicrobial substances in milk is one of the main concerns of the milk industry, as it poses a risk of toxicity to public health, and can seriously influence the technological properties of milk and dairy products. Moreover, the information available on the thermostability characteristics of these residues, particularly regarding the heat treatments used in control laboratories and the dairy industry, is very scarce. The aim of the study was, therefore, to analyze the effect of different heat treatments (40 degrees C for 10 min, 60 degrees C for 30 min, 83 degrees C for 10 min, 120 degrees C for 20 min, and 140 degrees C for 10 s) on milk samples fortified with three concentrations of nine beta-lactam antibiotics (penicillin G: 3, 6, and 12 microg/liter; ampicillin: 4, 8, and 16 microg/liter; amoxicillin: 4, 8, and 16 microg/liter; cloxacillin: 60, 120, and 240 microg/liter; cefoperazone: 55, 110, and 220 microg/liter; cefquinome: 100, 200, and 400 microg/liter; cefuroxime: 65, 130, and 260 microg/liter; cephalexin: 80, 160, and 220 microg/ liter; and cephalonium: 15, 30, and 60 microg/liter). The method used was a bioassay based on the inhibition of Geobacillus stearothermophilus var. calidolactis. The results showed that heating milk samples at 40 degrees C for 10 min hardly produced any heat inactivation at all, while the treatment at 83 degrees C for 10 min caused a 20% loss in penicillin G, 27% in cephalexin, and 35% in cefuroxime. Of the three dairy industry heat treatments studied in this work, low pasteurization (60 degrees C for 30 min) and treatment at 140 degrees C for 10 s only caused a small loss of antimicrobial activity, whereas classic sterilization (120 degrees C for 20 min) showed a high level of heat inactivation of over 65% for penicillins and 90% for cephalosporins. PMID:18592745

  9. Antibiotic-Driven Dysbiosis Mediates Intraluminal Agglutination and Alternative Segregation of Enterococcus faecium from the Intestinal Epithelium

    PubMed Central

    Top, Janetta; Bayjanov, Jumamurat R.; Kemperman, Hans; Rogers, Malbert R. C.; Paganelli, Fernanda L.; Bonten, Marc J. M.; Willems, Rob J. L.

    2015-01-01

    ABSTRACT The microbiota of the mammalian gastrointestinal tract is a complex ecosystem of bacterial communities that continuously interact with the mucosal immune system. In a healthy host, the mucosal immune system maintains homeostasis in the intestine and prevents invasion of pathogenic bacteria, a phenomenon termed colonization resistance. Antibiotics create dysbiosis of microbiota, thereby decreasing colonization resistance and facilitating infections caused by antibiotic-resistant bacteria. Here we describe how cephalosporin antibiotics create dysbiosis in the mouse large intestine, allowing intestinal outgrowth of antimicrobial-resistant Enterococcus faecium. This is accompanied by a reduction of the mucus-associated gut microbiota layer, colon wall, and Muc-2 mucus layer. E. faecium agglutinates intraluminally in an extracellular matrix consisting of secretory IgA (sIgA), polymeric immunoglobulin receptor (pIgR), and epithelial cadherin (E-cadherin) proteins, thereby maintaining spatial segregation of E. faecium from the intestinal wall. Addition of recombinant E-cadherin and pIgR proteins or purified IgA to enterococci in vitro mimics agglutination of E. faecium in vivo. Also, the Ca2+ levels temporarily increased by 75% in feces of antibiotic-treated mice, which led to deformation of E-cadherin adherens junctions between colonic intestinal epithelial cells and release of E-cadherin as an extracellular matrix entrapping E. faecium. These findings indicate that during antibiotic-induced dysbiosis, the intestinal epithelium stays separated from an invading pathogen through an extracellular matrix in which sIgA, pIgR, and E-cadherin are colocalized. Future mucosal vaccination strategies to control E. faecium or other opportunistic pathogens may prevent multidrug-resistant infections, hospital transmission, and outbreaks. PMID:26556272

  10. Prolonged antibiotic use induces intestinal injury in mice that is repaired after removing antibiotic pressure: implications for empiric antibiotic therapy

    PubMed Central

    Romick-Rosendale, Lindsey E.; Legomarcino, Anne; Patel, Neil B.; Morrow, Ardythe L.

    2015-01-01

    Metabolic profiling of urine and fecal extracts, histological investigation of intestinal ilea, and fecal metagenomics analyses were used to investigate effects of prolonged antibiotic use in mice. The study provides insight into the effects of extended empiric antibiotic therapy in humans. Mice were administered a broad-spectrum antibiotic for four consecutive days followed by oral gavage with Clostridium butyricum, an opportunistic gram-positive pathogenic bacteria commonly isolated in fecal and blood cultures of necrotizing enterocolitis patients. Metagenomics data indicated loss of bacterial diversity after 4 days on antibiotics that was restored after removing antibiotic pressure. Histological analyses indicated damage to ileal villi after antibiotic treatment that underwent repair after lifting antibiotic pressure. Metabolic profiling confirmed intestinal injury in antibiotic-treated mice indicated by increased urinary trans-4-hydroxy-l-proline, a breakdown product of collagen present in connective tissue of ileal villi that may serve as a biomarker for antibiotic-induced injury in at risk populations. PMID:26273236

  11. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    EPA Science Inventory

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  12. Conjugative transfer of plasmid-located antibiotic resistance genes within the gastrointestinal tract of lesser mealworm larvae, Alphitobius diaperinus (Coleoptera: Tenebrionidae).

    PubMed

    Crippen, Tawni L; Poole, Toni L

    2009-09-01

    The frequency of conjugative transfer of antimicrobial resistance plasmids between bacteria within the gastrointestinal tract of lesser mealworm larvae, a prevalent pest in poultry production facilities, was determined. Lesser mealworm larvae were exposed to a negative bacterial control, a donor Salmonella enterica serotype Newport strain, a recipient Escherichia coli, or both donor and recipient to examine horizontal gene transfer of plasmids. Horizontal gene transfer was validated post external disinfection, via a combination of selective culturing, testing of indole production by spot test, characterization of incompatibility plasmids by polymerase chain reaction, and profiling antibiotic susceptibility by a minimum inhibitory concentration (MIC) assay. Transconjugants were produced in all larvae exposed to both donor and recipient bacteria at frequencies comparable to control in vitro filter mating conjugation studies run concurrently. Transconjugants displayed resistance to seven antibiotics in our MIC panel and, when characterized for incompatibility plasmids, were positive for the N replicon and negative for the A/C replicon. The transconjugants did not display resistance to expanded-spectrum cephalosporins, which were associated with the A/C plasmid. This study demonstrates that lesser mealworm larvae, which infest poultry litter, are capable of supporting the horizontal transfer of antibiotic resistance genes and that this exchange can occur within their gastrointestinal tract and between different species of bacteria under laboratory conditions. This information is essential to science-based risk assessments of industrial antibiotic usage and its impact on animal and human health. PMID:19425825

  13. Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

    PubMed Central

    Ulu-Kilic, Ay?egül; Kilic, Selim; Karahocagil, Mustafa; Shehata, Ghaydaa; Eren-Tulek, Necla; Yetkin, Funda; Celen, Mustafa Kemal; Ceran, Nurgul; Gul, Hanefi Cem; Mert, Gurkan; Tekin-Koruk, Suda; Dizbay, Murat; Inal, Ayse Seza; Nayman-Alpat, Sayg?n; Bosilkovski, Mile; Inan, Dilara; Saltoglu, Nese; Abdel-Baky, Laila; Adeva-Bartolome, Maria Teresa; Ceylan, Bahad?r; Sacar, Suzan; Turhan, Vedat; Y?lmaz, Emel; Elaldi, Nazif; Kocak-Tufan, Zeliha; U?urlu, Kenan; Dokuzo?uz, Ba?ak; Y?lmaz, Hava; Gundes, Sibel; Guner, Rahmet; Ozgunes, Nail; Ulcay, Asim; Unal, Serhat; Dayan, Saim; Gorenek, Levent; Karakas, Ahmet; Tasova, Yesim; Usluer, Gaye; Bayindir, Yasar; Kurtaran, Behice; Sipahi, Oguz Resat; Leblebicioglu, Hakan

    2012-01-01

    No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol. PMID:22155822

  14. The origins of antibiotic resistance.

    PubMed

    Wright, Gerard D

    2012-01-01

    Antibiotics remain one of our most important pharmacological tools for the control of infectious disease. However, unlike most other drugs, the use of antibiotics selects for resistant organisms and erodes their clinical utility. Resistance can emerge within populations of bacteria by mutation and be retained by subsequent selection or by the acquisition of resistance elements laterally from other organisms. The source of these resistance genes is only now being understood. The evidence supports a large bacterial resistome-the collection of all resistance genes and their precursors in both pathogenic and nonpathogenic bacteria. These genes have arisen by various means including self-protection in the case of antibiotic producers, transport of small molecules for various reasons including nutrition and detoxification of noxious chemicals, and to accomplish other goals, such as metabolism, and demonstrate serendipitous selectivity for antibiotics. Regardless of their origins, resistance genes can rapidly move through bacterial populations and emerge in pathogenic bacteria. Understanding the processes that contribute to the evolution and selection of resistance is essential to mange current stocks of antibiotics and develop new ones. PMID:23090593

  15. New valid spectrofluorimetric method for determination of selected cephalosporins in different pharmaceutical formulations using safranin as fluorophore.

    PubMed

    Derayea, Sayed M; Ahmed, Hytham M; Abdelmageed, Osama H; Haredy, Ahmed M

    2016-01-15

    A new validated spectrofluorimetric method has been developed for the determination of some cephalosporins namely; cefepime, cefaclor, cefadroxil, cefpodoxime and cefexime. The method was based on the reaction of these drugs with safranin in slightly alkaline medium (pH8.0), to form ion-association complexes. The fluorescent products were extracted into chloroform and their fluorescence intensities were measured at 544-565nm after excitation at 518-524nm. The reaction conditions influencing the product formation and stability were investigated and optimized. The relative fluorescence intensity was proportional to the drug concentration in the linear ranges of 0.15-1.35, 0.35-1.25, 0.35-1.25, 0.20-1.44 and 0.20-1.25?g/mL for cefepime, cefaclor, cefadroxil, cefpodoxime proxetil and cefexime, respectively. The detection limits were 40, 100, 100, 60 and 70ng/mL, respectively. The performance of the developed method was evaluated in terms of Student's t-test and variance ratio F-test to find out the significance of proposed methods over the reference spectrophotometric method. Various pharmaceutical formulations were successfully analyzed using the proposed method and the results were in good agreement with those of the previously reported methods. PMID:26454688

  16. New valid spectrofluorimetric method for determination of selected cephalosporins in different pharmaceutical formulations using safranin as fluorophore

    NASA Astrophysics Data System (ADS)

    Derayea, Sayed M.; Ahmed, Hytham M.; Abdelmageed, Osama H.; Haredy, Ahmed M.

    2016-01-01

    A new validated spectrofluorimetric method has been developed for the determination of some cephalosporins namely; cefepime, cefaclor, cefadroxil, cefpodoxime and cefexime. The method was based on the reaction of these drugs with safranin in slightly alkaline medium (pH 8.0), to form ion-association complexes. The fluorescent products were extracted into chloroform and their fluorescence intensities were measured at 544-565 nm after excitation at 518-524 nm. The reaction conditions influencing the product formation and stability were investigated and optimized. The relative fluorescence intensity was proportional to the drug concentration in the linear ranges of 0.15-1.35, 0.35-1.25, 0.35-1.25, 0.20-1.44 and 0.20-1.25 ?g/mL for cefepime, cefaclor, cefadroxil, cefpodoxime proxetil and cefexime, respectively. The detection limits were 40, 100, 100, 60 and 70 ng/mL, respectively. The performance of the developed method was evaluated in terms of Student's t-test and variance ratio F-test to find out the significance of proposed methods over the reference spectrophotometric method. Various pharmaceutical formulations were successfully analyzed using the proposed method and the results were in good agreement with those of the previously reported methods.

  17. Antibiotic drugs targeting bacterial RNAs

    PubMed Central

    Hong, Weiling; Zeng, Jie; Xie, Jianping

    2014-01-01

    RNAs have diverse structures that include bulges and internal loops able to form tertiary contacts or serve as ligand binding sites. The recent increase in structural and functional information related to RNAs has put them in the limelight as a drug target for small molecule therapy. In addition, the recognition of the marked difference between prokaryotic and eukaryotic rRNA has led to the development of antibiotics that specifically target bacterial rRNA, reduce protein translation and thereby inhibit bacterial growth. To facilitate the development of new antibiotics targeting RNA, we here review the literature concerning such antibiotics, mRNA, riboswitch and tRNA and the key methodologies used for their screening.

  18. Forces shaping the antibiotic resistome.

    PubMed

    Perry, Julie A; Wright, Gerard D

    2014-12-01

    Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance. PMID:25213620

  19. Antibiotic treatment in acute pancreatitis.

    PubMed

    Uomo, G

    2005-01-01

    Severe acute pancreatitis is characterized by a poor prognosis with local and systemic complications, high morbidity and mortality. From the morphological standpoint, almost all patients suffering from severe forms of acute pancreatitis present various degree of pancreatic necrosis. In these patients the occurrence of infection of pancreatic necrosis certainly represents a very important prognostic factor as it has worldwide accepted as the leading cause of death. In addition, the discovery of an infected necrosis represents a crucial point in the treatment of these patients as it is the only clear-cut shift from medical to surgical treatment in necrotizing pancreatitis. Over the last years, earlier and more precise identification of pancreatic necrosis together with availability of new classes of antibiotics with documented activity against the most commonly involved bacteria and able to reach in therapeutic concentration the pancreatic necrosis give us the opportunity to perform some important controlled clinical trials on antibiotic prophylaxis in necrotizing acute pancreatitis. The great majority of these studies showed the usefulness of a prophylactic regimen (using antibiotics such as fluoroquinolones and carbapenems) in terms of reduction of pancreatic and extrapancreatic infections in comparison with untreated controls. Nevertheless, some questions on this topic still present controversial aspects such as the antibiotic of choice, the duration of treatment, the possible opportunistic infections with fungi and/or resistant strains. Antibiotics may prove very useful in patients with documented infected necrosis and high anaesthesiological risk unfit for surgical debridement and drainage; some initial experiences show the possibility that antibiotic treatment may be curative without surgery in these selected cases. PMID:16358949

  20. Assessing the combined effects from two kinds of cephalosporins on green alga (Chlorella pyrenoidosa) based on response surface methodology.

    PubMed

    Guo, Ruixin; Xie, Weishu; Chen, Jianqiu

    2015-04-01

    The present work evaluated the combined effects of cefradine and ceftazidime on the green alga Chlorella pyrenoidosa using response surface methodologies (RSM). After a 48?h-exposure, the population growth rate (PGR), the chlorophyll-a content and the SOD content of the alga increased with increased concentrations of two antibiotics. However, the three responses did not continue to demonstrate significant increases once antibiotic concentrations exceed a moderate level. Three two order polynomial regression equations were obtained to describe well the relationship between the responses of the alga and the two antibiotics' concentration (R(2)?=?0.9997, 0.9292 and 0.9039, respectively). Three 3?D-surface graphs and their contour plots showed directly the changing trends of the alga under the combined effects of two antibiotics. This study for the first time employed the RSM in ecotoxicology, which indicated that the RSM should be placed under a feasible and a potential application prospect in toxicity assessment. PMID:25684417

  1. Antibiotics Linked to Type 2 Diabetes Risk

    MedlinePLUS

    Antibiotics Linked to Type 2 Diabetes Risk Researchers don't know if the drugs signal developing disease, ... 2015 THURSDAY, Aug. 27, 2015 (HealthDay News) -- Taking antibiotics might increase the risk of developing type 2 ...

  2. When and How to Take Antibiotics

    MedlinePLUS

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References POLICY ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network Africa ...

  3. Antibiotics May Not Help After 'Complicated' Appendectomy

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_155473.html Antibiotics May Not Help After 'Complicated' Appendectomy Use of ... 2, 2015 MONDAY, Nov. 2, 2015 (HealthDay News) -- Antibiotics may not reduce the risk of infections in ...

  4. Antibiotics Might Cause Weight Gain in Kids

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_155294.html Antibiotics Might Cause Weight Gain in Kids Study finds ... 2015 THURSDAY, Oct. 22, 2015 (HealthDay News) -- Repeated antibiotic use is linked to greater weight gains in ...

  5. Alliance for the Prudent Use of Antibiotics

    MedlinePLUS

    ... Competencies Current Projects Completed Projects The Center for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance ... visit our partner lab at the Center for Adaptation Genetics and Drug Resistance . Antibiotic Resistance in the ...

  6. Antibiotic sensitivity pattern of uropathogens from pregnant women with urinary tract infection in Abakaliki, Nigeria

    PubMed Central

    Onoh, RC; Umeora, OUJ; Egwuatu, VE; Ezeonu, PO; Onoh, TJP

    2013-01-01

    Background Urinary tract infection (UTI) is a common bacterial infection during pregnancy and a significant cause of perinatal and maternal morbidity and mortality. The causative bacteria have remained virtually the same although with variations in individual prevalence. There has been an increasing resistance by these bacteria to the commonly available antibiotics. Objectives To determine the prevalence of UTI, the common causative bacteria, and their antibiotic sensitivity pattern among pregnant women with UTI. Methodology This is a descriptive study that was carried out at the Obstetrics Department of two tertiary institutions in Abakaliki, Ebonyi State, Nigeria (Federal Medical Center and Ebonyi State University Teaching Hospital) over a period of 12 months. Midstream urine specimens from selected pregnant women with clinical features of UTI were collected for microscopy, culture, and sensitivity. The results were analyzed with the 2008 Epi Info™ software. Results A total of 542 pregnant women presented with symptoms of UTI and were recruited for the study over the study period. Of the 542 pregnant women, 252 (46.5%) had significant bacteriuria with positive urine culture and varying antibiotic sensitivity pattern. The prevalence of symptomatic UTI was 3%. Escherichia coli was the most common bacteria isolated with a percentage of 50.8%. Other isolated micro organisms included Stapylococcus aereus (52 cultures, 20.6%), Proteus mirabilis (24 cultures, 9.5%), S. saprophyticus (18 cultures, 7.1%), Streptococcus spp. (14 cultures, 5.6%), Citrobacter spp. (5 cultures, 2.0%), Klebsiella spp. (4 cultures, 1.6%), Enterobacter spp. (4 cultures, 1.6%), and Pseudomonas spp. (3 cultures, 1.2%). Levofloxacin had the highest overall antibiotic sensitivity of 92.5%. Others with overall antibiotic sensitivity pattern greater than 50% included cefpodoxime (87.3%), ofloxacin (77.4%), ciprofloxacin (66.7%), ceftriaxone (66.7%), and gentamicin (50.8%). Conclusion E. coli was the most common etiological agent of UTI in pregnancy with Enterococcus (Staphylococcus) gaining prominence. Cephalosporin and quinolones were shown to be very effective against the organisms causing UTI in these pregnant women. PMID:24324344

  7. Antibiotic resistance in probiotic bacteria

    PubMed Central

    Gueimonde, Miguel; Sánchez, Borja; G. de los Reyes-Gavilán, Clara; Margolles, Abelardo

    2013-01-01

    Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The main probiotic bacteria are strains belonging to the genera Lactobacillus and Bifidobacterium, although other representatives, such as Bacillus or Escherichia coli strains, have also been used. Lactobacillus and Bifidobacterium are two common inhabitants of the human intestinal microbiota. Also, some species are used in food fermentation processes as starters, or as adjunct cultures in the food industry. With some exceptions, antibiotic resistance in these beneficial microbes does not constitute a safety concern in itself, when mutations or intrinsic resistance mechanisms are responsible for the resistance phenotype. In fact, some probiotic strains with intrinsic antibiotic resistance could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, are often detected in the typical probiotic genera, and constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue. PMID:23882264

  8. Spatial mapping of antibiotic resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A serious concern for modern animal production is the fear that feed antimicrobials, such as monensin, increase the potential for high levels of antibiotic resistant (AR) gene prevalence in the manure, which may subsequently be shared with soil communities and eventually be taken up by human pathoge...

  9. Antibiotic resistance: a geopolitical issue.

    PubMed

    Carlet, J; Pulcini, C; Piddock, L J V

    2014-10-01

    Antimicrobial resistance (AMR), associated with a lack of new antibiotics, is a major threat. Some countries have been able to contain resistance, but in most countries the numbers of antibiotic-resistant bacteria continue to increase, along with antibiotic consumption by humans and animals. AMR is a global issue, and concerns all decision-makers worldwide. Some initiatives have been undertaken in the last 15 years, in particular by the WHO, the European Centre for Disease Prevention and Control, and the CDC, but those initiatives were partial and poorly implemented, without coordination. Very recently, some important initiatives have been implemented by the WHO. Since 2009, a US and European joint task force, the Trans-Atlantic Task Force on Antibiotic Resistance, has been working on common recommendations. At a national level, some important initiatives have been implemented, in particular in European countries and in the USA. The Chennai declaration, in India, is also a good example of a multidisciplinary and national initiative that was highly political. Finally, several non-governmental non-profit organizations are also very active, and have helped to raise awareness about the problem of AMR. In the future, this global issue will need political involvement and strong cooperation between countries and between international agencies. PMID:25040923

  10. New business models for antibiotic innovation.

    PubMed

    So, Anthony D; Shah, Tejen A

    2014-05-01

    The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company's return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards. PMID:24646116

  11. Overcoming the current deadlock in antibiotic research.

    PubMed

    Schäberle, Till F; Hack, Ingrid M

    2014-04-01

    Antibiotic-resistant bacteria are on the rise, making it harder to treat bacterial infections. The situation is aggravated by the shrinking of the antibiotic development pipeline. To finance urgently needed incentives for antibiotic research, creative financing solutions are needed. Public-private partnerships (PPPs) are a successful model for moving forward. PMID:24698433

  12. [Rheological research in creating antibiotic hydrogels].

    PubMed

    Kagan, E Z; Sinitsyna, N I; Kovács, I; Aseva, E V; Fishman, V M

    1987-08-01

    Experimental design was used in studying the effect of certain qualitative factors on rheological properties of antibiotic hydrogels. It was shown that water solubility of antibiotics and the procedure of their addition to gel bases were important in developing hydrogels. Scanning electron microscopy was used in comparative analysis of antibiotic hydrogels. PMID:3674840

  13. New business models for antibiotic innovation

    PubMed Central

    Shah, Tejen A.

    2014-01-01

    The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company’s return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards. PMID:24646116

  14. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

    PubMed

    Brown, David

    2015-12-01

    Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation. PMID:26493767

  15. A High-Throughput Screen for Antibiotic Drug Discovery

    PubMed Central

    Scanlon, Thomas C.; Dostal, Sarah M.; Griswold, Karl E.

    2014-01-01

    We describe an ultra-high-throughput screening platform enabling discovery and/or engineering of natural product antibiotics. The methodology involves creation of hydrogel-in-oil emulsions in which recombinant microorganisms are co-emulsified with bacterial pathogens; antibiotic activity is assayed by use of a fluorescent viability dye. We have successfully utilized both bulk emulsification and microfluidic technology for the generation of hydrogel microdroplets that are size-compatible with conventional flow cytometry. Hydrogel droplets are ~25 pL in volume, and can be synthesized and sorted at rates exceeding 3,000 drops/s. Using this technique, we have achieved screening throughputs exceeding 5 million clones/day. Proof-of-concept experiments demonstrate efficient selection of antibiotic-secreting yeast from a vast excess of negative controls. In addition, we have successfully used this technique to screen a metagenomic library for secreted antibiotics that kill the human pathogen Staphylococcus aureus. Our results establish the practical utility of the screening platform, and we anticipate that the accessible nature of our methods will enable others seeking to identify and engineer the next generation of antibacterial biomolecules. PMID:23955804

  16. Acquired antibiotic resistance among wild animals: the case of Iberian Lynx (Lynx pardinus).

    PubMed

    Sousa, Margarida; Gonçalves, Alexandre; Silva, Nuno; Serra, Rodrigo; Alcaide, Eva; Zorrilla, Irene; Torres, Carmen; Caniça, Manuela; Igrejas, Gilberto; Poeta, Patrícia

    2014-01-01

    The selective pressure generated by the clinical misuse of antibiotics has been the major driving force leading to the emergence of antibiotic resistance among bacteria. Antibiotics or even resistant bacteria are released into the environment and contaminate the surrounding areas. Human and animal populations in contact with these sources are able to become reservoirs of these resistant organisms. Then, due to the convergence between habitats, the contact of wild animals with other animals, humans, or human sources is now more common and this leads to an increase in the exchange of resistance determinants between their microbiota. Indeed, it seems that wildlife populations living in closer proximity to humans have higher levels of antibiotic resistance. Now, the Iberian Lynx (Lynx pardinus) is a part of this issue, being suggested as natural reservoir of acquired resistant bacteria. The emerging public health concern regarding microbial resistance to antibiotics is becoming true: the bacteria are evolving and are now affecting unintentional hosts. PMID:25220796

  17. Antibiotics induce redox-related physiological alterations as part of their lethality.

    PubMed

    Dwyer, Daniel J; Belenky, Peter A; Yang, Jason H; MacDonald, I Cody; Martell, Jeffrey D; Takahashi, Noriko; Chan, Clement T Y; Lobritz, Michael A; Braff, Dana; Schwarz, Eric G; Ye, Jonathan D; Pati, Mekhala; Vercruysse, Maarten; Ralifo, Paul S; Allison, Kyle R; Khalil, Ahmad S; Ting, Alice Y; Walker, Graham C; Collins, James J

    2014-05-20

    Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality. PMID:24803433

  18. Antibiotics induce redox-related physiological alterations as part of their lethality

    PubMed Central

    Dwyer, Daniel J.; Belenky, Peter A.; Yang, Jason H.; MacDonald, I. Cody; Martell, Jeffrey D.; Takahashi, Noriko; Chan, Clement T. Y.; Lobritz, Michael A.; Braff, Dana; Schwarz, Eric G.; Ye, Jonathan D.; Pati, Mekhala; Vercruysse, Maarten; Ralifo, Paul S.; Allison, Kyle R.; Khalil, Ahmad S.; Ting, Alice Y.; Walker, Graham C.; Collins, James J.

