Engineering the Substrate Specificity of a Thermophilic Penicillin Acylase from Thermus thermophilus

Science.gov (United States)

Torres, Leticia L.; Cantero, Ángel; del Valle, Mercedes; Marina, Anabel; López-Gallego, Fernando; Guisán, José M.

2013-01-01

A homologue of the Escherichia coli penicillin acylase is encoded in the genomes of several thermophiles, including in different Thermus thermophilus strains. Although the natural substrate of this enzyme is not known, this acylase shows a marked preference for penicillin K over penicillin G. Three-dimensional models were created in which the catalytic residues and the substrate binding pocket were identified. Through rational redesign, residues were replaced to mimic the aromatic binding site of the E. coli penicillin G acylase. A set of enzyme variants containing between one and four amino acid replacements was generated, with altered catalytic properties in the hydrolyses of penicillins K and G. The introduction of a single phenylalanine residue in position α188, α189, or β24 improved the Km for penicillin G between 9- and 12-fold, and the catalytic efficiency of these variants for penicillin G was improved up to 6.6-fold. Structural models, as well as docking analyses, can predict the positioning of penicillins G and K for catalysis and can demonstrate how binding in a productive pose is compromised when more than one bulky phenylalanine residue is introduced into the active site. PMID:23263966

21 CFR 556.510 - Penicillin.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin. 556.510 Section 556.510 Food and Drugs... Residues of New Animal Drugs § 556.510 Penicillin. Tolerances are established for residues of penicillin and the salts of penicillin in food as follows: (a) 0.05 part per million (negligible residue) in the...

Penicillin V Potassium

Science.gov (United States)

Penicillin V potassium is used to treat certain infections caused by bacteria such as pneumonia and other ... heart valves and other symptoms) from coming back. Penicillin V potassium is in a class of medications ...

Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin.

Science.gov (United States)

Macy, Eric; Ngor, Eunis W

2013-01-01

Penicillin skin testing is rarely used to undiagnose penicillin "allergy" in the United States, partially because of concern that commercially available materials are inadequate. We determined whether skin testing with only commercially available penicilloyl-poly-lysine and penicillin followed by an oral amoxicillin challenge, if skin test-negative, can safely identify clinically significant penicillin allergy. Five hundred sequential persons with positive history of penicillin "allergy" were evaluated by skin testing with penicilloyl-poly-lysine and penicillin between June 8, 2010, and March 29, 2012. All persons with negative skin tests were given an oral amoxicillin challenge and observed for 1 hour. Persons undergoing penicillin allergy testing were representative of all health plan members with penicillin allergy. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had a positive skin test result. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had an acute objective oral amoxicillin challenge reaction. Fifteen persons (3.0%; 95% CI, 1.83%-4.98%) had subjective oral challenge reactions, either acute transient itching or dizziness. All were women and 11 (73.3%) had multiple drug intolerance syndrome. None had severe reactions or objective signs. These were not considered to be positive challenge reactions. Sixty-eight subjects (13.6%) who were negative on testing were exposed to 88 courses of penicillins during 90 days of follow-up. New reactions were reported after 4 courses (4.5%), 3 (75%) occurring in subjects with multiple drug intolerance syndrome. Penicillin skin testing, using only penicilloyl-poly-lysine and penicillin, followed by oral amoxicillin challenge, if negative, can safely identify clinically significant IgE-mediated penicillin allergy in patients who use health care in the United States at this time. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis

OpenAIRE

SPRATT, BG; ZHANG, QY; JONES, DM; HUTCHISON, A; BRANNIGAN, JA; DOWSON, CG

1989-01-01

Non-beta-lactamase-producing, penicillin-resistant strains of Neisseria meningitidis produce altered forms of penicillin-binding protein 2 that have decreased affinity for penicillin. The sequence of the penicillin-binding protein 2 gene (penA) from a penicillin-resistant strain of N. meningitidis was compared to the sequence of the same gene from penicillin-sensitive strains and from penicillin-sensitive and penicillin-resistant strains of Neisseria gonorrhoeae. The penA genes from penicilli...

Penicillin G (Potassium, Sodium) Injection

Science.gov (United States)

Penicillin G injection is used to treat and prevent certain infections caused by bacteria. Penicillin G injection is in a class of medications called penicillins. It works by killing bacteria that cause infections. ...

Poly(GMA/MA/MBAA) Copolymer Beads: a Highly Efficient Support Immobilizing Penicillin G Acylase

Institute of Scientific and Technical Information of China (English)

Ping XUE; Guan Zhong LU; Wan Yi LIU

2006-01-01

The hydrophilic, macroporous and beaded ternary copolymer of glycidyl methacrylate (GMA)/methacrylamide(MA)/N,N'-methylene-bis(acrylamide)(MBAA)was synthesized using the industrial agents by inverse suspension polymerization. The apparent activity of the immobilized penicillin G acylase reached 1096 IU/g for hydrolysis penicillin G on the beads with diameter of 0.11-0.13 mm, and it changed hardly after 50 cycles. It can be expected to be a good potential in industrial application.

Degradation kinetics and mechanism of penicillin G in aqueous matrices by ionizing radiation

Science.gov (United States)

Chu, Libing; Zhuang, Shuting; Wang, Jianlong

2018-04-01

The gamma radiation induced-degradation of a β-lactam antibiotic, penicillin G was investigated in aqueous solution. Special attention was paid to the effects of the organic substances such as peptone and glucose on penicillin G degradation, which can be found in the wastewater of the factories producing antibiotics. Results showed that gamma radiation was effective to degrade and deactivate penicillin G in pure water. With the initial concentrations of 0.27 mM, 1.34 mM and 2.68 mM, a complete removal of penicillin G could be achieved at the adsorbed doses of 2.5 kGy, 10 kGy and 20 kGy, respectively. Penicilloic acid from the β-lactam ring cleavage and a series of fragment compounds such as thiazolidine and penicillic acid were identified during gamma irradiation-induced degradation of penicillin G. Addition of Fe2+ was efficient to enhance the mineralization. The TOC removal efficiency of penicillin G was 21.7% using gamma irradiation alone at 10 kGy, which increased to 56.4% with 1.0 mM Fe2+ addition. The gamma radiation-induced degradation of penicillin G was inhibited in the presence of peptone and glucose and the inhibitive effect increased with increasing their concentrations. The rate constant, k of the pseudo first-order kinetics decreased by 74% and 64% in the presence of 1.0 g/L of peptone and glucose, respectively, and by 96% and 89% in the presence of 10 g/L of peptone and glucose, respectively. The ratio of k/k0 was increased by 1.3 times with H2O2 addition and by 3 times with Fe2+ addition, in the presence of 10 g/L of glucose. Adding Fe2+ was effective to improve the ionizing radiation induced degradation of penicillin G antibiotic in the glucose-containing wastewater.

Penicillin sensitivity among children without a positive history for penicillin allergy.

Science.gov (United States)

Cetinkaya, Feyzullah; Cag, Yakup

2004-06-01

To establish the prevalence of positive penicillin skin tests among outpatients without any drug reaction history. Skin testing was performed in 147 children (aged 6-13 years) who had had received a penicillin preparation at least three times in the last 12 months without any allergic reaction. Before testing, detailed pediatric and allergy history were learned and then all children were tested with benzyl penicilloyl polylysin (PPL) and mixture of minor antigenic determinants. The test procedures were made epidermally and intradermally subsequently in every subject. The overall frequency of positive skin reactions to penicillin antigens was 10.2%. A mild systemic reaction was observed in one of the children during testing with PPL. We concluded that frequent use of penicillin and other beta-lactam antibiotics leads to sensitization of children in our study population despite these children seem to be asymptomatic during testing time. Copyright 2004 Blackwell Munksgaard

Penicillin and Beta-Lactam Hypersensitivity.

Science.gov (United States)

Har, Daniel; Solensky, Roland

2017-11-01

Ten percent of patients report penicillin allergy, but more than 90% of these individuals can tolerate penicillins. Skin testing remains the optimal method for evaluation of possible IgE-mediated penicillin allergy and is recommended by professional societies, as the harms for alternative antibiotics include antimicrobial resistance, prolonged hospitalizations, readmissions, and increased costs. Removal of penicillin allergy leads to decreased utilization of broad-spectrum antibiotics, such as fluoroquinolones and vancomycin. There is minimal allergic cross-reactivity between penicillins and cephalosporins. IgE-mediated allergy to cephalosporins is usually side-chain specific and may warrant graded challenge with cephalosporins containing dissimilar R1 or R2 group side chains. Copyright © 2017 Elsevier Inc. All rights reserved.

In silico analysis of different generation β lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease.

Science.gov (United States)

Tripathi, Vijay; Tripathi, Pooja; Srivastava, Navita; Gupta, Dwijendra

2014-12-01

Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for β-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of β-lactam antibiotics and concluded that the third generation of β-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced β-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis.

US antibiotic stewardship and penicillin allergy.

Science.gov (United States)

Wada, Kara J; Calhoun, Karen H

2017-06-01

The purpose of this review is to improve otolaryngologists' antibiotic stewardship by detailing current approaches to penicillin allergy. Although up to 15% of hospitalized patients in the United States have a penicillin allergy recorded on their charts, fewer than 10% of these have a true penicillin allergy. Using a combination of a detailed allergy history, skin testing and graded-dose administration, many patients whose charts say 'penicillin-allergic' can safely be treated with penicillin and cross-reacting antibiotics. This permits use of narrower-spectrum antibiotics and saves money.

Penicillin allergy-getting the label right.

Science.gov (United States)

2017-03-01

Penicillin i allergy is a potentially serious adverse reaction that impacts on antibacterial treatment options. Although it is commonly reported and recorded in medical records, only a minority of patients with a label of penicillin allergy actually have the condition confirmed. The term 'allergy' may be incorrectly applied to adverse reactions that do not have an immunological basis and inappropriate labelling of penicillin allergy can lead to the unnecessary avoidance of penicillins and other beta-lactam antibacterials. Here, we discuss key features that help to distinguish patients at low or high risk of having a true penicillin allergy, summarise what is known about the risk of allergic reactions to other beta-lactam antibacterials in patients with penicillin allergy and discuss the steps to consider when assessing a label of penicillin allergy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk of redocumenting penicillin allergy in a cohort of patients with negative penicillin skin tests.

Science.gov (United States)

Rimawi, Ramzy H; Shah, Kaushal B; Cook, Paul P

2013-11-01

Even though electronic documentation of allergies is critical to patient safety, inaccuracies in documentation can potentiate serious problems. Prior studies have not evaluated factors associated with redocumenting penicillin allergy in the medical record despite a proven tolerance with a penicillin skin test (PST). Assess the prevalence of reinstating inaccurate allergy information and associated factors thereof. We conducted a retrospective observational study from August 1, 2012 to July 31, 2013 of patients who previously had a negative PST. We reviewed records from the hospital, long-term care facilities (LTCF), and primary doctors' offices. Vidant Health, a system of 10 hospitals in North Carolina. Patients with proven penicillin tolerance rehospitalized within a year period from the PST. We gauged hospital reappearances, penicillin allergy redocumentation, residence, antimicrobial use, and presence of dementia or altered mentation. Of the 150 patients with negative PST, 55 (37%) revisited a Vidant system hospital within a 1-year period, of whom 21 were LTCF residents. Twenty (36%) of the 55 patients had penicillin allergy redocumented without apparent reason. Factors associated with penicillin allergy redocumentation included age >65 years (P = 0.011), LTCF residence (P = 0.0001), acutely altered mentation (P Penicillin allergy was still listed in all 21 (100%) of the LTCF records. At our hospital system, penicillin allergies are often redocumented into the medical record despite proven tolerance. The benefits of PST may be limited by inadequately removing the allergy from different electronic/paper hospital, LTCF, primary physician, and community pharmacy records. © 2013 Society of Hospital Medicine.

21 CFR 558.155 - Chlortetracycline, sulfathiazole, penicillin.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlortetracycline, sulfathiazole, penicillin. 558... Specific New Animal Drugs for Use in Animal Feeds § 558.155 Chlortetracycline, sulfathiazole, penicillin... percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound...

[Determination of penicillin intermediate and three penicillins in milk by high performance capillary electrophoresis].

Science.gov (United States)

Tian, Chunqiu; Tan, Huarong; Gao, Liping; Shen, Huqin; Qi, Kezong

2011-11-01

A high performance capillary electrophoresis (HPCE) method was developed for the simultaneous determination of penicillin intermediate and penicillins in milk, including 6-amino-penicillanic acid (6-APA), penicillin G (PEN), ampicillin (AMP) and amoxicillin (AMO). The main parameters including the ion concentration and pH value of running buffer, separation voltage and column temperature were optimized systematically by orthogonal test. The four penicillins (PENs) were baseline separated within 4.5 min with the running buffer of 40 mmol/L potassium dihydrogen phosphate-20 mmol/L borax solution (pH 7.8), separation voltage of 28 kV and column temperature of 30 degrees C. The calibration curves showed good linearity in the range of 1.56 - 100 mg/L, and the correlation coefficients (r2) were between 0.9979 and 0.9998. The average recoveries at three spiked levels were in the range of 84.91% - 96.72% with acceptable relative standard deviations (RSDs) of 1.11% - 9.11%. The method is simple, fast, accurate and suitable for the determination of penicillins in real samples.

Positive Skin Test or Specific IgE to Penicillin Does Not Reliably Predict Penicillin Allergy

DEFF Research Database (Denmark)

Tannert, Line Kring; Mørtz, Charlotte G; Skov, Per Stahl

2017-01-01

INTRODUCTION: According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. OBJECTIVE: To investigate the clinical relevance...... of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. METHODS: A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged......-IgE measured (T0), and then skin tested and had s-IgE measured 4 weeks later (T1). RESULTS: Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T0. Positive ST result or positive s-IgE alone did not predict...

Studies on a possible using of penicillin and specific globulin for treatment of Siberia ulcer infection in irradiated animals

International Nuclear Information System (INIS)

Strel'nikov, V.A.; Mal'tsev, V.N.

1975-01-01

The efficiency of anti-anthracic globulin and penicillin for treating infectious anthrax was compared in experiments on 160 guinea pigs and 400 white mice irradiated with sub-lethal doses of cobalt-60 gamma rays. It was found that penicillin retained its effectiveness in the irradiated animals whereas anti-anthracic globulin lost much of its therapeutic efficiency. (auth.)

Penicillin and beta-lactam allergy: epidemiology and diagnosis.

Science.gov (United States)

Macy, Eric

2014-11-01

Penicillin is the most common beta-lactam antibiotic allergy and the most common drug class allergy, reported in about 8% of individuals using health care in the USA. Only about 1% of individuals using health care in the USA have a cephalosporin allergy noted in their medical record, and other specific non-penicillin, non-cephalosporin beta-lactam allergies are even rarer. Most reported penicillin allergy is not associated with clinically significant IgE-mediated reactions after penicillin rechallenge. Un-verified penicillin allergy is a significant and growing public health problem. Clinically significant IgE-mediated penicillin allergy can be safely confirmed or refuted using skin testing with penicilloyl-poly-lysine and native penicillin G and, if skin test is negative, an oral amoxicillin challenge. Acute tolerance of an oral therapeutic dose of a penicillin class antibiotic is the current gold standard test for a lack of clinically significant IgE-mediated penicillin allergy. Cephalosporins and other non-penicillin beta-lactams are widely, safely, and appropriately used in individuals, even with confirmed penicillin allergy. There is little, if any, clinically significant immunologic cross-reactivity between penicillins and other beta-lactams. Routine cephalosporin skin testing should be restricted to research settings. It is rarely needed clinically to safely manage patients and has unclear predictive value at this time. The use of alternative cephalosporins, with different side chains, is acceptable in the setting of a specific cephalosporin allergy. Carbapenems and monobactams are also safely used in individuals with confirmed penicillin allergy. A certain predictable, but low, rate of adverse reactions will occur with all beta-lactam antibiotic use both pre- and post-beta-lactam allergy evaluations.

Penicillin allergy: a practical approach to management.

OpenAIRE

Sussman, G L; Davis, K; Kohler, P F

1986-01-01

Although penicillin is nontoxic, it is highly immunogenic and is the most common drug that causes allergic reactions. A previous reaction to penicillin has been shown to be unreliable in predicting sensitivity in 75% to 90% of patients. To more accurately test for penicillin allergy, diagnostic skin test reagents have been developed; these include the major determinant (benzylpenicilloyl-polylysine) and the minor determinant mixture (penicillin G potassium, benzylpenicilloate sodium and benzy...

The Cost of Penicillin Allergy Evaluation.

Science.gov (United States)

Blumenthal, Kimberly G; Li, Yu; Banerji, Aleena; Yun, Brian J; Long, Aidan A; Walensky, Rochelle P

2017-09-22

Unverified penicillin allergy leads to adverse downstream clinical and economic sequelae. Penicillin allergy evaluation can be used to identify true, IgE-mediated allergy. To estimate the cost of penicillin allergy evaluation using time-driven activity-based costing (TDABC). We implemented TDABC throughout the care pathway for 30 outpatients presenting for penicillin allergy evaluation. The base-case evaluation included penicillin skin testing and a 1-step amoxicillin drug challenge, performed by an allergist. We varied assumptions about the provider type, clinical setting, procedure type, and personnel timing. The base-case penicillin allergy evaluation costs $220 in 2016 US dollars: $98 for personnel, $119 for consumables, and $3 for space. In sensitivity analyses, lower cost estimates were achieved when only a drug challenge was performed (ie, no skin test, $84) and a nurse practitioner provider was used ($170). Adjusting for the probability of anaphylaxis did not result in a changed estimate ($220); although other analyses led to modest changes in the TDABC estimate ($214-$246), higher estimates were identified with changing to a low-demand practice setting ($268), a 50% increase in personnel times ($269), and including clinician documentation time ($288). In a least/most costly scenario analyses, the lowest TDABC estimate was $40 and the highest was $537. Using TDABC, penicillin allergy evaluation costs $220; even with varied assumptions adjusting for operational challenges, clinical setting, and expanded testing, penicillin allergy evaluation still costs only about $540. This modest investment may be offset for patients treated with costly alternative antibiotics that also may result in adverse consequences. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A breakthrough in enzyme technology to fight penicillin resistance-industrial application of penicillin amidase.

Science.gov (United States)

Buchholz, Klaus

2016-05-01

Enzymatic penicillin hydrolysis by penicillin amidase (also penicillin acylase, PA) represents a Landmark: the first industrially and economically highly important process using an immobilized biocatalyst. Resistance of infective bacteria to antibiotics had become a major topic of research and industrial activities. Solutions to this problem, the antibiotics resistance of infective microorganisms, required the search for new antibiotics, but also the development of derivatives, notably penicillin derivatives, that overcame resistance. An obvious route was to hydrolyse penicillin to 6-aminopenicillanic acid (6-APA), as a first step, for the introduction via chemical synthesis of various different side chains. Hydrolysis via chemical reaction sequences was tedious requiring large amounts of toxic chemicals, and they were cost intensive. Enzymatic hydrolysis using penicillin amidase represented a much more elegant route. The basis for such a solution was the development of techniques for enzyme immobilization, a highly difficult task with respect to industrial application. Two pioneer groups started to develop solutions to this problem in the late 1960s and 1970s: that of Günter Schmidt-Kastner at Bayer AG (Germany) and that of Malcolm Lilly of Imperial College London. Here, one example of this development, that at Bayer, will be presented in more detail since it illustrates well the achievement of a solution to the problems of industrial application of enzymatic processes, notably development of an immobilization method for penicillin amidase suitable for scale up to application in industrial reactors under economic conditions. A range of bottlenecks and technical problems of large-scale application had to be overcome. Data giving an inside view of this pioneer achievement in the early phase of the new field of biocatalysis are presented. The development finally resulted in a highly innovative and commercially important enzymatic process to produce 6-APA that

Association between chronic urticaria and self-reported penicillin allergy.

Science.gov (United States)

Silverman, Susanna; Localio, Russell; Apter, Andrea J

2016-04-01

Penicillin allergy is the most commonly reported drug allergy and often presents with cutaneous symptoms. Other common diagnoses, such as chronic urticaria, may be falsely attributed to penicillin allergy. Because chronic urticaria is fairly common in the general population, evaluation of its prevalence in patients with self-reported penicillin allergy was of interest. Similarly, the prevalence of self-reported penicillin allergy in patients with chronic urticaria is not well known and also becomes interesting in light of the high prevalence of self-reported penicillin allergy in the general population. To determine the prevalence of self-reported penicillin allergy in patients with chronic urticaria and the prevalence of chronic urticaria in patients with self-reported penicillin allergy. This was a retrospective medical record review of 11,143 patients completed using the electronic health record of the University of Pennsylvania Allergy and Immunology clinic. The prevalence of self-reported penicillin allergy in patients with chronic urticaria was found to be approximately 3 times greater than in the general population. The prevalence of chronic urticaria in patients with self-reported penicillin allergy was also found to be approximately 3 times greater than in the population. This link between chronic urticaria and self-reported penicillin allergy highlights the need for clinicians to inquire about self-reported penicillin allergy in patients with chronic urticaria and to consider penicillin skin testing. Furthermore, patients who report penicillin allergy might actually have chronic urticaria, indicating the importance of inquiring about chronic urticaria symptoms in patients with self-reported penicillin allergy. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Elective penicillin skin testing in a pediatric outpatient setting.

Science.gov (United States)

Jost, Barbara Capes; Wedner, H James; Bloomberg, Gordon R

2006-12-01

Adverse reactions associated with penicillin-type antibiotics are common in pediatric practice, leading to the subsequent unnecessary use of alternative antibiotics. IgE-mediated penicillin allergy represents only a fraction of these adverse reactions. To examine (1) the trend of penicillin skin test reactivity during a recent 10-year interval, (2) the relative distribution of specific reagents related to a positive skin test result, and (3) skin test reactivity as a function of reaction history. Penicillin testing using 3 reagents--benzylpenicilloyl polylysine, penicillin G, and sodium penicilloate (penicillin A)--was conducted in a prospective study of 359 consecutive patients referred to an outpatient pediatric allergy clinic between January 1, 1993, and May 31, 2003. We also retrospectively reviewed penicillin skin test results for 562 children previously tested between January 1, 1979, and December 31, 1992. Between 1993 and 2003, the prevalence of penicillin skin test sensitivity markedly declined. Of all the positive skin test results between 1979 and 2002, either penicillin G or sodium penicilloate or both identified 34%, with sodium penicilloate alone responsible for 8.5%. The rate of positive skin test reactions was not significantly different between patients with vs without a history of suggestive IgE-mediated reactions. A marked decline in penicillin skin test sensitivity in the pediatric age group is identified. The minor determinant reagents penicillin G and sodium penicilloate are both necessary for determining potential penicillin allergy. Relating history alone to potential penicillin sensitivity is unreliable in predicting the presence or absence of a positive skin test result.

What if Fleming had not discovered penicillin?

Science.gov (United States)

Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A; Chinnathambi, Arunachalam

2014-09-01

What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called "supasulfas", and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents.

Short-time, high-dosage penicillin infusion therapy of syphilis

DEFF Research Database (Denmark)

Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

2003-01-01

The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

Meta-analysis of ceftriaxone compared with penicillin for the treatment of syphilis.

Science.gov (United States)

Liang, Zhen; Chen, Ya-Ping; Yang, Chun-Sheng; Guo, Wen; Jiang, Xiao-Xiao; Xu, Xi-Feng; Feng, Shou-Xin; Liu, Yan-Qun; Jiang, Guan

2016-01-01

Penicillin is the gold standard for treating syphilis. However, allergic reactions, poor drug tolerance and limited efficacy in patients remain a challenging problem. The objective of this meta-analysis was to compare the efficacy of ceftriaxone and penicillin based on data obtained from published randomised controlled trials (RCTs). The Cochrane Library, Medline, EBSCO, EMBASE and Ovid databases were searched for RCTs of ceftriaxone vs. penicillin for the treatment of syphilis. Estimated risk ratios (RRs) and 95% confidence intervals (CIs) were used to investigate the following outcome measures: 3-month response rate; 6-month response rate; 12-month response rate; relapse rate; serofast rate; and failure rate. Seven RCTs involving 281 participants (159 patients who received ceftriaxone and 122 patients who received penicillin) were included in the meta-analysis. There were no significant differences in 3-month response rate (RR=1.12, 95% CI 0.89-1.42), 6-month response rate (RR=1.02, 95% CI 0.75-1.38), 12-month response rate (RR=1.04, 95% CI 0.82-1.32), relapse rate (RR=0.91, 95% CI 0.45-1.84), serofast rate (RR=0.69, 95% CI 0.22-2.12) or failure rate (RR=0.66, 95% CI 0.03-15.76) in patients treated with ceftriaxone compared with those treated with penicillin. In conclusion, there is no evidence in the literature that ceftriaxone is less efficient than penicillin. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Positive Skin Test or Specific IgE to Penicillin Does Not Reliably Predict Penicillin Allergy.

Science.gov (United States)

Tannert, Line Kring; Mortz, Charlotte Gotthard; Skov, Per Stahl; Bindslev-Jensen, Carsten

According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. To investigate the clinical relevance of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged, but deemed allergic on the basis of a recent anaphylactic reaction or delayed reactions to skin testing. Another sample of convenience of 18 patients, 17 overlapping with the 25 challenged, with initial skin testing and s-IgE (median, 25; range, 3-121), months earlier (T -1 ), was repeat skin tested and had s-IgE measured (T 0 ), and then skin tested and had s-IgE measured 4 weeks later (T 1 ). Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T 0 . Positive ST result or positive s-IgE alone did not predict penicillin allergy. Among the 18 patients repeatedly tested, 46.2% (12 of 25) of positive ST results at T -1 were reproducibly positive at T 0 . For s-IgE, 54.2% (14 of 24) positive measurements were still positive at T 0 and 7 converted to positive at T 1 . The best predictor for a clinically significant (IgE-mediated) penicillin allergy is a combination of a positive case history with simultaneous positive ST result and s-IgE or a positive challenge result. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases of Actinobacteria.

Science.gov (United States)

Ogawara, Hiroshi

2016-09-01

PASTA domains (penicillin-binding protein and serine/threonine kinase-associated domains) have been identified in penicillin-binding proteins and serine/threonine kinases of Gram-positive Firmicutes and Actinobacteria. They are believed to bind β-lactam antibiotics, and be involved in peptidoglycan metabolism, although their biological function is not definitively clarified. Actinobacteria, especially Streptomyces species, are distinct in that they undergo complex cellular differentiation and produce various antibiotics including β-lactams. This review focuses on the distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases in Actinobacteria. In Actinobacteria, PASTA domains are detectable exclusively in class A but not in class B penicillin-binding proteins, in sharp contrast to the cases in other bacteria. In penicillin-binding proteins, PASTA domains distribute independently from taxonomy with some distribution bias. Particularly interesting thing is that no Streptomyces species have penicillin-binding protein with PASTA domains. Protein kinases in Actinobacteria possess 0 to 5 PASTA domains in their molecules. Protein kinases in Streptomyces can be classified into three groups: no PASTA domain, 1 PASTA domain and 4 PASTA domain-containing groups. The 4 PASTA domain-containing groups can be further divided into two subgroups. The serine/threonine kinases in different groups may perform different functions. The pocket region in one of these subgroup is more dense and extended, thus it may be involved in binding of ligands like β-lactams more efficiently.

A clinical decision-making algorithm for penicillin allergy.

Science.gov (United States)

Soria, Angèle; Autegarden, Elodie; Amsler, Emmanuelle; Gaouar, Hafida; Vial, Amandine; Francès, Camille; Autegarden, Jean-Eric

2017-12-01

About 10% of subjects report suspected penicillin allergy, but 85-90% of these patients are not truly allergic and could safely receive beta-lactam antibiotics Objective: To design and validate a clinical decision-making algorithm, based on anamnesis (chronology, severity, and duration of the suspected allergic reactions) and reaching a 100% sensitivity and negative predictive value, to assess allergy risk related to a penicillin prescription in general practise. All patients were included prospectively and explorated based on ENDA/EAACI recommendations. Results of penicillin allergy work-up (gold standard) were compared with results of the algorithm. Allergological work-up diagnosed penicillin hypersensitivity in 41/259 patients (15.8%) [95% CI: 11.5-20.3]. Three of these patients were diagnosed as having immediate-type hypersensitivity to penicillin, but had been misdiagnosed as low risk patients using the clinical algorithm. Thus, the sensitivity and negative predictive value of the algorithm were 92.7% [95% CI: 80.1-98.5] and 96.3% [95% CI: 89.6-99.2], respectively, and the probability that a patient with true penicillin allergy had been misclassified was 3.7% [95% CI: 0.8-10.4]. Although the risk of misclassification is low, we cannot recommend the use of this algorithm in general practice. However, the algorithm can be useful in emergency situations in hospital settings. Key messages True penicillin allergy is considerably lower than alleged penicillin allergy (15.8%; 41 of the 259 patients with suspected penicillin allergy). A clinical algorithm based on the patient's clinical history of the supposed allergic event to penicillin misclassified 3/41 (3.7%) truly allergic patients.

Back to the Future: Penicillin-Susceptible Staphylococcus aureus.

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Cheng, Matthew P; René, Pierre; Cheng, Alexandre P; Lee, Todd C

2016-12-01

Widespread penicillin usage rapidly resulted in the emergence of penicillin resistance in Staphylococcus aureus. However, new data suggest that penicillin susceptibility may be in a period of renaissance. The objective of our study was to quantify penicillin resistance in methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We retrospectively reviewed all adult MSSA bacteremia from April 2010 to April 2015 at the McGill University Health Centre (Montreal, QC, Canada). Susceptibility to penicillin, erythromycin, clindamycin, and trimethoprim-sulfamethoxazole (TMP-SMX) was determined in accordance with the Clinical & Laboratory Standards Institute guidelines. There were 324 unique episodes of MSSA bacteremia. Ninety (28%) isolates were susceptible to penicillin, 229 (71%) to erythromycin, 239 (74%) to clindamycin, and 317 (98%) to TMP-SMX. Isolates that were penicillin resistant were more likely to also be resistant to other antibiotics, but a statistically significant association was apparent only for erythromycin resistance (76/234, 32.2% vs 19/90, 21.1%, P = .04). The median age of patients was 67.5 years (interquartile range 52-78) and overall in-hospital 30-day mortality was 16.3% (53 deaths). After adjustment for patient age, there was no association between penicillin resistance and either intensive care unit admission or death. More than one-quarter of patients with MSSA bacteremia potentially could be treated with parenteral penicillin, which may offer pharmacokinetic advantages over other beta-lactam drugs and potentially improved outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Tackling inpatient penicillin allergies: Assessing tools for antimicrobial stewardship.

Science.gov (United States)

Blumenthal, Kimberly G; Wickner, Paige G; Hurwitz, Shelley; Pricco, Nicholas; Nee, Alexandra E; Laskowski, Karl; Shenoy, Erica S; Walensky, Rochelle P

2017-07-01

Reported penicillin allergy rarely reflects penicillin intolerance. Failure to address inpatient penicillin allergies results in more broad-spectrum antibiotic use, treatment failures, and adverse drug events. We aimed to determine the optimal approach to penicillin allergies among medical inpatients. We evaluated internal medicine inpatients reporting penicillin allergy in 3 periods: (1) standard of care (SOC), (2) penicillin skin testing (ST), and (3) computerized guideline application with decision support (APP). The primary outcome was use of a penicillin or cephalosporin, comparing interventions to SOC using multivariable logistic regression. There were 625 patients: SOC, 148; ST, 278; and APP, 199. Of 278 ST patients, 179 (64%) were skin test eligible; 43 (24%) received testing and none were allergic. In the APP period, there were 292 unique Web site views; 112 users (38%) completed clinical decision support. Although ST period patients did not have increased odds of penicillin or cephalosporin use overall (adjusted odds ratio [aOR] 1.3; 95% CI, 0.8-2.0), we observed significant increased odds of penicillin or cephalosporin use overall in the APP period (aOR, 1.8; 95% CI, 1.1-2.9) and in a per-protocol analysis of the skin tested subset (aOR, 5.7; 95% CI, 2.6-12.5). Both APP and ST-when completed-increased the use of penicillin and cephalosporin antibiotics among inpatients reporting penicillin allergy. While the skin tested subset showed an almost 6-fold impact, the computerized guideline significantly increased penicillin or cephalosporin use overall nearly 2-fold and was readily implemented. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

21 CFR 520.1696d - Penicillin V potassium tablets.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin V potassium tablets. 520.1696d Section... Penicillin V potassium tablets. (a) Specifications. Each tablet contains penicillin V potassium equivalent to 125 milligrams (200,000 units) or 250 milligrams (400,000 units) of penicillin V. (b) Sponsors. See...

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

Science.gov (United States)

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Labelling of pneumococcal penicillin-binding proteins with [3H]propionyl-ampicillin. A rapid method for monitoring penicillin-binding activity

International Nuclear Information System (INIS)

Hakenbeck, R.; Kohiyama, M.

1982-01-01

Penicillin-binding proteins (PBPs) are membrane components ubiquitous to all bacteria examined so far. Some of them are present in only a few copies per cell. The conventional method of visualizing these proteins consists in binding of radioactive penicillin to the fractions containing PBPs followed by SDS-PAGE and finally fluorography. Although this procedure is laborious, it is necessary for the determination of the identity as well as for the quantification of each PBP. On the other hand, when penicillin-binding conditions are to be examined or binding activity has to be followed through fractionation and purification of PBPs, no fast monitoring device for these proteins has been available. The authors developed a rapid and easy assay for penicillin-binding activity with a filter-binding technique using [ 3 H]propionyl ampicillin ( 3 H-PA) of high specific activity. As little 2μg of crude membranes obtained from the highly penicillin-sensitive, β-lactamase-negative organism Streptococcus pneumoniae, are sufficient to detect binding activity. In this paper they describe optimum conditions for the assay of PBPs and show that this binding activity correlates with the presence of native penicillin-binding proteins. (Auth.)

Double mutation of cell wall proteins CspB and PBP1a increases secretion of the antibody Fab fragment from Corynebacterium glutamicum

Science.gov (United States)

2014-01-01

Background Among other advantages, recombinant antibody-binding fragments (Fabs) hold great clinical and commercial potential, owing to their efficient tissue penetration compared to that of full-length IgGs. Although production of recombinant Fab using microbial expression systems has been reported, yields of active Fab have not been satisfactory. We recently developed the Corynebacterium glutamicum protein expression system (CORYNEX®) and demonstrated improved yield and purity for some applications, although the system has not been applied to Fab production. Results The Fab fragment of human anti-HER2 was successfully secreted by the CORYNEX® system using the conventional C. glutamicum strain YDK010, but the productivity was very low. To improve the secretion efficiency, we investigated the effects of deleting cell wall-related genes. Fab secretion was increased 5.2 times by deletion of pbp1a, encoding one of the penicillin-binding proteins (PBP1a), mediating cell wall peptidoglycan (PG) synthesis. However, this Δpbp1a mutation did not improve Fab secretion in the wild-type ATCC13869 strain. Because YDK010 carries a mutation in the cspB gene encoding a surface (S)-layer protein, we evaluated the effect of ΔcspB mutation on Fab secretion from ATCC13869. The Δpbp1a mutation showed a positive effect on Fab secretion only in combination with the ΔcspB mutation. The ΔcspBΔpbp1a double mutant showed much greater sensitivity to lysozyme than either single mutant or the wild-type strain, suggesting that these mutations reduced cell wall resistance to protein secretion. Conclusion There are at least two crucial permeability barriers to Fab secretion in the cell surface structure of C. glutamicum, the PG layer, and the S-layer. The ΔcspBΔpbp1a double mutant allows efficient Fab production using the CORYNEX® system. PMID:24731213

Next step in antibiotic stewardship: Pharmacist-provided penicillin allergy testing.

Science.gov (United States)

Gugkaeva, Z; Crago, J S; Yasnogorodsky, M

2017-08-01

Penicillin allergy limits therapeutic options for patients but often disappears over time, leaving patients erroneously labelled allergic and leading to the utilization of broad-spectrum and more expensive antibiotics. Penicillin allergy can be effectively assessed via skin testing. To improve patient access to penicillin allergy testing by implementing a pharmacist-provided service in a hospital setting. Beta-lactams remain a mainstream therapy for many infections due to their effectiveness, low side effects and affordability. Typically, patient access to penicillin allergy testing is limited by the availability of allergy specialists, who traditionally perform such testing. A pharmacist-provided penicillin allergy testing service was implemented at our hospital in 2015 and became a powerful antibiotic stewardship tool. Removing penicillin allergy from patient profiles significantly expanded therapeutic options, expedited discharges and reduced costs of care. Pharmacists can expand patient access to penicillin allergy testing. Pharmacist-provided penicillin allergy testing permitted optimized antibiotic treatment and expedited discharges. © 2017 John Wiley & Sons Ltd.

21 CFR 522.1696b - Penicillin G procaine aqueous suspension.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine aqueous suspension. 522... ANIMAL DRUGS § 522.1696b Penicillin G procaine aqueous suspension. (a) Specifications. Each milliliter contains penicillin G procaine equivalent to 300,000 units of penicillin G. (b) Sponsors. See sponsor...

Analysis of penicillin G in milk by liquid chromatography.

Science.gov (United States)

Boison, J O; Keng, L J; MacNeil, J D

1994-01-01

A liquid chromatographic (LC) method that was previously developed for penicillin G residues in animal tissues has been adapted to milk and milk products. After protein precipitation with sodium tungstate, samples are applied to a C18 solid-phase extraction cartridge, from which penicillin is eluted, derivatized with 1,2,4-triazole-mercuric chloride solution, and analyzed by isocratic liquid chromatography (LC) on a C18 column with UV detection at 325 nm. Quantitation is done with reference to penicillin V as an internal standard. Penicillin G recoveries were determined to be > 70% on standards fortified at 3-60 ppb. Accuracy approached 100% using the penicillin V internal standard. The detection limit for penicillin G residues was 3 ppb in fluid milk. Samples may be confirmed by thermospray/LC at concentrations approaching the detection limit of the UV method.

Isolation of Penicillium nalgiovense strains impaired in penicillin production by disruption of the pcbAB gene and application as starters on cured meat products.

Science.gov (United States)

Laich, Federico; Fierro, Francisco; Martin, Juan F

2003-06-01

The presence of some fungi on a variety of food products, like cheeses or cured meat products, is beneficial for the ripening of the product and for the development of specific flavour features. The utilization of these fungi as starters, which are inoculated normally as asexual spores on the food products at the beginning of the ripening process, is becoming a usual procedure in the food industry. The starter culture also prevents undesirable fungi or bacteria from growing on the product. Penicillium nalgiovense is the most frequently used starter for cured and fermented meat products, but the fact that this fungus can secrete penicillin to the meat product makes it important to get strains unable to synthesize this antibiotic. In this work we report that P. nalgiovense strains impaired in penicillin production can be obtained by disruption of the pcbAB gene (the first gene of the penicillin biosynthetic pathway). When applied as starter on cecina (a salted, smoke-cured beef meat product from the region of León, Spain), the pcbAB-disrupted strain showed no differences with respect to the parental penicillin-producing strain in its ability to colonize the meat pieces and to control their normal mycoflora. Both strains exerted a similar control on the presence of bacteria in cecina. A similar proportion of penicillin-sensitive and penicillin-resistant bacteria were isolated from pieces inoculated with the penicillin-producing or the non-producing P. nalgiovense strains. The decrease of the bacterial population on the surface of cecina seems to be due to the higher competition for nutrients as a consequence of the inoculation and development of the P. nalgiovense mycelium and not due to the production of penicillin by this fungus. Penicillin production was less affected than growth in a solid medium with high NaCl concentrations; this suggests that the high salt concentration present in cecina is not a limiting factor for penicillin production by P. nalgiovense.

Evaluation of aerobic co-composting of penicillin fermentation fungi residue with pig manure on penicillin degradation, microbial population dynamics and composting maturity.

Science.gov (United States)

Zhang, Zhenhua; Zhao, Juan; Yu, Cigang; Dong, Shanshan; Zhang, Dini; Yu, Ran; Wang, Changyong; Liu, Yan

2015-12-01

Improper treatment of penicillin fermentation fungi residue (PFFR), one of the by-products of penicillin production process, may result in environmental pollution due to the high concentration of penicillin. Aerobic co-composting of PFFR with pig manure was determined to degrade penicillin in PFFR. Results showed that co-composting of PFFR with pig manure can significantly reduce the concentration of penicillin in PFFR, make the PFFR-compost safer as organic fertilizer for soil application. More than 99% of penicillin in PFFR were removed after 7-day composting. PFFR did not affect the composting process and even promote the activity of the microorganisms in the compost. Quantitative PCR (qPCR) indicated that the bacteria and actinomycetes number in the AC samples were 40-80% higher than that in the pig-manure compost (CK) samples in the same composting phases. This research indicated that the aerobic co-composting was a feasible PFFR treatment method. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feasibility, Benefits, and Limitations of a Penicillin Allergy Skin Testing Service.

Science.gov (United States)

Narayanan, Prasanna P; Jeffres, Meghan N

2017-06-01

To critically examine the feasibility, benefits, and limitations of an inpatient penicillin skin testing service and how pharmacists can be utilized. A PubMed search was performed from July 2016 through September 2016 using the following search terms: penicillin skin testing, penicillin allergy, β-lactam allergy. Additional references were identified from a review of literature citations. All English-language studies assessing the use of penicillin skin testing as well as management and clinical outcomes of patients with a β-lactam allergy were evaluated. The prevalence of people self-identifying as penicillin allergic ranges from 10% to 20% in the United States. Being improperly labeled as penicillin allergic is associated with higher health care costs, worse clinical outcomes, and an increased prevalence of multidrug-resistant infections. Penicillin skin testing can be a tool used to clarify penicillin allergies and has been demonstrated to be a successful addition to antimicrobial stewardship programs in multiple health care settings. Prior to implementing a penicillin skin testing service, institutions will need to perform a feasibility analysis of who will supply labor and accept the financial burden as well as identify if the positive benefits of a penicillin skin testing service overcome the limitations of this diagnostic test. We conclude that institutions with high percentages of patients receiving non-β-lactams because of penicillin allergy labels would likely benefit the most from a penicillin skin testing service.

Effectiveness of penicillin, dicloxacillin and cefuroxime for penicillin-susceptible Staphylococcus aureus bacteraemia: a retrospective, propensity-score-adjusted case-control and cohort analysis.

Science.gov (United States)

Nissen, Jette Lindbjerg; Skov, Robert; Knudsen, Jenny Dahl; Ostergaard, Christian; Schønheyder, Henrik Carl; Frimodt-Møller, Niels; Benfield, Thomas

2013-08-01

Penicillin-susceptible Staphylococcus aureus isolates account for a fifth of cases of S. aureus bacteraemia (SAB) in Denmark, but little is known about treatment outcomes with penicillins or other antimicrobials. Here we compare penicillin, dicloxacillin and cefuroxime as definitive treatments in relation to 30 day mortality. A retrospective chart review of 588 penicillin-susceptible S. aureus cases at five centres from January 1995 to December 2010. Data on demographics, antimicrobial treatment, clinical signs and symptoms, and mortality at day 30 were collected. Hazard ratios (HRs) with 95% CIs associated with mortality were modelled using propensity-score-adjusted Cox proportional hazards regression analysis. Propensity-score-matched case-control studies were carried out. Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49-4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case-control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P = 0.037; and cefuroxime treatment (38%) versus dicloxacillin treatment (10%), P = 0.004. Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or dicloxacillin.

21 CFR 522.1696c - Penicillin G procaine in oil.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine in oil. 522.1696c Section... § 522.1696c Penicillin G procaine in oil. (a) Specifications. Each milliliter contains penicillin G procaine equivalent to 300,000 units of penicillin G. (b) Sponsor. See No. 053501 in § 510.600(c) of this...

75 FR 54017 - New Animal Drugs; Change of Sponsor; Penicillin G Benzathine and Penicillin G Procaine Suspension...

Science.gov (United States)

2010-09-03

... [Docket No. FDA-2010-N-0002] New Animal Drugs; Change of Sponsor; Penicillin G Benzathine and Penicillin G... animal drug regulations to reflect a change of sponsor for two new animal drug applications (NADAs) from..., Syracuse, NY 13201, has informed FDA that it has transferred ownership of, and all rights and interest in...

21 CFR 558.145 - Chlortetracycline, procaine penicillin, and sulfamethazine.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlortetracycline, procaine penicillin, and... FEEDS Specific New Animal Drugs for Use in Animal Feeds § 558.145 Chlortetracycline, procaine penicillin... pound, 4.4 percent (20 grams) of sulfamethazine, and procaine penicillin equivalent in activity to 10...

Comparative Efficacy of Penicillin and Doxycycline in Gonococcal Urethritis

Directory of Open Access Journals (Sweden)

Vinod K Sharma

1987-01-01

Full Text Available Ninety two episodes of gonococcal urethritis treated with one of the following regimens viz: (A 3 m. u. of fortified procaine penicillin made by adding 1 m.u. of crystalline penicillin to 2 m.u. of fortified procaine penicillin intramuscularly with one gram of probenecid orally, (B 3 m.u. of above fortified procaine penicillin intramuscularly alone, and (C 400 mg single oral dose of doxycycline produced success rates of 95,76.2 and 66.7% respectively. Post gonococcal urethritis was detected in 37% patients. Thirty four (45.94% of the 74 isolates of N. gonorrhoeae were relatively resistant (MIC 0. 12 units ml to penicillin. None of the 74 Neisseria gonorrhoeac strains was beta lactamase producing.

Allergy Testing in Children With Low-Risk Penicillin Allergy Symptoms.

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Vyles, David; Adams, Juan; Chiu, Asriani; Simpson, Pippa; Nimmer, Mark; Brousseau, David C

2017-08-01

Penicillin allergy is commonly reported in the pediatric emergency department (ED). True penicillin allergy is rare, yet the diagnosis results from the denial of first-line antibiotics. We hypothesize that all children presenting to the pediatric ED with symptoms deemed to be low-risk for immunoglobulin E-mediated hypersensitivity will return negative results for true penicillin allergy. Parents of children aged 4 to 18 years old presenting to the pediatric ED with a history of parent-reported penicillin allergy completed an allergy questionnaire. A prespecified 100 children categorized as low-risk on the basis of reported symptoms completed penicillin allergy testing by using a standard 3-tier testing process. The percent of children with negative allergy testing results was calculated with a 95% confidence interval. Five hundred ninety-seven parents completed the questionnaire describing their child's reported allergy symptoms. Three hundred two (51%) children had low-risk symptoms and were eligible for testing. Of those, 100 children were tested for penicillin allergy. The median (interquartile range) age at testing was 9 years (5-12). The median (interquartile range) age at allergy diagnosis was 1 year (9 months-3 years). Rash (97 [97%]) and itching (63 [63%]) were the most commonly reported allergy symptoms. Overall, 100 children (100%; 95% confidence interval 96.4%-100%) were found to have negative results for penicillin allergy and had their labeled penicillin allergy removed from their medical record. All children categorized as low-risk by our penicillin allergy questionnaire were found to have negative results for true penicillin allergy. The utilization of this questionnaire in the pediatric ED may facilitate increased use of first-line penicillin antibiotics. Copyright © 2017 by the American Academy of Pediatrics.

Penicillin-binding site on the Escherichia coli cell envelope

International Nuclear Information System (INIS)

Amaral, L.; Lee, Y.; Schwarz, U.; Lorian, V.

1986-01-01

The binding of 35 S-labeled penicillin to distinct penicillin-binding proteins (PBPs) of the cell envelope obtained from the sonication of Escherichia coli was studied at different pHs ranging from 4 to 11. Experiments distinguishing the effect of pH on penicillin binding by PBP 5/6 from its effect on beta-lactamase activity indicated that although substantial binding occurred at the lowest pH, the amount of binding increased with pH, reaching a maximum at pH 10. Based on earlier studies, it is proposed that the binding at high pH involves the formation of a covalent bond between the C-7 of penicillin and free epsilon amino groups of the PBPs. At pHs ranging from 4 to 8, position 1 of penicillin, occupied by sulfur, is considered to be the site that establishes a covalent bond with the sulfhydryl groups of PBP 5. The use of specific blockers of free epsilon amino groups or sulfhydryl groups indicated that wherever the presence of each had little or no effect on the binding of penicillin by PBP 5, the presence of both completely prevented binding. The specific blocker of the hydroxyl group of serine did not affect the binding of penicillin

Efficient Secretion of Recombinant Proteins from Rice Suspension-Cultured Cells Modulated by the Choice of Signal Peptide.

Science.gov (United States)

Huang, Li-Fen; Tan, Chia-Chun; Yeh, Ju-Fang; Liu, Hsin-Yi; Liu, Yu-Kuo; Ho, Shin-Lon; Lu, Chung-An

2015-01-01

Plant-based expression systems have emerged as a competitive platform in the large-scale production of recombinant proteins. By adding a signal peptide, αAmy3sp, the desired recombinant proteins can be secreted outside transgenic rice cells, making them easy to harvest. In this work, to improve the secretion efficiency of recombinant proteins in rice expression systems, various signal peptides including αAmy3sp, CIN1sp, and 33KDsp have been fused to the N-terminus of green fluorescent protein (GFP) and introduced into rice cells to explore the efficiency of secretion of foreign proteins. 33KDsp had better efficiency than αAmy3sp and CIN1sp for the secretion of GFP from calli and suspension-cultured cells. 33KDsp was further applied for the secretion of mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) from transgenic rice suspension-cultured cells; approximately 76%-92% of total rice-derived mGM-CSF (rmGM-CSF) was detected in the culture medium. The rmGM-CSF was bioactive and could stimulate the proliferation of a murine myeloblastic leukemia cell line, NSF-60. The extracellular yield of rmGM-CSF reached 31.7 mg/L. Our study indicates that 33KDsp is better at promoting the secretion of recombinant proteins in rice suspension-cultured cell systems than the commonly used αAmy3sp.

Is a positive intracutaneous test induced by penicillin mediated by histamine?

DEFF Research Database (Denmark)

Tannert, Line K; Falkencrone, Sidsel; Mortz, Charlotte G

2017-01-01

Background: Diagnostic workup of penicillin allergy comprises skin testing with penicillins, and patients are deemed allergic if skin test is positive. However, the literature suggests that skin test-positive patients may be challenge-negative, indicating that the skin test may be falsely positive....... Objective: To investigate real-time histamine release from a positive intracutaneous test induced by penicillin in patients with positive and negative challenges to penicillin. Methods: Skin microdialysis was performed in 21 penicillin-allergic patients with positive skin test, 13 non-allergic volunteers...... serving as negative controls, and 7 grass pollen-allergic patients serving as positive controls. Histamine was measured by microdialysis after skin test with penicillin/grass/NaCl. Penicillin challenge was subsequently performed in 12 of the patients. Results: Only 10/21 patients (47.6%) were skin test...

THE FACTS ABOUT PENICILLIN ALLERGY: A REVIEW

Directory of Open Access Journals (Sweden)

Sanjib Bhattacharya

2010-03-01

Full Text Available Hypersensitivity reactions are the major problem in the use of penicillins. Truepenicillin allergy is rare with the estimated frequency of anaphylaxis at 1-5 per 10 000cases of penicillin therapy. Hypersensitivity is however, its most important adversereaction resulting in nausea, vomiting, pruritus, urticaria, wheezing, laryngeal oedemaand ultimately, cardiovascular collapse. Identification of patients who erroneously carryß-lactam allergy leads to improved utilization of antibiotics and slows the spread ofmultiple drug-resistant bacteria. Cross-reactivity between penicillin and second and thirdgeneration cephalosporin is low and may be lower than the cross-reactivity betweenpenicillin and unrelated antibiotics.

New Mutations of Penicillin-Binding Proteins in Streptococcus agalactiae Isolates from Cattle with Decreased Susceptibility to Penicillin.

Science.gov (United States)

Hu, Yun; Kan, Yunchao; Zhang, Zhengtian; Lu, Zhanning; Li, Yanqiu; Leng, Chaoliang; Ji, Jun; Song, Shiyang; Shi, Hongfei

2018-02-23

Streptococcus agalactiae is a causal agent of bovine mastitis and is treated by β-lactam antibiotics (BLAs). Compared to penicillin-resistant S. agalactiae from humans, resistant strains in bovine are rarely reported. In this study, we aimed to investigate BLA resistance and mutations in penicillin-binding proteins (PBPs) of S. agalactiae in central and northeast China. The minimum inhibitory concentrations (MICs) of 129 penicillin-resistant S. agalactiae isolates from cows with mastitis were determined, and the related PBP genes were detected and sequenced. All strains were unsusceptible to penicillin G and mostly resistant to ampicillin, cefalexin, and ceftiofur sodium. One hundred twenty-nine strains were divided into 4 clonal groups and 8 sequence types by multilocus sequence typing analysis. We found a set of new substitutions in PBP1B, PBP2B, and PBP2X from most strains isolated from three provinces. The strains with high PBP mutations showed a broader unsusceptible spectrum and higher MICs than those with few or single mutation. Our research indicates unpredicted mutations in the PBP genes of S. agalactiae isolated from cows with mastitis treated by BLAs. This screening is the first of S. agalactiae from cattle.

Penicillin allergy: optimizing diagnostic protocols, public health implications, and future research needs.

Science.gov (United States)

Macy, Eric

2015-08-01

Unverified penicillin allergy is being increasingly recognized as a public health concern. The ideal protocol for verifying true clinically significant IgE-mediated penicillin allergy needs to use only commercially available materials, be well tolerated and easy to perform in both the inpatient and outpatient settings, and minimize false-positive determinations. This review concentrates on articles published in 2013 and 2014 that present new data relating to the diagnosis and management of penicillin allergy. Penicillin allergy can be safely evaluated at this time, in patients with an appropriate clinical history of penicillin allergy, using only penicilloyl-poly-lysine and native penicillin G as skin test reagents, if an oral challenge with amoxicillin 250 mg, followed by 1 h of observation, is given to all skin test negative individuals. Millions of individuals falsely labeled with penicillin allergy need to be evaluated to safely allow them to use penicillin-class antibiotics and avoid morbidity associated with penicillin avoidance. Further research is needed to determine optimal protocol(s). There will still be a 1-2% rate of adverse reactions reported with all future therapeutic penicillin-class antibiotic use, even with optimal methods used to determine acute penicillin tolerance. Only a small minority of these new reactions will be IgE-mediated.

21 CFR 524.1484h - Neomycin, penicillin, polymyxin, hydrocortisone suspension.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin, penicillin, polymyxin, hydrocortisone... NEW ANIMAL DRUGS § 524.1484h Neomycin, penicillin, polymyxin, hydrocortisone suspension. (a... milligrams of neomycin, 10,000 international units of penicillin G procaine, 5,000 international units of...

Penicillin-susceptible Staphylococcus aureus: susceptibility testing, resistance rates and outcome of infection.

Science.gov (United States)

Hagstrand Aldman, Malin; Skovby, Annette; I Påhlman, Lisa

2017-06-01

Staphylococcus aureus (SA) is an important human pathogen that causes both superficial and invasive infections. Penicillin is now rarely used in the treatment of SA infections due to widespread resistance and a concern about the accuracy of existing methods for penicillin susceptibility testing. The aims of the present study were to determine the frequency of penicillin-susceptible SA isolates from blood and wound cultures in Lund, Sweden, and to evaluate methods for penicillin testing in SA. We also wanted to investigate if penicillin-susceptible isolates are associated with higher mortality. Hundred blood culture isolates collected 2008/2009, 140 blood culture isolates from 2014/2015, and 141 superficial wound culture strains from 2015 were examined. Penicillin susceptibility was tested with disk diffusion according to EUCAST guidelines, and results were confirmed with a cloverleaf assay and PCR amplification of the BlaZ gene. Patient data for all bacteraemia cases were extracted from medical records. The disk diffusion method with assessment of both zone size and zone edge appearance had high accuracy in our study. About 57% of bacteraemia isolates from 2008/2009 were sensitive to penicillin compared to 29% in 2014/2015 (p penicillin susceptible. There was no difference in co-morbidity or mortality rates between patients with penicillin resistant and penicillin sensitive SA bacteraemia. Disk-diffusion is a simple and reliable method to detect penicillin resistance in SA, and susceptibility rates are significant. Penicillin has many theoretical advantages and should be considered in the treatment of SA bacteraemia when susceptible.