    2014-01-01

    Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets have been hypothesized to kill bacteria, in part by inducing production of damaging reactive species. This notion has been supported by many groups but has been challenged recently. Here we robustly test the hypothesis using biochemical, enzymatic, and biophysical assays along with genetic and phenotypic experiments. We first used a novel intracellular H2O2 sensor, together with a chemically diverse panel of fluorescent dyes sensitive to an array of reactive species to demonstrate that antibiotics broadly induce redox stress. Subsequent gene-expression analyses reveal that complex antibiotic-induced oxidative stress responses are distinct from canonical responses generated by supraphysiological levels of H2O2. We next developed a method to quantify cellular respiration dynamically and found that bactericidal antibiotics elevate oxygen consumption, indicating significant alterations to bacterial redox physiology. We further show that overexpression of catalase or DNA mismatch repair enzyme, MutS, and antioxidant pretreatment limit antibiotic lethality, indicating that reactive oxygen species causatively contribute to antibiotic killing. Critically, the killing efficacy of antibiotics was diminished under strict anaerobic conditions but could be enhanced by exposure to molecular oxygen or by the addition of alternative electron acceptors, indicating that environmental factors play a role in killing cells physiologically primed for death. This work provides direct evidence that, downstream of their target-specific interactions, bactericidal antibiotics induce complex redox alterations that contribute to cellular damage and death, thus supporting an evolving, expanded model of antibiotic lethality. PMID:24803433

  19. Antibiotics 2014, 3, 527-539; doi:10.3390/antibiotics3040527 antibiotics

    E-print Network

    Zhang, Yang

    .mdpi.com/journal/antibiotics Article Antimicrobial Activity of Chemokine CXCL10 for Dermal and Oral Microorganisms Grant O. Holdren 1 Abstract: CXCL10 (IP-10) is a small 10 kDa chemokine with antimicrobial activity. It is induced by IFN activity is not yet known. However, antimicrobial activity of CXCL10 may be related to its composition

  20. Antibiotic Treatment Suppresses Rotavirus Infection and Enhances Specific Humoral Immunity

    PubMed Central

    Uchiyama, Robin; Chassaing, Benoit; Zhang, Benyue; Gewirtz, Andrew T.

    2014-01-01

    Background.?Rotavirus causes 500 000 deaths and millions of physician visits and hospitalizations per year, with worse outcomes and reduced vaccine efficacy in developing countries. We hypothesized that the gut microbiota might modulate rotavirus infection and/or antibody response and thus potentially play a role in such regional differences. Methods.?The microbiota was ablated via germ-free or antibiotic approaches. Enhanced exposure to microbiota was achieved via low-dose dextran sodium sulfate (DSS) treatment. Rotavirus infection and replication was assessed by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse-transcription polymerase chain reaction. Diarrhea was scored visually. Humoral responses to rotavirus were measured by ELISA and enzyme-linked immunosorbent spot assay. Results.?Microbiota elimination delayed infection and reduced infectivity by 42%. Antibiotics did not alter ratios of positive-sense to negative-sense strands, suggesting that entry rather than replication was influenced. Antibiotics reduced the diarrhea incidence and duration, indicating that the reduction in the level of rotavirus antigen was biologically significant. Despite lowered antigen level, antibiotics resulted in a more durable rotavirus mucosal/systemic humoral response. Increased rotavirus antibody response durability correlated with increased small intestinal rotavirus-specific, immunoglobulin A–producing antibody-secreting cell concentration in antibiotic-treated mice. Conversely, DSS treatment impaired generation of rotavirus-specific antibodies. Conclusions.?Microbiota ablation resulted in reduced rotavirus infection/diarrhea and a more durable rotavirus antibody response, suggesting that antibiotic administration before rotavirus vaccination could raise low seroconversion rates that correlate with the vaccine's inefficacy in developing regions. PMID:24436449

  1. Antibiotic effectiveness: balancing conservation against innovation.

    PubMed

    Laxminarayan, Ramanan

    2014-09-12

    Antibiotic effectiveness is a natural societal resource that is diminished by antibiotic use. As with other such assets, keeping it available requires both conservation and innovation. Conservation encompasses making the best use of current antibiotic effectiveness by reducing demand through vaccination, infection control, diagnostics, public education, incentives for clinicians to prescribe fewer antibiotics, and restrictions on access to newer, last-resort antibiotics. Innovation includes improving the efficacy of current drugs and replenishing effectiveness by developing new drugs. In this paper, I assess the relative benefits and costs of these two approaches to maintaining our ability to treat infections. PMID:25214620

  2. Surface modeling of soil antibiotics.

    PubMed

    Shi, Wen-Jiao; Yue, Tian-Xiang; Du, Zheng-Ping; Wang, Zong; Li, Xue-Wen

    2016-02-01

    Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1?g/kg, and the MAEs of KED, StK, OK and IDW are 99.0?g/kg, 102.8?g/kg, 106.3?g/kg and 108.7?g/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2?g/kg (88.6?g/kg, 20.4?g/kg and 39.2?g/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints. PMID:26613514

  3. Occurrence and Distribution of Antibiotic-resistant Bacteria and Transfer of Resistance Genes in Lake Taihu

    PubMed Central

    Yin, Qian; Yue, Dongmei; Peng, Yuke; Liu, Ying; Xiao, Lin

    2013-01-01

    The overuse of antibiotics has accelerated antibiotic resistance in the natural environment, especially fresh water, generating a potential risk for public health around the world. In this study, antibiotic resistance in Lake Taihu was investigated and this was the first thorough data obtained through culture-dependent methods. High percentages of resistance to streptomycin and ampicillin among bacterial isolates were detected, followed by tetracycline and chloramphenicol. Especially high levels of ampicillin resistance in the western and northern regions were illustrated. Bacterial identification of the isolates selected for further study indicated the prevalence of some opportunistic pathogens and 62.0% of the 78 isolates exhibited multiple antibiotic resistance. The presence of ESBLs genes was in the following sequence: blaTEM > blaSHV > blaCTMX and 38.5% of the isolates had a class I integrase gene. Of all tested strains, 80.8% were able to transfer antibiotic resistance through conjugation. We also concluded that some new families of human-associated ESBLs and AmpC genes can be found in natural environmental isolates. The prevalence of antibiotic resistance and the dissemination of transferable antibiotic resistance in bacterial isolates (especially in opportunistic pathogens) was alarming and clearly indicated the urgency of realizing the health risks of antibiotic resistance to human and animal populations who are dependent on Lake Taihu for water consumption. PMID:24240317

  4. Biosynthesis of the Novel Macrolide Antibiotic Anthracimycin.

    PubMed

    Alt, Silke; Wilkinson, Barrie

    2015-11-20

    We report the identification of the biosynthetic gene cluster for the unusual antibiotic anthracimycin (atc) from the marine derived producer strain Streptomyces sp. T676 isolated off St. John's Island, Singapore. The 53?253 bps atc locus includes a trans-acyltransferase (trans-AT) polyketide synthase (PKS), and heterologous expression in Streptomyces coelicolor resulted in anthracimycin production. Analysis of the atc cluster revealed that anthracimycin is likely generated by four PKS gene products AtcC-AtcF without involvement of post-PKS tailoring enzymes, and a biosynthetic pathway is proposed. The availability of the atc cluster provides a basis for investigating the biosynthesis of anthracimycin and its subsequent bioengineering to provide novel analogues with improved pharmacological properties. PMID:26349074

  5. Use of antibiotics in plant agriculture.

    PubMed

    Stockwell, V O; Duffy, B

    2012-04-01

    Antibiotics are essential for control of bacterial diseases of plants, especially fire blight of pear and apple and bacterial spot of peach. Streptomycin is used in several countries; the use of oxytetracycline, oxolinic acid and gentamicin is limited to only a few countries. Springtime antibiotic sprays suppress pathogen growth on flowers and leaf surfaces before infection; after infection, antibiotics are ineffective. Antibiotics are applied when disease risk is high, and consequently the majority of orchards are not treated annually. In 2009 in the United States, 16,465 kg (active ingredient) was applied to orchards, which is 0.12% of the total antibiotics used in animal agriculture. Antibiotics are active on plants for less than a week, and significant residues have not been found on harvested fruit. Antibiotics have been indispensable for crop protection in the United States for more than 50 years without reports of adverse effects on human health or persistent impacts on the environment. PMID:22849276

  6. Resistance to Antibiotics Mediated by Target Alterations

    NASA Astrophysics Data System (ADS)

    Spratt, Brian G.

    1994-04-01

    The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

  7. Antibiotic Modification of Native Grafts: Improving upon nature's scaffolds

    NASA Astrophysics Data System (ADS)

    Ketonis, Constantinos

    The use of allograft bone in orthopaedics, spine surgery and dentistry is invaluable for helping restore bone defects and promote osteointegration. However, one, and perhaps the most important, problem associated with the use of allograft is infection. It is a devastating complication for patients and physicians alike, and necessitates repeated surgeries, extended treatment and often times results in increased morbidity and poor outcomes. Previous attempts to incorporate antibiotics into allograft by soaking the graft in antibiotic solution have enjoyed limited success in providing adequate protection against bacterial colonization. To overcome problems associated with controlled release systems, I have described a novel chemical modification that allows for the attachment of vancomycin, or other antibiotics, to free amines of allograft bone thus rendering the graft bactericidal over a long time period. This modification, as evaluated by immunohistochemistry, allowed for the uniform and stable attachment of antibiotics to allograft without adversely affecting its potential for incorporation with bone. Modified allograft, placed in the presence of S. aureus, did not allow colonization by bacteria as evaluated by fluorescent imaging, scanning microscopy, and direct bacterial counts. More importantly, inhibition of bacterial colonization resulted in prevention of biofilm formation. Furthermore, I show that the spectrum of activity of the parent antibiotic was maintained, as the construct was not active against E. coli challenges. Comparison of this technology with simple antibiotic incorporation demonstrated that the covalently-coupled antibiotic did not elute from the bone, but rather remained attached and active on the surface for times out to one year, times that are far longer than currently can be achieved with the elution technologies. Despite its potent activity against bacteria, modified bone remained biocompatible allowing attachment of osteoblastic-like cells with no increased toxicity. Furthermore, the antibiotic-modified allograft incorporated well into tibial defects in the rat. Finally, this construct was efficacious in decreasing the severity of infection and host reaction when impacted in an in vivo model of allograft-associated infection. Thus, our proposed modification in surface design serves as a starting point for the development of a new generation of bone grafts that are biologically active at sites of physiological importance.

  8. The relationship between blood and muscle samples to monitor for residues of the antibiotic enrofloxacin in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Use of antibiotics in food animals has generated concern as the presence of these residues in food may contribute to increased microbial resistance in humans. Fluoroquinolone antibiotics are thus now no longer allowed by the U.S. Food and Drug Administration for use in poultry and monitoring of the...

  9. Silica-based 2-(N,N-dimethylamino)-1,3-propanediol hydrophilic interaction liquid chromatography stationary phase for separating cephalosporins and carbapenems.

    PubMed

    Yin, Wei; Cheng, Lingping; Chai, Huihui; Guo, Ruiqiang; Liu, Renhua; Chu, Changhu; Palasota, John A; Cai, Xiaohui

    2015-08-01

    A silica-based stationary phase bearing both hydrophilic hydroxyl and amino groups was developed by covalently bonding a small molecular N,N-dimethylamino 1,3-propanediol moiety onto silica beads via copper(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC). This new stationary phase showed good HILIC characteristics and high column efficiency (the theoretical plate number is up to 37000 plates m(-1) in the case of inosine) in the separation of polar compounds, such as nucleosides and bases, organic acids, cephalosporins, and carbapenems. PMID:26022095

  10. Antibiotics and the gut microbiota

    PubMed Central

    Modi, Sheetal R.; Collins, James J.; Relman, David A.

    2014-01-01

    Antibiotics have been a cornerstone of innovation in the fields of public health, agriculture, and medicine. However, recent studies have shed new light on the collateral damage they impart on the indigenous host-associated communities. These drugs have been found to alter the taxonomic, genomic, and functional capacity of the human gut microbiota, with effects that are rapid and sometimes persistent. Broad-spectrum antibiotics reduce bacterial diversity while expanding and collapsing membership of specific indigenous taxa. Furthermore, antibiotic treatment selects for resistant bacteria, increases opportunities for horizontal gene transfer, and enables intrusion of pathogenic organisms through depletion of occupied natural niches, with profound implications for the emergence of resistance. Because these pervasive alterations can be viewed as an uncoupling of mutualistic host-microbe relationships, it is valuable to reconsider antimicrobial therapies in the context of an ecological framework. Understanding the biology of competitive exclusion, interspecies protection, and gene flow of adaptive functions in the gut environment may inform the design of new strategies that treat infections while preserving the ecology of our beneficial constituents. PMID:25271726

  11. Heteroresistance at the Single-Cell Level: Adapting to Antibiotic Stress through a Population-Based Strategy and Growth-Controlled Interphenotypic Coordination

    PubMed Central

    Wang, Xiaorong; Kang, Yu; Luo, Chunxiong; Zhao, Tong; Liu, Lin; Jiang, Xiangdan; Fu, Rongrong; An, Shuchang; Chen, Jichao; Jiang, Ning; Ren, Lufeng; Wang, Qi; Baillie, J. Kenneth; Gao, Zhancheng; Yu, Jun

    2014-01-01

    ABSTRACT Heteroresistance refers to phenotypic heterogeneity of microbial clonal populations under antibiotic stress, and it has been thought to be an allocation of a subset of “resistant” cells for surviving in higher concentrations of antibiotic. The assumption fits the so-called bet-hedging strategy, where a bacterial population “hedges” its “bet” on different phenotypes to be selected by unpredicted environment stresses. To test this hypothesis, we constructed a heteroresistance model by introducing a blaCTX-M-14 gene (coding for a cephalosporin hydrolase) into a sensitive Escherichia coli strain. We confirmed heteroresistance in this clone and that a subset of the cells expressed more hydrolase and formed more colonies in the presence of ceftriaxone (exhibited stronger “resistance”). However, subsequent single-cell-level investigation by using a microfluidic device showed that a subset of cells with a distinguishable phenotype of slowed growth and intensified hydrolase expression emerged, and they were not positively selected but increased their proportion in the population with ascending antibiotic concentrations. Therefore, heteroresistance—the gradually decreased colony-forming capability in the presence of antibiotic—was a result of a decreased growth rate rather than of selection for resistant cells. Using a mock strain without the resistance gene, we further demonstrated the existence of two nested growth-centric feedback loops that control the expression of the hydrolase and maximize population growth in various antibiotic concentrations. In conclusion, phenotypic heterogeneity is a population-based strategy beneficial for bacterial survival and propagation through task allocation and interphenotypic collaboration, and the growth rate provides a critical control for the expression of stress-related genes and an essential mechanism in responding to environmental stresses. PMID:24520060

  12. Synthesis, optimization, and characterization of silver nanoparticles from Acinetobacter calcoaceticus and their enhanced antibacterial activity when combined with antibiotics

    PubMed Central

    Singh, Richa; Wagh, Priyanka; Wadhwani, Sweety; Gaidhani, Sharvari; Kumbhar, Avinash; Bellare, Jayesh; Chopade, Balu Ananda

    2013-01-01

    Background The development of nontoxic methods of synthesizing nanoparticles is a major step in nanotechnology to allow their application in nanomedicine. The present study aims to biosynthesize silver nanoparticles (AgNPs) using a cell-free extract of Acinetobacter spp. and evaluate their antibacterial activity. Methods Eighteen strains of Acinetobacter were screened for AgNP synthesis. AgNPs were characterized using various techniques. Reaction parameters were optimized, and their effect on the morphology of AgNPs was studied. The synergistic potential of AgNPs on 14 antibiotics against seven pathogens was determined by disc-diffusion, broth-microdilution, and minimum bactericidal concentration assays. The efficacy of AgNPs was evaluated as per the minimum inhibitory concentration (MIC) breakpoints of the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results Only A. calcoaceticus LRVP54 produced AgNPs within 24 hours. Monodisperse spherical nanoparticles of 8–12 nm were obtained with 0.7 mM silver nitrate at 70°C. During optimization, a blue-shift in ultraviolet-visible spectra was seen. X-ray diffraction data and lattice fringes (d =0.23 nm) observed under high-resolution transmission electron microscope confirmed the crystallinity of AgNPs. These AgNPs were found to be more effective against Gram-negative compared with Gram-positive microorganisms. Overall, AgNPs showed the highest synergy with vancomycin in the disc-diffusion assay. For Enterobacter aerogenes, a 3.8-fold increase in inhibition zone area was observed after the addition of AgNPs with vancomycin. Reduction in MIC and minimum bactericidal concentration was observed on exposure of AgNPs with antibiotics. Interestingly, multidrug-resistant A. baumannii was highly sensitized in the presence of AgNPs and became susceptible to antibiotics except cephalosporins. Similarly, the vancomycin-resistant strain of Streptococcus mutans was also found to be susceptible to antibiotic treatment when AgNPs were added. These biogenic AgNPs showed significant synergistic activity on the ?-lactam class of antibiotics. Conclusion This is the first report of synthesis of AgNPs using A. calcoaceticus LRVP54 and their significant synergistic activity with antibiotics resulting in increased susceptibility of multidrug-resistant bacteria evaluated as per MIC breakpoints of the CLSI standard. PMID:24235826

  13. Salicylate-inducible antibiotic resistance in Pseudomonas cepacia associated with absence of a pore-forming outer membrane protein.

    PubMed Central

    Burns, J L; Clark, D K

    1992-01-01

    The most common mechanism of antibiotic resistance in multiply resistant Pseudomonas cepacia is decreased porin-mediated outer membrane permeability. In some gram-negative organisms this form of antibiotic resistance can be induced by growth in the presence of weak acids, such as salicylates, which suppress porin synthesis. To determine the effects of salicylates on outer membrane permeability of P. cepacia, a susceptible laboratory strain, 249-2, was grown in 10 mM sodium salicylate. Antibiotic susceptibility and uptake, as well as outer membrane protein patterns, were compared between strain 249-2 grown with and without salicylates. The MICs of chloramphenicol, trimethoprim, ciprofloxacin, and ceftazidime were compared between organisms grown in standard and salicylate-containing medium and are as follows: chloramphenicol, 12.5 versus 100 micrograms/ml; trimethoprim, 0.78 versus 3.125 micrograms/ml; ciprofloxacin, 0.4 versus 1.56 micrograms/ml; ceftazidime, 3.125 versus 3.125 micrograms/ml. The permeability of beta-lactam antibiotics was calculated from the rate of hydrolysis of the chromogenic cephalosporin, PADAC. There was no significant difference between strains grown in the presence and absence of salicylate. By using high-pressure liquid chromatography quantitation of loss from culture medium, the effect of 10 mM salicylate on the cellular permeability of chloramphenicol was measured in strain 249-2 by introduction of a plasmid which encodes production of chloramphenicol acetyltransferase. After 1 h of incubation, 18.5% +/- 1.54% versus 70.1% +/- 3.52%, and after 2 h, 4.20% +/- 1.65% versus 41.90% +/- 2.16% remained in supernatants from organisms grown in the absence and presence of 10 mM salicylate, respectively. Outer membrane protein pattern analysis demonstrated the absence of a protein of apparent molecular weight of 40,000 when strain 249-2 was grown in the presence of 10 mM salicylate. To determine whether this protein functioned as a porin, reconstituted membrane vesicles were constructed to assess antibiotic permeability. Vesicles constructed with this salicylate-suppressible outer membrane protein (OpcS) were permeable to chloramphenicol but not to penicillin G. These findings suggest that OpcS is a selective, antibiotic-permeable porin which can be suppressed by growth in the presence of salicylate. Further investigation will be required to determine the biochemical effects of salicylate on porin synthesis. Images PMID:1280056

  14. Probiotics or antibiotics: future challenges in medicine.

    PubMed

    Nami, Yousef; Haghshenas, Babak; Abdullah, Norhafizah; Barzegari, Abolfazl; Radiah, Dayang; Rosli, Rozita; Khosroushahi, Ahmad Yari

    2015-02-01

    Genetic and environmental factors can affect the intestinal microbiome and microbial metabolome. Among these environmental factors, the consumption of antibiotics can significantly change the intestinal microbiome of individuals and consequently affect the corresponding metagenome. The term 'probiotics' is related to preventive medicine rather than therapeutic procedures and is, thus, considered the opposite of antibiotics. This review discusses the challenges between these opposing treatments in terms of the following points: (i) antibiotic resistance, the relationship between antibiotic consumption and microbiome diversity reduction, antibiotic effect on the metagenome, and disease associated with antibiotics; and (ii) probiotics as living drugs, probiotic effect on epigenetic alterations, and gut microbiome relevance to hygiene indulgence. The intestinal microbiome is more specific for individuals and may be affected by environmental alterations and the occurrence of diseases. PMID:25525206

  15. Clinical Usefulness of the 2010 Clinical and Laboratory Standards Institute Revised Breakpoints for Cephalosporin Use in the Treatment of Bacteremia Caused by Escherichia coli or Klebsiella spp.

    PubMed Central

    Ku, Nam Su; Chung, Hae-Sun; Choi, Jun Yong; Yong, Dongeun; Lee, Kyungwon; Kim, June Myung; Chong, Yunsop

    2015-01-01

    We investigated the clinical usefulness of the revised 2010 Clinical and Laboratory Standards Institute (CLSI) breakpoints for Escherichia coli and Klebsiella spp. Of 2,623 patients with bacteremia caused by E. coli or Klebsiella spp., 573 who had been treated appropriately with cephalosporin based on the CLSI 2009 guidelines were enrolled. There were no differences in the rates of treatment failure or mortality between the appropriately and inappropriately treated groups according to the CLSI 2010 guidelines. Additionally, in the matched case-control analysis, the treatment failure rate was higher in bacteremic patients with extended-spectrum ?-lactamase- (ESBL-) producing but cephalosporin-susceptible organisms than in those with ESBL-nonproducing isolates when patients with urinary tract infections were excluded (44% and 0%, resp., P = 0.026). In patients with bacteremia caused by E. coli or Klebsiella spp., the revised CLSI 2010 guidelines did not lead to poorer outcomes. However, ESBL production appeared to be associated with poor clinical outcomes in patients with bacteremia from sources other than the urinary tract. PMID:25793209

  16. Amino Acid Substitutions at Ambler Position Gly238 in the SHV-1 ?-Lactamase: Exploring Sequence Requirements for Resistance to Penicillins and Cephalosporins

    PubMed Central

    Hujer, Andrea M.; Hujer, Kristine M.; Helfand, Marion S.; Anderson, Vernon E.; Bonomo, Robert A.

    2002-01-01

    Site saturation mutagenesis of the 238 position in the SHV ?-lactamase was performed to identify the complete sequence requirements needed for the extended spectrum ?-lactamase (ESBL) phenotype. MICs (in micrograms per milliliter) in an isogenic background, Escherichia coli DH10B, demonstrated that the Gly238Ala mutation conferred the most resistance to penicillins and cephalosporins. The absolute increase in resistance was greatest against cefotaxime for the Gly238Ala mutant (0.06 to 8 ?g/ml). Except for the strain possessing the Gly238Pro ?-lactamase, ceftazidime MICs were also elevated. None of the mutant SHV ?-lactamases were expressed in as great an amount as the wild-type ?-lactamase. Kinetic analysis of the Gly238Ala mutant revealed that penicillin and cephalosporin substrates have a lower Km for the enzyme because of this mutation. Ampicillin and piperacillin MICs were inversely proportional to the side chain volume of the amino acid in cases larger than Ser, suggesting that steric considerations may be a primary requirement for penicillin resistance. Secondary structural effects explain increased resistance to oxyiminocephalosporins. Based upon this study, we anticipate that additional mutations of Gly238 in the SHV ?-lactamase will continue to be discovered with an ESBL (ceftazidime or cefotaxime resistant) phenotype. PMID:12435703

  17. [INHALED ANTIBIOTICS IN TREATMENT OF NOSOCOMIAL PNEUMONIA].

    PubMed

    Kuzovlev, A N; Moroz, V V; Golubev, A M

    2015-01-01

    Nosocomial pneumonia is the most common infection in intensive care units. Currently the problem of resistance of noso-comial pathogens to miost of antibiotics is crucial. Using of inhaled antibiotics in combination with intravenous drugs is eff ective and safe method for treatment of nosocomial pneumonia. The literature review describes current opportunities of ihhaled antibiotic therapy of nosocomial pneumonia, descriptions of drugs, the advantages and disadvantages of this treatment. Special attention is paid for using inhaled aminoglycosides for nosocomial pneumonia. PMID:26596034

  18. General practitioner prescribing of antibiotics for asthma.

    PubMed Central

    Kljakovic, M; Mahadevan, G

    1998-01-01

    Although asthma management guidelines in New Zealand do not advise prescribing antibiotics, almost a quarter of asthma consultations result in a prescription for antibiotics. This study, as part of a repeat audit of asthma care at an after-hours medical centre, describes general practitioners' perspectives on prescribing antibiotics to patients presenting with asthma. The results show that GPs have tended to overestimate the risk of bacterial infection in such patients. PMID:10198487

  19. Anticonvulsant and antibiotic prophylaxis in head injury.

    PubMed Central

    Dunn, L. T.; Foy, P. M.