Improving the Effectiveness of Penicillin Allergy De-labeling.

Science.gov (United States)

Bourke, Jack; Pavlos, Rebecca; James, Ian; Phillips, Elizabeth

2015-01-01

Approximately 10-20% of hospitalized patients are labeled as penicillin allergic, and this is associated with significant health and economic costs. We looked at the effectiveness of penicillin allergy de-labeling in clinical practice with the aim of deriving risk stratification models to guide testing strategies. Consecutive patients aged 15 years or more, referred to a Western Australian public hospital drug allergy service between 2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and oral challenge (OC), and follow-up of post testing antibiotic usage were the main outcomes. SPT/IDT was performed in 401 consecutive patients with immediate (IMM) (≤ 1 hour) (n = 151) and nonimmediate (NIM) (>1 hour) (n = 250) reactions. Of 341 patients, 42 (12.3%) were SPT/IDT+ to ≥ 1 penicillin reagents, including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P penicillin VK (SPT/IDT negative predictive value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151 (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following the allergy label modifications (ALM) at the time of follow-up. Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and identifies selective beta-lactam allergies; however, incomplete adherence to ALM recommendations impairs effectiveness. Infrequent SPT/IDT+ and absent OC reactions in patients with NIM reactions suggest OC alone to be a safe and cost-effective de-labeling strategy that could improve the coverage of penicillin allergy de-labeling in lower risk populations. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Sensitivity of Amoxicillin-Resistant Helicobacter pylori to Other Penicillins

Science.gov (United States)

Dore, Maria P.; Graham, David Y.; Sepulveda, Antonia R.; Realdi, Giuseppe; Osato, Michael S.

1999-01-01

The sensitivities to penicillins and to a penicillin and β-lactamase inhibitor combination agent were determined for Helicobacter pylori strains that were sensitive, moderately resistant, or highly resistant to amoxicillin. All strains were resistant to nafcillin and oxacillin. Moderately resistant strains showed an intermediate zone of inhibition to ticarcillin, mezlocillin, piperacillin, and amoxicillin-clavulanic acid. High-level resistance was associated with the smallest zone size for all penicillins tested. PMID:10390249

Penicillin: the medicine with the greatest impact on therapeutic outcomes.

Science.gov (United States)

Kardos, Nelson; Demain, Arnold L

2011-11-01

The principal point of this paper is that the discovery of penicillin and the development of the supporting technologies in microbiology and chemical engineering leading to its commercial scale production represent it as the medicine with the greatest impact on therapeutic outcomes. Our nomination of penicillin for the top therapeutic molecule rests on two lines of evidence concerning the impact of this event: (1) the magnitude of the therapeutic outcomes resulting from the clinical application of penicillin and the subsequent widespread use of antibiotics and (2) the technologies developed for production of penicillin, including both microbial strain selection and improvement plus chemical engineering methods responsible for successful submerged fermentation production. These became the basis for production of all subsequent antibiotics in use today. These same technologies became the model for the development and production of new types of bioproducts (i.e., anticancer agents, monoclonal antibodies, and industrial enzymes). The clinical impact of penicillin was large and immediate. By ushering in the widespread clinical use of antibiotics, penicillin was responsible for enabling the control of many infectious diseases that had previously burdened mankind, with subsequent impact on global population demographics. Moreover, the large cumulative public effect of the many new antibiotics and new bioproducts that were developed and commercialized on the basis of the science and technology after penicillin demonstrates that penicillin had the greatest therapeutic impact event of all times. © Springer-Verlag 2011

Efficient production and secretion of bovine beta-lactoglobulin by Lactobacillus casei.

Science.gov (United States)

Hazebrouck, Stéphane; Pothelune, Laetitia; Azevedo, Vasco; Corthier, Gérard; Wal, Jean-Michel; Langella, Philippe

2007-04-06

Lactic acid bacteria (LAB) are attractive tools to deliver therapeutic molecules at the mucosal level. The model LAB Lactococcus lactis has been intensively used to produce and deliver such heterologous proteins. However, compared to recombinant lactococci, lactobacilli offer some advantages such as better survival in the digestive tract and immunomodulatory properties. Here, we compared different strategies to optimize the production of bovine beta-lactoglobulin (BLG), a major cow's milk allergen, in the probiotic strain Lactobacillus casei BL23. Using a nisin-inducible plasmid system, we first showed that L. casei BL23 strain could efficiently secrete a reporter protein, the staphylococcal nuclease (Nuc), with the lactococcal signal peptide SPUsp45 fused to its N-terminus. The fusion of SPUsp45 failed to drive BLG secretion but led to a 10-fold increase of intracellular BLG production. Secretion was significantly improved when the synthetic propeptide LEISSTCDA (hereafter called LEISS) was added to the N-terminus of the mature moiety of BLG. Secretion rate of LEISS-BLG was 6-fold higher than that of BLG alone while intracellular production reached then about 1 mg/L of culture. The highest yield of secretion was obtained by using Nuc as carrier protein. Insertion of Nuc between LEISS and BLG resulted in a 20-fold increase in BLG secretion, up to 27 microg/L of culture. Furthermore, the lactococcal nisRK regulatory genes were integrated into the BL23 chromosome. The nisRK insertion allowed a decrease of BLG synthesis in uninduced cultures while BLG production increased by 50% after nisin induction. Moreover, modification of the induction protocol led to increase the proportion of soluble BLG to around 74% of the total BLG production. BLG production and secretion in L. casei were significantly improved by fusions to a propeptide enhancer and a carrier protein. The resulting recombinant strains will be further tested for their ability to modulate the immune response

Efficient production and secretion of bovine β-lactoglobulin by Lactobacillus casei

Directory of Open Access Journals (Sweden)

Wal Jean-Michel

2007-04-01

Full Text Available Abstract Background Lactic acid bacteria (LAB are attractive tools to deliver therapeutic molecules at the mucosal level. The model LAB Lactococcus lactis has been intensively used to produce and deliver such heterologous proteins. However, compared to recombinant lactococci, lactobacilli offer some advantages such as better survival in the digestive tract and immunomodulatory properties. Here, we compared different strategies to optimize the production of bovine β-lactoglobulin (BLG, a major cow's milk allergen, in the probiotic strain Lactobacillus casei BL23. Results Using a nisin-inducible plasmid system, we first showed that L. casei BL23 strain could efficiently secrete a reporter protein, the staphylococcal nuclease (Nuc, with the lactococcal signal peptide SPUsp45 fused to its N-terminus. The fusion of SPUsp45 failed to drive BLG secretion but led to a 10-fold increase of intracellular BLG production. Secretion was significantly improved when the synthetic propeptide LEISSTCDA (hereafter called LEISS was added to the N-terminus of the mature moiety of BLG. Secretion rate of LEISS-BLG was 6-fold higher than that of BLG alone while intracellular production reached then about 1 mg/L of culture. The highest yield of secretion was obtained by using Nuc as carrier protein. Insertion of Nuc between LEISS and BLG resulted in a 20-fold increase in BLG secretion, up to 27 μg/L of culture. Furthermore, the lactococcal nisRK regulatory genes were integrated into the BL23 chromosome. The nisRK insertion allowed a decrease of BLG synthesis in uninduced cultures while BLG production increased by 50% after nisin induction. Moreover, modification of the induction protocol led to increase the proportion of soluble BLG to around 74% of the total BLG production. Conclusion BLG production and secretion in L. casei were significantly improved by fusions to a propeptide enhancer and a carrier protein. The resulting recombinant strains will be further tested

Antimicrobial susceptibility changes in Enterococcus faecalis following various penicillin exposure regimens.

OpenAIRE

Hodges, T L; Zighelboim-Daum, S; Eliopoulos, G M; Wennersten, C; Moellering, R C

1992-01-01

Penicillin-"virgin" strains of Enterococcus faecalis collected from a population of individuals with no previous antibiotic exposure were subjected in vitro to penicillin delivered as repeated pulses, stepwise increasing concentrations, or sustained levels of a single concentration. Changes in resistance to penicillin were assessed by determination of MICs, and time-kill studies were performed to evaluate changes in tolerance to the bactericidal effects of penicillin. Isogenic clones, derived...

[Penicillin allergy as a diagnostic problem. Overview and personal studies].

Science.gov (United States)

Walker, T; Jung, E G; Bayerl, C

2000-11-01

Penicillin allergy is a common clinical problem. The distinction between penicillin and para-infectious exanthems is difficult. We investigated the reliability of the history, as well as the sensitivity and specificity of skin tests and specific IgE levels. 160 patients with a history of penicillin allergy were retrospectively evaluated in the outpatient department of a dermatological clinic. Nearly 50% were diagnosed as allergic to penicillin by detection of specific IgE or skin test. About 60% of the patients with immediate type reactions, and 72% with maculo-papular erythema showed positive reactions in skin tests. Significantly more patients were diagnosed as allergic to penicillin by intradermal testing than by prick testing (p sensitivity of the specific IgE RAST was 17.9%; the specifity, 89.5%. For the prick test the sensitivity was 8.2%; the specificity 90.8%. For the intradermal test the sensitivity was 26%; the specifity 69.7%. We suggest a step by step procedure to detect penicillin allergy making the diagnostic results as valid as possible.

Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

Science.gov (United States)

Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

2012-01-01

Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

Effect of ionizing radiation on solid and water solution Penicillin G

International Nuclear Information System (INIS)

Ben Salem, I.; Amine, Kh.M.; Mabrouk, Y.; Saidi, M.; Mezni, M; Boulila, N; Hafez, E

2015-01-01

Penicillin G is a conventional antibiotic used for treatment of different kinds of infectious diseases. Due to its huge quantity production and resistance to biodegradability, this molecule has been a serious concern for clinicians and environmentalists. In this study, the effect of ionizing radiation on the penicillin G powder and in water solution was investigated. The Nuclear Magnetic Resonance (NMR) and fourier transform infrared spectroscopy (FTIR) analysis showed that the ionizing radiation at 50 kGy has no effect on the integrity of solid Penicillin G. The anti-microbial assays revealed that the activity of irradiated solid Penicillin G did not reduce and was stable after storage for one month. Ionizing radiation at 50 kGy led to degradation of water solution Penicillin G. The complete disappear of peaks observed in the control sample confirmed the broken of β-lactam ring, the decarboxylation and cleavage of the thiazolidine ring. The product issued from the irradiation of Penicillin G, was completely removed by the bacterium Cupriavidus.metallidurans. Thus, the ionizing irradiation followed by a biological treatment was very effective method for removing of Penicillin G antibiotics residuals from water solution.

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

Parent-Reported Penicillin Allergy Symptoms in the Pediatric Emergency Department.

Science.gov (United States)

Vyles, David; Chiu, Asriani; Simpson, Pippa; Nimmer, Mark; Adams, Juan; Brousseau, David C

2017-04-01

Children often present to the pediatric emergency department (ED) with a reported penicillin allergy. The true incidence of pediatric penicillin allergy is low, and patients may be inappropriately denied first-line antibiotics. We hypothesized that more than 70% of reported penicillin allergies in the pediatric ED are low risk for true allergy. Parents of children presenting to the pediatric ED with parent-reported penicillin allergy completed an allergy questionnaire. The questionnaire included age at allergy diagnosis, symptoms of allergy, and time to allergic reaction from first dose. The allergy symptoms were dichotomized into high and low risk in consultation with a pediatric allergist before questionnaire implementation. A total of 605 parents were approached; 500 (82.6%) completed the survey. The median (interquartile range) age of the children at diagnosis was 1 year (7 months, 2 years); 75% were diagnosed before their third birthday. Overall, 380 (76%) (95% confidence interval 72.3, 79.7) children had exclusively low-risk symptoms. The most commonly reported symptoms were rash (466, 92.8%) and itching (203, 40.6%). Of the 120 children with one or more high-risk symptom, facial swelling (50, 10%) was the most common. Overall, 354 children (71%) were diagnosed after their first exposure to penicillin. Symptom onset within 24 hours of medication administration occurred in 274 children (54.8%). Seventy-six percent of patients with parent-reported penicillin allergy have symptoms unlikely to be consistent with true allergy. Determination of true penicillin allergy in patients with low-risk symptoms may permit the increased use of first-line penicillin antibiotics. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Radiation-induced polymerization for the immobilization of penicillin acylase

International Nuclear Information System (INIS)

Boccu, E.; Carenza, M.; Lora, S.; Palma, G.; Veronese, F.M.

1987-01-01

The immobilization of Escherichia coli penicillin acylase was investigated by radiation-induced polymerization of 2-hydroxyethyl methacrylate at low temperature. A leak-proof composite that does not swell in water was obtained by adding the cross-linking agent trimethylolpropane trimethacrylate to the monomer-aqueous enzyme mixture. Penicillin acylase, which was immobilized with greater than 70% yield, possessed a higher Km value toward the substrate 6-nitro-3-phenylacetamidobenzoic acid than the free enzyme form (Km = 1.7 X 10(-5) and 1 X 10(-5) M, respectively). The structural stability of immobilized penicillin acylase, as assessed by heat, guanidinium chloride, and pH denaturation profiles, was very similar to that of the free-enzyme form, thus suggesting that penicillin acylase was entrapped in its native state into aqueous free spaces of the polymer matrix

Fleming's penicillin producing streain is not Penicillium chrysogenum but P. rubens

DEFF Research Database (Denmark)

Houbraken, Jos; Frisvad, Jens Christian; Samson, Robert A.

2011-01-01

Penicillium chrysogenum is a commonly occurring mould in indoor environments and foods, and has gained much attention for its use in the production of the antibiotic penicillin. Phylogenetic analysis of the most important penicillin producing P. chrysogenum isolates revealed the presence of two...... not produce these metabolites. Fleming’s original penicillin producing strain and the full genome sequenced strain of P. chrysogenum are re-identified as P. rubens. Furthermore, the well-known claim that Alexander Fleming misidentified the original penicillin producing strain as P. rubrum is discussed....

A re-appraisal of the conventional history of antibiosis and Penicillin.

Science.gov (United States)

Arseculeratne, S N; Arseculeratne, G

2017-05-01

The popular perception of the history of antibiosis and penicillin is that Alexander Fleming was the sole researcher on penicillin. The literature, however, has documentation of preceding persons who reported definitively on these topics, from the late 19 th century. Divergent reports on "firsts" in the discovery of antimicrobial activity of Penicillium and on the use of penicillin as a therapeutic agent, are present. This review adds knowledge from diverse sources, and restores historical priorities to the conventional story of Penicillin. © 2017 Blackwell Verlag GmbH.

21 CFR 520.1696 - Penicillin oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

An engineered diatom acting like a plasma cell secreting human IgG antibodies with high efficiency

Directory of Open Access Journals (Sweden)

Hempel Franziska

2012-09-01

Full Text Available Abstract Background Although there are many different expression systems for recombinant production of pharmaceutical proteins, many of these suffer from drawbacks such as yield, cost, complexity of purification, and possible contamination with human pathogens. Microalgae have enormous potential for diverse biotechnological applications and currently attract much attention in the biofuel sector. Still underestimated, though, is the idea of using microalgae as solar-fueled expression system for the production of recombinant proteins. Results In this study, we show for the first time that completely assembled and functional human IgG antibodies can not only be expressed to high levels in algal systems, but also secreted very efficiently into the culture medium. We engineered the diatom Phaeodactylum tricornutum to synthesize and secrete a human IgG antibody against the Hepatitis B Virus surface protein. As the diatom P. tricornutum is not known to naturally secrete many endogenous proteins, the secreted antibodies are already very pure making extensive purification steps redundant and production extremely cost efficient. Conclusions Microalgae combine rapid growth rates with all the advantages of eukaryotic expression systems, and offer great potential for solar-powered, low cost production of pharmaceutical proteins.

21 CFR 520.1696c - Penicillin V potassium for oral solution.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin V potassium for oral solution. 520....1696c Penicillin V potassium for oral solution. (a) Specifications. When reconstituted, each milliliter contains 25 milligrams (40,000 units) of penicillin V. (b) Sponsor. See No. 050604 in § 510.600(c) of this...

21 CFR 520.1696b - Penicillin G potassium in drinking water.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G potassium in drinking water. 520....1696b Penicillin G potassium in drinking water. (a) Specifications. When reconstituted, each milliliter contains penicillin G potassium equivalent to 20,000, 25,000, 40,000, 50,000, 80,000, or 100,000 units of...

Reappearance and treatment of penicillin-susceptible Staphylococcus aureus in a tertiary medical centre.

Science.gov (United States)

Chabot, Matthew R; Stefan, Mihaela S; Friderici, Jennifer; Schimmel, Jennifer; Larioza, Julius

2015-12-01

The purpose of this study was to describe trends in the prevalence and treatment patterns of penicillin-susceptible Staphylococcus aureus (SA) infections. This was a cross-sectional study of MSSA isolates from blood cultures at a tertiary-care centre between 1 January 2003 and 31 December 2012. All blood cultures positive for MSSA drawn during the study period were used to calculate the prevalence of penicillin-susceptible SA. Repeat cultures were excluded if they were isolated within 6 weeks of the index culture. The analysis was then restricted to inpatient blood cultures to assess treatment patterns. Antibiotics administered 48-96 h after the culture were analysed. A total of 446 blood cultures positive for MSSA were included in the analysis. There was a distinct trend showing an increase in the percentage of penicillin-susceptible SA over 10 years from 13.2% (95% CI 4.1%-22.3%) in 2003 to 32.4% (95% CI 17.3%-47.5%) in 2012 (P trend penicillin use for penicillin-susceptible SA bacteraemia increased from 0.0% in 2003-04 to 50.0% in 2011-12 (P trend = 0.007). Over a decade, there was an ∼3-fold increase in penicillin susceptibility among MSSA blood cultures at a large tertiary-care facility. Although treatment with penicillin increased over the study period, only 50% of penicillin-susceptible SA was treated with penicillin in the final study period. This study suggests that while susceptibility to penicillin appears to be returning in SA, the use of penicillin for penicillin-susceptible SA bacteraemia is low. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Proactive Approach to Penicillin Allergy Testing in Hospitalized Patients.

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Chen, Justin R; Tarver, Scott A; Alvarez, Kristin S; Tran, Trang; Khan, David A

Penicillin allergy testing is underutilized in inpatients despite its potential to immediately impact antibiotic treatment. Although most tested patients are able to tolerate penicillin, limited availability and awareness of this tool leads to the use of costly and harmful substitutes. We established an inpatient service at a large academic hospital to identify and test patients with a history of penicillin allergy with the goals of removing inaccurate diagnoses, reducing the use of beta-lactam alternatives, and educating patients and clinicians about the procedure. Eligible inpatients were flagged daily through the electronic medical record and prioritized via a specialized algorithm. A trained clinical pharmacist performed penicillin skin tests and challenges preemptively or by provider request. Clinical characteristics and antibiotic use were analyzed in tested patients. A total of 1203 applicable charts were detected by our system leading to 252 direct evaluations over 18 months. Overall, 228 subjects (90.5%) had their penicillin allergy removed. Of these, 223 were cleared via testing and 5 by discovery of prior penicillin tolerance. Among patients testing negative, 85 (38%) subsequently received beta-lactams, preventing 504 inpatient days and 648 outpatient days on alternative agents. Penicillin allergy testing using a physician-pharmacist team model effectively removes reported allergies in hospitalized patients. The electronic medical record is a valuable asset for locating and stratifying individuals who benefit most from intervention. Proactive testing substantially reduces unnecessary inpatient and outpatient use of beta-lactam alternatives that may otherwise go unaddressed. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Detection and determination of Oxytetracycline and Penicillin G ...

African Journals Online (AJOL)

Concentrations of oxytetracycline and penicillin G in all samples were between ranges of 45 -192 μg/l and 0-28 μg/l, respectively. The antibiotic residue positive samples which showed residues of oxytetracycline above the WTO/FAO/ CAC established maximum residue limit of 100μg/l were 40 (83.33%). For penicillin G, the ...

Electronic structure and physicochemical properties of selected penicillins

Science.gov (United States)

Soriano-Correa, Catalina; Ruiz, Juan F. Sánchez; Raya, A.; Esquivel, Rodolfo O.

Traditionally, penicillins have been used as antibacterial agents due to their characteristics and widespread applications with few collateral effects, which have motivated several theoretical and experimental studies. Despite the latter, their mechanism of biological action has not been completely elucidated. We present a theoretical study at the Hartree-Fock and density functional theory (DFT) levels of theory of a selected group of penicillins such as the penicillin-G, amoxicillin, ampicillin, dicloxacillin, and carbenicillin molecules, to systematically determine the electron structure of full ?-lactam antibiotics. Our results allow us to analyze the electronic properties of the pharmacophore group, the aminoacyl side-chain, and the influence of the substituents (R and X) attached to the aminoacyl side-chain at 6? (in contrast with previous studies focused at the 3? substituents), and to corroborate the results of previous studies performed at the semiempirical level, solely on the ?-lactam ring of penicillins. Besides, several density descriptors are determined with the purpose of analyzing their link to the antibacterial activity of these penicillin compounds. Our results for the atomic charges (fitted to the electrostatic potential), the bond orders, and several global reactivity descriptors, such as the dipole moments, ionization potential, hardness, and the electrophilicity index, led us to characterize: the active sites, the effect of the electron-attracting substituent properties and their physicochemical features, which altogether, might be important to understand the biological activity of these type of molecules.

A New Method to Determine the Half-Life for Penicillin Using Microcalorimeter

Science.gov (United States)

Li, Z. X.; Zhao, W. W.

2015-01-01

The dissolution process of penicillin in normal saline and isotonic glucose solution was reported using a microcalorimeter. Both the integral and differential heats of solution were measured. The quantitative relationships between the amount of heat released and the quantity of dissolved penicillin were established. Meanwhile, the kinetics and the half-life of the dissolution processes as well as the enthalpy of solution, the entropy of dissolution, and the free energy of dissolution were determined. The results showed that a change of the solvent from normal saline to isotonic glucose solution had little effect on the half-life of penicillin in the dissolution process, and there was no significant difference between the stabilities of penicillin in isotonic glucose solution and normal saline. Moreover, the dissolution process of penicillin in isotonic glucose solution followed the first-order kinetics. These results could provide a theoretical basis for the clinical applications of penicillin.

Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

Science.gov (United States)

Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

2015-01-01

Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

Improvement of Aspergillus nidulans penicillin production by targeting AcvA to peroxisomes.

Science.gov (United States)

Herr, Andreas; Fischer, Reinhard

2014-09-01

Aspergillus nidulans is able to synthesize penicillin and serves as a model to study the regulation of its biosynthesis. Only three enzymes are required to form the beta lactam ring tripeptide, which is comprised of l-cysteine, l-valine and l-aminoadipic acid. Whereas two enzymes, AcvA and IpnA localize to the cytoplasm, AatA resides in peroxisomes. Here, we tested a novel strategy to improve penicillin production, namely the change of the residence of the enzymes involved in the biosynthesis. We tested if targeting of AcvA or IpnA (or both) to peroxisomes would increase the penicillin yield. Indeed, AcvA peroxisomal targeting led to a 3.2-fold increase. In contrast, targeting IpnA to peroxisomes caused a complete loss of penicillin production. Overexpression of acvA, ipnA or aatA resulted in 1.4, 2.8 and 3.1-fold more penicillin, respectively in comparison to wildtype. Simultaneous overexpression of all three enzymes resulted even in 6-fold more penicillin. Combination of acvA peroxisomal targeting and overexpression of the gene led to 5-fold increase of the penicillin titer. At last, the number of peroxisomes was increased through overexpression of pexK. A strain with the double number of peroxisomes produced 2.3 times more penicillin. These results show that penicillin production can be triggered at several levels of regulation, one of which is the subcellular localization of the enzymes. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Breast abscess caused by penicillin resistant Pneumococci

Directory of Open Access Journals (Sweden)

Boppe Appalaraju

2011-01-01

Full Text Available Breast abscess is mostly caused by Staphylococcus aureus. A 26-year-old immunocompetent lady was admitted with breast abscess. Incision and drainage (I/D was done and Pneumococci were isolated from the drained pus. The patient was earlier treated with Augmentin which was later changed to linezolid after testing for antibiotic susceptibility. This strain showed a high level of resistance to penicillin. It had been noticed that there was a slow increase in the number of penicillin resistant Pneumococci isolated in our hospitals. The increase in penicillin-resistant Pneumococci correlates with the intensive use of beta-lactam antibiotics. Hence, antibiotics should be used judiciously, avoiding their use particularly in mild self-limiting upper respiratory infections. Attention therefore, should focus on monitoring resistance in Pneumococci to prevent mortality and morbidity associated with this organism, which continues to take a heavy toll on children and the elderly.

Penicillin G-Induced Chlamydial Stress Response in a Porcine Strain of Chlamydia pecorum

Directory of Open Access Journals (Sweden)

Cory Ann Leonard

2016-01-01

Full Text Available Chlamydia pecorum causes asymptomatic infection and pathology in ruminants, pigs, and koalas. We characterized the antichlamydial effect of the beta lactam penicillin G on Chlamydia pecorum strain 1710S (porcine abortion isolate. Penicillin-exposed and mock-exposed infected host cells showed equivalent inclusions numbers. Penicillin-exposed inclusions contained aberrant bacterial forms and exhibited reduced infectivity, while mock-exposed inclusions contained normal bacterial forms and exhibited robust infectivity. Infectious bacteria production increased upon discontinuation of penicillin exposure, compared to continued exposure. Chlamydia-induced cell death occurred in mock-exposed controls; cell survival was improved in penicillin-exposed infected groups. Similar results were obtained both in the presence and in the absence of the eukaryotic protein translation inhibitor cycloheximide and at different times of initiation of penicillin exposure. These data demonstrate that penicillin G induces the chlamydial stress response (persistence and is not bactericidal, for this chlamydial species/strain in vitro, regardless of host cell de novo protein synthesis.

What do I need to know about penicillin antibiotics?

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Barker, Charlotte I; Germovsek, Eva; Sharland, Mike

2017-02-01

The penicillins remain the class of antibiotics most commonly prescribed to children worldwide. In an era when the risks posed by antimicrobial resistance are growing, an understanding of antibiotic pharmacology and how to apply these principles in clinical practice is increasingly important. This paper provides an overview of the pharmacology of penicillins, focusing on those aspects of pharmacokinetics, pharmacodynamics and toxicity that are clinically relevant in paediatric prescribing. Penicillin allergy is frequently reported but a detailed history of suspected adverse reactions is essential to identify whether a clinically relevant hypersensitivity reaction is likely or not. The importance of additional factors such as antibiotic palatability, concordance and stewardship are also discussed, highlighting their relevance to optimal prescribing of the penicillins for children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prevalence and characteristics of reported penicillin allergy in an urban outpatient adult population.

Science.gov (United States)

Albin, Stephanie; Agarwal, Shradha

2014-01-01

Penicillin allergy remains the most common drug allergy, with a reported prevalence of 10% in the United States. Epidemiology of penicillin allergy in outpatient populations is relatively scarce. This study sought to determine the prevalence and characteristics of reported penicillin allergy in an urban outpatient population and to identify trends in clinical evaluation and management from a tertiary center serving a large inner-city population. A retrospective review of electronic medical records was performed of adult patients seen in the Internal Medicine Associates Clinic of Mount Sinai Hospital between January 31, 2012, and July 31, 2012. Medical records were selected based on the documentation of penicillin in patient's allergy section. Of the 11,761 patients seen in the clinic, 1348 patients (11.5%) reported a history of penicillin allergy. The most common allergic reactions were rash (37%), unknown/undocumented (20.2%), hives (18.9%), swelling/angioedema (11.8%), and anaphylaxis (6.8%). There was an increased prevalence of penicillin allergy in female patients compared with male patients (odds ratio [OR] = 1.82; 95% CI = 1.60, 2.08; p penicillin allergy compared with Caucasians (OR = 0.51; 95% CI = 0.32, 0.83; p = 0.007). However, only 78 (6%) of the patients reporting penicillin allergy had a referral to an allergy specialist. Overall, improved referral to an allergist will help to identify patients who have penicillin allergy requiring avoidance.

Poly(2-oxazoline)-Antibiotic Conjugates with Penicillins.

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Schmidt, Martin; Bast, Livia K; Lanfer, Franziska; Richter, Lena; Hennes, Elisabeth; Seymen, Rana; Krumm, Christian; Tiller, Joerg C

2017-09-20

The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. The conjugates are still antimicrobially active and up to 20 times more stable against penicillinase catalyzed hydrolysis. The antibiotic activity of the conjugates against Staphylococcus aureus in the presence of penicillinase is up to 350 times higher compared with the free antibiotics. Conjugates with a second antimicrobial function, a dodecyltrimethylammonium group (DDA-X), at the starting end of the PenG and PenV POx conjugates are more antimicrobially active than the conjugates without DDA-X and show high activity in the presence of penicillinase. For example, the conjugates DDA-X-PEtOx-PenG and DDA-X-PEtOx-PenV are 200 to 350 times more active against S. aureus in the presence of penicillinase and almost as effective as the penicillinase stable cloxacollin (Clox) under these conditions. These conjugates show even greater activity compared to cloxacollin without this enzyme present. Further, both conjugates kill Escherichia coli more effectively than PenG and Clox.

Clinical outcomes following inpatient penicillin allergy testing: A systematic review and meta-analysis.

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Sacco, K A; Bates, A; Brigham, T J; Imam, J S; Burton, M C

2017-09-01

A documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization. We performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included. Twenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], Pallergy testing was associated with decreased healthcare cost in four studies. Inpatient penicillin allergy testing is safe and effective in ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. Patients with a documented penicillin allergy who require penicillin should be tested during hospitalization given its benefit for individual patient outcomes and antibiotic stewardship. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

European Surveillance of Antimicrobial Consumption (ESAC): outpatient penicillin use in Europe (1997-2009).

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Versporten, Ann; Coenen, Samuel; Adriaenssens, Niels; Muller, Arno; Minalu, Girma; Faes, Christel; Vankerckhoven, Vanessa; Aerts, Marc; Hens, Niel; Molenberghs, Geert; Goossens, Herman

2011-12-01

Data on 13 years (1997-2009) of outpatient penicillin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project and analysed in detail. For the period 1997-2009, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient penicillin use in 33 European countries, we distinguished between narrow-spectrum penicillins (NSP), broad-spectrum penicillins (BSP), penicillinase-resistant penicillins (PRP) and combinations with β-lactamase inhibitors (COP). Total outpatient penicillin (ATC group J01C) use in 2009 varied by a factor of 3.8 between the countries with the highest (16.08 DID in France) and lowest (4.23 DID in the Russian Federation) use. COP represented 45.8%, BSP 40.7%, NSP 10.8% and PRP 2.6% of total European outpatient penicillin use. Total outpatient penicillin use significantly increased over time by 1.53 (SD 0.71) DID between 1997 and 2009. COP (mainly co-amoxiclav) increased by 2.17 (SD 0.40) DID, which was the result of its absolute increase as well as the observed shift from NSP and BSP towards COP. This increase exceeded 10% in 20 countries, where it coincided with a similar decrease in either BSP (15 countries) or NSP (5 countries). Penicillins represented the most widely used antibiotic subgroup in all 33 participating countries, albeit with considerable variation in their use patterns. For Europe, a continuous increase in overall penicillin use and of COP use was observed during the period 1997-2009.

Metronidazole in conjunction with penicillin neither prevents recurrence nor enhances recovery from peritonsillar abscess when compared with penicillin alone: a prospective, double-blind, randomized, placebo-controlled trial.

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Wikstén, Johanna E; Pitkäranta, Anne; Blomgren, Karin

2016-06-01

The objectives of this study were to evaluate the efficacy of metronidazole in conjunction with penicillin in preventing the recurrence of peritonsillar abscess (PTA) and to learn whether metronidazole enhances the recovery from PTA when compared with penicillin alone. In this prospective, double-blind, randomized, placebo-controlled trial, 200 adult outpatients with PTA at our ear, nose and throat emergency department received either penicillin (1 000 000IU) × 3 and metronidazole (400 mg) × 3 for 10 and 7 days orally (combination group, N = 100) or penicillin and placebo (penicillin group, N = 100) after incision and drainage of the PTA. Afterwards they received a symptom questionnaire via e-mail daily for 2 weeks, then weekly for 6 weeks. The primary outcome was efficacy of metronidazole in conjunction with penicillin in preventing PTA recurrence in 56 days; the secondary outcome was ability of metronidazole plus penicillin to enhance recovery from PTA in 28 days. All healthcare contacts were registered during follow-up. Registered on www.clinicaltrials.gov with the identifier NCT01255670. Of the 200 patients, 20 returned to hospital with recurrent symptoms, 10 in each group (P = 1.00). In the combination group, the mean (SD) duration of throat-related symptoms was 5.6 (5.0) days and in the penicillin group it was 5.3 (2.7) days, values for fever were 1.5 (0.9) and 1.6 (1.0) days, respectively, and those for poor overall physical condition were 4.0 (3.9) and 4.5 (4.9) days; there were no significant differences between groups. The adverse effects nausea and diarrhoea lasted longer in the combination group (P = 0.01). For healthy adult PTA patients treated with incision and drainage, metronidazole neither prevents recurrence nor enhances recovery when combined with penicillin compared with penicillin alone, but instead leads to increased adverse effects. © The Author 2016. Published by Oxford University Press on behalf of the British

Utility of minor determinants for skin testing in inpatient penicillin allergy evaluation.

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Geng, Bob; Eastman, Jacqueline J; Mori, Karen; Braskett, Melinda; Riedl, Marc A

2017-09-01

Most patients with a history of penicillin allergy can tolerate penicillin. Skin testing can identify tolerant patients, but not all known allergenic determinants are commercially available. Protocols exist that use only available reagents, but the sensitivity and safety of these protocols, particularly for hospitalized patients, are controversial. To determine the number of hospitalized patients referred for penicillin skin testing who showed unique positivity to the minor determinants penicilloate and penilloate. A retrospective chart review was conducted of all inpatients who underwent penicillin skin testing at 1 institution. Patients were referred by their treating physician. All patients underwent skin prick testing to benzylpenicilloyl polylysine (major determinant), penicillin G, penicilloate, penilloate (minor determinants), amoxicillin, and positive and negative controls. If the result was negative, then intradermal testing was done with the same penicillin determinants and the negative control. A 4-mm wheal with flare was considered a positive reaction. Inpatient penicillin skin testing was done in 528 subjects. Any positive test reaction was found in 107 subjects (20%). Three subjects (3%) reacted to penilloate only, 25 (23%) reacted to penicilloate only, 2 (2%) reacted to penicillin G only, and 8 (8%) reacted to amoxicillin only. Sixty-eight subjects (64%) reacted to a compound other than the major determinant. This study found a high rate of exclusively positive skin test reactions to the minor determinants penicilloate and penilloate. Because patients with positive test reactions are at increased risk of reaction to drug challenge, these data support the use of these reagents for penicillin skin testing in hospitalized patients. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Application of capillary electrophoresis to the simultaneous determination and stability study of four extensively used penicillin derivatives

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Brigitta Simon

2014-09-01

Full Text Available The applicability of capillary electrophoresis for the analysis of four extensively used penicillin derivatives (benzylpenicillin, ampicillin, amoxicillin, oxacilllin has been studied. Because of structural similarities, the electrophoretic behavior of these derivatives is very similar; consequently an efficient separation using the conventional capillary zone electrophoresis is hard to be achieved. Their simultaneous separation was solved by using micellar electrokinetic capillary chromatography, the separation being based on the differential partition of the analytes between the micellar and aqueous phase. Using a buffer solution containing 25 mM sodium tetraborate and 100 mM sodium dodecyl sulfate as surfactant, at a pH of 9.3, applying a voltage of + 25 kV at a temperature of 25 °C, we achieved the simultaneous separation of the studied penicillin derivatives in less then 5 minutes. The separation conditions were optimized and the analytical performance of the method was evaluated in terms of precision, linearity, limit of detection, and quantification. Also, a simple capillary zone electrophoresis method was applied to study the stability of the studied penicillin derivatives in water at different temperatures, using ciprofloxacin hydrochloride as internal standard. It was observed that the extent of the hydrolysis of penicillins in water is highly dependent on the time and also temperature.

Matroids and quantum-secret-sharing schemes

International Nuclear Information System (INIS)

Sarvepalli, Pradeep; Raussendorf, Robert

2010-01-01

A secret-sharing scheme is a cryptographic protocol to distribute a secret state in an encoded form among a group of players such that only authorized subsets of the players can reconstruct the secret. Classically, efficient secret-sharing schemes have been shown to be induced by matroids. Furthermore, access structures of such schemes can be characterized by an excluded minor relation. No such relations are known for quantum secret-sharing schemes. In this paper we take the first steps toward a matroidal characterization of quantum-secret-sharing schemes. In addition to providing a new perspective on quantum-secret-sharing schemes, this characterization has important benefits. While previous work has shown how to construct quantum-secret-sharing schemes for general access structures, these schemes are not claimed to be efficient. In this context the present results prove to be useful; they enable us to construct efficient quantum-secret-sharing schemes for many general access structures. More precisely, we show that an identically self-dual matroid that is representable over a finite field induces a pure-state quantum-secret-sharing scheme with information rate 1.

[Phase transfer catalyzed bioconversion of penicillin G to 6-APA by immobilized penicillin acylase in recyclable aqueous two-phase systems with light/pH sensitive copolymers].

Science.gov (United States)

Jin, Ke-ming; Cao, Xue-jun; Su, Jin; Ma, Li; Zhuang, Ying-ping; Chu, Ju; Zhang, Si-liang

2008-03-01

Immobilized penicillin acylase was used for bioconversion of penicillin PG into 6-APA in aqueous two-phase systems consisting of a light-sensitive polymer PNBC and a pH-sensitive polymer PADB. Partition coefficients of 6-APA was found to be about 5.78 in the presence of 1% NaCl. Enzyme kinetics showed that the reaction reached equilibrium at roughly 7 h. The 6-APA mole yields were 85.3% (pH 7.8, 20 degrees C), with about 20% increment as compared with the reaction of single aqueous phase buffer. The partition coefficient of PG (Na) varied scarcely, while that of the product, 6-APA and phenylacetic acid (PA) significantly varied due to Donnan effect of the phase systems and hydrophobicity of the products. The variation of the partition coefficients of the products also affected the bioconversion yield of the products. In the aqueous two-phase systems, the substrate, PG, the products of 6-APA and PA were biased in the top phase, while immobilized penicillin acylase at completely partitioned at the bottom. The substrate and PG entered the bottom phase, where it was catalyzed into 6-APA and PA and entered the top phase. Inhibition of the substrate and products was removed to result in improvement of the product yield, and the immobilized enzyme showed higher efficiency than the immobilized cells and occupied smaller volume. Compared with the free enzyme, immobilized enzyme had greater stability, longer life-time, and was completely partitioned in the bottom phase and recycle. Bioconversion in two-phase systems using immobilized penicillin acylase showed outstanding advantage. The light-sensitive copolymer forming aqueous two-phase systems could be recovered by laser radiation at 488 nm or filtered 450 nm light, while pH-sensitive polymer PADB could be recovered at the isoelectric point (pH 4.1). The recovery of the two copolymers was between 95% and 99%.

Full-course drug challenge test in the diagnosis of delayed allergic reactions to penicillin.

Science.gov (United States)

Borch, Jakob E; Bindslev-Jensen, Carsten

2011-01-01

Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy. To improve sensitivity of the diagnostic work-up in diagnosing penicillin allergics with histories of allergic reactions on day 2 or later in the course of penicillin treatment. A full-course DCT was added to the current protocol if specific IgE, skin tests and DCT were all negative in patients who had a nonimmediate reaction to penicillin treatment. Sixteen patients with a history of an immediate reaction to penicillin treatment underwent testing with negative outcomes. Fifty percent of patients undergoing full-course DCT experienced a cutaneous adverse drug reaction. None of the controls reacted (p = 0.001). The mean time of reaction was 6 days. Penicillin V accounted for most reactions. Urticaria was the most frequent clinical reaction observed. Full-course DCT offers an improvement of sensitivity and predictive values of the diagnostic work-up of allergic reactions to penicillin occurring on day 2 of penicillin treatment or later. Copyright © 2011 S. Karger AG, Basel.

Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark

DEFF Research Database (Denmark)

Egelund, Gertrud Baunbæk; Jensen, Andreas Vestergaard; Andersen, Stine Bang

2017-01-01

BACKGROUND: Community-acquired pneumonia (CAP) is a severe infection, with high mortality. Antibiotic strategies for CAP differ across Europe. The objective of the study was to describe the epidemiology of CAP in Denmark and evaluate the prognosis of patients empirically treated with penicillin...... penicillin-G/V using logistic regression analysis. RESULTS: We included 1320 patients. The incidence of hospitalized CAP was 3.1/1000 inhabitants. Median age was 71 years (IQR; 58-81) and in-hospital mortality was 8%. Median duration of antibiotic treatment was 10 days (IQR; 8-12). In total 45% were treated...... with penicillin-G/V as empiric monotherapy and they did not have a higher mortality compared to patients treated with broader-spectrum antibiotics (OR 0.92, CI 95% 0.55-1.53). CONCLUSION: The duration of treatment exceeded recommendations in European guidelines. Empiric monotherapy with penicillin...

Nuclear magnetic resonance of D(-)-α-amino-benzyl penicillin

International Nuclear Information System (INIS)

Aguiar, Monica R.M.P.; Gemal, Andre L.; San Gil, Rosane A.S.; Menezes, Sonia M.C.

1995-01-01

The development of new drugs from penicillins has induced the study of this substances by nuclear magnetic resonance. Several samples of D(-)-α-amino-benzyl penicillin were analysed using 13 C NMR techniques in aqueous solution and solid state. Spectral data of this compounds were shown and the results were presented and analysed

Reconstitution of TCA cycle with DAOCS to engineer Escherichia coli into an efficient whole cell catalyst of penicillin G.

Science.gov (United States)

Lin, Baixue; Fan, Keqiang; Zhao, Jian; Ji, Junjie; Wu, Linjun; Yang, Keqian; Tao, Yong

2015-08-11

Many medically useful semisynthetic cephalosporins are derived from 7-aminodeacetoxycephalosporanic acid (7-ADCA), which has been traditionally made by the polluting chemical method. Here, a whole-cell biocatalytic process based on an engineered Escherichia coli strain expressing 2-oxoglutarate-dependent deacetoxycephalosporin C synthase (DAOCS) for converting penicillin G to G-7-ADCA is developed. The major engineering strategy is to reconstitute the tricarboxylic acid (TCA) cycle of E. coli to force the metabolic flux to go through DAOCS catalyzed reaction for 2-oxoglutarate to succinate conversion. Then the glyoxylate bypass was disrupted to eliminate metabolic flux that may circumvent the reconstituted TCA cycle. Additional engineering steps were taken to reduce the degradation of penicillin G and G-7-ADCA in the bioconversion process. These steps include engineering strategies to reduce acetate accumulation in the biocatalytic process and to knock out a host β-lactamase involved in the degradation of penicillin G and G-7-ADCA. By combining these manipulations in an engineered strain, the yield of G-7-ADCA was increased from 2.50 ± 0.79 mM (0.89 ± 0.28 g/L, 0.07 ± 0.02 g/gDCW) to 29.01 ± 1.27 mM (10.31 ± 0.46 g/L, 0.77 ± 0.03 g/gDCW) with a conversion rate of 29.01 mol%, representing an 11-fold increase compared with the starting strain (2.50 mol%).

Penicillin at the late stage of leptospirosis: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Costa Everaldo

2003-01-01

Full Text Available There is evidence that an early start of penicillin reduces the case-fatality rate of leptospirosis and that chemoprophylaxis is efficacious in persons exposed to the sources of leptospira. The existent data, however, are inconsistent regarding the benefit of introducing penicillin at a late stage of leptospirosis. The present study was developed to assess whether the introduction of penicillin after more than four days of symptoms reduces the in-hospital case-fatality rate of leptospirosis. A total of 253 patients aged 15 to 76 years with advanced leptospirosis, i.e., more than four days of symptoms, admitted to an infectious disease hospital located in Salvador, Brazil, were selected for the study. The patients were randomized to one of two treatment groups: with intravenous penicillin, 6 million units day (one million unit every four hours for seven days (n = 125 and without (n = 128 penicillin. The main outcome was death during hospitalization. The case-fatality rate was approximately twice as high in the group treated with penicillin (12%; 15/125 than in the comparison group (6.3%; 8/128. This difference pointed in the opposite direction of the study hypothesis, but was not statistically significant (p = 0.112. Length of hospital stay was similar between the treatment groups. According to the results of the present randomized clinical trial initiation of penicillin in patients with severe forms of leptospirosis after at least four days of symptomatic leptospirosis is not beneficial. Therefore, more attention should be directed to prevention and earlier initiation of the treatment of leptospirosis.

Biological characterization of a new radioactive labeling reagent for bacterial penicillin-binding proteins

International Nuclear Information System (INIS)

Preston, D.A.; Wu, C.Y.; Blaszczak, L.C.; Seitz, D.E.; Halligan, N.G.

1990-01-01

Radiolabeled penicillin G is widely used as the imaging agent in penicillin-binding protein (PBP) assays. The disadvantages of most forms of labeled penicillin G are instability on storage and the long exposure times usually required for autoradiography or fluorography of electrophoretic gels. We investigated the utility of radioiodinated penicillin V as an alternative reagent. Radioiodination of p-(trimethylstannyl)penicillin V with [ 125 I]Na, using a modification of the chloramine-T method, is simple, high yielding, and site specific. We demonstrated the general equivalence of commercially obtained [ 3 H]penicillin G and locally synthesized [ 125 I]penicillin V (IPV) in their recognition of bacterial PBPs. Profiles of PBPs in membranes from Bacteroides fragilis, Escherichia coli, Providencia rettgeri, Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, and Enterococcus faecium labeled with IPV or [3H]penicillin G were virtually identical. Use of IPV as the imaging agent in competition experiments for determination of the affinities of various beta-lactam antibiotics for the PBPs of E. coli yielded results similar to those obtained in experiments with [ 3 H]penicillin G. Dried electrophoretic gels from typical PBP experiments, using IPV at 37.3 Ci/mmol and 30 micrograms/ml, exposed X-ray film in 8 to 24 h. The stability of IPV on storage at 4 degrees C was inversely proportional to specific activity. At 37.3 Ci/mmol and 60 micrograms/ml, IPV retained useful activity for at least 60 days at 4 degrees C. IPV represents a practical and stable reagent for rapid PBP assays

Regulation, circulation and distribution of penicillin in Portugal (1944-1954).

Science.gov (United States)

Bell, Victoria; Rui Pita, João; Pereira, Ana Leonor

Portugal did not participate in World War II but was one of the first countries in the world to receive penicillin for civilian use. The Portuguese Red Cross began to import the antibiotic from the United States of America in 1944 and appointed a controlling committee to oversee its distribution, due to the small amount available. In 1945, as world production increased, penicillin began to be distributed through the normal channels. An important role in its regulation was played by the official department responsible for controlling pharmaceutical and chemical products in Portugal, the Comissão Reguladora dos Produtos Químicos e Farmacêuticos (Regulatory Committee for Chemical and Pharmaceutical Products). Penicillin was imported as a raw material from 1947 and the first medicaments containing penicillin, prepared in Portugal, were released into the commercial circuit in 1948. A laboratory had been established in 1942 by the Comissão Reguladora for the analytical verification of medicaments and medicinal products with the aim of certifying their quality and minimizing the number of products with no attested therapeutic efficacy. The number of medicaments analysed by this laboratory increased substantially from 72 in the year of its foundation (1942) to 2478 in 1954, including, after 1948, medicaments containing penicillin. The aim of the present paper was to elucidate the role of the Comissão Reguladora dos Produtos Químicos e Farmacêuticos in regulating and controlling the distribution of penicillin in Portugal during the 1940s and 1950s.

Molecular epidemiology of penicillin-nonsusceptible Streptococcus pneumoniae among children in Greece

NARCIS (Netherlands)

D. Bogaert (Debby); G.A. Syrogiannopoulos; I.N. Grivea; R. de Groot (Ronald); N.G. Beratis; P.W.M. Hermans (Peter)

2000-01-01

textabstractA total of 145 penicillin-nonsusceptible Streptococcus pneumoniae strains were isolated from young carriers in Greece and analyzed by antibiotic susceptibility testing, serotyping, restriction fragment end labeling (RFEL), and penicillin-binding protein

The Molecular Structure of Penicillin

Science.gov (United States)

Bentley, Ronald

2004-01-01

Overviews of the observations that constitute a structure proof for penicillin, specifically aimed at the general student population, are presented. Melting points and boiling points were criteria of purity and a crucial tool was microanalysis leading to empirical formulas.

Depletion of penicillin G residues in sows after intramuscular injection

Science.gov (United States)

In 2011, the Food Safety Inspection Service (FSIS) switched from using the Fast Antimicrobial Screen Test (FAST) for screening animal tissues for penicillin to using the Charm-Kidney Inhibition Swab test (KIS). The switch provided a quicker test and lower detection limits for penicillin when used o...

Diagnosis of penicillin allergy revisited

DEFF Research Database (Denmark)

Hjortlund, J; Mørtz, Charlotte G; Skov, P S

2013-01-01

Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed...

Penicillin Hydrolysis: A Kinetic Study of a Multistep, Multiproduct Reaction.

Science.gov (United States)

McCarrick, Thomas A.; McLafferty, Fred W.

1984-01-01

Background, procedures used, and typical results are provided for an experiment in which students carry out the necessary measurements on the acid-catalysis of penicillin in two hours. By applying kinetic theory to the data obtained, the reaction pathways for the hydrolysis of potassium benzyl penicillin are elucidated. (JN)

Penicillin as empirical therapy for patients hospitalised with community acquired pneumonia at a Danish hospital

DEFF Research Database (Denmark)

Kirk, O; Glenthøj, Jonathan Peter; Dragsted, Ulrik Bak

2001-01-01

and outcome parameters were collected. Three groups were established according to the initial choice of antibiotic(s): penicillin only (n = 160); non-allergic patients starting broader spectrum therapy (n = 54); and patients with suspected penicillin allergy (n = 29). RESULTS: The overall mortality within...... treated with penicillin monotherapy. No differences in clinical outcomes were documented between patients treated empirically with broad-spectrum therapy and penicillin monotherapy. Therefore, penicillin seems to be a reasonable first choice for initial therapy of HCAP in Denmark as in other regions...

Efficient quantum secret sharing scheme with two-particle entangled states

International Nuclear Information System (INIS)

Zhu Zhen-Chao; Fu An-Min; Zhang Yu-Qing

2011-01-01

This paper proposes a protocol for multi-party quantum secret sharing utilizing four non-orthogonal two-particle entangled states following some ideas in the schemes proposed by Liu et al. (2006 Chin. Phys. Lett. 23 3148) and Zhang et al. (2009 Chin. Phys. B 18 2149) respectively. The theoretical efficiency for qubits of the new protocol is improved from 50% to approaching 100%. All the entangled states can be used for generating the private key except those used for the eavesdropping check. The validity of a probable attack called opaque cheat attack to this kind of protocols is considered in the paper for the first time. (general)

Comparison of Lateral Flow Assay, Kidney Inhibition Swab, and Liquid Chromatography-Tandem Mass Spectrometry for the Detection of Penicillin G Residues in Sow Urine.

Science.gov (United States)

Shelver, Weilin L; Chakrabarty, Shubhashis; Smith, David J

2017-03-01

Sows (n = 126) were administered penicillin G; urine, collected at slaughter, was screened by kidney inhibition swab (KIS; 4 h testing time) and then stored at -80 °C (∼1200 days) until analysis by lateral flow assay (LF, ∼5 min testing time) and tandem quadrupole LC-MS/MS (TQ) analysis. The stability of penicillin in urine during storage was verified using TQ analyses. Quantitative results were well-correlated (R 2 = 0.98) with only a ∼10% decrease in penicillin concentration during the 3-year storage period. KIS retesting of stored samples returned results consistent with the original analyses. Lateral flow assay results were highly correlated with the KIS and TQ results. A KIS positive sample, which was not confirmed by TQ or LF, was assayed by Triple-TOF LC-MS to determine the cause of the apparent false positive. This study suggests LF can be used to quickly and efficiently screen for penicillin G residues before slaughter.

Intrapartum antibiotic exposure for group B Streptococcus treatment did not increase penicillin allergy in children.

Science.gov (United States)

May, Sara M; Hartz, Martha F; Joshi, Avni Y; Park, Miguel A

2016-02-01

Group B Streptococcus (GBS) is the leading infectious cause of neonatal morbidity and mortality in the United States. Intrapartum administration of antibiotics to mothers with positivity to GBS is performed for prevention, with penicillin being the drug of choice. Previous studies have noted an increase in atopic diseases other than drug allergy associated with intrapartum antibiotic exposure. To determine whether intrapartum exposure to penicillin for GBS increases the likelihood of penicillin allergy in children. Retrospective chart review was performed for patients from a birth cohort. The birth cohort included children born in 2007 at a tertiary care hospital and had local addresses. Information on GBS status of the mother, intrapartum antibiotic exposure, delivery mode, and birth order was collected and analyzed. Of 927 children identified, 804 were included in the cohort. Eighty children (10%) had a reported penicillin allergy; most were white (79%) and boys (61%). Intrapartum exposure to penicillin (odds ratio 0.84, 95% confidence interval 0.45-1.57, P = .59) or to amoxicillin or ampicillin (odds ratio 0.22, 95% confidence interval 0.01-3.71, P = .29) did not increase the risk of penicillin allergy in children. In addition, all other factors evaluated did not affect the risk of penicillin allergy in children. To the authors' knowledge, this is the first study to evaluate intrapartum exposure to penicillin for GBS treatment and subsequent development of penicillin allergy in the child. In contrast to other atopic diseases, intrapartum antibiotic exposure does not alter the risk of penicillin allergy. Parents and obstetricians should be reassured when using penicillin for prevention of neonatal GBS. Published by Elsevier Inc.

Leptospirosis-associated acute kidney injury: penicillin at the late stage is still controversial.

Science.gov (United States)

Daher, E F; Silva, G B; de Abreu, K L S; Mota, R M S; Batista, D V; Rocha, N A; Araújo, S M H A; Libório, A B

2012-08-01

Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis-associated acute kidney injury (AKI). A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not. Two hundred and eighty-seven patients were included, with an average age of 36·8±15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32±14 years vs. 39±16 years, P=0·0002) and had a shorter hospital stay (8·4±5·0 vs. 11±7·7 days, Ppenicillin group (111±21 vs. 119±22 mmHg, P=0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin (Ppenicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late-stage leptospirosis. © 2011 Blackwell Publishing Ltd.

Use of cephalosporins in patients with immediate penicillin hypersensitivity: cross-reactivity revisited.

Science.gov (United States)

Lee, Q U

2014-10-01

A 10% cross-reactivity rate is commonly cited between penicillins and cephalosporins. However, this figure originated from studies in the 1960s and 1970s which included first-generation cephalosporins with similar side-chains to penicillins. Cephalosporins were frequently contaminated by trace amount of penicillins at that time. The side-chain hypothesis for beta-lactam hypersensitivity is supported by abundant scientific evidence. Newer generations of cephalosporins possess side-chains that are dissimilar to those of penicillins, leading to low cross-reactivity. In the assessment of cross-reactivity between penicillins and cephalosporins, one has to take into account the background beta-lactam hypersensitivity, which occurs in up to 10% of patients. Cross-reactivity based on skin testing or in-vitro test occurs in up to 50% and 69% of cases, respectively. Clinical reactivity and drug challenge test suggest an average cross-reactivity rate of only 4.3%. For third- and fourth-generation cephalosporins, the rate is probably less than 1%. Recent international guidelines are in keeping with a low cross-reactivity rate. Despite that, the medical community in Hong Kong remains unnecessarily skeptical. Use of cephalosporins in patients with penicillin hypersensitivity begins with detailed history and physical examination. Clinicians can choose a cephalosporin with a different side-chain. Skin test for penicillin is not predictive of cephalosporin hypersensitivity, while cephalosporin skin test is not sensitive. Drug provocation test by experienced personnel remains the best way to exclude or confirm the diagnosis of drug hypersensitivity and to find a safe alternative for future use. A personalised approach to cross-reactivity is advocated.

Effects of penicillin on procaine-elicited bursts of potential in central neuron of snail, Achatina fulica.

Science.gov (United States)

Chen, Yi-Hung; Lu, Kuan-Ling; Hsiao, Ru-Wan; Lee, Ya-Ling; Tsai, Hong-Chieh; Lin, Chia Hsien; Tsai, Ming-Cheng

2008-08-01

Effects of penicillin on changes in procaine-elicited bursts of potential (BoP) were studied in a central neuron (RP4) of snail, Achatina fulica Ferussac. Procaine elicited BoP in the RP4 neuron while penicillin elicited depolarization of the neuron. Penicillin decreased the BoP elicited by procaine in a concentration-dependent manner. The effect of penicillin on the procaine-elicited BoP was not altered in the preparations treated with ascorbate or L-NAME (N-nitro-L-arginine methyl ester). However, the inhibitory effect of penicillin on the procaine-elicited BoP was enhanced with a decrease in extracellular sodium ion. Sodium ion was one of the important ions contributing to the action potential of the neuron. Two-electrode voltage-clamp studies revealed that penicillin decreased the fast sodium inward current of the neuron. It is concluded that penicillin inhibited the BoP elicited by procaine and sodium ion altered the effect of penicillin on procaine-elicited BoP.

Polystyrene tube radioimmunoabsorbent assay for IgE anti-penicillin antibody

International Nuclear Information System (INIS)

Urena, V.; Delgado, R.G.; Daroca, P.; Lahoz, C.

1977-01-01

A radioimmunoassay technique has been developed based on the binding capacity of polystyrene for proteins. The method was tested on sera from thirteen patients with suspected penicillin allergy, five healthy controls, and three patients with seasonal pollen reactions. The results were compared with those obtained by the radio-allergoabsorbent method (RAST) and with basophil degranulation by penicillin. A penicillin/ovalbumin conjugate (pen-OA) was prepared and polystyrene tubes were incubated with pen-OA, 3% human serum albumin to block free sites, 1/10 dilution of test serum, anti-IgE antiserum specific for epsilon chains, and 125 I-IgE. The tubes were washed after the incubation period and the empty tubes counted in a γ scintillation counter. The specificity of the method was tested by an inhibition assay. The technique seemed more sensitive than the RAST method, the results were reproducible and in general showed good correlation with those of the RAST method. This polystyrene tube radioimmunoabsorbent method therefore provides a simple, specific and sensitive diagnostic technique for penicillin allergy. (U.K)

Simulated Batch Production of Penicillin

Science.gov (United States)

Whitaker, A.; Walker, J. D.

1973-01-01

Describes a program in applied biology in which the simulation of the production of penicillin in a batch fermentor is used as a teaching technique to give students experience before handling a genuine industrial fermentation process. Details are given for the calculation of minimum production cost. (JR)

Allergy test outcomes in patients self-reported as having penicillin allergy: Two-year experience.

Science.gov (United States)

Meng, Juan; Thursfield, David; Lukawska, Joanna J

2016-09-01

Penicillin allergy is associated with increased antibiotic resistance and health care costs. However, most patients with self-reported penicillin allergy are not truly allergic. To summarize our experience with allergy tests in patients with a history of penicillin allergy and to compare them with the results of other groups. We retrospectively reviewed all patients with a suspected clinical history of penicillin allergy referred to the Drug Allergy Unit at University College London Hospital between March 2013 and June 2015. In total, 84 patients were reviewed. The index drugs included: unidentified penicillin (n = 44), amoxicillin (n = 17), amoxicillin-clavulanic acid (n = 13), flucloxacillin (n = 4), and other penicillins (ampicillin, benzylpenicillin, piperacillin-tazobactam; n = 7). Allergy diagnoses were confirmed in 24 patients (28.6%) (16 to penicillin, 3 to flucloxacillin, 5 to clavulanic acid). Twenty-two patients (91.7%) had allergy diagnosed by positive skin test results. Two patients (8.3%) developed IgE-mediated allergic symptoms during oral challenge (although the skin test results were negative). In vitro specific IgE test results for penicilloyl V, penicilloyl G, and amoxicilloyl were positive in 3 of 16 patients (18.8%). Moreover, reactions to cefuroxime were observed in 3 of 15 patients with penicillin allergy (20%). Selective clavulanic acid and flucloxacillin responders tolerated amoxicillin challenge. The interval between the index reaction and evaluation was shorter (P penicillin allergy were confirmed to be allergic. Importantly, when the index drug is amoxicillin-clavulanic acid or flucloxacillin, the patients may tolerate amoxicillin. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clinical retrospective study of self-reported penicillin allergy on dental implant failures and infections.

Science.gov (United States)

French, David; Noroozi, Mehdi; Shariati, Batoul; Larjava, Hannu

2016-01-01

The aim of this retrospective study was to investigate whether self-reported allergy to penicillin may contribute to a higher rate of postsurgical infection and implant failure. This retrospective, non-interventional, open cohort study reports on implant survival and infection complications of 5,576 implants placed in private practice by one periodontist, and includes 4,132 implants that were followed for at least 1 year. Logistic regression was applied to examine the relationship between self-reported allergy to penicillin and implant survival, while controlling for potential confounders such as smoking, implant site, bone augmentation, loading protocol, immediate implantation, and bone level at baseline. The cumulative survival rate (CSR) was calculated according to the life table method and the Cox proportional hazard model was fitted to data. Out of 5,106 implants placed in patients taking penicillin it was found that 0.8% failed, while 2.1% failed of the 470 implants placed for patients with self-reported allergy to penicillin (P = .002). Odds of failure for implants placed in penicillin-allergic patients were 3.1 times higher than in non-allergic patients. For immediate implant placement, penicillin-allergic patients had a failure rate 10-times higher than the non-allergic cohort. Timing of implant failure occurring within 6 months following implantation was 80% in the penicillin-allergic group versus 54% in the non-allergic group. From the 48 implant sites showing postoperative infection: penicillin-allergic patients had an infection rate of 3.4% (n = 16/470) versus 0.6% in the non-allergic group (n = 32/5,106) (P penicillin allergy was associated with a higher rate of infection, and primarily affected early implant failure.

Risk Assessment and effect of Penicillin-G on bacterial diversity in drinking water

Science.gov (United States)

Wu, Qing; Zhao, Xiaofei; Peng, Sen; Wang, Lei; Zhao, Xinhua

2018-02-01

Penicillin-G was detected in drinking water by LC-MS/MS and the bacterial diversity was investigated by PCR and high-throughput sequencing. The results showed that bacteria community structure in drinking water has undergone major changes when added different concentrations of penicillin-G. The diversity index of each sample was calculated. The results showed that the total number and abundance of bacterial community species in drinking water samples decreased significantly after the addition of penicillin-G. However, the number and abundance of community structure did not change with the concentration. Penicillin-G inhibits the activity of bacterial community in drinking water and can reduce the bacterial diversity in drinking water.

Amoxicillin and Ceftriaxone as Treatment Alternatives to Penicillin for Maternal Syphilis.

Science.gov (United States)

Katanami, Yuichi; Hashimoto, Takehiro; Takaya, Saho; Yamamoto, Kei; Kutsuna, Satoshi; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Ohmagari, Norio

2017-05-01

There is no proven alternative to penicillin for treatment of maternal syphilis. We report 2 case-patients with maternal syphilis who were successfully treated without penicillin. We used amoxicillin and probenecid for the first case-patient and amoxicillin, probenecid, and ceftriaxone for the second case-patient.

Oral Challenge without Skin Testing Safely Excludes Clinically Significant Delayed-Onset Penicillin Hypersensitivity.

Science.gov (United States)

Confino-Cohen, Ronit; Rosman, Yossi; Meir-Shafrir, Keren; Stauber, Tali; Lachover-Roth, Idit; Hershko, Alon; Goldberg, Arnon

Penicillins are the drug family most commonly associated with hypersensitivity reactions. Current guidelines recommend negative skin tests (ST) before re-administering penicillins to patients with previous nonimmediate reactions (NIR). The objective of this study was to examine whether ST are necessary before re-administering penicillin to patients with NIR. Patients with NIR to penicillins starting longer than 1 hour after last dose administration or starting any time after the first treatment day or patients with vague recollection of their reaction underwent penicillin ST. Disregarding ST results, patients were challenged with the relevant penicillins. One-tenth of the therapeutic dose followed by the full dose was administered at 1-hour interval and patients continued taking the full dose for 5 days. A total of 710 patients with alleged BL allergy were evaluated. Patients with a history of immediate reaction (52, 7.3%) or cephalosporin allergy (16, 2.2%) were excluded. Of the remaining 642 patients, 62.3% had negative ST, 5.3% positive ST, and 32.4% equivocal ST. A total of 617 (96.1%) patients were challenged. Immediate reaction was observed in 9 patients (1.5%): 1-positive ST, 7-negative ST, and 1-equivocal ST (P = .7). Late reaction to the first-day challenge occurred in 24 patients (4%). An at-home challenge was continued by 491 patients. Complete 5-day and partial challenges were well tolerated by 417 (85%) and 44 patients (8.9%), respectively, disregarding ST results. Thirty patients (6.1%) developed mild reactions to the home challenge regardless of their ST results. A 5-day oral challenge without preceding ST is safe and sufficient to exclude penicillin allergy after NIR developing during penicillin treatment. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Absence of penicillin-binding protein 4 from an apparently normal strain of Bacillus subtilis.

OpenAIRE

Buchanan, C E

1987-01-01

The phenotype of a Bacillus subtilis 168 strain with no detectable penicillin-binding protein 4 was examined. Despite the fact that penicillin-binding protein 4 is one of the most penicillin-sensitive proteins in the species, its apparent loss had no obvious effect on the organism or its susceptibility to various beta-lactam antibiotics.

Radioprotective effect of penicillin on the x-ray induced chromosome aberrations in the Syrian hamster

International Nuclear Information System (INIS)

Dey, S.K.; Manna, G.K.

1981-01-01

The frequency of chromosome aberrations in the bone marrow cells of Syrian hamsters treated with penicillin and X-rays separately and conjointly was found to be 27% in X-irradiated series, 6.3% in penicillin treated series while it was 7.6%, 8% and 6.3% respectively for the treatment of penicillin prior to, almost simultaneously with and after X-irradiation. The results indicated the protective action of penicillin on the frequency of radiation-induced chromosome damages. (author)

Epithelial organization and cyst lumen expansion require efficient Sec13-Sec31-driven secretion.

Science.gov (United States)

Townley, Anna K; Schmidt, Katy; Hodgson, Lorna; Stephens, David J

2012-02-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.

A survey of inpatient practitioner knowledge of penicillin allergy at 2 community teaching hospitals.

Science.gov (United States)

Staicu, Mary L; Soni, Dipekka; Conn, Kelly M; Ramsey, Allison

2017-07-01

The negative effect of the penicillin allergy label on antibiotic use and patient outcomes has brought to light the need for thorough penicillin allergy assessments and heightened practitioner education. To evaluate practitioner knowledge of penicillin allergy and the clinical approach to the patients with penicillin allergy. An electronic survey was distributed to attending physicians, residents, pharmacists, nurse practitioners, and physician assistants practicing adult inpatient medicine at 2 community-based teaching hospitals from February to April 2016. A total of 276 (39%) of 716 practitioners completed surveys were analyzed. Most respondents were attending physicians (45%) with more than 10 years of experience (53%). Approximately half of the respondents indicated that they were unfamiliar with the rate of cross-reactivity between penicillin and cephalosporin (46%), carbapenem (42%), and monobactam (48%) antibiotics. When evaluating the role of penicillin skin testing and temporary induction of drug tolerance in the case vignettes, only 41% and 19% of respondents appropriately considered these options as the leading antibiotic management plan, respectively. Despite acknowledging the need for allergy/immunology consultation in clinical scenarios, 86% of respondents indicated that they never consult an allergist or immunologist or do so only once per year. Overall, pharmacists had a better understanding of the natural history of penicillin allergy and antibiotic cross-reactivity (P penicillin allergy in the hospital setting, where collaborative efforts between allergy and nonallergy health care practitioners are sparse. The expansion of a multidisciplinary approach may optimize antimicrobial prescribing in this subset of patients. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review

Directory of Open Access Journals (Sweden)

Gian Maria Pacifici

2010-08-01

Full Text Available Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2, clearance (Cl, and volume of distribution (Vd change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.

21 CFR 526.1696c - Penicillin G procaine-dihydrostreptomycin sulfate for intramammary infusion (dry cows).

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine-dihydrostreptomycin sulfate... INTRAMAMMARY DOSAGE FORMS § 526.1696c Penicillin G procaine-dihydrostreptomycin sulfate for intramammary infusion (dry cows). (a) Specifications. Each 10 milliliters of suspension contains penicillin G procaine...

The prevalence of suspected and challenge-verified penicillin allergy in a university hospital population

DEFF Research Database (Denmark)

Borch, Jacob Eli; Andersen, Klaus Ejner; Bindslev-Jensen, Carsten

2006-01-01

patterns and public economy as a consequence. We performed a cross-sectional case-control study with two visits to all clinical departments of a large university hospital in order to find in-patients with medical files labelled "penicillin allergy" or who reported penicillin allergy upon admission. Patient....... In a cohort of 3642 patients, 96 fulfilled the inclusion criteria giving a point-prevalence of alleged penicillin allergy of 5% in a hospital in-patient population. Mean time elapsed since the alleged first reaction to penicillin was 20 years. The skin was the most frequently affected organ (82.2%), maculo...

Penicillin-binding proteins of Escherichia coli identified with a 125I-derivative of ampicillin

International Nuclear Information System (INIS)

Schwarz, U.; Seeger, K.; Wengenmayer, F.; Strecker, H.

1981-01-01

Evaluation of the binding of β-lactam antibiotics to penicillin-binding proteins (PBPs) in the bacterial cell wall by the established method using 14 C-labelled penicillin G has some disadvantages. Due to the small number of PBP molecules and the relatively low specific activity of [ 14 C]penicillin G available, very long exposure times for autoradiography are required. Furthermore, additional radiolabelled derivatives of penicillin with modified binding patterns might reveal PBPs not known so far. The authors describe the synthesis of a 125 I-labelled derivative of ampicillin and the labelling of PBPs with this compound. (Auth.)

An amperometric penicillin biosensor with enhanced sensitivity based on co-immobilization of carbon nanotubes, hematein, and {beta}-lactamase on glassy carbon electrode

Energy Technology Data Exchange (ETDEWEB)

Chen Bi; Ma Ming [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081 (China); Su Xiaoli, E-mail: xsu@hunnu.edu.cn [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081 (China)

2010-07-26

An amperometric penicillin biosensor with enhanced sensitivity was successfully developed by co-immobilization of multi-walled carbon nanotubes (MWCNTs), hematein, and {beta}-lactamase on glassy carbon electrode using a layer-by-layer assembly technique. Under catalysis of the immobilized enzyme, penicillin was hydrolyzed, decreasing the local pH. The pH change was monitored amperometrically with hematein as a pH-sensitive redox probe. MWCNTs were used as an electron transfer enhancer as well as an efficient immobilization matrix for the sensitivity enhancement. The effects of immobilization procedure, working potential, enzyme quantity, buffer concentration, and sample matrix were investigated. The biosensor offered a minimum detection limit of 50 nM (19 {mu}g L{sup -1}) for penicillin V, lower than those of the conventional pH change-based biosensors by more than two orders of magnitude. The electrode-to-electrode variation of the response sensitivity was 7.0% RSD.

An amperometric penicillin biosensor with enhanced sensitivity based on co-immobilization of carbon nanotubes, hematein, and β-lactamase on glassy carbon electrode

International Nuclear Information System (INIS)

Chen Bi; Ma Ming; Su Xiaoli

2010-01-01

An amperometric penicillin biosensor with enhanced sensitivity was successfully developed by co-immobilization of multi-walled carbon nanotubes (MWCNTs), hematein, and β-lactamase on glassy carbon electrode using a layer-by-layer assembly technique. Under catalysis of the immobilized enzyme, penicillin was hydrolyzed, decreasing the local pH. The pH change was monitored amperometrically with hematein as a pH-sensitive redox probe. MWCNTs were used as an electron transfer enhancer as well as an efficient immobilization matrix for the sensitivity enhancement. The effects of immobilization procedure, working potential, enzyme quantity, buffer concentration, and sample matrix were investigated. The biosensor offered a minimum detection limit of 50 nM (19 μg L -1 ) for penicillin V, lower than those of the conventional pH change-based biosensors by more than two orders of magnitude. The electrode-to-electrode variation of the response sensitivity was 7.0% RSD.

Structural effect of the Asp345a insertion in penicillin-binding protein 2 from penicillin-resistant strains of Neisseria gonorrhoeae.

Science.gov (United States)

Fedarovich, Alena; Cook, Edward; Tomberg, Joshua; Nicholas, Robert A; Davies, Christopher

2014-12-09

A hallmark of penicillin-binding protein 2 (PBP2) from penicillin-resistant strains of Neisseria gonorrhoeae is insertion of an aspartate after position 345. The insertion resides on a loop near the active site and is immediately adjacent to an existing aspartate (Asp346) that forms a functionally important hydrogen bond with Ser363 of the SxN conserved motif. Insertion of other amino acids, including Glu and Asn, can also lower the rate of acylation by penicillin, but these insertions abolish transpeptidase function. Although the kinetic consequences of the Asp insertion are well-established, how it impacts the structure of PBP2 is unknown. Here, we report the 2.2 Å resolution crystal structure of a truncated construct of PBP2 containing all five mutations present in PBP2 from the penicillin-resistant strain 6140, including the Asp insertion. Commensurate with the strict specificity for the Asp insertion over similar amino acids, the insertion does not cause disordering of the structure, but rather induces localized flexibility in the β2c-β2d loop. The crystal structure resolves the ambiguity of whether the insertion is Asp345a or Asp346a (due to the adjacent Asp) because the hydrogen bond between Asp346 and Ser362 is preserved and the insertion is therefore Asp346a. The side chain of Asp346a projects directly toward the β-lactam-binding site near Asn364 of the SxN motif. The Asp insertion may lower the rate of acylation by sterically impeding binding of the antibiotic or by hindering breakage of the β-lactam ring during acylation because of the negative charge of its side chain.

Penicillin production by mutant strains of penicillium chrysogenum

International Nuclear Information System (INIS)

Tawfik, Z.S.; Ashour, M.S.; Shihab, A.

1986-01-01

The mutagenic agent 8-rays was used to initiate the penicillium chrysogenum isolated from local spices. After irradiation, colonies invariably differing from the parent strain in their morphological and cultural characteristics were tested for antibiotic production on fermentation agar medium. Twenty two isolates were found to be penicillin producing mutant strains. Mutant strain M 24 forming small colonies with white conidia was found to be a high yielding penicillin producer (9550 i.u/ml). All of the 22 isolates obtained lost their ability to produce the antibiotic after 11 months storage at 4 0 with subsequent subculturing

75 FR 55798 - North American Bioproducts Corporation; Filing of Food Additive Petition (Animal Use); Penicillin...

Science.gov (United States)

2010-09-14

...] North American Bioproducts Corporation; Filing of Food Additive Petition (Animal Use); Penicillin G... food additive regulations be amended to provide for the safe use of penicillin G procaine as an... Water of Animals (21 CFR part 573) to provide for the safe use of penicillin G procaine as an...

Cloning, purification, crystallization and preliminary structural studies of penicillin V acylase from Bacillus subtilis

International Nuclear Information System (INIS)

Rathinaswamy, Priya; Pundle, Archana V.; Prabhune, Asmita A.; SivaRaman, Hepzibah; Brannigan, James A.; Dodson, Guy G.; Suresh, C. G.

2005-01-01

An unannotated protein reported from B. subtilis has been expressed in E. coli and identified as possessing penicillin V acylase activity. The crystallization and preliminary crystallographic analysis of this penicillin V acylase is presented. Penicillin acylase proteins are amidohydrolase enzymes that cleave penicillins at the amide bond connecting the side chain to their β-lactam nucleus. An unannotated protein from Bacillus subtilis has been expressed in Escherichia coli, purified and confirmed to possess penicillin V acylase activity. The protein was crystallized using the hanging-drop vapour-diffusion method from a solution containing 4 M sodium formate in 100 mM Tris–HCl buffer pH 8.2. Diffraction data were collected under cryogenic conditions to a spacing of 2.5 Å. The crystals belonged to the orthorhombic space group C222 1 , with unit-cell parameters a = 111.0, b = 308.0, c = 56.0 Å. The estimated Matthews coefficient was 3.23 Å 3 Da −1 , corresponding to 62% solvent content. The structure has been solved using molecular-replacement methods with B. sphaericus penicillin V acylase (PDB code 2pva) as the search model

Is Penicillin plus Gentamicin Synergistic against Clinical Group B Streptococcus isolates?: A in-vitro Study.

Directory of Open Access Journals (Sweden)

Corinne Ruppen

2016-10-01

Full Text Available Group B Streptococcus (GBS is increasingly causing invasive infections in nonpregnant adults. Elderly patients and those with comorbidities are at increased risk. On the basis of previous studies focusing on neonatal infections, penicillin plus gentamicin is recommended for infective endocarditis (IE and periprosthetic joint infections (PJI in adults. The purpose of this study was to investigate whether a synergism with penicillin and gentamicin is present in GBS isolates that caused IE and PJI. We used 5 GBS isolates, two clinical strains and three control strains, including one displaying high-level gentamicin resistance (HLGR. The results from the checkerboard and time-kill assays (TKAs were compared. For TKAs, antibiotic concentrations for penicillin were 0.048 and 0.2 mg/L, and for gentamicin 4 mg/L or 12.5 mg/L. In the checkerboard assay, the median fractional inhibitory concentration indices (FICIs of all isolates indicated indifference. TKAs for all isolates failed to demonstrate synergism with penicillin 0.048 or 0.2 mg/L, irrespective of gentamicin concentrations used. Rapid killing was seen with penicillin 0.048 mg/L plus either 4 mg/L or 12.5 mg/L gentamicin, from 2 h up to 8 h hours after antibiotic exposure. TKAs with penicillin 0.2 mg/L decreased the starting inoculum below the limit of quantification within 4 h to 6 h, irrespective of the addition of gentamicin. Fast killing was seen with penicillin 0.2 mg/L plus 12.5 mg/L gentamicin within the first 2 h. Our in vitro results indicate that the addition of gentamicin to penicillin contributes to faster killing at low penicillin concentrations, but only within the first few hours. Twenty-four hours after antibiotic exposure, PEN alone was bactericidal and synergism was not seen.

Piezoelectric immunosensors for the detection of individual antibiotics and the total content of penicillin antibiotics in foodstuffs.

Science.gov (United States)

Karaseva, N A; Ermolaeva, T N

2014-03-01

Piezoelectric immunosensors on the basis of homologous and group-specificantibodies have been developed for detecting penicillin G, ampicillin, and the total content of penicillin antibiotics. The receptor coating of the sensor was obtained by the immobilization of penicillin G or ampicillin hapten-protein conjugates on the polypyrrole film obtained by electropolymerization and activated by glutaraldehyde. The affinity constants and the cross reactivity coefficients have been calculated. This made it possible to estimate the affinity and specificity of the polyclonal and monoclonal antibodies used. The calibration curves are linear in the range of concentrations 2.5-250.0 ng ml(-1) (penicillin G), 2.5-500.0 ng ml(-1) (ampicillin), and 1-500 ng ml(-1) (group of penicillin). The limits of detection are 0.8 ng ml(-1), 3.9 ng ml(-1), which are lower than MRL, established for penicillin antibiotics. The sensors were tested in detecting penicillins in milk, pork, beef, liver. Copyright © 2013 Elsevier B.V. All rights reserved.

Therapeutic relevance of penicillin-induced hypersensitivity of Staphylococcus aureus to killing by polymorphonuclear leukocytes.

OpenAIRE

Lam, C; Georgopoulos, A; Laber, G; Schütze, E

1984-01-01

There is an overwhelming body of evidence that certain Staphylococcus aureus strains become more sensitive to killing by polymorphonuclear leukocytes after their growth in media containing subinhibitory concentrations of penicillin. However, it is not clear to what extent this phenomenon contributes to the curative effect of penicillin in vivo. To explore its therapeutic relevance, we evaluated the interaction of staphylococci pretreated with penicillin in vitro with leukocytes in cell-proof ...

Epidemiological study on the penicillin resistance of clinical Streptococcus pneumoniae isolates identified as the common sequence types.

Science.gov (United States)

Gao, Wei; Shi, Wei; Chen, Chang-hui; Wen, De-nian; Tian, Jin; Yao, Kai-hu

2016-10-20

There were some limitation in the current interpretation about the penicillin resistance mechanism of clinical Streptococcus pneumoniae isolates at the strain level. To explore the possibilities of studying the mechanism based on the sequence types (ST) of this bacteria, 488 isolates collected in Beijing from 1997-2014 and 88 isolates collected in Youyang County, Chongqing and Zhongjiang County, Sichuan in 2015 were analyzed by penicillin minimum inhibitory concentration (MIC) distribution and annual distribution. The results showed that the penicillin MICs of the all isolates covering by the given ST in Beijing have a defined range, either penicillin MIC penicillin MICs in the first few years after it was identified. The penicillin MIC of isolates identified as common STs and collected in Youyang County, Chongqing and Sichuan Zhongjiang County, including the ST271, ST320 and ST81, was around 0.25~2 mg/L (≥0.25 mg/L). Our study revealed the epidemiological distribution of penicillin MICs of the given STs determined in clinical S. pneumoniae isolates, suggesting that it is reasonable to research the penicillin resistance mechanism based on the STs of this bacteria.

A kinetic model for the penicillin biosynthetic pathway in

DEFF Research Database (Denmark)

Nielsen, Jens; Jørgensen, Henrik

1996-01-01

A kinetic model for the first two steps in the penicillin biosynthetic pathway, i.e. the ACV synthetase (ACVS) and the isopenicillin N synthetase (IPNS) is proposed. The model is based on Michaelis-Menten type kinetics with non-competitive inhibition of the ACVS by ACV, and competitive inhibition...... of the IPNS by glutathione. The model predicted flux through the pathway corresponds well with the measured rate of penicillin biosynthesis. From the kinetic model the elasticity coefficients and the flux control coefficients are calculated throughout a fed-batch cultivation, and it is found...

The lethal interaction of x ray and penicillin induced lesions following x-irradiation of Escherichia coli B/r in the presence of hypoxic cell sensitizers

International Nuclear Information System (INIS)

Gillies, N.E.; Obioha, F.I.

1982-01-01

When Escherichia coli B/r were x-irradiated under anoxia in the presence of different electron-affinic sensitizers and then incubated in broth containing penicillin (at a concentration that did not kill unirradiated cells) additional killing of the bacteria occurred provided the sensitizers were of relatively high lipophilicity. The overall effect was to increase the efficiency of these sensitizers. It is concluded that sensitizer-dependent latent radiation lesions(s) are produced in membrane components of the cell envelope that interact with damage caused by penicillin in the peptidoglycan layer and this causes the additional lethality

21 CFR 211.176 - Penicillin contamination.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Penicillin contamination. 211.176 Section 211.176 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Laboratory Controls § 211.176...

The long postwar and the politics of penicillin: early circulation and smuggling in Spain, 1944-1954.

Science.gov (United States)

Santesmases, María Jesús

2014-01-01

In this paper I explore the early circulation of penicillin. I review the early distribution in Spain of a scarce product, reflect on the available sources about the illegal penicillin trade and discuss some cases of smuggling. I argue the early distribution of penicillin involved time and geography, a particular chronology of post Second World War geopolitics. Penicillin practices and experiences belong to this period, in a dictatorship that tolerated smuggling and illegal trade of other products, some, like penicillin, produced in neighbouring countries. As a commodity that crossed borders, penicillin, transiting between the law and hidden trade, between countries and social domains--between war fronts and from a war front to an urban site to be sold--reveals practices of the early years of prosperity in the 1950s. These transits were permanent tests of a society based on taxes and exchanges, law and bureaucracy, control, discipline and the creation of standards.

Crystallization and X-ray structure analysis of a thermostable penicillin G acylase from Alcaligenes faecalis

International Nuclear Information System (INIS)

Varshney, Nishant Kumar; Suresh Kumar, R.; Ignatova, Zoya; Prabhune, Asmita; Pundle, Archana; Dodson, Eleanor; Suresh, C. G.

2012-01-01

A thermostable penicillin G acylase from A. faecalis has been crystallized in two space groups: C222 1 and P4 1 2 1 2. X-ray diffraction data were collected to 3.3 and 3.5 Å resolution, respectively. The enzyme penicillin G acylase (EC 3.5.1.11) catalyzes amide-bond cleavage in benzylpenicillin (penicillin G) to yield 6-aminopenicillanic acid, an intermediate chemical used in the production of semisynthetic penicillins. A thermostable penicillin G acylase from Alcaligenes faecalis (AfPGA) has been crystallized using the hanging-drop vapour-diffusion method in two different space groups: C222 1 , with unit-cell parameters a = 72.9, b = 86.0, c = 260.2 Å, and P4 1 2 1 2, with unit-cell parameters a = b = 85.6, c = 298.8 Å. Data were collected at 293 K and the structure was determined using the molecular-replacement method. Like other penicillin acylases, AfPGA belongs to the N-terminal nucleophilic hydrolase superfamily, has undergone post-translational processing and has a serine as the N-terminal residue of the β-chain. A disulfide bridge has been identified in the structure that was not found in the other two known penicillin G acylase structures. The presence of the disulfide bridge is perceived to be one factor that confers higher stability to this enzyme

Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion

Science.gov (United States)

Townley, Anna K.; Schmidt, Katy; Hodgson, Lorna; Stephens, David J.

2012-01-01

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture. PMID:22331354

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

Impact of Penicillin Allergy on Time to First Dose of Antimicrobial Therapy and Clinical Outcomes.

Science.gov (United States)

Conway, Erin L; Lin, Ken; Sellick, John A; Kurtzhalts, Kari; Carbo, James; Ott, Michael C; Mergenhagen, Kari A

2017-11-01

The objective of this study was to evaluate the impact of a listed penicillin allergy on the time to first dose of antibiotic in a Veterans Affairs hospital. Additional clinical outcomes of patients with penicillin allergies were compared with those of patients without a penicillin allergy. A retrospective chart review of veterans admitted through the emergency department with a diagnosis of pneumonia, urinary tract infection, bacteremia, and sepsis from January 2006 to December 2015 was conducted. The primary outcome was time to first dose of antibiotic treatment, defined as the time from when the patient presented to the emergency department to the medication administration time. Secondary outcomes included total antibiotic therapy duration and treatment outcomes, including mortality, length of stay, and 30-day readmission rate. A total of 403 patients were included in the final analysis; 57 patients (14.1%) had a listed penicillin allergy. The average age of the population was 75 years and 99% of the population was male. The mean time to first dose of antibiotic treatment for patients with a penicillin allergy was prolonged compared with those without a penicillin allergy (236.1 vs 186.6 minutes; P = 0.03), resulting in an approximately 50-minute delay. Penicillin-allergic patients were more likely to receive a carbapenem or fluoroquinolone antibiotic (P penicillin allergy had a prolonged time to first dose of antibiotic therapy. No significant differences were found in total antibiotic duration, length of stay, or 30-day readmission rate. The small sample size, older population, and single-center nature of this study may limit the generalizability of the present findings to other populations. Published by Elsevier Inc.

Nonlinear secret image sharing scheme.

Science.gov (United States)

Shin, Sang-Ho; Lee, Gil-Je; Yoo, Kee-Young

2014-01-01

Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t⌈log2 m⌉ bit-per-pixel (bpp), respectively.

Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans

DEFF Research Database (Denmark)

Larsen, Emil List; Cejvanovic, Vanja; Kjaer, Laura Kofoed

2017-01-01

, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation.......7% (95% CI: 5.8–37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde. Conclusion Clarithromycin significantly increases oxidative nucleic acid...... modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications....

cular benzathine penicillin in relieving manifestations of ...

African Journals Online (AJOL)

2014-12-01

Dec 1, 2014 ... sponses to intramuscular benzathine penicillin G. (BPG) and single dose of ... diagnosis and treatment of GAS pharyngitis is very important. Many studies ... standard method with 90-95% sensitivity. The samples were sent to a ...

75 FR 35044 - Notice of Approval of a Supplemental New Animal Drug Application; Penicillin G Procaine Suspension

Science.gov (United States)

2010-06-21

...] Notice of Approval of a Supplemental New Animal Drug Application; Penicillin G Procaine Suspension AGENCY... Laboratories, Ltd. The supplemental NADA provides for a revised formulation of penicillin G procaine injectable... of NOROCILLIN (penicillin G procaine) Injectable Suspension by intramuscular injection in cattle...

Deregulation of the Arginine Deiminase (arc) Operon in Penicillin-Tolerant Mutants of Streptococcus gordonii

OpenAIRE

Caldelari, I.; Loeliger, B.; Langen, H.; Glauser, M. P.; Moreillon, P.

2000-01-01

Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent Streptococcus gordonii mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log10 CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost ≤2 log10 CFU/ml/24 h. The mutants had unchanged penicillin-binding proteins but contained increased amounts of two proteins ...

Penicillin resistance and serotype distribution of Streptococcus pneumoniae in Ghanaian children less than six years of age

DEFF Research Database (Denmark)

Dayie, Nicholas T. K. D.; Arhin, Reuben E.; Newman, Mercy J.

2013-01-01

Background: The objective of this study was to determine the prevalence of nasopharyngeal carriage, serotype distribution, and penicillin resistance of Streptococcus pneumoniae in children 2 mu g/ml and were classified as fully penicillin resistant with 45% of the isolates having intermediate...... serotypes detected. The two penicillin resistant isolates (MIC 32 mu g/ml) were serotypes included in both PCV-13 and PPV-23. A nationwide monitoring system of penicillin susceptibility patterns and pneumococcal serotypes is recommended....

Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting

Directory of Open Access Journals (Sweden)

Diana Tilevik

2016-05-01

Full Text Available Background: The increasing prevalence of penicillin non-susceptible pneumococci (PNSP throughout the world threatens successful treatment of infections caused by this important bacterial pathogen. The rate at which PNSP clones spread in the community is thought to mainly be determined by two key determinants; the volume of penicillin use and the magnitude of the fitness cost in the absence of treatment. The aim of the study was to determine the impacts of penicillin consumption and fitness cost on pneumococcal transmission dynamics in a developed country setting. Methods: An individual-based network model based on real-life demographic data was constructed and applied in a developed country setting (Sweden. A population structure with transmission of carriage taking place within relevant mixing groups, i.e. families, day care groups, school classes, and other close contacts, was considered to properly assess the transmission dynamics for susceptible and PNSP clones. Several scenarios were simulated and model outcomes were statistically analysed. Results: Model simulations predicted that with an outpatient penicillin use corresponding to the sales in Sweden 2010 (118 recipes per 1,000 inhabitants per year, the magnitude of a fitness cost for resistance must be at least 5% to offset the advantage of penicillin resistance. Moreover, even if there is a fitness cost associated with penicillin resistance, a considerable reduction of penicillin usage appears to be required to significantly decrease the incidence of PNSP in a community. Conclusion: The frequency of PNSP clones is hard to reverse by simply reducing the penicillin consumption even if there is a biological cost associated with resistance. However, because penicillin usage does promote further spread of PNSP clones, it is important to keep down penicillin consumption considering future resistance problems.

Use of Cefazolin for Group B Streptococci Prophylaxis in Women Reporting a Penicillin Allergy Without Anaphylaxis.

Science.gov (United States)

Briody, Victoria A; Albright, Catherine M; Has, Phinnara; Hughes, Brenna L

2016-03-01

To estimate the proportion of group B streptococci (GBS)-colonized women with a reported penicillin allergy without anaphylaxis receiving appropriate intrapartum antibiotic prophylaxis. We performed a retrospective cohort study of GBS-colonized, penicillin-allergic women delivering at term receiving intrapartum antibiotic prophylaxis during labor. Scheduled cesarean deliveries were excluded. The primary outcome was the proportion of women who received appropriate antibiotic coverage, defined as penicillin or cefazolin. Secondary outcomes included neonatal outcomes such as Apgar score, blood draws, antibiotic use, length of hospital stay, and composite morbidity. Of 165 women reporting a penicillin allergy without anaphylaxis, 73 (44.2%) received an appropriate antibiotic and 92 (55.8%) received an inappropriate antibiotic. Of those receiving an inappropriate antibiotic, 56 (60.9%) were given clindamycin, 1 (1.1%) erythromycin, and 35 (38.0%) vancomycin. Women reporting rash as a penicillin reaction were more likely to receive cefazolin than another antibiotic (44 [60.3%] compared with 24 [26.1%], respectively; Ppenicillin without anaphylaxis received an antibiotic other than penicillin or cefazolin as prophylaxis, indicating poor adherence to national guidelines.

Improved activity and pH stability of E-coli ATCC 11105 penicillin acylase by error-prone PCR

NARCIS (Netherlands)

Balci, Huseyin; Ozturk, Merve Tuzlakoglu; Pijning, Tjaard; Ozturk, Saliha Issever; Gumusel, Fusun

Penicillin G acylase is the key enzyme used in the industrial production of β-lactam antibiotics. This enzyme hydrolyzes penicillin G and related β-lactam antibiotics releasing 6-aminopenicillanic acid, which is an intermediate in the production of semisynthetic penicillins. To improve the enzymatic

Identification of a group of Haemophilus influenzae penicillin-binding proteins that may have complementary physiological roles

International Nuclear Information System (INIS)

Malouin, F.; Parr, T.R. Jr.; Bryan, L.E.

1990-01-01

[35S]penicillin bound to different Haemophilus influenzae proteins in assays performed at 20, 37, or 42 degrees C. Penicillin-binding proteins 3a, 3b, 4, and 4' formed a group characterized by their affinity for moxalactam, cefotaxime, and piperacillin. Penicillin-binding protein 4' showed specific properties that may reflect its complementary role in septation

Penicillin allergy and surgical prophylaxis: Cephalosporin cross-reactivity risk in a pediatric tertiary care center.

Science.gov (United States)

Beltran, Ralph J; Kako, Hiromi; Chovanec, Thomas; Ramesh, Archana; Bissonnette, Bruno; Tobias, Joseph D

2015-05-01

First generation cephalosporins are commonly used as antibiotic prophylaxis prior to surgery. Patients labeled as penicillin-allergic are often precluded from receiving cephalosporins because of an allergic cross-reactivity. The aims of this study were to evaluate the clinical practice for surgical prophylaxis at Nationwide Children's Hospital and to determine the incidence of adverse effects and allergic reactions when using cephalosporins in patients labeled as penicillin-allergic. A retrospective chart review was performed to identify patients who were allergic to penicillin, penicillin antibiotic family, who required surgical treatment for an existing medical condition, and received an antibiotic to prevent surgical site infection. Five hundred thirteen penicillin-allergic patients were identified, encompassing 624 surgical cases. Cephalosporins were administered in 153 cases (24.5%) with cefazolin used 83% of the time. Only one documented case of nonanaphylactic reaction was reported. Clindamycin was the most common cephalosporin substitute (n=387), and the reported adverse reaction rate was 1.5%. No cases of anaphylaxis were documented. Our data suggest that the administration of cephalosporins for surgical prophylaxis following induction of anesthesia in a patient with a known or reported penicillin-allergy appears appropriate and results in a lower adverse event rate that when clindamycin is administered. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced biogas production from penicillin bacterial residue by thermal-alkaline pretreatment

International Nuclear Information System (INIS)

Zhong, Weizhang; Li, Guixia; Gao, Yan; Li, Zaixing; Geng, Xiaoling; Li, Yubing; Yang, Jingliang; Zhou, Chonghui

2015-01-01

In this study, the orthogonal experimental design was used to determine the optimum conditions for the effect of thermal alkaline; pretreatment on the anaerobic digestion of penicillin bacterial residue. The biodegradability of the penicillin; bacterial residue was evaluated by biochemical methane potential tests in laboratory. The optimum values of temperature,; alkali concentration, pretreatment time and moisture content for the thermal-alkaline pretreatment were determined as; 70 °C, 6% (w/v), 30 min, and 85%, respectively. Thermal-alkaline pretreatment could significantly enhance the soluble; chemical oxygen demand solubilization, the suspended solid solubilization and the biodegradability. Biogas production; was enhanced by the thermal-alkaline pretreatment, probably as a result of the breakdown of cell walls and membranes of; micro-organisms, which may facilitate the contact between organic molecules and anaerobic microorganisms.; Keywords: penicillin bacterial residue; anaerobic digestion; biochemical methane potential tests; pretreatment

Enhanced secretion of natto phytase by Bacillus subtilis.

Science.gov (United States)

Tsuji, Shogo; Tanaka, Kosei; Takenaka, Shinji; Yoshida, Ken-ichi

2015-01-01

Phytases comprise a group of phosphatases that trim inorganic phosphates from phytic acid (IP6). In this study, we aimed to achieve the efficient secretion of phytase by Bacillus subtilis. B. subtilis laboratory standard strain 168 and its derivatives exhibit no phytase activity, whereas a natto starter secretes phytase actively. The natto phytase gene was cloned into strain RIK1285, a protease-defective derivative of 168, to construct a random library of its N-terminal fusions with 173 different signal peptides (SPs) identified in the 168 genome. The library was screened to assess the efficiency of phytase secretion based on clear zones around colonies on plates, which appeared when IP6 was hydrolyzed. The pbp SP enhanced the secretion of the natto phytase most efficiently, i.e. twice that of the original SP. Thus, the secreted natto phytase was purified and found to remove up to 3 phosphates from IP6.

Proactive penicillin allergy testing in primary care patients labeled as allergic: outcomes and barriers.

Science.gov (United States)

Sundquist, Britta K; Bowen, Brady J; Otabor, Uwa; Celestin, Jocelyn; Sorum, Paul C

2017-11-01

To promote penicillin allergy testing in an outpatient setting in patients labeled as penicillin allergic, to determine the number of those who are truly allergic, evaluate patient satisfaction with the testing, and educate both patients and clinicians about testing. Patients with a history of penicillin allergy listed in their EHR were screened and recruited by their primary care office and referred for penicillin allergy testing. The results of allergy testing and patient satisfaction after testing were the main outcomes. We also surveyed the primary care physicians about perceived barriers to recruitment. A total of 82 patients were recruited, although only 37 actually underwent testing. None of these 37 had a positive skin test, and none of 36 had a positive oral challenge (1 refused it). Following testing, 2 patients (5%) had subjective reactions within 24 h. Thirty-one patients (84%) responded to a post-testing follow-up questionnaire; 3 (10%) were subsequently treated with a beta-lactam, and all reported that testing provided important information to their medical history. Providers identified time constraints, either their or their patients lack of time, as the major barrier to recruitment. Penicillin allergy testing safely evaluates patients labeled as penicillin allergic. It is well tolerated, and embraced by the patients who undergo testing. In our study, none of the patients tested had an allergic reaction, but we identified multiple barriers to developing a protocol for testing patients from the primary care setting.

Preliminary study of tissue concentrations of penicillin after local administration into the guttural pouches in four healthy horses.

Science.gov (United States)

Kendall, A; Mayhew, I G; Petrovski, K

2016-08-01

Treatment of subclinical carriers of Streptococcus equi subsp. equi with a gelatine-penicillin formulation deposited in the guttural pouch has been empirically proposed, but data on local tissue penicillin concentrations after treatment are lacking. We analysed tissue levels of penicillin after administration into the guttural pouches of four healthy horses. Two horses received local treatment with gelatine-penicillin and two horses received local treatment with an intramammary formulation of penicillin. Tissues were harvested for analysis either 12 or 24 h later. Results indicate that local treatment may be effective, but more research on optimal drug formulations in a larger sample size is warranted. © 2016 Australian Veterinary Association.

Characterization of the β-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies

NARCIS (Netherlands)

Alkema, Wynand B.L.; Hensgens, Charles M.H.; Kroezinga, Els H.; de Vries, Erik; Floris, René; Laan, Jan-Metske van der; Dijkstra, Bauke W.; Janssen, Dick B.

2000-01-01

The binding of penicillin to penicillin acylase was studied by X-ray crystallography. The structure of the enzyme–substrate complex was determined after soaking crystals of an inactive βN241A penicillin acylase mutant with penicillin G. Binding of the substrate induces a conformational change, in

Characterization of the beta-lactam binding site of penicillin acylase of Escherichia coli by structural and site-directed mutagenesis studies

NARCIS (Netherlands)

Alkema, WBL; Hensgens, CMH; Kroezinga, EH; de Vries, E; Floris, R; van der Laan, JM; Dijkstra, BW; Janssen, DB

2000-01-01

The binding of penicillin to penicillin acylase was studied by X-ray crystallography, The structure of the enzyme-substrate complex was determined after soaking crystals of an inactive beta N241A penicillin acylase mutant with penicillin G, Binding of the substrate induces a conformational change,

Penicillin production in industrial strain Penicillium chrysogenum P2niaD18 is not dependent on the copy number of biosynthesis genes.

Science.gov (United States)

Ziemons, Sandra; Koutsantas, Katerina; Becker, Kordula; Dahlmann, Tim; Kück, Ulrich

2017-02-16

Multi-copy gene integration into microbial genomes is a conventional tool for obtaining improved gene expression. For Penicillium chrysogenum, the fungal producer of the beta-lactam antibiotic penicillin, many production strains carry multiple copies of the penicillin biosynthesis gene cluster. This discovery led to the generally accepted view that high penicillin titers are the result of multiple copies of penicillin genes. Here we investigated strain P2niaD18, a production line that carries only two copies of the penicillin gene cluster. We performed pulsed-field gel electrophoresis (PFGE), quantitative qRT-PCR, and penicillin bioassays to investigate production, deletion and overexpression strains generated in the P. chrysogenum P2niaD18 background, in order to determine the copy number of the penicillin biosynthesis gene cluster, and study the expression of one penicillin biosynthesis gene, and the penicillin titer. Analysis of production and recombinant strain showed that the enhanced penicillin titer did not depend on the copy number of the penicillin gene cluster. Our assumption was strengthened by results with a penicillin null strain lacking pcbC encoding isopenicillin N synthase. Reintroduction of one or two copies of the cluster into the pcbC deletion strain restored transcriptional high expression of the pcbC gene, but recombinant strains showed no significantly different penicillin titer compared to parental strains. Here we present a molecular genetic analysis of production and recombinant strains in the P2niaD18 background carrying different copy numbers of the penicillin biosynthesis gene cluster. Our analysis shows that the enhanced penicillin titer does not strictly depend on the copy number of the cluster. Based on these overall findings, we hypothesize that instead, complex regulatory mechanisms are prominently implicated in increased penicillin biosynthesis in production strains.

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment.

Science.gov (United States)

Meyer, C N; Samuelsson, I S; Galle, M; Bangsborg, J M

2004-08-01

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.

ESTIMATION OF THE NUMBER OF NEURONS IN THE HIPPOCAMPUS OF RATS WITH PENICILLIN INDUCED EPILEPSY

Directory of Open Access Journals (Sweden)

Ilgaz Akdogan

2011-05-01

Full Text Available Epilepsy is a neurological disease arising from strong and uncontrollable electrical firings of a group of neurons in the central nervous system. Experimental epileptic models have been developed to assess the physiopathology of epileptic seizures. This study was undertaken to estimate the number of neurons in the rat hippocampus with penicillin induced epilepsy, using a stereological method, "the optical fractionator". In the experimental group, 500 IU penicillin-G was injected intra-cortically, and in the control group, the same volume of saline was administered. A week later, the animals were decapitated and their brains were removed by craniatomy. Frozen brains were cut with a thickness of 150 ěm in a cryostat. Sections were collected by systematic random sampling and stained with hematoxylen-eosin. Microscopic images of pyramidal cell layers from hippocampus CA1, CA2 and CA3 subfields were then transferred to a monitor, using a 100x objective (N.A. = 1.25. Using the optical disector method, the neurons were counted in the frames and determined with a fractionator sampling scheme. The total pyramidal neuron number was then estimated using the optical fractionator method. The total pyramidal neuron number was found to be statistically lower in the experimental group (mean = 142,888 ± 11,745 than in the control group (mean = 177,953 ± 10,907 (p < 0.05. The results suggest that a decrease in the hippocampal neuronal number in a penicillin model of epilepsy can be determined objectively and efficiently using the optical fractionator method.

Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

Science.gov (United States)

Ashraf, Zaman; Bais, Abdul; Manir, Md Maniruzzaman; Niazi, Umar

2015-01-01

A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

Full-course drug challenge test in the diagnosis of delayed allergic reactions to penicillin

DEFF Research Database (Denmark)

Borch, Jakob E; Bindslev-Jensen, Carsten

2011-01-01

Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy.......Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy....

The penicillin-binding protein 4 of Escherichia coli : primary structure, biochemical and genetic studies

NARCIS (Netherlands)

Mottl, Harald

1992-01-01

De ß-lactam antibiotica ("de penicillines") zijn zowel in medisch als ecomisch opzicht de belangrijkste groep antibiotica: De werking van deze antibiotica berust op verstoring van de synthese van de bacteriele celwand. De doeleiwitten van deze antibiotica worden penicillin-binding proteins, kortweg

Impact of a clinical guideline for prescribing antibiotics to inpatients reporting penicillin or cephalosporin allergy.

Science.gov (United States)

Blumenthal, Kimberly G; Shenoy, Erica S; Varughese, Christy A; Hurwitz, Shelley; Hooper, David C; Banerji, Aleena

2015-10-01

Self-reported penicillin allergy infrequently reflects an inability to tolerate penicillins. Inpatients reporting penicillin allergy receive alternative antibiotics that might be broader spectrum, more toxic, or less effective. To develop and assess a clinical guideline for the general inpatient provider that directs taking a history and prescribing antibiotics for patients with penicillin or cephalosporin allergy. A guideline was implemented to assist providers with assessing allergy history and prescribing antibiotics for patients with reported penicillin or cephalosporin allergy. The guideline used a standard 2-step graded challenge or test dose. A quasi-experimental study was performed to assess safety, feasibility, and impact on antibiotic use by comparing treatment 21 months before guideline implementation with 12 months after guideline implementation. Significantly more test doses to β-lactam antibiotics were performed monthly after vs before guideline implementation (median 14.5, interquartile range 13-16.25, vs 2, interquartile range 1-3.25, P  .5) between periods. Guideline-driven test doses decreased alternative antimicrobial therapy after the test dose, including vancomycin (68.3% vs 37.2%, P penicillin or cephalosporin allergy was associated with an almost 7-fold increase in the number of test doses to β-lactams without increased adverse drug reactions. Patients assessed with guideline-driven test doses were observed to have significantly decreased alternative antibiotic exposure. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Context-dependent modulation of alphabetagamma and alphabetadelta GABA A receptors by penicillin: implications for phasic and tonic inhibition.

Science.gov (United States)

Feng, Hua-Jun; Botzolakis, Emmanuel J; Macdonald, Robert L

2009-01-01

Penicillin, an open-channel blocker of GABA(A) receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and context-dependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABA(A) receptors expressed in HEK293T cells. When co-applied with saturating GABA, penicillin decreased peak amplitude, induced rebound, and prolonged deactivation of currents evoked from both synaptic and extrasynaptic receptor isoforms. However, penicillin had isoform-specific effects on the extent of desensitization, reflecting its ability to differentially modulate peak (non-equilibrium) and residual (near-equilibrium) currents. This suggested that the context of activation could determine the apparent sensitivity of a given receptor isoform to penicillin. To test this hypothesis, we explored the ability of penicillin to modulate synaptic and extrasynaptic isoform currents that were activated under more physiologically relevant conditions. Interestingly, while currents evoked from synaptic isoforms under phasic conditions (transient activation by a saturating concentration of GABA) were substantially inhibited by penicillin, currents evoked from extrasynaptic isoforms under tonic conditions (prolonged application by a sub-saturating concentration of GABA) were minimally affected. We therefore concluded that the reported inability of penicillin to modulate tonic currents could not simply be attributed to insensitivity of extrasynaptic receptors, but rather, reflected an inability to modulate these receptors in their native context of activation.

Penicillin G acylase from Achromobacter sp CCM 4824 An efficient biocatalyst for syntheses of beta-lactam antibiotics under conditions employed in large-scale processes

Czech Academy of Sciences Publication Activity Database

Bečka, Stanislav; Štěpánek, Václav; Vyasarayani, W. R.; Grulich, Michal; Maršálek, Jaroslav; Plháčková, Kamila; Dobišová, Marie; Marešová, Helena; Plačková, Martina; Valešová, Renata; Palyzová, Andrea; Datla, A.; Ashar, T. K.; Kyslík, Pavel

2014-01-01

Roč. 98, č. 3 (2014), s. 1195-1203 ISSN 0175-7598 Institutional support: RVO:61388971 Keywords : Achromobacter sp. * Penicillin G acylase * beta-Lactam antibiotics Subject RIV: EE - Microbiology, Virology Impact factor: 3.337, year: 2014

An Efficient Secret Key Homomorphic Encryption Used in Image Processing Service

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Pan Yang

2017-01-01

Full Text Available Homomorphic encryption can protect user’s privacy when operating on user’s data in cloud computing. But it is not practical for wide using as the data and services types in cloud computing are diverse. Among these data types, digital image is an important personal data for users. There are also many image processing services in cloud computing. To protect user’s privacy in these services, this paper proposed a scheme using homomorphic encryption in image processing. Firstly, a secret key homomorphic encryption (IGHE was constructed for encrypting image. IGHE can operate on encrypted floating numbers efficiently to adapt to the image processing service. Then, by translating the traditional image processing methods into the operations on encrypted pixels, the encrypted image can be processed homomorphically. That is, service can process the encrypted image directly, and the result after decryption is the same as processing the plain image. To illustrate our scheme, three common image processing instances were given in this paper. The experiments show that our scheme is secure, correct, and efficient enough to be used in practical image processing applications.

Hydroxylamine technique for in vitro prevention of penicillin inactivation of tobramycin.

Science.gov (United States)

Falkowski, A J; Creger, R J

1984-01-01

Hydroxylamine was evaluated and found to be a highly effective agent for the in vitro prevention of penicillin inactivation of tobramycin. This inactivation reaction resulted in an underestimation of tobramycin concentrations and was dependent on time, temperature, amount and type of penicillin, and amount of tobramycin. Plasma samples containing tobramycin and three clinically relevant concentrations of ticarcillin, carbenicillin, azlocillin, or piperacillin were incubated with and without hydroxylamine, and tobramycin concentrations were monitored at 0, 12, 24, 48, and 72 h. The inactivation reaction was found to be completely inhibited by hydroxylamine (1 mg/ml) compared with a 27 to 50% loss of measured tobramycin concentration in the unprotected tobramycin-penicillin samples. Hydroxylamine did not interfere with the Emit enzyme immunoassay (Syva Co.) at either high or low tobramycin concentrations. Hydroxylamine was effective in inhibiting the tobramycin inactivation at both room and refrigerator temperatures and was 100% effective in protecting tobramycin on a 1:1 molar basis. PMID:6393865

Effect of secondary penicillin prophylaxis on valvular changes in patients with rheumatic heart disease in Far North Queensland.