    1994-01-01

    The evidence for and against the prophylactic use of anticonvulsants and antibiotics in head injury is reviewed. There is a lack of blinded placebo-controlled trials in this area. On balance there is no compelling evidence to support the use of either anticonvulsant or antibiotic prophylaxis in head injury, with the possible exception of antibiotic prophylaxis in compound depressed skull fractures and penetrating brain injuries. PMID:8017807

  20. Antibiotic Resistance Spreads Internationally Across Borders.

    PubMed

    Barlam, Tamar F; Gupta, Kalpana

    2015-01-01

    Antibiotic-resistant (ABR) bacteria develop when bacteria are exposed to antibiotics either during treatments in humans or animals or through environmental sources contaminated with antibiotic residues. Resistant bacteria selected by medical, agricultural, and industrial use spread globally through international travel, the export of animals and retail products, and the environment. It is essential that nations work together to identify how to reduce emergence and amplification of resistant bacteria through sensible antibiotic treatment guidelines and restrictions, concerted efforts for surveillance, and infection control. PMID:26243237

  1. Tackling antibiotic resistance: the environmental framework.

    PubMed

    Berendonk, Thomas U; Manaia, Célia M; Merlin, Christophe; Fatta-Kassinos, Despo; Cytryn, Eddie; Walsh, Fiona; Bürgmann, Helmut; Sørum, Henning; Norström, Madelaine; Pons, Marie-Noëlle; Kreuzinger, Norbert; Huovinen, Pentti; Stefani, Stefania; Schwartz, Thomas; Kisand, Veljo; Baquero, Fernando; Martinez, José Luis

    2015-05-01

    Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment. PMID:25817583

  2. Antibiotic research and development: business as usual?

    PubMed

    Harbarth, S; Theuretzbacher, U; Hackett, J

    2015-01-01

    The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is that it is scientifically challenging to discover new antibiotics that are active against the antibiotic-resistant bacteria of current clinical concern. However, the main hurdle is diminishing economic incentives. Increased global calls to minimize the overuse of antibiotics, the cost of meeting regulatory requirements and the low prices of currently marketed antibiotics are strong deterrents to antibacterial drug development programmes. New economic models that create incentives for the discovery of new antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue. DRIVE-AB is a €9.4 million public-private consortium, funded by the EU Innovative Medicines Initiative, that aims to define a standard for the responsible use of antibiotics and to develop, test and recommend new economic models to incentivize investment in producing new anti-infective agents. PMID:25673635

  3. New antibiotic dosing in infants.

    PubMed

    Pineda, Leslie C; Watt, Kevin M

    2015-03-01

    To prevent the devastating consequences of infection, most infants admitted to the neonatal intensive care unit are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, pharmacokinetic modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, pharmacokinetic data and dosing regimens for infants are now available for ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam. PMID:25678003

  4. Antibiotics

    NASA Astrophysics Data System (ADS)

    Anhalt, John P.

    A 28-year-old man was transferred to our hospital and underwent surgery for resection of an aortic graft infected with Klebsiella pneumoniae. Antimicrobial therapy consisted of amikacin, cefazolin, chloramphenicol, sulfamethoxazole, and trimethoprim. A request for amikacin and sulfamethoxazole assays was received by the laboratory along with information that the patient had received tobramycin until 24 h before the serum was obtained.

  5. Follow up of serial urea breath test results in patients after consumption of antibiotics for non-gastric infections

    PubMed Central

    Leung, Wai-Keung; Hung, Lawrence Cheung-Tsui; Kwok, Carrie Ka-Li; Leong, Rupert Wing-Loong; Ng, Daniel Kwok-Keung; Sung, Joseph Jao-Yiu

    2002-01-01

    AIM: The widespread use of antibacterial therapy has been suggested to be the cause for the decline in the prevalence of Helicobacter pylori infection. This study examine the serial changes of urea breath test results in a group of hospitalized patients who were given antibacterial therapy for non-gastric infections. METHODS: Thirty-five hospitalized patients who were given antibacterial therapy for clinical infections, predominantly chest and urinary infections, were studied. Most (91%) patients were given single antibiotic of either a penicillin or cephalosporin group. Serial 13C-urea breath tests were performed within 24 h of initiation of antibiotics, at one-week and at six-week post-therapy. H. pylori infection was diagnosed when one or more urea breath tests was positive. RESULTS: All 35 patients completed three serial urea breath tests and 26 (74%) were H. pylori-positive. Ten (38%) H. pylori-infected patients had at least one negative breath test results during the study period. The medium delta 13C values were significantly lower at baseline (8.8) than at one-week (20.3) and six-week (24.5) post-treatment in H. pylori-positive individuals (P = 0.022). Clearance of H. pylori at six-week was only seen in one patient who had received anti-helicobacter therapy from another source. CONCLUSION: Our results suggested that one-third of H. pylori-infected individuals had transient false-negative urea breath test results during treatment with antibacterial agent. However, clearance of H. pylori infection by regular antibiotic consumption is rare. PMID:12174382

  6. Prevalence and predictors of antibiotic prescription errors in an emergency department, Central Saudi Arabia

    PubMed Central

    Alanazi, Menyfah Q; Al-Jeraisy, Majed I; Salam, Mahmoud

    2015-01-01

    Background Inappropriate antibiotic (ATB) prescriptions are a threat to patients, leading to adverse drug reactions, bacterial resistance, and subsequently, elevated hospital costs. Our aim was to evaluate ATB prescriptions in an emergency department of a tertiary care facility. Methods A cross-sectional study was conducted by reviewing charts of patients complaining of infections. Patient characteristics (age, sex, weight, allergy, infection type) and prescription characteristics (class, dose, frequency, duration) were evaluated for appropriateness based on the AHFS Drug Information and the Drug Information Handbook. Descriptive and analytic statistics were applied. Results Sample with equal sex distribution constituted of 5,752 cases: adults (?15 years) =61% and pediatrics (<15 years) =39%. Around 55% complained of respiratory tract infections, 25% urinary tract infections (UTIs), and 20% others. Broad-spectrum coverage ATBs were prescribed for 76% of the cases. Before the prescription, 82% of pediatrics had their weight taken, while 18% had their weight estimated. Allergy checking was done in 8% only. Prevalence of inappropriate ATB prescriptions with at least one type of error was 46.2% (pediatrics =58% and adults =39%). Errors were in ATB selection (2%), dosage (22%), frequency (4%), and duration (29%). Dosage and duration errors were significantly predominant among pediatrics (P<0.001 and P<0.0001, respectively). Selection error was higher among adults (P=0.001). Age stratification and binary logistic regression were applied. Significant predictors of inappropriate prescriptions were associated with: 1) cephalosporin prescriptions (adults: P<0.001, adjusted odds ratio [adj OR] =3.31) (pediatrics: P<0.001, adj OR =4.12) compared to penicillin; 2) UTIs (adults: P<0.001, adj OR =2.78) (pediatrics: P=0.039, adj OR =0.73) compared to respiratory tract infections; 3) obtaining weight for pediatrics before the prescription of ATB (P<0.001, adj OR =1.83) compared to those whose weight was estimated; and 4) broad-spectrum ATBs in adults (P=0.002, adj OR =0.67). Conclusion Prevalence of ATB prescription errors in this emergency department was generally high and was particularly common with cephalosporin, narrow-spectrum ATBs, and UTI infections. PMID:26082662

  7. This journal is c The Royal Society of Chemistry 2012 Chem. Commun., 2012, 48, 17391741 1739 Cite this: Chem. Commun., 2012, 48, 17391741

    E-print Network

    Xing, Bengang

    pathogens. Since the last century, b-lactam antibiotics such as penicillins and cephalosporins have been of bacterial enzymes that can effectively cleave penicillin and cephalosporin derivatives before

  8. Identification of Multiresistant Salmonella Isolates Capable of Subsisting on Antibiotics?

    PubMed Central

    Barnhill, Alison E.; Weeks, Katherine E.; Xiong, Nalee; Day, Tim A.; Carlson, Steve A.

    2010-01-01

    This study assessed the ability of Salmonella (572 isolates) to subsist on 12 different antibiotics. The majority (11/12) of the antibiotics enabled subsistence for at least 1 of 140 isolates. Furthermore, 40 isolates were able to subsist on more than one antibiotic. Antibiotic resistance and antibiotic subsistence do not appear to be equivalent. PMID:20173063

  9. 9 CFR 114.10 - Antibiotics as preservatives.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Antibiotics as preservatives. 114.10... BIOLOGICAL PRODUCTS § 114.10 Antibiotics as preservatives. Antibiotics are authorized for use as... section. (a) When an antibiotic or combination of antibiotics, with or without a fungistat is to be...

  10. Reducing Parental Demand for Antibiotics by Promoting Communication Skills

    ERIC Educational Resources Information Center

    Alder, Stephen C.; Trunnell, Eric P.; White, George L., Jr.; Lyon, Joseph L.; Reading, James P.; Samore, Matthew H.; Magill, Michael K.

    2005-01-01

    Antibiotic-resistant strains of bacteria are continuing to emerge as high rates of antibiotic use persist. Children are among the highest users of antibiotics, with parents influencing physician decision-making regarding antibiotic prescription. An intervention based on Social Cognitive Theory (SCT) to reduce parents' expectations for antibiotics

  11. 9 CFR 114.10 - Antibiotics as preservatives.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Antibiotics as preservatives. 114.10... BIOLOGICAL PRODUCTS § 114.10 Antibiotics as preservatives. Antibiotics are authorized for use as... section. (a) When an antibiotic or combination of antibiotics, with or without a fungistat is to be...

  12. 9 CFR 114.10 - Antibiotics as preservatives.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Antibiotics as preservatives. 114.10... BIOLOGICAL PRODUCTS § 114.10 Antibiotics as preservatives. Antibiotics are authorized for use as... section. (a) When an antibiotic or combination of antibiotics, with or without a fungistat is to be...

  13. Effects of temperature and antibiotics on persistence of antibiotic-resistant bacteria and antibiotic resistance genes in poultry litter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of low, residual concentrations of antibiotics in manure and other environmental matrices is not well understood. It has been hypothesized that antibiotic concentrations below clinical MIC (minimal inhibitory concentrations) are still capable of selecting for resistance. The objective of ...

  14. A biosensing strategy for the rapid detection and classification of antibiotic resistance.

    PubMed

    Chen, Qun; Andersson, Anneli; Mecklenburg, Michael; Xie, Bin

    2015-11-15

    Antibiotic resistance (AR) poses an ever growing threat to global public health. Methods are urgently needed that simplify and accelerate the clinical detection and classification of AR. Here we describe a function-based antibiotic resistance assay (FARA) biosensing strategy. The scheme comprises three key components: i) FARA directly measures the thermal signal generated from the catalytic break-down of antibiotics by AR enzymes, ii) a sample specific AR profile is created by analyzing a panel of antibiotics which enhances informational content and iii) meta-analysis of the AR profile database to correlate profiles with diagnosis, treatments and outcomes. In order to test the ability of the scheme to identify and classify AR, two well-studied antibiotic resistance enzymes, penicillinase and metallo-beta-lactamase (MBL), were profiled using a panel of 5 antibiotics: penicillin G, penicillin V, ampicillin, oxacillin and imipenem. The results show that the profiles of the two enzymes could easily detect AR and differentially classified these enzymes. More importantly, both enzymes showed a significant and distinct secondary catalytic profile, which dramatically increases informational content. FARA profiles can be generated and analyzed in 1h. FARA is a fast, simple, cost effective alternative for detecting and classifying AR. FARA will speed up AR detection and classification will allow more accurate individualized treatment. This will reduce the spread of resistance and personalized treatments will improve patient outcomes. Other potential applications of FARA technology are discussed, including the possibility of developing an in vitro blood model for studying AR. PMID:26092129

  15. Antibiotic use, resistance development and environmental factors: a qualitative study among healthcare professionals in Orissa, India

    PubMed Central

    2010-01-01

    Background Antibiotic resistance is a major public health problem affecting both current and future generations. The influence of environmental factors on antibiotic use and resistance development in bacteria is largely unknown. This study explored the perceptions of healthcare providers on antibiotic use and resistance development in relation to environmental factors i.e. physical, natural, social and behavioural factors. Methods A qualitative interview study was conducted using face-to-face, semi-structured interviews among registered allopathic doctors, veterinarians and drug dispensers in Orissa, India. The interview transcripts were analyzed using latent content analysis. Results The main findings of this study relate to two themes: 'Interrelationship between antibiotic use, resistance development and environment' and 'Antibiotic management contributing to the development and spread of resistance'. The interviewees viewed the following as possible contributors to antibiotic use/misuse and resistance development: changes in the natural and physical environment i.e. climate variability, pollution, physiography and population growth; the socioeconomic environment affecting health-seeking behaviour and noncompliance with medication; a lack of healthcare facilities and poor professional attitudes; and ineffective law enforcement regarding medicine dispensing and disposal. Conclusions Generally, the interviewees perceived that although behavioural and social environmental factors are major contributors to resistance development, changes in the physical and natural environment also influence development of antibiotic resistance. The respondents also perceived that there is a lack of information about, and poor awareness of, what constitutes prudent use of antibiotics. They suggested a need for information, education, dissemination and proper implementation and enforcement of legislation at all levels of the drug delivery and disposal system in order to improve antibiotic use and prevent pharmaceutical contamination of the environment. PMID:20964815

  16. Environmental Scientists Find Antibiotics, Bacteria, Resistance Genes in Feedlot Dust

    E-print Network

    Rock, Chris

    Environmental Scientists Find Antibiotics, Bacteria, Resistance Genes in Feedlot Dust :: Texas Tech Today http://today.ttu.edu/2015/01/environmental-scientists-find-antibiotics-bacteria-resistance Print Email + Font - Font Environmental Scientists Find Antibiotics, Bacteria, Resistance Genes

  17. Antibiotics: When They Can and Can't Help

    MedlinePLUS

    ... and most coughs and sore throats. What is "antibiotic resistance?" “Antibiotic resistance” and “bacterial resistance” are two ways of describing the same thing. Usually, antibiotics kill bacteria or stop them from growing. However, ...

  18. Laehnemann et al. Genomics of rapid adaptation to antibiotics

    E-print Network

    Beardmore, Robert

    Laehnemann et al. RESEARCH Genomics of rapid adaptation to antibiotics: Convergent evolution of antibiotic resistance in bacteria. The genomic underpinnings of such rapid changes may provide information antibiotic resistance evolution. Results: Our new analyses demonstrate that amplification of a sequence

  19. Cooperative behaviors in the evolution of antibiotic resistance

    E-print Network

    Yurtsev, Evgene

    2015-01-01

    Through a combination of experiments and modeling, I explored how inactivation of antibiotics by antibiotic-resistant bacteria affects the evolution of antibiotic resistance in two simple microbial communities. First, I ...

  20. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false First aid antibiotic active ingredients. 333.110 Section...OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...

  1. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 false First aid antibiotic active ingredients. 333.110 Section...OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...

  2. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false First aid antibiotic active ingredients. 333.110 Section...OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...

  3. Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin

    E-print Network

    Cudic, Predrag

    Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin) The peptide antibiotic ramoplanin inhibits bacterial peptidoglycan (PG) biosynthesis by interrupting late ramoplanin is structurally less complex than glycopeptide antibiotics such as vancomycin, peptidomimetic

  4. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false First aid antibiotic active ingredients. 333.110 Section...OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...

  5. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false First aid antibiotic active ingredients. 333.110 Section...OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The...

  6. Evolution of resistance to a last-resort antibiotic in Staphyloccocus aureus via bacterial competition

    PubMed Central

    Koch, Gudrun; Yepes, Ana; Förstner, Konrad U.; Wermser, Charlotte; Stengel, Stephanie T.; Modamio, Jennifer; Ohlsen, Knut; Foster, Kevin R.; Lopez, Daniel

    2014-01-01

    Summary Antibiotic resistance is a key medical concern, with antibiotic use likely being an important cause. However, here we describe an alternative route to clinically-relevant antibiotic resistance that occurs solely due to competitive interactions between bacterial cells. We consistently observe that isolates of Methicillin-resistant Staphylococcus aureus diversify spontaneously into two distinct, sequentially arising strains. The first evolved strain outgrows the parent strain via secretion of surfactants and a toxic bacteriocin. The second is resistant to the bacteriocin. Importantly, this second strain is also resistant to intermediate levels of vancomycin. This so-called VISA (vancomycin-intermediate S. aureus) phenotype is seen in many hard-to-treat clinical isolates. This strain diversification also occurs during in vivo infection in a mouse model, consistent with the fact that both coevolved phenotypes resemble strains commonly found in clinic. Our study shows how competition between coevolving bacterial strains can generate antibiotic resistance and recapitulate key clinical phenotypes. PMID:25171407

  7. Antibiotics and Allergic Disorders in Childhood

    PubMed Central

    Jordan, Sue; Storey, Mel; Morgan, Gareth

    2008-01-01

    Aim: This paper explores the possible association between antibiotics prescribed in infancy and allergic disorders, mainly eczema and asthma, in childhood. Background: No-one fully understands why childhood asthma and eczema have become so common. Some authorities suggest that there may be an association between eczema and asthma and antibiotics prescribed in childhood; however, others disagree. Method/Evaluation: The available literature was reviewed to examine the links between prescribed antibiotics and childhood eczema and asthma. Findings/Key Issue: Some, but not all, research indicates that antibiotic administration in pregnancy, childbirth or infancy may be linked to childhood asthma and eczema, but much uncertainty remains. None of the papers identified stated the doses of antibiotics prescribed. In addition, we were unable to locate studies reporting the interactions between antibiotics and the developing immune system. Conclusion: Health care professionals should be selective when prescribing antibiotics. Further prospective work is needed to guide the prescribing of antibiotics in childbirth and infancy. PMID:19319220

  8. Microbiology Lab 7 Determination of Antibiotic Sensitivity

    E-print Network

    species, E. coli, and Staphylococcus epidermidis for sensitivity to several standard antibiotics. Use your E.coli broth culture 1 tube S. epidermidis broth culture 2 sterile plastic pipettes antibiotic and with one of the 2 organisms names. (one plate E.coli, the other, S. epidermidis) 2. inoculate

  9. Antibiotic-Resistant Bacteria: There is Hope.

    ERIC Educational Resources Information Center

    Offner, Susan

    1998-01-01

    Argues that reduction in the use of antibiotics would enable antibiotic-sensitive bacteria to flourish. Presents an activity designed to show students how a small, seemingly unimportant difference in doubling time can, over a period of time, make an enormous difference in population size. (DDR)

  10. Analysis of antibiotic consumption in burn patients

    PubMed Central

    Soleymanzadeh-Moghadam, Somayeh; Azimi, Leila; Amani, Laleh; Rastegar Lari, Aida; Alinejad, Faranak; Rastegar Lari, Abdolaziz

    2015-01-01

    Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used. The results indicated that P. aeruginosa is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR) microorganisms, but it can also decrease the cost of treatment. PMID:26124986

  11. Analysis of antibiotic consumption in burn patients.

    PubMed

    Soleymanzadeh-Moghadam, Somayeh; Azimi, Leila; Amani, Laleh; Rastegar Lari, Aida; Alinejad, Faranak; Rastegar Lari, Abdolaziz

    2015-01-01

    Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used. The results indicated that P. aeruginosa is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR) microorganisms, but it can also decrease the cost of treatment. PMID:26124986

  12. Mining metagenomic datasets for antibiotic resistance genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics are medicines that are used to kill, slow down, or prevent the growth of susceptible bacteria. They became widely used in the mid 20th century for controlling disease in humans, animals, and plants, and for a variety of industrial purposes. Antibiotic resistance is a broad term. There ...

  13. POULTRY PRODUCTION WITHOUT THE USE OF ANTIBIOTICS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Regulatory pressures to limit antibiotic use in livestock and recent international marketing agreements that prohibit treating poultry with antibiotics have limited the disease-fighting tools available to poultry and livestock producers, particularly in Europe. There is a need to evaluate potential...

  14. Metabolic engineering of antibiotic factories: new tools for antibiotic production in actinomycetes.

    PubMed

    Weber, Tilmann; Charusanti, Pep; Musiol-Kroll, Ewa Maria; Jiang, Xinglin; Tong, Yaojun; Kim, Hyun Uk; Lee, Sang Yup

    2015-01-01

    Actinomycetes are excellent sources for novel bioactive compounds, which serve as potential drug candidates for antibiotics development. While industrial efforts to find and develop novel antimicrobials have been severely reduced during the past two decades, the increasing threat of multidrug-resistant pathogens and the development of new technologies to find and produce such compounds have again attracted interest in this field. Based on improvements in whole-genome sequencing, novel methods have been developed to identify the secondary metabolite biosynthetic gene clusters by genome mining, to clone them, and to express them in heterologous hosts in much higher throughput than before. These technologies now enable metabolic engineering approaches to optimize production yields and to directly manipulate the pathways to generate modified products. PMID:25497361

  15. Influence of therapeutic ceftiofur treatments of feedlot cattle on fecal and hide prevalences of commensal Escherichia coli resistant to expanded-spectrum cephalosporins, and molecular characterization of resistant isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the United States the bla**CMY-2** gene contained within incompatibility type A/C (IncA/C) plasmids is frequently identified in extended-spectrum cephalosporin-resistant Escherichia coli (ESCr) from both human and cattle sources. Concerns have been raised that therapeutic use of ceftiofur in catt...

  16. Linking microbial community structure and function to characterize antibiotic resistant bacteria and antibiotic resistant genes from cattle feces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is widespread interest in monitoring the development of antibiotic resistant bacteria and antibiotic resistance genes in agriculturally impacted environments, however little is known about the relationships between bacterial community structure, and antibiotic resistance gene profiles. Cattl...

  17. Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance

    E-print Network

    Collins, James J.

    Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance Nicole Salmonella typhimurium increases its antibiotic toler- ance in response to indole, even though S. typhimurium

  18. Nonribosomal biosynthesis of peptide antibiotics.

    PubMed

    Kleinkauf, H; von Döhren, H

    1990-08-28

    Peptide antibiotics are known to contain non-protein amino acids, D-amino acids, hydroxy acids, and other unusual constituents. In addition they may be modified by N-methylation and cyclization reactions. Their biosynthetic origin has been connected in many cases to an enzymatic system referred to as the 'thiotemplate multienzymic mechanism'. This mechanism includes the activation of the constituent residues as adenylates on the enzymic template, the acylation of specific template thiol groups, epimerization or N-methylation at this thioester stage, and polymerization in the sequence directed by the multienzymic structure with the aid of 4'-phosphopantetheine as a cofactor, including possible cyclization or terminal modification reactions. The reaction sequences leading to gramicidin S, tyrocidine, cyclosporine, bacitracin, polymyxin, actinomycin, enniatin, beauvericin, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine and linear gramicidin are discussed. The structures of the multienzymes, their genetic organization, the biological functions of these peptides and results on related systems are discussed. PMID:2205497

  19. "Practical knowledge" and perceptions of antibiotics and antibiotic resistance among drugsellers in Tanzanian private drugstores

    PubMed Central

    2010-01-01

    Background Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Methods Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Results Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85%) said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic resistance based on practical experience. Conclusions The drugsellers have considerable "practical knowledge" of antibiotics and a perception of antibiotic resistance based on practical experience. In the process of upgrading private drugstores and formalizing the sale of antibiotics from these outlets in resource-constrained settings, their "practical knowledge" as well as their perceptions must be taken into account in order to attain rational dispensing practices. PMID:20846407

  20. The antibiotic effects of vitamin D.

    PubMed

    Guo, Chunxiao; Gombart, Adrian F

    2014-01-01

    The recent discovery that vitamin D regulates expression of the cathelicidin antimicrobial peptide gene has generated renewed interest in using vitamin D to fight infectious diseases. This review describes the historical use of vitamin D or its sources to treat infections, the mechanism of action through which vitamin D mediates its "antibiotic" effects, findings from epidemiological studies associating vitamin D deficiency with increased susceptibility to infection and clinical trials with vitamin D supplementation to treat or prevent infections. Further studies examining an association between vitamin D levels and cathelicidin expression are discussed. The role of cathelcidin throughout the course of infection from the initial encounter of the pathogen to the resolution of tissue damage and inflammation indicates that individuals need to maintain adequate levels of vitamin D for an optimal immune response. In addition, for treating infections, carefully designed randomized, clinical trials that are appropriately powered to detect modest effects, target populations that are severely deficient in vitamin D,and optimized dose, dosing frequency and safety are needed. PMID:25008764

  1. Treatment of antibiotics and antibiotic resistant bacteria in swine wastewater with free chlorine.

    PubMed

    Qiang, Zhimin; Macauley, John J; Mormile, Melanie R; Surampalli, Rao; Adams, Craig D

    2006-10-18

    Recent recognition of the occurrence of antibiotics in the environment has highlighted concerns regarding potential threats of antibiotics to humans and wildlife. Antibiotics are commonly applied to animals to prevent diseases and promote growth, making livestock agriculture a major source of antibiotic pollution. The purpose of our study was to examine chlorination technology as a method for preventing the release of antibiotics as well as antibiotic-resistant bacteria into the environment from concentrated animal feeding operations. Wastewaters from various sites of two anaerobic lagoon systems, one aerated and the other not, on a swine facility were investigated. Each system consisted of a primary treatment lagoon and a subsequent polishing lagoon. Free chlorine (or monochloramine for comparison) was applied to oxidize antibiotics and to disinfect lagoon bacteria as well. Results indicate that aeration substantially improves lagoon functionality, thereby adding both organic and ammonia removal. Ammonia present in the wastewaters plays a critical role in antibiotics decomposition and bacterial inactivation due to its rapid competition for free chlorine to form monochloramine. Generally, a chlorine dose close to breakpoint is required to achieve complete removal of antibiotics, leading to high consumption of free chlorine in most of the wastewaters examined. However, because of a low ammonia concentration in the polishing lagoon wastewater of the aerated system, a chlorine dose of 100 mg/L can effectively achieve complete removal of both antibiotics and bacteria. On the basis of our experimental findings, a possible strategy for the treatment of swine wastewater is suggested. PMID:17032022

  2. Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics

    PubMed Central

    Berglund, Björn

    2015-01-01

    Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment. PMID:26356096

  3. Antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci.

    PubMed

    McMurray, Claire L; Hardy, Katherine J; Verlander, Neville Q; Hawkey, Peter M

    2015-12-01

    Staphylococci are a significant cause of hospital-acquired infection. Nasal carriage of Staphylococcus aureus is an important risk factor for infection in surgical patients and coagulase-negative staphylococci (CNS) are a major cause of prosthetic joint infections. The impact that antibiotic surgical prophylaxis has on the nasal carriage of staphylococci has not been studied. Daily nasal swabs were taken from 63 patients who received antibiotic surgical prophylaxis and 16 patients who received no antibiotics. Total aerobic bacterial count, S. aureus and CNS were enumerated by culture from nasal swabs. Representative isolates were typed by staphylococcal interspersed repeat units (SIRU) typing and PFGE, and MICs to nine antibiotics were determined. After antibiotic administration, there was a reduction in S. aureus counts (median -?2.3?log10c.f.u. ml-?1) in 64.0?% of S. aureus carriers, compared with only a 0.89?log10c.f.u. ml-?1 reduction in 75.0?% of S. aureus carriers who did not receive antibiotics. A greater increase in the nasal carriage rate of meticillin-resistant CNS was observed after antibiotic surgical prophylaxis compared with hospitalization alone, with increases of 16.4 and 4.6?%, respectively. Antibiotic-resistant S. epidermidis carriage rate increased by 16.6?% after antibiotic administration compared with 7.5?% with hospitalization alone. Antibiotic surgical prophylaxis impacts the nasal carriage of both S. aureus and CNS. PMID:26445858

  4. Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

    PubMed Central

    Liu, Gang; Chandra, Govind; Niu, Guoqing

    2013-01-01

    SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

  5. Pharmacokinetics of intravitreal antibiotics in endophthalmitis

    PubMed Central

    2014-01-01

    Intravitreal antibiotics are the mainstay of treatment in the management of infectious endophthalmitis. Basic knowledge of the commonly used intravitreal antibiotics, which includes their pharmacokinetics, half-life, duration of action and clearance, is essential for elimination of intraocular infection without any iatrogenic adverse effect to the ocular tissue. Various drugs have been studied over the past century to achieve this goal. We performed a comprehensive review of the antibiotics which have been used for intravitreal route and the pharmacokinetic factors influencing the drug delivery and safety profile of these antibiotics. Using online resources like PubMed and Google Scholar, articles were reviewed. The articles were confined to the English language only. We present a broad overview of pharmacokinetic concepts fundamental for use of intravitreal antibiotics in endophthalmitis along with a tabulated compendium of the intravitreal antibiotics using available literature. Recent advances for increasing bioavailability of antibiotics to the posterior segment with the development of controlled drug delivery devices are also described. PMID:25667683

  6. Antibiotics, Bacteria, and Antibiotic Resistance Genes: Aerial Transport from Cattle Feed Yards via Particulate Matter

    PubMed Central

    McEachran, Andrew D.; Blackwell, Brett R.; Hanson, J. Delton; Wooten, Kimberly J.; Mayer, Gregory D.; Cox, Stephen B.

    2015-01-01

    Background: Emergence and spread of antibiotic resistance has become a global health threat and is often linked with overuse and misuse of clinical and veterinary chemotherapeutic agents. Modern industrial-scale animal feeding operations rely extensively on veterinary pharmaceuticals, including antibiotics, to augment animal growth. Following excretion, antibiotics are transported through the environment via runoff, leaching, and land application of manure; however, airborne transport from feed yards has not been characterized. Objectives: The goal of this study was to determine the extent to which antibiotics, antibiotic resistance genes (ARG), and ruminant-associated microbes are aerially dispersed via particulate matter (PM) derived from large-scale beef cattle feed yards. Methods: PM was collected downwind and upwind of 10 beef cattle feed yards. After extraction from PM, five veterinary antibiotics were quantified via high-performance liquid chromatography with tandem mass spectrometry, ARG were quantified via targeted quantitative polymerase chain reaction, and microbial community diversity was analyzed via 16S rRNA amplification and sequencing. Results: Airborne PM derived from feed yards facilitated dispersal of several veterinary antibiotics, as well as microbial communities containing ARG. Concentrations of several antibiotics in airborne PM immediately downwind of feed yards ranged from 0.5 to 4.6 ?g/g of PM. Microbial communities of PM collected downwind of feed yards were enriched with ruminant-associated taxa and were distinct when compared to upwind PM assemblages. Furthermore, genes encoding resistance to tetracycline antibiotics were significantly more abundant in PM collected downwind of feed yards as compared to upwind. Conclusions: Wind-dispersed PM from feed yards harbors antibiotics, bacteria, and ARGs. Citation: McEachran AD, Blackwell BR, Hanson JD, Wooten KJ, Mayer GD, Cox SB, Smith PN. 2015. Antibiotics, bacteria, and antibiotic resistance genes: aerial transport from cattle feed yards via particulate matter. Environ Health Perspect 123:337–343;?http://dx.doi.org/10.1289/ehp.1408555 PMID:25633846

  7. Determination of Bacterial Antibiotic Resistance Based on Osmotic Shock Response

    E-print Network

    Manalis, Scott

    Determination of Bacterial Antibiotic Resistance Based on Osmotic Shock Response Scott M. Knudsen. This behavior can be used to differentiate between an antibiotic-resistant and an antibiotic-susceptible strain- sion of the SMR for rapid detection of antibiotic resistance. The buoyant densities of bacterial cells

  8. Simple Models of Antibiotic Cycling Timothy C. Reluga

    E-print Network

    Reluga, Tim

    Simple Models of Antibiotic Cycling Timothy C. Reluga Department of Applied Mathematics University: Antibiotic cycling Key words: heterogeneous environments, resistance management 1 #12;Abstract The use of antibiotic usage to control antibiotic resistance. This paper presents a theory for the optimization

  9. SURGICAL PERSPECTIVE Antibiotic Overuse: The Influence of Social Norms

    E-print Network

    Otto, Sarah

    SURGICAL PERSPECTIVE Antibiotic Overuse: The Influence of Social Norms The McDonnell Norms Group Since the introduction of penicillin in the 1940s, antibiot- ics ("antibiotics" refers to antibacterial to human life are now readily treated. This widespread use of antibiotics has led to at least two

  10. Antibiotics DOI: 10.1002/anie.200801801

    E-print Network

    Nizet, Victor

    that has over- come every antibiotic cam- paign. Methicillin-resistant S. aureus (MRSA) infections proceeds through the same early steps as sterol biosynthesis. A recent anti- MRSA drug-discovery effort

  11. Aerosolized antibiotics in cystic fibrosis: an update.

    PubMed

    Fiel, Stanley B

    2014-06-01

    Inhaled antibiotic therapy, targeting Pseudomonas aeruginosa, is a fundamental component of cystic fibrosis (CF) management. Tobramycin inhalation solution (TIS) was approved in the United States (US) in 1998. Subsequent research efforts focused on developing products with a reduced treatment time burden. Aztreonam for inhalation solution (AZLI), administered via a more efficient nebulizer than TIS, was approved in the US in 2010. Dry powder for inhalation (DPI) formulations provide alternatives to nebulized therapy: tobramycin powder for inhalation (also known as TIP™) was approved in the US in 2013, and colistimethate sodium DPI received European approval in 2012. Other aerosolized antibiotics and regimens combining inhaled antibiotics are in development. Inhaled antibiotic rotation (e.g., TIS alternating with AZLI) is an important concept being actively tested in CF. PMID:24838090

  12. A Supramolecular Antibiotic Switch for Antibacterial Regulation.

    PubMed

    Bai, Haotian; Yuan, Huanxiang; Nie, Chenyao; Wang, Bing; Lv, Fengting; Liu, Libing; Wang, Shu

    2015-11-01

    A supramolecular antibiotic switch is described that can reversibly "turn-on" and "turn-off" its antibacterial activity on demand, providing a proof-of-concept for a way to regulate antibacterial activity of biotics. The switch relies on supramolecular assembly and disassembly of cationic poly(phenylene vinylene) derivative (PPV) with cucurbit[7]uril (CB[7]) to regulate their different interactions with bacteria. This simple but efficient strategy does not require any chemical modification on the active sites of the antibacterial agent, and could also regulate the antibacterial activity of classical antibiotics or photosensitizers in photodynamic therapy. This supramolecular antibiotic switch may be a successful strategy to fight bacterial infections and decrease the emergence of bacterial resistance to antibiotics from a long-term point of view. PMID:26307170

  13. Mechanisms of antibiotic resistance in enterococci

    PubMed Central

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2015-01-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

  14. Mobilome and antibiotic resistance in Acinetobacter baumannii 

    E-print Network

    Opazo, Andres Felipe

    2014-11-28

    Acinetobacter baumannii is an important microorganism involved in hospital-acquired infections with a remarkable ability to develop resistance to multiple antibiotics (multidrug-resistance, MDR) which makes it a highly ...

  15. New Antibiotics May One Day Beat Superbugs

    MedlinePLUS

    ... news/fullstory_154705.html New Antibiotics May One Day Beat Superbugs But research is still in early ... said. The researchers said their findings might one day provide new hope for more than 2 million ...

  16. Abiotic degradation of antibiotic ionophores.

    PubMed

    Bohn, Pernille; Bak, Søren A; Björklund, Erland; Krogh, Kristine A; Hansen, Martin

    2013-11-01

    Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C for maximum 34 days. Using LC-MS/MS for chemical analysis, lasalocid was not found to hydrolyse in any of the tested environments. Monensin, salinomycin, and narasin were all stable in neutral or alkaline solution but hydrolysed in the solution with a pH of 4. Half-lives at 25 °C were calculated to be 13, 0.6, and 0.7 days for monensin, salinomycin, and narasin, respectively. Absorbance spectra from each compound indicated that only lasalocid is degraded by photolysis (half-life below 1 h) due to an absorbance maximum around 303 nm, and monensin, salinomycin, and narasin are resistant to direct photolysis because they absorb light of environmentally irrelevant wavelengths. PMID:23917220

  17. Assessing Antibiotic Resistance of Staphyloccocus: Students Use Their Own Microbial Flora To Explore Antibiotic Resistance.

    ERIC Educational Resources Information Center

    Omoto, Charlotte K.; Malm, Kirstin

    2003-01-01

    Describes a microbiology laboratory experiment in which students test their own microbial flora of Staphylococcus for antibiotic resistance. Provides directions on how to conduct the experiment. (YDS)

  18. Small-plasmid-mediated antibiotic resistance is enhanced by increases in plasmid copy number and bacterial fitness.

    PubMed

    San Millan, Alvaro; Santos-Lopez, Alfonso; Ortega-Huedo, Rafael; Bernabe-Balas, Cristina; Kennedy, Sean P; Gonzalez-Zorn, Bruno

    2015-01-01

    Plasmids play a key role in the horizontal spread of antibiotic resistance determinants among bacterial pathogens. When an antibiotic resistance plasmid arrives in a new bacterial host, it produces a fitness cost, causing a competitive disadvantage for the plasmid-bearing bacterium in the absence of antibiotics. On the other hand, in the presence of antibiotics, the plasmid promotes the survival of the clone. The adaptations experienced by plasmid and bacterium in the presence of antibiotics during the first generations of coexistence will be crucial for the progress of the infection and the maintenance of plasmid-mediated resistance once the treatment is over. Here we developed a model system using the human pathogen Haemophilus influenzae carrying the small plasmid pB1000 conferring resistance to ?-lactam antibiotics to investigate host and plasmid adaptations in the course of a simulated ampicillin therapy. Our results proved that plasmid-bearing clones compensated for the fitness disadvantage during the first 100 generations of plasmid-host adaptation. In addition, ampicillin treatment was associated with an increase in pB1000 copy number. The augmentation in both bacterial fitness and plasmid copy number gave rise to H. influenzae populations with higher ampicillin resistance levels. In conclusion, we show here that the modulations in bacterial fitness and plasmid copy number help a plasmid-bearing bacterium to adapt during antibiotic therapy, promoting both the survival of the host and the spread of the plasmid. PMID:25824216

  19. Acquired Antibiotic Resistance Genes: An Overview

    PubMed Central

    van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

  20. DNA-Aptamers Binding Aminoglycoside Antibiotics

    PubMed Central

    Nikolaus, Nadia; Strehlitz, Beate

    2014-01-01

    Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given. PMID:24566637

  1. [Inhaled antibiotic therapy in cystic fibrosis].

    PubMed

    Girón Moreno, Rosa M; Salcedo Posadas, Antonio; Mar Gómez-Punter, Rosa

    2011-06-01

    Cystic fibrosis is the most frequent fatal genetically-transmitted disease among Caucasians. Chronic bronchial infection, especially by Pseudomonas aeruginosa, is the main cause of morbidity and mortality in this disease. Aerosolized antibiotic therapy achieves high drug concentrations in the airway with low toxicity, allowing chronic use. Currently, two antibiotics have been approved for inhalation therapy, tobramycin inhalation solution and colistimethate sodium aerosol. There is less evidence from clinical trials for the latter. The main indication for these drugs is chronic bronchial colonization by P. aeruginosa, although there is increasing evidence of the importance of the primary infection by this bacterium, whether treated by oral or intravenous antibiotics or not. More controversial is the use of aerosolized antibiotic therapy in bacterial prophylaxis or respiratory exacerbations. For many years, intravenous formulations of distinct antibiotics for aerosolized use have been employed, which are in distinct phases of research for use in nebulizer therapy. In addition to being used to treat P. aeruginosa infection, aerosolized antibiotics have been used to treat other pathogens such as methicillin-resistant Staphylococus aureus, Mycobacterium abscessus and Aspergillus fumigatus. PMID:21703474

  2. NOTE: Dielectrophoretic assay of bacterial resistance to antibiotics

    NASA Astrophysics Data System (ADS)

    Johari, Juliana; Hübner, Yvonne; Hull, Judith C.; Dale, Jeremy W.; Hughes, Michael P.

    2003-07-01

    The dielectrophoretic collection spectra of antibiotic-sensitive and antibiotic-resistant strains of Staphylococcus epidermidis have been determined. These indicate that in the absence of antibiotic treatment there is a strong similarity between the dielectric properties of sensitive and resistant strains, and that there is a significant difference between the sensitive strains before and after treatment with the antibiotic streptomycin after 24 h exposure. This method offers possibilities for the assessment of bacterial resistance to antibiotics.

  3. A Site-Specific Recombinase-Based Method to Produce Antibiotic Selectable Marker Free Transgenic Cattle

    PubMed Central

    Tong, Qi; Liu, Xu; Su, Feng; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2013-01-01

    Antibiotic selectable marker genes have been widely used to generate transgenic animals. Once transgenic animals have been obtained, the selectable marker is no longer necessary but raises public concerns regarding biological safety. The aim of this study was to prepare competent antibiotic selectable marker free transgenic cells for somatic cell nuclear transfer (SCNT). PhiC31 intergrase was used to insert a transgene cassette into a “safe harbor” in the bovine genome. Then, Cre recombinase was employed to excise the selectable marker under the monitoring of a fluorescent double reporter. By visually tracking the phenotypic switch from red to green fluorescence, antibiotic selectable marker free cells were easily detected and sorted by fluorescence-activated cell sorting. For safety, we used phiC31 mRNA and cell-permeant Cre protein in this study. When used as donor nuclei for SCNT, these safe harbor integrated marker-free transgenic cells supported a similar developmental competence of SCNT embryos compared with that of non-transgenic cells. After embryo transfer, antibiotic selectable marker free transgenic cattle were generated and anti-bacterial recombinant human ?-defensin-3 in milk was detected during their lactation period. Thus, this approach offers a rapid and safe alternative to produce antibiotic selectable marker free transgenic farm animals, thereby making it a valuable tool to promote the healthy development and welfare of transgenic farm animals. PMID:23658729

  4. 21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

  5. 21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

  6. 21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

  7. 21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

  8. 21 CFR 510.106 - Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing animals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Labeling of antibiotic and antibiotic-containing drugs intended for use in milk-producing...Rulings and Decisions § 510.106 Labeling of antibiotic and antibiotic-containing drugs intended...

  9. Fate and transport of veterinary antibiotics, antibiotic-resistant bacteria, and antibiotic resistance gene from fields receiving poultry manure during storm events

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobials are used in production agriculture to treat disease and promote animal growth, but the presence of antibiotics in the environment raises concern about widespread antibiotic resistance. This study documents the occurrence and transport of tylosin, tetracycline, enterococci resistant to...

  10. Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment

    PubMed Central

    Pruden, Amy; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K.; Graham, David W.; Lazorchak, James M.; Suzuki, Satoru; Silley, Peter; Snape, Jason R.; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

    2013-01-01

    Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. PMID:23735422

  11. Urine Antibiotic Activity in Patients Presenting to Hospitals in Laos: Implications for Worsening Antibiotic Resistance

    PubMed Central

    Khennavong, Manisone; Davone, Viengmon; Vongsouvath, Manivanh; Phetsouvanh, Rattanaphone; Silisouk, Joy; Rattana, Olay; Mayxay, Mayfong; Castonguay-Vanier, Josée; Moore, Catrin E.; Strobel, Michel; Newton, Paul N.

    2011-01-01

    Widespread use of antibiotics may be important in the spread of antimicrobial resistance. We estimated the proportion of Lao in- and outpatients who had taken antibiotics before medical consultation by detecting antibiotic activity in their urine added to lawns of Bacillus stearothermophilus, Escherichia coli, and Streptococcus pyogenes. In the retrospective (N = 2,058) and prospective studies (N = 1,153), 49.7% (95% confidence interval [CI] = 47.4–52.0) and 36.2% (95% CI = 33.4–38.9), respectively, of Vientiane patients had urinary antibiotic activity detected. The highest frequency of estimated antibiotic pre-treatment was found in patients recruited with suspected central nervous system infections and community-acquired septicemia (both 56.8%). In Vientiane, children had a higher frequency of estimated antibiotic pre-treatment than adults (60.0% versus 46.5%; P < 0.001). Antibiotic use based on patients histories was significantly less frequent than when estimated from urinary antibiotic activity (P < 0.0001). PMID:21813851

  12. Inhaled Antibiotics for Lower Airway Infections

    PubMed Central

    Quon, Bradley S.; Goss, Christopher H.

    2014-01-01

    Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post–lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized “off-label” to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated. PMID:24673698

  13. Nudging Guideline-Concordant Antibiotic Prescribing

    PubMed Central

    Meeker, Daniella; Knight, Tara K.; Friedberg, Mark W.; Linder, Jeffrey A.; Goldstein, Noah J.; Fox, Craig R.; Rothfeld, Alan; Diaz, Guillermo; Doctor, Jason N.

    2015-01-01

    IMPORTANCE “Nudges” that influence decision making through subtle cognitive mechanisms have been shown to be highly effective in a wide range of applications, but there have been few experiments to improve clinical practice. OBJECTIVE To investigate the use of a behavioral “nudge” based on the principle of public commitment in encouraging the judicious use of antibiotics for acute respiratory infections (ARIs). DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial in 5 outpatient primary care clinics. A total of 954 adults had ARI visits during the study timeframe: 449 patients were treated by clinicians randomized to the posted commitment letter (335 in the baseline period, 114 in the intervention period); 505 patients were treated by clinicians randomized to standard practice control (384 baseline, 121 intervention). INTERVENTIONS The intervention consisted of displaying poster-sized commitment letters in examination rooms for 12 weeks. These letters, featuring clinician photographs and signatures, stated their commitment to avoid inappropriate antibiotic prescribing for ARIs. MAIN OUTCOMES AND MEASURES Antibiotic prescribing rates for antibiotic-inappropriate ARI diagnoses in baseline and intervention periods, adjusted for patient age, sex, and insurance status. RESULTS Baseline rates were 43.5% and 42.8% for control and poster, respectively. During the intervention period, inappropriate prescribing rates increased to 52.7% for controls but decreased to 33.7% in the posted commitment letter condition. Controlling for baseline prescribing rates, we found that the posted commitment letter resulted in a 19.7 absolute percentage reduction in inappropriate antibiotic prescribing rate relative to control (P = .02). There was no evidence of diagnostic coding shift, and rates of appropriate antibiotic prescriptions did not diminish over time. CONCLUSIONS AND RELEVANCE Displaying poster-sized commitment letters in examination rooms decreased inappropriate antibiotic prescribing for ARIs. The effect of this simple, low-cost intervention is comparable in magnitude to costlier, more intensive quality-improvement efforts. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT01767064 PMID:24474434

  14. Assessment of five screening strategies for optimal detection of carriers of third-generation cephalosporin-resistant Enterobacteriaceae in intensive care units using daily sampling.

    PubMed

    Grohs, P; Podglajen, I; Guerot, E; Bellenfant, F; Caumont-Prim, A; Kac, G; Tillecovidin, B; Carbonnelle, E; Chatellier, G; Meyer, G; Fagon, J Y; Gutmann, L

    2014-11-01

    There is no consensus on optimal screening procedures for multidrug-resistant Enterobacteriaceae (MDRE) in intensive care units (ICUs). Therefore, we assessed five strategies for the detection of extended-spectrum beta-lactamase (ESBL) and high-level expressed AmpC cephalosporinase (HL-CASE) producers. During a 3-month period, a rectal screening swab sample was collected daily from every ICU patient, from the first 24 h to the last day of ICU stay. Samples were plated on MDRE-selective media. Bacteria were identified using MALDI-TOF mass spectrometry and antibiograms were performed using disk diffusion. MDREs were isolated from 682/2348 (29.0%) screening samples collected from 93/269 (34.6%) patients. Incidences of patients with ESBL and HL-CASE producers were 17.8 and 19.3 per 100 admissions, respectively. In 48/93 patients, MDRE carriage was intermittent. Compared with systematic screening at admission, systematic screening at discharge did not significantly increase the rate of MDRE detection among the 93 patients (62% vs. 70%). In contrast, screening at admission and discharge, screening at admission and weekly thereafter, and screening at admission and weekly thereafter and at discharge significantly increased MDRE detection (77%, p 0.02; 76%, p 0.01; 86%, p<0.001, respectively). The difference in MDRE detection between these strategies relies essentially on the levels of detection of patients with HL-CASE producers. The most reasonable strategy would be to collect two samples, one at admission and one at discharge, which would detect 87.5% of the ESBL strains, 67.3% of the HL-CASE strains and 77.4% of all MDRE strains. This study should facilitate decision-making concerning the most suitable screening policy for MDRE detection in a given ICU setting. PMID:24807791

  15. Early antibiotic treatment and later asthma.

    PubMed

    Wjst, M; Hoelscher, B; Frye, C; Wichmann, H E; Dold, S; Heinrich, J

    2001-06-28

    The reasons for the asthma epidemic are poorly understood. As the asthma prevalence follows the geographical and temporal trend of antibiotic use into clinical medicine, we examined a possible association in a population-based study of 2,512 children age 5-14 in East Germany. Wheezing was associated with increasing number of antibiotic courses (never versus one time odds ratio 1.9, P = 0.012, 2 to 5 times odds ratio 3.0, P<0.001 and more than 5 times, odds ratio 6.9, P<0.001) which was also seen for asthma diagnosis. The risk increased with earlier administration (never versus second year odds ratio 4.6, month 7-12 odds ratio 5.4 and birth until month 6 odds ratio 7.9, all P<0.001). Also non pulmonary treatment indication was associated with later wheezing (odds ratio 3.9, P<0.001). The most likely possible explanation is reverse causation indicating that frequent upper respiratory infections, an early symptom of asthma, are treated with antibiotics. Antibiotic therapy could also be a proxy of another closely associated genetic or environmental factor. The high dose effect, the time dependency of the administration and the effect by non-pulmonary indications raises the possibility that early antibiotic treatment could itself be related to later asthma. PMID:11432798

  16. [Pharmacokinetic and pharmacodynamic aspects in antibiotic treatment].

    PubMed

    Bellmann, R

    2014-04-01

    Severe sepsis and septic shock have a high mortality and, therefore require fast and effective antibiotic treatment with low toxicity. Because of sepsis-induced pathophysiological changes, pharmacokinetics of antimicrobial agents can be altered. Particularly water-soluble drugs display an enhanced volume of distribution during early sepsis. Therefore high loading doses are necessary. Renal clearance can also be increased at this time. Later on, organ damage frequently occurs resulting in delayed drug elimination which requires further dose adjustment. The different classes of antibiotics differ in their relevant pharmacokinetic-pharmacodynamic target parameters. Thus, the efficacy of an antimicrobial agent can depend on its concentration, on the exposure time, and on the total exposure as expressed by the area under the time-concentration curve. During treatment with time-dependent antibiotics (e.g. ?-lactams), their concentration should be maintained above the minimal inhibitory concentration (MIC) warranting more frequent administration or continuous infusion. For concentration dependent agents (e.g. aminoglycosides), the single dose is pivotal, whereas the dosage interval can be extended. Drug-drug interactions involving antibiotics are mainly caused by inhibition of their metabolism, particularly of cytochrome P 450 iso-enzymes, or by additive toxic effects. They can result in severe complications such as renal failure or ventricular arrhythmias. Conversely, enzyme induction may lead to subtherapeutic drug levels. When continuous renal replacement therapy is required, the dosage of antibiotics has to be adapted according to the results of respective pharmacokinetic studies. PMID:24643839

  17. The Biogeography of Putative Microbial Antibiotic Production.

    PubMed

    Morlon, Hélène; O'Connor, Timothy K; Bryant, Jessica A; Charkoudian, Louise K; Docherty, Kathryn M; Jones, Evan; Kembel, Steven W; Green, Jessica L; Bohannan, Brendan J M

    2015-01-01

    Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

  18. Antibiotic prophylaxis in primary immune deficiency disorders.

    PubMed

    Kuruvilla, Merin; de la Morena, Maria Teresa

    2013-01-01

    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options. PMID:24565703

  19. Antibiotic resistance: are we all doomed?

    PubMed

    Collignon, P

    2015-11-01

    Antibiotic resistance is a growing and worrying problem associated with increased deaths and suffering for people. Overall, there are only two factors that drive antimicrobial resistance, and both can be controlled. These factors are the volumes of antimicrobials used and the spread of resistant micro-organisms and/or the genes encoding for resistance. The One Health concept is important if we want to understand better and control antimicrobial resistance. There are many things we can do to better control antimicrobial resistance. We need to prevent infections. We need to have better surveillance with good data on usage patterns and resistance patterns available across all sectors, both human and agriculture, locally and internationally. We need to act on these results when we see either inappropriate usage or resistance levels rising in bacteria that are of concern for people. We need to ensure that food and water sources do not spread multi-resistant micro-organisms or resistance genes. We need better approaches to restrict successfully what and how antibiotics are used in people. We need to restrict the use of 'critically important' antibiotics in food animals and the entry of these drugs into the environment. We need to ensure that 'One Health' concept is not just a buzz word but implemented. We need to look at all sectors and control not only antibiotic use but also the spread and development of antibiotic resistant bacteria - both locally and internationally. PMID:26563691

  20. The Biogeography of Putative Microbial Antibiotic Production

    PubMed Central

    Bryant, Jessica A.; Charkoudian, Louise K.; Docherty, Kathryn M.; Jones, Evan; Kembel, Steven W.; Green, Jessica L.; Bohannan, Brendan J. M.