Science.gov (United States)

Haran, Shankar; Crane, Natalie; Kazi, Saniya; Axford-Haines, Louise; White, Andrew

2018-04-01

To determine the effect of secondary penicillin prophylaxis on echocardiographic diagnosed valvular changes in patients with rheumatic heart disease or history of acute rheumatic fever in the Townsville Health district. Patients with known were identified from the North Queensland register, serial echocardiogram results and number of secondary penicillin prophylaxis doses received in 2014 were collated. Descriptive statistics were utilised. Townsville Hospital and outreach clinics within the Townsville Health catchment zone. All patients diagnosed with acute rheumatic fever or rheumatic heart disease between 2010 and October 2013 who had serial echocardiograms prior to and post commencement of secondary penicillin prophylaxis were included. All patients were of Aboriginal or Torres Strait Islander descent. Progression of echocardiographic valvular changes and association with secondary penicillin prophylaxis compliance. Compliance with secondary penicillin prophylaxis among the study population was a secondary outcome measure. Twenty-three patients were recruited. Only those patients who were compliant with secondary penicillin prophylaxis had any improvement in valvular changes on echocardiogram. Four of six patients without any baseline valvular involvement developed new valvular changes. Seventy percent of patients received >75% of secondary penicillin prophylaxis doses. This small study of patients in Townsville suggests that with good secondary penicillin prophylaxis compliance there is regression of some cardiac lesions over time in people with rheumatic heart disease. Furthermore the natural history of acute rheumatic fever in the Indigenous population is progressive requiring strict adherence to secondary penicillin prophylaxis. Prospective studies or use of data from the nationwide RHD register and standardised reporting of cardiac echocardiograms will provide more robust evidence. © 2017 National Rural Health Alliance Inc.

Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

Science.gov (United States)

Gisbert, Javier P; Barrio, Jesús; Modolell, Inés; Molina-Infante, Javier; Aisa, Angeles Perez; Castro-Fernández, Manuel; Rodrigo, Luis; Cosme, Angel; Gisbert, Jose Luis; Fernández-Bermejo, Miguel; Marcos, Santiago; Marín, Alicia C; McNicholl, Adrián G

2015-02-01

Helicobacter pylori eradication is a challenge in penicillin allergy. To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

Role of penA polymorphisms for penicillin susceptibility in Neisseria lactamica and Neisseria meningitidis.

Science.gov (United States)

Karch, André; Vogel, Ulrich; Claus, Heike

2015-10-01

In meningococci, reduced penicillin susceptibility is associated with five specific mutations in the transpeptidase region of penicillin binding protein 2 (PBP2). We showed that the same set of mutations was present in 64 of 123 Neisseria lactamica strains obtained from a carriage study (MIC range: 0.125-2.0mg/L). The PBP2 encoding penA alleles in these strains were genetically similar to those found in intermediate resistant meningococci suggesting frequent interspecies genetic exchange. Fifty-six N. lactamica isolates with mostly lower penicillin MICs (range: 0.064-0.38mg/L) exhibited only three of the five mutations. The corresponding penA alleles were unique to N. lactamica and formed a distinct genetic clade. PenA alleles with no mutations on the other hand were unique to meningococci. Under penicillin selective pressure, genetic transformation of N. lactamica penA alleles in meningococci was only possible for alleles encoding five mutations, but not for those encoding three mutations; the transfer resulted in MICs comparable to those of meningococci harboring penA alleles that encoded PBP2 with five mutations, but considerably lower than those of the corresponding N. lactamica donor strains. Due to a transformation barrier the complete N. lactamica penA could not be transformed into N. meningitidis. In summary, penicillin MICs in N. lactamica were associated with the number of mutations in the transpeptidase region of PBP2. Evidence for interspecific genetic transfer was only observed for penA alleles associated with higher MICs, suggesting that alleles encoding only three mutations in the transpeptidase region are biologically not effective in N. meningitidis. Factors other than PBP2 seem to be responsible for the high levels of penicillin resistance in N. lactamica. A reduction of penicillin susceptibility in N. meningitidis by horizontal gene transfer from N. lactamica is unlikely to happen. Copyright © 2015 Elsevier GmbH. All rights reserved.

Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

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Zaman Ashraf

Full Text Available A number of penicillin derivatives (4a-h were synthesized by the condensation of 6-amino penicillinic acid (6-APA with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

Administration of perioperative penicillin reduces postoperative serum amyloid A response in horses being castrated standing

DEFF Research Database (Denmark)

Busk, Peter; Jacobsen, Stine; Martinussen, Torben

2010-01-01

Objectives: To compare postoperative inflammatory responses in horses administered perioperative procaine penicillin and those not administered penicillin using acute phase protein serum amyloid A (SAA) as a marker of inflammation. Study Design: Randomized clinical trial. Animals: Stallions (n = 50......) castrated under field conditions. Methods: SAA concentrations were determined on days 0, 3, and 8. Six horses were subsequently excluded because of elevated SAA concentrations on day 0. Of the remaining 50 horses, 26 were administered nonsteroidal anti-inflammatory drug (NSAID) therapy and 24 were...... administered NSAID and 25,000 U/kg procaine penicillin on day 0, 1, and 2. Results: SAA concentrations increased significantly from preoperative levels in both groups, and on day 8 concentrations were significantly (P o .02) higher in horses administered only NSAID than in those administered procaine penicillin...

Myositis complicating benzathine penicillin-G injection in a case of rheumatic heart disease

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Joshua R. Francis

2016-01-01

Full Text Available A 7-year old boy developed myositis secondary to intramuscular injection of benzathine penicillin-G in the context of secondary prophylaxis for rheumatic heart disease. Side effects of intramuscular delivery of benzathine penicillin-G are well described and include injection site pain and inflammation, but myositis, as depicted on magnetic resonance imaging in this case, has not previously been described.

Frequency of resistance to penicillin and erythromycin of pneumococcal strains that caused ottis media

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Jovanović Luka

2017-01-01

Full Text Available Introduction: Streptococcus pneumoniae is an important human pathogen and the most common cause of acute otitis media (AOM, especially in children. It is also a common cause of community acquired pneumonia, sepsis and bacterial meningitis. Drug of choice in the treatment of these disease are beta lactam antibiotics, and the first alternative are macrolides. The increasing prevalence of resistance to penicillin and macrolides, among pneumococci, has considerably complicated the treatment. Aim: The aim of this study was to determine susceptibility of pneumococcal isolates from pediatric AOM in Serbia to antibiotics. Material and methods: Antimicrobial susceptibility testing of 61 pneumococcal AOM was performed, collected from December 2014 to December 2015, using disk diffusion method and E test. Macrolide resistance profile was determined by double disk diffusion test. Results: In our study, 40 strains (65.6% showed reduced sensitivity to penicillin and erythromycin. There were 9 (14.8% high resistant isolates to penicillin, while 31 (50.8% showed reduced susceptibility. The most frequent resistance phenotype was cMLS. Co-resistance to penicillin and macrolides was found in 14.8% strains. Conclusion: Our results showed high resistance rate of S. pneumoniae, which causes AOM among children, to penicillin and macrolides. Further active surveillance of pneumococcal susceptibility to antibiotics is necessary, and use of these medications in empirical therapy should be limited.

On-line monitoring of Glucose and penicillin by sequential injection analysis

DEFF Research Database (Denmark)

Min, R.W.; Nielsen, Jens Bredal; Villadsen, John

1996-01-01

and a detector. The glucose analyzer is based on an enzymatic reaction using glucose oxidase, which converts glucose to glucono-lactone with formation of hydrogen peroxide and subsequent detection of H2O2 by a chemiluminescence reaction involving luminol. The penicillin analysis is based on formation......A sequential injection analysis (SIA) system has been developed for on-line monitoring of glucose and penicillin during cultivations of the filamentous fungus Penicillium chrysogenum. The SIA system consists of a peristaltic pump, an injection valve, two piston pumps, two multi-position valves...

Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test.

Science.gov (United States)

Qiao, H-L; Li, Z; Yang, J; Tian, X; Gao, N; Jia, L-J

2009-06-01

Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. Radioallergosorbent test is a good complementary test in persons who are skin-test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross-reactivity.

Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital.

Science.gov (United States)

Picard, Matthieu; Bégin, Philippe; Bouchard, Hugues; Cloutier, Jonathan; Lacombe-Barrios, Jonathan; Paradis, Jean; Des Roches, Anne; Laufer, Brian; Paradis, Louis

2013-01-01

Prescribing antibiotics to patients with a history of penicillin allergy is common in clinical practice. Opting for non-beta-lactam antibiotics has its inconveniences and is often unnecessary, because most of these patients are in fact not allergic. This study aimed to determine how physicians in a large Canadian tertiary-care academic hospital without allergists on staff treat patients with a history of penicillin allergy. A retrospective study was conducted during a 1-year period among all patients hospitalized in the intensive care unit, coronary care unit, and internal medicine wards. Files of patients with a record of penicillin allergy were reviewed to assess the need for antibiotics during their hospitalization and the decision-making process underlying the choice of antibiotic. The additional costs of alternative antibiotics were calculated. The files of 1738 patients admitted over a 1-year period were hand reviewed. A history of penicillin allergy was found in 172 patients (9.9%). The allergic reaction was described in only 30% of cases and left unmentioned in 20.7%. Beta-lactam antibiotics were used on 56 occasions despite a history of penicillin allergy. The use of alternative antibiotics in place of the beta-lactam standard of care carried an additional cost of $15,672 Canadian. Alleged penicillin allergy is common among hospitalized patients and leads to substantial additional costs. Poor documentation of penicillin allergy likely reflects a lack of knowledge on this issue in the medical community, which impairs optimal treatment of these patients. Increased education on this matter is needed, and allergists on staff could be part of the solution. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Does macrolide use confer risk of out-of-hospital cardiac arrest compared with penicillin V?

DEFF Research Database (Denmark)

Hertz, Frederik Boetius; Jensen, Aksel; Knudsen, Jenny D

2018-01-01

were examined by conditional logistic regression analyses in case-crossover and case-time-control models, using penicillin-V treatment as the comparative reference. From nationwide registries, we identified all OHCAs in Denmark from 2001 to 2010 and use of antibiotics. ETHICS: The present study...... was approved by the Danish Data Protection Agency (Danish Data Protection Agency (ref.no. 2007-58-0015, local ref.no. GEH-2014-017, (I-Suite.nr. 02 735)). PARTICIPANTS: We identified 29 111 patients with an OHCA. Of these, 514 were in macrolide treatment ≤7 days before OHCA and 1237 in penicillin-V treatment....... RESULTS: In the case-crossover analyses, overall macrolide use was not associated with OHCA with penicillin V as negative comparative reference (OR=0.90; 95% CI 0.73 to 1.10). Compared with penicillin-V treatment, specific macrolides were not associated with increased risk of OHCA: roxithromycin (OR=0...

Use of collagen hydrolysate as a complex nitrogen source for the synthesis of penicillin by Penicillium chrysogenum.

Science.gov (United States)

Leonhartsberger, S; Lafferty, R M; Korneti, L

1993-09-01

Optimal conditions for both biomass formation and penicillin synthesis by a strain of Penicillium chrysogenum were determined when using a collagen-derived nitrogen source. Preliminary investigations were carried out in shaken flask cultures employing a planned experimental program termed the Graeco-Latin square technique (Auden et al., 1967). It was initially determined that up to 30% of a conventional complex nitrogen source such as cottonseed meal could be replaced by the collagen-derived nitrogen source without decreasing the productivity with respect to the penicillin yield. In the pilot scale experiments using a 30 l stirred tank type of bioreactor, higher penicillin yields were obtained when 70% of the conventional complex nitrogen source in the form of cottonseed meal was replaced by the collagen hydrolysate. Furthermore, the maximum rate of penicillin synthesis continued for over a longer period when using collagen hydrolysate as a complex nitrogen source. Penicillin synthesis rates were determined using a linear regression.

Influence of the dissolved oxygen concentration on the penicillin biosynthetic pathway in steady-state cultures of Penicillium chrysogenum

DEFF Research Database (Denmark)

Henriksen, Claus Maxel; Nielsen, Jens Bredal; Villadsen, John

1997-01-01

The influence the of dissolved oxygen concentration on penicillin biosynthesis was studied in steady-state continuous cultures of a high-yielding strain of Penicillium chrysogenum operated at a dilution rate of 0.05 h-l. The dissolved oxygen concentration was varied between 0.019 and 0.344 m...... penicillin productivity decreases, and a value of 17 (mu mol/g of DW)/h was obtained when the dissolved oxygen concentration was 0.042 mM. A further lowering of the dissolved oxygen concentration to 0.019 mM resulted in the loss of penicillin production. However, penicillin productivity was instantly...

Prelude to rational scale-up of penicillin production: a scale-down study.

Science.gov (United States)

Wang, Guan; Chu, Ju; Noorman, Henk; Xia, Jianye; Tang, Wenjun; Zhuang, Yingping; Zhang, Siliang

2014-03-01

Penicillin is one of the best known pharmaceuticals and is also an important member of the β-lactam antibiotics. Over the years, ambitious yields, titers, productivities, and low costs in the production of the β-lactam antibiotics have been stepwise realized through successive rounds of strain improvement and process optimization. Penicillium chrysogenum was proven to be an ideal cell factory for the production of penicillin, and successful approaches were exploited to elevate the production titer. However, the industrial production of penicillin faces the serious challenge that environmental gradients, which are caused by insufficient mixing and mass transfer limitations, exert a considerably negative impact on the ultimate productivity and yield. Scale-down studies regarding diverse environmental gradients have been carried out on bacteria, yeasts, and filamentous fungi as well as animal cells. In accordance, a variety of scale-down devices combined with fast sampling and quenching protocols have been established to acquire the true snapshots of the perturbed cellular conditions. The perturbed metabolome information stemming from scale-down studies contributed to the comprehension of the production process and the identification of improvement approaches. However, little is known about the influence of the flow field and the mechanisms of intracellular metabolism. Consequently, it is still rather difficult to realize a fully rational scale-up. In the future, developing a computer framework to simulate the flow field of the large-scale fermenters is highly recommended. Furthermore, a metabolically structured kinetic model directly related to the production of penicillin will be further coupled to the fluid flow dynamics. A mathematical model including the information from both computational fluid dynamics and chemical reaction dynamics will then be established for the prediction of detailed information over the entire period of the fermentation process and

Flow cytometry as a rapid test for detection of penicillin resistance directly in bacterial cells in Enterococcus faecalis and Staphylococcus aureus.

Science.gov (United States)

Jarzembowski, T; Wiśniewska, K; Józwik, A; Bryl, E; Witkowski, J

2008-08-01

We studied the usefulness of flow cytometry for detection of penicillin resistance in E. faecalis and S. aureus by direct binding of commercially available fluorescent penicillin, Bocillin FL, to cells obtained from culture. There were significantly lower percentages of fluorescent cells and median and mean fluorescence values per particle in penicillin-resistant than in penicillin-sensitive strains of both species observed. The method allows rapid detection of penicillin resistance in S. aureus and E. faecalis. The results encourage further investigations on the detection of antibiotic resistance in bacteria using flow cytometry.

SERS Detection of Penicillin G Using Magnetite Decorated with Gold Nanoparticles

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Paula C. Pinheiro

2017-10-01

Full Text Available Sensitive and reliable procedures for detecting vestigial antibiotics are of great relevance for water quality monitoring due to the occurrence of such emergent pollutants in the aquatic environment. As such, we describe here research concerning the use of multifunctional nanomaterials combining magnetic and plasmonic components. These nanomaterials have been prepared by decorating magnetite nanoparticles (MNP with colloidal gold nanoparticles (Au NPs of distinct particle size distributions. Several analytical conditions were investigated in order to optimize the surface enhanced Raman scattering (SERS detection of penicillin G (PG dissolved in water. In particular, the dependence of the SERS signal by using distinct sized Au NPs adsorbed at the MNP was investigated. Additionally, microscopic methods, including Raman confocal microscopy, were employed to characterize the SERS substrates and then to qualitatively detect penicillin G using such substrates. For example, magnetic–plasmonic nanocomposites can be employed for magnetically concentrate analyte molecules and their removal from solution. As a proof of concept, we applied magneto-plasmonic nanosorbents in the removal of aqueous penicillin G and demonstrate the possibility of SERS sensing this antibiotic.

Osmotic Pressure, Bacterial Cell Walls, and Penicillin: A Demonstration.

Science.gov (United States)

Lennox, John E.

1984-01-01

An easily constructed apparatus that models the effect of penicillin on the structure of bacterial cells is described. Background information and procedures for using the apparatus during a classroom demonstration are included. (JN)

Studies on chelation properties of ampicillin with trace metal ions and comparison with penicillin complexes

International Nuclear Information System (INIS)

Rehmani, F.S.; Hameed, W.

2003-01-01

The penicillin is highly effective antibiotic with extremely wide margin of safety. Ampicillin e is the penicillin group of antibiotic in which side chain is phenyl group i.e. D-amino benzyl penicillin. The side chain determines many of anti bacterial and pharmacological characteristics. They inhibit the protein synthesis in bacterial cell wall. The chelating properties of the antibiotic may be used in the metal transport across the membrane. The present investigations are helpful in drug metabolism and their effects on minerals contents of the body. The complex formation between Ampicillin and penicillin with trace metal ions such as Fe(III), Cr(III), Al(III), Mn(II), Ni(II), Co(II), Ca(II), Mg(II), Cu(III) and Zn(II) were studied by potentiometric titrations and spectrophotometric methods. Stoichiometry of these complexes were studied by mole ratio method. It was found that the Fe(III) and Cu(II) ions form most stable complexes near physiological pH and the mole ratio was 1:1. (author)

Penicillin-Bound Polyacrylate Nanoparticles: Restoring the Activity of β-Lactam Antibiotics Against MRSA

OpenAIRE

Turos, Edward; Reddy, G. Suresh Kumar; Greenhalgh, Kerriann; Ramaraju, Praveen; Abeylath, Sampath C.; Jang, Seyoung; Dickey, Sonja; Lim, Daniel V.

2007-01-01

This report describes the preparation of antibacterially-active emulsified polyacrylate nanoparticles in which a penicillin antibiotic is covalently conjugated onto the polymeric framework. These nanoparticles were prepared in water by emulsion polymerization of an acrylated penicillin analogue pre-dissolved in a 7:3 (w:w) mixture of butyl acrylate and styrene in the presence of sodium dodecyl sulfate (surfactant) and potassium persulfate (radical initiator). Dynamic light scattering analysis...

Non-gaseous radiolysis products of procaine benzylpenicillin and Na salt 3-ortho-chloro-5-methyl-4-isoxasolyl penicillin

International Nuclear Information System (INIS)

Dziegielewski, J.; Jezowska-Trzebiatowska, B.

1974-01-01

Radiolysis products of procaine benzylpenicillin and Na salt 3-ortho-chlorophenyl-5-methyl-4-isoxasolyl penicillin were isolated and spectroscopic studies were made over the NMR, IR, UV and mass spectrometric ranges. On the basis of the results obtained, the bond breakage sites resulting from irradiation were determined and the modes of radiolysis decomposition were suggested. Irradiation of penicillins has been found to result in decomposition of the β-lactam and thiazolidine rings. Besides, decarboxylation of penicillins and bond cleavages within the amide group were observed as well as dehydrogenation and abstraction of simple hydrocarbons. The role of procaine and crystallization water in the radiolysis of penicillins was determined. (author)

In vitro interaction between caffeine and some penicillin antibiotics ...

African Journals Online (AJOL)

In vitro interaction between caffeine and some penicillin antibiotics against ... Minimum inhibitory concentrations (MIC) of the drugs were determined separately ... coffee, beverages or from other food sources may affect the effectiveness of a co ...

The Cellular Mechanisms that Ensure an Efficient Secretion in Streptomyces

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Sonia Gullón

2018-04-01

Full Text Available Gram-positive soil bacteria included in the genus Streptomyces produce a large variety of secondary metabolites in addition to extracellular hydrolytic enzymes. From the industrial and commercial viewpoints, the S. lividans strain has generated greater interest as a host bacterium for the overproduction of homologous and heterologous hydrolytic enzymes as an industrial application, which has considerably increased scientific interest in the characterization of secretion routes in this bacterium. This review will focus on the secretion machinery in S. lividans.

Determination of penicillin G in heavy sow urine using immunochromatographic assay and microbial inhibition swab tests

Science.gov (United States)

Introduction: Penicillin is a commonly used antibiotic in food animals. Unfortunately, violative penicillin residues in animal carcasses are sometimes identified by the USDA Food Safety and Inspection Service. Ante-mortem matrices such as urine could prove valuable for predicting possible violativ...

Detection and Prevalence of Penicillin-Susceptible Staphylococcus aureus in the United States in 2013

Science.gov (United States)

Doern, G. V.; Heilmann, K. P.; Miner, S.; Tendolkar, S.; Riahi, F.; Diekema, D. J.

2016-01-01

Using blaZ PCR as the “gold standard,” the sensitivities of CLSI penicillin zone edge and nitrocefin-based tests for β-lactamase production in Staphylococcus aureus were 64.5% and 35.5%, respectively, with specificity of 99.8% for both methods. In 2013, 13.5% of 3,083 S. aureus isolates from 31 U.S. centers were penicillin susceptible. PMID:26763960

Penicillin sensitivity of gonococci isolated in Australia, 1981-6. Australian Gonococcal Surveillance Programme.

OpenAIRE

1988-01-01

The sensitivity to penicillin of about 25,000 gonococcal isolates tested in Australia during the five years to 30 June 1986 was assessed in a collaborative multicentric study. Increasing resistance to the penicillin group of antibiotics was observed during the course of this study and was manifested both as increased levels of chromosomally mediated intrinsic resistance and by an increasing incidence of penicillinase producing strains of Neisseria gonorrhoeae (PPNG). Pronounced regional diffe...

De-labelling self-reported penicillin allergy within the emergency department through the use of skin tests and oral drug provocation testing.

Science.gov (United States)

Marwood, Joseph; Aguirrebarrena, Gonzalo; Kerr, Stephen; Welch, Susan A; Rimmer, Janet

2017-10-01

Self-reported penicillin allergy is common among patients attending the ED, but is a poor predictor of true immunoglobulin E-mediated hypersensitivity to penicillin. We hypothesise that with a combination of skin testing and drug provocation testing, selected patients can be safely de-labelled of their allergy. This prospective study enrolled a sample of patients presenting to an urban academic ED between 2011 and 2016 with a self-reported allergy to penicillin. Standardised skin prick and intradermal testing with amoxicillin and both major and minor determinants of penicillin was performed in the department. If negative, testing was followed by a graded oral challenge of amoxicillin over 9 days. The primary end point was the allergy status of participants at the end of the study. A total of 100 patients (mean age 42; standard deviation 14 years; 54% women) completed the testing. Of these, 81% (95% confidence interval 71.9-88.2) showed no hypersensitivity to penicillin and were labelled non-allergic. The majority (16/19) of allergies were confirmed by skin testing, with three suspected allergies detected by the oral challenge. Women were more likely than men to have a true penicillin allergy, with odds ratio of 4.0 (95% confidence interval 1.23-13.2). There were no serious adverse events. Selected patients in the ED who self-report an allergy to penicillin can be safely tested there for penicillin allergy, using skin tests and oral drug provocation testing. This testing allows a significant de-labelling of penicillin allergy, with the majority of these patients able to tolerate penicillin without incident. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge.

Science.gov (United States)

Hjortlund, J; Mortz, C G; Skov, P S; Bindslev-Jensen, C

2013-08-01

Skin testing in duplicate, correlation between case history of immediate and nonimmediate reactions and challenge outcome and prolonged oral treatment with penicillin in the diagnostic evaluation of allergic reactions to β-lactam antibiotics, mimicking real-life situations, have only been addressed in few studies. A total of 342 patients suspected of having β-lactam allergy were investigated according to the European Network for Drug Allergy (ENDA) guidelines and patients found to be negative in the ENDA program were supplemented with a 7-day oral treatment with penicillin. Skin testing with penicillins was performed in duplicate. Patients with case histories of reactions to other β-lactams were also subsequently challenged with the culprit drug. Nineteen patients were IgE-sensitized to penicillin. Then, intracutaneous tests (ICTs) were performed, in which 35 patients tested positive for allergy, 21 with delayed and 14 with immediate reactions. Only three patients tested positive for the major (PPL) and/or minor (MDM) penicillin determinants, all being positive for penicillin G in ICT. The remaining 291 patients were challenged with penicillin: 10 tested positive in single-dose challenge and 23 tested positive in the 7-day challenge. A total of 17 of 78 patients with a negative penicillin challenge tested positive during challenges with other β-lactams. We found no correlation between case histories of immediate and nonimmediate reactions and reaction time during challenge. The data suggest that case history is often insufficient to discriminate between immediate reactors and nonimmediate reactors. A 7-day challenge with the culprit β-lactam may yield more positive reactions than the accepted one- or 2-day challenge. Interpretation of skin testing should be made with caution. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Integrated Analysis of the Transcriptome and Metabolome of Corynebacterium glutamicum during Penicillin-Induced Glutamic Acid Production.

Science.gov (United States)

Hirasawa, Takashi; Saito, Masaki; Yoshikawa, Katsunori; Furusawa, Chikara; Shmizu, Hiroshi

2018-05-01

Corynebacterium glutamicum is known for its ability to produce glutamic acid and has been utilized for the fermentative production of various amino acids. Glutamic acid production in C. glutamicum is induced by penicillin. In this study, the transcriptome and metabolome of C. glutamicum is analyzed to understand the mechanism of penicillin-induced glutamic acid production. Transcriptomic analysis with DNA microarray revealed that expression of some glycolysis- and TCA cycle-related genes, which include those encoding the enzymes involved in conversion of glucose to 2-oxoglutaric acid, is upregulated after penicillin addition. Meanwhile, expression of some TCA cycle-related genes, encoding the enzymes for conversion of 2-oxoglutaric acid to oxaloacetic acid, and the anaplerotic reactions decreased. In addition, expression of NCgl1221 and odhI, encoding proteins involved in glutamic acid excretion and inhibition of the 2-oxoglutarate dehydrogenase, respectively, is upregulated. Functional category enrichment analysis of genes upregulated and downregulated after penicillin addition revealed that genes for signal transduction systems are enriched among upregulated genes, whereas those for energy production and carbohydrate and amino acid metabolisms are enriched among the downregulated genes. As for the metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry, the intracellular content of most metabolites of the glycolysis and the TCA cycle decreased dramatically after penicillin addition. Overall, these results indicate that the cellular metabolism and glutamic acid excretion are mainly optimized at the transcription level during penicillin-induced glutamic acid production by C. glutamicum. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cryptanalysis of quantum secret sharing based on GHZ states

International Nuclear Information System (INIS)

Liu Xiaofen; Pan Rijing

2011-01-01

In a recent paper (Hwang et al 2011 Phys. Scr. 83 045004), a subtle quantum secret sharing (QSS) protocol was proposed. One major advantage of this protocol is its high efficiency; that is, it is more efficient than other QSS protocols using the Greenberger-Horne-Zeilinger states. However, we analyzed the security of this protocol and found that it is insecure for one agent who may deduce half of the information about the deal's secret directly just by his/her piece of secret. Finally, a feasible improvement of this QSS protocol is put forward.

Alternative protein secretion: The Mam1 ABC transporter supports secretion of M-factor linked GFP in fission yeast

International Nuclear Information System (INIS)

Kjaerulff, Soren; Mueller, Sven; Jensen, Martin Roland

2005-01-01

To examine whether the fission yeast Mam1 ABC transporter can be used for secretion of heterologous proteins, thereby bypassing the classical secretion pathway, we have analyzed chimeric forms of the M-factor precursor. It was demonstrated that GFP can be exported when fused to both the amino-terminal prosequence from mfm1 and a CaaX motif. This secretion was dependent on the Mam1 transporter and not the classical secretion pathway. The secretion efficiency of GFP, however, was relatively low and most of the reporter protein was trapped in the vacuolar membranes. Our findings suggest that the Mam1 ABC protein is a promiscuous peptide transporter that can accommodate globular proteins of a relatively large size. Furthermore, our results help in defining the sequences required for processing and secretion of natural M-factor

of market milk supplies a survey of penicillin contaminatio

African Journals Online (AJOL)

to the preparation used and the dosage administered. The excretion of penicillin in milk ... of antibiotic contamination of the milk supply as a veterinary and public health problem .... milk samples, and to the Director of the Abattoir and Livestock.

Genetic diversity of penicillin-binding protein 2B and 2X genes from Streptococcus pneumoniae in South Africa.

OpenAIRE

Smith, A M; Klugman, K P; Coffey, T J; Spratt, B G

1993-01-01

Streptococcus pneumoniae (the pneumococcus) is believed to have developed resistance to penicillin by the production of altered forms of penicillin-binding proteins (PBPs) that have decreased affinity for penicillin. Sixty-eight clinical isolates of serogroup 6 and 19 pneumococci (MICs, < 0.015 to 8 micrograms/ml) were randomly selected from hospitals across South Africa which are at substantial geographic distance from each other. The polymerase chain reaction was used to isolate the penicil...

Antibiotic prophylaxis in cataract surgery in the setting of penicillin allergy: A decision-making algorithm.

Science.gov (United States)

LaHood, Benjamin R; Andrew, Nicholas H; Goggin, Michael

Cataract surgery is the most commonly performed surgical procedure in many developed countries. Postoperative endophthalmitis is a rare complication with potentially devastating visual outcomes. Currently, there is no global consensus regarding antibiotic prophylaxis in cataract surgery despite growing evidence of the benefits of prophylactic intracameral cefuroxime at the conclusion of surgery. The decision about which antibiotic regimen to use is further complicated in patients reporting penicillin allergy. Historic statistics suggesting crossreactivity of penicillins and cephalosporins have persisted into modern surgery. It is important for ophthalmologists to consider all available antibiotic options and have an up-to-date knowledge of antibiotic crossreactivity when faced with the dilemma of choosing appropriate antibiotic prophylaxis for patients undergoing cataract surgery with a history of penicillin allergy. Each option carries risks, and the choice may have medicolegal implications in the event of an adverse outcome. We assess the options for antibiotic prophylaxis in cataract surgery in the setting of penicillin allergy and provide an algorithm to assist decision-making for individual patients. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Group B Streptococcus prophylaxis in patients who report a penicillin allergy: a follow-up study.

Science.gov (United States)

Critchfield, Agatha S; Lievense, Stacey P; Raker, Christina A; Matteson, Kristen A

2011-02-01

The purpose of this study was to compare adherence to the 2002 Centers for Disease Control (CDC) guidelines for the prevention of perinatal group B Streptococcus (GBS) disease in patients who are allergic to penicillin during the years 2004-2006 and 2008. Previous data from our institution revealed suboptimal adherence to the 2002 CDC guidelines for GBS prophylaxis among women who are allergic to penicillin. These data caused the hospital to implement a series of interventions. The original cohort (2004-2006) was compared with a cohort of women who delivered between April 2008 and January 2009 (n = 74) to determine whether the proportion of women who had antimicrobial sensitivity testing and who had received an appropriate antibiotic had improved. In 2008, 76% (95% confidence interval, 66-84%) of GBS-positive women who are allergic to penicillin received an appropriate antibiotic (compared with 16.2% in 2004-2006; P sensitivity testing was performed in 79.4% of cases (95% confidence interval, 68-87%), compared with 11.4% in 2004-2006 (P penicillin improved dramatically. Copyright © 2011 Mosby, Inc. All rights reserved.

Evaluation the mechanisms of erythromycin and penicillin resistance ...

African Journals Online (AJOL)

user

2012-01-12

Jan 12, 2012 ... primer (Table 1) and 10 µl of DNA templates (Fukushima et al.,. 2008). PCR amplification was carried with the cycling parameters as follows: after an initial denaturation .... isolated from children in Japan. Mutations in pbp2x were observed in several strains presenting intermediate resistance to penicillin.

Detection and determination of Oxytetracycline and Penicillin G ...

African Journals Online (AJOL)

Antibiotic residues are small amounts of drugs or their active metabolites ... able daily intake and maximum residue limits in foods (FAO and WHO, 1995). Regulatory limits for antibiotic residues have been imposed on the dairy in- dustry in many ... Methods for oxytetracycline and penicillin G residue analysis. The milk ...

Resistance to penicillin of Staphylococcus aureus isolates from cows with high somatic cell counts in organic and conventional dairy herds in Denmark

DEFF Research Database (Denmark)

Bennedsgaard, Torben W.; Thamsborg, Stig M.; Aarestrup, Frank Møller

2006-01-01

Background: Quarter milk samples from cows with high risk of intramammary infection were examined to determine the prevalence of Staphylococcus aureus (SA) and penicillin resistant SA (SAr) in conventional and organic dairy herds and herds converting to organic farming in a combined longitudinal......: 2%-5%) respectively. The prevalence of penicillin resistance among SA infected cows was 12% (95% confidence interval: 6%-19%) when calculated from the first herd visits. No statistically significant differences were observed in the prevalence of SAr or the proportion of isolates resistant...... to penicillin between herd groups. Conclusion: The proportion of isolates resistant to penicillin was low compared to studies in other countries except Norway and Sweden. Based on the low prevalence of penicillin resistance of SA, penicillin should still be the first choice of antimicrobial agent for treatment...

The Impact of Reporting a Prior Penicillin Allergy on the Treatment of Methicillin-Sensitive Staphylococcus aureus Bacteremia.

Science.gov (United States)

Blumenthal, Kimberly G; Shenoy, Erica S; Huang, Mingshu; Kuhlen, James L; Ware, Winston A; Parker, Robert A; Walensky, Rochelle P

2016-01-01

Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection with mortality benefit from receipt of parenteral β-lactam therapy. A substantial portion of MSSA bacteremia patients report penicillin allergy, but infrequently have true allergy. To determine the frequency and predictors of optimal and adequate therapy in patients with MSSA bacteremia. Retrospective cohort. Adult inpatients with MSSA bacteremia, January 2009 through October 2013. The primary measure was a trial of optimal therapy (OT), defined as ≥3 inpatient days or discharge on any first-line agents (nafcillin, oxacillin, cefazolin, or penicillin G, if susceptible). The secondary measure was completion of adequate therapy (AT), defined as ≥10 inpatient days or discharge on an agent appropriate for MSSA bacteremia. Data were electronically gathered with key variables manually validated through chart review. Log-binomial regression models were used to determine the frequency and predictors of outcomes. Of 456 patients, 346 (76%) received a trial of OT. Patients reporting penicillin allergy (13%) were less likely to receive OT trial than those without penicillin allergy (47% vs. 80%, p penicillin allergy was the largest negative predictor of OT trial (RR 0.64 [0.49, 0.83]). Infectious Disease (ID) consultation was the largest positive predictor of OT trial across all patients (RR 1.34 [1.14, 1.57]). Allergy/Immunology consultation was the single most important predictor of OT trial among patients reporting penicillin allergy (RR 2.33 [1.44, 3.77]). Of 440 patients, 391 (89%) completed AT, with ID consultation the largest positive predictor of the outcome (RR 1.28 [1.15, 1.43]). Nearly 25% of patients with MSSA bacteremia did not receive OT trial and about 10% did not receive AT completion. Reported penicillin allergy reduced, and ID consult increased, the likelihood of OT. Allergy evaluation, coupled with ID consultation, may improve outcomes in MSSA bacteremic patients.

[Five days ceftibuten versus 10 days penicillin in the treatment of 2099 patients with A-streptococcal tonsillopharyngitis].

Science.gov (United States)

Adam, D; Scholz, H; Helmerking, M

2001-07-19

Group A Streptococci have remained sensitive to penicillins and other betalactam antibiotics, e. g. cephalosporins. Since the beginning of the 1950s oral penicillin V given three times daily in a dose of 50,000 IU daily has been the drug of choice against Group A streptococcal infection. The German Society for Pediatric Infectious Diseases (DGPI) undertook a large scale multicenter randomized study of culture-proven A-streptococcal tonsillopharyngitis to compare the efficacy and safety of a five day regimen of ceftibuten (9 mg/kg KG, once daily) with 10 days of penicillin V (50,000 I.E./kg KG, divided in three doses), testing for equivalence of clinical and bacteriological efficacy. A one year follow-up served to assess poststreptococcal sequelae like rheumatic fever or glomerulonephritis. The clinical efficacy at the clinical end-point 7-9 days after end of treatment was 86.9% (419/482) for ceftibuten and 88.6% (1,198/1,352) for penicillin V. This result is statistically equivalent (P = 0.0152). Resolution of clinical symptoms was significantly faster in the ceftibuten group (P = 0.043/Fisher-Test) and compliance was significantly superior as well (P (0.001). Eradication of group A streptococci at an early control 2-4 days after end of treatment was not equivalent, 78.49% for ceftibuten and 84.42% for penicillin V (P = 0.5713). Both eradication rates were comparable 7-8 weeks after end of treatment (84.65%, 375/443 ceftibuten vs. 86.82%, 1,067/1,229 penicillin V), the difference not being significant. No cases of poststreptococcal sequelae, e.g. rheumatic fever or glomerulonephritis, attributable to either ceftibuten or penicillin were observed in the course of the study.

Multi-objective optimization of an industrial penicillin V bioreactor train using non-dominated sorting genetic algorithm.

Science.gov (United States)

Lee, Fook Choon; Rangaiah, Gade Pandu; Ray, Ajay Kumar

2007-10-15

Bulk of the penicillin produced is used as raw material for semi-synthetic penicillin (such as amoxicillin and ampicillin) and semi-synthetic cephalosporins (such as cephalexin and cefadroxil). In the present paper, an industrial penicillin V bioreactor train is optimized for multiple objectives simultaneously. An industrial train, comprising a bank of identical bioreactors, is run semi-continuously in a synchronous fashion. The fermentation taking place in a bioreactor is modeled using a morphologically structured mechanism. For multi-objective optimization for two and three objectives, the elitist non-dominated sorting genetic algorithm (NSGA-II) is chosen. Instead of a single optimum as in the traditional optimization, a wide range of optimal design and operating conditions depicting trade-offs of key performance indicators such as batch cycle time, yield, profit and penicillin concentration, is successfully obtained. The effects of design and operating variables on the optimal solutions are discussed in detail. Copyright 2007 Wiley Periodicals, Inc.

Context-Dependent Modulation of αβγ and αβγ GABAA Receptors by Penicillin: Implications for Phasic and Tonic Inhibition

Science.gov (United States)

Feng, Hua-Jun; Botzolakis, Emmanuel J.; Macdonald, Robert L.

2009-01-01

Summary Penicillin, an open-channel blocker of GABAA receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and context-dependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABAA receptors expressed in HEK293T cells. When co-applied with saturating GABA, penicillin decreased peak amplitude, induced rebound, and prolonged deactivation of currents evoked from both synaptic and extrasynaptic receptor isoforms. However, penicillin had isoform-specific effects on the extent of desensitization, reflecting its ability to differentially modulate peak (non-equilibrium) and residual (near-equilibrium) currents. This suggested that the context of activation could determine the apparent sensitivity of a given receptor isoform to penicillin. To test this hypothesis, we explored the ability of penicillin to modulate synaptic and extrasynaptic isoforms that were activated under more physiologically relevant conditions. Interestingly, while currents evoked from synaptic isoforms under phasic conditions (transient activation by a saturating concentration of GABA) were substantially inhibited by penicillin, currents evoked from extrasynaptic isoforms under tonic conditions (prolonged application by a sub-saturating concentration of GABA) were minimally affected. We therefore concluded that the reported inability of penicillin to modulate tonic currents could not simply be attributed to insensitivity of extrasynaptic receptors, but rather, reflected an inability to modulate these receptors in their native context of activation. PMID:18775733

The radiation-sterilization of semi-synthetic penicillins

International Nuclear Information System (INIS)

Jacobs, G.P.

1979-01-01

Gamma-irradiation in the dry state of the semi-synthetic penicillins, amoxycillin trihydrate, flucloxacillin-Na, methicillin-Na results in minimal degradation even following a 5 Mrad dose, suggesting the feasibility of their radiation-sterilization. Carbenicillin-Na is more susceptible to radiation-induced degradation but is nevertheless not affected by 1 Mrad dose. This 'low' dose may be suitable for carbenicillin with very low initial contamination. (author)

[Use of semisynthetic penicillin in the treatment of infectious mastitis in cows during the dry period].

Science.gov (United States)

Vasil', M; Federic, F

1990-03-01

During two years in a herd of dairy cows with an average number of 94 cows the effects on infection level were investigated of single nonselective antibiotics treatment of cow's udder in the dry period. The treatment influenced favourably the results of complex periodic three-months examinations: --level of infection with infectious mastitis was reduced from 38.3% to 9.8%; --occurrence of clinical forms of mastitis dropped from 17.4% to 5.9%;--occurrence of NK-test positive reactions decreased from 55.8% to 21.8%. An investigation into therapeutic efficiency of three intramammary preparations revealed the highest total therapeutic effect of Stapenor retard (Bayer, FRG)--93.2%; Syntarpene 500 (Polfa, Poland) had the total therapeutic efficiency of 92.6% and the efficiency of Oxaclene foam (Spofa, CSSR) made 86.5%. The results demonstrate good efficiency of the method because the levels of mastitis infection in the herd were positively influenced, and excellent therapeutic efficiency of semisynthetic penicillins containing intramammary preparations used for mastitis treatment of dairy cows in the dry period.

Are two penicillins better than one? A systematic review of oral flucloxacillin and penicillin V versus oral flucloxacillin alone for the emergency department treatment of cellulitis.

Science.gov (United States)

Quirke, Michael; O'Sullivan, Ronan; McCabe, Aileen; Ahmed, Jameel; Wakai, Abel

2014-06-01

Flucloxacillin either alone or combined with penicillin V is still the first-line antibiotic drug of choice for the treatment of cellulitis in emergency departments (EDs) in Ireland. The rationale for this antibiotic regimen is their anti-staphylococcal and anti-streptococcal activity. To determine the clinical efficacy, tolerability and safety of oral flucloxacillin alone (monotherapy) compared with a combination of flucloxacillin with penicillin V (dual therapy) in the ED-directed outpatient treatment of cellulitis. We searched the following electronic databases: MEDLINE (1950 to August 2011), EMBASE (1980 to August 2011), Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2011, Issue), OpenGrey, Current Controlled Trials metaRegister of Clinical Trials (August 2011) and reference lists and websites of potential trials. We performed cross-referencing from the reference lists of major articles on the subject. We imposed no language restriction. Despite a comprehensive literature search to identify relevant studies, no randomized-controlled trials that fulfilled the inclusion criteria were found. Despite its common use, there are no published randomized-controlled trials comparing flucloxacillin monotherapy with a combination of flucloxacillin and penicillin V in the ED management of cellulitis. We discuss existing European and North American prescribing rationale and current guidelines.

Normal and abnormal secretion by haemopoietic cells

Science.gov (United States)

STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M

2001-01-01

The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687

Development and application of a population physiologically based pharmacokinetic model for penicillin G in swine and cattle for food safety assessment

NARCIS (Netherlands)

Li, Miao; Gehring, Ronette; Riviere, Jim E; Lin, Zhoumeng

Penicillin G is a widely used antimicrobial in food-producing animals, and one of the most predominant drug residues in animal-derived food products. Due to reduced sensitivity of bacteria to penicillin, extralabel use of penicillin G is common, which may lead to violative residues in edible tissues

Dispatched and Scube Mediate the Efficient Secretion of the Cholesterol-Modified Hedgehog Ligand

Directory of Open Access Journals (Sweden)

Hanna Tukachinsky

2012-08-01

Full Text Available The Hedgehog (Hh signaling pathway plays critical roles in metazoan development and in cancer. How the Hh ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hh ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, mediated by two proteins that are essential for vertebrate Hh signaling: the membrane protein Dispatched (Disp and a member of the Scube family of secreted proteins. Cholesterol modification is sufficient for a heterologous protein to interact with Scube and to be secreted in a Scube-dependent manner. Disp and Scube recognize different structural aspects of cholesterol similarly to how Niemann-Pick disease proteins 1 and 2 interact with cholesterol, suggesting a hand-off mechanism for transferring Hh from Disp to Scube. Thus, Disp and Scube cooperate to dramatically enhance the secretion and solubility of the cholesterol-modified Hh ligand.

Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark: a retrospective cohort study.

Science.gov (United States)

Egelund, Gertrud Baunbæk; Jensen, Andreas Vestergaard; Andersen, Stine Bang; Petersen, Pelle Trier; Lindhardt, Bjarne Ørskov; von Plessen, Christian; Rohde, Gernot; Ravn, Pernille

2017-04-20

Community-acquired pneumonia (CAP) is a severe infection, with high mortality. Antibiotic strategies for CAP differ across Europe. The objective of the study was to describe the epidemiology of CAP in Denmark and evaluate the prognosis of patients empirically treated with penicillin-G/V monotherapy. Retrospective cohort study including hospitalized patients with x-ray confirmed CAP. We calculated the population-based incidence, reviewed types of empiric antibiotics and duration of antibiotic treatment. We evaluated the association between mortality and treatment with empiric penicillin-G/V using logistic regression analysis. We included 1320 patients. The incidence of hospitalized CAP was 3.1/1000 inhabitants. Median age was 71 years (IQR; 58-81) and in-hospital mortality was 8%. Median duration of antibiotic treatment was 10 days (IQR; 8-12). In total 45% were treated with penicillin-G/V as empiric monotherapy and they did not have a higher mortality compared to patients treated with broader-spectrum antibiotics (OR 0.92, CI 95% 0.55-1.53). The duration of treatment exceeded recommendations in European guidelines. Empiric monotherapy with penicillin-G/V was commonly used and not associated with increased mortality in patients with mild to moderate pneumonia. Our results are in agreement with current conservative antibiotic strategy as outlined in the Danish guidelines.

Untersuchungen zur Anwendbarkeit eines integrierten Nachweissystems für Penicillin-Rückstände in Kuhmilch und Ziegenmilch

OpenAIRE

Kress, Claudia

2010-01-01

In der vorliegenden Arbeit wurde die Anwendbarkeit eines integrierten Nachweissystems für Penicillin-Rückstände in Kuhmilch und Ziegenmilch überprüft. Der zweite Schwerpunkt dieser Arbeit lag auf der Hemmstoffbelastung von Ziegenmilch, d.h. es sollte ein Überblick über die Belastung der in Hessen produzierten Ziegenmilch mit Penicillin-Rückständen gewonnen werden. Die „Kernmethode“ des integrierten Nachweissystems für Penicillin-Rückstände in Kuhmilch und Ziegenmilch ist ein...

Cryptanalysis of quantum secret sharing based on GHZ states

Energy Technology Data Exchange (ETDEWEB)

Liu Xiaofen; Pan Rijing, E-mail: liuxiaofen23@fjnu.edu.cn [School of Mathematics and Computer Science, Fujian Normal University, Fuzhou 350007 (China); Key Laboratory of Network Security and Cryptography, Fujian Normal University, Fuzhou 350007 (China)

2011-10-15

In a recent paper (Hwang et al 2011 Phys. Scr. 83 045004), a subtle quantum secret sharing (QSS) protocol was proposed. One major advantage of this protocol is its high efficiency; that is, it is more efficient than other QSS protocols using the Greenberger-Horne-Zeilinger states. However, we analyzed the security of this protocol and found that it is insecure for one agent who may deduce half of the information about the deal's secret directly just by his/her piece of secret. Finally, a feasible improvement of this QSS protocol is put forward.

Meningococcal B Vaccine Failure With a Penicillin-Resistant Strain in a Young Adult on Long-Term Eculizumab.

Science.gov (United States)

Parikh, Sydel R; Lucidarme, Jay; Bingham, Coralie; Warwicker, Paul; Goodship, Tim; Borrow, Ray; Ladhani, Shamez N

2017-09-01

We describe a case of invasive meningococcal disease due to a vaccine-preventable and penicillin-resistant strain in a fully immunized young adult on long-term complement inhibitor therapy and daily penicillin chemoprophylaxis. Eculizumab is a humanized monoclonal antibody that binds human complement C5 protein and inhibits the terminal complement pathway. It is currently recommended for the treatment of complement-mediated thrombotic microangiopathies. An unwanted complication of inhibiting complement, however, is an increased risk of invasive meningococcal disease. Here, we report the first case of meningococcal group B vaccine failure in a young adult receiving eculizumab for atypical hemolytic uremic syndrome. She developed invasive meningococcal disease due to a vaccine-preventable and penicillin-resistant meningococcal group B strain 4 months after receiving 2 doses of meningococcal group B vaccine while on oral penicillin prophylaxis against meningococcal infection. Copyright © 2017 by the American Academy of Pediatrics.

Positive serum specific IgE has a short half-life in patients with penicillin allergy and reversal does not always indicate tolerance.

Science.gov (United States)

Hjortlund, Janni; Mortz, Charlotte Gotthard; Stage, Tore Bjerregaard; Skov, Per Stahl; Dahl, Ronald; Bindslev-Jensen, Carsten

2014-01-01

The positive and negative predictive values of specific IgE to penicillins are not well established for penicillin hypersensitivity. One reason may be that serum IgE levels to penicillin diminish over time. The objective in this study was to investigate variations in serum half-life (T½) for specific IgE to penicillins (s-IgE) and to evaluate the outcome of penicillin challenges in patients with previous but not present specific IgE to penicillins. Two subgroups were investigated. All included patients had a history of penicillin allergy with reported symptoms such as urticaria/angioedema or unclassified cutaneous rash. T½ of specific IgE to penicillins was calculated based on sera from 29 patients with repeated measurements of s-IgE. Twenty-two patients with a previous positive s-IgE was followed and challenged with penicillin when IgE had become negative. The T½ for s-IgE varied between the 26 patients with decreasing s-IgE from 1.6 months to 76.4 months and 52% had a T½ of less than a year. The three patients with stable and increasing IgE-values showed T½ approaching infinity A total of 29 challenges with β-lactams were performed. Four different patterns were seen when evaluating the clinical reaction to challenge (positive/negative) and post-challenge boost of s-IgE (yes/no). Eight (36.4%) had negative challenge and negative post-challenge s-IgE, eight (36.4%) negative challenge, but positive post-challenge s-IgE levels. 3 (13.6%) had positive challenge and positive post-challenge s-IgE whereas 3 (13.6%) were challenge positive, but had negative post-challenge s-IgE. Specific IgE to penicillins declines over time stressing the importance of a close time relation between diagnostic work-up and clinical reaction. Reversal of previously positive s-IgE may still be associated with positive penicillin challenges and/or re-boostering of s-IgE to positivity.

Current state and perspectives of penicillin G acylase-based biocatalyses

Czech Academy of Sciences Publication Activity Database

Marešová, Helena; Plačková, Martina; Grulich, Michal; Kyslík, Pavel

2014-01-01

Roč. 98, č. 7 (2014), s. 2867-2879 ISSN 0175-7598 Institutional support: RVO:61388971 Keywords : Penicillin G acylase * beta lactam biocatalysis * Enantioselectivity Subject RIV: EE - Microbiology, Virology Impact factor: 3.337, year: 2014

Improved X-ray diffraction from Bacillus megaterium penicillin G acylase crystals through long cryosoaking dehydration

International Nuclear Information System (INIS)

Rojviriya, Catleya; Pratumrat, Thunyaluck; Saper, Mark A.; Yuvaniyama, Jirundon

2011-01-01

Penicillin G acylase from the Gram-positive bacterium B. megaterium was crystallized and X-ray diffraction from these crystals could be substantially improved by slight dehydration through a long cryo-soak. Penicillin G acylase from Bacillus megaterium (BmPGA) is currently used in the pharmaceutical industry as an alternative to PGA from Escherichia coli (EcPGA) for the hydrolysis of penicillin G to produce 6-aminopenicillanic acid (6-APA), a penam nucleus for semisynthetic penicillins. Despite the significant differences in amino-acid sequence between PGAs from Gram-positive and Gram-negative bacteria, a representative PGA structure of Gram-positive origin has never been reported. In this study, crystallization and diffraction studies of BmPGA are described. Poor diffraction patterns with blurred spots at higher resolution were typical for BmPGA crystals cryocooled after a brief immersion in cryoprotectant solution. Overnight soaking in the same cryo-solution substantially improved both the mosaicity and resolution limit through the establishment of a new crystal-packing equilibrium. A crystal of BmPGA diffracted X-rays to 2.20 Å resolution and belonged to the monoclinic space group P2 1 with one molecule of BmPGA in the asymmetric unit

Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial.

Science.gov (United States)

Demiroglu, H; Ozcebe, O I; Barista, I; Dündar, S; Eldem, B

2000-02-19

Sight-threatening eye involvement is a serious complication of Behçet's disease. Extraocular complications such as arthritis, vascular occlusive disorders, mucocutaneous lesions, and central-nervous-system disease may lead to morbidity and even death. We designed a prospective study in newly diagnosed patients without previous eye disease to assess whether prevention of eye involvement and extraocular manifestations, and preservation of visual acuity are possible with combination treatments with and without interferon alfa-2b. Patients were randomly assigned 3 million units interferon alfa-2b subcutaneously every other day for the first 6 months plus 1.5 mg colchicine orally daily and 1.2 million units benzathine penicillin intramuscularly every 3 weeks (n=67), or colchicine and benzathine penicillin alone (n=68). The primary endpoint was visual-acuity loss. Analysis was by intention to treat. Significantly fewer patients who were treated with interferon had eye involvement than did patients who did not receive interferon (eight vs 27, relative risk 0.21 [95% CI 0.09-0.50], p<0.001). Ocular attack rate was 0.2 (SD 0.62) per year with interferon therapy and 1.02 (1.13) without interferon therapy (p=0.0001). Visual-acuity loss was significantly lower among patients treated with interferon than in those without interferon (two vs 13, relative risk 0.13 [95% CI 0.03-0.60], p=0.003). Arthritis episodes, vascular events, and mucocutaneous lesions were also less frequent in patients treated with interferon than in those not receiving interferon. No serious side-effects were reported. Therapy with interferon alfa-2b, colchicine, and benzathine penicillin seems to be an effective regimen in Behçet's disease for the prevention of recurrent eye attacks and extraocular complications, and for the protection of vision.

Dispatched and scube mediate the efficient secretion of the cholesterol-modified hedgehog ligand.

Science.gov (United States)

Tukachinsky, Hanna; Kuzmickas, Ryan P; Jao, Cindy Y; Liu, Jing; Salic, Adrian

2012-08-30

The Hedgehog (Hh) signaling pathway plays critical roles in metazoan development and in cancer. How the Hh ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hh ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, mediated by two proteins that are essential for vertebrate Hh signaling: the membrane protein Dispatched (Disp) and a member of the Scube family of secreted proteins. Cholesterol modification is sufficient for a heterologous protein to interact with Scube and to be secreted in a Scube-dependent manner. Disp and Scube recognize different structural aspects of cholesterol similarly to how Niemann-Pick disease proteins 1 and 2 interact with cholesterol, suggesting a hand-off mechanism for transferring Hh from Disp to Scube. Thus, Disp and Scube cooperate to dramatically enhance the secretion and solubility of the cholesterol-modified Hh ligand. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Estimating Benzathine Penicillin Need for the Treatment of Pregnant Women Diagnosed with Syphilis during Antenatal Care in High-Morbidity Countries

Science.gov (United States)

Taylor, Melanie M.; Nurse-Findlay, Stephen; Zhang, Xiulei; Hedman, Lisa; Kamb, Mary L.; Broutet, Nathalie; Kiarie, James

2016-01-01

Background Congenital syphilis continues to be a preventable cause of global stillbirth and neonatal morbidity and mortality. Shortages of injectable penicillin, the only recommended treatment for pregnant women and infants with syphilis, have been reported by high-morbidity countries. We sought to estimate current and projected annual needs for benzathine penicillin in antenatal care settings for 30 high morbidity countries that account for approximately 33% of the global burden of congenital syphilis. Methods Proportions of antenatal care attendance, syphilis screening coverage in pregnancy, syphilis prevalence among pregnant women, and adverse pregnancy outcomes due to untreated maternal syphilis reported to WHO were applied to 2012 birth estimates for 30 high syphilis burden countries to estimate current and projected benzathine penicillin need for prevention of congenital syphilis. Results Using current antenatal care syphilis screening coverage and seroprevalence, we estimated the total number of women requiring treatment with at least one injection of 2.4 MU of benzathine penicillin in these 30 countries to be 351,016. Syphilis screening coverage at or above 95% for all 30 countries would increase the number of women requiring treatment with benzathine penicillin to 712,030. Based on WHO management guidelines, 351,016 doses of weight-based benzathine penicillin would also be needed for the live-born infants of mothers who test positive and are treated for syphilis in pregnancy. Assuming availability of penicillin and provision of treatment for all mothers diagnosed with syphilis, an estimated 95,938 adverse birth outcomes overall would be prevented including 37,822 stillbirths, 15,814 neonatal deaths, and 34,088 other congenital syphilis cases. Conclusion Penicillin need for maternal and infant syphilis treatment is high among this group of syphilis burdened countries. Initiatives to ensure a stable and adequate supply of benzathine penicillin for treatment

Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.

Science.gov (United States)

Zeelenberg, Ingrid S; Ostrowski, Matias; Krumeich, Sophie; Bobrie, Angélique; Jancic, Carolina; Boissonnas, Alexandre; Delcayre, Alain; Le Pecq, Jean-Bernard; Combadière, Béhazine; Amigorena, Sebastian; Théry, Clotilde

2008-02-15

Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII-like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols.

A linear construction of perfect secret sharing schemes

NARCIS (Netherlands)

Dijk, van M.; Santis, De A.

1995-01-01

In this paper, we generalize the vector space construction due to Brickell [5]. This generalization, introduced by Bertilsson [1], leads to perfect secret sharing schemes with rational information rates in which the secret can be computed efficiently by each qualified group. A one to one

Penicillin sensitivity of gonococci isolated in Australia, 1981-6. Australian Gonococcal Surveillance Programme.

Science.gov (United States)

1988-06-01

The sensitivity to penicillin of about 25,000 gonococcal isolates tested in Australia during the five years to 30 June 1986 was assessed in a collaborative multicentric study. Increasing resistance to the penicillin group of antibiotics was observed during the course of this study and was manifested both as increased levels of chromosomally mediated intrinsic resistance and by an increasing incidence of penicillinase producing strains of Neisseria gonorrhoeae (PPNG). Pronounced regional differences in the levels of intrinsic resistance, the incidence of infections with PPNG, and the endemic spread of PPNG strains were observed.

Effect of 60Co-irradiation on penicillin G procaine in veterinary mastitis products

International Nuclear Information System (INIS)

Tsuji, K.; Goetz, J.F.; Vanmeter, W.

1979-01-01

The effect of 60 Co-irradation on penicillin G procaine in a peanut oil-based veterinary mastitis product was examined by reversed-phase high-performance liquid chromatography (HPLC). The HPLC method is capable of separating and quantifiying procaine, penicillin G, and various degradation compounds. Values obtained by the HPLC method on the product irradiated and stored at various temperatures correlated well with those of the microbiological assay. No significant decrease in the procaine was detected even after 4.0-Mrad irradiation. The HPLC method is applicable for analysis of other beta-lactam antibiotics

Oral penicillin prescribing for children in the UK: a comparison with BNF for Children age-band recommendations

Science.gov (United States)

Saxena, Sonia; Ismael, Zareen; Murray, Macey L; Barker, Charlotte; Wong, Ian CK; Sharland, Mike; Long, Paul F

2014-01-01

Background The British National Formulary for Children (BNFC) recommends dosing oral penicillins according to age-bands, weight-bands, or weight-based calculations. Because of the rising prevalence of childhood obesity, age-band-based prescribing could lead to subtherapeutic dosing. Aim To investigate actual oral penicillin prescribing by GPs in the UK with reference to the current BNFC age-band recommendations. Design and setting Descriptive analysis of UK prescriptions in the 2010 IMS Disease-Analyzer database (IMS-DA). Method A detailed database analysis was undertaken of oral penicillin prescriptions for 0–18 year olds from the 2010 IMS-DA. The prescription analysis included all available data on formulation, strength (mg), prescription quantity unit, package size, prescribed quantity, and volume. Results Considering amoxicillin alone, no infants (aged penicillins for children in UK primary care, with very few children being prescribed the current national recommended doses. There is an urgent need to review dosing guidelines, in relation to the weights of children today. PMID:24686886

Serological Response to Treatment of Syphilis with Doxycycline Compared with Penicillin in HIV-infected Individuals

DEFF Research Database (Denmark)

Salado-Rasmussen, Kirsten; Hoffmann, Steen; Cowan, Susan

2016-01-01

Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios...... (ORs) with 95% confidence intervals (CI) associated with serological outcome were modelled using propensity-score-adjusted logistic regression analysis. In total, 202 cases were treated with doxycycline or intramuscular penicillin. At 12 months, serological failure was observed in 12 cases (15......%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0...

Proteochemometric model for predicting the inhibition of penicillin-binding proteins

Science.gov (United States)

Nabu, Sunanta; Nantasenamat, Chanin; Owasirikul, Wiwat; Lawung, Ratana; Isarankura-Na-Ayudhya, Chartchalerm; Lapins, Maris; Wikberg, Jarl E. S.; Prachayasittikul, Virapong

2015-02-01

Neisseria gonorrhoeae infection threatens to become an untreatable sexually transmitted disease in the near future owing to the increasing emergence of N. gonorrhoeae strains with reduced susceptibility and resistance to the extended-spectrum cephalosporins (ESCs), i.e. ceftriaxone and cefixime, which are the last remaining option for first-line treatment of gonorrhea. Alteration of the penA gene, encoding penicillin-binding protein 2 (PBP2), is the main mechanism conferring penicillin resistance including reduced susceptibility and resistance to ESCs. To predict and investigate putative amino acid mutations causing β-lactam resistance particularly for ESCs, we applied proteochemometric modeling to generalize N. gonorrhoeae susceptibility data for predicting the interaction of PBP2 with therapeutic β-lactam antibiotics. This was afforded by correlating publicly available data on antimicrobial susceptibility of wild-type and mutant N. gonorrhoeae strains for penicillin-G, cefixime and ceftriaxone with 50 PBP2 protein sequence data using partial least-squares projections to latent structures. The generated model revealed excellent predictability ( R 2 = 0.91, Q 2 = 0.77, Q Ext 2 = 0.78). Moreover, our model identified amino acid mutations in PBP2 with the highest impact on antimicrobial susceptibility and provided information on physicochemical properties of amino acid mutations affecting antimicrobial susceptibility. Our model thus provided insight into the physicochemical basis for resistance development in PBP2 suggesting its use for predicting and monitoring novel PBP2 mutations that may emerge in the future.

Optogenetic control of thalamus as a tool for interrupting penicillin induced seizures.

Science.gov (United States)

Han, Yechao; Ma, Feiqiang; Li, Hongbao; Wang, Yueming; Xu, Kedi

2015-01-01

Penicillin epilepsy model, whose discharge resembles that of human absence epilepsy, is one of the most useful acute experimental epilepsy models. Though closed-loop optogenetic strategy of interrupting seizures was proved sufficient to switch off epilepsy by controlling thalamus in the post-lesion partial chronic epilepsy model, doubts still exist in absence epilepsy attenuation through silencing thalamus. Here we directly arrested the thalamus to modulate penicillin-induced absence seizures through pseudorandom responsive stimulation on eNpHR-transfected rats. Our data suggested that the duration of epileptiform bursts under light conditions, compared with no light conditions, did not increase or decrease when modulated specific eNpHR-expressing neurons in thalamus.

Penicillin improves the milt quality of Persian sturgeon, Acipenser persicus during short-term storage

Directory of Open Access Journals (Sweden)

Mostafa Halimi

2014-04-01

Full Text Available This study was conducted to examine the effects of antibiotic (5000 units of penicillin on sperm quality of Persian sturgeon, Acipenser persicus during 9 days in vitro storage of milt. For this purpose, the milt samples were stored in the presence and absence of 5000 units of penicillin. Freshwater was used as sperm activator. The milt samples were stored at 4°C and the motility indices were measured 0, 3, 6 and 9 days after storage. The sperm duration and percentage of sperm motility decreased after 6 days of storage both in the presence and absence of antibiotic, although this decrease was more significant in the absence of antibiotic. After 9 days of storage, the lowest values of sperm motility indices was recorded for antibiotic receiving milt samples while no motile spermatozoa observed for antibiotic-free milt samples. In conclusion, our results demonstrated that 5000 units of penicillin improve the Persian sturgeon milt quality during short-term storage.

Seasonal Variation in Penicillin Use in Mexico and Brazil: Analysis of the Impact of Over-the-Counter Restrictions

Science.gov (United States)

Santa-Ana-Tellez, Yared; Mantel-Teeuwisse, Aukje K.; Leufkens, Hubert G. M.

2014-01-01

During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. We used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level, and variation in use between quarters for total penicillin use and by active substance. The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation in penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction, mainly due to changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, overall and in the breakdown by individual active substances. For Mexico, inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil, increasing use and no change in seasonal variation suggest that further efforts are needed to reduce inappropriate penicillin use. PMID:25313222

Structure-selective hot-spot Raman enhancement for direct identification and detection of trace penicilloic acid allergen in penicillin.

Science.gov (United States)

Zhang, Liying; Jin, Yang; Mao, Hui; Zheng, Lei; Zhao, Jiawei; Peng, Yan; Du, Shuhu; Zhang, Zhongping

2014-08-15

Trace penicilloic acid allergen frequently leads to various fatal immune responses to many patients, but it is still a challenge to directly discriminate and detect its residue in penicillin by a chemosensing way. Here, we report that silver-coated gold nanoparticles (Au@Ag NPs) exhibit a structure-selective hot-spot Raman enhancement capability for direct identification and detection of trace penicilloic acid in penicillin. It has been demonstrated that penicilloic acid can very easily link Au@Ag NPs together by its two carboxyl groups, locating itself spontaneously at the interparticle of Au@Ag NPs to form strong Raman hot-spot. At the critical concentration inducing the nanoparticle aggregation, Raman-enhanced effect of penicilloic acid is ~60,000 folds higher than that of penicillin. In particular, the selective Raman enhancement to the two carboxyl groups makes the peak of carboxyl group at C6 of penicilloic acid appear as a new Raman signal due to the opening of β-lactam ring of penicillin. The surface-enhanced Raman scattering (SERS) nanoparticle sensor reaches a sensitive limit lower than the prescribed 1.0‰ penicilloic acid residue in penicillin. The novel strategy to examine allergen is more rapid, convenient and inexpensive than the conventional separation-based assay methods. Copyright © 2014 Elsevier B.V. All rights reserved.

Penicillin tolerance among Beta-hemolytic streptococci and production of the group carbohydrates, hemolysins, hyaluronidases and deoxyribonucleases

Directory of Open Access Journals (Sweden)

Cássia C. Avelino

1995-08-01

Full Text Available Penicillin tolerance among 67 strains of beta-hemolytic streptococci was examined by determining the ratio of the minimal bactericidal concentration to the minimal inhibitory concentration as 32 or greater. Tolerance was demonstrated in 15 group A strains and in 11,7, and 4 of groups B, C and G, respectively. Thereafter the effects of a subminimal inhibitory concentration (1/2MIC of penicillin on the bacterial products of four tolerant and four nontolerant strains (two of each Lancefield group were analyzed and compared. The antibiotic caused a marked increase in the expression of the group carbo-hydrates for strains of group B. Penicillin was found to reduce the cell-bound hemolysin activities of the four tolerant strains and to increase the activity of the other (free form of nontolerant groups A, C and G hemolysins. Penicillin caused an increase in the extracellular hyaluronidase activities of one group A and groups B, C and G streptococci. With added antibiotic the production of deoxyribonuclease by tolerant groups A, C and G was greatly enhanced and that of the group B streptococcus was arrested.

Development of the radiation-resistant strain of Moraxella osloensis and effect of penicillin G on its growth

International Nuclear Information System (INIS)

Lim, Sangyong; Yun, Hyejeong; Joe, Minho; Kim, Dongho

2009-01-01

A series of repeated exposures to γ-radiation with intervening outgrowth of survivors was used to develop radioresistant cultures of Moraxella osloensis that have been recognized as potential pathogenic microorganism. The D 10 value of the radiation-resistant strain, 5.903±0.006 kGy, was increased by four-fold compared to the parent wild-type strain, 1.637±0.004 kGy. Since most strains of M. osloensis are sensitive to penicillin, we have surveyed the sensitivity of radiation-resistant strain to this antibiotic. When the optical density was monitored after the addition of penicillin G, the radioresistant strain appeared to be more resistant to only a low concentration of penicillin G (0.5 U/ml) than the parent strain. Interestingly, however, there was no apparent difference in the number of viable cells between both strains. Scanning electron microscope data showed that the resistance cells were generally larger than the parent cells, suggesting that this increase in size may cause a higher optical density of radioresistant cells. In conclusion, radiation mutation does not affect the penicillin resistance of M. osloensis.

Development of the radiation-resistant strain of Moraxella osloensis and effect of penicillin G on its growth

Science.gov (United States)

Lim, Sangyong; Yun, Hyejeong; Joe, Minho; Kim, Dongho

2009-07-01

A series of repeated exposures to γ-radiation with intervening outgrowth of survivors was used to develop radioresistant cultures of Moraxella osloensis that have been recognized as potential pathogenic microorganism. The D10 value of the radiation-resistant strain, 5.903±0.006 kGy, was increased by four-fold compared to the parent wild-type strain, 1.637±0.004 kGy. Since most strains of M. osloensis are sensitive to penicillin, we have surveyed the sensitivity of radiation-resistant strain to this antibiotic. When the optical density was monitored after the addition of penicillin G, the radioresistant strain appeared to be more resistant to only a low concentration of penicillin G (0.5 U/ml) than the parent strain. Interestingly, however, there was no apparent difference in the number of viable cells between both strains. Scanning electron microscope data showed that the resistance cells were generally larger than the parent cells, suggesting that this increase in size may cause a higher optical density of radioresistant cells. In conclusion, radiation mutation does not affect the penicillin resistance of M. osloensis.

Development of the radiation-resistant strain of Moraxella osloensis and effect of penicillin G on its growth

Energy Technology Data Exchange (ETDEWEB)

Lim, Sangyong; Yun, Hyejeong; Joe, Minho [Radiation Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Dongho [Radiation Research Division for Biotechnology, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: fungikim@kaeri.re.kr

2009-07-15

A series of repeated exposures to {gamma}-radiation with intervening outgrowth of survivors was used to develop radioresistant cultures of Moraxella osloensis that have been recognized as potential pathogenic microorganism. The D{sub 10} value of the radiation-resistant strain, 5.903{+-}0.006 kGy, was increased by four-fold compared to the parent wild-type strain, 1.637{+-}0.004 kGy. Since most strains of M. osloensis are sensitive to penicillin, we have surveyed the sensitivity of radiation-resistant strain to this antibiotic. When the optical density was monitored after the addition of penicillin G, the radioresistant strain appeared to be more resistant to only a low concentration of penicillin G (0.5 U/ml) than the parent strain. Interestingly, however, there was no apparent difference in the number of viable cells between both strains. Scanning electron microscope data showed that the resistance cells were generally larger than the parent cells, suggesting that this increase in size may cause a higher optical density of radioresistant cells. In conclusion, radiation mutation does not affect the penicillin resistance of M. osloensis.

Thermodynamics of metabolic pathways for penicillin production: Analysis of thermodynamic feasibility and free energy changes during fed-batch cultivation

DEFF Research Database (Denmark)

Pissarra, P.D.; Nielsen, Jens Bredal

1997-01-01

This paper describes the thermodynamic analysis of pathways related to penicillin production in Penicillium chrysogenum. First a thermodynamic feasibility analysis is performed of the L-lysine pathway of which one of the precursors for penicillin biosynthesis (alpha-aminoadipic acid......) is an intermediate. It is found that the L-lysine pathway in P. chrysogenum is thermodynamically feasible and that the calculated standard Gibbs free energy values of the two enzymes controlling the pathway flux indicate that they operate far from equilibrium. It is therefore proposed that the regulation of alpha......-aminoadipate reductase by lysine is important to maintain a high concentration of alpha-aminoadipate in order to direct the carbon flux to penicillin production. Secondly the changes in Gibbs free energy in the penicillin biosynthetic pathway during fed-batch cultivation were studied. The analysis showed that all...

Molecular characterization of a fungal gene paralogue of the penicillin penDE gene of Penicillium chrysogenum

Science.gov (United States)

2009-01-01

Background Penicillium chrysogenum converts isopenicillin N (IPN) into hydrophobic penicillins by means of the peroxisomal IPN acyltransferase (IAT), which is encoded by the penDE gene. In silico analysis of the P. chrysogenum genome revealed the presence of a gene, Pc13g09140, initially described as paralogue of the IAT-encoding penDE gene. We have termed this gene ial because it encodes a protein with high similarity to IAT (IAL for IAT-Like). We have conducted an investigation to characterize the ial gene and to determine the role of the IAL protein in the penicillin biosynthetic pathway. Results The IAL contains motifs characteristic of the IAT such as the processing site, but lacks the peroxisomal targeting sequence ARL. Null ial mutants and overexpressing strains indicated that IAL lacks acyltransferase (penicillin biosynthetic) and amidohydrolase (6-APA forming) activities in vivo. When the canonical ARL motif (leading to peroxisomal targeting) was added to the C-terminus of the IAL protein (IALARL) by site-directed mutagenesis, no penicillin biosynthetic activity was detected. Since the IAT is only active after an accurate self-processing of the preprotein into α and β subunits, self-processing of the IAL was tested in Escherichia coli. Overexpression experiments and SDS-PAGE analysis revealed that IAL is also self-processed in two subunits, but despite the correct processing, the enzyme remained inactive in vitro. Conclusion No activity related to the penicillin biosynthesis was detected for the IAL. Sequence comparison among the P. chrysogenum IAL, the A. nidulans IAL homologue and the IAT, revealed that the lack of enzyme activity seems to be due to an alteration of the essential Ser309 in the thioesterase active site. Homologues of the ial gene have been found in many other ascomycetes, including non-penicillin producers. Our data suggest that like in A. nidulans, the ial and penDE genes might have been formed from a single ancestral gene that became

The invasive MenC cc103 lineage with penicillin reduced susceptibility persisting in Brazil.

Science.gov (United States)

Fonseca, Érica L; Marin, Michel A; Freitas, Fernanda S; Vitório, Bruna S A; de Araújo, Flávio M G; Camargo, Dhian R A; Coimbra, Roney S; De Filippis, Ivano R; Vicente, Ana Carolina P

2017-09-01

Penicillin is the antibiotic of choice for the treatment of meningococcal infections, and mutations in penA gene are involved with reduced susceptibility (pen I ) emergence to this antibiotic. This study aimed to characterize the penA allelic diversity, their association with pen I phenotype and distribution among prevalent meningococci serogroups in Brazil. The entire penA from 49 invasive strains of distinct serogroups circulating in Brazil for more than two decades were obtained by PCR and sequencing. Additionally, the penA from 22 publicly available complete Neisseria meningitidis genomes from Brazil were included in the study. The allelic diversity was determined and a genetic tree was built using the penA sequence alignment. The penicillin MIC was obtained by the E-Test method. In general, the identified penA alleles correlated with the observed pen I phenotype. The canonical penA1 was the most prevalent allele, however, several altered penA were also identified in strains presenting increased penicillin MICs. It was identified a new penA amino acid position (residue 480) that possibly influence the penicillin MIC in some strains. Interestingly, the altered penA14 was found in pen I invasive MenC cc103 strains spread in Brazil and persisting since 2011, indicating that the biological cost imposed by pen I phenotype can be ameliorated by particular features present in this lineage, which represents an additional public health threat. Copyright © 2017 Elsevier GmbH. All rights reserved.

Deregulation of the arginine deiminase (arc) operon in penicillin-tolerant mutants of Streptococcus gordonii.

Science.gov (United States)

Caldelari, I; Loeliger, B; Langen, H; Glauser, M P; Moreillon, P

2000-10-01

Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent Streptococcus gordonii mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log(10) CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (arc) operon of these organisms. Partial nucleotide sequencing and insertion inactivation of the S. gordonii arc locus indicated that tolerance was not a direct consequence of arc alteration. On the other hand, genetic transformation of tolerance by Tol1 DNA always conferred arc deregulation. In nontolerant recipients, arc was repressed during exponential growth and up-regulated during postexponential growth. In tolerant transformants, arc was constitutively expressed. Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10(-2) to 10(-3)). The tolerance mutation mapped on a specific chromosomal fragment but was physically distant from arc. Importantly, arc deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants. Thus, although not exclusive, the association between arc deregulation and tolerance was not fortuitous. Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment, arc deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.

Context-Dependent Modulation of αβγ and αβγ GABAA Receptors by Penicillin: Implications for Phasic and Tonic Inhibition

OpenAIRE

Feng, Hua-Jun; Botzolakis, Emmanuel J.; Macdonald, Robert L.

2008-01-01

Penicillin, an open-channel blocker of GABAA receptors, was recently reported to inhibit phasic, but not tonic, currents in hippocampal neurons. To distinguish between isoform-specific and context-dependent modulation as possible explanations for this selectivity, the effects of penicillin were evaluated on recombinant GABAA receptors expressed in HEK293T cells. When co-applied with saturating GABA, penicillin decreased peak amplitude, induced rebound, and prolonged deactivation of currents e...

Effects of Cornus mas L. and Morus rubra L. extracts on penicillin-induced epileptiform activity: an electrophysiological and biochemical study.

Science.gov (United States)

Tubaş, Filiz; Per, Sedat; Taşdemir, Abdulkadir; Bayram, Ayşe Kaçar; Yıldırım, Mehmet; Uzun, Aydın; Saraymen, Recep; Gümüş, Hakan; Elmalı, Ferhan; Per, Hüseyin

2017-01-01

Traditionally, Morus rubra L. (Moraceae) (red mulberry) and Cornus mas L. (Cornacea) (cornelian cherry) fruits are eaten fresh and are also used in marmalades, juices, jam, natural dyes in Turkey and are believed to have beneficial effects in case of multiple health issues such as antipyretic, diarrhea and intestinal parasites. However, the effects of M. rubra and C. mas on epilepsy has not been known. This study evaluates the effects of M. rubra and C. mas extracts on penicillin-induced epileptiform activity. Sixty Wistar rats randomly divided into ten groups (n=6): control, sham, penicillin, penicillin+M. rubra extract (2.5, 5, 10, 20 mg/kg) and penicillin+C. mas extract (2.5, 5, 10 mg/kg). Epileptiform activity was induced by using penicillin (500 IU, i.c.) and electrocorticogram records (150 min) were obtained. Also, biochemical analysis in blood samples were evaluated. According to the electrocorticogram analysis, the effective dose was detected as 10 mg/kg for both C. mas and M. rubra. This dose decreased the spike frequencies of convulsions while amplitude wasn't changed by both substances. In erythrocyte studies, there were significant differences regarding nitric oxide in the control, sham and penicillin groups. There were significant differences regarding malondialdehyde in all groups. In the plasma, there were significant differences among groups regarding xanthine oxidase in the penicillin‑C. mas and penicillin‑M. rubra groups. There were differences regarding malondialdehyde in the penicillin-C. mas and M. rubra-C. mas groups. Both extracts reduced the frequency of epileptiform activity. After administration of the extracts malondialdehyde levels decreased also in both erythrocytes and plasma.

Seasonal variation in penicillin use in Mexico and Brazil: analysis of the impact of over-the-counter restrictions.

Science.gov (United States)

Santa-Ana-Tellez, Yared; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Wirtz, Veronika J

2015-01-01

During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. We used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level, and variation in use between quarters for total penicillin use and by active substance. The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation in penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction, mainly due to changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, overall and in the breakdown by individual active substances. For Mexico, inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil, increasing use and no change in seasonal variation suggest that further efforts are needed to reduce inappropriate penicillin use. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Heterologous protein secretion in Lactococcus lactis: a novel antigen delivery system

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Langella P.

1999-01-01

Full Text Available Lactic acid bacteria (LAB are Gram-positive bacteria and are generally regarded as safe (GRAS organisms. Therefore, LAB could be used for heterologous protein secretion and they are good potential candidates as antigen delivery vehicles. To develop such live vaccines, a better control of protein secretion is required. We developed an efficient secretion system in the model LAB, Lactococcus lactis. Staphylococcal nuclease (Nuc was used as the reporter protein. We first observed that the quantity of secreted Nuc correlated with the copy number of the cloning vector. The nuc gene was cloned on a high-copy number cloning vector and no perturbation of the metabolism of the secreting strain was observed. Replacement of nuc native promoter by a strong lactococcal one led to a significant increase of nuc expression. Secretion efficiency (SE of Nuc in L. lactis was low, i.e., only 60% of the synthesized Nuc was secreted. Insertion of a synthetic propeptide between the signal peptide and the mature moiety of Nuc increased the SE of Nuc. On the basis of these results, we developed a secretion system and we applied it to the construction of an L. lactis strain which secretes a bovine coronavirus (BCV epitope-protein fusion (BCV-Nuc. BCV-Nuc was recognized by both anti-BCV and anti-Nuc antibodies. Secretion of this antigenic fusion is the first step towards the development of a novel antigen delivery system based on LAB-secreting strains.

Selection of resistant Streptococcus pneumoniae during penicillin treatment in vitro and in three animal models

DEFF Research Database (Denmark)

Knudsen, Jenny Dahl; Odenholt, Inga; Erlendsdottir, Helga

2003-01-01

Pharmacokinetic (PK) and pharmacodynamic (PD) properties for the selection of resistant pneumococci were studied by using three strains of the same serotype (6B) for mixed-culture infection in time-kill experiments in vitro and in three different animal models, the mouse peritonitis, the mouse.......016 micro g/ml; erythromycin resistant)/ml, 10(6) CFU of strain B (MIC of penicillin, 0.25 micro g/ml)/ml, and 10(5) CFU of strain C (MIC of penicillin, 4 micro g/ml)/ml, was used in the two mouse models, and a mixture of 10(5) CFU of strain A/ml, 10(4) CFU of strain B/ml, and 10(3) CFU of strain C....../ml was used in the rabbit tissue cage model. During the different treatment regimens, the differences in numbers of CFU between treated and control animals were calculated to measure the efficacies of the regimens. Selective media with erythromycin or different penicillin concentrations were used to quantify...

Simultaneous determination of paracetamol and penicillin V by square-wave voltammetry at a bare boron-doped diamond electrode

International Nuclear Information System (INIS)

Švorc, Ľubomír; Sochr, Jozef; Tomčík, Peter; Rievaj, Miroslav; Bustin, Dušan

2012-01-01

Highlights: ► Unmodified BDD electrode = sensitive electrochemical sensor for drugs determination. ► No special pretreatment of samples except simple dilution. ► Selective method, common compounds present in urine do not interfere in high excess. ► Simultaneous determination of PAR and PEN has yet not been published in literature. - Abstract: A simple, sensitive and selective square-wave voltammetry method for simultaneous determination of paracetamol and penicillin V on a bare (unmodified) boron-doped diamond electrode has been developed. The good potential separation of about 0.35 V between the oxidation peak potentials of both drugs present in mixture was found. It was found by cyclic voltammetry that paracetamol gave quasireversible wave and penicillin V provided irreversible oxidation peak. The effect of supporting electrolyte, pH and scan rate on voltammetric response of both drugs was studied to select the optimum experimental conditions. The optimal conditions for quantitative simultaneous determination were obtained in acetate buffer solution at pH 5.0. The oxidation peak of paracetamol and penicillin V showed a systematic increase in peak currents with increase of their concentration. The calibration curves for the simultaneous determination of paracetamol and penicillin V exhibited the good linear responses within the concentration range from 0.4 to 100 μM for both drugs. The detection limit was established to 0.21 and 0.32 μM for paracetamol and penicillin V, respectively. The method proved the good sensitivity, repeatability (RSD of 1.5 and 2.1% for mixture solution of 10 μM PCM and PEN) and selectivity when influence of interferents commonly existing in human urine was negligible. The practical analytical utility of proposed method was demonstrated by simultaneous determination of paracetamol and penicillin V in human urine samples, with results similar to those obtained using a high-performance liquid chromatography method as an

Design of penicillin fermentation process simulation system

Science.gov (United States)

Qi, Xiaoyu; Yuan, Zhonghu; Qi, Xiaoxuan; Zhang, Wenqi

2011-10-01

Real-time monitoring for batch process attracts increasing attention. It can ensure safety and provide products with consistent quality. The design of simulation system of batch process fault diagnosis is of great significance. In this paper, penicillin fermentation, a typical non-linear, dynamic, multi-stage batch production process, is taken as the research object. A visual human-machine interactive simulation software system based on Windows operation system is developed. The simulation system can provide an effective platform for the research of batch process fault diagnosis.

Depletion of penicillin G residues in heavy sows after intramuscular injection. Part II: application of kidney inhibition swab tests.

Science.gov (United States)

Shelver, Weilin L; Lupton, Sara J; Newman, David J; Larsen, Steven; Smith, David J

2014-07-30

Sows (n = 126; 228 ± 30.1 kg) were administered daily IM doses of penicillin G procaine (33 000 IU/kg bw; 5× the label dose) for 3 consecutive days using three different administration patterns. Within treatment, six sows each were slaughtered on withdrawal day 5, 10, 15, 20, 25, 32, and 39. Tissues (injection site, kidney, liver, skeletal muscle) or body fluids (serum and urine) were screened for penicillin G using the KIS test, recently adopted by the USDA Food Safety and Inspection Service. The IM administration patterns had no discernible effect on penicillin G depletion. Residues were depleted more rapidly from liver and skeletal muscle and more slowly from kidney and urine. Kidney was the most sensitive and suitable tissue for detecting penicillin G residues on-site, with two positive results after a 39-day withdrawal period. Urine was the most suitable ante-mortem surrogate to predict the results of kidney tests.

Security of the AES with a Secret S-Box

DEFF Research Database (Denmark)

Tiessen, Tyge; Knudsen, Lars Ramkilde; Kölbl, Stefan

2015-01-01

How does the security of the AES change when the S-box is replaced by a secret S-box, about which the adversary has no knowledge? Would it be safe to reduce the number of encryption rounds? In this paper, we demonstrate attacks based on integral cryptanalysis which allow to recover both the secret...... key and the secret S-box for respectively four, five, and six rounds of the AES. Despite the significantly larger amount of secret information which an adversary needs to recover, the attacks are very efficient with time/data complexities of 217/216, 238/240 and 290/264, respectively. Another...

Effect of Periodontal Therapy With Amoxicillin-Metronidazole on Pharyngeal Carriage of Penicillin- and Erythromycin-Resistant Viridans Streptococci.

Science.gov (United States)

Mombelli, Andrea; Cionca, Norbert; Almaghlouth, Adnan; Cherkaoui, Abdessalam; Schrenzel, Jacques; Giannopoulou, Catherine

2016-05-01

Previous studies have focused on antibiotic resistance of Gram-negative bacteria before and after periodontal therapy. The purpose of this analysis is to assess changes in resistance patterns of the commensal Gram-positive microbiota. The viridans group streptococci (VGS) have been suggested to serve as reservoirs of resistance genes for more pathogenic streptococci and may be implicated in some non-oral infections. In this randomized clinical trial, 80 patients with periodontitis are distributed randomly into two groups. In group A, patients received 375 mg amoxicillin and 500 mg metronidazole three times per day for 7 days during the non-surgical treatment phase (T1). In group B, the antibiotics were administered during the surgical phase (T2). Resistance of VGS to penicillin and erythromycin was determined by the epsilometer test. At baseline, VGS from 12.5% (group A) and 11.8% (group B) of patients had a minimum inhibitory concentration (MIC) >2 μg/mL to penicillin. Three months after T1, VGS from 15.6% and 16.7% of patients had an MIC >2 μg/mL, respectively. Six months after T2 VGS from 5.9% and 5.9% and 12 months after T2 VGS from 6.1% and 6.3% patients had an MIC >2 μg/mL. There was no effect of therapy with antibiotics, administered either in T1 or T2, on the carriage of penicillin-resistant VGS. Erythromycin resistance was high at baseline and remained unchanged throughout the study. MICs for penicillin and erythromycin were correlated (P penicillin or erythromycin.

Nuclear magnetic resonance of D(-)-{alpha}-amino-benzyl penicillin; Ressonancia magnetica nuclear da D(-)-{alpha}-amino-benzil penicilina

Energy Technology Data Exchange (ETDEWEB)

Aguiar, Monica R.M.P.; Gemal, Andre L.; San Gil, Rosane A.S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Quimica; Menezes, Sonia M.C. [PETROBRAS, Rio de Janeiro, RJ (Brazil). Centro de Pesquisas

1995-12-31

The development of new drugs from penicillins has induced the study of this substances by nuclear magnetic resonance. Several samples of D(-)-{alpha}-amino-benzyl penicillin were analysed using {sup 13} C NMR techniques in aqueous solution and solid state. Spectral data of this compounds were shown and the results were presented and analysed 7 figs., 4 tabs.

Cloning and over-expression of Penicillin G acylase in Escherichia ...

African Journals Online (AJOL)

STORAGESEVER

2010-05-03

May 3, 2010 ... Penicillin G acylase (PGA) is one of the most important enzymes in the pharmaceutical industry. It is ... isolates harboring PGA enzyme with higher industrial compatibilities is of high interest. The aim ... expression of PGA for high level enzyme production. ..... Small bugs, big business: the economic power of.

Structural characterization of the α-mating factor prepro-peptide for secretion of recombinant proteins in Pichia pastoris.

Science.gov (United States)

Chahal, Sabreen; Wei, Peter; Moua, Pachai; Park, Sung Pil James; Kwon, Janet; Patel, Arth; Vu, Anthony T; Catolico, Jason A; Tsai, Yu Fang Tina; Shaheen, Nadia; Chu, Tiffany T; Tam, Vivian; Khan, Zill-E-Huma; Joo, Hyun Henry; Xue, Liang; Lin-Cereghino, Joan; Tsai, Jerry W; Lin-Cereghino, Geoff P

2017-01-20

The methylotrophic yeast Pichia pastoris has been used extensively for expressing recombinant proteins because it combines the ease of genetic manipulation, the ability to provide complex posttranslational modifications and the capacity for efficient protein secretion. The most successful and commonly used secretion signal leader in Pichia pastoris has been the alpha mating factor (MATα) prepro secretion signal. However, limitations exist as some proteins cannot be secreted efficiently, leading to strategies to enhance secretion efficiency by modifying the secretion signal leader. Based on a Jpred secondary structure prediction and knob-socket modeling of tertiary structure, numerous deletions and duplications of the MATα prepro leader were engineered to evaluate the correlation between predicted secondary structure and the secretion level of the reporters horseradish peroxidase (HRP) and Candida antarctica lipase B. In addition, circular dichroism analyses were completed for the wild type and several mutant pro-peptides to evaluate actual differences in secondary structure. The results lead to a new model of MATα pro-peptide signal leader, which suggests that the N and C-termini of MATα pro-peptide need to be presented in a specific orientation for proper interaction with the cellular secretion machinery and for efficient protein secretion. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae

DEFF Research Database (Denmark)

Liu, Lifang; Feizi, Amir; Osterlund, Tobias

2014-01-01

related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three a-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER......Background: The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due...... to the poorly annotated proteome. Results: Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely...

Fabric phase sorptive extraction of selected penicillin antibiotic residues from intact milk followed by high performance liquid chromatography with diode array detection.

Science.gov (United States)

Samanidou, Victoria; Michaelidou, Katia; Kabir, Abuzar; Furton, Kenneth G

2017-06-01

Fabric phase sorptive extraction (FPSE), a novel sorbent-based microextraction method, was evaluated as a simple and rapid strategy for the extraction of four penicillin antibiotic residues (benzylpenicillin, cloxacillin, dicloxacillin and oxacillin) from cows' milk, without prior protein precipitation. Time-consuming solvent evaporation and reconstitution steps were eliminated successfully from the sample preparation workflow. FPSE utilizes a flexible fabric substrate, chemically coated with sol-gel derived, highly efficient, organic-inorganic hybrid sorbent as the extraction medium. Herein short-chain poly(ethylene glycol) provided optimum extraction sensitivity for the selected penicillins, which were analysed using an RP-HPLC method, validated according to the European Decision 657/2002/EC. The limit of quantitation was 10μg/kg for benzylpenicillin, 20μg/kg for cloxacillin, 25μg/kg dicloxacillin and 30μg/kg oxacillin. These are a similar order of magnitude with those reported in the literature and (with the exception of benzylpenicillin) are less than the maximum residue limits (MRL) set by European legislation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of penicillin administration in early life on murine gut microbiota and blood lymphocyte subsets.

Science.gov (United States)

Daniluk, Jaroslaw; Daniluk, Urszula; Rusak, Malgorzata; Dabrowska, Milena; Reszec, Joanna; Garbowicz, Magdalena; Huminska, Kinga; Dabrowski, Andrzej

2017-10-01

Antibiotics have many beneficial effects but their uncontrolled use may lead to increased risk of serious diseases in the future. Our hypothesis is that an early antibiotic exposition may affect immune system by altering gut microbiota. Therefore, the aim of the study was to determine the effect of penicillin treatment on gut microorganisms and immune system of mice. 21-days old C57BL6/J/cmdb male mice were treated with low-dose of penicillin (study group) or water only (control group) for 4 weeks. Tissue and stool samples for histology or microbiome assessment and peripheral blood for CBC and flow cytometry evaluation were collected. We found high variability in microbiota composition at different taxonomic levels between littermate mice kept in the same conditions, independently of treatment regimen. Interestingly, low-dose of penicillin caused significant increase of Parabacteroides goldsteinii in stool and in colon tissue in comparison to control group (9.5% vs. 4.9%, p = 0.008 and 10.7% vs. 6.1%, p = 0.008, respectively). Moreover, mice treated with penicillin demonstrated significantly elevated percentage of B cells (median 10.5% vs 8.0%, p = 0.01) and decrease in the percentage of total CD4 + cell (median 75.4% vs 82.5%, p = 0.0039) with subsequent changes among subsets - increased percentage of regulatory T cells (Treg), T helper 1 (Th1) and T helper 2 (Th2) cells. Our study showed significant effect of penicillin on B and T cells in peripheral blood of young mice. This effect may be mediated through changes in gut microbiota represented by the expansion of Parabacteroides goldsteinii. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation, transport aspects and degeneration of penicillin biosynthesis in Penicillium chrysogenum

NARCIS (Netherlands)

Douma, R.D.

2010-01-01

Penicillin has been produced on an industrial scale for several decades. The improvements in its production process, in terms of product yields and production rates, present an unprecedented success in fermentation technology. However, the obtained product yields still remain far from their

Removal of Penicillin G by combination of sonolysis and Photocatalytic (sonophotocatalytic) process from aqueous solution: process optimization using RSM (Response Surface Methodology).

Science.gov (United States)

Almasi, Ali; Dargahi, Abdollah; Mohamadi, Mitra; Biglari, Hamed; Amirian, Farhad; Raei, Mehdi

2016-09-01

Penicillin G (PG) is used in a variety of infectious diseases, extensively. Generally, when antibiotics are introduced into the food chain, they pose a threat to the environment and can risk health outcomes. The aim of the present study was the removal of Penicillin G from an aqueous solution through an integrated system of UV/ZnO and UV/WO 3 with Ultrasound pretreatment. In this descriptive-analytical work dealing with the removal of Penicillin G from an aqueous solution, four significant variables, contact time (60-120 min), Penicillin G concentration (50-150 mg/L), ZnO dose (200-400 mg/L), and WO 3 dose (100-200 mg/L) were investigated. Experiments were performed in a Pyrex reactor (batch, 1 Lit) with an artificial UV 100-Watt medium pressure mercury lamp, coupled with ultrasound (100 W, 40 KHz) for PG pre-treatment. Chemical Oxygen Demand (COD) was selected to follow the performance of the photo-catalytic process and sonolysis. The experiments were based on a Central Composite Design (CCD) and analyzed by Response Surface Methodology (RSM). A mathematical model of the process was designed according to the proposed degradation scheme. The results showed that the maximum removal of PG occurred in ultrasonic/UV/WO 3 in the presence of 50 mg/L WO 3 and contact time of 120 minutes. In addition, an increase in the PG concentration caused a decrease in COD removal. As the initial concentration of the catalyst increased, the COD removal also increased. The maximum COD removal (91.3%) achieved by 200 mg/L WO 3 and 400 mg/l ZnO, a contact time of 120 minutes, and an antibiotic concentration of 50 mg/L. All of the variables in the process efficiency were found to be significant (p research data supported the conclusion that the combination of advanced oxidation process of sonolysis and photocatalytic (sonophotocatalytic) were applicable and environmentally friendly processes, which preferably can be applied extensively.

Nicolau Syndrome after Intramuscular Benzathine Penicillin Injection

Directory of Open Access Journals (Sweden)

Morteza Noaparast

2014-11-01

Full Text Available A 3-year-old boy was admitted to the emergency department with right lower limb pain, edema, and livedoid discoloration that occurred immediately after intramuscular injection of benzathine penicillin. The patient was diagnosed with Nicolau syndrome, a rare complication of intramuscular injection presumed to be related to the inadvertent intravascular injection. It was first reported following intramuscular injection of bismuth salt, but it can occur as a complication of various other drugs. Fasciotomy was carried out due to the resultant compartment syndrome and medical therapy with heparin, corticosteroid, and pentoxifyllin was initiated.

Involvement of the Eukaryote-Like Kinase-Phosphatase System and a Protein That Interacts with Penicillin-Binding Protein 5 in Emergence of Cephalosporin Resistance in Cephalosporin-Sensitive Class A Penicillin-Binding Protein Mutants in Enterococcus faecium

Directory of Open Access Journals (Sweden)

Charlene Desbonnet

2016-04-01

Full Text Available The intrinsic resistance of Enterococcus faecium to ceftriaxone and cefepime (here referred to as “cephalosporins” is reliant on the presence of class A penicillin-binding proteins (Pbps PbpF and PonA. Mutants lacking these Pbps exhibit cephalosporin susceptibility that is reversible by exposure to penicillin and by selection on cephalosporin-containing medium. We selected two cephalosporin-resistant mutants (Cro1 and Cro2 of class A Pbp-deficient E. faecium CV598. Genome analysis revealed changes in the serine-threonine kinase Stk in Cro1 and a truncation in the associated phosphatase StpA in Cro2 whose respective involvements in resistance were confirmed in separate complementation experiments. In an additional effort to identify proteins linked to cephalosporin resistance, we performed tandem affinity purification using Pbp5 as bait in penicillin-exposed E. faecium; these experiments yielded a protein designated Pbp5-associated protein (P5AP. Transcription of the P5AP gene was increased after exposure to penicillin in wild-type strains and in Cro2 and suppressed in Cro2 complemented with the wild-type stpA. Transformation of class A Pbp-deficient strains with the plasmid-carried P5AP gene conferred cephalosporin resistance. These data suggest that Pbp5-associated cephalosporin resistance in E. faecium devoid of typical class A Pbps is related to the presence of P5AP, whose expression is influenced by the activity of the serine-threonine phosphatase/kinase system.

Synthesis of tritium-labelled isopenicillin N, penicillin N and 6-aminopenicillanic acid

International Nuclear Information System (INIS)

Usher, J.J.; Loder, B.; Abraham, E.P.

1975-01-01

1. Phenoxymethylpenicillin sulphoxide 4-methoxybenzyl ester was labelled with 3 H in its 2-β-methyl group. Its specific radioactivity was 362mCi/mmol. 2. Removal of the side chain of this compound yielded the corresponding ester of 6-aminopenicillanic acid sulphoxide and coupling of the latter with the appropriate protected α-aminoadipic acid gave 4-methoxybenzyloxycarbonylisopenicillin N sulphoxide di-4-methoxybenzyl ester or the corresponding derivative of penicillin N. 3. Removal of the protective groups by hydrogenolysis and reduction of the sulphoxide group yielded 3 H-labelled isopenicillin N or penicillin N. 4. 3 H-labelled phenoxymethylpenicillin sulphoxide was obtained by hydrogenolysis from its 4-methoxybenzyl ester. Reducton of its sulphoxide group and subsequent removal of the side chain gave 3 H-labelled 6-aminopenicillanic acid. (author)

Effect of penicillin on fatty acid synthesis and excretion in Streptococcus mutans BHT

International Nuclear Information System (INIS)

Brissette, J.L.; Pieringer, R.A.

1985-01-01

Treatment of exponentially growing cultures of Streptococcus mutans BHT with growth-inhibitory concentrations (0.2 microgram/ml) of benzylpenicillin stimulates the incorporation of [2- 14 C] acetate into lipids excreted by the cells by as much as 69-fold, but does not change the amount of 14 C incorporated into intracellular lipids. At this concentration of penicillin cellular lysis does not occur. The radioactive label is incorporated exclusively into the fatty acid moieties of the glycerolipids. During a 4-hr incubation in the presence of penicillin, the extracellular fatty acid ester concentration increases 1.5 fold, even though there is no growth or cellular lysis. An indication of the relative rate of fatty acid synthesis was most readily obtained by placing S. mutans BHT in a buffer containing 14 C-acetate. Under these nongrowing conditions free fatty acids are the only lipids labeled, a factor which simplifies the assay. The addition of glycerol to the buffer causes all of the nonesterified fatty acids to be incorporated into glycerolipid. The cells excrete much of the lipid whether glycerol is present or not. Addition of penicillin to the nongrowth supporting buffer system does not stimulate the incorporation of [ 14 C]-acetate into fatty acids

Exposure to β-lactams results in the alteration of penicillin-binding proteins in Clostridium perfringens.

Science.gov (United States)

Park, Miseon; Rafii, Fatemeh

2017-06-01

Clostridium perfringens causes a variety of mild to severe infections in humans and other animals. A decrease in the affinity of penicillin-binding protein (PBP) transpeptidases for β-lactams is considered one of the mechanisms of β-lactam resistance in bacteria. Two strains of C. perfringens isolated from bovines and one isolated from a chicken, which had decreased susceptibility to β-lactams, had variations in the amino acid sequences of the central penicillin-binding regions of the PBPs. β-Lactam-resistant mutants of another C. perfringens strain, ATCC 13124, were selected in vitro to determine the effects of exposure to β-lactams on the PBP genes. Cultures of the wild type rapidly developed resistance to penicillin G, cephalothin and ceftriaxone. The susceptibilities of all of the selected mutants to some other β-lactams also decreased. The largest PBP found in C. perfringens, CPF_2395, appeared to be the primary target of all three drugs. Strain resistant to penicillin G had mutation resulting in the substitution of one amino acid within the central penicillin-binding/transpeptidase domain, but the ceftrioxane and cephalothin-resistant strains had mutations resulting in the substitution of two amino acids in this region. The cephalothin-resistant mutant also had additional mutations in the CPF_0340 and CPF_2218 genes in this critical region. No other mutations were observed in the three other PBPs of the in vitro resistant mutants. Resistance development also altered the growth rate and cell morphology of the mutants, so in addition to the PBPs, some other genes, including regulatory genes, may have been affected during the interaction with β-lactam antibiotics. This is the first study showing the effects of β-lactam drugs on the substitution of amino acids in PBPs of C. perfringens and points to the need for studies to detect other unknown alterations affecting the physiology of resistant strains. Published by Elsevier Ltd.

A Phytase-Based Reporter System for Identification of Functional Secretion Signals in Bifidobacteria

Science.gov (United States)

Osswald, Annika; Westermann, Christina; Sun, Zhongke; Riedel, Christian U.

2015-01-01

Health-promoting effects have been attributed to a number of Bifidobacterium sp. strains. These effects as well as the ability to colonise the host depend on secreted proteins. Moreover, rational design of protein secretion systems bears the potential for the generation of novel probiotic bifidobacteria with improved health-promoting or therapeutic properties. To date, there is only very limited data on secretion signals of bifidobacteria available. Using in silico analysis, we demonstrate that all bifidobacteria encode the major components of Sec-dependent secretion machineries but only B. longum strains harbour Tat protein translocation systems. A reporter plasmid for secretion signals in bifidobacteria was established by fusing the coding sequence of the signal peptide of a sialidase of Bifidobacterium bifidum S17 to the phytase gene appA of E. coli. The recombinant strain showed increased phytase activity in spent culture supernatants and reduced phytase levels in crude extracts compared to the control indicating efficient phytase secretion. The reporter plasmid was used to screen seven predicted signal peptides in B. bifidum S17 and B. longum E18. The tested signal peptides differed substantially in their efficacy to mediate protein secretion in different host strains. An efficient signal peptide was used for expression and secretion of a therapeutically relevant protein in B. bifidum S17. Expression of a secreted cytosine deaminase led to a 100-fold reduced sensitivity of B. bifidum S17 to 5-fluorocytosine compared to the non-secreted cytosine deaminase suggesting efficient conversion of 5-fluorocytosine to the cytotoxic cancer drug 5-fluorouracil by cytosine deaminase occurred outside the bacterial cell. Selection of appropriate signal peptides for defined protein secretion might improve therapeutic efficacy as well as probiotic properties of bifidobacteria. PMID:26086721

A Phytase-Based Reporter System for Identification of Functional Secretion Signals in Bifidobacteria.

Directory of Open Access Journals (Sweden)

Annika Osswald

Full Text Available Health-promoting effects have been attributed to a number of Bifidobacterium sp. strains. These effects as well as the ability to colonise the host depend on secreted proteins. Moreover, rational design of protein secretion systems bears the potential for the generation of novel probiotic bifidobacteria with improved health-promoting or therapeutic properties. To date, there is only very limited data on secretion signals of bifidobacteria available. Using in silico analysis, we demonstrate that all bifidobacteria encode the major components of Sec-dependent secretion machineries but only B. longum strains harbour Tat protein translocation systems. A reporter plasmid for secretion signals in bifidobacteria was established by fusing the coding sequence of the signal peptide of a sialidase of Bifidobacterium bifidum S17 to the phytase gene appA of E. coli. The recombinant strain showed increased phytase activity in spent culture supernatants and reduced phytase levels in crude extracts compared to the control indicating efficient phytase secretion. The reporter plasmid was used to screen seven predicted signal peptides in B. bifidum S17 and B. longum E18. The tested signal peptides differed substantially in their efficacy to mediate protein secretion in different host strains. An efficient signal peptide was used for expression and secretion of a therapeutically relevant protein in B. bifidum S17. Expression of a secreted cytosine deaminase led to a 100-fold reduced sensitivity of B. bifidum S17 to 5-fluorocytosine compared to the non-secreted cytosine deaminase suggesting efficient conversion of 5-fluorocytosine to the cytotoxic cancer drug 5-fluorouracil by cytosine deaminase occurred outside the bacterial cell. Selection of appropriate signal peptides for defined protein secretion might improve therapeutic efficacy as well as probiotic properties of bifidobacteria.

ACYLTRANSFERASE ACTIVITIES OF THE HIGH-MOLECULAR-MASS ESSENTIAL PENICILLIN-BINDING PROTEINS

NARCIS (Netherlands)

ADAM, M; DAMBLON, C; JAMIN, M; ZORZI, W; DUSART, [No Value; GALLENI, M; ELKHARROUBI, A; PIRAS, G; SPRATT, BG; KECK, W; COYETTE, J; GHUYSEN, JM; NGUYENDISTECHE, M; FRERE, JM

1991-01-01

The high-molecular-mass penicillin-binding proteins (HMM-PBPs), present in the cytoplasmic membranes of all eubacteria, are involved in important physiological events such as cell elongation, septation or shape determination. Up to now it has, however, been very difficult or impossible to study the

Properties of immobilised penicillin G Acylase in beta-lactam antibiotic synthesis

NARCIS (Netherlands)

Janssen, M.H.A.

2006-01-01

The beta-lactam antibiotics are the most important class of antibiotics used today. In the last decade the production routes of these antibiotics have shifted from chemical routes to more environmentally benign routes using the enzyme penicillin G acylase. For both practical and economical reasons

New penicillin-producing Penicillium species and an overview of section Chrysogena

NARCIS (Netherlands)

Houbraken, J.; Frisvad, J.C.; Seifert, K.A.; Overy, D.P.; Tuthill, D.M.; Valdez, J.G.; Samson, R.A.

2012-01-01

Species classified in Penicillium sect. Chrysogena are primary soil-borne and the most well-known members are P. chrysogenum and P. nalgiovense. Penicillium chrysogenum has received much attention because of its role in the production on penicillin and as a contaminant of indoor environments and

Effects of two novel amino acid substitutions on the penicillin binding properties of the PBP5 C‑terminal from Enterococcus faecium.

Science.gov (United States)

Zhou, Chengjiang; Niu, Haiying; Yu, Hui; Zhou, Lishe; Wang, Zhanli

2015-10-01

The low‑affinity penicillin‑binding protein (PBP)5 is responsible for resistance to β‑lactam antibiotics in Enterococcus faecium. (E. faecium). In order to evaluate more fully the potential of this species for the development of resistance to β-lactam antibiotics, the present study aimed to examine the extent of penicillin-binding protein (PBP) variations in a collection of clinical E. faecium isolates. In the present study, the C‑terminal domain of PBP5 (PBP5‑CD) of 13 penicillin‑resistant clinical isolates of E. faecium were sequenced and the correlation between penicillin resistance and particular amino acid changes were analyzed. The present study identified for the first time, to the best of our knowledge, two novel substitutions (Tyr460Phe and Ala462Thr or Val462Thr) of E. faecium PBP5‑CD. The covalent interaction between penicillin and PBP5‑CD was also investigated using homology modeling and molecular docking methods. The theoretical calculation revealed that Phe460 and Thr462 were involved in penicillin binding, suggesting that substitutions at these positions exert effects on the affinity for penicillin, and this increased affinity translates into lower resistance in vitro.

Application of kidney inhibition swab tests to evaluate penicillin-G residues in sow tissues and body fluids following intramuscular injection

Science.gov (United States)

Kidney inhibition swab (KIS) tests, recently adapted by the US FSIS for antibiotics on-site screening, were employed to evaluate the depletion of penicillin-G residues from kidney, liver, muscle, serum, and urine of sows after intramuscular (IM) penicillin-G procaine administration. Sows (n=130; 22...

Resistance to β-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins.

Science.gov (United States)

Zapun, André; Morlot, Cécile; Taha, Muhamed-Kheir

2016-09-28

Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens that cause a variety of life-threatening systemic and local infections, such as meningitis or gonorrhoea. The treatment of such infection is becoming more difficult due to antibiotic resistance. The focus of this review is on the mechanism of reduced susceptibility to penicillin and other β-lactams due to the modification of chromosomally encoded penicillin-binding proteins (PBP), in particular PBP2 encoded by the penA gene. The variety of penA alleles and resulting variant PBP2 enzymes is described and the important amino acid substitutions are presented and discussed in a structural context.

Secure direct communication based on secret transmitting order of particles

International Nuclear Information System (INIS)

Zhu Aidong; Zhang Shou; Xia Yan; Fan Qiubo

2006-01-01

We propose the schemes of quantum secure direct communication based on a secret transmitting order of particles. In these protocols, the secret transmitting order of particles ensures the security of communication, and no secret messages are leaked even if the communication is interrupted for security. This strategy of security for communication is also generalized to a quantum dialogue. It not only ensures the unconditional security but also improves the efficiency of communication

Empiric penicillin monotherapy of CAP is not associated with increased mortality; experiences from the retrospective CAP-North cohort

DEFF Research Database (Denmark)

Baunbæk-Knudsen, Getrud; Vestergaard Jensen, Andreas; Andersen, Stine

2016-01-01

Background: Community-acquired pneumonia (CAP) is a severe infection, with high morbidity and mortality. The antibiotic strategies for CAP differ across Europe. Objective: To assess the usage of Penicillin monotherapy in a real-life cohort and to evaluate predictors of treatment duration and the ......Background: Community-acquired pneumonia (CAP) is a severe infection, with high morbidity and mortality. The antibiotic strategies for CAP differ across Europe. Objective: To assess the usage of Penicillin monotherapy in a real-life cohort and to evaluate predictors of treatment duration......, and evaluated predictors of treatment duration by linear regression. Mortality of patients receiving empiric penicillin-G/V was compared to others by logistic regression analysis. The CAPNETZ database technology was used for data-capture. Results: We included 1320 patients. The incidence of hospitalized CAP...... was 3.1 per 1000 inhabitants. The median age was 71 years (IQR; 58.81). In-hospital mortality was 8%. Patients treated with penicillin-G/V as empiric monotherapy (45%) did not have a higher mortality than those treated with broader spectrum antibiotics (OR 1.30, CI 95% 0.84-2-02). The median duration...

Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins.

Science.gov (United States)

Fernández, T D; Torres, M J; Blanca-López, N; Rodríguez-Bada, J L; Gomez, E; Canto, G; Mayorga, C; Blanca, M

2009-02-01

Skin test sensitivity in patients with immediate allergy to penicillins tends to decrease over time, but no information is available concerning in vitro tests. We analysed the negativization rates of two in vitro methods that determine specific immunoglobulin E (IgE) antibodies, the basophil activation test using flow cytometry (BAT) and the radioallergosorbent test (RAST), in immediate allergic reactions to penicillins. Forty-one patients with immediate allergic reactions to amoxicillin were followed up over a 4-year period. BAT and RAST were performed at 6-month intervals. Patients were randomized into groups: Group I, skin tests carried out at regular intervals; Group II, skin tests made only at the beginning of the study. Differences were observed between RAST and BAT (P testing influenced the rate of negativization of the RAST assay, contributing to maintenance of in vitro sensitivity. Because of the loss of sensitivity over time, the determination of specific IgE antibodies to penicillins in patients with immediate allergic reactions must be done as soon as possible after the reaction.

Efficacy of high doses of penicillin versus amoxicillin in the treatment of uncomplicated community acquired pneumonia in adults. A non-inferiority controlled clinical trial.

Science.gov (United States)

Llor, Carl; Pérez, Almudena; Carandell, Eugenia; García-Sangenís, Anna; Rezola, Javier; Llorente, Marian; Gestoso, Salvador; Bobé, Francesc; Román-Rodríguez, Miguel; Cots, Josep M; Hernández, Silvia; Cortés, Jordi; Miravitlles, Marc; Morros, Rosa

2017-10-20

Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries. To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP. Multicentre, parallel, double-blind, controlled, randomized clinical trial. 31 primary care centers in Spain. Patients from 18 to 75 years of age with no significant associated comorbidity and with symptoms of lower respiratory tract infection and radiological confirmation of CAP were randomized to receive either penicillin V 1.6 million units, or amoxicillin 1000mg three times per day for 10 days. The main outcome was clinical cure at 14 days, and the primary hypothesis was that penicillin V would be non-inferior to amoxicillin with regard to this outcome, with a margin of 15% for the difference in proportions. EudraCT register 2012-003511-63. A total of 43 subjects (amoxicillin: 28; penicillin: 15) were randomized. Clinical cure was observed in 10 (90.9%) patients assigned to penicillin and in 25 (100%) patients assigned to amoxicillin with a difference of -9.1% (95% CI, -41.3% to 6.4%; p=.951) for non-inferiority. In the intention-to-treat analysis, amoxicillin was found to be 28.6% superior to penicillin (95% CI, 7.3-58.1%; p=.009 for superiority). The number of adverse events was similar in both groups. There was a trend favoring high-dose amoxicillin versus high-dose penicillin in adults with uncomplicated CAP. The main limitation of this trial was the low statistical power due to the low number of patients included. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The role of jasmonates in floral nectar secretion.

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Venkatesan Radhika

Full Text Available Plants produce nectar in their flowers as a reward for their pollinators and most of our crops depend on insect pollination, but little is known on the physiological control of nectar secretion. Jasmonates are well-known for their effects on senescence, the development and opening of flowers and on plant defences such as extrafloral nectar. Their role in floral nectar secretion has, however, not been explored so far. We investigated whether jasmonates have an influence on floral nectar secretion in oil-seed rape, Brassica napus. The floral tissues of this plant produced jasmonic acid (JA endogenously, and JA concentrations peaked shortly before nectar secretion was highest. Exogenous application of JA to flowers induced nectar secretion, which was suppressed by treatment with phenidone, an inhibitor of JA synthesis. This effect could be reversed by additional application of JA. Jasmonoyl-isoleucine and its structural mimic coronalon also increased nectar secretion. Herbivory or addition of JA to the leaves did not have an effect on floral nectar secretion, demonstrating a functional separation of systemic defence signalling from reproductive nectar secretion. Jasmonates, which have been intensively studied in the context of herbivore defences and flower development, have a profound effect on floral nectar secretion and, thus, pollination efficiency in B. napus. Our results link floral nectar secretion to jasmonate signalling and thereby integrate the floral nectar secretion into the complex network of oxylipid-mediated developmental processes of plants.

Cloning, preparation and preliminary crystallographic studies of penicillin V acylase autoproteolytic processing mutants

International Nuclear Information System (INIS)

Chandra, P. Manish; Brannigan, James A.; Prabhune, Asmita; Pundle, Archana; Turkenburg, Johan P.; Dodson, G. Guy; Suresh, C. G.

2004-01-01

The production, crystallization and characterization of three inactive mutants of penicillin V acylase from B. sphaericus in their respective precursor and processed forms are reported. The space groups are different for the native enzyme and the mutants. The crystallization of three catalytically inactive mutants of penicillin V acylase (PVA) from Bacillus sphaericus in precursor and processed forms is reported. The mutant proteins crystallize in different primitive monoclinic space groups that are distinct from the crystal forms for the native enzyme. Directed mutants and clone constructs were designed to study the post-translational autoproteolytic processing of PVA. The catalytically inactive mutants will provide three-dimensional structures of precursor PVA forms, plus open a route to the study of enzyme–substrate complexes for this industrially important enzyme

Dispatched and Scube Mediate the Efficient Secretion of the Cholesterol-Modified Hedgehog Ligand

OpenAIRE

Hanna Tukachinsky; Ryan P. Kuzmickas; Cindy Y. Jao; Jing Liu; Adrian Salic

2012-01-01

The Hedgehog signaling pathway plays critical roles in metazoan development and in cancer. How the Hedgehog ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hedgehog ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, one mediated by the membrane protein Dispatched and the other by a...

Nicolau syndrome following intramuscular benzathine penicillin

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De Sousa R

2008-01-01

Full Text Available Nicolau syndrome (NS is a rare complication of an intramuscular injection characterized by severe pain, skin discoloration, and varying levels of tissue necrosis. The case outcomes vary from atrophic ulcers and severe pain to sepsis and limb amputation. We describe a case of a seven-year-old boy with diagnosis of NS after intramuscular benzathine penicillin injection to the ventrolateral aspect of the left thigh. Characteristic violaceous discoloration of skin and immediate injection site pain identified it as a case of NS. The case was complicated by rapid progression of compartment syndrome of the lower limb, proceeding to acute renal failure and death. Associated compartment syndrome can be postulated as a poor prognostic factor for NS.

Functional expression of a penicillin acylase from the extreme thermophile Thermus thermophilus HB27 in Escherichia coli

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Torres Leticia L

2012-08-01

Full Text Available Abstract Background Penicillin acylases (PACs are enzymes of industrial relevance in the manufacture of β-lactam antibiotics. Development of a PAC with a longer half-life under the reaction conditions used is essential for the improvement of the operational stability of the process. A gene encoding a homologue to Escherichia coli PAC was found in the genome of the thermophilic bacterium Thermus thermophilus (Tth HB27. Because of the nature of this PAC and its complex maturation that is crucial to reach its functional heterodimeric final conformation, the overexpression of this enzyme in a heterologous mesophilic host was a challenge. Here we describe the purification and characterization of the PAC protein from Tth HB27 overexpressed in Escherichia coli. Results Fusions to a superfolder green fluorescent protein and differential membrane solubilization assays indicated that the native enzyme remains attached through its amino-terminal end to the outer side of the cytoplasmic membrane of Tth cells. In order to overexpress this PAC in E. coli cells, a variant of the protein devoid of its membrane anchoring segment was constructed. The effect of the co-expression of chaperones and calcium supplementation of the culture medium was investigated. The total production of PAC was enhanced by the presence of DnaK/J and GrpE and even more by trigger factor and GroEL/ES. In addition, 10 mM calcium markedly improved both PAC specific and volumetric activities. Recombinant PAC was affinity-purified and proper maturation of the protein was confirmed by SDS-PAGE and MALDI-TOF analysis of the subunits. The recombinant protein was tested for activity towards several penicillins, cephalosporins and homoserine lactones. Hydrophobic acyl-chain penicillins were preferred over the rest of the substrates. Penicillin K (octanoyl penicillin was the best substrate, with the highest specificity constant value (16.12 mM-1.seg-1. The optimum pH was aprox. 4 and the optimum

Functional expression of a penicillin acylase from the extreme thermophile Thermus thermophilus HB27 in Escherichia coli.

Science.gov (United States)

Torres, Leticia L; Ferreras, Eloy R; Cantero, Angel; Hidalgo, Aurelio; Berenguer, José

2012-08-09

Penicillin acylases (PACs) are enzymes of industrial relevance in the manufacture of β-lactam antibiotics. Development of a PAC with a longer half-life under the reaction conditions used is essential for the improvement of the operational stability of the process. A gene encoding a homologue to Escherichia coli PAC was found in the genome of the thermophilic bacterium Thermus thermophilus (Tth) HB27. Because of the nature of this PAC and its complex maturation that is crucial to reach its functional heterodimeric final conformation, the overexpression of this enzyme in a heterologous mesophilic host was a challenge. Here we describe the purification and characterization of the PAC protein from Tth HB27 overexpressed in Escherichia coli. Fusions to a superfolder green fluorescent protein and differential membrane solubilization assays indicated that the native enzyme remains attached through its amino-terminal end to the outer side of the cytoplasmic membrane of Tth cells. In order to overexpress this PAC in E. coli cells, a variant of the protein devoid of its membrane anchoring segment was constructed. The effect of the co-expression of chaperones and calcium supplementation of the culture medium was investigated. The total production of PAC was enhanced by the presence of DnaK/J and GrpE and even more by trigger factor and GroEL/ES. In addition, 10 mM calcium markedly improved both PAC specific and volumetric activities. Recombinant PAC was affinity-purified and proper maturation of the protein was confirmed by SDS-PAGE and MALDI-TOF analysis of the subunits. The recombinant protein was tested for activity towards several penicillins, cephalosporins and homoserine lactones. Hydrophobic acyl-chain penicillins were preferred over the rest of the substrates. Penicillin K (octanoyl penicillin) was the best substrate, with the highest specificity constant value (16.12 mM-1.seg-1). The optimum pH was aprox. 4 and the optimum temperature was 75 °C. The half-life of

Aluminum based metal-organic framework-polymer monolith in solid-phase microextraction of penicillins in river water and milk samples.

Science.gov (United States)

Lirio, Stephen; Liu, Wan-Ling; Lin, Chen-Lan; Lin, Chia-Her; Huang, Hsi-Ya

2016-01-08

In this study, aluminum based metal-organic framework (Al-MOF)-organic polymer monoliths were prepared via microwave-assisted polymerization of ethylene dimethacrylate (EDMA), butyl methacrylate (BMA) with different weight percentages of Al-MOF (MIL-53; 37.5-62.5%) and subsequently utilized as sorbent in solid-phase microextraction (SPME) of penicillins (penicillin G, penicillin V, oxacillin, cloxacillin, dicloxacillin, nafcillin). The Al-MOF-polymer was characterized using Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and SEM-energy-dispersive X-ray spectroscopy (SEM-EDS) to clarify the retained crystalline structure well as the homogeneous dispersion of Al-MOF (MIL-53) in polymer monolith. The developed Al-MOF-polymer (MIL-53) monolithic column was evaluated according to its extraction recovery of penicillins. Several parameters affecting the extraction recoveries of penicillins using fabricated Al-MOF-polymer (MIL-53) monolithic column including different MIL-53 weight percentages, column length, pH, desorption solvent, and mobile phase flow rate were investigated. For comparison, different Al-based MOFs (MIL-68, CYCU-4 and DUT-5) were fabricated using the optimized condition for MIL-53-polymer (sample matrix at pH 3, 200μL desorption volume using methanol, 37.5% of MOF, 4-cm column length at 0.100mLmin(-1) flow rate). Among all the Al-MOF-polymers, MIL-53(Al)-polymer still afforded the best extraction recovery for penicillins ranging from 90.5 to 95.7% for intra-day with less than 3.5% relative standard deviations (RSDs) and inter-day precision were in the range of 90.7-97.6% with less than 4.2% RSDs. Meanwhile, the recoveries for column-to-column were in the range of 89.5-93.5% (<3.4% RSDs) while 88.5-90.5% (<5.8% RSDs) for batch-to-batch (n=3). Under the optimal conditions, the limit of detections were in the range of 0.06-0.26μgL(-1) and limit of quantifications between 0.20 and 0.87�

Crystal structures of the transpeptidase domain of the Mycobacterium tuberculosis penicillin-binding protein PonA1 reveal potential mechanisms of antibiotic resistance.

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Filippova, Ekaterina V; Kieser, Karen J; Luan, Chi-Hao; Wawrzak, Zdzislaw; Kiryukhina, Olga; Rubin, Eric J; Anderson, Wayne F

2016-06-01

Mycobacterium tuberculosis is a human respiratory pathogen that causes the deadly disease tuberculosis. The rapid global spread of antibiotic-resistant M. tuberculosis makes tuberculosis infections difficult to treat. To overcome this problem new effective antimicrobial strategies are urgently needed. One promising target for new therapeutic approaches is PonA1, a class A penicillin-binding protein, which is required for maintaining physiological cell wall synthesis and cell shape during growth in mycobacteria. Here, crystal structures of the transpeptidase domain, the enzymatic domain responsible for penicillin binding, of PonA1 from M. tuberculosis in the inhibitor-free form and in complex with penicillin V are reported. We used site-directed mutagenesis, antibiotic profiling experiments, and fluorescence thermal shift assays to measure PonA1's sensitivity to different classes of β-lactams. Structural comparison of the PonA1 apo-form and the antibiotic-bound form shows that binding of penicillin V induces conformational changes in the position of the loop β4'-α3 surrounding the penicillin-binding site. We have also found that binding of different antibiotics including penicillin V positively impacts protein stability, while other tested β-lactams such as clavulanate or meropenem resulted in destabilization of PonA1. Our antibiotic profiling experiments indicate that the transpeptidase activity of PonA1 in both M. tuberculosis and M. smegmatis mediates tolerance to specific cell wall-targeting antibiotics, particularly to penicillin V and meropenem. Because M. tuberculosis is an important human pathogen, these structural data provide a template to design novel transpeptidase inhibitors to treat tuberculosis infections. Structural data are available in the PDB database under the accession numbers 5CRF and 5CXW. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Efficient protein production by yeast requires global tuning of metabolism

DEFF Research Database (Denmark)

Huang, Mingtao; Bao, Jichen; Hallstrom, Bjorn M.

2017-01-01

The biotech industry relies on cell factories for production of pharmaceutical proteins, of which several are among the top-selling medicines. There is, therefore, considerable interest in improving the efficiency of protein production by cell factories. Protein secretion involves numerous...... intracellular processes with many underlying mechanisms still remaining unclear. Here, we use RNA-seq to study the genome-wide transcriptional response to protein secretion in mutant yeast strains. We find that many cellular processes have to be attuned to support efficient protein secretion. In particular...... that by tuning metabolism cells are able to efficiently secrete recombinant proteins. Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion....

Visualization of glucagon secretion from pancreatic α cells by bioluminescence video microscopy: Identification of secretion sites in the intercellular contact regions

International Nuclear Information System (INIS)

Yokawa, Satoru; Suzuki, Takahiro; Inouye, Satoshi; Inoh, Yoshikazu; Suzuki, Ryo; Kanamori, Takao; Furuno, Tadahide; Hirashima, Naohide

2017-01-01

We have firstly visualized glucagon secretion using a method of video-rate bioluminescence imaging. The fusion protein of proglucagon and Gaussia luciferase (PGCG-GLase) was used as a reporter to detect glucagon secretion and was efficiently expressed in mouse pancreatic α cells (αTC1.6) using a preferred human codon-optimized gene. In the culture medium of the cells expressing PGCG-GLase, luminescence activity determined with a luminometer was increased with low glucose stimulation and KCl-induced depolarization, as observed for glucagon secretion. From immunochemical analyses, PGCG-GLase stably expressed in clonal αTC1.6 cells was correctly processed and released by secretory granules. Luminescence signals of the secreted PGCG-GLase from the stable cells were visualized by video-rate bioluminescence microscopy. The video images showed an increase in glucagon secretion from clustered cells in response to stimulation by KCl. The secretory events were observed frequently at the intercellular contact regions. Thus, the localization and frequency of glucagon secretion might be regulated by cell-cell adhesion. - Highlights: • The fused protein of proglucagon to Gaussia luciferase was used as a reporter. • The fusion protein was highly expressed using a preferred human-codon optimized gene. • Glucagon secretion stimulated by depolarization was determined by luminescence. • Glucagon secretion in α cells was visualized by bioluminescence imaging. • Glucagon secretion sites were localized in the intercellular contact regions.

Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: An efficient carrier for immobilizing penicillin G acylase

Energy Technology Data Exchange (ETDEWEB)

Xue, Ping; Su, Weiguang, E-mail: weiguangsu@nxu.edu.cn; Gu, Yaohua; Liu, Haifeng; Wang, Julan

2015-03-15

Magnetic hydrophilic polymeric microspheres containing oxirane groups were prepared by inverse suspension polymerization of glycidyl methacrylate (GMA), N, N′-methylene bisacrylamide (MBAA) and N-vinyl pyrrolidone (NVP) in the existence of formamide, which were denoted as magnetic poly(GMA-MBAA-NVP) microspheres. The magnetic poly(GMA-MBAA-NVP) microspheres were characterized by scanning electron microscopy (SEM), FT-IR spectroscopy, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and so on. The results showed that poly(GMA-MBAA-NVP) microspheres possessed well spherical shape, narrow size distribution, abundant porous structure, reactive oxirane groups and superparamagnetic properties. Formamide used in the present work served as a modifier, a dispersant and a porogen to form final porous polymer microspheres. The penicillin G acylase (PGA) was covalently immobilized onto the magnetic microspheres through the reaction between the amino groups of enzyme and the oxirane groups on the microspheres for producing 6-aminopenicillanic acid (6-APA). The effects of GMA/NVP ratio and crosslink density on the activity of immobilized PGA were investigated. The highest apparent activity, enzyme loading and coupling yield of immobilized PGA were 821 IU/g, 65.3 mg/g and 42.3% respectively when the mass ratio of GMA/NVP was 1:1 and crosslink density was 60%. Compared with the free PGA, immobilized PGA showed a wider range of pH value and reaction temperature. The relative activity and reaction rate of immobilized PGA remained almost constant after 20 recycles. The magnetic poly(GMA-MBAA-NVP) microspheres would be very promising carriers for immobilizing enzymes in industrial application. - Highlights: • The magnetic poly(GMA-MBAA-NVP) microspheres were successfully synthesized. • Formamide served as a modifier, a dispersant and a porogen to form microspheres. • The magnetic microspheres were highly efficient carriers for immobilizing PGA. • Immobilized PGA

Increasing penicillin resistance in pneumococci isolated from cerebrospinal fluid samples: Fifteen-year experience from a teaching hospital

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Filiz Pehlivanoğlu

2014-12-01

Full Text Available Objective: There have been prominent changes in evaluation of resistance patterns of pneumococci and breakpoint values in recent years. We aimed to investigate the penicillin sensitivity of pneumococcal strains isolated from the ce­rebrospinal fluid specimens between the years 1997-2011 in our hospital and determine the MIC values under the light of these changes. Methods: Identification of pneumococci was made with conventional methods in patients with meningitis. MIC values for penicillin G were investigated by E test method in all strains. MIC values of pneumococci strains were evaluated ac­cording to values determined by CLSI for meningitis isolates in 2008. Results: A total of 57 strains were investigated in this study. The MIC range for penicillin was 0.016 - 0.75 μg/ml in S. pneumoniae strains. Seventy five percent of the strains were sensitive and eight strains (14% had resistance. MIC50 value was sensitive, and a MIC90 value was resistant. The first resistant strain was detected in 2000, and three strains were resistant in the last year. When examined over the years increased resistance was 5.3% in the first five-year period seems to be 28.6% in the last five-year period. Conclusions: Knowledge on penicillin resistance patterns and surveillance is very important in the empirical treatment in pneumococcal meningitis. J Microbiol Infect Dis 2014; 4(4: 136-140

Peptidoglycan transpeptidase inhibition in Pseudomonas aeruginosa and Escherichia coli by Penicillins and Cephalosporins.

Science.gov (United States)

Moore, B A; Jevons, S; Brammer, K W

1979-04-01

Peptidoglycan transpeptidase activity has been studied in cells of Escherichia coli 146 and Pseudomonas aeruginosa 56 made permeable to exogenous, nucleotide-sugar peptidoglycan precursors by ether treatment. Transpeptidase activity was inhibited, in both organisms, by a range of penicillins and cephalosporins, the Pseudomonas enzyme being more sensitive to inhibition in each case. Conversely, growth of E. coli 146 was more susceptible to these antibiotics than growth of P. aeruginosa 56. Furthermore, similar transpeptidase inhibition values were ob-obtained for the four penicillins examined against the Pseudomonas enzyme, although only two of these (carbenicillin and pirbenicillin) inhibited the growth of this organism. We therefore conclude that the high resistance of P. aeruginosa 56 to growth inhibition by most beta-lactam antibiotics cannot be due to an insensitive peptidoglycan transpeptidase.

Radiolabelling of penicillin-binding proteins (PBPs) in intact Pseudomonas aeruginosa cells; consequences of β-lactamase activity by PBP-5

International Nuclear Information System (INIS)

Livermore, D.M.

1987-01-01

The time-course of labelling of penicillin-binding proteins (PBPs) was compared for intact and sonicated cell preparations of nine Pseudomonas aeruginosa strains, all of which gave identical PBP profiles. Saturation of all the PBPs in cell-sonicates occurred within 2 min of exposure to 14 [C] benzylpenicillin. PBP-5 formed an unstable penicilloyl-complex: the other PBPs formed highly stable complexes. Saturation of PBP-4 in intact cells occurred within 2 min of exposure to the antibiotic, correlating with the high affinity of this protein for penicillin. Labelling of PBPs 1a, 1b and 3 was slow but progressive, suggesting that these proteins were shielded by the permeability barrier(s) of the cell. Labelling of PBP-5 in intact cells achieved 10-20% saturation within 2-10 min of exposure to 14 [C] benzylpenicillin, but did not increase subsequently. This behaviour may indicate that establishment of a steady state between the formation and breakdown of the PBP-5-penicillin complex, suggesting that PBP-5, potentiated by the permeability barrier, functions as a feeble β-lactamase. Such activity may distort the labelling of other PBPs by reducing the concentration of penicillin in the periplasm. (author)

Identification and characterization of a type III secretion-associated chaperone in the type III secretion system 1 of Vibrio parahaemolyticus.

Science.gov (United States)

Akeda, Yukihiro; Okayama, Kanna; Kimura, Tomomi; Dryselius, Rikard; Kodama, Toshio; Oishi, Kazunori; Iida, Tetsuya; Honda, Takeshi

2009-07-01

Vibrio parahaemolyticus causes human gastroenteritis. Genomic sequencing of this organism has revealed that it has two sets of type III secretion systems, T3SS1 and T3SS2, both of which are important for its pathogenicity. However, the mechanism of protein secretion via T3SSs is unknown. A characteristic of many effectors is that they require specific chaperones for efficient delivery via T3SSs; however, no chaperone has been experimentally identified in the T3SSs of V. parahaemolyticus. In this study, we identified candidate T3SS1-associated chaperones from genomic sequence data and examined their roles in effector secretion/translocation and binding to their cognate substrates. From these experiments, we concluded that there is a T3S-associated chaperone, VecA, for a cytotoxic T3SS1-dependent effector, VepA. Further analysis using pulldown and secretion assays characterized the chaperone-binding domain encompassing the first 30-100 amino acids and an amino terminal secretion signal encompassing the first 5-20 amino acids on VepA. These findings will provide a strategy to clarify how the T3SS1 of V. parahaemolyticus secretes its specific effectors.

Benzathine penicillin G: a model for long-term pharmacokinetic comparison of parenteral long-acting formulations.

Science.gov (United States)

Shahbazi, M A; Azimi, K; Hamidi, M

2013-04-01

  Long-acting intramuscular penicillin G injection is an important product for the management of some severe infections. However, testing the bioequivalence of such long-acting formulations is difficult. Our aim was to undertake such a test using a generic formulation containing 1 200 000 IU of benzathine penicillin G powder and an innovator's product (Retarpen(®) 1·2 million units; Sandoz, Switzerland).   In an open, double-blind, randomized, two-periods, two-group crossover study, 12 healthy male volunteers received both formulations of benzathine penicillin G on two different days with a 5-month washout period between the doses and a sampling period of over 500 h. A simple, sensitive and rapid high-performance liquid chromatography (HPLC)-UV method was developed and validated for determination of penicillin G plasma concentrations and other pharmacokinetic (PK) parameters.   The analytical method used produced linear responses within a wide analyte concentration range with average within-run and between-run variations of below 15% with acceptable recovery, accuracy and sensitivity. The primary PK parameters we used were maximum plasma concentration (Cmax ), time to reach the maximal concentration (Tmax ) and the area under the plasma concentration vs. time curve from time zero to the last sampling time (AUC0→t ) using a standard non-compartmental approach. Based on these parameters, the two formulations were bioequivalent.   We illustrate the bioequivalence testing of a very long-acting product. The data indicate that the generic test formulation and the branded reference formulation were bioequivalent in fasting healthy Iranian male volunteers. © 2013 Blackwell Publishing Ltd.

Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia

Science.gov (United States)

Wang, Chi-Chuan; Lin, Chia-Hui; Lin, Kuan-Yin; Chuang, Yu-Chung; Sheng, Wang-Huei

2016-01-01

Abstract Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics. This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups. After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77–0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92–1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30–1.62) between the 2 groups. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted. PMID:26871827

New Aspects of the Interplay between Penicillin Binding Proteins, murM, and the Two-Component System CiaRH of Penicillin-Resistant Streptococcus pneumoniae Serotype 19A Isolates from Hungary.

Science.gov (United States)

Schweizer, Inga; Blättner, Sebastian; Maurer, Patrick; Peters, Katharina; Vollmer, Daniela; Vollmer, Waldemar; Hakenbeck, Regine; Denapaite, Dalia

2017-07-01

The Streptococcus pneumoniae clone Hungary 19A -6 expresses unusually high levels of β-lactam resistance, which is in part due to mutations in the MurM gene, encoding a transferase involved in the synthesis of branched peptidoglycan. Moreover, it contains the allele ciaH232 , encoding the histidine kinase CiaH (M. Müller, P. Marx, R. Hakenbeck, and R. Brückner, Microbiology 157:3104-3112, 2011, https://doi.org/10.1099/mic.0.053157-0). High-level penicillin resistance primarily requires the presence of low-affinity (mosaic) penicillin binding protein (PBP) genes, as, for example, in strain Hu17, a closely related member of the Hungary 19A -6 lineage. Interestingly, strain Hu15 is β-lactam sensitive due to the absence of mosaic PBPs. This unique situation prompted us to investigate the development of cefotaxime resistance in transformation experiments with genes known to play a role in this phenotype, pbp2x , pbp1a , murM , and ciaH , and penicillin-sensitive recipient strains R6 and Hu15. Characterization of phenotypes, peptidoglycan composition, and CiaR-mediated gene expression revealed several novel aspects of penicillin resistance. The murM gene of strain Hu17 ( murM Hu17 ), which is highly similar to murM of Streptococcus mitis , induced morphological changes which were partly reversed by ciaH232. murM Hu17 conferred cefotaxime resistance only in the presence of the pbp2x o f strain Hu17 ( pbp2x Hu17 ). The ciaH232 allele contributed to a remarkable increase in cefotaxime resistance in combination with pbp2x Hu17 and pbp1a of strain Hu17 ( pbp1a Hu17 ), accompanied by higher levels of expression of CiaR-regulated genes, documenting that ciaH232 responds to PBP1a Hu17 -mediated changes in cell wall synthesis. Most importantly, the proportion of branched peptides relative to the proportion of linear muropeptides increased in cells containing mosaic PBPs, suggesting an altered enzymatic activity of these proteins. Copyright © 2017 Schweizer et al.

Sexual reproduction and mating-type–mediated strain development in the penicillin-producing fungus Penicillium chrysogenum

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Böhm, Julia; Hoff, Birgit; O’Gorman, Céline M.; Wolfers, Simon; Klix, Volker; Binger, Danielle; Zadra, Ivo; Kürnsteiner, Hubert; Pöggeler, Stefanie; Dyer, Paul S.; Kück, Ulrich

2013-01-01

Penicillium chrysogenum is a filamentous fungus of major medical and historical importance, being the original and present-day industrial source of the antibiotic penicillin. The species has been considered asexual for more than 100 y, and despite concerted efforts, it has not been possible to induce sexual reproduction, which has prevented sexual crosses being used for strain improvement. However, using knowledge of mating-type (MAT) gene organization, we now describe conditions under which a sexual cycle can be induced leading to production of meiotic ascospores. Evidence of recombination was obtained using both molecular and phenotypic markers. The identified heterothallic sexual cycle was used for strain development purposes, generating offspring with novel combinations of traits relevant to penicillin production. Furthermore, the MAT1-1–1 mating-type gene, known primarily for a role in governing sexual identity, was also found to control transcription of a wide range of genes with biotechnological relevance including those regulating penicillin production, hyphal morphology, and conidial formation. These discoveries of a sexual cycle and MAT gene function are likely to be of broad relevance for manipulation of other asexual fungi of economic importance. PMID:23307807

Sexual reproduction and mating-type-mediated strain development in the penicillin-producing fungus Penicillium chrysogenum.

Science.gov (United States)

Böhm, Julia; Hoff, Birgit; O'Gorman, Céline M; Wolfers, Simon; Klix, Volker; Binger, Danielle; Zadra, Ivo; Kürnsteiner, Hubert; Pöggeler, Stefanie; Dyer, Paul S; Kück, Ulrich

2013-01-22

Penicillium chrysogenum is a filamentous fungus of major medical and historical importance, being the original and present-day industrial source of the antibiotic penicillin. The species has been considered asexual for more than 100 y, and despite concerted efforts, it has not been possible to induce sexual reproduction, which has prevented sexual crosses being used for strain improvement. However, using knowledge of mating-type (MAT) gene organization, we now describe conditions under which a sexual cycle can be induced leading to production of meiotic ascospores. Evidence of recombination was obtained using both molecular and phenotypic markers. The identified heterothallic sexual cycle was used for strain development purposes, generating offspring with novel combinations of traits relevant to penicillin production. Furthermore, the MAT1-1-1 mating-type gene, known primarily for a role in governing sexual identity, was also found to control transcription of a wide range of genes with biotechnological relevance including those regulating penicillin production, hyphal morphology, and conidial formation. These discoveries of a sexual cycle and MAT gene function are likely to be of broad relevance for manipulation of other asexual fungi of economic importance.

Screening of antibiotics and chemical analysis of penicillin residue in fresh milk and traditional dairy products in Oyo state, Nigeria

Directory of Open Access Journals (Sweden)

Isaac Olufemi Olatoye

2016-09-01

Full Text Available Background and Aim: There are global public health and economic concerns on chemical residues in food of animal origin. The use of antibiotics in dairy cattle for the treatment of diseases such as mastitis has contributed to the presence of residues in dairy products. Penicillin residues as low as 1 ppb can lead to allergic reactions and shift of resistance patterns in microbial population as well as interfere with the processing of several dairy products. Antibiotic monitoring is an essential quality control measure in safe milk production. This study was aimed at determining antibiotic residue contamination and the level of penicillin in dairy products from Fulani cattle herds in Oyo State. Materials and Methods: The presence of antibiotic residues in 328 samples of fresh milk, 180 local cheese (wara, and 90 fermented milk (nono from Southwest, Nigeria were determined using Premi® test kit (R-Biopharm AG, Germany followed by high-performance liquid chromatography analysis of penicillin-G residue. Results: Antibiotic residues were obtained in 40.8%, 24.4% and 62.3% fresh milk, wara and nono, respectively. Penicillin-G residue was also detected in 41.1% fresh milk, 40.2% nono and 24.4% wara at mean concentrations of 15.22±0.61, 8.24±0.50 and 7.6±0.60 μg/L with 39.3%, 36.7% and 21.1%, respectively, containing penicillin residue above recommended Codex maximum residue limit (MRL of 5 μg/L in dairy. There was no significant difference between the mean penicillin residues in all the dairy products in this study. Conclusion: The results are of food safety concern since the bulk of the samples and substantial quantities of dairy products in Oyo state contained violative levels of antibiotic residues including penicillin residues in concentrations above the MRL. This could be due to indiscriminate and unregulated administration of antibiotics to dairy cattle. Regulatory control of antibiotic use, rapid screening of milk and dairy farmers�

Misonidazole radiosensitization in vivo: A therapeutic gain by penicillin pretreatment

International Nuclear Information System (INIS)

Sheldon, P.W.; Clarke, C.; Dawson, K.B.; Simpson, W.; Simmons, D.J.C.; Adams, G.E.

1984-01-01

Because intestinal microflora have the potential to metabolize nitroimidazole compounds (possibly to toxic species), the authors investigated their influence on the pharmacological, neurotoxic and radiosensitizing properties of misonidazole (MIS) in mice. This was done by comparing the responses obtained in 'normal' mice to those obtained in mice whose microflora had been depleted by pretreatment for 7-14 days with penicillin (PEN) at the rate of 0.5g/1 of drinking water. Bacteriological studies showed this treatment to C57B1 mice eliminated more than 99% of the flora from the caeca and, furthermore, this efficacy of penicillin was not interfered with by MIS administered IP at 0.3mg/g between days 7-14. This pretreatment resulted not only in the elimination of the caecal flora, but also in an increase in the pharmacokinetic exposure to MIS, an increase in Lewis lung tumour radiosensitization by MIS and a decrease in MIS-induced neurotoxicity. The authors conclude pretreatment with PEN can give a therapeutic gain with MIS radiosensitization. Further, assuming no direct interaction between the PEN and MIS, these findings indicate that the intestinal flora may produce neurotoxic species by their metabolism of MIS

Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae.

Science.gov (United States)

Liu, Lifang; Feizi, Amir; Österlund, Tobias; Hjort, Carsten; Nielsen, Jens

2014-06-24

The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due to the poorly annotated proteome. Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three α-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER-associated processes (including components involved in the regulation of transport between ER and Golgi) were significantly up-regulated, with many of them never been identified for A. oryzae before. Furthermore, we defined a complete list of the putative A. oryzae secretome and monitored how it was affected by overproducing amylase. In combination with the transcriptome data, the most complete secretory component list and the putative secretome, we improved the systemic understanding of the secretory machinery of A. oryzae in response to high levels of protein secretion. The roles of many newly predicted secretory components were experimentally validated and the enriched component list provides a better platform for driving more mechanistic studies of the protein secretory pathway in this industrially important fungus.

The Three Major Spanish Clones of Penicillin-Resistant Streptococcus pneumoniae Are the Most Common Clones Recovered in Recent Cases of Meningitis in Spain

Science.gov (United States)

Enright, Mark C.; Fenoll, Asunción; Griffiths, David; Spratt, Brian G.

1999-01-01

One hundred six isolates of Streptococcus pneumoniae recovered in Spain from patients with meningitis in 1997 and 1998 were characterized by multilocus sequence typing. A heterogeneous collection of genotypes was associated with meningitis in Spain: 65 different sequence types were resolved and, even at a genetic distance of 0.43, there were 37 distinct lineages. Thirty-eight percent of the isolates, including all isolates of serotypes 6B, 9V, 14, and 23F, were resistant to penicillin, and 24% of the isolates were members of the three major Spanish penicillin-resistant or multidrug-resistant clones of serotypes 6B, 9V, and 23F or serotype variants of these clones. These three clones (MICs, 1 to 2 μg of penicillin/ml) were the most common clones associated with pneumococcal meningitis in Spain during 1997 and 1998. Only two of the other clones associated with meningitis were penicillin resistant (MICs, 0.12 to 0.5 μg/ml). One of the two most prevalent penicillin-susceptible clones causing meningitis (serotype 3) has not been detected outside of Spain, whereas the other (serotype 18C) has been recovered from patients with meningitis in the United Kingdom, The Netherlands, and Denmark. The prevalence of meningitis caused by isolates of the three major Spanish penicillin-resistant or multiply antibiotic-resistant clones, which are now globally distributed, is disturbing and clearly establishes their ability to cause life-threatening disease. PMID:10488179

Penicillin-Resistant trend of Streptococcus pneumoniae in Asia: A systematic review.

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Mamishi, Setareh; Moradkhani, Sepideh; Mahmoudi, Shima; Hosseinpour-Sadeghi, Reihaneh; Pourakbari, Babak

2014-08-01

The high prevalence of resistance to penicillin by Streptococcus pneumoniaeis considered as a great concern, particularly in Asian countries. The aim of this study was to investigate the changing trend of penicillin-resistant S. pneumoniae (PRSP) in Asia over a 20 years period. A review of the literature was conducted using the PubMed database, Google Scholar, Scopus, two Persian scientific search engines "Scientific Information Database" (www.sid.ir), and "Mag Iran" (www.magiran.com) through 1993 to 2013. Our study provides a unique chance to investigate the changing trend in PSSP in Asia over a 20 years period. Susceptibility rates among different centers in each country varied widely. In Malaysia, the PSSP rate decreased from 97.2% in 1995-1996 to 69% in 2000. In Singapore, PSSP levels decreased from 72.6% in 1997 to 30.5% in 2007-2008. In Iran, PSSP ranged from 0% to 100%. In Taiwan, the rate of PSSP was 60.3% in 1995 and countries such as Vietnam, Singapore, Philippines, Pakistan, Nepal, Kuwait, Korea and Indonesia.

Multi-party semi-quantum key distribution-convertible multi-party semi-quantum secret sharing

Science.gov (United States)

Yu, Kun-Fei; Gu, Jun; Hwang, Tzonelih; Gope, Prosanta

2017-08-01

This paper proposes a multi-party semi-quantum secret sharing (MSQSS) protocol which allows a quantum party (manager) to share a secret among several classical parties (agents) based on GHZ-like states. By utilizing the special properties of GHZ-like states, the proposed scheme can easily detect outside eavesdropping attacks and has the highest qubit efficiency among the existing MSQSS protocols. Then, we illustrate an efficient way to convert the proposed MSQSS protocol into a multi-party semi-quantum key distribution (MSQKD) protocol. The proposed approach is even useful to convert all the existing measure-resend type of semi-quantum secret sharing protocols into semi-quantum key distribution protocols.

Increasing incidence of penicillin- and cefotaxime-resistant Streptococcus pneumoniae causing meningitis in India: Time for revision of treatment guidelines?

Science.gov (United States)

Verghese, Valsan Philip; Veeraraghavan, Balaji; Jayaraman, Ranjith; Varghese, Rosemol; Neeravi, Ayyanraj; Jayaraman, Yuvaraj; Thomas, Kurien; Mehendale, Sanjay M

2017-01-01

Pneumococcal meningitis is a life-threatening infection, requiring prompt diagnosis and effective treatment. Penicillin resistance in pneumococcal infections is a concern. Here, we present the antibiotic susceptibility profile of pneumococcal meningeal isolates from January 2008 to August 2016 to elucidate treatment guidelines for pneumococcal meningitis. Invasive pneumococcal isolates from all age groups, were included in this study. Minimum inhibitory concentrations for the isolates were identified by agar dilution technique and VITEK System 2. Serotyping of isolates was done by co-agglutination technique. Out of 830 invasive pneumococcal isolates, 167 (20.1%) isolates were from meningeal infections. Cumulative penicillin resistance in pneumococcal meningitis was 43.7% and cefotaxime non-susceptibility was 14.9%. Penicillin resistance amongst meningeal isolates in those younger than 5 years, 5-16 years of age and those aged 16 years and older was 59.7%, 50% and 27.3%, respectively, with non-susceptibility to cefotaxime in the same age groups being 18%, 22.2% and 10.4%. Penicillin resistance amongst pneumococcal meningeal isolates increased from 9.5% in 2008 to 42.8% in 2016, whereas cefotaxime non-susceptibility increased from 4.7% in 2008 to 28.5% in 2016. Serotypes 14, 19F, 6B, 6A, 23F, 9V and 5 were the most common serotypes causing meningitis, with the first five accounting for over 75% of resistant isolates. The present study reports increasing penicillin resistance and cefotaxime non-susceptibility to pneumococcal meningitis in our setting. This highlights the need for empiric therapy with third-generation cephalosporins and vancomycin for all patients with meningitis while awaiting results of culture and susceptibility testing.

21 CFR 526.1696d - Penicillin G procaine-novobiocin for intramammary infusion.

Science.gov (United States)

2010-04-01

... of use—(1) Lactating cows—(i) Amount. 10 milliliters in each infected quarter after milking. Repeat once after 24 hours. (ii) Indications for use. Treating lactating cows for mastitis caused by... novobiocin as novobiocin sodium. For dry cows: 200,000 units of penicillin G procaine and 400 milligrams of...

DETECTION OF PNEUMOCOCCAL CAPSULAR ANTIGEN IN THE PRESENCE OF PENICILLIN IN-VITRO

NARCIS (Netherlands)

HOLLOWAY, Y; BOERSMA, WG; KUTTSCHRUTTER, H; SNIJDER, JAM

1993-01-01

Eight strains of Streptococcus pneumoniae were tested in vitro for their ability to produce capsular antigen in the presence of penicillin. It was found that, provided 10(6) to 10(7) pneumococci/ml were present, capsular antigen could be detected during the 72 h in which the experiment was

An oxygen dependent X-ray lesion in Escherichia coli strain B/r detected by penicillin

International Nuclear Information System (INIS)

Gillies, N.E.; Obioha, F.I.; Ratnajothi, N.H.

1979-01-01

Enhancement of lethal damage to E. coli B/r by penicillin was observed after X-irradiation under aerobic conditions, but not after exposure to X-rays under anoxia or after U.V. (260 nm) irradiation. No enhancement of damage occurred when incubation with penicillin was delayed for 2 hours after aerobic X-irradiation. This enhancing effect was only detected in this strain and not in the filamentous strain E. coli B. It was concluded that an X-ray induced lesion, sensitive to the presence of oxygen at the time of irradiation and probably located in the cell envelope, initiates filamentation in E. coli B/r, which results in lethal damage in this strain. (author)

Paired methods to measure biofilm killing and removal: a case study with Penicillin G treatment of Staphylococcus aureus biofilm.

Science.gov (United States)

Ausbacher, D; Lorenz, L; Pitts, B; Stewart, P S; Goeres, D M

2018-03-01

revealed efficient biofilm removal properties of Penicillin G which were not detected during efficacy testing. © 2017 The Society for Applied Microbiology.

The effects of octanol on penicillin induced epileptiform activity in rats: an in vivo study.

Science.gov (United States)

Bostanci, M Omer; Bağirici, Faruk

2006-10-01

The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. The reason for the pathologically synchronized discharges of the neuron is not exactly known yet. Recent reports claim that gap junctions have a critical role in neuronal synchronization. The present study was planned to investigate the effects of octanol, a gap junction blocker, on penicillin-induced experimental epilepsy. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. After the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When epileptiform activity, monitored from a digital recording system, reached at its maximum intensity, octanol was applied in the same way as penicillin administered. Application of octanol caused an inhibition in the epileptiform activity. Vehicle solution alone did not affect the epileptiform activity. Results of this study suggest that the blockade of electrical synapses may contribute to the prevention and amelioration of epileptic activity. Production of gap junction blockers selective for connexin types is needed. Further studies on the differential roles of gap junctions on certain epileptiform activities are required.

Burkholderia cenocepacia type VI secretion system mediates escape of type II secreted proteins into the cytoplasm of infected macrophages.

Directory of Open Access Journals (Sweden)

Roberto Rosales-Reyes

Full Text Available Burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. We have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (BcCVs resembling arrested autophagosomes. Intracellular bacteria stimulate IL-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion system (T6SS is required for these phenotypes but surprisingly it is not required for the maturation arrest of the BcCV. Here, we show that macrophages infected with B. cenocepacia employ the NLRP3 inflammasome to induce IL-1β secretion and pyroptosis. Moreover, IL-1β secretion by B. cenocepacia-infected macrophages is suppressed in deletion mutants unable to produce functional Type VI, Type IV, and Type 2 secretion systems (SS. We provide evidence that the T6SS mediates the disruption of the BcCV membrane, which allows the escape of proteins secreted by the T2SS into the macrophage cytoplasm. This was demonstrated by the activity of fusion derivatives of the T2SS-secreted metalloproteases ZmpA and ZmpB with adenylcyclase. Supporting this notion, ZmpA and ZmpB are required for efficient IL-1β secretion in a T6SS dependent manner. ZmpA and ZmpB are also required for the maturation arrest of the BcCVs and bacterial intra-macrophage survival in a T6SS-independent fashion. Our results uncover a novel mechanism for inflammasome activation that involves cooperation between two bacterial secretory pathways, and an unanticipated role for T2SS-secreted proteins in intracellular bacterial survival.

Penicillin-binding proteins in Actinobacteria.

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Ogawara, Hiroshi

2015-04-01

Because some Actinobacteria, especially Streptomyces species, are β-lactam-producing bacteria, they have to have some self-resistant mechanism. The β-lactam biosynthetic gene clusters include genes for β-lactamases and penicillin-binding proteins (PBPs), suggesting that these are involved in self-resistance. However, direct evidence for the involvement of β-lactamases does not exist at the present time. Instead, phylogenetic analysis revealed that PBPs in Streptomyces are distinct in that Streptomyces species have much more PBPs than other Actinobacteria, and that two to three pairs of similar PBPs are present in most Streptomyces species examined. Some of these PBPs bind benzylpenicillin with very low affinity and are highly similar in their amino-acid sequences. Furthermore, other low-affinity PBPs such as SCLAV_4179 in Streptomyces clavuligerus, a β-lactam-producing Actinobacterium, may strengthen further the self-resistance against β-lactams. This review discusses the role of PBPs in resistance to benzylpenicillin in Streptomyces belonging to Actinobacteria.

Open Secrets

OpenAIRE

Madison, Michael

2017-01-01

The law of trade secrets is often conceptualized in bilateral terms, as creating and enforcing rights between trade secret owners, on the one hand, and misappropriators on the other hand. This paper, a chapter in a forthcoming collection on the law of trade secrets, argues that trade secrets and the law that guards them can serve structural and insitutional roles as well. Somewhat surprisingly, given the law’s focus on secrecy, among the institutional products of trade secrets law are commons...

Quantum chemical study of penicillin: Reactions after acylation

Science.gov (United States)

Li, Rui; Feng, Dacheng; Zhu, Feng

The density functional theory methods were used on the model molecules of penicillin to determine the possible reactions after their acylation on ?-lactamase, and the results were compared with sulbactam we have studied. The results show that, the acylated-enzyme tetrahedral intermediate can evolves with opening of ?-lactam ring as well as the thiazole ring; the thiazole ring-open products may be formed via ?-lactam ring-open product or from tetrahedral intermediate directly. Those products, in imine or enamine form, can tautomerize via hydrogen migration. In virtue of the water-assisted, their energy barriers are obviously reduced.

Spread of Staphylococcus aureus resistant to penicillin and tetracycline within and between dairy herds

DEFF Research Database (Denmark)

Waage, S.; Bjorland, J.; Caugant, D. A.

2002-01-01

One hundred and seven bovine isolates of penicillin and tetracycline resistant Staphylococcus aureus, recovered from 25 different dairy herds in various parts of Norway, were characterized using antimicrobial susceptibility testing, multilocus enzyme electrophoresis, ribotyping, plasmid analysis ...

AtlA Functions as a Peptidoglycan Lytic Transglycosylase in the Neisseria gonorrhoeae Type IV Secretion System▿

OpenAIRE

Kohler, Petra L.; Hamilton, Holly L.; Cloud-Hansen, Karen; Dillard, Joseph P.

2007-01-01

Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We chara...

The prevalence and epidemiology of plasmid-mediated penicillin and tetracycline resistance among Neisseria gonorrhoeae isolates in Guangzhou, China, 2002-2012.

Science.gov (United States)

Zheng, Heping; Wu, Xingzhong; Huang, Jinmei; Qin, Xiaolin; Xue, Yaohua; Zeng, Weiying; Lan, Yinyuan; Ou, Jiangli; Tang, Sanmei; Fang, Mingheng

2015-10-09

Gonococcal antimicrobial resistance is a global problem. Different resistance plasmids have emerged and spread among the isolates of Neisseria gonorrhoeae worldwide and in China. We conducted this study to monitor the plasmid-mediated penicillin and tetracycline resistance among N. gonorrhoeae isolates in Guangzhou from 2002 to 2012. Consecutive isolates of N. gonorrhoeae were collected from outpatients with gonorrhea attending the STD clinic in Guangdong Provincial Centre for Skin Diseases and STIs Control and Prevention. Penicillinase-producing N. gonorrhoeae (PPNG) isolates were analyzed by the paper acidometric method. Plasmid-mediated resistance to tetracycline in N. gonorrhoeae (TRNG) isolates was screened by the agar plate dilution method. Plasmid types were determined for TRNG and PPNG isolates using polymerase chain reaction (PCR). Minimum inhibitory concentrations (MICs) to penicillin and tetracycline were detected by the agar plate dilution. Of 1378 consecutive N. gonorrhoeae isolates, 429 PPNG and 639 TRNG isolates were identified. The prevalence of PPNG, TRNG, and PPNG/TRNG increased from 18.3 to 47.1 % (χ (2) = 31.57, p penicillin G and tetracycline persisted at high levels and the MIC90s were 32-fold higher than the resistant cutoff point over 11 years. The prevalence rates of penicillin- and tetracycline-resistant N. gonorrhoeae varied from 90.9 to 91.1 % and from 88.3 to 89.3 % during 2002 to 2012, respectively. Resistance to penicillin and tetracycline among N. gonorrhoeae isolates remained at high levels in Guangzhou. The Asian type PPNG continued to spread and Dutch type TRNG was still the dominant strain. The African type PPNG has emerged and is spreading rapidly.

A systematic review: can one prescribe carbapenems to patients with IgE-mediated allergy to penicillins or cephalosporins?

Science.gov (United States)

Kula, Brittany; Djordjevic, Gordana; Robinson, Joan L

2014-10-15

Cross-reactivity between penicillins or cephalosporins and carbapenems is anticipated as all have a beta lactam ring. However, the true incidence of immunoglobulin (Ig)E-mediated cross-reactivity is not known. A systematic review was conducted to collect and combine all published data on children and adults reported to have a clinical history of IgE-mediated hypersensitivity to a penicillin and/or cephalosporin who were subsequently given a carbapenem. Reactions were classified as proven, suspected, or possible IgE-mediated and non-IgE-mediated. Ten studies and 12 case reports describing 854 participants fit the study criteria. For patients with previous proven, suspected, or possible IgE-mediated penicillin reactions (N = 838), the incidence of any type of suspected hypersensitivity reaction to a carbapenem was 36/838 (4.3%; 95% confidence interval [CI], 3.1%-5.9%) and the incidence of proven (1/838), suspected (0/838), or possible (19/838) IgE-mediated reactions was 20/838 (2.4%; 95% CI, 1.6%-3.7%). Of the subset of patients with positive penicillin skin tests (n = 295), only 1 had a hypersensitivity reaction (0.3%; 95% CI, .06%-1.9%), and this was a possible IgE-mediated reaction. For patients with previous proven, suspected, or possible IgE-mediated cephalosporin reactions (N = 12), the incidence of any type of hypersensitivity reaction to a carbapenem was 3/12 (25%); this included 2 non-IgE-mediated reactions and 1 possible IgE-mediated reaction. The cross-reactivity between penicillins and carbapenems for IgE-mediated reactions is very low, but caution is still advised. Cross-reactivity rates may be higher between cephalosporins and carbapenems; however, minimal data are available. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Synthesis of gold nanoparticles on the surface of pyrolytic graphite using penicillin as a stabilizing reagent and the catalytic oxidation of α-naphthylamine

Science.gov (United States)

Song, Y. Z.; Song, Y.; Cheng, Z. P.; Zhou, J. F.; Wei, C.

2013-01-01

Electrochemical synthesis of gold nanoparticles on the surface of pyrolytic graphite using penicillin as a stabilizing reagent was proposed. The gold nanoparticles were characterized by scanning electron microscopy, cyclic voltammetry, IR spectra, UV spectra, and powder X-ray diffraction spectra. The electro-chemical catalysis of penicillin for α-naphthylamine was demonstrated.

Multiparty quantum secret sharing of classical messages based on entanglement swapping

International Nuclear Information System (INIS)

Zhang Zhanjun; Man Zhongxiao

2005-01-01

A multiparty quantum secret sharing (QSS) protocol of classical messages (i.e., classical bits) is proposed by using swapping quantum entanglement of Bell states. The secret messages are imposed on Bell states by local unitary operations. The secret messages are split into several parts, and each part is distributed to a separate party so that no action of a subset of all the parties without the cooperation of the entire group is able to read out the secret messages. In addition, dense coding is used in this protocol to achieve a high efficiency. The security of the present multiparty QSS against eavesdropping has been analyzed and confirmed even in a noisy quantum channel

Production and characterization of two major Aspergillus oryzae secreted prolyl endopeptidases able to efficiently digest proline-rich peptides of gliadin.

Science.gov (United States)

Eugster, Philippe J; Salamin, Karine; Grouzmann, Eric; Monod, Michel

2015-12-01

Prolyl endopeptidases are key enzymes in the digestion of proline-rich proteins. Fungal extracts rich in prolyl endopeptidases produced by a species such as Aspergillus oryzae used in food fermentation would be of particular interest for the development of an oral enzyme therapy product in patients affected by intolerance to gluten. Two major A. oryzae secreted prolyl endopeptidases of the MEROPS S28 peptidase family, AoS28A and AoS28B, were identified when this fungus was grown at acidic pH in a medium containing soy meal protein or wheat gliadin as the sole source of nitrogen. AoS28B was produced by 12 reference A. oryzae strains used in food fermentation. AoS28A was secreted by six of these 12 strains. This protease is the orthologue of the previously characterized Aspergillus fumigatus (AfuS28) and Aspergillus niger (AN-PEP) prolyl endopeptidases which are encoded by genes with a similar intron-exon structure. Large amounts of secreted AoS28A and AoS28B were obtained by gene overexpression in A. oryzae. AoS28A and AoS28B are endoproteases able to cleave N-terminally blocked proline substrates. Both enzymes very efficiently digested the proline-rich 33-mer of gliadin, the most representative immunotoxic peptide deriving from gliadin, with some differences in terms of specificity and optimal pH. Digestion of the gliadin peptide in short peptides with both enzymes was found to occur from its N terminus.

A novel genetic system for recombinant protein secretion in the Antarctic Pseudoalteromonas haloplanktis TAC125

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Marino Gennaro

2006-12-01

Full Text Available Abstract Background The final aim of recombinant protein production is both to have a high specific production rate and a high product quality. It was already shown that using cold-adapted bacteria as host vectors, some "intractable" proteins can be efficiently produced at temperature as low as 4°C. Results A novel genetic system for the production and secretion of recombinant proteins in the Antarctic Gram-negative bacterium Pseudoalteromonas haloplanktis TAC125 was set up. This system aims at combining the low temperature recombinant product production with the advantages of extra-cellular protein targeting. The psychrophilic α-amylase from Pseudoalteromonas haloplanktis TAB23 was used as secretion carrier. Three chimerical proteins were produced by fusing intra-cellular proteins to C-terminus of the psychrophilic α-amylase and their secretion was analysed. Data reported in this paper demonstrate that all tested chimeras were translocated with a secretion yield always higher than 80%. Conclusion Data presented here demonstrate that the "cold" gene-expression system is efficient since the secretion yield of tested chimeras is always above 80%. These secretion performances place the α-amylase derived secretion system amongst the best heterologous secretion systems in Gram-negative bacteria reported so far. As for the quality of the secreted passenger proteins, data presented suggest that the system also allows the correct disulphide bond formation of chimera components, secreting a fully active passenger.