    2015-01-01

    Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics. PMID:26102275

  1. Antibiotic dose optimization in critically ill patients.

    PubMed

    Cotta, M O; Roberts, J A; Lipman, J

    2015-12-01

    The judicious use of existing antibiotics is essential for preserving their activity against infections. In the era of multi-drug resistance, this is of particular importance in clinical areas characterized by high antibiotic use, such as the ICU. Antibiotic dose optimization in critically ill patients requires sound knowledge not only of the altered physiology in serious infections - including severe sepsis, septic shock and ventilator-associated pneumonia - but also of the pathogen-drug exposure relationship (i.e. pharmacokinetic/pharmacodynamic index). An important consideration is the fact that extreme shifts in organ function, such as those seen in hyperdynamic patients or those with multiple organ dysfunction syndrome, can have an impact upon drug exposure, and constant vigilance is required when reviewing antibiotic dosing regimens in the critically ill. The use of continuous renal replacement therapy and extracorporeal membrane oxygenation remain important interventions in these patients; however, both of these treatments can have a profound effect on antibiotic exposure. We suggest placing emphasis on the use of therapeutic drug monitoring and dose individualization when optimizing therapy in these settings. PMID:26415688

  2. Mobile Display of Information about Aggregated Antibiotic Resistance in the Hospital Setting Supported by Near Field Communication.

    PubMed

    Meng, Philipp; Fehre, Karsten; Rappelsberger, Andrea; Adlassnig, Klaus-Peter

    2014-01-01

    Antibiotic resistance is a heterogeneous phenomenon. It does not only differ between countries or states, but also between wards of hospitals, where different resistance patterns have been found. To support clinicians in administering empiric antibiotic therapy, we developed software to present information about antibiotic resistance using a mobile concept. A pre-existing infrastructure was deployed as the server component. The systems analyze and aggregate data from laboratory information systems, generating statistical data on antibiotic resistance. The information is presented to the Android client using a Representational State Transfer (REST) interface. Geographical localization is performed using near field communication (NFC) tags. The prototype provides tabulated data concerning antibiotic resistance patterns in the wards of a hospital. Using Android, NFC, and data caching, the usability of the system is estimated to be high. We hypothesize that antibiotic stewardship in hospitals can be supported by this software, thus improving medical monitoring of antibiotic resistance. Future studies in a productive environment are needed to measure the impact of the system on the outcome of patient care. PMID:24851968

  3. Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

    NASA Astrophysics Data System (ADS)

    Surawicz, Christina M.

    Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

  4. Do human extraintestinal Escherichia coli infections resistant to expanded-spectrum cephalosporins originate from food-producing animals? A systematic review.

    PubMed

    Lazarus, Benjamin; Paterson, David L; Mollinger, Joanne L; Rogers, Benjamin A

    2015-02-01

    To find out whether food-producing animals (FPAs) are a source of extraintestinal expanded-spectrum cephalosporin-resistant Escherichia coli (ESCR-EC) infections in humans, Medline, Embase, and the Cochrane Database of Systematic Reviews were systematically reviewed. Thirty-four original, peer-reviewed publications were identified for inclusion. Six molecular epidemiology studies supported the transfer of resistance via whole bacterium transmission (WBT), which was best characterized among poultry in the Netherlands. Thirteen molecular epidemiology studies supported transmission of resistance via mobile genetic elements, which demonstrated greater diversity of geography and host FPA. Seventeen molecular epidemiology studies did not support WBT and two did not support mobile genetic element-mediated transmission. Four observational epidemiology studies were consistent with zoonotic transmission. Overall, there is evidence that a proportion of human extraintestinal ESCR-EC infections originate from FPAs. Poultry, in particular, is probably a source, but the quantitative and geographical extent of the problem is unclear and requires further investigation. PMID:25301206

  5. Fluorogenic Probes with Substitutions at the 2 and 7 Positions of Cephalosporin are Highly BlaC-Specific for Rapid Mycobacterium tuberculosis Detection**

    PubMed Central

    Cheng, Yunfeng; Xie, Hexin; Sule, Preeti; Hassounah, Hany; Graviss, Edward A; Kong, Ying; Cirillo, Jeffrey D; Rao, Jianghong

    2014-01-01

    Current methods for the detection of Mycobacterium tuberculosis (Mtb) are either time consuming or require expensive instruments and are thus are not suitable for point-of-care diagnosis. The design, synthesis, and evaluation of fluorogenic probes with high specificity for BlaC, a biomarker expressed by Mtb, are described. The fluorogenic probe CDG-3 is based on cephalosporin with substitutions at the 2 and 7?positions and it demonstrates over 120?000-fold selectivity for BlaC over TEM-1 Bla, the most common ?-lactamase. CDG-3 can detect 10 colony-forming units of the attenuated Mycobacterium bovis strain BCG in human sputum in the presence of high levels of contaminating ?-lactamases expressed by other clinically prevalent bacterial strains. In a trial with 50 clinical samples, CDG-3 detected tuberculosis with 90?% sensitivity and 73?% specificity relative to Mtb culture within one hour, thus demonstrating its potential as a low-cost point-of-care test for use in resource-limited areas. PMID:24989449

  6. tRNAs as Antibiotic Targets

    PubMed Central

    Chopra, Shaileja; Reader, John

    2014-01-01

    Transfer RNAs (tRNAs) are central players in the protein translation machinery and as such are prominent targets for a large number of natural and synthetic antibiotics. This review focuses on the role of tRNAs in bacterial antibiosis. We will discuss examples of antibiotics that target multiple stages in tRNA biology from tRNA biogenesis and modification, mature tRNAs, aminoacylation of tRNA as well as prevention of proper tRNA function by small molecules binding to the ribosome. Finally, the role of deacylated tRNAs in the bacterial “stringent response” mechanism that can lead to bacteria displaying antibiotic persistence phenotypes will be discussed. PMID:25547494

  7. The fitness costs of antibiotic resistance mutations

    PubMed Central

    Melnyk, Anita H; Wong, Alex; Kassen, Rees

    2015-01-01

    Antibiotic resistance is increasing in pathogenic microbial populations and is thus a major threat to public health. The fate of a resistance mutation in pathogen populations is determined in part by its fitness. Mutations that suffer little or no fitness cost are more likely to persist in the absence of antibiotic treatment. In this review, we performed a meta-analysis to investigate the fitness costs associated with single mutational events that confer resistance. Generally, these mutations were costly, although several drug classes and species of bacteria on average did not show a cost. Further investigations into the rate and fitness values of compensatory mutations that alleviate the costs of resistance will help us to better understand both the emergence and management of antibiotic resistance in clinical settings. PMID:25861385

  8. [Therapeutic monitoring of antibiotics: New methodologies: biosensors].

    PubMed

    Soto, Dagoberto; Silva, Camila; Andresen V, Max; Soto, Natalia; Wong, Kwok-Yin; Andresen, Max

    2015-08-01

    The pharmacokinetics of antibiotics, especially in severely ill patients, may be profoundly altered due to multiple pathophysiological changes. Recent studies have shown that empiric dosing recommendations for ICU patients are inadequate to effectively treat a broad range of susceptible organisms and need to be reconsidered. Therapeutic drug monitoring (TDM) is an important mean for optimizing drug utilization and doses for the purpose of improving the clinical effectiveness. However, it is very challenging to quantify plasma antibiotic concentrations in clinical situations as a routine practice, because of the high costs and complexities associated with advanced instrumental techniques. Currently there are not routine and low cost methods to determine the presence and concentration of ?-lactam antibiotics in plasma patients in a clinical setup. Indeed, such analytical methods are based on chromatographic techniques mainly used in research. Here we describe and comment different techniques, focusing on our preliminary experience using biosensors. PMID:26436935

  9. Treatment with antibiotics that interfere with peptidoglycan biosynthesis inhibits chloroplast division in the desmid Closterium.

    PubMed

    Matsumoto, Hiroko; Takechi, Katsuaki; Sato, Hiroshi; Takio, Susumu; Takano, Hiroyoshi

    2012-01-01

    Charophytes is a green algal group closely related to land plants. We investigated the effects of antibiotics that interfere with peptidoglycan biosynthesis on chloroplast division in the desmid Closterium peracerosum-strigosum-littorale complex. To detect cells just after division, we used colchicine, which inhibits Closterium cell elongation after division. Although normal Closterium cells had two chloroplasts before and after cell division, cells treated with ampicillin, D-cycloserine, or fosfomycin had only one chloroplast after cell division, suggesting that the cells divided without chloroplast division. The antibiotics bacitracin and vancomycin showed no obvious effect. Electron microscopic observation showed that irregular-shaped chloroplasts existed in ampicillin-treated Closterium cells. Because antibiotic treatments resulted in the appearance of long cells with irregular chloroplasts and cell death, we counted cell types in the culture. The results suggested that cells with one chloroplast appeared first and then a huge chloroplast was generated that inhibited cell division, causing elongation followed by cell death. PMID:22815801

  10. Incentives for new antibiotics: the Options Market for Antibiotics (OMA) model

    PubMed Central

    2013-01-01

    Background Antimicrobial resistance is a growing threat resulting from the convergence of biological, economic and political pressures. Investment in research and development of new antimicrobials has suffered secondary to these pressures, leading to an emerging crisis in antibiotic resistance. Methods Current policies to stimulate antibiotic development have proven inadequate to overcome market failures. Therefore innovative ideas utilizing market forces are necessary to stimulate new investment efforts. Employing the benefits of both the previously described Advanced Market Commitment and a refined Call Options for Vaccines model, we describe herein a novel incentive mechanism, the Options Market for Antibiotics. Results This model applies the benefits of a financial call option to the investment in and purchase of new antibiotics. The goal of this new model is to provide an effective mechanism for early investment and risk sharing while maintaining a credible purchase commitment and incentives for companies to ultimately bring new antibiotics to market. Conclusions We believe that the Options Market for Antibiotics (OMA) may help to overcome some of the traditional market failures associated with the development of new antibiotics. Additional work must be done to develop a more robust mathematical model to pave the way for practical implementation. PMID:24199835

  11. Sensitivity of antibiotic resistant and antibiotic susceptible Escherichia coli, Enterococcus and Staphylococcus strains against ozone.

    PubMed

    Heß, Stefanie; Gallert, Claudia

    2015-12-01

    Tolerance of antibiotic susceptible and antibiotic resistant Escherichia coli, Enterococcus and Staphylococcus strains from clinical and wastewater samples against ozone was tested to investigate if ozone, a strong oxidant applied for advanced wastewater treatment, will affect the release of antibiotic resistant bacteria into the aquatic environment. For this purpose, the resistance pattern against antibiotics of the mentioned isolates and their survival after exposure to 4 mg/L ozone was determined. Antibiotic resistance (AR) of the isolates was not correlating with higher tolerance against ozone. Except for ampicillin resistant E. coli strains, which showed a trend towards increased resistance, E. coli strains that were also resistant against cotrimoxazol, ciprofloxacin or a combination of the three antibiotics were similarly or less resistant against ozone than antibiotic sensitive strains. Pigment-producing Enterococcus casseliflavus and Staphylococcus aureus seemed to be more resistant against ozone than non-pigmented species of these genera. Furthermore, aggregation or biofilm formation apparently protected bacteria in subsurface layers from inactivation by ozone. The relatively large variance of tolerance against ozone may indicate that resistance to ozone inactivation most probably depends on several factors, where AR, if at all, does not play a major role. PMID:26608763

  12. Triple antibiotic paste in root canal therapy

    PubMed Central

    Vijayaraghavan, Rangasamy; Mathian, Veerabathran Mahesh; Sundaram, Alagappan Meenakshi; Karunakaran, Ramachandran; Vinodh, Selvaraj

    2012-01-01

    The success of the endodontic treatment depends on the microbial suppression in the root canal and periapical region. Endodontic instrumentation alone cannot achieve a sterile condition. With the advent of non-instrumentation endodontic treatment and lesion sterilization and tissue repair, local application of antibiotics has been investigated. Triple antibiotic paste (TAP) containing metronidazole, ciprofloxacin, and minocycline has been reported to be a successful regimen in controlling the root canal pathogen and in managing non-vital young permanent tooth. This paper reviews the existing literature on biocompatibility, efficiency, drawbacks of TAP in endodontic therapy and pulp revascularization. PMID:23066258

  13. Revolutionising bacteriology to improve treatment outcomes and antibiotic stewardship.

    PubMed

    Livermore, David M; Wain, John

    2013-03-01

    LABORATORY INVESTIGATION OF BACTERIAL INFECTIONS GENERALLY TAKES TWO DAYS: one to grow the bacteria and another to identify them and to test their susceptibility. Meanwhile the patient is treated empirically, based on likely pathogens and local resistance rates. Many patients are over-treated to prevent under-treatment of a few, compromising antibiotic stewardship. Molecular diagnostics have potential to improve this situation by accelerating precise diagnoses and the early refinement of antibiotic therapy. They include: (i) the use of 'biomarkers' to swiftly distinguish patients with bacterial infection, and (ii) molecular bacteriology to identify pathogens and their resistance genes in clinical specimens, without culture. Biomarker interest centres on procalcitonin, which has given good results particularly for pneumonias, though broader biomarker arrays may prove superior in the future. PCRs already are widely used to diagnose a few infections (e.g. tuberculosis) whilst multiplexes are becoming available for bacteraemia, pneumonia and gastrointestinal infection. These detect likely pathogens, but are not comprehensive, particularly for resistance genes; there is also the challenge of linking pathogens and resistance genes when multiple organisms are present in a sample. Next-generation sequencing offers more comprehensive profiling, but obstacles include sensitivity when the bacterial load is low, as in bacteraemia, and the imperfect correlation of genotype and phenotype. In short, rapid molecular bacteriology presents great potential to improve patient treatments and antibiotic stewardship but faces many technical challenges; moreover it runs counter to the current nostrum of defining resistance in pharmacodynamic terms, rather than by the presence of a mechanism, and the policy of centralising bacteriology services. PMID:24265945

  14. Revolutionising Bacteriology to Improve Treatment Outcomes and Antibiotic Stewardship

    PubMed Central

    Livermore, David M

    2013-01-01

    Laboratory investigation of bacterial infections generally takes two days: one to grow the bacteria and another to identify them and to test their susceptibility. Meanwhile the patient is treated empirically, based on likely pathogens and local resistance rates. Many patients are over-treated to prevent under-treatment of a few, compromising antibiotic stewardship. Molecular diagnostics have potential to improve this situation by accelerating precise diagnoses and the early refinement of antibiotic therapy. They include: (i) the use of 'biomarkers' to swiftly distinguish patients with bacterial infection, and (ii) molecular bacteriology to identify pathogens and their resistance genes in clinical specimens, without culture. Biomarker interest centres on procalcitonin, which has given good results particularly for pneumonias, though broader biomarker arrays may prove superior in the future. PCRs already are widely used to diagnose a few infections (e.g. tuberculosis) whilst multiplexes are becoming available for bacteraemia, pneumonia and gastrointestinal infection. These detect likely pathogens, but are not comprehensive, particularly for resistance genes; there is also the challenge of linking pathogens and resistance genes when multiple organisms are present in a sample. Next-generation sequencing offers more comprehensive profiling, but obstacles include sensitivity when the bacterial load is low, as in bacteraemia, and the imperfect correlation of genotype and phenotype. In short, rapid molecular bacteriology presents great potential to improve patient treatments and antibiotic stewardship but faces many technical challenges; moreover it runs counter to the current nostrum of defining resistance in pharmacodynamic terms, rather than by the presence of a mechanism, and the policy of centralising bacteriology services. PMID:24265945

  15. Antibiotic resistance gene discovery in food-producing animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous environmental reservoirs contribute to the widespread antibiotic resistance problem in human pathogens. One environmental reservoir of particular importance is the intestinal bacteria of food-producing animals. In this review I examine recent discoveries of antibiotic resistance genes in ...

  16. Many Patients with Acne Take Antibiotics Too Long

    MedlinePLUS

    ... medlineplus/news/fullstory_155447.html Many Patients With Acne Take Antibiotics Too Long: Study Prescription Accutane can ... 30, 2015 (HealthDay News) -- Many patients with severe acne remain on antibiotics too long before they are ...

  17. Engineering Synthetic Bacteriophage to Combat Antibiotic-Resistant Bacteria

    E-print Network

    Lu, Timothy Kuan-Ta

    Antibiotic resistance is a rapidly evolving problem that is not being adequately met by new antimicrobial drugs. Thus, there is a pressing need for effective antibacterial therapies that can be adapted against antibiotic-resistant ...

  18. Get Smart: Know When Antibiotics Work - Symptom Relief

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  19. Get Smart: Know When Antibiotics Work - Influenza (Flu)

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  20. Get Smart: Know When Antibiotics Work - Sore Throat

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  1. Get Smart: Know When Antibiotics Work - What You Can Do

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  2. Get Smart: Know When Antibiotics Work - Urinary Tract Infection

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  3. Get Smart: Know When Antibiotics Work - Sinus Infection (Sinusitis)

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  4. Get Smart: Know When Antibiotics Work - Bronchitis (Chest Cold)

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  5. Get Smart: Know When Antibiotics Work - Ear Infections

    MedlinePLUS

    ... Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not supported ... Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews of Outpatient Stewardship Audit and Feedback ...

  6. Combating biofilms and antibiotic resistance using synthetic biology

    E-print Network

    Lu, Timothy K. (Timothy Kuan-Ta), 1981-

    2008-01-01

    Bacterial infections represent a significant source of morbidity and mortality. Biofilms and antibiotic resistance pose challenges to our future ability to treat bacterial diseases with antibiotics (1). Bacteria frequently ...

  7. CURRENT ISSUES REGARDING ENDOCRINE DISRUPTING CHEMICALS AND ANTIBIOTIC RESISTANCE

    EPA Science Inventory

    Recently public concern has increased regarding industrial and environmental substances that may have adverse hormonal effects in human and wildlife populations. This concern has also been expanded to include antibiotic-resistant bacteria and the presence of various antibiotics a...

  8. Widely Used Antibiotics May Raise Heart Risks, Review Finds

    MedlinePLUS

    ... gov/medlineplus/news/fullstory_155614.html Widely Used Antibiotics May Raise Heart Risks, Review Finds Macrolides were ... 2015 (HealthDay News) -- A widely used class of antibiotics is associated with a small but measurable increased ...

  9. Cooperative Antibiotic Resistance in a Multi-Drug Environment

    NASA Astrophysics Data System (ADS)

    Yurtsev, Eugene; Dai, Lei; Gore, Jeff

    2013-03-01

    The emergence of antibiotic resistance in bacteria is a significant health concern. A frequent mechanism of antibiotic resistance involves the production of an enzyme which inactivates the antibiotic. By inactivating the antibiotic, resistant cells can ``share'' their resistance with other cells in the bacterial population, suggesting that it may be possible to observe cooperation between strains that inactivate different antibiotics. Here, we experimentally track the population dynamics of two E. coli strains in the presence of two different antibiotics. We find that together the strains are able to grow in antibiotic concentrations that inhibit growth of either of the strains individually. We observe that even when there is stable coexistence between the two strains, the population size of each strain can undergo large oscillations. We expect that our results will provide insight into the evolution of antibiotic resistance and the evolutionary origin of phenotypic diversity and cooperative behaviors.

  10. Antibiotic-containing polymers for localized, sustained drug delivery

    PubMed Central

    Stebbins, Nicholas D.; Ouimet, Michelle A.; Uhrich, Kathryn E.

    2014-01-01

    Many currently used antibiotics suffer from issues such as systemic toxicity, short half-life, and increased susceptibility to bacterial resistance. Although most antibiotic classes are administered systemically through oral or intravenous routes, a more efficient delivery system is needed. This review discusses the chemical conjugation of antibiotics to polymers, achieved by forming covalent bonds between antibiotics and a pre-existing polymer or by developing novel antibiotic-containing polymers. Through conjugating antibiotics to polymers, unique polymer properties can be taken advantage of. These polymeric antibiotics display controlled, sustained drug release and vary in antibiotic class type, synthetic method, polymer composition, bond lability, and antibacterial activity. The polymer synthesis, characterization, drug release, and antibacterial activities, if applicable, will be presented to offer a detailed overview of each system. PMID:24751888

  11. Isolated cell behavior drives the evolution of antibiotic resistance

    E-print Network

    Artemova, Tatiana

    Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard ...

  12. Scientists Spot Gene That Could Make Bacteria Resistant to All Antibiotics

    MedlinePLUS

    ... Health News on: Antibiotic Resistance Antibiotics Genes and Gene Therapy Recent Health News Related MedlinePlus Health Topics Antibiotic Resistance Antibiotics Genes and Gene Therapy About MedlinePlus Site Map FAQs Contact Us Get ...

  13. Editorial overview: Antimicrobials: Grappling with the complexities of antibiotics and resistance

    E-print Network

    Collins, James J.

    Editorial overview: Antimicrobials: Grappling with the complexities of antibiotics and resistance. The increasing incidence of antibiotic-resistant infections coupled with a declining antibiotic pipeline and other lethal stresses. Resistance to antibiotics is acquired either vertically through de novo mutations

  14. Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage

    E-print Network

    Suresh, Subra

    Article Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage Graphical Abstract Highlights d Diverse bactericidal antibiotics induced similar metabolic changes d Bactericidal antibiotics induced biomarkers of oxidative stress d Bactericidal antibiotics induced dsDNA breaks

  15. Antibiotics induce redox-related physiological alterations as part of their lethality

    E-print Network

    Collins, James J.

    Antibiotics induce redox-related physiological alterations as part of their lethality Daniel J 30, 2014) Deeper understanding of antibiotic-induced physiological responses is critical to identifying means for enhancing our current antibiotic arsenal. Bactericidal antibiotics with diverse targets

  16. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis

    PubMed Central

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-01-01

    The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor ?. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy. PMID:23123626

  17. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis.

    PubMed

    Szkudlarek-Mikho, Maria; Saunders, Rudel A; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-11-30

    The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor ?. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy. PMID:23123626

  18. ANTIBIOTIC RESISTANCE IN HUMANS AND FEED ANIMALS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Few issues evoke as much discussion and disagreement as the use or misuse of antibiotics in feed animal production systems. Increased concern over the development of antimicrobial resistance in human bacterial pathogens that are also carried by feed animals has led many public health and medical pro...

  19. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    SciTech Connect

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  20. Physics and the Production of Antibiotics: 2

    ERIC Educational Resources Information Center

    Fairbrother, Robert; Riddle, Wendy; Fairbrother, Neil

    2006-01-01

    In an article in the preceding issue we discussed the design and construction of fermenters in which antibiotics are cultured. For industrial purposes these fermenters can range in size up to 500 m[cube]. They have to be sterilized, filled with sterile culture medium and the culture itself and supplied with oxygen continuously. In some cases they…

  1. RIFAMPICIN: an antibiotic with brain protective function.

    PubMed

    Yulug, Burak; Hanoglu, Lütfü; Kilic, Ertugrul; Schabitz, Wolf Rüdiger

    2014-08-01

    Besides its well known antibiotic activity rifampicin exerts multiple brain protective functions in acute cerebral ischemia and chronic neurodegeneration. The present mini-review gives an update of the unique activity of rifampicin in different diseases including Parkinson's disease, meningitis, stroke, Alzheimer's disease and optic nerve injury. PMID:24905548

  2. Fast measurement of bacterial susceptibility to antibiotics

    NASA Technical Reports Server (NTRS)

    Chappelle, E. W.; Picciolo, G. L.; Schrock, C. G.

    1977-01-01

    Method, based on photoanalysis of adenosine triphosphate using light-emitting reaction with luciferase-luciferin technique, saves time by eliminating isolation period required by conventional methods. Technique is also used to determine presence of infection as well as susceptibilities to several antibiotics.

  3. Audiological Management of Patients Receiving Aminoglycoside Antibiotics

    ERIC Educational Resources Information Center

    Konrad-Martin, Dawn; Wilmington, Debra J.; Gordon, Jane S.; Reavis, Kelly M.; Fausti, Stephen A.

    2005-01-01

    Aminoglycoside antibiotics, commonly prescribed for adults and children to treat a wide range of bacterial infections, are potentially ototoxic, often causing irreversible damage to the auditory and vestibular systems. Ototoxic hearing loss usually begins at the higher frequencies and can progress to lower frequencies necessary for understanding…

  4. Rapid Antibiotic Resistance Evolution of GASP Mutants

    NASA Astrophysics Data System (ADS)

    Zhang, Qiucen; Kim, Hyunsung; Pourmand, Nader; Austin, Robert

    2012-02-01

    The GASP phenotype in bacteria is due to a mutation which enables the bacteria to grow under high stress conditions where other bacteria stop growing. We probe using our Death Galaxy microenvironment how rapidly the GASP mutant can evolve resistance to mutagenic antibiotics compared to wild-type bacteria, and explore the genomic landscape changes due to the evolution of resistance.

  5. Bioavailability of veterinary antibiotics in surface water

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Veterinary antibiotics are commonly used as feed additives in livestock production for growth promotion and disease prevention. These pharmaceuticals are often excreted by the livestock in urine and feces, and enter the environment via manure application. Little is known about the fate of veterinary...

  6. Multiplex De Novo Sequencing of Peptide Antibiotics

    PubMed Central

    Mohimani, Hosein; Liu, Wei-Ting; Yang, Yu-Liang; Gaudêncio, Susana P.; Fenical, William; Dorrestein, Pieter C.

    2011-01-01

    Abstract Proliferation of drug-resistant diseases raises the challenge of searching for new, more efficient antibiotics. Currently, some of the most effective antibiotics (i.e., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. The isolation and sequencing of cyclic peptide antibiotics, unlike the same activity with linear peptides, is time-consuming and error-prone. The dominant technique for sequencing cyclic peptides is nuclear magnetic resonance (NMR)–based and requires large amounts (milligrams) of purified materials that, for most compounds, are not possible to obtain. Given these facts, there is a need for new tools to sequence cyclic non-ribosomal peptides (NRPs) using picograms of material. Since nearly all cyclic NRPs are produced along with related analogs, we develop a mass spectrometry approach for sequencing all related peptides at once (in contrast to the existing approach that analyzes individual peptides). Our results suggest that instead of attempting to isolate and NMR-sequence the most abundant compound, one should acquire spectra of many related compounds and sequence all of them simultaneously using tandem mass spectrometry. We illustrate applications of this approach by sequencing new variants of cyclic peptide antibiotics from Bacillus brevis, as well as sequencing a previously unknown family of cyclic NRPs produced by marine bacteria. Supplementary Material is available online at www.liebertonline.com/cmb PMID:22035290

  7. Emergence of antibiotic resistance from multinucleated bacterial filaments

    PubMed Central

    Bos, Julia; Zhang, Qiucen; Vyawahare, Saurabh; Rogers, Elizabeth; Rosenberg, Susan M.; Austin, Robert H.