Penicillin treatment for patients with Community-Acquired Pneumonia in Denmark

DEFF Research Database (Denmark)

Egelund, Gertrud Baunbæk; Jensen, Andreas Vestergaard; Andersen, Stine Bang

2017-01-01

BACKGROUND: Community-acquired pneumonia (CAP) is a severe infection, with high mortality. Antibiotic strategies for CAP differ across Europe. The objective of the study was to describe the epidemiology of CAP in Denmark and evaluate the prognosis of patients empirically treated with penicillin......-G/V was commonly used and not associated with increased mortality in patients with mild to moderate pneumonia. Our results are in agreement with current conservative antibiotic strategy as outlined in the Danish guidelines....

Degradation of Penicillin G by heat activated persulfate in aqueous solution.

Science.gov (United States)

Norzaee, Samira; Taghavi, Mahmoud; Djahed, Babak; Kord Mostafapour, Ferdos

2018-06-01

We used Heat Activated of Persulfate (HAP) to decompose Penicillin G (PEN G) in aqueous solution. The effect of pH (3-11), temperature (313-353 K), and initial concentration of Sodium Persulfate (SPS) (0.05-0.5 mM) on the decomposition level of PEN G were investigated. The residue of PEN G was determined by spectrophotometry at the wavelength of 290 nm. Also, the Chemical Oxygen Demand (COD) was measured in each experiment. The Total Organic Carbon (TOC) analysis was utilized for surveying the mineralization of PEN G. In addition, based on Arrhenius equation, the activation energy of PEN G decomposition was calculated. The results indicated that the maximum PEN G removal rate was obtained at pH 5 and by increasing the doses of SPS from 0.05 to 0.5 mM, the PEN G decomposition was enhanced. It was found that an increase in temperature is accompanied by an increase in removal efficiency of PEN G. The activation energy of the studied process was determined to be 94.8 kJ mol -1 , suggesting that a moderate activation energy is required for PEN G decomposition. The TOC measurements indicate that the HAP can efficiently mineralize PEN G. Besides, the presence of the scavengers significantly suppressed the HAP process to remove the PEN G. Overall, the results of this study demonstrate that using HAP process can be a suitable method for decomposing of PEN G in aqueous solutions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Saturation mutagenesis reveals the importance of residues alpha R145 and alpha F146 of penicillin acylase in the synthesis of beta-lactam antibiotics

NARCIS (Netherlands)

Jager, Simon A. W.; Shapovalova, Irina V.; Jekel, Peter A.; Alkema, Wynand B. L.; Svedas, Vytas K.; Janssen, Dick B.; Švedas, Vytas K.

2008-01-01

Penicillin acylase (PA) from Escherichia coli can catalyze the coupling of an acyl group to penicillin- and cephalosporin-derived beta-lactam nuclei, a conversion that can be used for the industrial synthesis of beta-lactam. antibiotics. The modest synthetic properties of the wild-type enzyme make

Matching the proteome to the genome : the microbody of penicillin-producing Penicillium chrysogenum cells

NARCIS (Netherlands)

Kiel, Jan A. K. W.; van den Berg, Marco A.; Fusetti, Fabrizia; Poolman, Bert; Bovenberg, Roel A. L.; Veenhuis, Marten; van der Klei, Ida J.

In the filamentous fungus Penicillium chrysogenum, microbodies are essential for penicillin biosynthesis. To better understand the role of these organelles in antibiotics production, we determined the matrix enzyme contents of P. chrysogenum microbodies. Using a novel in silico approach, we first

Resolving Phenylalanine Metabolism Sheds Light on Natural Synthesis of Penicillin G in Penicillium chrysogenum

NARCIS (Netherlands)

Veiga, T.; Solis-Escalante, D.; Romagnoli, G.; Ten Pierick, A.; Hanemaaijer, M.; Deshmuhk, A.; Wahl, A.; Pronk, J.T.; Daran, J.M.

2011-01-01

The industrial production of penicillin G by Penicillium chrysogenum requires the supplementation of the growth medium with the side chain precursor phenylacetate. The growth of P. chrysogenum with phenylalanine as the sole nitrogen source resulted in the extracellular production of phenylacetate

Clonal relationships among penicillin-susceptible, multiresistant serotype 6B Streptococcus pneumoniae isolates recovered in Greece and France.

Science.gov (United States)

Syrogiannopoulos, G A; Doit, C; Grivea, I N; Geslin, P; Bingen, E

2001-01-01

In January 1996 the emergence of penicillin-susceptible, multiresistant serotype 6B Streptococcus pneumoniae isolates resistant to chloramphenicol, tetracycline, erythromycin, clindamycin and trimethoprim-sulfamethoxazole was observed in young carriers in the city of Patras, located in the southwestern region of Greece. Later, a significant spread of pneumococci with this unusual phenotype was noted in carriers living in various other areas of the country. Using restriction fragment length polymorphism of the ribosomal RNA genes, clonal relationships were found between these Greek strains and serotype 6B penicillin-susceptible, multiresistant pneumococci isolated in France between January 1992 and September 1996. The French and Greek isolates appear to have a common ancestry.

High Efficiency of Two Efficient QSDC with Authentication Is at the Cost of Their Security

International Nuclear Information System (INIS)

Su-Juan, Qin; Qiao-Yan, Wen; Luo-Ming, Meng; Fu-Chen, Zhu

2009-01-01

Two efficient protocols of quantum secure direct communication with authentication [Chin. Phys. Lett. 25 (2008) 2354] were recently proposed by Liu et al. to improve the efficiency of two protocols presented in [Phys. Rev. A 75 (2007) 026301] by four Pauli operations. We show that the high efficiency of the two protocols is at the expense of their security. The authenticator Trent can reach half the secret by a particular attack strategy in the first protocol. In the second protocol, not only Trent but also an eavesdropper outside can elicit half-information about the secret from the public declaration

A new (k,n verifiable secret image sharing scheme (VSISS

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Amitava Nag

2014-11-01

Full Text Available In this paper, a new (k,n verifiable secret image sharing scheme (VSISS is proposed in which third order LFSR (linear-feedback shift register-based public key cryptosystem is applied for the cheating prevention and preview before decryption. In the proposed scheme the secret image is first partitioned into several non-overlapping blocks of k pixels. Every k pixel is then used to form m=⌈k/4⌉+1 pixels of one encrypted share. The original secret image can be reconstructed by gathering any k or more encrypted shared images. The experimental results show that the proposed VSISS is an efficient and safe method.

Biosynthesis of ketomycin. (II) biomimetic model for beta-lactamase catalysis: host-guest interactions in cyclodextrin-penicillin inclusion complex

International Nuclear Information System (INIS)

Mak, H.W.

1986-01-01

The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid. Phenylalanine and 2',5'-dihydrophenylalanine derived from shikimic acid are not intermediates in the biosynthesis. Degradation of ketomycin derived from [1,6- 14 C]shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexane ring of ketomycin. The resistance of pathogenic bacteria to the action of β-lactam antibiotics is mainly ascribed to their ability to produce β-lactamase to cleave the β-lactam ring. It is essential to understand the molecular nature of β-lactamase-penicillin recognition for designing and formulating more effective β-lactam antibiotics. A biomimetic study of β-lactamase is therefore initiated. To meet the requirements of hydrophobic and serine protease characteristics of β-lactamase, α-cyclodextrin is chosen as a biomimetic model for β-lactamase. The structural specificity and the chemical dynamics of α-cyclodextrin-phenoxymethyl penicillin inclusion complex in solid state and in solution have been determined by IR and NMR spectroscopy. The spectral results strongly indicate that the phenyl portion of the phenoxymethyl penicillin forms a stable inclusion complex with the hydrophobic cavity of α-cyclodextrin in solution as well as in the solid state. Kinetic studies followed by 1 HNMR and HPLC analyses under alkaline condition have shown that the α-cyclodextrin mimics the catalytic function of serine of β-lactamase in the stereospecific hydrolysis of the β-lactam ring of phenoxymethyl penicillin

Important Mutations Contributing to High-Level Penicillin Resistance in Taiwan19F-14, Taiwan23F-15, and Spain23F-1 of Streptococcus pneumoniae Isolated from Taiwan.

Science.gov (United States)

Liu, Esther Yip-Mei; Chang, Jen-Chang; Lin, Jung-Chung; Chang, Feng-Yee; Fung, Chang-Phone

2016-12-01

Penicillin-resistant Streptococcus pneumoniae is a serious concern worldwide. In this study, we analyzed the cause of β-lactam resistance in pandemic multidrug-resistant clones. A total of 41 penicillin-nonsusceptible clinical isolates were collected from 1996 to 2012. Sero- and molecular typing confirmed that these isolates were clonal types of Taiwan 19F -14, Taiwan 23F -15, and Spain 23F -1. Sero-switching was found in four isolates. All isolates were multidrug resistant. Sequencing analysis of the penicillin binding proteins (PBPs) was performed on PBP1a, 2b, and 2x, and a large number of mutations were identified in comparing to clinical penicillin-susceptible isolates and the recipient strain R6 used for homologous recombination. The T 451 A substitution was the key amino acid in PBP2b that contributed to penicillin resistance. T 338 A in PBP2x played a role in resistance and reached the highest level of resistance when combined with other mutations in PBP2x. High-level penicillin resistance could not be obtained without the combination of mutations in PBP1a with PBP2b and 2x. The amino acid substitutions in PBP1a, 2b, and 2x were the crucial factors for β-lactam resistance.

Secret Sharing of a Quantum State.

Science.gov (United States)

Lu, He; Zhang, Zhen; Chen, Luo-Kan; Li, Zheng-Da; Liu, Chang; Li, Li; Liu, Nai-Le; Ma, Xiongfeng; Chen, Yu-Ao; Pan, Jian-Wei

2016-07-15

Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

Multiparty quantum secret sharing based on GHZ states

Energy Technology Data Exchange (ETDEWEB)

Hwang, Tzonelih; Hwang, Cheng-Chieh [Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, 701 Taiwan (China); Li, Chuan-Ming, E-mail: hwangtl@ismail.csie.ncku.edu.tw [Department of Information Management, Shu-Zen College of Medicine and Management, Kaohsiung, 821 Taiwan (China)

2011-04-15

Gao (2009 Commun. Theor. Phys. 52 421-4) has proposed an efficient multiparty quantum secret sharing (MQSS) with two-photon three-dimensional Einstein-Podolsky-Rosen (EPR) pairs. This work shows that a similar idea can also be used to construct an MQSS using the Greenberger-Horne-Zeilinger (GHZ) states. Compared to other MQSSs using GHZ-related states, the newly proposed protocol is more efficient in the aspect of qubit utilization.

Diversity and composition of vaginal microbiota of pregnant women at risk for transmitting Group B Streptococcus treated with intrapartum penicillin.

Directory of Open Access Journals (Sweden)

Luiz Fernando Wurdig Roesch

Full Text Available Administering intravenous antibiotics during labor to women at risk for transmitting Group B Streptococcus (GBS can prevent infections in newborns. However, the impact of intrapartum antibiotic prophylaxis on mothers' microbial community composition is largely unknown. We compared vaginal microbial composition in pregnant women experiencing preterm birth at ≤ 32 weeks gestation that received intrapartum antibiotic prophylaxis with that in controls.Microbiota in vaginal swabs collected shortly before delivery from GBS positive women that received penicillin intravenously during labor or after premature rupture of membranes was compared to controls. Microbiota was analyzed by 16S rRNA sequencing using the PGM Ion Torrent to determine the effects of penicillin use during hospitalization and GBS status on its composition.Penicillin administration was associated with an altered vaginal microbial community composition characterized by increased microbial diversity. Lactobacillus sp. contributed only 13.1% of the total community in the women that received penicillin compared to 88.1% in the controls. Streptococcus sp. were present in higher abundance in GBS positive woman compared to controls, with 60% of the total vaginal microbiota in severe cases identified as Streptococcus sp.Vaginal communities of healthy pregnant women were dominated by Lactobacillus sp. and contained low diversity, while Group B Streptococcus positive women receiving intrapartum antibiotic prophylaxis had a modified vaginal microbiota composition with low abundance of Lactobacillus but higher microbial diversity.

Diversity and composition of vaginal microbiota of pregnant women at risk for transmitting Group B Streptococcus treated with intrapartum penicillin.

Science.gov (United States)

Roesch, Luiz Fernando Wurdig; Silveira, Rita C; Corso, Andréa L; Dobbler, Priscila Thiago; Mai, Volker; Rojas, Bruna S; Laureano, Álvaro M; Procianoy, Renato S

2017-01-01

Administering intravenous antibiotics during labor to women at risk for transmitting Group B Streptococcus (GBS) can prevent infections in newborns. However, the impact of intrapartum antibiotic prophylaxis on mothers' microbial community composition is largely unknown. We compared vaginal microbial composition in pregnant women experiencing preterm birth at ≤ 32 weeks gestation that received intrapartum antibiotic prophylaxis with that in controls. Microbiota in vaginal swabs collected shortly before delivery from GBS positive women that received penicillin intravenously during labor or after premature rupture of membranes was compared to controls. Microbiota was analyzed by 16S rRNA sequencing using the PGM Ion Torrent to determine the effects of penicillin use during hospitalization and GBS status on its composition. Penicillin administration was associated with an altered vaginal microbial community composition characterized by increased microbial diversity. Lactobacillus sp. contributed only 13.1% of the total community in the women that received penicillin compared to 88.1% in the controls. Streptococcus sp. were present in higher abundance in GBS positive woman compared to controls, with 60% of the total vaginal microbiota in severe cases identified as Streptococcus sp. Vaginal communities of healthy pregnant women were dominated by Lactobacillus sp. and contained low diversity, while Group B Streptococcus positive women receiving intrapartum antibiotic prophylaxis had a modified vaginal microbiota composition with low abundance of Lactobacillus but higher microbial diversity.

Nanocrystalline-diamond thin films with high pH and penicillin sensitivity prepared on a capacitive Si-SiO2 structure

International Nuclear Information System (INIS)

Poghossian, A.; Abouzar, M.H.; Razavi, A.; Baecker, M.; Bijnens, N.; Williams, O.A.; Haenen, K.; Moritz, W.; Wagner, P.; Schoening, M.J.

2009-01-01

A capacitive field-effect EDIS (electrolyte-diamond-insulator-semiconductor) sensor with improved pH and penicillin sensitivity has been realised using a nanocrystalline-diamond (NCD) film as sensitive gate material. The NCD growth process on SiO 2 as well as an additional surface treatment in oxidising medium have been optimised to provide high pH-sensitive, non-porous O-terminated films without damage of the underlying SiO 2 layer. The surface morphology of O-terminated NCD thin films and the layer structure of EDIS sensors have been studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. To establish the relative coverage of the surface functional groups generated by the oxidation of NCD surfaces, X-ray photoelectron spectroscopy analysis was carried out. The hydrophilicity of NCD thin films has been studied by water contact-angle measurements. A nearly Nernstian pH sensitivity of 54-57 mV/pH has been observed for O-terminated NCD films treated in an oxidising boiling mixture for 80 min and in oxygen plasma. The high pH-sensitive properties of O-terminated NCD have been used to develop an EDIS-based penicillin biosensor. A freshly prepared penicillin biosensor possesses a high sensitivity of 85 mV/decade in the concentration range of 0.1-2.5 mM penicillin G. The lower detection limit is 5 μM.

Improving the secretion of a methyl parathion hydrolase in Pichia pastoris by modifying its N-terminal sequence.

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Ping Wang

Full Text Available Pichia pastoris is commonly used to express and secrete target proteins, although not all recombinant proteins can be successfully produced. In this study, we used methyl parathion hydrolase (MPH from Ochrobactrum sp. M231 as a model to study the importance of the N-terminus of the protein for its secretion. While MPH can be efficiently expressed intracellularly in P. pastoris, it is not secreted into the extracellular environment. Three MPH mutants (N66-MPH, D10-MPH, and N9-MPH were constructed through modification of its N-terminus, and the secretion of each by P. pastoris was improved when compared to wild-type MPH. The level of secreted D10-MPH was increased to 0.21 U/mL, while that of N9-MPH was enhanced to 0.16 U/mL. Although N66-MPH was not enzymatically active, it was secreted efficiently, and was identified by SDS-PAGE. These results demonstrate that the secretion of heterologous proteins in P. pastoris may be improved by modifying their N-terminal structures.

High level secretion of cellobiohydrolases by Saccharomyces cerevisiae

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Ahlgren Simon

2011-09-01

Full Text Available Abstract Background The main technological impediment to widespread utilization of lignocellulose for the production of fuels and chemicals is the lack of low-cost technologies to overcome its recalcitrance. Organisms that hydrolyze lignocellulose and produce a valuable product such as ethanol at a high rate and titer could significantly reduce the costs of biomass conversion technologies, and will allow separate conversion steps to be combined in a consolidated bioprocess (CBP. Development of Saccharomyces cerevisiae for CBP requires the high level secretion of cellulases, particularly cellobiohydrolases. Results We expressed various cellobiohydrolases to identify enzymes that were efficiently secreted by S. cerevisiae. For enhanced cellulose hydrolysis, we engineered bimodular derivatives of a well secreted enzyme that naturally lacks the carbohydrate-binding module, and constructed strains expressing combinations of cbh1 and cbh2 genes. Though there was significant variability in the enzyme levels produced, up to approximately 0.3 g/L CBH1 and approximately 1 g/L CBH2 could be produced in high cell density fermentations. Furthermore, we could show activation of the unfolded protein response as a result of cellobiohydrolase production. Finally, we report fermentation of microcrystalline cellulose (Avicel™ to ethanol by CBH-producing S. cerevisiae strains with the addition of beta-glucosidase. Conclusions Gene or protein specific features and compatibility with the host are important for efficient cellobiohydrolase secretion in yeast. The present work demonstrated that production of both CBH1 and CBH2 could be improved to levels where the barrier to CBH sufficiency in the hydrolysis of cellulose was overcome.

Investigation of β-lactam antibacterial drugs, β-lactamases, and penicillin-binding proteins with fluorescence polarization and anisotropy: a review

Science.gov (United States)

Shapiro, Adam B.

2016-06-01

This review covers the uses of fluorescence polarization and anisotropy for the investigation of bacterial penicillin binding proteins (PBPs), which are the targets of β-lactam antibacterial drugs (penicillins, cephalosporins, carbapenems, and monobactams), and of the β-lactamase enzymes that destroy these drugs and help to render bacterial pathogens resistant to them. Fluorescence polarization and anisotropy-based methods for quantitation of β-lactam drugs are also reviewed. A particular emphasis is on methods for quantitative measurement of the interactions of β-lactams and other inhibitors with PBPs and β-lactamases.

In-silico driven engineering of enantioselectivity of a penicillin G acylase towards active pharmaceutical ingredients

Czech Academy of Sciences Publication Activity Database

Grulich, Michal; Brezovský, J.; Štěpánek, Václav; Palyzová, Andrea; Marešová, Helena; Zahradník, Jiří; Kyslíková, Eva; Kyslík, Pavel

2016-01-01

Roč. 133, Supplement 1 (2016), s. 53-59 ISSN 1381-1177 Institutional support: RVO:61388971 Keywords : Docking experiments * Enantioselectivity * Penicillin G acylase Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.269, year: 2016

On Converting Secret Sharing Scheme to Visual Secret Sharing Scheme

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Wang Daoshun

2010-01-01

Full Text Available Abstract Traditional Secret Sharing (SS schemes reconstruct secret exactly the same as the original one but involve complex computation. Visual Secret Sharing (VSS schemes decode the secret without computation, but each share is m times as big as the original and the quality of the reconstructed secret image is reduced. Probabilistic visual secret sharing (Prob.VSS schemes for a binary image use only one subpixel to share the secret image; however the probability of white pixels in a white area is higher than that in a black area in the reconstructed secret image. SS schemes, VSS schemes, and Prob. VSS schemes have various construction methods and advantages. This paper first presents an approach to convert (transform a -SS scheme to a -VSS scheme for greyscale images. The generation of the shadow images (shares is based on Boolean XOR operation. The secret image can be reconstructed directly by performing Boolean OR operation, as in most conventional VSS schemes. Its pixel expansion is significantly smaller than that of VSS schemes. The quality of the reconstructed images, measured by average contrast, is the same as VSS schemes. Then a novel matrix-concatenation approach is used to extend the greyscale -SS scheme to a more general case of greyscale -VSS scheme.

Authentication Without Secrets

Energy Technology Data Exchange (ETDEWEB)

Pierson, Lyndon G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Robertson, Perry J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-11-01

This work examines a new approach to authentication, which is the most fundamental security primitive that underpins all cyber security protections. Current Internet authentication techniques require the protection of one or more secret keys along with the integrity protection of the algorithms/computations designed to prove possession of the secret without actually revealing it. Protecting a secret requires physical barriers or encryption with yet another secret key. The reason to strive for "Authentication without Secret Keys" is that protecting secrets (even small ones only kept in a small corner of a component or device) is much harder than protecting the integrity of information that is not secret. Promising methods are examined for authentication of components, data, programs, network transactions, and/or individuals. The successful development of authentication without secret keys will enable far more tractable system security engineering for high exposure, high consequence systems by eliminating the need for brittle protection mechanisms to protect secret keys (such as are now protected in smart cards, etc.). This paper is a re-release of SAND2009-7032 with new figures numerous edits.

Highly sensitive bacterial susceptibility test against penicillin using parylene-matrix chip.

Science.gov (United States)

Park, Jong-Min; Kim, Jo-Il; Song, Hyun-Woo; Noh, Joo-Yoon; Kang, Min-Jung; Pyun, Jae-Chul

2015-09-15

This work presented a highly sensitive bacterial antibiotic susceptibility test through β-lactamase assay using Parylene-matrix chip. β-lactamases (EC 3.5.2.6) are an important family of enzymes that confer resistance to β-lactam antibiotics by catalyzing the hydrolysis of these antibiotics. Here we present a highly sensitive assay to quantitate β-lactamase-mediated hydrolysis of penicillin into penicilloic acid. Typically, MALDI-TOF mass spectrometry has been used to quantitate low molecular weight analytes and to discriminate them from noise peaks of matrix fragments that occur at low m/z ratios (m/ztest was carried out using Parylene-matrix chip and MALDI-TOF mass spectrometry. The Parylene-matrix chip was successfully used to quantitate penicillin (m/z: [PEN+H](+)=335.1 and [PEN+Na](+)=357.8) and penicilloic acid (m/z: [PA+H](+)=353.1) in a β-lactamase assay with minimal interference of low molecular weight noise peaks. The β-lactamase assay was carried out with an antibiotic-resistant E. coli strain and an antibiotic-susceptible E. coli strain, revealing that the minimum number of E. coli cells required to screen for antibiotic resistance was 1000 cells for the MALDI-TOF mass spectrometry/Parylene-matrix chip assay. Copyright © 2015 Elsevier B.V. All rights reserved.

A new insight about pharmaceutical dosage forms for benzathine penicillin G

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K. G. Holanda e Silva

2009-01-01

Full Text Available

In this work, a micellar system of benzathine penicillin G (BPG in sodium deoxycholate (NaDC was developed and evaluated physicochemically. The solubility profile of the drug in water and buffer solutions at various pH was determined, as well as its n-octanol/water partition coefficient. The Critical Micellar Concentration of NaDC and its ability to incorporate BPG were also assessed. The study was carried out at low and high ionic strength which was adjusted by the addition of sodium chloride. The results demonstrated the ability of the micellar system to incorporate BPG, as well as to increase its apparent solubility in water. The enhancement of the solubility of BPG by the presence of NaDC micelles could be analyzed quantitatively within the framework of the pseudo-phase model. Concentration analysis showed that the micellar system could attain up to 90% incorporation of BPG. The incorporated drug is expected to exhibit improved stability, since the antibiotic enclosed in the hydrophobic core of micelles is rather shielded from the aqueous external environment. Keywords: Benzathine Penicillin G; micellar solubilization; micelles; pre-formulation; sodium deoxycholate.

Interleukin 18 secretion and its effect in improving Chimeric Antigen Receptors efficiency

Science.gov (United States)

Kim, Jae-Kun

Clinical trials have shown that chimeric antigen receptor T cells modified to target cancer cells expressing a surface antigen found on immature B-cells. The purpose of this experiment is to take a pro-inflammatory cytokine, and analyze its effect in improving the efficiency of the T cells. IL-18 has been previously shown to recruit T cells to the tumor site and improve their secretion of cytotoxic cytokines. A human model of the proposed armored T cell has been created and has shown success in combating cancer cells in vitro. The next step is to design and produce a murine model to test in vivo in immunocompetent mice. This research project aimed to create two models: one utilizing 2A peptides and another utilizing IRES elements as a multicistronic vector. Both models would require the insertion of the desired genes into SFG backbones. IRES, a DNA element which acts as a binding site for the transcriptional machinery to recognize which part of the DNA to transcribe, commonly found in bicistronic vectors, is large with 500-600 base pairs, and has a lower transgene expression rate. P2A is smaller, only consisting of about 20 amino acids, and typically has a higher transgene expression rate, which may or may not result in higher effectiveness of the model. I would like to thank Dr. Renier Brentjens for being a mentor who cared about giving his interns as much educational value as possible.

Influence of conversion of penicillin G into a basic derivative on its accumulation and subcellular localization in cultured macrophages

International Nuclear Information System (INIS)

Renard, C.; Vanderhaeghe, H.J.; Claes, P.J.; Zenebergh, A.; Tulkens, P.M.

1987-01-01

beta-Lactam antibiotics do not accumulate in phagocytes, probably because of their acidic character. We therefore synthesized a basic derivative of penicillin G, namely, 14 C-labeled N-(3-dimethylamino-propyl)benzylpenicillinamide (ABP), and studied its uptake and subcellular localization in J774 macrophages compared with that of 14 C-labeled penicillin G. Whereas the intracellular concentration (Ci) of penicillin G remained lower than its extracellular concentration (Ce), ABP reached a Ci/Ce ratio of 4 to 5. Moreover, approximately 50% of intracellular ABP was found associated with lysosomes after isopycnic centrifugation of cell homogenates in isoosmotic Percoll or hyperosmotic sucrose gradients. The behavior of ABP was thus partly consistent with the model of de Duve et al., in which they described the intralysosomal accumulation of weak organic bases in lysosomes. Although ABP is microbiologically inactive, our results show that beta-lactam antibiotics can be driven into cells by appropriate modification. Further efforts therefore may be warranted in the design of active compounds or prodrugs that may prove useful in the chemotherapy of intracellular infections

Resolution of alpha/beta-amino acids by enantioselective penicillin G acylase from Achromobacter sp

Czech Academy of Sciences Publication Activity Database

Grulich, Michal; Brezovský, J.; Štěpánek, Václav; Palyzová, Andrea; Kyslíková, Eva; Kyslík, Pavel

2015-01-01

Roč. 122, DEC 2015 (2015), s. 240-247 ISSN 1381-1177 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Penicillin G acylase * Enantioselectivity * Homologous model Subject RIV: CE - Biochemistry Impact factor: 2.189, year: 2015

The experience of intramuscular benzathine penicillin for prophylaxis of recurrent cellulitis: A cohort study

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Hsien-Meng Chen

2017-10-01

Conclusion: Intramuscular benzathine penicillin at a 4-week interval may be an effective prophylactic strategy to reduce the incidence of cellulitis. Further studies are necessary to determine the factors associated with failure of prophylaxis as well as optimal individualized dosage and dosing interval of the prophylactic agent.

Improving the industrial production of 6-APA: enzymatic hydrolysis of penicillin G in the presence of organic solvents.

Science.gov (United States)

Abian, Olga; Mateo, César; Fernández-Lorente, Gloria; Guisán, José M; Fernández-Lafuente, Roberto

2003-01-01

The hydrolysis of penicillin G in the presence of an organic solvent, used with the purpose of extracting it from the culture medium, may greatly simplify the industrial preparation of 6-APA. However, under these conditions, PGA immobilized onto Eupergit displays very low stability (half-life of 5 h in butanone-saturated water) and a significant degree of inhibition by the organic solvent (30%). The negative effect of the organic solvent strongly depended on the type of solvent utilized: water saturated with butanone (around 28% v/v) had a much more pronounced negative effect than that of methylisobutyl ketone (MIBK) (solubility in water was only 2%). These problems were sorted out by using a new penicillin G acylase derivative designed to work in the presence of organic solvents (with each enzyme molecule surrounded by an hydrophilic artificial environment) and a suitable organic solvent (MIBK). Using such solvent, this derivative kept its activity unaltered for 1 week at 32 degrees C. Moreover, the enzyme activity was hardly inhibited by the presence of the organic solvent. In this way, the new enzyme derivative thus prepared enables simplification of the industrial hydrolysis of penicillin G.

A lower isoelectric point increases signal sequence-mediated secretion of recombinant proteins through a bacterial ABC transporter.

Science.gov (United States)

Byun, Hyunjong; Park, Jiyeon; Kim, Sun Chang; Ahn, Jung Hoon

2017-12-01

Efficient protein production for industrial and academic purposes often involves engineering microorganisms to produce and secrete target proteins into the culture. Pseudomonas fluorescens has a TliDEF ATP-binding cassette transporter, a type I secretion system, which recognizes C-terminal LARD3 signal sequence of thermostable lipase TliA. Many proteins are secreted by TliDEF in vivo when recombined with LARD3, but there are still others that cannot be secreted by TliDEF even when LARD3 is attached. However, the factors that determine whether or not a recombinant protein can be secreted through TliDEF are still unknown. Here, we recombined LARD3 with several proteins and examined their secretion through TliDEF. We found that the proteins secreted via LARD3 are highly negatively charged with highly-acidic isoelectric points (pI) lower than 5.5. Attaching oligo-aspartate to lower the pI of negatively-charged recombinant proteins improved their secretion, and attaching oligo-arginine to negatively-charged proteins blocked their secretion by LARD3. In addition, negatively supercharged green fluorescent protein (GFP) showed improved secretion, whereas positively supercharged GFP did not secrete. These results disclosed that proteins' acidic pI and net negative charge are major factors that determine their secretion through TliDEF. Homology modeling for TliDEF revealed that TliD dimer forms evolutionarily-conserved positively-charged clusters in its pore and substrate entrance site, which also partially explains the pI dependence of the TliDEF-dependent secretions. In conclusion, lowering the isoelectric point improved LARD3-mediated protein secretion, both widening the range of protein targets for efficient production via secretion and signifying an important aspect of ABC transporter-mediated secretions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[A case of mucosa-associated lymphoid tissue lymphoma with penicillin allergy successfully treated with levofloxacin, minomycin and rabeprazole].

Science.gov (United States)

Konno, Tomoko; Motoori, Shigeatsu; Iwamoto, Nozomi; Miyazawa, Tomoe; Saito, Shigeyo; Kitagawa, Naoko; Saisho, Hiromitsu; Furuse, Junji; Itabashi, Masayuki

2010-10-01

A 52-year-old Japanese woman was referred to our Institute because of Helicobacter pylori(H. pylori)-positive gastric mucosa-associated lymphoid tissue(MALT)lymphoma. Since she had a penicillin allergy, we could not eradicate H. pylori using the standard triple therapy including amoxicillin. Additionally, H. pylori was resistant to both clarithromycin and metronidazole. So she was treated with minomycin (MINO), levofloxacin (LVFX), and rabeprazole (RPZ) based on a drug sensitivity test. MINO+LVFX+RPZ appear to be a promising, appropriate, and well-tolerated eradication regimen for H. pylori demonstrating resistance to both clarithromycin and metronidazole, and for patients who are allergic to penicillin.

Authenticated quantum secret sharing with quantum dialogue based on Bell states

International Nuclear Information System (INIS)

Abulkasim, Hussein; Hamad, Safwat; El Bahnasy, Khalid; Rida, Saad Z

2016-01-01

This work proposes a scheme that combines the advantages of a quantum secret sharing procedure and quantum dialogue. The proposed scheme enables the participants to simultaneously make mutual identity authentications, in a simulated scenario where the boss, Alice, shares a secret with her two agents Bob and Charlie. The secret is protected by checking photons to keep untrustworthy agents and outer attacks from getting useful information. Before the two agents cooperate to recover Alice’s secret, they must authenticate their identity using parts of a pre-shared key. In addition, the whole pre-shared key is reused as part of recovering the secret data to avoid any leaks of information. In comparison with previous schemes, the proposed method can efficiently detect eavesdropping and it is free from information leaks. Furthermore, the proposed scheme proved to be secure against man-in-the-middle attacks, impersonation attacks, entangled-and-measure attacks, participant attacks, modification attacks and Trojan-horse attacks. (paper)

Influencia de la concentración inhibitoria mínima de penicilina en la acción sinérgica de su combinación con gentamicina frente a estreptococos del grupo viridans Influence of penicillin minimal inhibitory concentration in the synergy between penicillin and gentamicin in viridans group streptococci

Directory of Open Access Journals (Sweden)

L. Vigliarolo

2007-06-01

Full Text Available Los porcentajes de resistencia a penicilina entre los estreptococos del grupo viridans han llegado a niveles superiores al 60% en algunos estudios realizados en la década pasada, y en recientes trabajos se los encontró asociados a un mayor índice de mortalidad en las bacteriemias. Aún no se conoce cuál es el nivel de concentración inhibitoria mínima de penicilina para el cual resulta imposible lograr un efecto sinérgico con algún aminoglucósido. Con este propósito, se estudió la sensibilidad a penicilina de 28 cepas de estreptococos del grupo viridans aisladas de materiales clínicamente significativos en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan". Se seleccionaron siete aislamientos pertenecientes al grupo mitis con distintas características de sensibilidad, y con ellos se ensayó la curva de muerte frente a penicilina, gentamicina y penicilina más gentamicina, con concentraciones de penicilina por encima y por debajo de su concentración inhibitoria mínima. En ningún caso se observó sinergia cuando la concentración de penicilina fue inferior a la concentración inhibitoria mínima, al menos en este grupo particular de estreptococos que presentaron concentraciones inhibitorias mínimas de gentamicina ³ 16 µg/ml. Se encontró sinergia en cinco de las siete cepas cuando se trabajó con concentraciones de penicilina superiores a la concentración inhibitoria mínima. En las otras dos, se detectaron enzimas modificadoras de aminoglucósidos.Penicillin resistance rates higher than 60% have been recorded in viridans group streptococci by some authors during the 90's and recently such resistance was associated with higher levels of mortality in bacteremia. The lowest minimal inhibitory concentration of penicillin for which synergy with aminoglycosides is not yet possible is still unknown. In order to try to dilucidate this puzzle, a study on the susceptibility to penicillin of 28 strains of viridans group streptococci

Nanocrystalline-diamond thin films with high pH and penicillin sensitivity prepared on a capacitive Si-SiO{sub 2} structure

Energy Technology Data Exchange (ETDEWEB)

Poghossian, A. [Institute of Nano- and Biotechnologies (INB), Aachen University of Applied Sciences, Campus Juelich, Juelich (Germany); Institute of Bio- and Nanosystems (IBN-2), Research Centre Juelich GmbH, Juelich (Germany)], E-mail: a.poghossian@fz-juelich.de; Abouzar, M.H.; Razavi, A.; Baecker, M. [Institute of Nano- and Biotechnologies (INB), Aachen University of Applied Sciences, Campus Juelich, Juelich (Germany); Institute of Bio- and Nanosystems (IBN-2), Research Centre Juelich GmbH, Juelich (Germany); Bijnens, N. [Institute for Materials Research, Hasselt University, Diepenbeek (Belgium); Williams, O.A.; Haenen, K. [Institute for Materials Research, Hasselt University, Diepenbeek (Belgium); Division IMOMEC, IMEC vzw., Diepenbeek (Belgium); Moritz, W. [Humboldt University Berlin, Berlin (Germany); Wagner, P. [Institute for Materials Research, Hasselt University, Diepenbeek (Belgium); Schoening, M.J. [Institute of Nano- and Biotechnologies (INB), Aachen University of Applied Sciences, Campus Juelich, Juelich (Germany); Institute of Bio- and Nanosystems (IBN-2), Research Centre Juelich GmbH, Juelich (Germany)

2009-10-30

A capacitive field-effect EDIS (electrolyte-diamond-insulator-semiconductor) sensor with improved pH and penicillin sensitivity has been realised using a nanocrystalline-diamond (NCD) film as sensitive gate material. The NCD growth process on SiO{sub 2} as well as an additional surface treatment in oxidising medium have been optimised to provide high pH-sensitive, non-porous O-terminated films without damage of the underlying SiO{sub 2} layer. The surface morphology of O-terminated NCD thin films and the layer structure of EDIS sensors have been studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. To establish the relative coverage of the surface functional groups generated by the oxidation of NCD surfaces, X-ray photoelectron spectroscopy analysis was carried out. The hydrophilicity of NCD thin films has been studied by water contact-angle measurements. A nearly Nernstian pH sensitivity of 54-57 mV/pH has been observed for O-terminated NCD films treated in an oxidising boiling mixture for 80 min and in oxygen plasma. The high pH-sensitive properties of O-terminated NCD have been used to develop an EDIS-based penicillin biosensor. A freshly prepared penicillin biosensor possesses a high sensitivity of 85 mV/decade in the concentration range of 0.1-2.5 mM penicillin G. The lower detection limit is 5 {mu}M.

The F309S mutation increases factor VIII secretion in human cell line

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Daianne Maciely Carvalho Fantacini

2016-06-01

Full Text Available ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

Culture Negative Listeria monocytogenes Meningitis Resulting in Hydrocephalus and Severe Neurological Sequelae in a Previously Healthy Immunocompetent Man with Penicillin Allergy

DEFF Research Database (Denmark)

Gaini, Shahin; Karlsen, Gunn Hege; Nandy, Anirban

2015-01-01

A previously healthy 74-year-old Caucasian man with penicillin allergy was admitted with evolving headache, confusion, fever, and neck stiffness. Treatment for bacterial meningitis with dexamethasone and monotherapy ceftriaxone was started. The cerebrospinal fluid showed negative microscopy...... the catheter. The patient had severe neurological sequelae. This case report emphasises the importance of covering empirically for Listeria monocytogenes in all patients with penicillin allergy with suspected bacterial meningitis. The case also shows that it is possible to have significant infection...

Distribution of Penicillin G Residues in Culled Dairy Cow Muscles: Implications for Residue Monitoring

Science.gov (United States)

The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which type of muscle should be analyzed. In order to determine if antibiotic residue levels are dependent on muscle type, 7 culled dairy cows were dosed with Penicillin G (Pen G) from ...

Device-independent secret-key-rate analysis for quantum repeaters

Science.gov (United States)

Holz, Timo; Kampermann, Hermann; Bruß, Dagmar

2018-01-01

The device-independent approach to quantum key distribution (QKD) aims to establish a secret key between two or more parties with untrusted devices, potentially under full control of a quantum adversary. The performance of a QKD protocol can be quantified by the secret key rate, which can be lower bounded via the violation of an appropriate Bell inequality in a setup with untrusted devices. We study secret key rates in the device-independent scenario for different quantum repeater setups and compare them to their device-dependent analogon. The quantum repeater setups under consideration are the original protocol by Briegel et al. [Phys. Rev. Lett. 81, 5932 (1998), 10.1103/PhysRevLett.81.5932] and the hybrid quantum repeater protocol by van Loock et al. [Phys. Rev. Lett. 96, 240501 (2006), 10.1103/PhysRevLett.96.240501]. For a given repeater scheme and a given QKD protocol, the secret key rate depends on a variety of parameters, such as the gate quality or the detector efficiency. We systematically analyze the impact of these parameters and suggest optimized strategies.

Heterologous protein secretion in Lactobacilli with modified pSIP vectors.

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Ingrid Lea Karlskås

Full Text Available We describe new variants of the modular pSIP-vectors for inducible gene expression and protein secretion in lactobacilli. The basic functionality of the pSIP system was tested in Lactobacillus strains representing 14 species using pSIP411, which harbors the broad-host-range Lactococcus lactis SH71rep replicon and a β-glucuronidase encoding reporter gene. In 10 species, the inducible gene expression system was functional. Based on these results, three pSIP vectors with different signal peptides were modified by replacing their narrow-host-range L. plantarum 256rep replicon with SH71rep and transformed into strains of five different species of Lactobacillus. All recombinant strains secreted the target protein NucA, albeit with varying production levels and secretion efficiencies. The Lp_3050 derived signal peptide generally resulted in the highest levels of secreted NucA. These modified pSIP vectors are useful tools for engineering a wide variety of Lactobacillus species.

Preparation of a 125I labeled derivative of penicillin to be used for radioimmunoassay

International Nuclear Information System (INIS)

Wal, J.-M.; Kann, Guy; Centre National de Recherches Zootechniques

1975-01-01

A 125 I-BSA Penicilloyl conjugate was prepared by coupling penicillin G to Bovine Serum Albumine previously labeled with iodine-125. The reaction of fixation by covalent binding was made in alkaline solution without the use of carbodiimide. Immunoreactivity and specific activity of this labeled conjugate enable radioimmunoassay of penicilloyl groups [fr

New penicillin-producing Penicillium species and an overview of section Chrysogena

DEFF Research Database (Denmark)

Houbraken, J.; Frisvad, Jens Christian; Seifert, K. A.

2012-01-01

Species classified in Penicillium sect. Chrysogena are primary soil-borne and the most well-known members are P. chrysogenum and P. nalgiovense. Penicillium chrysogenum has received much attention because of its role in the production on penicillin and as a contaminant of indoor environments....... Each species produces a unique extrolite profile. The species share phenotypic characters, such as good growth on CYA supplemented with 5 % NaCl, ter- or quarterverticillate branched conidiophores and short, ampulliform phialides (colours, production of ascomata and ascospores, shape...

High-yield secretion of recombinant proteins from the microalga Chlamydomonas reinhardtii

DEFF Research Database (Denmark)

Ramos Martinez, Erick Miguel; Fimognari, Lorenzo; Sakuragi, Yumiko

2017-01-01

Microalga-based biomanufacturing of recombinant proteins is attracting growing attention due to its advantages in safety, metabolic diversity, scalability and sustainability. Secretion of recombinant proteins can accelerate the use of microalgal platforms by allowing post......-translational modifications and easy recovery of products from the culture media. However, currently, the yields of secreted recombinant proteins are low, which hampers the commercial application of this strategy. This study aimed at expanding the genetic tools for enhancing secretion of recombinant proteins in Chlamydomonas...... in the endoplasmic reticulum (ER). Taken together, the results demonstrate the utility of the gametolysin signal sequence and (SP)n glycomodule to promote a more efficient biomanufacturing of microalgae-based recombinant proteins....

The Smart Grid - A saucerful of secrets?

International Nuclear Information System (INIS)

Wissner, Matthias

2011-01-01

To many, a lot of secrets are at the bottom of the often-cited catchphrase 'Smart Grid'. This article gives an overview of the options that information and communication technology (ICT) offers for the restructuring and modernisation of the German power system, in particular with a view towards its development into a Smart Grid and thus tries to reveal these secrets. After a short outline on the development of ICT in terms of technology types and their availability, the further analysis highlights upcoming challenges in all parts of the power value chain and possible solutions for these challenges through the intensified usage of ICT applications. They are examined with regard to their effectiveness and efficiency in the fields of generation, transmission, distribution and supply. Finally, potential obstacles that may defer the introduction of ICT into the power system are shown. The analysis suggests that if certain hurdles are taken, the huge potential of ICT can create additional value in various fields of the whole power value chain. This ranges from increased energy efficiency and the more sophisticated integration of decentralised (renewable) energy plants to a higher security of supply and more efficient organisation of market processes. The results are true for the German power market but can in many areas also be transferred to other industrialised nations with liberalised power markets.

LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

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Matson Jyl S

2008-02-01

Full Text Available Abstract Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

Tamper-proof secret image-sharing scheme for identifying cheated secret keys and shared images

Science.gov (United States)

Chen, Chien-Chang; Liu, Chong-An

2013-01-01

A (t,n) secret image-sharing scheme shares a secret image to n participants, and the t users recover the image. During the recovery procedure of a conventional secret image-sharing scheme, cheaters may use counterfeit secret keys or modified shared images to cheat other users' secret keys and shared images. A cheated secret key or shared image leads to an incorrect secret image. Unfortunately, the cheater cannot be identified. We present an exponent and modulus-based scheme to provide a tamper-proof secret image-sharing scheme for identifying cheaters on secret keys or shared images. The proposed scheme allows users to securely select their secret key. This assignment can be performed over networks. Modulus results of each shared image is calculated to recognize cheaters of a shared image. Experimental results indicate that the proposed scheme is excellent at identifying cheated secret keys and shared images.

[Proper antibiotic therapy. From penicillin to pharmacogenomic].

Science.gov (United States)

Caramia, G; Ruffini, E

2012-04-01

Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical

Proteomic Identification of Novel Secreted Antibacterial Toxins of the Serratia marcescens Type VI Secretion System*

Science.gov (United States)

Fritsch, Maximilian J.; Trunk, Katharina; Diniz, Juliana Alcoforado; Guo, Manman; Trost, Matthias; Coulthurst, Sarah J.

2013-01-01

It has recently become apparent that the Type VI secretion system (T6SS) is a complex macromolecular machine used by many bacterial species to inject effector proteins into eukaryotic or bacterial cells, with significant implications for virulence and interbacterial competition. “Antibacterial” T6SSs, such as the one elaborated by the opportunistic human pathogen, Serratia marcescens, confer on the secreting bacterium the ability to rapidly and efficiently kill rival bacteria. Identification of secreted substrates of the T6SS is critical to understanding its role and ability to kill other cells, but only a limited number of effectors have been reported so far. Here we report the successful use of label-free quantitative mass spectrometry to identify at least eleven substrates of the S. marcescens T6SS, including four novel effector proteins which are distinct from other T6SS-secreted proteins reported to date. These new effectors were confirmed as antibacterial toxins and self-protecting immunity proteins able to neutralize their cognate toxins were identified. The global secretomic study also unexpectedly revealed that protein phosphorylation-based post-translational regulation of the S. marcescens T6SS differs from that of the paradigm, H1-T6SS of Pseudomonas aeruginosa. Combined phosphoproteomic and genetic analyses demonstrated that conserved PpkA-dependent threonine phosphorylation of the T6SS structural component Fha is required for T6SS activation in S. marcescens and that the phosphatase PppA can reverse this modification. However, the signal and mechanism of PpkA activation is distinct from that observed previously and does not appear to require cell–cell contact. Hence this study has not only demonstrated that new and species-specific portfolios of antibacterial effectors are secreted by the T6SS, but also shown for the first time that PpkA-dependent post-translational regulation of the T6SS is tailored to fit the needs of different bacterial

Wrapped up in Covers: Preschoolers' Secrets and Secret Hiding Places

Science.gov (United States)

Corson, Kimberly; Colwell, Malinda J.; Bell, Nancy J.; Trejos-Castillo, Elizabeth

2014-01-01

In this qualitative study, interviews about children's secret hiding places were conducted with 3-5-year-olds (n?=?17) in a university sponsored preschool programme using art narratives. Since prior studies indicate that children understand the concept of a secret as early as five and that they associate secrets with hiding places, the purpose of…

Utility of surface enhanced Raman spectroscopy (SERS) for elucidation and simultaneous determination of some penicillins and penicilloic acid using hydroxylamine silver nanoparticles.

Science.gov (United States)

El-Zahry, Marwa R; Refaat, Ibrahim H; Mohamed, Horria A; Rosenberg, Erwin; Lendl, Bernhard

2015-11-01

Elucidation and quantitative determination of some of commonly used penicillins (ampicillin, penicillin G and carbenicillin) in the presence of their main degradation product (penicilloic acid) were developed. Forced acidic and basic degradation processes were applied at different time intervals. The formed degradation products were elucidated and quantified using surface enhanced Raman spectroscopy (SERS). Silver nanoparticles (AgNPs) prepared by reduction of silver nitrate using hydroxylamine-HCl in alkaline medium were used as SERS substrate. The results obtained in SERS were confirmed by the application of LC/MS method. The concentration range was 100-600 ng/ml in case of the studied penicillins and 100-700 ng/ml in case of penicilloic acid. An excellent correlation coefficient was found in case of ampicillin (r=0.9993) and in the case of penicilloic acid (r=0.9997). Validation procedures were carried out including precision, robustness and accuracy by comparing F- and t-values of both the proposed and reported methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Translation quality control is maintained by the penicillin resistance factor MurM in Streptococcus pneumoniae

DEFF Research Database (Denmark)

Shepherd, Jennifer; Ibba, Michael

2013-01-01

Streptococcus pneumoniae is a causative agent of nosocomial infections such as pneumonia, meningitis and septicaemia. Penicillin resistance in S. pneumoniae depends in part upon MurM, an aminoacyl-tRNA-ligase that attaches L-serine or L-alanine to the stem peptide lysine of Lipid II in cell wall...

Salmonella-secreted Virulence Factors

Energy Technology Data Exchange (ETDEWEB)

Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

2011-05-01

In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

Prophylactic penicillin by the full moon: a novel approach in Central Australia that may help to reduce the risk of rheumatic heart disease.

Science.gov (United States)

Kearns, T M; Schultz, R; McDonald, V; Andrews, R M

2010-01-01

Uptake of penicillin prophylaxis to prevent recurrent rheumatic fever and its sequela rheumatic heart disease (RHD) is not optimal in the Northern Territory of Australia. The Full Moon Strategy (the Strategy) was introduced in the Central Australian region in June 2006 to improve the uptake of prophylactic penicillin: clients and healthcare workers were encouraged to use the full moon as a cue for the timing of the 4 weekly prophylactic penicillin injection. To determine the impact and effectiveness of the Strategy on knowledge and uptake of benzathine penicillin prophylaxis for clients at risk of RHD, and for primary healthcare workers in Central Australia. Clients at risk of RHD in four remote Aboriginal communities and the town camps of Alice Springs were identified from the RHD database. Consenting clients or their carers were interviewed about their knowledge of the Strategy and the health promotional tools used. Their healthcare records were then reviewed for prophylaxis uptake 2 years prior to and 2 years following the introduction of the Strategy. Primary healthcare workers in the four remote communities who were available at the time of the study visit were interviewed about their knowledge and use of the Strategy and the health promotional tools. Fifty RHD clients and 19 healthcare workers were interviewed. Most were aware of the flipchart but less than half knew of the calendar poster, hand-held card or radio advertisement. Prophylaxis uptake increased significantly from 47% in the 2 years prior to the introduction of the Strategy, to 57% 2 years after the Strategy was introduced. Introduction of the Strategy coincided with an improvement in uptake of prophylaxis but not around the time of the full moon. Uptake of benzathine penicillin remains inadequate and further innovative measures are needed to control rheumatic fever and its sequela in Aboriginal and Torres Strait Islander people.

Cloning, purification, crystallization and preliminary crystallographic analysis of a penicillin-binding protein homologue from Pyrococcus abyssi

International Nuclear Information System (INIS)

Delfosse, Vanessa; Hugonnet, Jean-Emmanuel; Sougakoff, Wladimir; Mayer, Claudine

2005-01-01

The crystallization of a hypothetical penicillin-binding protein from the archaeon P. abyssi in space group C2 by hanging-drop vapour diffusion is reported. The genome of the hyperthermophilic archaeon Pyrococcus abyssi contains a gene (pab0087) encoding a penicillin-binding protein (PBP) homologue. This sequence consists of 447 residues and shows significant sequence similarity to low-molecular-weight PBPs and class C β-lactamases. The Pab0087 protein was overexpressed, purified and crystallized. Diffraction data from two different crystal forms were collected to 2.7 and 2.0 Å resolution. Both crystals belong to space group C2, with unit-cell parameters a = 160.59, b = 135.74, c = 113.02 Å, β = 117.36° and a = 166.97, b = 131.25, c = 189.39 Å, β = 113.81°, respectively. The asymmetric unit contains four and eight molecules, respectively, with fourfold non-crystallographic symmetry

Constants of the Alper and Howard-Flanders oxygen equation for damage to bacterial membrane, deduced from observations on the radiation-induced penicillin-sensitive lesion

International Nuclear Information System (INIS)

Obioha, F.I.; Gillies, N.E.; Cullen, B.M.; Walker, H.C.; Alper, T.

1984-01-01

E. coli were irradiated in the presence of 100% oxygen, oxygen-free nitrogen and mixtures of 1.01, 0.59, 0.3, 0.1 and 0.06% oxygen in nitrogen. Changes in sensitivity with pO 2 conformed with the Alper and Howard-Flanders equation for bacteria treated after irradiation by penicillin as well as for the untreated ones. Values of m were respectively 4.8 and 3.3; values of K were identical, within experimental error, (4.4 mmHg). Sensitivity to induction of the bacterial membrane penicillin-sensitive lesion was calculated from the difference in the reciprocals of D 0 values proper to untreated and treated bacteria, for every gas used. The value of m could not be directly calculated because the effect of penicillin on anoxically irradiated bacteria was not detectable. For that reason, a transformation of the oxygen equation was used, allowing estimates to be made of both m and K, provided the results conformed with the equation. Within experimental error they did. Calculated values of m and K for induction of the penicillin-sensitive lesion were respectively 8 and 5.9 mmHg, but it is shown that the oxygen enhancement ratio was probably underestimated and the value overestimated. (author)

The etiology of community-acquired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate therapy.

Science.gov (United States)

Charles, Patrick G P; Whitby, Michael; Fuller, Andrew J; Stirling, Robert; Wright, Alistair A; Korman, Tony M; Holmes, Peter W; Christiansen, Keryn J; Waterer, Grant W; Pierce, Robert J P; Mayall, Barrie C; Armstrong, John G; Catton, Michael G; Nimmo, Graeme R; Johnson, Barbara; Hooy, Michelle; Grayson, M L

2008-05-15

Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide. The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded. The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified. The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Cloning, overexpression, crystallization and preliminary X-ray crystallographic analysis of a slow-processing mutant of penicillin G acylase from Kluyvera citrophila

International Nuclear Information System (INIS)

Varshney, Nishant Kumar; Ramasamy, Sureshkumar; Brannigan, James A.; Wilkinson, Anthony J.; Suresh, C. G.

2013-01-01

The pac gene encoding penicillin G acylase from K. citrophila was cloned and a slow-processing site-directed mutant was prepared, expressed, purified and crystallized. Triclinic and monoclinic crystal forms were obtained which diffracted to 2.5 and 3.5 Å resolution, respectively. Kluyvera citrophila penicillin G acylase (KcPGA) has recently attracted increased attention relative to the well studied and commonly used Escherichia coli PGA (EcPGA) because KcPGA is more resilient to harsh conditions and is easier to immobilize for the industrial hydrolysis of natural penicillins to generate the 6-aminopenicillin (6-APA) nucleus, which is the starting material for semi-synthetic antibiotic production. Like other penicillin acylases, KcPGA is synthesized as a single-chain inactive pro-PGA, which upon autocatalytic processing becomes an active heterodimer of α and β chains. Here, the cloning of the pac gene encoding KcPGA and the preparation of a slow-processing mutant precursor are reported. The purification, crystallization and preliminary X-ray analysis of crystals of this precursor protein are described. The protein crystallized in two different space groups, P1, with unit-cell parameters a = 54.0, b = 124.6, c = 135.1 Å, α = 104.1, β = 101.4, γ = 96.5°, and C2, with unit-cell parameters a = 265.1, b = 54.0, c = 249.2 Å, β = 104.4°, using the sitting-drop vapour-diffusion method. Diffraction data were collected at 100 K and the phases were determined using the molecular-replacement method. The initial maps revealed electron density for the spacer peptide

Sustained release of bactericidal concentrations of penicillin in the pleural space via an antibiotic-eluting pigtail catheter coated with electrospun nanofibers: results from in vivo and in vitro studies.

Science.gov (United States)

Chao, Yin-Kai; Lee, Cheng-Hung; Liu, Kuo-Sheng; Wang, Yi-Chuan; Wang, Chih-Wei; Liu, Shih-Jung

2015-01-01

Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space. Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared. In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (Ppenicillin concentrations remained above the minimum inhibitory concentration breakpoint throughout the entire study period. In contrast, serum penicillin levels were significantly higher in Group 2 than in Group 1 (P<0.001). Notably, all Group 2 rabbits showed signs of systemic toxicity (paralytic ileus and weight loss). We conclude that our antibiotic-eluting catheter may serve as a novel therapeutic option to treat empyema.