    2015-01-01

    Bacteria can rapidly evolve resistance to antibiotics via the SOS response, a state of high-activity DNA repair and mutagenesis. We explore here the first steps of this evolution in the bacterium Escherichia coli. Induction of the SOS response by the genotoxic antibiotic ciprofloxacin changes the E. coli rod shape into multichromosome-containing filaments. We show that at subminimal inhibitory concentrations of ciprofloxacin the bacterial filament divides asymmetrically repeatedly at the tip. Chromosome-containing buds are made that, if resistant, propagate nonfilamenting progeny with enhanced resistance to ciprofloxacin as the parent filament dies. We propose that the multinucleated filament creates an environmental niche where evolution can proceed via generation of improved mutant chromosomes due to the mutagenic SOS response and possible recombination of the new alleles between chromosomes. Our data provide a better understanding of the processes underlying the origin of resistance at the single-cell level and suggest an analogous role to the eukaryotic aneuploidy condition in cancer. PMID:25492931

  8. Treatment of urinary tract infections: selecting an appropriate broad-spectrum antibiotic for nosocomial infections.

    PubMed

    Sharifi, R; Geckler, R; Childs, S

    1996-06-24

    Clinical and in vitro data indicate that cefepime, a fourth-generation cephalosporin, may be a valuable addition in the treatment of serious infections. In this study, hospitalized patients with complicated and uncomplicated urinary tract infection (UTI), for which parenteral therapy was appropriate, were enrolled in a 2:1 ratio open, randomized trial comparing the efficacy and safety of cefepime and ceftazidime. A total of 180 patients, including 6 with concurrent bacteremia, were evaluated for their response to cefepime (n = 118) or ceftazidime (n = 62), both of which were administered by intravenous infusion or intramuscular injection in doses of 500 mg every 12 hours. In cases of complicated UTI, cefepime produced a satisfactory clinical response in 83 of 93 (89%) patients and eradicated 83 of 98 (85%) pathogens. A satisfactory clinical response to ceftazidime was experienced by 43 of 50 (86%) patients; and in 39 of 50 (78%) cases pathogens were eradicated. In uncomplicated cases, the clinical response and bacterial eradication rates for cefepime were 23 of 25 (92%) and 22 of 26 (85%), respectively, and for ceftazidime 12 of 12 (100%) and 11 of 12 (92%). Of the 6 patients with concomitant bacteremia, 5 received cefepime and 1, ceftazidime. The infecting organisms, Escherichia coli and Proteus mirabilis, were eradicated in all cases, although one cefepime-treated patient had an unsatisfactory clinical response. The most common adverse events in both groups were headache, diarrhea, and vomiting; most events were unrelated to therapy. Adverse events forced only a 2% withdrawal of patients in either group. There was local tolerance to both agents, and abnormalities in laboratory values were judged to be clinically insignificant. The results of this study indicate that cefepime can be used safely and successfully to treat both complicated and uncomplicated nosocomial infection of the urinary tract, including cases associated with concurrent bacteremia. Moreover, its safety profile appears comparable to those of other cephalosporins, and local tolerance is similar to that of ceftazidime. No patient in either group required discontinuation of therapy because of local intolerance at the infusion or injection site. PMID:8678101

  9. Identification of Multiresistant Salmonella Capable of Subsisting on Antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study assessed the ability of Salmonella (572 isolates) to subsist on 12 different antibiotics. The majority (11/12) of the antibiotics provided subsistence to at least one of 140 isolates while 40 of these isolates displayed the ability to subsist on more than one antibiotic. This is the fir...

  10. Collateral effects of antibiotics on mammalian gut microbiomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics are an essential component of the modern lifestyle. They improve our lives by treating disease, preventing disease, and in the case of agricultural animals by improving feed efficiency. However, antibiotic usage is not without collateral effects. The development and spread of antibiot...

  11. Antibiotic efficacy is linked to bacterial cellular respiration

    PubMed Central

    Lobritz, Michael A.; Belenky, Peter; Porter, Caroline B. M.; Gutierrez, Arnaud; Yang, Jason H.; Schwarz, Eric G.; Dwyer, Daniel J.; Khalil, Ahmad S.; Collins, James J.

    2015-01-01

    Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes—the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy. PMID:26100898

  12. Trends in Antibiotic Resistance Genes Occurrence in the Haihe

    E-print Network

    Alvarez, Pedro J.

    Trends in Antibiotic Resistance Genes Occurrence in the Haihe River, China Y I L U O , D A Q I N G and antibiotic resistance genes (ARGs) was quantified in water and sediment samples collected from a 72 km-5). These antibiotics may exert selective pressure for resistant bacteria (6, 7), which is a major public health concern

  13. The epidemiology of antibiotic resistance in hospitals: Paradoxes and prescriptions

    E-print Network

    Grünbaum, Daniel

    The epidemiology of antibiotic resistance in hospitals: Paradoxes and prescriptions Marc Lipsitch of an antibiotic for which resistance is not yet present in a hospital will be positively associated at the individual level (odds ratio) with carriage of bacteria resistant to other antibiotics, but negatively

  14. Antibiotic interactions that select against resistance Remy Chait1

    E-print Network

    Kishony, Roy

    LETTERS Antibiotic interactions that select against resistance Remy Chait1 , Allison Craney1 & Roy Kishony1,2 Multidrug combinations are increasingly important in combating the spread of antibiotic-resistance resistance and the alarming slowdown in development of new antibiotics is spurring attention towards

  15. Analysis of Antibiotic Resistant Genes in Aquacultural Bacteria

    E-print Network

    Kane, Andrew S.

    1 Analysis of Antibiotic Resistant Genes in Aquacultural Bacteria JY Wang* YJ Geng RX Wang J Feng resistance genes Su1II of Vibrio harveyi contents #12;2 Introduction 1. present status · Antibiotics transfer among different bacteria · Resistant bacteria transfer to human · Antibiotic agents residue human

  16. 1810 Brief Communication Phenotypic switching of antibiotic resistance circumvents

    E-print Network

    Buckling, Angus

    1810 Brief Communication Phenotypic switching of antibiotic resistance circumvents permanent costs in Staphylococcus aureus Ruth C. Massey*, Angus Buckling and Sharon J. Peacock* Bacterial antibiotic resistance to be resistant to which suggests that S. aureus has evolved an antibiotic cure, manifested by persistence

  17. Structural basis for cross-resistance to ribosomal PTC antibiotics

    E-print Network

    Yonath, Ada E.

    Structural basis for cross-resistance to ribosomal PTC antibiotics Chen Davidovich, Anat Bashan BY THE AUTHORS #12;Structural basis for cross-resistance to ribosomal PTC antibiotics Chen Davidovich, Anat trigger modulations of the shape of the anti- biotic binding pocket. Resistance to these antibiotics

  18. Ribosomal antibiotics: structural basis for resistance, synergism and

    E-print Network

    Yonath, Ada E.

    Ribosomal antibiotics: structural basis for resistance, synergism and selectivity Tamar Auerbach, Israel Various antibiotics bind to ribosomes at functionally relevant locations such as the peptidyl-transferase center (PTC) and the exit tunnel for nascent proteins. High-resolution structures of antibiotics bound

  19. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  20. Demonstrating Effectiveness of Antibiotics Against Known Bacteria Strains

    ERIC Educational Resources Information Center

    Keefe, Lois M.

    1977-01-01

    Procedures are described for showing the effectiveness of antibiotics (penicillin, ampicillin, and tetracycline) against a nonpathogenic bacteria strain (Bacillus cereus). Methods are outlined for preparing nutrient agar, sterilizing tubes, pouring agar plates, preparing antibiotic discs, and transferring antibiotic discs to agar plates. (CS)

  1. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  2. Imaging peptidoglycan biosynthesis in Bacillus subtilis with fluorescent antibiotics

    E-print Network

    Rudner, David

    Imaging peptidoglycan biosynthesis in Bacillus subtilis with fluorescent antibiotics Kittichoat that labeled antibiotics that bind to PG precursors may be useful for imaging PG to help determine the genes subtilis using fluorescent derivatives of two PG-binding antibiotics, vancomycin and ramoplanin

  3. A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics

    E-print Network

    Collins, James J.

    A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics Michael A. Kohanski,1 antibiotics, regardless of drug-target interaction, stimulate the produc- tion of highly deleterious hydroxyl that the mechanism of hydroxyl radical formation induced by bactericidal antibiotics is the end product

  4. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  5. Improving Antibiotic Therapy of Ventilator Associated Pneumonia using

    E-print Network

    Utrecht, Universiteit

    Improving Antibiotic Therapy of Ventilator Associated Pneumonia using a Probabilistic Approach­tree colonisation by pathogens, and symptoms and signs actually present in the patient. Optimal antibiotic therapy of providing advice about the administration of appropriate antibiotic therapy to patients with pneumonia

  6. Antibiotics have dramatically increased life expectancy by reducing

    E-print Network

    Langendoen, Koen

    Antibiotics have dramatically increased life expectancy by reducing mortality due to infectious diseases. Unfortunately, the spread of antibiotic resistance is a major threat to society. A team of TU Delft scientists succeeded in developing a method to produce novel antibiotics on an industrial scale

  7. A Robust Platform for the Synthesis of New Tetracycline Antibiotics

    E-print Network

    A Robust Platform for the Synthesis of New Tetracycline Antibiotics Cuixiang Sun, Qiu Wang, Jason D potent antibiotic activities, both in bacterial cell culture and in vivo. The platform for tetracycline for the discovery and, perhaps, development of new tetracycline antibiotics. Introduction In prior research we

  8. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  9. Modelling Antibiotic Production using Standard and Sequential Hybridised Symbolic Annealing

    E-print Network

    Fernandez, Thomas

    Modelling Antibiotic Production using Standard and Sequential Hybridised Symbolic Annealing Mark A and antibiotic concentrations of an industrial fermentation process. The models are developed using both for predicting the biomass and antibiotic concentrations of a fermentation process, which is based on Simulated

  10. Antibiotic Development DOI: 10.1002/anie.201310843

    E-print Network

    Antibiotic Development DOI: 10.1002/anie.201310843 The Evolving Role of Chemical Synthesis: antibiotics · chemical synthesis · drug discovery · semisynthesis .Angewandte Reviews A. G. Myers et al. 8840 antibiotics is a major public health concern and one of particular importance in clinical settings. The World

  11. Improving Antibiotic Therapy of Ventilator Associated Pneumonia using

    E-print Network

    Lucas, Peter

    Improving Antibiotic Therapy of Ventilator Associated Pneumonia using a Probabilistic Approach-tree colonisation by pathogens, and symptoms and signs actually present in the patient. Optimal antibiotic therapy of appropriate antibiotic therapy to patients with pneumonia. The aim of the development of this system

  12. Structural basis for the interaction of antibiotics with the peptidyl

    E-print Network

    Martin, Jan M.L.

    Structural basis for the interaction of antibiotics with the peptidyl transferase centre ............................................................................................................................................................................................................................................................................ Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely

  13. ORIGINAL ARTICLES Preoperative Antibiotics and Mortality in the Elderly

    E-print Network

    George, Edward I.

    ORIGINAL ARTICLES Preoperative Antibiotics and Mortality in the Elderly Jeffrey H. Silber, MD, Ph*§ Objective and Background: It is generally thought that the use of preoperative antibiotics reduces the risk of postoperative infection, yet few studies have described the association between preoperative antibiotics

  14. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false First aid antibiotic active ingredients. 333.110 Section 333.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  15. Antibiotic resistance in agricultural and non-agricultural settings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of antibiotics in animal agriculture is an issue that has captured national attention, with the primary concern being the transfer of antibiotic resistance from animals to humans via food or water. It has also been proposed that antibiotic resistance genes themselves be considered an enviro...

  16. Antibiotic efficacy is linked to bacterial cellular respiration

    E-print Network

    Napp, Nils

    Antibiotic efficacy is linked to bacterial cellular respiration Michael A. Lobritza,b,c,d,e,1 antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, sup- pression of cellular respiration

  17. In-feed antibiotic effects on the swine intestinal microbiome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 years. The impact of such antibiotic use on the treatment of human diseases is hotly debated. Based on metagenomic and qPCR analysis, we show that antibiotic resis...

  18. Antibiotic efficacy is linked to bacterial cellular respiration.

    PubMed

    Lobritz, Michael A; Belenky, Peter; Porter, Caroline B M; Gutierrez, Arnaud; Yang, Jason H; Schwarz, Eric G; Dwyer, Daniel J; Khalil, Ahmad S; Collins, James J

    2015-07-01

    Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes--the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy. PMID:26100898

  19. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    PubMed Central

    Investigators, The PARITY

    2015-01-01

    Objective Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. Methods We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. Results We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. Conclusions It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162 PMID:26423584

  20. Audit and Feedback of Antibiotic Use

    PubMed Central

    Baysari, M. T.; Oliver, K.; Egan, B.; Li, L.; Richardson, K.; Sandaradura, I.; Westbrook, J. I.; Day, R. O.

    2013-01-01

    Summary Background There is now little doubt that improving antimicrobial use is necessary for the containment of resistance. Objective To determine whether providing individualised feedback to doctors about their recent compliance with the hospital’s antibiotic policy improves compliance with the policy. Methods This study was conducted at a teaching hospital in Sydney, Australia. Computerised alerts integrated into the electronic prescribing system (ePS) inform prescribers of the local antibiotic policy. We utilised prescribing data extracted from the ePS for ‘audit and feedback’. Thirty-six prescribers were sent feedback letters via email. We also interviewed doctors who had received letters to explore their views of the feedback and the policy in general. Results There was no significant change in compliance with the policy following implementation of the feedback intervention (0% compliant vs 11.9%; p = 0.07). Several problems with the policy and the approval process were identified by researchers during auditing and by prescribers during interviews. Some problems identified made it difficult to accurately assess compliance and for doctors to comply with the policy. Conclusion Our intervention did not result in improved compliance with the antibiotic policy but revealed practical problems with the policy and approval process that had not been identified prior to the trial. Greater support for the policy by senior doctors and the assignment of more clearly defined roles and responsibilities associated with antibiotic use and approval may result in improved compliance. Harnessing the full potential of technology would streamline the antimicrobial approval process and allow more efficient and reliable monitoring of antibiotic use and compliance. Many of the problems we identified are generic issues of importance to all organisations seeking to integrate antimicrobial stewardship into ePS. PMID:24454584

  1. An antibiotic selection marker for schistosome transgenesis.

    PubMed

    Rinaldi, Gabriel; Suttiprapa, Sutas; Tort, José F; Folley, Anne E; Skinner, Danielle E; Brindley, Paul J

    2012-01-01

    Drug selection is widely used in transgene studies of microbial pathogens, mammalian cell and plant cell lines. Drug selection of transgenic schistosomes would be desirable to provide a means to enrich for populations of transgenic worms. We adapted murine leukaemia retrovirus vectors - widely used in human gene therapy research - to transduce schistosomes, leading to integration of transgenes into the genome of the blood fluke. A dose-response kill curve and lethal G418 (geneticin) concentrations were established: 125-1,000?g/ml G418 were progressively more toxic for schistosomules of Schistosoma mansoni with toxicity increasing with antibiotic concentration and with duration of exposure. By day 6 of exposure to ?500?g/ml, significantly fewer worms survived compared with non-exposed controls and by day 8, significantly fewer worms survived than controls at ?250?g/ml G418. When schistosomules were transduced with murine leukaemia retrovirus encoding the neomycin resistance (neoR) transgene and cultured in media containing G418, the neoR transgene rescued transgenic schistosomules from the antibiotic; by day 4 in 1,000?g/ml and by day 8 in 500?g/ml G418, significantly more transgenic worms survived the toxic effects of the antibiotic. More copies of neoR were detected per nanogram of genomic DNA from populations of transgenic schistosomes cultured in G418 than from transgenic schistosomes cultured without G418. This trend was G418 dose-dependent, demonstrating enrichment of transgenic worms from among the schistosomules exposed to virions. Furthermore, higher expression of neoR was detected in transgenic schistosomes cultured in the presence of G418 than in transgenic worms cultured without antibiotic. The availability of antibiotic selection can be expected to enhance progress with functional genomics research on the helminth parasites responsible for major neglected tropical diseases. PMID:22155152

  2. The host effects of Gambusia affinis with an antibiotic-disrupted microbiome.

    PubMed

    Carlson, Jeanette M; Hyde, Embriette R; Petrosino, Joseph F; Manage, Ananda B W; Primm, Todd P

    2015-12-01

    While serving as critical tools against bacterial infections, antimicrobial therapies can also result in serious side effects, such as antibiotic-associated entercolitis. Recent studies utilizing next generation sequencing to generate community 16S gene profiles have shown that antibiotics can strongly alter community composition and deplete diversity. However, how these community changes in the microbiota are related to the host side effects is still unclear. We have used the freshwater Western mosquitofish (Gambusia affinis) as a tractable vertebrate model system to study host effects following exposure to a broad spectrum antibiotic, rifampicin. After 3days of exposure, the bacterial communities of the mucosal skin and gut microbiomes lost diversity and shifted composition. Compared to unexposed controls, treated fish were more susceptible to a specific pathogen, Edwardsiella ictaluri, yet displayed no survival differences when subjected to a polymicrobial water challenge of soil or feces. Treated fish were more susceptible to osmotic stress from NaCl, but not to the toxin nitrate. Treated fish failed to gain weight as well as controls over one month when fed a matched diet. Because of small sample sizes, pathogen susceptibility and weight gain differences were not statistically significant. This study provides supporting evidence in an experimental laboratory system that an antibiotic can have significant and persistent negative host effects, and provides for future study into the mechanisms of these effects. PMID:26475244

  3. One hundred and twelve infected arthroplasties treated with ‘DAIR’ (debridement, antibiotics and implant retention): antibiotic duration and outcome

    PubMed Central

    Byren, I.; Bejon, P.; Atkins, B. L.; Angus, B.; Masters, S.; McLardy-Smith, P.; Gundle, R.; Berendt, A.

    2009-01-01

    Objectives We describe treatment failure rates by antibiotic duration for prosthetic joint infection (PJI) managed with debridement, antibiotics and implant retention (DAIR). Methods We retrospectively collected data from all the cases of PJI that were managed with DAIR over a 5 year period. Surgical debridement, microbiological sampling, early intravenous antibiotics and prolonged oral follow-on antibiotics were used. Results One hundred and twelve cases of PJI were identified. Twenty infections (18%) recurred during a mean follow-up of 2.3 years. The mean duration of antibiotic use was 1.5 years. Failure was more common after arthroscopic debridement, for previously revised joints and for Staphylococcus aureus infection. There were 12 failures after stopping antibiotics and 8 while on antibiotics [hazard ratio (HR) = 4.3, 95% confidence interval (CI) 1.4–12.8, P = 0.01]. However, during the first 3 months of follow-up, there were eight failures after stopping antibiotics and two while on antibiotics (HR = 7.0, 95% CI 1.5–33, P = 0.015). The duration of antibiotic therapy prior to stopping did not predict outcome. Conclusions PJI may be managed by DAIR. The risk of failure with this strategy rises after stopping oral antibiotics, but lengthening antibiotic therapy may simply postpone, rather than prevent, failure. PMID:19336454

  4. Fate and transport of antibiotic residues and antibiotic resistance genetic determinants during manure storage, treatment, and land application

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics are used in swine production for therapeutic treatment of disease and at sub-therapeutic levels for growth promotion and improvement of feed efficiency. It is estimated that ca.75% of antibiotics are not absorbed by animals and are excreted in waste. Antibiotic resistance selection occur...

  5. Effects of residual antibiotics in groundwater on Salmonella typhimurium: changes in antibiotic resistance, in vivo and in vitro pathogenicity

    E-print Network

    Maduro, Morris F.

    Effects of residual antibiotics in groundwater on Salmonella typhimurium: changes in antibiotic An outbreak-causing strain of Salmonella enterica serovar Typhimurium was exposed to groundwater with residual groundwater (AGW). Antibiotic susceptibility analysis and the virulence response of stressed Salmonella were

  6. Antibiotics in Canadian poultry productions and anticipated alternatives

    PubMed Central

    Diarra, Moussa S.; Malouin, François

    2014-01-01

    The use of antibiotics in food-producing animals has significantly increased animal health by lowering mortality and the incidence of diseases. Antibiotics also have largely contributed to increase productivity of farms. However, antibiotic usage in general and relevance of non-therapeutic antibiotics (growth promoters) in feed need to be reevaluated especially because bacterial pathogens of humans and animals have developed and shared a variety of antibiotic resistance mechanisms that can easily be spread within microbial communities. In Canada, poultry production involves more than 2600 regulated chicken producers who have access to several antibiotics approved as feed additives for poultry. Feed recipes and mixtures vary greatly geographically and from one farm to another, making links between use of a specific antibiotic feed additive and production yields or selection of specific antibiotic-resistant bacteria difficult to establish. Many on-farm studies have revealed the widespread presence of antibiotic-resistant bacteria in broiler chickens. While some reports linked the presence of antibiotic-resistant organisms to the use of feed supplemented with antibiotics, no recent studies could clearly demonstrate the benefit of antimicrobial growth promoters on performance and production yields. With modern biosecurity and hygienic practices, there is a genuine concern that intensive utilization of antibiotics or use of antimicrobial growth promoters in feed might no longer be useful. Public pressure and concerns about food and environmental safety (antibiotic residues, antibiotic-resistant pathogens) have driven researchers to actively look for alternatives to antibiotics. Some of the alternatives include pre- and probiotics, organic acids and essential oils. We will describe here the properties of some bioactive molecules, like those found in cranberry, which have shown interesting polyvalent antibacterial and immuno-stimulatory activities. PMID:24987390

  7. Antibiotic resistance shaping multi-level population biology of bacteria

    PubMed Central

    Baquero, Fernando; Tedim, Ana P.; Coque, Teresa M.

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent “population biologies.” Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of “clinical” antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi-level population biology of bacteria. PMID:23508522

  8. Antibiotic resistance shaping multi-level population biology of bacteria.

    PubMed

    Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi-level population biology of bacteria. PMID:23508522

  9. Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation.

    PubMed

    Bengtsson-Palme, Johan; Larsson, D G Joakim

    2016-01-01

    There are concerns that selection pressure from antibiotics in the environment may accelerate the evolution and dissemination of antibiotic-resistant pathogens. Nevertheless, there is currently no regulatory system that takes such risks into account. In part, this is due to limited knowledge of environmental concentrations that might exert selection for resistant bacteria. To experimentally determine minimal selective concentrations in complex microbial ecosystems for all antibiotics would involve considerable effort. In this work, our aim was to estimate upper boundaries for selective concentrations for all common antibiotics, based on the assumption that selective concentrations a priori need to be lower than those completely inhibiting growth. Data on Minimal Inhibitory Concentrations (MICs) were obtained for 111 antibiotics from the public EUCAST database. The 1% lowest observed MICs were identified, and to compensate for limited species coverage, predicted lowest MICs adjusted for the number of tested species were extrapolated through modeling. Predicted No Effect Concentrations (PNECs) for resistance selection were then assessed using an assessment factor of 10 to account for differences between MICs and minimal selective concentrations. The resulting PNECs ranged from 8ng/L to 64?g/L. Furthermore, the link between taxonomic similarity between species and lowest MIC was weak. This work provides estimated upper boundaries for selective concentrations (lowest MICs) and PNECs for resistance selection for all common antibiotics. In most cases, PNECs for selection of resistance were below available PNECs for ecotoxicological effects. The generated PNECs can guide implementation of compound-specific emission limits that take into account risks for resistance promotion. PMID:26590482

  10. Rational Design of Antibiotic Treatment Plans: A Treatment Strategy for Managing Evolution and Reversing Resistance

    PubMed Central

    Mira, Portia M.; Crona, Kristina; Greene, Devin; Meza, Juan C.; Sturmfels, Bernd; Barlow, Miriam

    2015-01-01

    The development of reliable methods for restoring susceptibility after antibiotic resistance arises has proven elusive. A greater understanding of the relationship between antibiotic administration and the evolution of resistance is key to overcoming this challenge. Here we present a data-driven mathematical approach for developing antibiotic treatment plans that can reverse the evolution of antibiotic resistance determinants. We have generated adaptive landscapes for 16 genotypes of the TEM ?-lactamase that vary from the wild type genotype “TEM-1” through all combinations of four amino acid substitutions. We determined the growth rate of each genotype when treated with each of 15 ?-lactam antibiotics. By using growth rates as a measure of fitness, we computed the probability of each amino acid substitution in each ?-lactam treatment using two different models named the Correlated Probability Model (CPM) and the Equal Probability Model (EPM). We then performed an exhaustive search through the 15 treatments for substitution paths leading from each of the 16 genotypes back to the wild type TEM-1. We identified optimized treatment paths that returned the highest probabilities of selecting for reversions of amino acid substitutions and returning TEM to the wild type state. For the CPM model, the optimized probabilities ranged between 0.6 and 1.0. For the EPM model, the optimized probabilities ranged between 0.38 and 1.0. For cyclical CPM treatment plans in which the starting and ending genotype was the wild type, the probabilities were between 0.62 and 0.7. Overall this study shows that there is promise for reversing the evolution of resistance through antibiotic treatment plans. PMID:25946134

  11. Bacteriocins – Exploring Alternatives to Antibiotics in Mastitis Treatment

    PubMed Central

    Pieterse, Reneé; Todorov, Svetoslav D.

    2010-01-01

    Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease. PMID:24031528

  12. Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes

    PubMed Central

    Baym, Michael; Kim, Seungsoo; Veres, Adrian; Bershtein, Shimon; Kishony, Roy

    2015-01-01

    Predicting evolutionary paths to antibiotic resistance is key for understanding and controlling drug resistance. When considering a single final resistant genotype, epistatic contingencies among mutations restricts evolution to a small number of adaptive paths. Less attention has been given to multi-peak landscapes, and while specific peaks can be favored, it is unknown whether and how early a commitment to final fate is made. Here we characterized a multi-peaked adaptive landscape for trimethoprim resistance by constructing all combinatorial alleles of seven resistance-conferring mutations in dihydrofolate reductase. We observe that epistatic interactions increase rather than decrease the accessibility of each peak; while they restrict the number of direct paths, they generate more indirect paths, where mutations are adaptively gained and later adaptively lost or changed. This enhanced accessibility allows evolution to proceed through many adaptive steps while delaying commitment to genotypic fate, hindering our ability to predict or control evolutionary outcomes. PMID:26060115

  13. In-feed antibiotic effects on the swine intestinal microbiome

    PubMed Central

    Looft, Torey; Johnson, Timothy A.; Allen, Heather K.; Bayles, Darrell O.; Alt, David P.; Stedtfeld, Robert D.; Sul, Woo Jun; Stedtfeld, Tiffany M.; Chai, Benli; Cole, James R.; Hashsham, Syed A.; Tiedje, James M.; Stanton, Thad B.

    2012-01-01

    Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1–11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses. PMID:22307632

  14. Heavy Metal Induced Antibiotic Resistance in Bacterium LSJC7.

    PubMed

    Chen, Songcan; Li, Xiaomin; Sun, Guoxin; Zhang, Yingjiao; Su, Jianqiang; Ye, Jun

    2015-01-01

    Co-contamination of antibiotics and heavy metals prevails in the environment, and may play an important role in disseminating bacterial antibiotic resistance, but the selective effects of heavy metals on bacterial antibiotic resistance is largely unclear. To investigate this, the effects of heavy metals on antibiotic resistance were studied in a genome-sequenced bacterium, LSJC7. The results showed that the presence of arsenate, copper, and zinc were implicated in fortifying the resistance of LSJC7 towards tetracycline. The concentrations of heavy metals required to induce antibiotic resistance, i.e., the minimum heavy metal concentrations (MHCs), were far below (up to 64-fold) the minimum inhibition concentrations (MIC) of LSJC7. This finding indicates that the relatively low heavy metal levels in polluted environments and in treated humans and animals might be sufficient to induce bacterial antibiotic resistance. In addition, heavy metal induced antibiotic resistance was also observed for a combination of arsenate and chloramphenicol in LSJC7, and copper/zinc and tetracycline in antibiotic susceptible strain Escherichia coli DH5?. Overall, this study implies that heavy metal induced antibiotic resistance might be ubiquitous among various microbial species and suggests that it might play a role in the emergence and spread of antibiotic resistance in metal and antibiotic co-contaminated environments. PMID:26426011

  15. Heavy Metal Induced Antibiotic Resistance in Bacterium LSJC7

    PubMed Central

    Chen, Songcan; Li, Xiaomin; Sun, Guoxin; Zhang, Yingjiao; Su, Jianqiang; Ye, Jun

    2015-01-01

    Co-contamination of antibiotics and heavy metals prevails in the environment, and may play an important role in disseminating bacterial antibiotic resistance, but the selective effects of heavy metals on bacterial antibiotic resistance is largely unclear. To investigate this, the effects of heavy metals on antibiotic resistance were studied in a genome-sequenced bacterium, LSJC7. The results showed that the presence of arsenate, copper, and zinc were implicated in fortifying the resistance of LSJC7 towards tetracycline. The concentrations of heavy metals required to induce antibiotic resistance, i.e., the minimum heavy metal concentrations (MHCs), were far below (up to 64-fold) the minimum inhibition concentrations (MIC) of LSJC7. This finding indicates that the relatively low heavy metal levels in polluted environments and in treated humans and animals might be sufficient to induce bacterial antibiotic resistance. In addition, heavy metal induced antibiotic resistance was also observed for a combination of arsenate and chloramphenicol in LSJC7, and copper/zinc and tetracycline in antibiotic susceptible strain Escherichia coli DH5?. Overall, this study implies that heavy metal induced antibiotic resistance might be ubiquitous among various microbial species and suggests that it might play a role in the emergence and spread of antibiotic resistance in metal and antibiotic co-contaminated environments. PMID:26426011

  16. Nonmedical Uses of Antibiotics: Time to Restrict Their Use?

    PubMed Central

    Meek, Richard William; Vyas, Hrushi; Piddock, Laura Jane Violet

    2015-01-01

    The global crisis of antibiotic resistance has reached a point where, if action is not taken, human medicine will enter a postantibiotic world and simple injuries could once again be life threatening. New antibiotics are needed urgently, but better use of existing agents is just as important. More appropriate use of antibiotics in medicine is vital, but the extensive use of antibiotics outside medical settings is often overlooked. Antibiotics are commonly used in animal husbandry, bee-keeping, fish farming and other forms of aquaculture, ethanol production, horticulture, antifouling paints, food preservation, and domestically. This provides multiple opportunities for the selection and spread of antibiotic-resistant bacteria. Given the current crisis, it is vital that the nonmedical use of antibiotics is critically examined and that any nonessential use halted. PMID:26444324

  17. Nonmedical Uses of Antibiotics: Time to Restrict Their Use?

    PubMed

    Meek, Richard William; Vyas, Hrushi; Piddock, Laura Jane Violet

    2015-10-01

    The global crisis of antibiotic resistance has reached a point where, if action is not taken, human medicine will enter a postantibiotic world and simple injuries could once again be life threatening. New antibiotics are needed urgently, but better use of existing agents is just as important. More appropriate use of antibiotics in medicine is vital, but the extensive use of antibiotics outside medical settings is often overlooked. Antibiotics are commonly used in animal husbandry, bee-keeping, fish farming and other forms of aquaculture, ethanol production, horticulture, antifouling paints, food preservation, and domestically. This provides multiple opportunities for the selection and spread of antibiotic-resistant bacteria. Given the current crisis, it is vital that the nonmedical use of antibiotics is critically examined and that any nonessential use halted. PMID:26444324

  18. Botanical alternatives to antibiotics for use in organic poultry production.

    PubMed

    Diaz-Sanchez, Sandra; D'Souza, Doris; Biswas, Debrabrata; Hanning, Irene

    2015-06-01

    The development of antibiotic resistant pathogens has resulted from the use of sub-therapeutic concentrations of antibiotics delivered in poultry feed. Furthermore, there are a number of consumer concerns regarding the use of antibiotics in food animals including residue contamination of poultry products and antibiotic resistant bacterial pathogens. These issues have resulted in recommendations to reduce the use of antibiotics as growth promoters in livestock in the United States. Unlike conventional production, organic systems are not permitted to use antibiotics. Thus, both conventional and organic poultry production need alternative methods to improve growth and performance of poultry. Herbs, spices, and various other plant extracts are being evaluated as alternatives to antibiotics and some do have growth promoting effects, antimicrobial properties, and other health-related benefits. This review aims to provide an overview of herbs, spices, and plant extracts, currently defined as phytobiotics as potential feed additives. PMID:25743421

  19. Antibiotic Synthesis and Morphological Differentiation of Cephalosporium acremonium

    PubMed Central

    Nash, C. H.; Huber, F. M.

    1971-01-01

    In submerged cultures, Cephalosporium acremonium exists in four morphological forms: hyphae, arthrospores, conidia, and germlings. The phase of hyphal differentiation into arthrospores coincides with the maximum rate of ?-lactam antibiotic synthesis. Furthermore, arthrospores, separated by density-gradient centrifugation, possess 40% greater antibiotic-producing activity than any other morphological cell type. In a series of mutants, each with an increased potential to produce ?-lactam antibiotics, differentiation into arthrospores was proportional to the increased titer of these antibiotics. Thus, arthrospores exhibit enhanced synthesis of ?-lactam antibiotics and appear to be a determining factor in high-yielding mutants. Since a non-antibiotic-producing mutant readily differentiated into arthrospores, antibiotic synthesis and cellular differentiation are not obligately related. Images PMID:5165105

  20. Cooperative Bacterial Growth Dynamics Predict the Evolution of Antibiotic Resistance

    NASA Astrophysics Data System (ADS)

    Artemova, Tatiana; Gerardin, Ylaine; Hsin-Jung Li, Sophia; Gore, Jeff

    2011-03-01

    Since the discovery of penicillin, antibiotics have been our primary weapon against bacterial infections. Unfortunately, bacteria can gain resistance to penicillin by acquiring the gene that encodes beta-lactamase, which inactivates the antibiotic. However, mutations in this gene are necessary to degrade the modern antibiotic cefotaxime. Understanding the conditions that favor the spread of these mutations is a challenge. Here we show that bacterial growth in beta-lactam antibiotics is cooperative and that the nature of this growth determines the conditions in which resistance evolves. Quantitative analysis of the growth dynamics predicts a peak in selection at very low antibiotic concentrations; competition between strains confirms this prediction. We also find significant selection at higher antibiotic concentrations, close to the minimum inhibitory concentrations of the strains. Our results argue that an understanding of the evolutionary forces that lead to antibiotic resistance requires a quantitative understanding of the evolution of cooperation in bacteria.

  1. Bacterial Cheating Limits the Evolution of Antibiotic Resistance

    NASA Astrophysics Data System (ADS)

    Yurtsev, Eugene; Xiao Chao, Hui; Datta, Manoshi; Artemova, Tatiana; Gore, Jeff

    2012-02-01

    The emergence of antibiotic resistance in bacteria is a significant health concern. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removal of the antibiotic. The presence of a cooperative mechanism of resistance suggests that a cheater strain - which does not contribute to breaking down the antibiotic - may be able to take advantage of resistant cells. We find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We use a simple model in conjunction with difference equations to explain the observed population dynamics as a function of cell density and antibiotic concentration. Our experimental difference equations resemble the logistic map, raising the possibility of oscillations or even chaotic dynamics.

  2. Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives.

    PubMed

    Venkatesh, M; Bairavi, V G; Sasikumar, K C

    2011-01-01

    Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20(th) century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.. PMID:21430959

  3. Antibiotic Use in Sore Throat: Are We Judicious?

    PubMed

    Agarwal, Mohit; Raghuwanshi, Shiv Kumar; Asati, Dinesh Prasad

    2015-09-01

    Introduction Sore throat (acute tonsillitis/pharyngitis) is one of the most common clinical diagnosis encountered in ENT practice. It is a common practice to advice antibiotics in patients of sore throat not only in otolaryngology practice but also in pediatricians, GP's and internists. This is now becoming a matter of concern for two reasons, for the side effects of antibiotics and bacterial drug resistance. Methods To analyse patients on their symptoms and rapid streptococcal test for group A Stretococcus and determine antibiotic use. A prospective study was done in 600 patients who were clinically diagnosed as acute tonsillitis or acute pharyngitis and results analysed. Discussion Results showed that 24 % patients needed antibiotics while the rest did well without antibiotics. Results Rapid streptococcal test is a useful test in determining whether the patient needs antibiotic and help is reducing irrational use of antibiotics. PMID:26405662

  4. Comparative post-antibiotic effect of five antibiotics against ten aerobic gram-positive cocci.

    PubMed

    Drabu, Y J; Blakemore, P H

    1990-01-01

    The post-antibiotic effect (PAE) is the persistent suppression of bacterial growth after a short antibiotic exposure. It is well documented with a variety of antibiotics and micro-organisms and may have important therapeutic implications. The authors have evaluated the PAE produced by teicoplanin, fucidin, gentamicin, rifampicin and ciprofloxacin against a total of ten Gram-positive organisms (S. aureus (2), MRSA (2), S. epidermis (2) S. haemolyticus (2) and E. faecalis (2)). All the organisms were clinical isolates with variable sensitivity patterns confirmed by disc and MIC testing. MICs were performed by the broth dilution method using a final inoculum of 10 x 5 cfu/ml. The PAE was estimated by adding 5 x MIC of each antibiotic to a log phase of growth of approximately 10 x 7 cfu/ml, and incubating at 37 degrees C for 1 h. Antibiotic was removed by 1000-fold dilution in nutrient broth, and total viable counts were carried out hourly by the Miles and Misra method for a further 9 h. All the antibiotics tested showed a PAE against the organisms tested, except for fucidin and ciprofloxacin against the enterococci. Overall, teicoplanin showed a maximum PAE of 5 h against MSRA and a minimum of 0.6 h against E. faecalis. Gentamicin, rifampicin and ciprofloxacin also showed a variable range. Fucidin showed the least PAE against the ten organisms, ranging from 0-1.3 h, except for S. epidermidis (FUC-R) which had a PAE of up to 4.5 h. The duration of PAE of each antibiotic/organism combination varied and was associated with the sensitivity pattern of the organism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2151661

  5. Low-density polypropylene meshes coated with resorbable and biocompatible hydrophilic polymers as controlled release agents of antibiotics.

    PubMed

    Fernandez-Gutierrez, Mar; Olivares, Enrique; Pascual, Gemma; Bellon, Juan M; San Román, Julio

    2013-04-01

    The application of bioactive meshes in abdominal surgery for the repair of hernias is an increasing clinical activity in a wide sector of the population. The main secondary effect is the appearance of infections from bacteria, specifically Staphylococcus aureus and S. epidermidis. This paper describes the development and application of low-density polypropylene meshes coated with a biocompatible and resorbable polymer as a controlled release system of the antibiotic vancomycin. The polymeric coating (a non-cross-linked copolymer of 2-hydroxyethyl methacrylate and 2-acrylamido-2-methylpropanesulfonic acid) has a thickness of 14-15?m and contains 0.32mgcm(-2) of the antibiotic vancomycin. The in vitro experiments demonstrate the excellent inhibitory character of the coated meshes loaded with the antibiotic, following the standard protocol of inhibition of halo in agar diffusion test. This inhibitory effect is maintained for a relatively long period (at least 14days) with a low concentration of antibiotic. The acrylic polymer system regulates the release of the antibiotic with a rate of 24?gh(-1), due to its slow dissolution in the medium. Experiments in vivo, based on the implantation of coated meshes, demonstrate that the system controls the infection in the animal (rabbits) for at least 30days. The concentration of antibiotic in the blood stream of the rabbits was below the detection limit of the analytical technique (<1-2?gml(-1)), which demonstrates that the antibiotic is released in the local area of the implant and remains concentrated at the implantation site, without diffusion to the blood stream. The systems can be applied to other medical devices and implants for the application of new-generation antibiotics in a controlled release and targeted applications. PMID:23261925

  6. Maternal antibiotic exposure and risk of antibiotic resistance in neonatal early-onset sepsis: a case-cohort study.

    PubMed

    Wright, Alissa Jade; Unger, Sharon; Coleman, Brenda L; Lam, Po-Po; McGeer, Allison J

    2012-11-01

    In a case-cohort study of early-onset sepsis, antibiotic resistance was more likely for infections in neonates born to mothers who were given antibiotics during pregnancy (odds ratio 4.6; 95% confidence interval: 1.1-19;P = 0.05). Risk of resistance increased with duration of antibiotics and number of antibiotic courses during pregnancy. Preterm birth and hospitalization during pregnancy were also associated with resistance. These risk factors should be considered when selecting empiric antibiotics for therapy of early-onset sepsis in infants. PMID:22926208

  7. Structural origins of gentamicin antibiotic action.

    PubMed Central

    Yoshizawa, S; Fourmy, D; Puglisi, J D

    1998-01-01

    Aminoglycoside antibiotics that bind to the ribosomal A site cause misreading of the genetic code and inhibit translocation. The clinically important aminoglycoside, gentamicin C, is a mixture of three components. Binding of each gentamicin component to the ribosome and to a model RNA oligonucleotide was studied biochemically and the structure of the RNA complexed to gentamicin C1a was solved using magnetic resonance nuclear spectroscopy. Gentamicin C1a binds in the major groove of the RNA. Rings I and II of gentamicin direct specific RNA-drug interactions. Ring III of gentamicin, which distinguishes this subclass of aminoglycosides, also directs specific RNA interactions with conserved base pairs. The structure leads to a general model for specific ribosome recognition by aminoglycoside antibiotics and a possible mechanism for translational inhibition and miscoding. This study provides a structural rationale for chemical synthesis of novel aminoglycosides. PMID:9822590

  8. Vancomycin Molecular Interactions: Antibiotic and Enantioselective Mechanisms

    NASA Astrophysics Data System (ADS)

    Ward, Timothy J.; Gilmore, Aprile; Ward, Karen; Vowell, Courtney

    Medical studies established that vancomycin and other related macrocyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide structurally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin's mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition.

  9. Multidrug evolutionary strategies to reverse antibiotic resistance.

    PubMed

    Baym, Michael; Stone, Laura K; Kishony, Roy

    2016-01-01

    Antibiotic treatment has two conflicting effects: the desired, immediate effect of inhibiting bacterial growth and the undesired, long-term effect of promoting the evolution of resistance. Although these contrasting outcomes seem inextricably linked, recent work has revealed several ways by which antibiotics can be combined to inhibit bacterial growth while, counterintuitively, selecting against resistant mutants. Decoupling treatment efficacy from the risk of resistance can be achieved by exploiting specific interactions between drugs, and the ways in which resistance mutations to a given drug can modulate these interactions or increase the sensitivity of the bacteria to other compounds. Although their practical application requires much further development and validation, and relies on advances in genomic diagnostics, these discoveries suggest novel paradigms that may restrict or even reverse the evolution of resistance. PMID:26722002

  10. New Antibiotic Candidates against Helicobacter pylori.

    PubMed

    Wang, Shanzhi; Cameron, Scott A; Clinch, Keith; Evans, Gary B; Wu, Zhimeng; Schramm, Vern L; Tyler, Peter C

    2015-11-18

    Helicobacter pylori is a Gram-negative bacterium that colonizes the gut of over 50% of the world's population. It is responsible for most peptic ulcers and is an important risk factor for gastric cancer. Antibiotic treatment for H. pylori infections is challenging as drug resistance has developed to antibiotics with traditional mechanisms of action. H. pylori uses an unusual pathway for menaquinone biosynthesis with 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzing an essential step. We validated MTAN as a target with a transition-state analogue of the enzyme [Wang, S.; Haapalainen, A. M.; Yan, F.; et al. Biochemistry 2012, 51, 6892-6894]. MTAN inhibitors will only be useful drug candidates if they can both include tight binding to the MTAN target and have the ability to penetrate the complex cell membrane found in Gram-negative H. pylori. Here we explore structural scaffolds for MTAN inhibition and for growth inhibition of cultured H. pylori. Sixteen analogues reported here are transition-state analogues of H. pylori MTAN with dissociation constants of 50 pM or below. Ten of these prevent growth of the H. pylori with IC90 values below 0.01 ?g/mL. These remarkable compounds meet the criteria for potent inhibition and cell penetration. As a consequence, 10 new H. pylori antibiotic candidates are identified, all of which prevent H. pylori growth at concentrations 16-2000-fold lower than the five antibiotics, amoxicillin, metronidazole, levofloxacin, tetracyclin, and clarithromycin, commonly used to treat H. pylori infections. X-ray crystal structures of MTAN cocrystallized with several inhibitors show them to bind in the active site making interactions consistent with transition-state analogues. PMID:26494017

  11. Antibiotics and Aresenicals in Poultry Nutrition. 

    E-print Network

    Couch, J. R.; Quisenberry, J. H.; Camp, A. A.; Creech, B. G.; Reid, B. L.

    1957-01-01

    and through intramuscular injection. The administration of oral or injected peni- cillin increased the growth rate of the chicks (Figure 1). TABLE 2. EFFECT OF DIFFERENT LEVELS OF APF CON- CENTRATE 199-B ON Tm AVERAGE WEIGHT, FEED EFFICIENCY.... The injection of peni- cillin decomposition products failed to exert a stimulating effect on growth (Table 7). .. ,.. As in the previous study, the feeding of anti- biotics again produced a significant reduction nunt is altered in antibiotic feeding and may...

  12. New life for an old antibiotic.

    PubMed

    Mishra, Rahul Kumar; Segal, Elad; Lipovsky, Anat; Natan, Michal; Banin, Ehud; Gedanken, Aharon

    2015-04-01

    Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we present, for the first time, the formation and deposition of stable antibiotic nanoparticles (NPs) on graphene oxide (GO) sheets by a facile one-step sonochemical technique. Sonochemically synthesized graphene oxide/tetracycline (GO/TET) composite shows enhanced activity against both sensitive and resistant Staphylococcus aureus (S. aureus). The size and deposition of tetracycline (TET) nanoparticles on GO can be controlled by varying the sonication time. The synthesized NPs ranged from 21 to 180 nm. Moreover, ultrasonic irradiation does not cause any structural and chemical changes to the TET molecule as confirmed by Fourier transform infrared spectroscopy (FTIR). The virtue of ?-? stacking between GO and TET additionally facilitate the coating of TET NPs upon GO. A time dependent release kinetics of TET NPs from the GO surface is also monitored providing important insights regarding the mechanism of antibacterial activity of GO/TET composites. Our results show that the GO/TET composite is bactericidal in nature, resulting in similar values of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). This composite is found to be active against TET resistant S. aureus at a concentration four times lower than the pristine TET. The sensitive S. aureus follows the same trend showing six times lower MIC values compared to pristine TET. GO shows no activity against both sensitive and resistant S. aureus even at a concentration as high as 1 mg/mL but influences the biocidal activity of the GO/TET composite. We propose that the unique structure and composition manifested by GO/TET composites may be further utilized for different formulations of antibiotics with GO. The sonochemical method used in this work can be precisely tailored for the stable deposition of a variety of antibiotics on the GO surface to reduce health risks and increase the spectrum of applications. PMID:25768259

  13. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial

    PubMed Central

    Schuetz, Philipp; Christ-Crain, Mirjam; Wolbers, Marcel; Schild, Ursula; Thomann, Robert; Falconnier, Claudine; Widmer, Isabelle; Neidert, Stefanie; Blum, Claudine A; Schönenberger, Ronald; Henzen, Christoph; Bregenzer, Thomas; Hoess, Claus; Krause, Martin; Bucher, Heiner C; Zimmerli, Werner; Müller, Beat

    2007-01-01

    Background: Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections. Methods and design: We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections <28 days of duration. Patients with no informed consent, not fluent in German, a previous hospital stay within 14 days, severe immunosuppression or chronic infection, intravenous drug use or a terminal condition are excluded. Randomization to either guidelines-enforced management or procalcitonin-guided antibiotic therapy is stratified by centre and type of lower respiratory tract infections. During hospitalization, all patients are reassessed at days 3, 5, 7 and at the day of discharge. After 30 and 180 days, structured phone interviews by blinded medical students are conducted. Depending on the randomization allocation, initiation and discontinuation of antibiotics is encouraged or discouraged based on evidence-based guidelines or procalcitonin cut off ranges, respectively. The primary endpoint is the risk of combined disease-specific failure after 30 days. Secondary outcomes are antibiotic exposure, side effects from antibiotics, rate and duration of hospitalization, time to clinical stability, disease activity scores and cost effectiveness. The study hypothesis is that procalcitonin-guidance is non-inferior (i.e., at worst a 7.5% higher combined failure rate) to the management with enforced guidelines, but is associated with a reduced total antibiotic use and length of hospital stay. Discussion: Use of and prolonged exposure to antibiotics in lower respiratory tract infections is high. The proposed trial investigates whether procalcitonin-guidance may safely reduce antibiotic consumption along with reductions in hospitalization costs and antibiotic resistance. It will additionally generate insights for improved prognostic assessment of patients with lower respiratory tract infections. Trial registration: ISRCTN95122877 PMID:17615073

  14. Biosynthesis of the manumycin group antibiotics

    SciTech Connect

    Thiericke, R.; Zeeck, A. ); Nakagawa, Akira; Omura, Satoshi ); Herrold, R.E.; Wu, S.T.S. ); Beale, J.M.; Floss, H.G. )

    1990-05-09

    The biosynthesis of the manumycin group antibiotics manumycin (1) and asukamycin (2) was studied in Streptomyces parvulus Tue 64 and Streptomyces nodosus ssp. asukaensis ATCC 29,757 by using radioactive and stable isotope tracer techniques and high-field NMR spectroscopy. The results have demonstrated that the central, multifunctional mC{sub 7}N unit typical of this group of antibiotics, which serves as the starter unit for a short polyketide chain, is biosynthesized from a C{sub 4} Krebs cycle and a C{sub 3} triose phosphate pool intermediate by a new pathway, distinct from the shikimate, polyketide, or pentose phosphate routes leading to other mC{sub 7}N units in nature. The C{sub 5} unit in both 1 and 2 arises by a novel intramolecular cyclization of 5-aminolevulinic acid, and a cyclohexane ring and the adjacent carbon in 2 arise from the seven carbon atoms of shikimic acid. The side chains of both antibiotics represent typical polyketide-derived moieties, differing with respect to their combinations of starter and elongation units.