Tolerance of Norway spruce (Picea abies [L.] Karst.) embryogenic tissue to penicillin, carbapenem and aminoglycoside antibiotics

Czech Academy of Sciences Publication Activity Database

Malá, J.; Pavingerová, Daniela; Cvrčková, H.; Bříza, Jindřich; Dostál, J.; Šíma, P.

2009-01-01

Roč. 55, č. 4 (2009), s. 156-161 ISSN 1212-4834 R&D Projects: GA MZe QH71290 Institutional research plan: CEZ:AV0Z50510513 Keywords : somatic embryogenesis * Norway spruce * penicillin antibiotics * Agrobacterium tumefaciens * carbapenem antibiotics Subject RIV: EB - Genetics ; Molecular Biology

A SIMULATION OF THE PENICILLIN G PRODUCTION BIOPROCESS APPLYING NEURAL NETWORKS

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A.J.G. da Cruz

1997-12-01

Full Text Available The production of penicillin G by Penicillium chrysogenum IFO 8644 was simulated employing a feedforward neural network with three layers. The neural network training procedure used an algorithm combining two procedures: random search and backpropagation. The results of this approach were very promising, and it was observed that the neural network was able to accurately describe the nonlinear behavior of the process. Besides, the results showed that this technique can be successfully applied to control process algorithms due to its long processing time and its flexibility in the incorporation of new data

OPTICAL STUDIES OF PENICILLIN GROUP IN RELATION TO THEIR MEDICAL ACTIVITY

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R. Jeevan Kumar

2017-11-01

Full Text Available The study of Medical activity of antibiotics is gaining momentum now a days owing to the importance of their curative values.  The Medical Activity correlated to molecular interactions,can be studied by various physical techniques, at present optical methods like Refractometry and Polarization are used to study the activity of a few antibiotics like Penicillin.  The Refractive Indices Mean Molecular Polarizability Diamagnetic Susceptibilities and Electron Ionisation Cross Section are interpreted in terms of dosages and the toxic effects if any due to over dosages are discussed critically.

Meaningful Share Generation for Increased Number of Secrets in Visual Secret-Sharing Scheme

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Mustafa Ulutas

2010-01-01

Full Text Available This paper presents a new scheme for hiding two halftone secret images into two meaningful shares created from halftone cover images. Meaningful shares are more desirable than noise-like (meaningless shares in Visual Secret Sharing because they look natural and do not attract eavesdroppers' attention. Previous works in the field focus on either increasing number of secrets or creating meaningful shares for one secret image. The method outlined in this paper both increases the number of secrets and creates meaningful shares at the same time. While the contrast ratio of shares is equal to that of Extended Visual Cryptography, two secrets are encoded into two shares as opposed to one secret in the Extended Visual Cryptography. Any two natural-looking images can be used as cover unlike the Halftone Visual Cryptography method where one cover should be the negative of the other cover image and can only encode one secret. Effectiveness of the proposed method is verified by an experiment.

A genome-wide RNAi screen identifies regulators of cholesterol-modified hedgehog secretion in Drosophila.

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Reid Aikin

Full Text Available Hedgehog (Hh proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development. It is currently not known how lipid-modified Hh is secreted and released from producing cells. We have performed a genome-wide RNAi screen in Drosophila melanogaster cells to identify regulators of Hh secretion. We found that cholesterol-modified Hh secretion is strongly dependent on coat protein complex I (COPI but not COPII vesicles, suggesting that cholesterol modification alters the movement of Hh through the early secretory pathway. We provide evidence that both proteolysis and cholesterol modification are necessary for the efficient trafficking of Hh through the ER and Golgi. Finally, we identified several putative regulators of protein secretion and demonstrate a role for some of these genes in Hh and Wingless (Wg morphogen secretion in vivo. These data open new perspectives for studying how morphogen secretion is regulated, as well as provide insight into regulation of lipid-modified protein secretion.

Establishment of an inducing medium for type III effector secretion in Xanthomonas campestris pv. campestris

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Guo-Feng Jiang

2013-09-01

Full Text Available It is well known that the type III secretion system (T3SS and type III (T3 effectors are essential for the pathogenicity of most bacterial phytopathogens and that the expression of T3SS and T3 effectors is suppressed in rich media but induced in minimal media and plants. To facilitate in-depth studies on T3SS and T3 effectors, it is crucial to establish a medium for T3 effector expression and secretion. Xanthomonas campestris pv. campestris (Xcc is a model bacterium for studying plant-pathogen interactions. To date no medium for Xcc T3 effector secretion has been defined. Here, we compared four minimal media (MME, MMX, XVM2, and XOM2 which are reported for T3 expression induction in Xanthomonas spp. and found that MME is most efficient for expression and secretion of Xcc T3 effectors. By optimization of carbon and nitrogen sources and pH value based on MME, we established XCM1 medium, which is about 3 times stronger than MME for Xcc T3 effectors secretion. We further optimized the concentration of phosphate, calcium, and magnesium in XCM1 and found that XCM1 with a lower concentration of magnesium (renamed as XCM2 is about 10 times as efficient as XCM1 (meanwhile, about 30 times stronger than MME. Thus, we established an inducing medium XCM2 which is preferred for T3 effector secretion in Xcc.

Diversity and subcellular distribution of archaeal secreted proteins

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Mechthild ePohlschroder

2012-07-01

Full Text Available Secreted proteins make up a significant percentage of a prokaryotic proteome and play critical roles in important cellular processes such as polymer degradation, nutrient uptake, signal transduction, cell wall biosynthesis and motility. The majority of archaeal proteins are believed to be secreted either in an unfolded conformation via the universally conserved Sec pathway or in a folded conformation via the Twin arginine transport (Tat pathway. Extensive in vivo and in silico analyses of N-terminal signal peptides that target proteins to these pathways have led to the development of computational tools that not only predict Sec and Tat substrates with high accuracy but also provide information about signal peptide processing and targeting. Predictions therefore include indications as to whether a substrate is a soluble secreted protein, a membrane or cell-wall anchored protein, or a surface structure subunit, and whether it is targeted for post-translational modification such as glycosylation or the addition of a lipid. The use of these in silico tools, in combination with biochemical and genetic analyses of transport pathways and their substrates, has resulted in improved predictions of the subcellular localization of archaeal secreted proteins, allowing for a more accurate annotation of archaeal proteomes, and has led to the identification of potential adaptations to extreme environments, as well as archaeal kingdom-specific pathways. A more comprehensive understanding of the transport pathways and post-translational modifications of secreted archaeal proteins will also generate invaluable insights that will facilitate the identification of commercially valuable archaeal enzymes and the development of heterologous systems in which to efficiently express them.

Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis.

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Daniil M Prigozhin

Full Text Available Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows that Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.

Cholecystokinin inhibits gastrin secretion independently of paracrine somatostatin secretion in the pig

DEFF Research Database (Denmark)

Schmidt, P T; Hansen, L; Hilsted, L

2004-01-01

BACKGROUND: Cholecystokinin inhibits the secretion of gastrin from antral G cells, an effect that is speculated to be mediated by D cells secreting somatostatin. The aim of the study was to test directly whether cholecystokinin inhibition of antral gastrin secretion is mediated by somatostatin....... METHODS: The effects of CCK on gastrin and somatostatin secretion were studied in isolated vascularly perfused preparations of pig antrum before and after immunoneutralization brought about by infusion of large amounts of a high affinity monoclonal antibody against somatostatin. RESULTS: CCK infusion...... at 10(-9) M and 10(-8) M decreased gastrin output to 70.5% +/- 7.6% (n = 8) and 76.3% +/- 3.6% (n = 7) of basal output, respectively. CCK at 10(-10) M had no effect (n = 6). Somatostatin secretion was dose-dependently increased by CCK infusion and increased to 268 +/- 38.2% (n = 7) of basal secretion...

A Proposal for Six Sigma Integration for Large-Scale Production of Penicillin G and Subsequent Conversion to 6-APA.

Science.gov (United States)

Nandi, Anirban; Pan, Sharadwata; Potumarthi, Ravichandra; Danquah, Michael K; Sarethy, Indira P

2014-01-01

Six Sigma methodology has been successfully applied to daily operations by several leading global private firms including GE and Motorola, to leverage their net profits. Comparatively, limited studies have been conducted to find out whether this highly successful methodology can be applied to research and development (R&D). In the current study, we have reviewed and proposed a process for a probable integration of Six Sigma methodology to large-scale production of Penicillin G and its subsequent conversion to 6-aminopenicillanic acid (6-APA). It is anticipated that the important aspects of quality control and quality assurance will highly benefit from the integration of Six Sigma methodology in mass production of Penicillin G and/or its conversion to 6-APA.

A Proposal for Six Sigma Integration for Large-Scale Production of Penicillin G and Subsequent Conversion to 6-APA

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Anirban Nandi

2014-01-01

Full Text Available Six Sigma methodology has been successfully applied to daily operations by several leading global private firms including GE and Motorola, to leverage their net profits. Comparatively, limited studies have been conducted to find out whether this highly successful methodology can be applied to research and development (R&D. In the current study, we have reviewed and proposed a process for a probable integration of Six Sigma methodology to large-scale production of Penicillin G and its subsequent conversion to 6-aminopenicillanic acid (6-APA. It is anticipated that the important aspects of quality control and quality assurance will highly benefit from the integration of Six Sigma methodology in mass production of Penicillin G and/or its conversion to 6-APA.

Multiparty Quantum Direct Secret Sharing of Classical Information with Bell States and Bell Measurements

Science.gov (United States)

Song, Yun; Li, Yongming; Wang, Wenhua

2018-02-01

This paper proposed a new and efficient multiparty quantum direct secret sharing (QDSS) by using swapping quantum entanglement of Bell states. In the proposed scheme, the quantum correlation between the possible measurement results of the members (except dealer) and the original local unitary operation encoded by the dealer was presented. All agents only need to perform Bell measurements to share dealer's secret by recovering dealer's operation without performing any unitary operation. Our scheme has several advantages. The dealer is not required to retain any photons, and can further share a predetermined key instead of a random key to the agents. It has high capacity as two bits of secret messages can be transmitted by an EPR pair and the intrinsic efficiency approaches 100%, because no classical bit needs to be transmitted except those for detection. Without inserting any checking sets for detecting the eavesdropping, the scheme can resist not only the existing attacks, but also the cheating attack from the dishonest agent.

Dynamic quantum secret sharing

International Nuclear Information System (INIS)

Jia, Heng-Yue; Wen, Qiao-Yan; Gao, Fei; Qin, Su-Juan; Guo, Fen-Zhuo

2012-01-01

In this Letter we consider quantum secret sharing (QSS) between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications. -- Highlights: ► We consider quantum secret sharing between a sender and a dynamic agent group, called dynamic quantum secret sharing (DQSS). ► In the DQSS, the change of the agent group is allowable during the procedure of sharing classical and quantum information. ► Two DQSS schemes are proposed based on a special kind of entangled state, starlike cluster states. ► Without redistributing all the shares, the changed agent group can reconstruct the sender's secret by their cooperation. ► Compared with the previous quantum secret sharing scheme, our schemes are more flexible and suitable for practical applications.

Comparison of secretory signal peptides for heterologous protein expression in microalgae: Expanding the secretion portfolio for Chlamydomonas reinhardtii.

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João Vitor Dutra Molino

Full Text Available Efficient protein secretion is a desirable trait for any recombinant protein expression system, together with simple, low-cost, and defined media, such as the typical media used for photosynthetic cultures of microalgae. However, low titers of secreted heterologous proteins are usually obtained, even with the most extensively studied microalga Chlamydomonas reinhardtii, preventing their industrial application. In this study, we aimed to expand and evaluate secretory signal peptides (SP for heterologous protein secretion in C. reinhardtii by comparing previously described SP with untested sequences. We compared the SPs from arylsulfatase 1 and carbonic anhydrase 1, with those of untried SPs from binding protein 1, an ice-binding protein, and six sequences identified in silico. We identified over 2000 unique SPs using the SignalP 4.0 software. mCherry fluorescence was used to compare the protein secretion of up to 96 colonies for each construct, non-secretion construct, and parental wild-type cc1690 cells. Supernatant fluorescence varied according to the SP used, with a 10-fold difference observed between the highest and lowest secretors. Moreover, two SPs identified in silico secreted the highest amount of mCherry. Our results demonstrate that the SP should be carefully selected and that efficient sequences can be coded in the C. reinhardtii genome. The SPs described here expand the portfolio available for research on heterologous protein secretion and for biomanufacturing applications.

Depletion of penicillin G residues in heavy sows after intramuscular injection. Part I: Tissue residue depletion

Science.gov (United States)

Heavy sows (n=126) were treated with penicillin G procaine at a 5x label dose (33,000 IU/kg) for 3 consecutive days by intramuscular (IM) injection using 3 separate patterns (treatments) of drug administration (42 sows per treatment). Treatments differed by pattern and maximum injection volume per s...

A note on the flora and fauna in the rumen of steers fed a feedlot bloat-provoking ration and the effect of penicillin.

Science.gov (United States)

BRYANT, M P; ROBINSON, I M; LINDAHL, I L

1961-11-01

A study was made of the predominant culturable bacteria and ciliate protozoa present in the rumen of two steers that were regularly bloating on a pelleted ratio containing 22% alfalfa meal, 16% soybean oil meal, 61% barley, and 1% common salt. The ruminal microorganisms in the two animals differed as indicated by a high total culture count of bacteria, an almost complete absence of ciliate protozoa, a low pH, and a difference in the proportions of presumptively identified predominant bacterial groups in one animal (steer 26) as compared with the other (steer 32). The first exposure of the animals to procaine penicillin (75 or 150 mg per day on 2 successive days) resulted in an abnormal ruminal flora 31 hr after the first treatment as indicated by drastic drops in total and cellulolytic bacterial counts and a change in the proportions of predominant bacterial groups. The animals refused feed for 32 to 48 hr after the first treatment. After feed consumption resumed, further treatment with 75 mg penicillin on 4 successive days did not appear to greatly alter the flora and did not result in feed refusal in animal 32. In animal 26, amounts of penicillin progressing from 50 to 200 mg per day did not result in feed refusals and observations on rumen ingesta samples during this period indicated a decrease in total bacterial count, a great increase in numbers of ciliate protozoa, a higher pH, and a change in the proportions of predominant bacterial groups so that the ruminal picture was much more similar to that of animal 32 than to its own during the pre-penicillin period. Bloat was not relieved except during the period of feed refusal. The results indicate that the ruminal flora rapidly adapts to penicillin and that bloat of the feedlot type can occur in animals with widely differing numbers and kinds of bacteria and protozoa. Feedlot bloat does not appear to be correlated with the occurrence or numbers of any of the individual predominant groups of bacteria cultured.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

Science.gov (United States)

Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

1993-05-01

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

Evaluation of a rapid immunochromatographic ODK-0901 test for detection of pneumococcal antigen in middle ear fluids and nasopharyngeal secretions.

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Muneki Hotomi

Full Text Available Since the incidence of penicillin-resistant Streptococcus pneumoniae has been increasing at an astonishing rate throughout the world, the need for accurate and rapid identification of pneumococci has become increasingly important to determine the appropriate antimicrobial treatment. We have evaluated an immunochromatographic test (ODK-0901 that detects pneumococcal antigens using 264 middle ear fluids (MEFs and 268 nasopharyngeal secretions (NPSs. A sample was defined to contain S. pneumoniae when optochin and bile sensitive alpha hemolytic streptococcal colonies were isolated by culture. The sensitivity and specificity of the ODK-0901 test were 81.4% and 80.5%, respectively, for MEFs from patients with acute otitis media (AOM. In addition, the sensitivity and specificity were 75.2% and 88.8%, respectively, for NPSs from patients with acute rhinosinusitis. The ODK-0901 test may provide a rapid and highly sensitive evaluation of the presence of S. pneumoniae and thus may be a promising method of identifying pneumococci in MEFs and NPSs.

Quantification of the physiochemical constraints on the export of spider silk proteins by Salmonella type III secretion

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Voigt Christopher A

2010-10-01

Full Text Available Abstract Background The type III secretion system (T3SS is a molecular machine in gram negative bacteria that exports proteins through both membranes to the extracellular environment. It has been previously demonstrated that the T3SS encoded in Salmonella Pathogenicity Island 1 (SPI-1 can be harnessed to export recombinant proteins. Here, we demonstrate the secretion of a variety of unfolded spider silk proteins and use these data to quantify the constraints of this system with respect to the export of recombinant protein. Results To test how the timing and level of protein expression affects secretion, we designed a hybrid promoter that combines an IPTG-inducible system with a natural genetic circuit that controls effector expression in Salmonella (psicA. LacO operators are placed in various locations in the psicA promoter and the optimal induction occurs when a single operator is placed at the +5nt (234-fold and a lower basal level of expression is achieved when a second operator is placed at -63nt to take advantage of DNA looping. Using this tool, we find that the secretion efficiency (protein secreted divided by total expressed is constant as a function of total expressed. We also demonstrate that the secretion flux peaks at 8 hours. We then use whole gene DNA synthesis to construct codon optimized spider silk genes for full-length (3129 amino acids Latrodectus hesperus dragline silk, Bombyx mori cocoon silk, and Nephila clavipes flagelliform silk and PCR is used to create eight truncations of these genes. These proteins are all unfolded polypeptides and they encompass a variety of length, charge, and amino acid compositions. We find those proteins fewer than 550 amino acids reliably secrete and the probability declines significantly after ~700 amino acids. There also is a charge optimum at -2.4, and secretion efficiency declines for very positively or negatively charged proteins. There is no significant correlation with hydrophobicity

Antimicrobial treatment of infective endocarditis caused by viridans streptococci highly susceptible to penicillin: historic overview and future considerations

NARCIS (Netherlands)

Verhagen, D. W. M.; Vedder, A. C.; Speelman, P.; van der Meer, J. T. M.

2006-01-01

In this article we present the path that led to current concepts regarding antimicrobial treatment of endocarditis caused by viridans streptococci highly susceptible to penicillin. Early treatment trials indicate that some patients with subacute endocarditis can be cured with shorter treatment

In-vitro activity and beta-lactamase stability of methicillin, isoxazolyl penicillins and cephalothin against coagulase-negative staphylococci

DEFF Research Database (Denmark)

Jarløv, J O; Rosdahl, V T; Mortensen, I

1988-01-01

-level of the isoxazolyl penicillins showed a high degree of uniformity. However more strains were resistant to cloxacillin and oxacillin than to dicloxacillin and flucloxacillin. Only a weak correlation was found between beta-lactamase production, and resistance to the six antibiotics. Methicillin was the most stable...

Frequency of resistance to penicillin and erythromycin of pneumococcal strains that caused ottis media

OpenAIRE

Jovanović Luka; Isailović Katarina; Opavski Nataša

2017-01-01

Introduction: Streptococcus pneumoniae is an important human pathogen and the most common cause of acute otitis media (AOM), especially in children. It is also a common cause of community acquired pneumonia, sepsis and bacterial meningitis. Drug of choice in the treatment of these disease are beta lactam antibiotics, and the first alternative are macrolides. The increasing prevalence of resistance to penicillin and macrolides, among pneumococci, has considerably complicated the treatment. Aim...

Evaluation of polymorphisms in pbp4 gene and genetic diversity in penicillin-resistant, ampicillin-susceptible Enterococcus faecalis from hospitals in different states in Brazil.

Science.gov (United States)

Infante, Victor Hugo Pacagnelli; Conceição, Natália; de Oliveira, Adriana Gonçalves; Darini, Ana Lúcia da Costa

2016-04-01

The aim of the present study was to verify whether penicillin-resistant, ampicillin-susceptible Enterococcus faecalis (PRASEF) occurred in Brazil prior to the beginning of the 21st century, and to verify whether ampicillin susceptibility can predict susceptibility to other β-lactams in E. faecalis with this inconsistent phenotype. The presence of polymorphisms in the pbp4 gene and genetic diversity among the isolates were investigated. Of 21 PRASEF analyzed, 5 (23.8%) and 4 (19.0%) were imipenem and piperacillin resistant simultaneously by disk diffusion and broth dilution respectively, contradicting the current internationally accepted standards of susceptibility testing. Sequencing of pbp4 gene revealed an amino acid substitution (Asp-573→Glu) in all PRASEF isolates but not in the penicillin-susceptible, ampicillin-susceptible E. faecalis. Most PRASEF (90.5%) had related pulsed-field gel electrophoresis profiles, but were different from other PRASEF described to date. Results demonstrate that penicillin-resistant, ampicillin-susceptible phenotype was already a reality in the 1990s in E. faecalis isolates in different Brazilian states, and some of these isolates were also imipenem- and piperacillin-resistant; therefore, internationally accepted susceptibility criteria cannot be applied to these isolates. According to pbp4 gene sequencing, this study suggests that a specific amino acid substitution in pbp4 gene found in all PRASEF analyzed is associated with penicillin resistance. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of pH values on the extracellular polysaccharide secreted by Acidithiobacillus ferrooxidans during chalcopyrite bioleaching

Science.gov (United States)

Yu, Run-lan; Liu, Jing; Tan, Jian-xi; Zeng, Wei-min; Shi, Li-juan; Gu, Guo-hua; Qin, Wen-qing; Qiu, Guan-zhou

2014-04-01

The pH value plays an important role in the bioleaching of sulphide minerals. The effect of pH values on the extracellular polysaccharide secreted by Acidithiobacillus ferrooxidans was investigated in different phases of bacterial growth during chalcopyrite bioleaching. It is found that extracellular polysaccharide secretion from the cells attached to chalcopyrite is more efficiently than that of the free cells in the bioleaching solution. Three factors, pH values, the concentration of soluble metal ions, and the bacterial growth and metabolism, affect extracellular polysaccharide secretion in the free cells, and are related to the bacterial growth phase. Extracellular polysaccharide secretion from the attached cells is mainly dependent on the pH value of the bacterial culture.

Simulating cloud environment for HIS backup using secret sharing.

Science.gov (United States)

Kuroda, Tomohiro; Kimura, Eizen; Matsumura, Yasushi; Yamashita, Yoshinori; Hiramatsu, Haruhiko; Kume, Naoto

2013-01-01

In the face of a disaster hospitals are expected to be able to continue providing efficient and high-quality care to patients. It is therefore crucial for hospitals to develop business continuity plans (BCPs) that identify their vulnerabilities, and prepare procedures to overcome them. A key aspect of most hospitals' BCPs is creating the backup of the hospital information system (HIS) data at multiple remote sites. However, the need to keep the data confidential dramatically increases the costs of making such backups. Secret sharing is a method to split an original secret message so that individual pieces are meaningless, but putting sufficient number of pieces together reveals the original message. It allows creation of pseudo-redundant arrays of independent disks for privacy-sensitive data over the Internet. We developed a secret sharing environment for StarBED, a large-scale network experiment environment, and evaluated its potential and performance during disaster recovery. Simulation results showed that the entire main HIS database of Kyoto University Hospital could be retrieved within three days even if one of the distributed storage systems crashed during a disaster.

Fatal and Near-Fatal Non-allergic Reactions in Patients with Underlying Cardiac Disease Receiving Benzathine Penicillin G in Israel and Switzerland

Directory of Open Access Journals (Sweden)

Matitiahu Berkovitch

2017-11-01

Full Text Available Benzathine Penicillin G (BPG is commonly used for treatment of penicillin-susceptible infections and secondary prevention of rheumatic fever. Death following administration of BPG is extremely rare—only a handful of cases have been described in the literature since the 1950's. In this case series from Israel and Switzerland, we describe nine cases of serious adverse reactions—six fatal reactions and three near-fatalities—occurring within minutes of receiving intramuscular BPG. Allergic reactions or faulty administration were not implicated in any of the cases; however, all patients had cardiac risk factors. This case series describes a relatively rare risk that should be borne in mind when prescribing BPG.

The localization of key Bacillus subtilis penicillin binding proteins during cell growth is determined by substrate availability

NARCIS (Netherlands)

Lages, Marta Carolina Afonso; Beilharz, Katrin; Angeles, Danae Morales; Veening, Jan-Willem; Scheffers, Dirk-Jan

2013-01-01

The shape of bacteria is maintained by the cell wall. The main component of the cell wall is peptidoglycan (PG) that is synthesized by penicillin binding proteins (PBPs). The correct positioning of PBPs is essential for the maintenance of cell shape. In the literature, two different models for

Crystallization and preliminary crystallographic analysis of the transpeptidase domain of penicillin-binding protein 2B from Streptococcus pneumoniae

Energy Technology Data Exchange (ETDEWEB)

Yamada, Mototsugu, E-mail: mototsugu-yamada@meiji.co.jp; Watanabe, Takashi; Baba, Nobuyoshi; Miyara, Takako; Saito, Jun; Takeuchi, Yasuo [Pharmaceutical Research Center, Meiji Seika Kaisha Ltd, 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567 (Japan)

2008-04-01

The selenomethionyl-substituted transpeptidase domain of penicillin-binding protein (PBP) 2B from S. pneumoniae was isolated from a limited proteolysis digest of the soluble form of recombinant PBP 2B and then crystallized. MAD data were collected to 2.4 Å resolution. Penicillin-binding protein (PBP) 2B from Streptococcus pneumoniae catalyzes the cross-linking of peptidoglycan precursors that occurs during bacterial cell-wall biosynthesis. A selenomethionyl (SeMet) substituted PBP 2B transpeptidase domain was isolated from a limited proteolysis digest of a soluble form of recombinant PBP 2B and then crystallized. The crystals belonged to space group P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 86.39, c = 143.27 Å. Diffraction data were collected to 2.4 Å resolution using the BL32B2 beamline at SPring-8. The asymmetric unit contains one protein molecule and 63.7% solvent.

Crystallization and preliminary crystallographic analysis of the transpeptidase domain of penicillin-binding protein 2B from Streptococcus pneumoniae

International Nuclear Information System (INIS)

Yamada, Mototsugu; Watanabe, Takashi; Baba, Nobuyoshi; Miyara, Takako; Saito, Jun; Takeuchi, Yasuo

2008-01-01

The selenomethionyl-substituted transpeptidase domain of penicillin-binding protein (PBP) 2B from S. pneumoniae was isolated from a limited proteolysis digest of the soluble form of recombinant PBP 2B and then crystallized. MAD data were collected to 2.4 Å resolution. Penicillin-binding protein (PBP) 2B from Streptococcus pneumoniae catalyzes the cross-linking of peptidoglycan precursors that occurs during bacterial cell-wall biosynthesis. A selenomethionyl (SeMet) substituted PBP 2B transpeptidase domain was isolated from a limited proteolysis digest of a soluble form of recombinant PBP 2B and then crystallized. The crystals belonged to space group P4 3 2 1 2, with unit-cell parameters a = b = 86.39, c = 143.27 Å. Diffraction data were collected to 2.4 Å resolution using the BL32B2 beamline at SPring-8. The asymmetric unit contains one protein molecule and 63.7% solvent

Quantum strongly secure ramp secret sharing

DEFF Research Database (Denmark)

Zhang, Paul; Matsumoto, Rytaro Yamashita

2015-01-01

Quantum secret sharing is a scheme for encoding a quantum state (the secret) into multiple shares and distributing them among several participants. If a sufficient number of shares are put together, then the secret can be fully reconstructed. If an insufficient number of shares are put together...... however, no information about the secret can be revealed. In quantum ramp secret sharing, partial information about the secret is allowed to leak to a set of participants, called an unqualified set, that cannot fully reconstruct the secret. By allowing this, the size of a share can be drastically reduced....... This paper introduces a quantum analog of classical strong security in ramp secret sharing schemes. While the ramp secret sharing scheme still leaks partial information about the secret to unqualified sets of participants, the strong security condition ensures that qudits with critical information can...

Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.

Science.gov (United States)

Torres, M J; Romano, A; Mayorga, C; Moya, M C; Guzman, A E; Reche, M; Juarez, C; Blanca, M

2001-09-01

Penicillin is no longer the most commonly prescribed beta-lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin-allergic subjects from a population where benzylpenicillin is not now the most frequently used beta-lactam. Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake. After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders. Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.

Penicillin-mediated changes in viable benthic diatom assemblages – insights about the relevance of bacteria across spatial and seasonal scales.

Digital Repository Service at National Institute of Oceanography (India)

DeCosta, P.M.; Anil, A.C.

environment) and seasonal (post-monsoon, pre-monsoon, monsoon) scales. Penicillin treatment resulted in bacterial suppression and a reduction in diatoms at the intertidal and mangrove sites having stable pennate-dominated assemblages. Diatom response...

21 CFR 526.1696b - Penicillin G procaine-dihydrostreptomycin in soybean oil for intramammary infusion (dry cows).

Science.gov (United States)

2010-04-01

... subclinical mastitis in dairy cows at the time of drying off, specifically against infections caused by... soybean oil for intramammary infusion (dry cows). 526.1696b Section 526.1696b Food and Drugs FOOD AND DRUG... infusion (dry cows). (a) Specifications. Each 10 milliliters of suspension contains penicillin G procaine...

Dynamic secrets in communication security

CERN Document Server

Xiao, Sheng; Towsley, Donald

2013-01-01

Dynamic secrets are constantly generated and updated from messages exchanged between two communication users. When dynamic secrets are used as a complement to existing secure communication systems, a stolen key or password can be quickly and automatically reverted to its secret status without disrupting communication. 'Dynamic Secrets in Communication Security' presents unique security properties and application studies for this technology. Password theft and key theft no longer pose serious security threats when parties frequently use dynamic secrets. This book also illustrates that a dynamic

Oxytetracycline and penicillin-G residues in cattle slaughtered in south-western Nigeria: implications for livestock disease management and public health.

Science.gov (United States)

Adesokan, Hezekiah K; Agada, Charity A; Adetunji, Victoria O; Akanbi, Ibikunle M

2013-01-01

After the discovery of indiscriminate antibiotic use in ready-for-slaughter cattle in south-western Nigeria, 90 tissue samples from randomly selected slaughtered cattle were evaluated for oxytetracycline and penicillin-G residues using high performance liquid chromatography and the data analysed by one-way Analysis of variance (ANOVA). The findings revealed residues of oxytetracycline (kidney: 9.47 µ/kg ± 3.24 µ/kg; liver: 12.73 µ/kg ± 4.39 µ/kg; muscle: 16.17 µ/kg ± 5.52 µ/kg) and penicillin-G (kidney: 6.27 µ/kg ± 2.46 µ/kg; liver: 8.5 µ/kg ± 2.80 µ/kg; muscle: 11.67 µ/kg ± 2.94 µ/kg) in all tissues screened. Significantly high levels (oxytetracycline: F = 16.77; penicillin-G: F = 29.38) were, however, found in muscles, followed by liver and then kidney – findings confirming recent antibiotic administration to the animals before slaughter. The dietary intakes through the tissues screened were 0.024% (oxytetracycline) and 0.017% (penicillin-G) of the acceptable daily intake (ADI). Although the concentrations in the tissues screened were below the maximum residue limits despite recent administration of these antibiotics before slaughter, the lower concentrations are suggestive of the probable low dosages often administered by those involved in indiscriminate use of antibiotics. This therefore raises serious concerns for the livestock industry as well as human health, given the resultant emergence and spread of resistant strains of bacterial pathogens that could ensue from prolonged use of low dosages of antibiotics. Additionally, the lower concentrations of the daily intakes notwithstanding, the plausible exposure to these antibiotics from other food sources is a cause for concern. Since antimicrobial misuse and its consequent effects are not just a problem limited to Nigeria but also a concern in sub-Saharan Africa, the need for national and international stakeholder intervention is emphasised.

Oxytetracycline and penicillin-G residues in cattle slaughtered in south-western Nigeria: Implications for livestock disease management and public health

Directory of Open Access Journals (Sweden)

Hezekiah K. Adesokan

2013-07-01

Full Text Available After the discovery of indiscriminate antibiotic use in ready-for-slaughter cattle in south-western Nigeria, 90 tissue samples from randomly selected slaughtered cattle were evaluated for oxytetracycline and penicillin-G residues using high performance liquid chromatography and the data analysed by one-way Analysis of variance (ANOVA. The findings revealed residues of oxytetracycline (kidney: 9.47 µ/kg ± 3.24 µ/kg; liver: 12.73 µ/kg ± 4.39 µ/kg; muscle: 16.17 µ/kg ± 5.52 µ/kg and penicillin-G (kidney: 6.27 µ/kg ± 2.46 µ/kg; liver: 8.5 µ/kg ± 2.80 µ/kg; muscle: 11.67 µ/kg ± 2.94 µ/kg in all tissues screened. Significantly high levels (oxytetracycline: F = 16.77; penicillin-G: F = 29.38 were, however, found in muscles, followed by liver and then kidney – findings confirming recent antibiotic administration to the animals before slaughter. The dietary intakes through the tissues screened were 0.024% (oxytetracycline and 0.017% (penicillin-G of the acceptable daily intake (ADI. Although the concentrations in the tissues screened were below the maximum residue limits despite recent administration of these antibiotics before slaughter, the lower concentrations are suggestive of the probable low dosages often administered by those involved in indiscriminate use of antibiotics. This therefore raises serious concerns for the livestock industry as well as human health, given the resultant emergence and spread of resistant strains of bacterial pathogens that could ensue from prolonged use of low dosages of antibiotics. Additionally, the lower concentrations of the daily intakes notwithstanding, the plausible exposure to these antibiotics from other food sources is a cause for concern. Since antimicrobial misuse and its consequent effects are not just a problem limited to Nigeria but also a concern in sub-Saharan Africa, the need for national and international stakeholder intervention is emphasised.

Efficient quantum secure communication with a publicly known key

International Nuclear Information System (INIS)

Li Chunyan; Li Xihan; Deng Fuguo; Zhou Hongyu

2008-01-01

This paper presents a simple way for an eavesdropper to eavesdrop freely the secret message in the experimental realization of quantum communication protocol proposed by Beige et al (2002 Acta Phys. Pol. A 101 357). Moreover, it introduces an efficient quantum secure communication protocol based on a publicly known key with decoy photons and two biased bases by modifying the original protocol. The total efficiency of this new protocol is double that of the original one. With a low noise quantum channel, this protocol can be used for transmitting a secret message. At present, this protocol is good for generating a private key efficiently. (general)

Influence of external mass transfer limitation on apparent kinetic parameters of penicillin G acylase immobilized on nonporous ultrafine silica particles.

Science.gov (United States)

Kheirolomoom, Azadeh; Khorasheh, Farhad; Fazelinia, Hossein

2002-01-01

Immobilization of enzymes on nonporous supports provides a suitable model for investigating the effect of external mass transfer limitation on the reaction rate in the absence of internal diffusional resistance. In this study, deacylation of penicillin G was investigated using penicillin acylase immobilized on ultrafine silica particles. Kinetic studies were performed within the low-substrate-concentration region, where the external mass transfer limitation becomes significant. To predict the apparent kinetic parameters and the overall effectiveness factor, knowledge of the external mass transfer coefficient, k(L)a, is necessary. Although various correlations exist for estimation of k(L)a, in this study, an optimization scheme was utilized to obtain this coefficient. Using the optimum values of k(L)a, the initial reaction rates were predicted and found to be in good agreement with the experimental data.

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

Energy Technology Data Exchange (ETDEWEB)

Lee, Je Min, E-mail: jemin@knu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of); Department of Horticultural Science, Kyungpook National University, Daegu (Korea, Republic of); Lee, Sang-Jik [Biotechnology Institute, Nongwoo Bio Co, Ltd, Yeoju (Korea, Republic of); Department of Plant Biology, Cornell University, Ithaca, NY (United States); Rose, Jocelyn K.C. [Department of Plant Biology, Cornell University, Ithaca, NY (United States); Yeam, Inhwa [Department of Horticulture and Breeding, Andong National University, Andong (Korea, Republic of); Kim, Byung-Dong [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seoul (Korea, Republic of)

2014-04-18

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening.

Mining secreted proteins that function in pepper fruit development and ripening using a yeast secretion trap (YST)

International Nuclear Information System (INIS)

Lee, Je Min; Lee, Sang-Jik; Rose, Jocelyn K.C.; Yeam, Inhwa; Kim, Byung-Dong

2014-01-01

Highlights: • Yeast secretion trap (YST) is a valuable tool for mining secretome. • A total of 80 secreted proteins are newly identified via YST in pepper fruits. • The secreted proteins are differentially regulated during pepper development and ripening. • Transient GFP-fusion assay and in planta secretion trap can effectively validate the secretion of proteins. - Abstract: Plant cells secrete diverse sets of constitutively- and conditionally-expressed proteins under various environmental and developmental states. Secreted protein populations, or secretomes have multiple functions, including defense responses, signaling, metabolic processes, and developmental regulation. To identify genes encoding secreted proteins that function in fruit development and ripening, a yeast secretion trap (YST) screen was employed using pepper (Capsicum annuum) fruit cDNAs. The YST screen revealed 80 pepper fruit-related genes (CaPFRs) encoding secreted proteins including cell wall proteins, several of which have not been previously described. Transient GFP-fusion assay and an in planta secretion trap were used to validate the secretion of proteins encoded by selected YST clones. In addition, RNA gel blot analyses provided further insights into their expression and regulation during fruit development and ripening. Integrating our data, we conclude that the YST provides a valuable functional genomics tool for the identification of substantial numbers of novel secreted plant proteins that are associated with biological processes, including fruit development and ripening

Testing the sensitivity of Staphylococcus aureus antibiotics

Directory of Open Access Journals (Sweden)

Marioara Nicoleta FILIMON

2009-11-01

Full Text Available This study has in view to establish and test the sensitivity of Staphylococcus aureus antibiotics. There are different injuries caused by superficial skin infections: from simple pimples to infections that endanger our lives, like an abscess, furuncle septicemia, meningitis, toxic food, urinary tract infection at sexually active young women. Samples have been taken from 30 people with staphylococcus infections. They were nineteen women and eleven men, between the age of 2 and 79. During this study some antibiograms have been made, based on pharyngeal exudates, acne secretion and urine culture. It has been established that the most efficient recommended antibiotics are: oxacilin, erythromycin, rifampicin and ciprofloxacin. The penicillin turned out to be less efficient to remove and destroy the Staphylococcus aureus species.

Immunoglobins in mammary secretions

DEFF Research Database (Denmark)

Hurley, W L; Theil, Peter Kappel

2013-01-01

Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... the immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

Inhibition of bacterial DD-peptidases (penicillin-binding proteins) in membranes and in vivo by peptidoglycan-mimetic boronic acids.

Science.gov (United States)

Dzhekieva, Liudmila; Kumar, Ish; Pratt, R F

2012-04-03

The DD-peptidases or penicillin-binding proteins (PBPs) catalyze the final steps of bacterial peptidoglycan biosynthesis and are inhibited by the β-lactam antibiotics. There is at present a question of whether the active site structure and activity of these enzymes is the same in the solubilized (truncated) DD-peptidase constructs employed in crystallographic and kinetics studies as in membrane-bound holoenzymes. Recent experiments with peptidoglycan-mimetic boronic acids have suggested that these transition state analogue-generating inhibitors may be able to induce reactive conformations of these enzymes and thus inhibit strongly. We have now, therefore, measured the dissociation constants of peptidoglycan-mimetic boronic acids from Escherichia coli and Bacillus subtilis PBPs in membrane preparations and, in the former case, in vivo, by means of competition experiments with the fluorescent penicillin Bocillin Fl. The experiments showed that the boronic acids bound measurably (K(i) DD-peptidase inhibitors are more or less effective in vivo than in homogeneous solution.

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

Science.gov (United States)

Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

2017-01-01

There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

Extracellular secretion of recombinant proteins

Science.gov (United States)

Linger, Jeffrey G.; Darzins, Aldis

2014-07-22

Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

AtlA functions as a peptidoglycan lytic transglycosylase in the Neisseria gonorrhoeae type IV secretion system.

Science.gov (United States)

Kohler, Petra L; Hamilton, Holly L; Cloud-Hansen, Karen; Dillard, Joseph P

2007-08-01

Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We characterized the enzymatic function of AtlA in order to examine its role in the type IV secretion system. Purified AtlA was found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro peptidoglycan monomers, characteristic of lytic transglycosylase activity. We found that AtlA can functionally replace the lambda endolysin to lyse Escherichia coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing strain. The gonococcal type IV secretion system secretes DNA during growth. A deletion of ltgX or a substitution in the putative active site of AtlA severely decreased DNA secretion. These results indicate that AtlA and LtgX are actively involved in type IV secretion and that AtlA is not involved in lysis of gonococci to release DNA. This is the first demonstration that a type IV secretion peptidoglycanase has lytic transglycosylase activity. These data show that AtlA plays a role in type IV secretion of DNA that requires peptidoglycan breakdown without cell lysis.

Pituitary-hormone secretion by thyrotropinomas.

Science.gov (United States)

Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M; Biermasz, Nienke R; Smit, Jan W; Frolich, Marijke; Keenan, Daniel M; Veldhuis, Johannes D; Romijn, Johannes A

2009-01-01

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.

Semiquantum secret sharing using entangled states

International Nuclear Information System (INIS)

Li Qin; Chan, W. H.; Long Dongyang

2010-01-01

Secret sharing is a procedure for sharing a secret among a number of participants such that only the qualified subsets of participants have the ability to reconstruct the secret. Even in the presence of eavesdropping, secret sharing can be achieved when all the members are quantum. So what happens if not all the members are quantum? In this paper, we propose two semiquantum secret sharing protocols by using maximally entangled Greenberger-Horne-Zeilinger-type states in which quantum Alice shares a secret with two classical parties, Bob and Charlie, in a way that both parties are sufficient to obtain the secret, but one of them cannot. The presented protocols are also shown to be secure against eavesdropping.

Identification of a Novel Conjugative Plasmid in Mycobacteria That Requires Both Type IV and Type VII Secretion

KAUST Repository

Ummels, R.

2014-09-23

Conjugative plasmids have been identified in a wide variety of different bacteria, ranging from proteobacteria to firmicutes, and conjugation is one of the most efficient routes for horizontal gene transfer. The most widespread mechanism of plasmid conjugation relies on different variants of the type IV secretion pathway. Here, we describe the identification of a novel type of conjugative plasmid that seems to be unique for mycobacteria. Interestingly, while this plasmid is efficiently exchanged between different species of slow-growing mycobacteria, including Mycobacterium tuberculosis, it could not be transferred to any of the fast-growing mycobacteria tested. Genetic analysis of the conjugative plasmid showed the presence of a locus containing homologues of three type IV secretion system components and a relaxase. In addition, a new type VII secretion locus was present. Using transposon insertion mutagenesis, we show that in fact both these secretion systems are essential for conjugation, indicating that this plasmid represents a new class of conjugative plasmids requiring two secretion machineries. This plasmid could form a useful new tool to exchange or introduce DNA in slow-growing mycobacteria. IMPORTANCE: Conjugative plasmids play an important role in horizontal gene transfer between different bacteria and, as such, in their adaptation and evolution. This effect is most obvious in the spread of antibiotic resistance genes. Thus far, conjugation of natural plasmids has been described only rarely for mycobacterial species. In fact, it is generally accepted that M. tuberculosis does not show any recent sign of horizontal gene transfer. In this study, we describe the identification of a new widespread conjugative plasmid that can also be efficiently transferred to M. tuberculosis. This plasmid therefore poses both a threat and an opportunity. The threat is that, through the acquisition of antibiotic resistance markers, this plasmid could start a rapid spread of

Probabilistic Infinite Secret Sharing

OpenAIRE

Csirmaz, László

2013-01-01

The study of probabilistic secret sharing schemes using arbitrary probability spaces and possibly infinite number of participants lets us investigate abstract properties of such schemes. It highlights important properties, explains why certain definitions work better than others, connects this topic to other branches of mathematics, and might yield new design paradigms. A probabilistic secret sharing scheme is a joint probability distribution of the shares and the secret together with a colle...

Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce l-Glutamic Acid Production▿

OpenAIRE

Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

2007-01-01

Corynebacterium glutamicum is a biotin auxotroph that secretes l-glutamic acid in response to biotin limitation; this process is employed in industrial l-glutamic acid production. Fatty acid ester surfactants and penicillin also induce l-glutamic acid secretion, even in the presence of biotin. However, the mechanism of l-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in l-gluta...

Advantages of using non-isothermal bioreactors for the enzymatic synthesis of antibiotics: the penicillin G acylase as enzyme model

NARCIS (Netherlands)

Travascio, P.; Zito, E.; Maio, de A.; Schroën, C.G.P.H.; Durante, D.; Luca, de P.; Bencivenga, U.

2002-01-01

A new hydrophobic and catalytic membrane was prepared by immobilizing Penicillin G acylase (PGA, EC.3.5.1.11) from E. coli on a nylon membrane, chemically grafted with butylmethacrylate (BMA). Hexamethylenediamine (HMDA) and glutaraldehyde (Glu) were used as a spacer and coupling agent,

Structural studies on New Delhi Metallo-β-lactamase (NDM-2) suggest old β-lactam, penicillin to be better antibiotic for NDM-2-harbouring Acinetobacter baumanni.

Science.gov (United States)

Tiwari, Vishvanath; Moganty, Rajeswari R

2013-01-01

Acinetobacter baumannii, a Gram-negative pathogen causes nosocomial infections including pneumonia, urinary tract and respiratory infections. Carbapenem group of β-lactam antibiotics are routinely used to treat A. baumannii including multidrug-resistant clinical strains. The emergence of New Delhi Metallo-β-lactamase (NDM-2), a new type of β-lactamase and one of the major resistant determinants in A. baumannii, opened up challenges in the treatment of resistant strains. Thus, understanding the structure-function relationship of NDM-2 with different analogues of β-lactams becomes crucial. We carried out in silico studies on the interaction of various β-lactams with NDM-2 and with OXA-24, a carbapenem hydrolyzing non-NDM type β-lactamase. The binding affinity of the β-lactams to NDM-2 was found to be in the order: ceftazidime ≈ imipenem ≈ doripenem > oxacillin > aztreonam > penicillin; however, the order of their affinity to OXA-24 was quite different: ceftazidime > aztreonam > penicillin > oxacillin > doripenem > imipenem. Further, NDM-2 in comparison to OXA-24 showed stronger interaction (less X-score) with most of the β-lactams except penicillin. This suggests higher lethality posed by clinical strains expressing NDM-2 than those without NDM-2. Weak interaction between NDM-2 and penicillin clearly points out that penicillin is perhaps better option in treating A. baumannii harbouring NDM-2. Present findings provide new insights in drug resistance at the molecular level of NDM-2 and can help in designing structure-based drugs.

RSA-Based Secret Handshakes

OpenAIRE

Vergnaud , Damien

2006-01-01

A secret handshake mechanism allows two entities, members of a same group, to authenticate each other secretly. This primitive was introduced recently by Balfanz, Durfee, Shankar, Smetters, Staddon and Wong and, so far, all the schemes proposed are based on discrete log systems. This paper proposes three new secret handshake protocols secure against active impersonator and detector adversaries. Inspired by two RSA-based key agreement protocols introduced by Okamoto and Tanaka in 1989 and Gira...

The problem of using trade secrets in economic relations

Directory of Open Access Journals (Sweden)

А. О. Олефір

2015-05-01

. The objects of trade secrets, depending on the fields may be the following types of information: (1 scientific and technical; (2 management; (3 commercial; (4 financial. At this stage, there is a growing role of know-how, compared with patents, because as their special advantages and drop interest in patenting innovations as an independent factor, as well as economic and legal efficiency mode of trade secrets. Under the know-how necessary to understand the technical, manufacturing, engineering knowledge, experience and skills related to the design, development, manufacture, sale, operation, maintenance, repair, improve technology and other innovative objects which have the status of trade secrets, and a factor of competitiveness entity. Given the fact that the administrative and jurisdictional mechanisms for the protection of trade secrets are more or less clear, we focused on internal corporate events. First, this is consolidation in the basic documents of the entity (statute, founding and collective agreements, work rules on trade secret law such provision as law on ownership and protection of trade secrets. Second, the order of the head of the entity to approve the list of information to be protected as a trade secret. Third, develop and adopt regulations on trade secrets. Fourth, to approve the regulations on the organization of the documents containing trade secrets. Fifth, to include in a labor agreement (contract the condition of non-disclosure of trade secrets or employee expected signing of enhancing privacy protection. Conclusions of the research. In order to stimulate innovation growth and protection of corporate security entities we should propose changes to the legislation: (1 secure the definition of the concept of «know-how (secret production» indicating that the exclusive right to the secret of acting as long as the relation of production secrets operating mode of trade secrets; (2 add Tax Code of Ukraine following types of tax benefits: (a exemption

The secreted L-arabinose isomerase displays anti-hyperglycemic effects in mice.

Science.gov (United States)

Rhimi, Moez; Bermudez-Humaran, Luis G; Huang, Yuan; Boudebbouze, Samira; Gaci, Nadia; Garnier, Alexandrine; Gratadoux, Jean-Jacques; Mkaouar, Héla; Langella, Philippe; Maguin, Emmanuelle

2015-12-21

The L-arabinose isomerase is an intracellular enzyme which converts L-arabinose into L-ribulose in living systems and D-galactose into D-tagatose in industrial processes and at industrial scales. D-tagatose is a natural ketohexose with potential uses in pharmaceutical and food industries. The D-galactose isomerization reaction is thermodynamically equilibrated, and leads to secondary subproducts at high pH. Therefore, an attractive L-arabinose isomerase should be thermoactive and acidotolerant with high catalytic efficiency. While many reports focused on the set out of a low cost process for the industrial production of D-tagatose, these procedures remain costly. When compared to intracellular enzymes, the production of extracellular ones constitutes an interesting strategy to increase the suitability of the biocatalysts. The L-arabinose isomerase (L-AI) from Lactobacillus sakei was expressed in Lactococcus lactis in fusion with the signal peptide of usp45 (SP(Usp45)). The L-AI protein and activity were detected only in the supernatant of the induced cultures of the recombinant L. lactis demonstrating the secretion in the medium of the intracellular L. sakei L-AI in an active form. Moreover, we showed an improvement in the enzyme secretion using either (1) L. lactis strains deficient for their two major proteases, ClpP and HtrA, or (2) an enhancer of protein secretion in L. lactis fused to the recombinant L-AI with the SP(Usp45). Th L-AI enzyme secreted by the recombinant L. lactis strains or produced intracellularly in E. coli, showed the same functional properties than the native enzyme. Furthermore, when mice are fed with the L. lactis strain secreting the L-AI and galactose, tagatose was produced in vivo and reduced the glycemia index. We report for the first time the secretion of the intracellular L-arabinose isomerase in the supernatant of food grade L. lactis cultures with hardly display other secreted proteins. The secreted L-AI originated from the food

Simultaneous determination of penicillin G salts by infrared spectroscopy: Evaluation of combining orthogonal signal correction with radial basis function-partial least squares regression

Science.gov (United States)

Talebpour, Zahra; Tavallaie, Roya; Ahmadi, Seyyed Hamid; Abdollahpour, Assem

2010-09-01

In this study, a new method for the simultaneous determination of penicillin G salts in pharmaceutical mixture via FT-IR spectroscopy combined with chemometrics was investigated. The mixture of penicillin G salts is a complex system due to similar analytical characteristics of components. Partial least squares (PLS) and radial basis function-partial least squares (RBF-PLS) were used to develop the linear and nonlinear relation between spectra and components, respectively. The orthogonal signal correction (OSC) preprocessing method was used to correct unexpected information, such as spectral overlapping and scattering effects. In order to compare the influence of OSC on PLS and RBF-PLS models, the optimal linear (PLS) and nonlinear (RBF-PLS) models based on conventional and OSC preprocessed spectra were established and compared. The obtained results demonstrated that OSC clearly enhanced the performance of both RBF-PLS and PLS calibration models. Also in the case of some nonlinear relation between spectra and component, OSC-RBF-PLS gave satisfactory results than OSC-PLS model which indicated that the OSC was helpful to remove extrinsic deviations from linearity without elimination of nonlinear information related to component. The chemometric models were tested on an external dataset and finally applied to the analysis commercialized injection product of penicillin G salts.

Withdrawal of amoxicillin and penicillin G procaine from milk after intramammary administration in dairy cows with mastitis

Directory of Open Access Journals (Sweden)

Burmańczuk Artur

2017-03-01

Full Text Available Introduction: There are many veterinary products containing β-lactam antibiotics which are used for mastitis treatment in cows. The aim of the study was to determine whether mastitis could have any effect on amoxicillin (AMX or penicillin G procaine (PEN withdrawal period from milk, in the context of current maximum residue limits established by the European Commission.

Penicillin for acute sore throat : randomised double blind trial of seven days versus three days treatment or placebo in adults

NARCIS (Netherlands)

Zwart, S; Sachs, APE; Ruijs, GJHM; Gubbels, JW; Hoes, AW; de Melker, RA

2000-01-01

Objective To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo. Design Randomised double blind placebo controlled trial. Setting 43

A putative low-molecular-mass penicillin-binding protein (PBP) of Mycobacterium smegmatis exhibits prominent physiological characteristics of DD-carboxypeptidase and beta-lactamase.

Science.gov (United States)

Bansal, Ankita; Kar, Debasish; Murugan, Rajagopal A; Mallick, Sathi; Dutta, Mouparna; Pandey, Satya Deo; Chowdhury, Chiranjit; Ghosh, Anindya S

2015-05-01

DD-carboxypeptidases (DD-CPases) are low-molecular-mass (LMM) penicillin-binding proteins (PBPs) that are mainly involved in peptidoglycan remodelling, but little is known about the dd-CPases of mycobacteria. In this study, a putative DD-CPase of Mycobacterium smegmatis, MSMEG_2433 is characterized. The gene for the membrane-bound form of MSMEG_2433 was cloned and expressed in Escherichia coli in its active form, as revealed by its ability to bind to the Bocillin-FL (fluorescent penicillin). Interestingly, in vivo expression of MSMEG_2433 could restore the cell shape oddities of the septuple PBP mutant of E. coli, which was a prominent physiological characteristic of DD-CPases. Moreover, expression of MSMEG_2433 in trans elevated beta-lactam resistance in PBP deletion mutants (ΔdacAdacC) of E. coli, strengthening its physiology as a dd-CPase. To confirm the biochemical reason behind such physiological behaviours, a soluble form of MSMEG_2433 (sMSMEG_2433) was created, expressed and purified. In agreement with the observed physiological phenomena, sMSMEG_2433 exhibited DD-CPase activity against artificial and peptidoglycan-mimetic DD-CPase substrates. To our surprise, enzymic analyses of MSMEG_2433 revealed efficient deacylation for beta-lactam substrates at physiological pH, which is a unique characteristic of beta-lactamases. In addition to the MSMEG_2433 active site that favours dd-CPase activity, in silico analyses also predicted the presence of an omega-loop-like region in MSMEG_2433, which is an important determinant of its beta-lactamase activity. Based on the in vitro, in vivo and in silico studies, we conclude that MSMEG_2433 is a dual enzyme, possessing both DD-CPase and beta-lactamase activities. © 2015 The Authors.

Sequential Quantum Secret Sharing Using a Single Qudit

Science.gov (United States)

Bai, Chen-Ming; Li, Zhi-Hui; Li, Yong-Ming

2018-05-01

In this paper we propose a novel and efficient quantum secret sharing protocol using d-level single particle, which it can realize a general access structure via the thought of concatenation. In addition, Our scheme includes all advantages of Tavakoli’s scheme [Phys. Rev. A 92 (2015) 030302(R)]. In contrast to Tavakoli’s scheme, the efficiency of our scheme is 1 for the same situation, and the access structure is more general and has advantages in practical significance. Furthermore, we also analyze the security of our scheme in the primary quantum attacks. Sponsored by the National Natural Science Foundation of China under Grant Nos. 61373150 and 61602291, and Industrial Research and Development Project of Science and Technology of Shaanxi Province under Grant No. 2013k0611

Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: An efficient carrier for immobilizing penicillin G acylase