  15. Colistin: Revival of an Old Polymyxin Antibiotic.

    PubMed

    Dijkmans, Anneke C; Wilms, Erik B; Kamerling, Ingrid M C; Birkhoff, Willem; Ortiz-Zacarías, Natalia V; van Nieuwkoop, Cees; Verbrugh, Henri A; Touw, Daan J

    2015-08-01

    Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined. PMID:25549206

  16. Antibiotic-resistant bacteria in drinking water.

    PubMed Central

    Armstrong, J L; Shigeno, D S; Calomiris, J J; Seidler, R J

    1981-01-01

    We analyzed drinking water from seven communities for multiply antibiotic-resistant (MAR) bacteria (bacteria resistant to two or more antibiotics) and screened the MAR bacterial isolates obtained against five antibiotics by replica plating. Overall, 33.9% of 2,653 standard plate count bacteria from treated drinking waters were MAR. Two different raw water supplies for two communities carried MAR standard plate count bacteria at frequencies of 20.4 and 18.6%, whereas 36.7 and 67.8% of the standard plate count populations from sites within the respective distribution systems were MAR. Isolate identification revealed that MAR gram-positive cocci (Staphylococcus) and MAR gram-negative, nonfermentative rods (Pseudomonas, Alcaligenes, Moraxella-like group M, and Acinetobacter) were more common in drinking waters than in untreated source waters. Site-to-site variations in generic types and differences in the incidences of MAR organisms indicated that shedding of MAR bacteria living in pipelines may have contributed to the MAR populations in tap water. We conclude that the treatment of raw water and its subsequent distribution select for standard plate count bacteria exhibiting the MAR phenotype. PMID:7283426

  17. Hfq regulates antibacterial antibiotic biosynthesis and extracellular lytic-enzyme production in Lysobacter enzymogenes OH11

    PubMed Central

    Xu, Gaoge; Zhao, Yuxin; Du, Liangcheng; Qian, Guoliang; Liu, Fengquan

    2015-01-01

    Lysobacter enzymogenes is an important biocontrol agent with the ability to produce a variety of lytic enzymes and novel antibiotics. Little is known about their regulatory mechanisms. Understanding these will be helpful for improving biocontrol of crop diseases and potential medical application. In the present study, we generated an hfq (encoding a putative ribonucleic acid chaperone) deletion mutant, and then utilized a new genomic marker-free method to construct an hfq-complemented strain. We showed for the first time that Hfq played a pleiotropic role in regulating the antibacterial antibiotic biosynthesis and extracellular lytic enzyme activity in L.?enzymogenes. Mutation of hfq significantly increased the yield of WAP-8294A2 (an antibacterial antibiotic) as well as the transcription of its key biosynthetic gene, waps1. However, inactivation of hfq almost abolished the extracellular chitinase activity and remarkably decreased the activity of both extracellular protease and cellulase in L.?enzymogenes. We further showed that the regulation of hfq in extracellular chitinase production was in part through the impairment of the secretion of chitinase A. Collectively, our results reveal the regulatory roles of hfq in antibiotic metabolite and extracellular lytic enzymes in the underexplored genus of Lysobacter. PMID:25683974

  18. Mechanism of electrical enhancement of efficacy of antibiotics in killing biofilm bacteria.

    PubMed Central

    Costerton, J W; Ellis, B; Lam, K; Johnson, F; Khoury, A E

    1994-01-01

    The bioelectric effect, in which electric fields are used to enhance the efficacy of biocides and antibiotics in killing biofilm bacteria, has been shown to reduce the very high concentrations of these antibacterial agents needed to kill biofilm bacteria to levels very close to those needed to kill planktonic (floating) bacteria of the same species. In this report, we show that biofilm bacteria are readily killed by an antibiotic on all areas of the active electrodes and on the surfaces of conductive elements that lie within the electric field but do not themselves function as electrodes. Considerations of electrode geometry indicate that very low (< 100 microA/cm2) current densities may be effective in this electrical enhancement of antibiotic efficacy against biofilm bacteria, and flow experiments indicate that this bioelectric effect does not appear to depend entirely on the possible local electrochemical generation of antibacterial molecules or ions. These data are expected to facilitate the use of the bioelectric effect in the prevention and treatment of device-related bacterial infections that are caused by bacteria that grow in biofilms and thereby frustrate antibiotic chemotherapy. Images PMID:7695266

  19. Efflux pump-deficient mutants as a platform to search for microbes that produce antibiotics

    PubMed Central

    Molina-Santiago, Carlos; Udaondo, Zulema; Daddaoua, Abdelali; Roca, Amalia; Martín, Jesús; Pérez-Victoria, Ignacio; Reyes, Fernando; Ramos, Juan-Luis

    2015-01-01

    Pseudomonas putida?DOT-T1E-18 is a strain deficient in the major antibiotic efflux pump (TtgABC) that exhibits an overall increased susceptibility to a wide range of drugs when compared with the wild-type strain. We used this strain as a platform to search for microbes able to produce antibiotics that inhibit growth. A collection of 2400 isolates from soil, sediments and water was generated and a drop assay developed to identify, via growth inhibition halos, strains that prevent the growth of DOT-T1E-18 on solid Luria–Bertani plates. In this study, 35 different isolates that produced known and unknown antibiotics were identified. The most potent inhibitor of DOT-T1E-18 growth was an isolate named 250J that, through multi-locus sequence analysis, was identified as a Pseudomonas sp. strain. Culture supernatants of 250J contain four different xantholysins that prevent growth of Gram-positive bacteria, Gram-negative and fungi. Two of the xantholysins were produced in higher concentrations and purified. Xantholysin A was effective against Bacillus, Lysinibacillus and Rhodococcus strains, and the effect against these microbes was enhanced when used in combination with other antibiotics such as ampicillin, gentamicin and kanamycin. Xantholysin C was also efficient against Gram-positive bacteria and showed an interesting antimicrobial effect against Pseudomonas strains, and a synergistic inhibitory effect with ampicillin, chloramphenicol and gentamicin. PMID:26059350

  20. Hfq regulates antibacterial antibiotic biosynthesis and extracellular lytic-enzyme production in Lysobacter enzymogenes OH11.

    PubMed

    Xu, Gaoge; Zhao, Yuxin; Du, Liangcheng; Qian, Guoliang; Liu, Fengquan

    2015-05-01

    Lysobacter enzymogenes is an important biocontrol agent with the ability to produce a variety of lytic enzymes and novel antibiotics. Little is known about their regulatory mechanisms. Understanding these will be helpful for improving biocontrol of crop diseases and potential medical application. In the present study, we generated an hfq (encoding a putative ribonucleic acid chaperone) deletion mutant, and then utilized a new genomic marker-free method to construct an hfq-complemented strain. We showed for the first time that Hfq played a pleiotropic role in regulating the antibacterial antibiotic biosynthesis and extracellular lytic enzyme activity in L.?enzymogenes. Mutation of hfq significantly increased the yield of WAP-8294A2 (an antibacterial antibiotic) as well as the transcription of its key biosynthetic gene, waps1. However, inactivation of hfq almost abolished the extracellular chitinase activity and remarkably decreased the activity of both extracellular protease and cellulase in L.?enzymogenes. We further showed that the regulation of hfq in extracellular chitinase production was in part through the impairment of the secretion of chitinase A. Collectively, our results reveal the regulatory roles of hfq in antibiotic metabolite and extracellular lytic enzymes in the underexplored genus of Lysobacter. PMID:25683974

  1. Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class

    PubMed Central

    Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera; Linninge, Caroline; Ahrné, Siv; Højberg, Ole; Licht, Tine Rask; Bahl, Martin Iain

    2015-01-01

    Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10–11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did not always result from major changes in microbiota and vice versa. PMID:26691591

  2. The Goldilocks Principle and Rapid Evolution of Antibiotic Resistance in Bacteria

    NASA Astrophysics Data System (ADS)

    Zhang, Qiucen; Austin, Robert

    2011-03-01

    Goldilocks sampled the three bear's wares for the ``just right'' combination of taste, fit and comfort. Like Goldilocks's need for the just right parameters, evolution proceeds most rapidly when there is the just right combination of a large number of mutants and rapid fixation of the mutants. We show here using a two-dimensional micro-ecology that it is possible to fix resistance to the powerful antibiotic ciprofloxacin (Cipro) in wild-type E. coli in 10 hours through a combination of extremely high population gradients, which generate rapid fixation, convolved with the just right level of antibiotic which generates a large number of mutants and the motility of the organism. Although evolution occurs in well-stirred chemostats without such Goldilocks conditions, natural environments are rarely well stirred in nature.For complex environments such as the Galapagos Islands, spatial population gradients and movement of mutants along these population gradients can be as important as genomic heterogeneity in setting the speed of evolution. The design of our micro-ecology is unique in that it provides two overlapping gradients, one an emergent and self generated bacterial population gradient due to food restriction and the other a mutagenic antibiotic gradient. Further, it exploits the motility of the bacteria moving across these gradients to drive the rate of resistance to Cipro to extraordinarily high rates. The research described was supported by Award Number U54CA143803 from the National Cancer Institute.

  3. Prevalence of antibiotic-resistant E. coli in retail chicken: comparing conventional, organic, kosher, and raised without antibiotics

    PubMed Central

    Price, Lance B; Hungate, Bruce A

    2013-01-01

    Retail poultry products are known sources of antibiotic-resistant Escherichia coli, a major human health concern. Consumers have a range of choices for poultry, including conventional, organic, kosher, and raised without antibiotics (RWA) – designations that are perceived to indicate differences in quality and safety. However, whether these categories vary in the frequency of contamination with antibiotic-resistant E. coli is unknown. We examined the occurrence of antibiotic-resistant E. coli on raw chicken marketed as conventional, organic, kosher and RWA. From April – June 2012, we purchased 213 samples of raw chicken from 15 locations in the New York City metropolitan area. We screened E. coli isolates from each sample for resistance to 12 common antibiotics. Although the organic and RWA labels restrict the use of antibiotics, the frequency of antibiotic-resistant E. coli tended to be only slightly lower for RWA, and organic chicken was statistically indistinguishable from conventional products that have no restrictions. Kosher chicken had the highest frequency of antibiotic-resistant E. coli, nearly twice that of conventional products, a result that belies the historical roots of kosher as a means to ensure food safety. These results indicate that production methods influence the frequency of antibiotic-resistant E. coli on poultry products available to consumers. Future research to identify the specific practices that cause the high frequency of antibiotic-resistant E. coli in kosher chicken could promote efforts to reduce consumer exposure to this potential pathogen. PMID:24555073

  4. Genome Sequence of Acinetobacter baumannii Strain D36, an Antibiotic-Resistant Isolate from Lineage 2 of Global Clone 1

    PubMed Central

    Hamidian, Mohammad; Hawkey, Jane

    2015-01-01

    Multiply antibiotic-resistant Acinetobacter baumannii isolate D36 was recovered in Australia in 2008 and belongs to a distinct lineage of global clone 1 (GC1). Here, we present the complete 4.13 Mbp genome sequence (chromosome plus 4 plasmids), generated via long read sequencing (PacBio). PMID:26679588

  5. Genome Sequence of Acinetobacter baumannii Strain D36, an Antibiotic-Resistant Isolate from Lineage 2 of Global Clone 1.

    PubMed

    Hamidian, Mohammad; Hawkey, Jane; Holt, Kathryn E; Hall, Ruth M

    2015-01-01

    Multiply antibiotic-resistant Acinetobacter baumannii isolate D36 was recovered in Australia in 2008 and belongs to a distinct lineage of global clone 1 (GC1). Here, we present the complete 4.13 Mbp genome sequence (chromosome plus 4 plasmids), generated via long read sequencing (PacBio). PMID:26679588

  6. Get Smart: Know When Antibiotics Work - What Everyone Should Know

    MedlinePLUS

    ... Adult Treatment Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving ...

  7. Estimating the use of antibiotics for humans across China.

    PubMed

    Bu, Qingwei; Wang, Bin; Huang, Jun; Liu, Kai; Deng, Shubo; Wang, Yujue; Yu, Gang

    2016-02-01

    The present study aimed to propose a method to estimate the spatially resolved dataset for human-use antibiotics, which are highly needed in exposure models dealing with regions of various environmental characteristics. In this study, a regression model describing the relationship between the use of antibiotics and a set of socio-economic determinants was developed. It has been demonstrated that economic status (expressed using per capita gross domestic production) dominates the antibiotic use at least in China. Linear regression analysis was used to build the model, resulting in high goodness-of-fit, R(2) (>0.75). Internal and external validations along with residue plot indicated that the model was robust and predictive. The model was successfully applied to allocate the use of antibiotics in China in 2011 at national-, provincial-, prefectural-, and county-level, which are comparable to that back-calculated from the available data of wastewater analysis in some cities. Antibiotic uses were higher in East China than other regions and it was found that uses of total antibiotics vary among Chinese counties on four orders of magnitude (0.186-1645 t antibiotics per year per county). Also management practice could be worked out according to our exploration of the impact transition of social-economic factors on antibiotic uses. To our knowledge, this is the first endeavor to explore this economic dominated relationship for estimating spatially resolved use map of antibiotics in China. PMID:26492425

  8. Isolated cell behavior drives the evolution of antibiotic resistance.

    PubMed

    Artemova, Tatiana; Gerardin, Ylaine; Dudley, Carmel; Vega, Nicole M; Gore, Jeff

    2015-07-01

    Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the collective inactivation of antibiotic by the bacterial population can cause the measured MIC to depend strongly on the initial cell density. In cases where this inoculum effect is strong, the relationship between MIC and bacterial fitness in the antibiotic is not well defined. Here, we demonstrate that the resistance of a single, isolated cell-which we call the single-cell MIC (scMIC)-provides a superior metric for quantifying antibiotic resistance. Unlike the MIC, we find that the scMIC predicts the direction of selection and also specifies the antibiotic concentration at which selection begins to favor new mutants. Understanding the cooperative nature of bacterial growth in antibiotics is therefore essential in predicting the evolution of antibiotic resistance. PMID:26227664

  9. Antibiotic resistance in food lactic acid bacteria--a review.

    PubMed

    Mathur, Shalini; Singh, Rameshwar

    2005-12-15

    Antibiotics are a major tool utilized by the health care industry to fight bacterial infections; however, bacteria are highly adaptable creatures and are capable of developing resistance to antibiotics. Consequently, decades of antibiotic use, or rather misuse, have resulted in bacterial resistance to many modern antibiotics. This antibiotic resistance can cause significant danger and suffering for many people with common bacterial infections, those once easily treated with antibiotics. For several decades studies on selection and dissemination of antibiotic resistance have focused mainly on clinically relevant species. However, recently many investigators have speculated that commensal bacteria including lactic acid bacteria (LAB) may act as reservoirs of antibiotic resistance genes similar to those found in human pathogens. The main threat associated with these bacteria is that they can transfer resistance genes to pathogenic bacteria. Genes conferring resistance to tetracycline, erythromycin and vancomycin have been detected and characterized in Lactococcus lactis, Enterococci and, recently, in Lactobacillus species isolated from fermented meat and milk products. A number of initiatives have been recently launched by various organizations across the globe to address the biosafety concerns of starter cultures and probiotic microorganisms. The studies can lead to better understanding of the role played by the dairy starter microorganisms in horizontal transfer of antibiotic resistance genes to intestinal microorganisms and food-associated pathogenic bacteria. PMID:16289406

  10. Isolated cell behavior drives the evolution of antibiotic resistance

    PubMed Central

    Artemova, Tatiana; Gerardin, Ylaine; Dudley, Carmel; Vega, Nicole M; Gore, Jeff

    2015-01-01

    Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the collective inactivation of antibiotic by the bacterial population can cause the measured MIC to depend strongly on the initial cell density. In cases where this inoculum effect is strong, the relationship between MIC and bacterial fitness in the antibiotic is not well defined. Here, we demonstrate that the resistance of a single, isolated cell—which we call the single-cell MIC (scMIC)—provides a superior metric for quantifying antibiotic resistance. Unlike the MIC, we find that the scMIC predicts the direction of selection and also specifies the antibiotic concentration at which selection begins to favor new mutants. Understanding the cooperative nature of bacterial growth in antibiotics is therefore essential in predicting the evolution of antibiotic resistance. PMID:26227664

  11. Protective role of E. coli outer membrane vesicles against antibiotics.

    PubMed

    Kulkarni, Heramb M; Nagaraj, R; Jagannadham, Medicharla V

    2015-12-01

    The outer membrane vesicles (OMVs) from bacteria are known to posses both defensive and protective functions and thus participate in community related functions. In the present study, outer membrane vesicles have been shown to protect the producer bacterium and two other bacterial species from the growth inhibitory effects of some antibiotics. The OMVs isolated from E. coli MG1655 protected the bacteria against membrane-active antibiotics colistin, melittin. The OMVs of E. coli MG1655 could also protect P. aeruginosa NCTC6751 and A. radiodioresistens MMC5 against these membrane-active antibiotics. However, OMVs could not protect any of these bacteria against the other antibiotics ciprofloxacin, streptomycin and trimethoprim. Hence, OMVs appears to protect the bacterial community against membrane-active antibiotics and not other antibiotics, which have different mechanism of actions. The OMVs of E. coli MG1655 sequester the antibiotic colistin, whereas their protein components degrade the antimicrobial peptide melittin. Proteomic analysis of OMVs revealed the presence of proteases and peptidases which appear to be involved in this process. Thus, the protection of bacteria by OMVs against antibiotics is situation dependent and the mechanism differs for different situations. These studies suggest that OMVs of bacteria form a common defense for the bacterial community against specific antibiotics. PMID:26640046

  12. Intrinsic antibiotic resistance: mechanisms, origins, challenges and solutions.

    PubMed

    Cox, Georgina; Wright, Gerard D

    2013-08-01

    The intrinsic antibiotic resistome is a naturally occurring phenomenon that predates antibiotic chemotherapy and is present in all bacterial species. In addition to the intrinsic resistance mediated by the bacterial outer membrane and active efflux, studies have shown that a surprising number of additional genes and genetic loci also contribute to this phenotype. Antibiotic resistance is rife in both the clinic and the environment; novel therapeutic strategies need to be developed in order to prevent a major global clinical threat. The possibility of inhibiting elements comprising the intrinsic resistome in bacterial pathogens offers the promise for repurposing existing antibiotics against intrinsically resistant bacteria. PMID:23499305

  13. Antibiotic-Resistant Vibrios in Farmed Shrimp

    PubMed Central

    Albuquerque Costa, Renata; Araújo, Rayza Lima; Souza, Oscarina Viana; Vieira, Regine Helena Silva dos Fernandes

    2015-01-01

    Antimicrobial susceptibility pattern was determined in 100 strains of Vibrio isolated from the Litopenaeus vannamei shrimp and identified phenotypically. A high antibiotic-resistance index (75%) was observed, with the following phenotypic profiles: monoresistance (n = 42), cross-resistance to ?-lactams (n = 20) and multiple resistance (n = 13). Plasmid resistance was characterized for penicillin (n = 11), penicillin + ampicillin (n = 1), penicillin + aztreonam (n = 1), and ampicillin (n = 1). Resistance to antimicrobial drugs by the other strains (n = 86) was possibly mediated by chromosomal genes. The findings of this study support the conclusion that the cultured shrimps can be vehicles of vibrios resistant to ?-lactam and tetracycline. PMID:25918714

  14. Remission of refractory pyoderma gangrenosum, severe acne, and hidradenitis suppurativa (PASH) syndrome using targeted antibiotic therapy in 4 patients.

    PubMed

    Join-Lambert, Olivier; Duchatelet, Sabine; Delage, Maïa; Miskinyte, Snaigune; Coignard, Hélène; Lemarchand, Nicolas; Alemy-Carreau, Murielle; Lortholary, Olivier; Nassif, Xavier; Hovnanian, Alain; Nassif, Aude

    2015-11-01

    Pyoderma gangrenosum, severe acne, and suppurative hidradenitis (PASH) syndrome can prove refractory to treatment and is characterized by relapses and recurrences. The combination of antibiotic therapy and surgery can produce success in the management of the syndrome. Acute treatment is required, but maintenance therapy is also necessary to prevent disease relapse. The response to antibiotic therapy is hypothesis generating, raising the issue of a modified host response. To date, anecdotal reports support the use of surgery and medical therapy, but controlled investigations with extended follow-up are necessary to substantiate preliminary data observed with individual cases. PMID:26470620

  15. Sept/Oct 2002 Antibiotics in Honey Apicure is Here (On Paper)

    E-print Network

    Ishida, Yuko

    Sept/Oct 2002 ________________________________________________________________ Antibiotics in Honey ________________________________________________________________ Antibiotics in Honey The recent discovery of traces (0.3 to 34.0 ppb) of the antibiotic chloramphen- icol for illegal antibiotic residues. How could an antibiotic get into honey (or crayfish)? Probably by the use

  16. Fate of antibiotic resistant cultivable heterotrophic bacteria and antibiotic resistance genes in wastewater treatment processes.

    PubMed

    Zhang, Songhe; Han, Bing; Gu, Ju; Wang, Chao; Wang, Peifang; Ma, Yanyan; Cao, Jiashun; He, Zhenli

    2015-09-01

    Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants of environmental concern. Heterotrophic bacteria in activated sludge have an important role in wastewater treatment plants (WWTPs). However, the fate of cultivable heterotrophic ARB and ARGs in WWPTs process remains unclear. In the present study, we investigated the antibiotic-resistant phenotypes of cultivable heterotrophic bacteria from influent and effluent water of three WWTPs and analysed thirteen ARGs in ARB and in activated sludge from anoxic, anaerobic and aerobic compartments. From each influent or effluent sample of the three plants, 200 isolates were randomly tested for susceptibility to 12 antibiotics. In these samples, between 5% and 64% isolates showed resistance to >9 antibiotics and the proportion of >9-drug-resistant bacteria was lower in isolates from effluent than from influent. Eighteen genera were identified in 188 isolates from influent (n=94) and effluent (n=94) of one WWTP. Six genera (Aeromonas, Bacillus, Lysinibacillus, Microbacterium, Providencia, and Staphylococcus) were detected in both influent and effluent samples. Gram-negative and -positive isolates dominated in influent and effluent, respectively. The 13 tetracycline-, sulphonamide-, streptomycin- and ?-lactam-resistance genes were detected at a higher frequency in ARB from influent than from effluent, except for sulA and CTX-M, while in general, the abundances of ARGs in activated sludge from two of the three plants were higher in aerobic compartments than in anoxic ones, indicating abundant ARGs exit in the excess sledges and/or in uncultivable bacteria. These findings may be useful for elucidating the effect of WWTP on ARB and ARGs. PMID:25950407

  17. Antibiotic resistance profiles among mesophilic aerobic bacteria in Nigerian chicken litter and associated antibiotic resistance genes1.

    PubMed

    Olonitola, Olayeni Stephen; Fahrenfeld, Nicole; Pruden, Amy

    2015-05-01

    The effect of global antibiotic use practices in livestock on the emergence of antibiotic resistant pathogens is poorly understood. There is a paucity of data among African nations, which suffer from high rates of antibiotic resistant infections among the human population. Escherichia (29.5%), Staphylococcus (15.8%), and Proteus (15.79%) were the dominant bacterial genera isolated from chicken litter from four different farms in Zaria, Nigeria, all of which contain human pathogenic members. Escherichia isolates were uniformly susceptible to augmentin and cefuroxime, but resistant to sulfamethoxazole (54.5%), ampicillin (22.7%), ciprofloxacin (18.2%), cephalothin (13.6%) and gentamicin (13.6%). Staphylococcus isolates were susceptible to ciprofloxacin, gentamicin, and sulfamethoxazole, but resistant to tetracycline (86.7%), erythromycin (80%), clindamycin (60%), and penicillin (33.3%). Many of the isolates (65.4%) were resistant to multiple antibiotics, with a multiple antibiotic resistance index (MARI) ? 0.2. sul1, sul2, and vanA were the most commonly detected antibiotic resistance genes among the isolates. Chicken litter associated with antibiotic use and farming practices in Nigeria could be a public health concern given that the antibiotic resistant patterns among genera containing pathogens indicate the potential for antibiotic treatment failure. However, the MARI values were generally lower than reported for Escherichia coli from intensive poultry operations in industrial nations. PMID:25725076

  18. Use of Sodium Polyanethol Sulfonate to Selectively Inhibit Aminoglycoside and Polymyxin Antibiotics in a Rapid Blood Level Antibiotic Assay

    PubMed Central

    Edberg, Stephen C.; Bottenbley, Cecil J.; Gam, Kalman

    1976-01-01

    Sodium polyanethol sulfonate inhibits aminoglycoside and polymyxin classes of antibiotics in direct proportion to its concentration. Aminoglycoside and polymyxin class antibiotics are selectively inactivated; penicillin, including the semisynthetic penicillins, cephalothin, chloramphenicol, clindamycin, tetracycline, erythromycin, and vancomycin are not inhibited. By incorporating sodium polyanethol sulfonate directly into the test medium it is possible, in a 4-h antibiotic blood level assay, to selectively obviate the activity of the aminoglycosides and polymyxins to determine the concentration of other antibiotics present in the same serum sample. Images PMID:176933

  19. Using steric hindrance to design new inhibitors of class C beta-lactamases

    SciTech Connect

    Trehan, Indi; Morandi, F.; Blaszczak, L.C.; Shoichet, Brian K.

    2010-03-08

    {beta}-lactamases confer resistance to {beta}-lactam antibiotics such as penicillins and cephalosporins. However, {beta}-lactams that form an acyl-intermediate with the enzyme but subsequently are hindered from forming a catalytically competent conformation seem to be inhibitors of {beta}-lactamases. This inhibition may be imparted by specific groups on the ubiquitous R1 side chain of {beta}-lactams, such as the 2-amino-4-thiazolyl methoxyimino (ATMO) group common among third-generation cephalosporins. Using steric hindrance of deacylation as a design guide, penicillin and carbacephem substrates were converted into effective {beta}-lactamase inhibitors and antiresistance antibiotics. To investigate the structural bases of inhibition, the crystal structures of the acyl-adducts of the penicillin substrate amoxicillin and the new analogous inhibitor ATMO-penicillin were determined. ATMO-penicillin binds in a catalytically incompetent conformation resembling that adopted by third-generation cephalosporins, demonstrating the transferability of such sterically hindered groups in inhibitor design.

  20. Rapid optical determination of ?-lactamase and antibiotic activity

    PubMed Central

    2014-01-01

    Background The absence of rapid tests evaluating antibiotic susceptibility results in the empirical prescription of antibiotics. This can lead to treatment failures due to escalating antibiotic resistance, and also furthers the emergence of drug-resistant bacteria. This study reports a rapid optical method to detect ?-lactamase and thereby assess activity of ?-lactam antibiotics, which could provide an approach for targeted prescription of antibiotics. The methodology is centred on a fluorescence quenching based probe (?-LEAF – ?-Lactamase Enzyme Activated Fluorophore) that mimics the structure of ?-lactam antibiotics. Results The ?-LEAF assay was performed for rapid determination of ?-lactamase production and activity of ?-lactam antibiotic (cefazolin) on a panel of Staphylococcus aureus ATCC strains and clinical isolates. Four of the clinical isolates were determined to be lactamase producers, with the capacity to inactivate cefazolin, out of the twenty-five isolates tested. These results were compared against gold standard methods, nitrocefin disk test for ?-lactamase detection and disk diffusion for antibiotic susceptibility, showing results to be largely consistent. Furthermore, in the sub-set of ?-lactamase producers, it was demonstrated and validated that multiple antibiotics (cefazolin, cefoxitin, cefepime) could be assessed simultaneously to predict the antibiotic that would be most active for a given bacterial isolate. Conclusions The study establishes the rapid ?-LEAF assay for ?-lactamase detection and prediction of antibiotic activity using S. aureus clinical isolates. Although the focus in the current study is ?-lactamase-based resistance, the overall approach represents a broad diagnostic platform. In the long-term, these studies form the basis for the development of assays utilizing a broader variety of targets, pathogens and drugs. PMID:24708478